trimethoprim--sulfamethoxazole-drug-combination and Malaria

Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.. We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.. We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.. Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.. In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.

Topics: Anti-Infective Agents; Child; Female; HIV Infections; Humans; Infant; Malaria; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; World Health Organization

This comprehensive review explores the intricate relationship between 2 major global health challenges, malaria and HIV, with a specific focus on their impact on children. These diseases, both endemic in sub-Saharan Africa, create a dual burden that significantly elevates the risk of morbidity and mortality, particularly in children with compromised immune systems due to HIV. The review delves into the complex mechanisms by which these infections interact, from heightened clinical malaria frequencies in HIV-infected individuals to the potential impact of antiretroviral therapy on malaria treatment. Different research engines were utilized in writing this paper such as Web of Science, Google Scholar, Pubmed Central, ResearchGate, and Academia Edu. To address this critical health concern, the study identifies and discusses various regulatory and treatment strategies. It emphasizes the importance of daily cotrimoxazole prophylaxis and insecticide-treated nets in preventing malaria in children with HIV. The potential of antiretroviral protease inhibitors and mRNA-based vaccines as innovative solutions is highlighted. Additionally, the study underscores the significance of climate data and artificial intelligence in improving diagnostics and drug development. Furthermore, the review introduces the concept of genetically modified mosquitoes as a novel approach to vector control, offering a promising avenue to protect HIV-positive individuals from mosquito-borne diseases like malaria. Through a comprehensive analysis of these strategies, the study aims to provide a foundation for policymakers, healthcare professionals, and researchers to develop effective regulations and interventions that reduce the dual burden of malaria and HIV in children, improving public health outcomes in endemic regions.

Topics: Animals; Antimalarials; Artificial Intelligence; Child; HIV Infections; Humans; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination

The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine.. To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:• the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and• the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.. We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials.. Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen.. Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting.. Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria.Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo.Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes.When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I. Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women.

Topics: Abortion, Spontaneous; Africa South of the Sahara; Antimalarials; Dizziness; Drug Combinations; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant, Low Birth Weight; Insecticide-Treated Bednets; Malaria; Mefloquine; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine.. To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:• the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and• the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.. We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials.. Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen.. Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting.. Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria.Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo.Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes.When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I. Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women.

Topics: Anemia; Antimalarials; Drug Combinations; Drug Therapy, Combination; Female; HIV Seronegativity; Humans; Malaria; Mefloquine; Parasitemia; Placenta Diseases; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pyrimethamine; Randomized Controlled Trials as Topic; Stillbirth; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

HIV-infected adults are at increased risk of severe malaria and death. Malaria prevention in people living with HIV (PLHIV) consists of several interventions, including cotrimoxazole (CTX) prophylaxis and insecticide-treated nets (ITNs). We conducted a systematic review of the available evidence.. MEDLINE, EmBase, Global Health, CINAHL, SOCA, and African Index Medicus were used to identify articles relevant to the CTX prophylaxis and ITNs interventions from 1995 to July 2014. For each individual study, we assessed the quality of evidence and the impact of the 2 interventions on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. For each outcome, we summarized the quality of the overall body of evidence, the expected impact, and costing and cost-effectiveness (CE).. The overall quality of evidence regarding malaria-related morbidity was rated as "good" for CTX prophylaxis and "fair" for ITN use; the expected "impact" of these interventions on morbidity was rated "high" and "uncertain," respectively. Three studies that addressed the costing and CE of ITN provision for malaria prevention in PLHIV consisted of 2 full "level 1" and 1 partial "level 2" economic evaluations.. CTX prophylaxis is effective in reducing malaria-related morbidity among PLHIV. Limited evidence is available with respect to the impact and the CE of ITN use and/or provision in this population.

Topics: Adult; Antimalarials; Cost-Benefit Analysis; Developing Countries; Health Impact Assessment; Health Resources; HIV Infections; Humans; Insecticide-Treated Bednets; Malaria; Morbidity; Outcome Assessment, Health Care; Quality of Life; Trimethoprim, Sulfamethoxazole Drug Combination

Malaria and HIV are amongst the two main diseases worldwide and creating troubles of our time. Together, they grounds extra than four million deaths a year. Malaria causes around about for more than a million deaths each year, of which over 80-90 % come about in tropical Africa, somewhere malaria is the primary source of mortality in children below six years of age. Sideways as of adolescent, children, pregnant women are surrounded by the largest part exaggerated by the disease. In the wide geographical extend beyond in event and the follow-on co-infection, the interface flanked as a result of the two diseases visibly has foremost communal strength results. Thus both are dangerous for health at the same time.

Topics: Acquired Immunodeficiency Syndrome; Coinfection; Female; Humans; Malaria; Pregnancy; Pregnancy Complications; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa.. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses.. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire.. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.

Topics: Africa South of the Sahara; Antimalarials; Child; Drug Combinations; Drug Resistance; HIV Infections; Humans; Malaria; Mutation; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Female; HIV Infections; Humans; Insecticide-Treated Bednets; Malaria; Mefloquine; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Trimethoprim, Sulfamethoxazole Drug Combination

Despite provisional recommendations from the World Health Organization and UNAIDS that cotrimoxazole (CTX) prophylaxis be offered to all individuals living with AIDS, including HIV-positive patients with TB, its routine use in developing countries particularly Africa has been minimal. Concerns were expressed regarding its effectiveness in areas of high bacterial resistance, that its widespread use might substantially increase bacterial cross-resistance in the community and that this intervention might promote resistance of malaria parasites to sulphadoxine-pyrimethamine. We review the current evidence on the above concerns and highlight the main operational considerations related to implementing CTX prophylaxis as a basic component of care for HIV-positive TB patients in developing countries.

Topics: Adult; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Drug Resistance; Humans; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4 + cell count among adults on ART.. We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4 +  cells/μl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ).. We defined clinical malaria as symptoms consistent with malaria and positive blood smear, and malaria infection as Plasmodium falciparum DNA detected from dried blood spots (collected every 4-12 weeks). CD4 + cell count and viral load were measured every 24 weeks. We used Poisson regression and survival analysis to compare the incidence of malaria infection and clinical malaria. Clinicaltrials.gov NCT01650558.. Among 1499 participants enrolled, clinical malaria incidence was 21.4/100 person-years of observation (PYO), 2.4/100 PYO and 1.9/100 PYO in the no prophylaxis, TS, and CQ arms, respectively. We identified twelve cases of malaria that led to hospitalization and all individuals recovered. The preventive effect of staying on prophylaxis was approximately 90% compared to no prophylaxis (TS: incidence rate ratio [IRR] 0.11, 95% confidence interval [CI] 0.08, 0.15 and CQ: IRR 0.09, 95% CI 0.06, 0.13). P. falciparum infection prevalence among all visits was 187/1475 (12.7%), 48/1563 (3.1%), and 29/1561 (1.9%) in the no prophylaxis, TS, and CQ arms, respectively. Malaria infection and clinical malaria were not associated with changes in CD4 + cell count or viral load.. In clinically stable adults living with HIV on ART, clinical malaria was common after chemoprophylaxis stopped. However, neither malaria infection nor clinical illness appeared to affect HIV disease progression.

Topics: Adult; Antimalarials; CD4 Lymphocyte Count; Chemoprevention; HIV Infections; Humans; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination

The main objective of the MACOMBA (Maternity and Control of Malaria-HIV co-infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than sulphadoxine-pyremethamine-IPTp (IPTp-SP) to prevent placental malaria infection (primary end point) among HIV-positive pregnant women with a CD4+ count ≥350 cells/mm. MACOMBA is a multicentre, open-label randomised trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomised and 112 (59 and 53 in CTX and IPTp-SP arms, respectively) were assessed for placental infection defined by microscopic parasitaemia or PCR.. Thirteen women had a placental infection: five in the CTX arm (one by microscopic placental parasitaemia and four by PCR) and eight by PCR in the SP-IPTp (8.5% vs. 15.1%, p = 0.28). The percentage of newborns with low birthweight (<2500 g) did not differ statistically between the two arms. Self-reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms.. Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV-infected pregnant women, as currently recommended by WHO.

Topics: Adult; Antimalarials; Central African Republic; Drug Combinations; Female; HIV Infections; Humans; Malaria; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes. Concentrations of CHI3L1, CRP, IL-18BP, IL-6, sICAM-1, and sTNFR2 were quantified by ELISA in 1115 plasma samples collected over pregnancy from 326 women. MiP was associated with increased sTNFR2, sICAM-1 and IL-18BP concentrations across pregnancy. Women who delivered preterm had elevated concentrations of sTNFR2 and altered levels of IL-6 during pregnancy. Women with sTNFR2 concentrations in the highest quartile within 6 weeks of delivery had an increased relative risk of preterm birth. Our results indicate that despite daily TMP/SXT, MiP in WLHIV induced a systemic inflammatory response that was associated with an increased risk of preterm birth. These findings highlight the need for additional strategies to protect WLHIV from malaria infection in pregnancy to promote healthy outcomes for mother and child.

Topics: Adult; Anti-Retroviral Agents; Cohort Studies; Female; HIV; HIV Infections; Humans; Incidence; Infant, Newborn; Inflammation; Malaria; Pregnancy; Premature Birth; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide-treated nets remain the main interventions for prevention of malaria in human immunodeficiency virus (HIV)-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these interventions, and new ones are needed.. We conducted a double-blinded, randomized, placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide had recently been implemented. Participants were enrolled between gestation weeks 12 and 28 and given an insecticide-treated net. The primary outcome was detection of active or past placental malarial infection by histopathologic analysis. Secondary outcomes included incidence of malaria, parasite prevalence, and adverse birth outcomes.. All 200 women enrolled were followed through delivery, and the primary outcome was assessed in 194. There was no statistically significant difference in the risk of histopathologically detected placental malarial infection between the daily TMP-SMX plus DP arm and the daily TMP-SMX alone arm (6.1% vs. 3.1%; relative risk, 1.96; 95% confidence interval, .50-7.61; P = .50). Similarly, there were no differences in secondary outcomes.. Among HIV-infected pregnant women in the setting of indoor residual spraying of insecticide, adding monthly DP to daily TMP-SMX did not reduce the risk of placental or maternal malaria or improve birth outcomes.. NCT02282293.

Topics: Adult; Antimalarials; Artemisinins; Double-Blind Method; Endpoint Determination; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Malaria; Pregnancy; Pregnancy Complications, Infectious; Quinolines; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

The World Health Organisation (WHO) recommends parasitological diagnosis of malaria before treatment, but use of malaria rapid diagnostic tests (mRDTs) by community health workers (CHWs) has not been fully tested within health services in south and central Asia. mRDTs could allow CHWs to diagnose malaria accurately, improving treatment of febrile illness.. A cluster randomised trial in community health services was undertaken in Afghanistan. The primary outcome was the proportion of suspected malaria cases correctly treated for polymerase chain reaction (PCR)-confirmed malaria and PCR negative cases receiving no antimalarial drugs measured at the level of the patient. CHWs from 22 clusters (clinics) received standard training on clinical diagnosis and treatment of malaria; 11 clusters randomised to the intervention arm received additional training and were provided with mRDTs. CHWs enrolled cases of suspected malaria, and the mRDT results and treatments were compared to blind-read PCR diagnosis.. In total, 256 CHWs enrolled 2400 patients with 2154 (89.8%) evaluated. In the intervention arm, 75.3% (828/1099) were treated appropriately vs. 17.5% (185/1055) in the control arm (cluster adjusted risk ratio: 3.72, 95% confidence interval 2.40-5.77; p < 0.001). In the control arm, 85.9% (164/191) with confirmed Plasmodium vivax received chloroquine compared to 45.1% (70/155) in the intervention arm (p < 0.001). Overuse of chloroquine in the control arm resulted in 87.6% (813/928) of those with no malaria (PCR negative) being treated vs. 10.0% (95/947) in the intervention arm, p < 0.001. In the intervention arm, 71.4% (30/42) of patients with P. falciparum did not receive artemisinin-based combination therapy, partly because operational sensitivity of the RDTs was low (53.2%, 38.1-67.9). There was high concordance between recorded RDT result and CHW prescription decisions: 826/950 (87.0%) with a negative test were not prescribed an antimalarial. Co-trimoxazole was prescribed to 62.7% of malaria negative patients in the intervention arm and 15.0% in the control arm.. While introducing mRDT reduced overuse of antimalarials, this action came with risks that need to be considered before use at scale: an appreciable proportion of malaria cases will be missed by those using current mRDTs. Higher sensitivity tests could be used to detect all cases. Overtreatment with antimalarial drugs in the control arm was replaced with increased antibiotic prescription in the intervention arm, resulting in a probable overuse of antibiotics.. ClinicalTrials.gov, NCT01403350 . Prospectively registered.

Topics: Adolescent; Afghanistan; Antimalarials; Artemisinins; Child; Child, Preschool; Chloroquine; Community Health Workers; Diagnostic Tests, Routine; Female; Humans; Infant; Infant, Newborn; Malaria; Malaria, Falciparum; Male; Plasmodium vivax; Trimethoprim, Sulfamethoxazole Drug Combination

 Cotrimoxazole (CTX) discontinuation increases malaria incidence in human immunodeficiency virus (HIV)-infected individuals. Rates, quantity, and timing of parasitemia rebound following CTX remain undefined..  Serial specimens from a trial of HIV-infected individuals receiving antiretroviral treatment (ART) randomized to continue (the CTX arm) or discontinue (the STOP-CTX arm) were examined for malaria parasites by quantitative reverse transcription polymerase chain reaction (PCR). Specimens obtained at enrollment and then quarterly for 12 months and at sick visits were assessed; multiplicity of infection was evaluated by PCR that targeted the polymorphic msp-1/msp-2 alleles..  Discontinuation of CTX by HIV-infected adults receiving ART resulted in progressive increases in malaria parasitemia prevalence and burden..  NCT01425073.

Topics: Adult; Anti-HIV Agents; Antimalarials; Female; HIV Infections; Humans; Kenya; Malaria; Male; Medication Adherence; Parasite Load; Parasitemia; Plasmodium falciparum; Polymerase Chain Reaction; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Previous unblinded trials have shown increased malaria among HIV-infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV-infected adults on ART in a double-blind, placebo-controlled trial.. HIV-infected Ugandan adults stable on ART and CTX with CD4 cell count at least 250 cells/μl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes.. A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2-10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74-4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18-0.49). There was one malaria-related death (CTX arm).. HIV-infected adults - who are stable on ART and stop prophylactic CTX - experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis.

Topics: Adult; Anti-Retroviral Agents; Antimalarials; Chemoprevention; Double-Blind Method; Female; HIV Infections; Humans; Incidence; Malaria; Male; Middle Aged; Placebos; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed.. A double-blinded, placebo-controlled study was conducted with 124 HIV-infected, pregnant women on a standard regimen of sulfamethoxazole/trimethoprim prophylaxis. Seventy-two subjects received three doses of mefloquine (15 mg/kg) at monthly intervals. Dried blood spots were collected from both placebo and mefloquine arms four to 672 h post-administration and on day 7 following a second monthly dose of mefloquine. A novel high-performance liquid chromatographic method was developed to simultaneously measure mefloquine, sulfamethoxazole and trimethoprim from each blood spot. Non-compartmental methods using a naïve-pooled data approach were used to determine mefloquine pharmacokinetic parameters.. Sulfamethoxazole/trimethoprim prophylaxis did not noticeably influence mefloquine pharmacokinetics relative to reported values. The mefloquine half-life, observed clearance (CL/f), and area-under-the-curve (AUC0→∞) were 12.0 days, 0.035 l/h/kg and 431 µg-h/ml, respectively. Although trimethoprim steady-state levels were not significantly different between arms, sulfamethoxazole levels showed a significant 53% decrease after mefloquine administration relative to the placebo group and returning to pre-dose levels at 28 days.. Although a transient decrease in sulfamethoxazole levels was observed, there was no change in hospital admissions due to secondary bacterial infections, implying that mefloquine may have provided antimicrobial protection.

Topics: Adolescent; Adult; Antimalarials; Double-Blind Method; Female; HIV Infections; Humans; Kenya; Malaria; Male; Mefloquine; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX).. This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use.. 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30.. The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Retroviral Agents; Antimalarials; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Chemoprevention; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Malaria; Male; Middle Aged; Placebos; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

Before antiretroviral therapy (ART) became widely available in sub-Saharan Africa, several studies demonstrated that daily trimethoprim-sulfamethoxazole (TS) prophylaxis reduced morbidity and mortality among HIV-infected adults. As a result, the World Health Organization (WHO) recommended administering TS prophylaxis to this group. However, the applicability of the results to individuals taking ART and living in sub-Saharan Africa has not been definitively evaluated. This study aims to determine if TS prophylaxis benefits HIV-infected Malawian adults after a good response to ART. If TS prophylaxis does indeed show benefit, it is important to determine if this is due to its antibacterial and/or antimalarial properties.. A randomized, controlled, open-label, phase III trial of continued standard of care prophylaxis with daily trimethoprim-sulfamethoxazole (TS) compared to discontinuation of standard of care TS prophylaxis and starting weekly chloroquine (CQ) prophylaxis or discontinuation of standard of care TS prophylaxis. The study will randomize 1400-1500 HIV-infected adults (equally divided over the three study arms) with a nondetectable viral load and a CD4 count of 250/mm(3) or more from antiretroviral therapy clinics in Blantyre and Zomba. The expected rate of primary endpoint events of death and WHO stage 3 and 4 events is 6.8 per 100 person-years of follow-up in all participants. Assuming the number of events follows a Poisson distribution and average participant follow-up after 10 % loss to follow-up is 41.6 months, the study will have approximately 85 % power to rule out a reduction of 35 % or more in primary endpoint events in the TS or CQ arms compared to discontinuation of TS prophylaxis-i.e., to show that discontinuation of TS prophylaxis is noninferior to either TS or CQ, with a noninferiority margin of 35 %. Ethical and regulatory approvals were obtained from the University of Malawi College of Medicine Research Ethics Committee; the Malawi Pharmacy, Medicines and Poisons Board; and the University of Maryland Baltimore Institutional Review Board.. The study began recruitment activities at the Ndirande site in November 2012. The sponsor agreed to extend and expand the study in early 2015, and a second site, Zomba, was added for recruitment and follow-up in mid-2015.. ClinicalTrials.gov Identifier: NCT01650558 (registered on 6 July 2012).. Letter of amendment #1 to the DAIDS-ES 10822 TSCQ Malawi Protocol, Version 4.0, 16 December 2014.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Retroviral Agents; Antimalarials; Chloroquine; Drug Administration Schedule; HIV Infections; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

HIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited.. The incidence of febrile illnesses and malaria were evaluated in a birth cohort of HEU infants. Infants were prescribed daily trimethoprim-sulfamethoxazole (TS) prophylaxis from 6 weeks of age until exclusion of HIV-infection after cessation of breastfeeding. Infants were followed for all illnesses using passive surveillance and routine blood smears were done monthly. Malaria was diagnosed as a positive blood smear plus fever. Placental malaria was determined by histopathology, placental blood smear and PCR. Risk factors for time to first episode of malaria were assessed using a Cox proportional hazards model. Malaria incidence among HEU infants aged 6-12 months was compared to that in other cohorts of HEU and HUU infants from the same region.. Among 361 HEU infants enrolled, 248 completed 12 months of follow-up resulting in 1562 episodes of febrile illness and 253 episodes of malaria after 305 person-years of follow-up. The incidence of febrile illness was 5.12 episodes per person-year (PPY), ranging from 4.13 episodes PPY in the first 4 months of life to 5.71 episodes PPY between 5 and 12 months of age. The overall malaria incidence was 0.83 episodes per person-year (PPY), increasing from 0.03 episodes PPY in the first 2 months of life to 2.00 episodes PPY between 11 and 12 months of age. There were no episodes of complicated malaria. The prevalence of asymptomatic parasitaemia was 1.2 % (19 of 1568 routine smears positive). Infants born to mothers with parasites detected from placental blood smears were at higher risk of malaria (hazard ratio = 4.51, P < 0.001). HEU infants in this study had a 2.4- to 3.5-fold lower incidence of malaria compared to HUU infants in other cohort studies from the same area.. The burden of malaria in this birth cohort of HEU infants living in a high-transmission setting and taking daily TS prophylaxis was relatively low. Alternative etiologies of fever should be considered in HEU-infants taking daily TS prophylaxis who present with fever. Trial Registration NCT00993031, registered 8 October, 2009.

Topics: Antimalarials; Chemoprevention; Cohort Studies; Female; Humans; Incidence; Infant; Infant, Newborn; Malaria; Male; Maternal Exposure; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.. We conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia.. At delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found.. CTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.

Topics: Adult; Antimalarials; Benin; Chemoprevention; Dizziness; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Infant; Infant, Newborn; Malaria; Mefloquine; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole.. We conducted a randomized, noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Uganda and Zimbabwe. Eligible participants were older than 3 years of age, had been receiving ART for more than 96 weeks, were using insecticide-treated bed nets (in malaria-endemic areas), and had not had Pneumocystis jirovecii pneumonia. Coprimary end points were hospitalization or death and adverse events of grade 3 or 4.. A total of 758 participants were randomly assigned to stop or continue co-trimoxazole (382 and 376 participants, respectively), after receiving ART for a median of 2.1 years (interquartile range, 1.8 to 2.3). The median age was 7.9 years (interquartile range, 4.6 to 11.1), and the median CD4 T-cell percentage was 33% (interquartile range, 26 to 39). Participants who stopped co-trimoxazole had higher rates of hospitalization or death than those who continued (72 participants [19%] vs. 48 [13%]; hazard ratio, 1.64; 95% confidence interval [CI], 1.14 to 2.37; P = 0.007; noninferiority not shown). There was no evidence of variation across ages (P=0.93 for interaction). A total of 2 participants in the prophylaxis-stopped group (1%) died, as did 3 in the prophylaxis-continued group (1%). Most hospitalizations in the prophylaxis-stopped group were for malaria (49 events, vs. 21 in the prophylaxis-continued group) or infections other than malaria (53 vs. 25), particularly pneumonia, sepsis, and meningitis. Rates of adverse events of grade 3 or 4 were similar in the two groups (hazard ratio, 1.20; 95% CI, 0.83 to 1.72; P=0.33), but more grade 4 adverse events occurred in the prophylaxis-stopped group (hazard ratio, 2.04; 95% CI, 0.99 to 4.22; P=0.05), with anemia accounting for the largest number of events (12, vs. 2 with continued prophylaxis).. Continuing co-trimoxazole prophylaxis after 96 weeks of ART was beneficial, as compared with stopping prophylaxis, with fewer hospitalizations for both malaria and infection not related to malaria. (Funded by the United Kingdom Medical Research Council and others; ARROW Current Controlled Trials number, ISRCTN24791884.).

Topics: Adolescent; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Female; Follow-Up Studies; HIV Infections; Hospitalization; Humans; Kaplan-Meier Estimate; Malaria; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment; Zimbabwe

Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.. Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.. Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.. Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.. Clinicaltrials.gov NCT00711906.

Topics: Adult; Antimalarials; Birth Weight; Drug Administration Schedule; Female; Gestational Age; HIV Infections; Humans; Malaria; Male; Maternal Exposure; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pregnancy Outcome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Zambia

Human immunodeficiency virus (HIV)-infected pregnant women are at increased risk of malaria and its complications. In vitro and in vivo data suggest that the HIV protease inhibitors lopinavir/ritonavir may have potent antimalarial activity. We sought to evaluate whether lopinavir/ritonavir-based antiretroviral therapy (ART) reduced the risk of placental malaria.. HIV-infected, ART-naive pregnant women were enrolled between gestational weeks 12 and 28 and randomly assigned to receive lopinavir/ritonavir-based or efavirenz-based ART. Women received daily trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bed nets at enrollment and were followed up to 1 year after delivery. The primary outcome was placental malaria, defined by the detection of malaria parasites, using microscopy or polymerase chain reaction (PCR) analysis of placental blood specimens. Secondary outcomes included placental malaria, defined by histopathologic results; adverse birth outcomes; incidence of malaria; and prevalence of asymptomatic parasitemia. Analyses were done using an intention-to-treat approach.. Of 389 subjects randomly assigned to a treatment group, 377 were followed through to delivery. There was no significant difference in the risk of placental malaria, as defined by thick smear or PCR findings, between the lopinavir/ritonavir-based and efavirenz-based ART arms (7.4% vs 9.8%; P = .45). Similarly, there were no differences in secondary outcomes between the 2 treatment arms.. Lopinavir/ritonavir-based ART did not reduce the risk of placental or maternal malaria or improve birth outcomes, compared with efavirenz-based ART.. NCT00993031.

Topics: Adolescent; Adult; Alkynes; Anti-HIV Agents; Antimalarials; Antiretroviral Therapy, Highly Active; Benzoxazines; Cyclopropanes; Female; HIV Infections; Humans; Infant, Newborn; Lopinavir; Malaria; Pregnancy; Pregnancy Complications, Infectious; Ritonavir; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Chemoprevention offers a promising strategy for prevention of malaria in African children. However, the optimal chemoprevention drug and dosing strategy is unclear in areas of year-round transmission and resistance to many antimalarial drugs. To compare three available regimens, we conducted an open-label randomized controlled trial of chemoprevention in Ugandan children.. This study was conducted between June 28, 2010, and September 25, 2013. 400 infants were enrolled and 393 randomized at 6 mo of age to no chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily trimethoprim-sulfamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered at home without supervision. Piperaquine (PQ) levels were used as a measure of compliance in the DP arm. Participants were given insecticide-treated bednets, and caregivers were encouraged to bring their child to a study clinic whenever they were ill. Chemoprevention was stopped at 24 mo of age, and participants followed-up an additional year. Primary outcome was the incidence of malaria during the intervention period. During the intervention, the incidence of malaria in the no chemoprevention arm was 6.95 episodes per person-year at risk. Protective efficacy was 58% (95% CI, 45%-67%, p<0.001) for DP, 28% (95% CI, 7%-44%, p = 0.01) for TS, and 7% for SP (95% CI, -19% to 28%, p = 0.57). PQ levels were below the detection limit 52% of the time when malaria was diagnosed in the DP arm, suggesting non-adherence. There were no differences between the study arms in the incidence of serious adverse events during the intervention and the incidence of malaria during the 1-y period after the intervention was stopped.. For preventing malaria in children living in an area of high transmission intensity, monthly DP was the most efficacious and safe, although adherence may pose a problem. Monthly SP and daily TS may not be appropriate in areas with high transmission intensity and frequent resistance to antifolates.. www.ClinicalTrials.gov NCT00948896 Please see later in the article for the Editors' Summary.

Topics: Antimalarials; Artemisinins; Cohort Studies; Drug Combinations; Female; Humans; Incidence; Infant; Malaria; Male; Pyrimethamine; Quinolines; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).. A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.. An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.. ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.

Topics: Adult; Antimalarials; Double-Blind Method; Female; Follow-Up Studies; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Kenya; Malaria; Mefloquine; Mozambique; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pregnancy Outcome; Tanzania; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

WHO recommends daily co-trimoxazole for children born to HIV-infected mothers from 6 weeks of age until breastfeeding cessation and exclusion of HIV infection. We have previously reported on the effectiveness of continuation of co-trimoxazole prophylaxis up to age 2 years in these children. We assessed the protective efficacy and safety of prolonging co-trimoxazole prophylaxis until age 4 years in HIV-exposed children.. We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern Uganda, an area with high HIV prevalence, malaria transmission intensity, and antifolate resistance. We enrolled HIV-exposed infants between 6 weeks and 9 months of age and prescribed them daily co-trimoxazole until breastfeeding cessation and HIV-status confirmation. At the end of breastfeeding, children who remained HIV-uninfected were randomly assigned (1:1) to discontinue co-trimoxazole or to continue taking it up to age 2 years. At age 2 years, children who continued co-trimoxazole prophylaxis were randomly assigned (1:1) to discontinue or continue prophylaxis from age 2 years to age 4 years. The primary outcome was incidence of malaria (defined as the number of treatments for new episodes of malaria diagnosed with positive thick smear) at age 4 years. For additional comparisons, we observed 48 HIV-infected children who took continuous co-trimoxazole prophylaxis and 100 HIV-unexposed uninfected children who never received prophylaxis. We measured grade 3 and 4 serious adverse events and hospital admissions. All children were followed up to age 5 years and all analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00527800.. 203 HIV-exposed infants were enrolled between Aug 10, 2007, and March 28, 2008. After breastfeeding ended, 185 children were not infected with HIV and were randomly assigned to stop (n=87) or continue (n=98) co-trimoxazole up to age 2 years. At age 2 years, 91 HIV-exposed children who had remained on co-trimoxazole prophylaxis were randomly assigned to discontinue (n=46) or continue (n=45) co-trimoxazole from age 2 years to age 4 years. We recorded 243 malaria episodes (2·91 per person-years) in the 45 HIV-exposed children assigned to continue co-trimoxazole until age 4 years compared with 503 episodes (5·60 per person-years) in the 46 children assigned to stop co-trimoxazole at age 2 years (incidence rate ratio 0·53, 95% CI 0·39-0·71; p< 0·0001). There was no evidence of malaria incidence rebound in the year after discontinuation of co-trimoxazole in the HIV-exposed children who stopped co-trimoxazole at age 2 years, but incidence increased significantly in HIV-exposed children who stopped co-trimoxazole at age 4 years (odds ratio 1·78, 95% CI 1·19-2·66; p= 0·005). Incidence of grade 3 or 4 serious adverse events, hospital admissions, or deaths did not significantly differ between HIV-exposed, HIV-unexposed, and HIV-infected children.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Breast Feeding; CD4 Lymphocyte Count; Child, Preschool; Female; HIV Infections; Humans; Infant; Malaria; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Trimethoprim-sulfamethoxazole prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children.. An open-label, randomized controlled trial.. Tororo, Uganda, a rural area with intense, year-round, malaria transmission.. Two hundred infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age).. No chemoprevention, monthly sulfadoxine-pyrimethamine, daily trimethoprim-sulfamethoxazole or monthly dihydroartemisinin-piperaquine given from randomization to 24 months of age.. The primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrhoeal illness, or respiratory tract infection; prevalence of anaemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped.. During the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% [95% confidence interval (95% CI) 53-80, P < 0.001] for dihydroartemisinin-piperaquine, 49% (95% CI 23-66, P = 0.001) for trimethoprim-sulfamethoxazole and 9% for sulfadoxine-pyrimethamine (95% CI -35 to 38, P = 0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the dihydroartemisinin-piperaquine arm.. Monthly chemoprevention with dihydroartemisinin-piperaquine was well tolerated and associated with a significant reduction in malaria in young HIV-exposed children.

Topics: Antimalarials; Artemisinins; Chemoprevention; Child, Preschool; Cohort Studies; Drug Combinations; Female; Humans; Infant; Malaria; Male; Pyrimethamine; Quinolines; Sulfadoxine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking.. We conducted a prospective PK/PD study of piperaquine in 107 young children in Uganda. Samples were collected up to 28 days after 218 episodes of malaria treatment, which occurred during follow-up periods of up to 5 months. Malaria follow-up was conducted actively to day 28 and passively to day 63.. The median capillary piperaquine concentration on day 7 after treatment was 41.9 ng/mL. Low piperaquine concentrations were associated with an increased risk of recurrent malaria for up to 42 days, primarily in those receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In children not receiving TMP-SMX, low piperaquine concentrations were only modestly associated with an increased risk of recurrent malaria. However, for children receiving TMP-SMX, associations were strong and evident for all sampling days, with PQ concentrations of ≤ 27.3 ng/mL on day 7 associated with a greatly increased risk of recurrent malaria. Notably, of 132 cases of recurrent malaria, 119 had detectable piperaquine concentrations at the time of presentation with recurrent malaria.. These piperaquine PK/PD data represent the first in children <2 years of age. Piperaquine exposure on day 7 correlated with an increased risk of recurrent malaria after DP treatment in children receiving TMP-SMX prophylaxis. Interestingly, despite strong associations, infants remained at risk for malaria, even if they had residual levels of piperaquine.

Topics: Antimalarials; Artemisinins; Chemoprevention; Female; Follow-Up Studies; Humans; Infant; Malaria; Male; Plasma; Prospective Studies; Quinolines; Secondary Prevention; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp).. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count.. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ μ L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ μ L, 95% CI: -58.6, -8.8).. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Infant, Low Birth Weight; Malaria; Malawi; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/μL. However, this practice has not been evaluated in sub-Saharan Africa.. Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/μL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/μL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea.. At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/μL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001).. HIV-infected adults on ART with CD4 counts >200 cells/μL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. Clinical Trials Registration. NCT00119093.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chemoprevention; Diarrhea; Female; HIV Infections; Humans; Incidence; Malaria; Male; Risk Assessment; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Withholding Treatment

The World Health Organization guidelines recommend cotrimoxazole prophylactic treatment (CPT) for all HIV-exposed infants from age 6 weeks to the cessation of breastfeeding and the exclusion of HIV infection. There are limited data on the effects of CPT among this population of infants. We examined the effects of CPT on adverse health outcomes among HIV-exposed infants during the first 36 weeks of life using data from the Breastfeeding, Antiretrovirals and Nutrition study, a large clinical trial of antiretroviral drugs given to the mother or infant for the prevention of HIV transmission during breastfeeding.. For the analysis, we assigned a status of CPT-exposed to infants who were participating in the study after the CPT program started. We estimated unadjusted and adjusted hazard ratios for the effect of CPT status on time to incident malaria, severe illness or death, anemia, and weight-for-age Z score < -2.0. Participation in the study was limited to focus exclusively on HIV-exposed, uninfected infants.. The hazard ratio for the effect of CPT on incident malaria was 0.35 (95% confidence interval: 0.21, 0.57) during the first 10 weeks of CPT exposure and 0.93 (95% confidence interval: 0.67, 1.29) for the remaining 20 weeks. CPT was not associated with the other outcomes examined.. CPT offered temporary protection against malaria among HIV-exposed, uninfected infants. However, CPT offered no protection against anemia, low weight for age or the collapsed outcome of severe illness or death.

Topics: Anemia; Anti-Retroviral Agents; Antibiotic Prophylaxis; Antimalarials; Body Weight; Breast Feeding; Chi-Square Distribution; Female; HIV Infections; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Malaria; Mothers; Statistics, Nonparametric; Trimethoprim, Sulfamethoxazole Drug Combination

The impact of cotrimoxazole (CTX) on growth and/or anemia was investigated in 541 human immunodeficiency virus-infected, antiretroviral therapy-naive Zambian children enrolled in the Children with HIV Antibiotic Prophylaxis trial. Compared with children randomized to receive placebo, children randomized to receive CTX had slower decreases in weight-for-age (P=.04) and height-for-age (P=.01), and greater increase in hemoglobin level (P=.01). These findings argue for expanded early CTX use.

Topics: Adolescent; Anemia; Antimalarials; Body Height; Body Weight; Chemoprevention; Child; Child Development; Child, Preschool; Female; HIV Infections; Humans; Infant; Malaria; Male; Placebos; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.. Non-blinded randomised control trial. Tororo district, rural Uganda, an area of high malaria transmission intensity. 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age. Co-trimoxazole prophylaxis from enrollment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n = 185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old.. Incidence of malaria, calculated as the number of antimalarial treatments per person year.. The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P = 0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms.. Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800.

Topics: Antimalarials; Breast Feeding; Diarrhea, Infantile; Female; HIV Infections; HIV Seronegativity; Humans; Incidence; Infant; Malaria; Pregnancy; Pregnancy Complications, Infectious; Respiratory Tract Infections; Rural Health; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)-infected populations.. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines.. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; p = .08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; p < .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, <750 cells/mm(3)). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; p < .001).. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.

Topics: Amodiaquine; Anti-HIV Agents; Antimalarials; Artemisinins; Artesunate; Chemoprevention; Child; Child, Preschool; Drug Therapy, Combination; HIV Infections; Humans; Infant; Malaria; Neutropenia; Sesquiterpenes; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

In Malawi, trimethoprim-sulfamethoxazole (TS) is the recommended first-line treatment for children with Integrated Management of Childhood Illness dual classifications of malaria and pneumonia, and sulfadoxine-pyrimethyamine (SP) plus five days of treatment with erythromycin (SP plus E) is the recommended second-line treatment. Using a 14-day, modified World Health Organization protocol, children with dual IMCI classifications of malaria and pneumonia with Plasmodium falciparum parasitemia were randomized to receive TS or SP plus E. Clinical and parasitologic responses and gametocytemia prevalence were obtained. A total of 87.2% of children receiving TS and 80.0% receiving SP plus E reached adequate clinical and parasitologic responses (ACPRs) (P = 0.19). Severely malnourished children were less likely to achieve ACPRs than those better nourished (relative risk = 3.34, P = 0.03). Day 7 gametocyte prevalence was 55% and 64% among children receiving TS and SP plus E, respectively (P = 0.19). Thus, TS and SP plus E remain efficacious treatment of P. falciparum malaria in this setting. However, patient adherence and effectiveness of five days of treatment with TS is unknown.

Topics: Anti-Infective Agents; Child, Preschool; Drug Combinations; Erythromycin; Humans; Infant; Malaria; Malawi; Nutritional Status; Pneumonia, Bacterial; Pyrimethamine; Risk Factors; Sulfadoxine; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Treatment of malaria with sulfadoxine/pyrimethamine and of presumed bacterial infections with trimethoprim/sulfamethoxazole (cotrimoxazole) was assessed to see if either increases the carriage of cotrimoxazole-resistant Streptococcus pneumoniae in Malawian children. Children <5 years old treated with sulfadoxine/pyrimethamine, cotrimoxazole, or no antimicrobial agent were enrolled in a prospective observational study. Nasopharyngeal swabs were taken before treatment and 1 and 4 weeks later. Pneumococci were tested for antibiotic susceptibility by broth microdilution. In sulfadoxine/pyrimethamine-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 38.1% at the initial visit to 44.1% at the 4-week follow-up visit (P=.048). For cotrimoxazole-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 41.5% at the initial visit to 52% at the 1-week follow-up visit (P=.0017) and returned to 41.7% at the 4-week follow-up. Expanding use of sulfadoxine/pyrimethamine to treat chloroquine-resistant malaria may have implications for national pneumonia programs in developing countries where cotrimoxazole is widely used.

Topics: Anti-Bacterial Agents; Antimalarials; Carrier State; Child; Disease Susceptibility; Drug Resistance, Microbial; Female; Humans; Malaria; Malawi; Male; Prospective Studies; Pyrimethamine; Streptococcus pneumoniae; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sample. 60 microL supernatant was added to 60 microL mobile phase, modified with 50microL 1 M sodium hydroxide/mL. The mobile phase consisted of 20% acetonitrile and 80% phosphate buffer adjusted to pH 6.15. Using 125 microL of the sample, limits of quantitation were 0.1 microg/mL for TMP, 1.0 microg/mL for SMX, and 1.0 microg/mL for AcSMX. The precision of the method was 2% to 11% over the range of concentrations tested, 0.5-30 microg/mL for TMP, 5-300 microg/mL for SMX, and 2.5-150 microg/mL for AcSMX, respectively. No interference with other commonly used drugs was observed. The method is rapid, simple, specific, and sensitive enough for pharmacokinetic studies. The small amount of blood required makes it suitable for pediatric patients. The method was used to analyze samples from Tanzanian children aged 6-59 months participating in a cotrimoxazole (TMP/SMX)/chloroquine randomized trial for the treatment of uncomplicated malaria. Venous blood samples from 68 children were collected 2 hours after the first dose of TMP/SMX (4 mg/kg TMP/20 mg/kg SMX at two divided doses for 5 days) and again at treatment day 4. Individual variations in plasma concentrations of TMP, SMX, and AcSMX were considerable. The mean and SEM plasma concentrations (g/mL) of TMP, SMX, and AcSMX 2 hours after the first treatment dose were 2.0 +/- 1.0 (range 0.5-6), 53 +/- 22 (range 24-146), and 13.5 +/- 12 (range 0-65), respectively. On the fourth day the attained plasma concentrations were not significantly different from samples collected after the first dose.

Topics: Acetonitriles; Antimalarials; Child, Preschool; Chromatography, High Pressure Liquid; Drug Interactions; Humans; Infant; Malaria; Phosphates; Sensitivity and Specificity; Sodium Hydroxide; Tanzania; Trichloroacetic Acid; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy of co-trimoxazole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mg/kg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone.

Topics: Acute Disease; Animals; Child, Preschool; Drug Administration Schedule; Drug Evaluation; Fever; Humans; Infant; Lung Diseases, Parasitic; Malaria; Malawi; Plasmodium falciparum; Prevalence; Respiratory Tract Infections; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Two dosage schedules of co-trimoxazole, the standard antibacterial and a 2-day high-dose schedule, were compared with a standard course of chloroquine in the treatment of uncomplicated Plasmodium falciparum malaria. Parasites were cleared from the blood at similar rates, but pyrexia responded more slowly following the standard cotrimoxazole dose. No recrudescences were detected in those observed for up to 60 days after treatment.

Topics: Adolescent; Adult; Antimalarials; Child; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation; Female; Follow-Up Studies; Humans; Malaria; Male; Plasmodium falciparum; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Responses of parasitemia and fever in vivax malaria to standard doses of chloroquine and different dosage schedules of co-trimoxazole were compared in 165 children. Though both the drugs were effective, chloroquine was significantly faster in clearing parasitemia than all the dosage schedules of co-trimoxazole. No statistically significant difference was observed in rapidity of defervescence between chloroquine and the two high daily dosage regimens of co-trimoxazole. Gastrointestinal intolerance was persistently higher with chloroquine. Asymptomatic sulphonamide crystalluria was seen in a large number of cases receiving the two high daily dosage schedules of co-trimoxazole.

Topics: Administration, Oral; Child; Child, Preschool; Chloroquine; Clinical Trials as Topic; Drug Combinations; Humans; Infant; Malaria; Plasmodium vivax; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Malarial protozoa commonly infect both wild and captive lizards but the effects on the general health of these animals are not fully understood. We describe four clinical cases of Plasmodium infection in captive black and white tegus (Salvator merianae). The animals presented with lethargy, anorexia, dehydration and stomatitis. Plasmodium infection was identified in blood smears from all animals. Treatment with a sulphamethoxazole-trimethoprim combination resolved the infection and clinical improvement was observed within 21 days. This is the first report of successful treatment of clinical plasmodiid infection in captive tegus.

Topics: Animals; Animals, Zoo; Lizards; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Topics: Adolescent; Ambulatory Care; Amoxicillin; Anti-Bacterial Agents; Child; Child, Preschool; Disease Management; Endemic Diseases; Female; Fever; Gastroenteritis; Humans; Malaria; Malawi; Male; Musculoskeletal Pain; Prevalence; Respiratory Tract Infections; Sepsis; Soft Tissue Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Although WHO recommends cotrimoxazole (CTX) discontinuation among HIV patients who have undergone immune recovery and are living in areas of low prevalence of malaria, some countries including Uganda recommend CTX discontinuation despite having a high malaria burden. We estimated the prevalence and factors associated with malaria parasitaemia among adults living with HIV attending hospital outpatient clinic before and after discontinuation of CTX prophylaxis.. Between March and April 2019, 599 participants aged 18 years and above, and attending Kitgum hospital HIV clinic in Uganda were enrolled in a cross study. A standardized questionnaire was administered and physical examination conducted. A finger-prick blood sample was collected for identification of malaria parasites by microscopy. The prevalence of parasitaemia was estimated and compared among participants on and those who had discontinued CTX prophylaxis, and factors associated with malaria parasitaemia assessed.. Of the enrolled participants, 27 (4.5%) had malaria parasites and 452 (75.5%) had stopped CTX prophylaxis. Prevalence of malaria parasitaemia was significantly higher in participants who had stopped CTX prophylaxis (5.5% versus 1.4% p = 0.03) and increased with increasing duration since the discontinuation of prophylaxis. Compared to participants taking CTX, those who discontinued prophylaxis for 3-5 months and >5 months were more likely to have malaria parasites (adjusted prevalence ratio (aPR) = 1.64, 95% CI 0.37-7.29, p = 0.51, and aPR = 6.06, 95% CI 1.34-27.3, P = 0.02). Low CD4 count (< 250cells/mm3) was also associated with increased risk of having parasites (aPR = 4.31, 95% CI 2.13-8.73, p <0.001).. People from malaria endemic settings living with HIV have a higher prevalence of malaria parasitaemia following discontinuation of CTX compared to those still on prophylaxis. The risk increased with increasing duration since discontinuation of the prophylaxis. HIV patients should not discontinue CTX prophylaxis in areas of Uganda where the burden of malaria remains high. Other proven malaria control interventions may also be encouraged in HIV patients following discontinuation of CTX prophylaxis.

Topics: Adult; Antimalarials; Cross-Sectional Studies; Female; HIV Infections; Humans; Malaria; Male; Middle Aged; Parasitemia; Plasmodium; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

HIV and malaria geographically overlap. Trimethoprim-sulfamethoxazole (TMP-SMX) is a drug widely used in HIV-exposed uninfected and infected children in malaria-endemic areas, and is known to have antimalarial effects. Further study in terms of antimalarial impact and effect on development of malaria-specific immunity is therefore essential. Using rodent malaria models, we previously showed that repeated Plasmodium exposure during TMP-SMX administration, or chemoprophylaxis vaccination (CVac), induces CD8 T-cell-dependent preerythrocytic immunity. However, humoral immune responses have been shown to be important in models of preerythrocytic immunity. Herein, we demonstrate that antibody-mediated responses contribute to protective immunity induced by CVac immune sera using TMP-SMX in models of homologous, but not heterologous, parasite species. Clinical studies must account for potential anti-Plasmodium antibody induced during TMP-SMX prophylaxis.

Topics: Animals; Female; Immunization; Malaria; Mice; Mice, Inbred BALB C; Plasmodium berghei; Plasmodium yoelii; Sporozoites; Trimethoprim, Sulfamethoxazole Drug Combination

This observational study recorded the malaria and sickle cell disease (SCD) profile of people living with HIV/AIDS (PLHA) and determined whether prophylactic co-trimoxazole (CTX) and the haemoglobin S (Hb S) allele influenced malaria episodes.. Sickling status, malaria episodes, and HIV type, as well as other data, were extracted retrospectively from the clinical records of 1001 patients attending the antiretroviral therapy clinic at Ridge Regional Hospital in Accra, Ghana between 2010 and 2015. Finger-prick capillary blood of returning patients (n=501) was tested for the haemoglobin (Hb) level and malaria, after information on malaria prevention methods was obtained through the administration of a questionnaire.. The use of insecticide-treated mosquito nets was low (22.8%). CTX prophylaxis showed no significant influence on the overall number of malaria episodes from 2010 to 2015; however, it did show a statistically significant relationship (p=0.026) with the time elapsed since the last malaria episode. Even though 19% of participants possessed Hb S, it had no influence on malaria episodes.. Hb S did not influence malaria in PLHA. Further studies in Hb SS and Hb SC are needed, as there are suggestions of increased frequency and severity of malaria. The impact of CTX prophylaxis on this cohort will be insightful.

Topics: Adult; AIDS-Related Opportunistic Infections; Anemia, Sickle Cell; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Female; Ghana; HIV Infections; Humans; Malaria; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In sub-Saharan Africa, HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes. In Kenya, policy states women should be tested for all four conditions (malaria only if febrile) at first antenatal care (ANC) visit. In practice, while HIV screening is conducted, coverage of screening for the others is suboptimal and early pregnancy management of illnesses is compromised. This is particularly evident at rural dispensaries that lack laboratories and have parallel programmes for HIV, reproductive health and malaria, resulting in fractured and inadequate care for women.. A longitudinal eight-month implementation study integrating point-of-care diagnostic tests for the four conditions into routine ANC was conducted in seven purposively selected dispensaries in western Kenya. Testing proficiency of healthcare workers was observed at initial training and at three monthly intervals thereafter. Adoption of testing was compared using ANC register data 8.5 months before and eight months during the intervention. Fidelity to clinical management guidelines was determined by client exit interviews with success defined as ≥90% adherence.. For first ANC visits at baseline (n = 529), testing rates were unavailable for malaria, low for syphilis (4.3%) and anaemia (27.8%), and near universal for HIV (99%). During intervention, over 95% of first attendees (n = 586) completed four tests and of those tested positive, 70.6% received penicillin or erythromycin for syphilis, 65.5% and 48.3% received cotrimoxazole and antiretrovirals respectively for HIV, and 76.4% received artemether/lumefantrine, quinine or dihydroartemisinin-piperaquine correctly for malaria. Iron and folic supplements were given to nearly 90% of women but often at incorrect doses.. Integrating point-of-care testing into ANC at dispensaries with established HIV testing programmes resulted in a significant increase in testing rates, without disturbing HIV testing rates. While more cases were detected and treated, treatment fidelity still requires strengthening and an integrated monitoring and evaluation system needs to be established.

Topics: Adult; Anemia; Anti-Bacterial Agents; Anti-HIV Agents; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Dietary Supplements; Erythromycin; Female; Folic Acid; Guideline Adherence; Health Personnel; HIV Infections; Humans; Iron, Dietary; Kenya; Laboratory Proficiency Testing; Longitudinal Studies; Malaria; Penicillins; Point-of-Care Testing; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Complications, Infectious; Prenatal Care; Quinine; Quinolines; Syphilis; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria.. To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement.. This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables.. Of the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9).. The study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and ART. Six hematological indices differed significantly between the two groups. Malaria and HIV co-infection significantly reduces CD4 count. In general, to achieve better management of all HIV patients in this setting, diagnosing malaria, prompt antiretroviral therapy, monitoring CD4 and some hematology indices on regular basis is critical.

Topics: Adult; Anti-Retroviral Agents; Antimalarials; CD4 Lymphocyte Count; Coinfection; Cross-Sectional Studies; Female; HIV; HIV Infections; Humans; Malaria; Male; Middle Aged; Nigeria; Plasmodium; Plasmodium falciparum; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV)-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear.. We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of (1) CPT and (2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6 to 36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEIs) at 8 weeks of age (n = 1984) were included when CPT was the exposure. A subset of HEIs (n = 471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity.. CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio [HR], 0.64 [95% confidence interval {CI}, .60-.69]) and a 41% reduction in diarrheal morbidity (HR, 0.59 [95% CI, .54-.65]). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR, 1.40 [95% CI, 1.13-1.74]) and a 50% increase in diarrheal morbidity (HR, 1.50 [95% CI, 1.09-2.06]), after adjusting for CPT.. CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings.

Topics: Adolescent; Adult; Antimalarials; Asymptomatic Infections; Female; HIV Infections; Humans; Infant; Malaria; Malawi; Male; Middle Aged; Morbidity; Parasitemia; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

We describe two Malawian adults on successful antiretroviral therapy who experienced frequent malaria episodes after stopping cotrimoxazole prophylaxis. We argue that, in addition to stopping cotrimoxazole, diminished malaria immunity and drug interactions between efavirenz and artemether-lumefantrine may have played a causative role in the recurrent malaria our patients experienced.

Topics: Adult; Anti-HIV Agents; Antimalarials; Antiretroviral Therapy, Highly Active; Drug Interactions; Female; HIV Infections; Humans; Malaria; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm. Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm. Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region.

Topics: Adult; Africa, Western; Anti-HIV Agents; Antimalarials; CD4 Lymphocyte Count; Cohort Studies; Female; HIV Infections; HIV-1; Humans; Incidence; Malaria; Male; Multivariate Analysis; Proportional Hazards Models; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Given the potential of cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV-exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with antiretroviral agents that have overlapping toxicity profiles.. We used data from the Breastfeeding, Antiretrovirals, and Nutrition study (2004-2010) to evaluate the association of CPT and antiretrovirals with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2006 HEU infants in Lilongwe, Malawi. Hazards of severe outcomes (anemia, neutropenia, and elevated alanine aminotransferase), as defined by the National Institutes of Health, were compared using Cox regression models, according to time-varying CPT (implemented June 2006), antiretroviral treatment arm (maternal triple antiretroviral, infant nevirapine, or none during 6 months of breastfeeding), and their interaction. The effects of these treatments on hemoglobin, neutrophil, and alanine aminotransferase levels were assessed using linear mixed models.. In Cox models, CPT was associated with an increase in severe neutropenia [hazard ratio 1.97 (1.01, 3.86)] and a decrease in severe anemia (hazard ratio 0.65 (0.48, 0.88)]. Interactions between CPT and antiretroviral treatment were not significant. By 36 weeks, there was a significant association of CPT with increased hemoglobin levels regardless of antiretroviral drug exposure.. In addition to expected associations with increased hazard of severe neutropenia and decreased neutrophil count, CPT was associated with reduced hazard of severe anemia and higher infant blood hemoglobin. This provides further support for CPT use in HEU infants in malaria-endemic resource-limited settings where anemia is prevalent.

Topics: Adolescent; Adult; Alanine Transaminase; Anti-Bacterial Agents; Anti-Retroviral Agents; Antimalarials; Bacterial Infections; Chemoprevention; Drug Interactions; Female; Hemoglobins; HIV Infections; Humans; Infant; Infant, Newborn; Leukocyte Count; Malaria; Malawi; Male; Pregnancy; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed.. A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX.. Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy.. In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

Topics: Africa South of the Sahara; Antimalarials; Coinfection; Cost-Benefit Analysis; Drug Combinations; Female; HIV Infections; Humans; Malaria; Models, Theoretical; Pregnancy; Pyrimethamine; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009-2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.

Topics: Antimalarials; Asymptomatic Infections; Case-Control Studies; Child; Child, Preschool; Cluster Analysis; Humans; Incidence; Infant; Longitudinal Studies; Malaria; Mali; Plasmodium falciparum; Seasons; Spatio-Temporal Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8

Topics: Animals; Antimalarials; CD8-Positive T-Lymphocytes; HIV Infections; Immunization; Interferon-gamma; Life Cycle Stages; Malaria; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Opportunistic Infections; Plasmodium; Sporozoites; Trimethoprim, Sulfamethoxazole Drug Combination

Raquel Gonzalez and colleagues highlight an urgent need to evaluate antimalarials that can be safely administered to HIV-infected pregnant women on antiretroviral treatment and cotrimoxazole prophylaxis.

Topics: Africa; Anti-HIV Agents; Antimalarials; Female; HIV Infections; Humans; Malaria; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination

Coinfection with malaria and HIV is common in Sub-Saharan Africa. In the advent of a decline in the global incidence of malaria, it is important to generate updated data on the burden of malaria in people living with HIV (PLWHIV). This study was designed to determine the prevalence of malaria in PLWHIV in Yaounde, Cameroon, as well determine the association between CD4 (+) T cell count and malaria in the study population.. In a cross sectional study performed between April 2015 and June 2016, 355 PLWHIV were enrolled and blood samples were collected for analysis. Complete blood count was performed using an automated haematology analyser (Mindray®, BC-2800) and CD4 (+) T cell count was performed using a flow cytometer (BD FASCount™). Giemsa-stained blood films were examined to detect malaria parasite. The Pearson's chi-square, student's T-test, ANOVA, and correlation analysis were all performed as part of the statistical analyses.. The prevalence of malaria observed in the study was 7.3 % (95 % CI: 4.8-10.6). No significant association was observed between the prevalence of malaria and age or gender. The prevalence of malaria was higher in participants who were not sleeping in insecticide treated bed nets, ITNs (p < 0.001); and in participants who were not on cotrimoxazole prophylaxis (p = 0.002). The prevalence of malaria (p < 0.001) and malaria parasite density (p = 0.005) were observed to be progressively higher in participants with CD4 (+) T cell count below 200cells/μl. Furthermore, the mean CD4 (+) T cell count was observed to be lower in participants coinfected with malaria compared to non-coinfected participants (323.5 vs 517.7) (p < 0.001). In this study, a negative correlation was observed between malaria parasite density and CD4 (+) T cell count (p = 0.019).. A low prevalence of malaria was observed in the study population. Some of the factors accounting for the low prevalence of malaria in this study population may include the health seeking habit of PLWHIV, the use of cotrimoxazole based chemoprophylaxis, and their cautious use of ITNs.

Topics: Adult; Antimalarials; Cameroon; Coinfection; Cross-Sectional Studies; Female; HIV Infections; Humans; Incidence; Insecticide-Treated Bednets; Malaria; Male; Middle Aged; Pre-Exposure Prophylaxis; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

Despite recent progress, pneumonia remains the largest infectious killer of children globally. This paper describes outcomes of not treating community-diagnosed fast-breathing pneumonia on patient recovery.. We conducted an exploratory subanalysis of an observational prospective cohort study in Malawi. We recruited children (2-59 months) diagnosed by community health workers with fast-breathing pneumonia using WHO integrated community case management (iCCM) guidelines. Children were followed at days 5 and 14 with a clinical assessment of recovery. We conducted bivariate and multivariable logistic regression for the association between treatment of fast-breathing pneumonia and recovery, adjusting for potential confounders.. We followed up 847 children, of whom 78 (9%) had not been given antibiotics (non-treatment). Non-treatment cases had higher baseline rates of diarrhoea, non-severe hypoxaemia and fever. Non-recovery (persistence or worsening of symptoms) was 13% and 23% at day 5 in those who did receive and those who did not receive co-trimoxazole. Non-recovery, when defined as worsening of symptoms only, at day 5 was 7% in treatment and 10% in non-treatment cases. For both definitions, combined co-trimoxazole and lumefantrine-artemether (LA) treatment trended towards protection (adjusted OR (aOR) 0.28; 95% CI 0.12 to 0.68/aOR 0.29; 95% CI 0.08 to 1.01).. We found that children who did not receive co-trimoxazole treatment had worse clinical outcomes; malaria co-diagnosis and treatment also play a significant role in non-recovery. Further research into non-treatment of fast-breathing pneumonia, using a pragmatic approach with consideration for malaria co-diagnosis and HIV status is needed to guide refinement of community treatment algorithms in this region.

Topics: Anti-Bacterial Agents; Child, Preschool; Coinfection; Community Health Services; Female; Humans; Infant; Logistic Models; Malaria; Malawi; Male; Multivariate Analysis; Pneumonia; Prospective Studies; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

Cotrimoxazole preventive therapy (CPT) is recommended for all human immunodeficiency virus (HIV)-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown.. We conducted an observational cohort study using data and dried blood spots (DBSs) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence 1 year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBSs at 12, 24, and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections.. CPT was associated with a 70% (95% confidence interval, 53%-81%) relative reduction in the risk of asymptomatic infection between 6 and 36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics.. CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits.

Topics: Antimalarials; Asymptomatic Infections; Drug Resistance; Female; HIV Infections; Humans; Infant; Malaria; Malawi; Male; Parasitemia; Plasmodium falciparum; Random Allocation; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole prophylaxis has an antimalarial effect which could have an additional protective effect against malaria in HIV-infected children on antiretroviral therapy (ART). We measured the incidence and associated factors of malaria in HIV-infected children on ART and/or cotrimoxazole in Abidjan, Côte d'Ivoire.. All HIV-infected children <16 years, followed-up in the IeDEA West-African paediatric cohort (pWADA) in Abidjan, were prospectively included from May to August 2012, the rainy season. Children presenting signs suggesting malaria had a thick blood smear and were classified as confirmed or probable malaria. We calculated incidence density rates (IR) per 100 child-years (CY). Risk factors were assessed using a Poisson regression model.. Overall, 1117 children were included, of whom 89 % were ART-treated and 67 % received cotrimoxazole. Overall, there were 51 malaria events occurring in 48 children: 28 confirmed and 23 probable; 94 % were uncomplicated malaria. The overall IR of malaria (confirmed and probable) was 18.3/100 CY (95 % CI: 13.3-23.4), varying from 4.2/100 CY (95 % CI: 1.1-7.3) in children on ART and cotrimoxazole to 57.3/100 CY (95 % CI: 7.1-107.6) for those receiving no treatment at all. In univariate analysis, age < 5 years was significantly associated with a 2-fold IR of malaria compared to age >10 years (incidence rate ratio [IRR] = 2.18, 95 % CI: 1.04-4.58). Adjusted for severe immunodeficiency, cotrimoxazole reduced significantly the IR of first malarial episode (adjusted IRR [aIRR] = 0.13, 95 % CI: 0.02-0.69 and aIRR = 0.05, 95 % CI:0.02-0.18 in those off and on ART respectively). Severe immunodeficiency increased significantly the malaria IR (aIRR = 4.03, 95 % CI: 1.55-10.47). When considering the IR of confirmed malaria only, this varied from 2.4/100 CY (95 % CI: 0.0-4.8) in children on ART and cotrimoxazole to 34.4/100 CY (95 % CI: 0.0-73.3) for those receiving no treatment at all. In adjusted analyses, the IR of malaria in children on both cotrimoxazole and ART was significantly reduced (aIRR = 0.05, 95 % CI: 0.01-0.24) compared to those receiving no treatment at all.. Cotrimoxazole prophylaxis was strongly protective against the incidence of malaria when associated with ART in HIV-infected children. Thus, these drugs should be provided as widely and durably as possible in all HIV-infected children <5 years of age.

Topics: Anti-HIV Agents; Antimalarials; Child; Child, Preschool; Cohort Studies; Cote d'Ivoire; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Malaria; Male; Prospective Studies; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Malaria and HIV/AIDS constitute major public health problems in Ethiopia, but the burden associated with malaria-HIV co-infection has not been well documented. In this study, the burden of malaria among HIV positive and HIV negative adult outpatients attending health facilities in Oromia National Regional State, Ethiopia was investigated.. A comparative cross-sectional study among HIV-positive patients having routine follow-up visits at HIV care and treatment clinics and HIV-seronegative patients attending the general medical outpatient departments in 12 health facilities during the peak malaria transmission season was conducted from September to November, 2011. A total of 3638 patients (1819 from each group) were enrolled in the study. Provider initiated testing and counseling of HIV was performed for 1831 medical outpatients out of whom 1819 were negative and enrolled into the study. Malaria blood microscopy and hemoglobin testing were performed for all 3638 patients. Data was analyzed using descriptive statistics, Chi square test and multivariate logistic regression.. Of the 3638 patients enrolled in the study, malaria parasitaemia was detected in 156 (4.3%); malaria parasitaemia prevalence was 0.7% (13/1819) among HIV-seropositive patients and 7.9% (143/1819) among HIV-seronegative patients. Among HIV-seropositive individuals 65.4% slept under a mosquito bed net the night before data collection, compared to 59.4% of HIV-seronegative individuals. A significantly higher proportion of HIV-seropositive malaria-negative patients were on co-trimoxazole (CTX) prophylaxis as compared to HIV-malaria co-infected patients: 82% (1481/1806) versus 46% (6/13) (P = 0.001). HIV and malaria co-infected patients were less likely to have the classical symptoms of malaria (fever, chills and headache) compared to the HIV-seronegative and malaria positive counterparts. Multivariate logistic regression showed that HIV-seropositive patients who come for routine follow up were less likely to be infected by malaria (OR = 0.23, 95% CI = 0.09-0.74).. The study documented lower malaria prevalence among the HIV-seropositive attendants who come for routine follow up. Clinical symptoms of malaria were more pronounced among HIV-seronegative than HIV-seropositive patients. This study also re-affirmed the importance of co-trimoxazole in preventing malaria symptoms and parasitaemia among HIV-positive patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Chemoprevention; Coinfection; Cross-Sectional Studies; Ethiopia; Female; HIV Infections; Humans; Malaria; Male; Middle Aged; Outpatients; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy.. This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin <11 g/dl). Data were collected on the adherence to co-trimoxazole prophylaxis and other risk factors for malaria infection and anaemia. Pearson chi-square test, Fischer's exact test and multivariate logistic regression were used in the statistical analysis.. This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95% CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95% CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy.. The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women.

Topics: Adult; Anemia; Anti-Infective Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; Hemoglobins; HIV Infections; Humans; Malaria; Pregnancy; Prevalence; Tanzania; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Medicines are kept in households Worldwide for first aid, treatment of chronic or acute disease conditions. This promotes inappropriate use of medicines and hence the associated risks. The study explored the factors which predict availability and utilization of medicines in households of Northern Uganda.. A cross sectional survey of 892 households was performed from November-to-December 2012. Five data collectors administered the questionnaires, respondents were requested to bring out any medicines present in their households. Demographic characteristics, drug name, quantity, source, formulation, legibility of drug labels and reasons why the medicines were being kept at home was collected. Data was analyzed using STATA 12.0 at 95% level of significance.. Of the households visited, 35.1% (313/892) had drugs. Paracetamol (11.8%), coartem (11.3%), cotrimoxazole (10%), amoxicillin (9.2%) and metronidazole (8.2%) were the major medicines found. Antibacterial drugs were the most commonly (40.1%) kept type of drugs. The medicines present in households were for on-going treatment (48%); 'leftover' (30.5%) and anticipated future use (21.6%). Symptoms of malaria (34.1%) were common in households which had drugs. The medicines kept in homes were mainly from the private sector 60.5% (497/821). The rate of home drug storage was higher 85.3% (267/313) amongst the educated individuals. There was high prevalence 76% (238/313) of self-medication among respondents in households which stored drugs. The average number of medicines in each household was 6 ± 5 with majority (68.1%) having between 1-10 drugs. Previous successful treatment (OR: 1.3; 95% CI: 0.95-1.77), regular income (OR: 1.8; 95% CI: 1.2-2.6) and sex (OR: 0.63; 95% CI: 0.5-0.9) predicted storage of medicines in households in northern Uganda.. Over a third of households in Northern Uganda store medicines with antibacterial agents being the most common. Self-medication is common among individuals in households which keep drugs. Past successful treatment, regular income and sex predict community home drug storage.

Topics: Acetaminophen; Adolescent; Adult; Anti-Infective Agents; Artemether, Lumefantrine Drug Combination; Artemisinins; Cross-Sectional Studies; Data Collection; Drug Combinations; Drug Storage; Ethanolamines; Family Characteristics; Female; Fluorenes; Humans; Malaria; Male; Metronidazole; Middle Aged; Self Medication; Socioeconomic Factors; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Young Adult

To document the prevalence of malaria parasitaemia among the HIV infected febrile children in a malaria endemic area.. A cross-sectional study.. An ambulatory paediatric HIV clinic in Western Kenya, between November 2011 and December 2012.. A total of 245 febrile HIV infected children aged less than 14 years attending the HIV clinic in the Webuye level IV hospital were included in the study. A systematic sampling method was used.. A blood sample was taken for malaria parasite testing. Presence or absence of malaria parasites was documented. Clinical and socio-demographic characteristics of the participants were also recorded.. A total of 245 participants were recruited mean age being 5.53 years. Malaria prevalence was 81.9%. Most participants (97%) were on cotrimoxazole prophylaxis. Some of the factors found to be positively associated with malaria parasitaemia were; male sex, care taker category (parent), WHO stage 3 and 4 of HIV disease, and a high absolute CD4 count. However, only the caretaker association was statistically significant.. The frequency of malaria parasitaemia among febrile HIV infected children is still high regardless of the high cotrimoxazole prophylaxis uptake. It is also noted that there is a shift in the age group of fever among children toward the older age group. This implies that policies may need to be relooked at to include the older age group in the aggressive malaria prevention measures to avoid losing on the already made gains.

Topics: Antimalarials; CD4 Lymphocyte Count; Child; Child, Preschool; Comorbidity; Cross-Sectional Studies; Endemic Diseases; Female; Fever; HIV Infections; Humans; Infant; Malaria; Male; Parasitemia; Prevalence; Standard of Care; Trimethoprim, Sulfamethoxazole Drug Combination

Although nonnucleoside reverse transcriptase inhibitors (NNRTIs) are usually part of first-line treatment regimens for human immunodeficiency virus (HIV), their activity on Plasmodium liver stages remains unexplored. Additionally, trimethoprim-sulfamethoxazole (TMP-SMX), used for opportunistic infection prophylaxis in HIV-exposed infants and HIV-infected patients, reduces clinical episodes of malaria; however, TMP-SMX effect on Plasmodium liver stages requires further study.. We characterized NNRTI and TMP-SMX effects on Plasmodium liver stages in vivo using Plasmodium yoelii. On the basis of these results, we conducted in vitro studies assessing TMP-SMX effects on the rodent parasites P. yoelii and Plasmodium berghei and on the human malaria parasite Plasmodium falciparum.. Our data showed NNRTI treatment modestly reduced P. yoelii liver stage parasite burden and minimally extended prepatent period. TMP-SMX administration significantly reduced liver stage parasite burden, preventing development of patent parasitemia in vivo. TMP-SMX inhibited development of rodent and P. falciparum liver stage parasites in vitro.. NNRTIs modestly affect liver stage Plasmodium parasites, whereas TMP-SMX prevents patent parasitemia. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Understanding HIV drug effects on Plasmodium liver stages will aid in optimizing treatment regimens for HIV-exposed and HIV-infected infected patients in malaria-endemic areas.

Topics: Animals; Antimalarials; Female; Humans; Liver; Malaria; Mice; Parasitemia; Plasmodium; Reverse Transcriptase Inhibitors; Species Specificity; Trimethoprim, Sulfamethoxazole Drug Combination

Effectiveness of cotrimoxazole (CTX) compared with sulfadoxine-pyrimethamine (SP) intermittent-preventive-therapy (IPTp) for malaria in HIV-infected pregnant women is unknown. We examined effectiveness of CTX with or without SP-IPTp versus SP-IPTp at reducing malaria parasitemia and anemia.. From 2005 to 2009, we conducted a cross-sectional study of HIV-infected pregnant women at Thyolo Hospital, Malawi. Blood was tested for malaria parasitemia and anemia (hemoglobin<11 g/dl). Data were collected on use of anti-malaria interventions and other risk factors. CTX prophylaxis policy for HIV-infected pregnant women was introduced in 2007, but implementation problems resulted in some women receiving both CTX and SP-IPTp.. We enrolled 1,142 women, of whom 1,121 had data on CTX and/or SP-IPTp intake. Of these, 49.7%, 29.8%, and 15.4% reported taking SP-IPTp only, CTX only and SP-IPTp plus CTX, respectively. Compared with women taking SP-IPTp, those taking SP-IPTp plus CTX and CTX were less likely to have malaria parasitemia (OR, [95%CI]: 0.09, [0.01-0.66] and 0.43, [0.19-0.97], respectively) or anemia (PR, [95% CI]: 0.67, [0.54-0.83] and 0.72, [0.61-0.83], respectively).. In HIV-infected pregnant women, daily CTX was associated with reduced malaria parasitemia and anemia compared with SP-IPTp. CTX plus SP-IPTp was associated with further reduction in malaria parasitemia but toxicity was not fully assessed.

Topics: Adolescent; Adult; Anemia; Antimalarials; Chemoprevention; Cross-Sectional Studies; Drug Combinations; Female; HIV Infections; Humans; Malaria; Malawi; Middle Aged; Parasitemia; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Pyrimethamine; Sulfadoxine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Malaria and Tuberculosis (TB) are important causes of morbidity and mortality in Africa. Malaria prevention reduces mortality among HIV patients, pregnant women and children, but its role in TB patients is not clear. In the TB National Reference Center in Guinea-Bissau, admitted patients are in severe clinical conditions and mortality during the rainy season is high. We performed a three-step malaria prevention program to reduce mortality in TB patients during the rainy season.. Since 2005 Permethrin treated bed nets were given to every patient. Since 2006 environmental prevention with permethrin derivates was performed both indoor and outdoor during the rainy season. In 2007 cotrimoxazole prophylaxis was added during the rainy season. Care was without charge; health education on malaria prevention was performed weekly. Primary outcomes were death, discharge, drop-out.. 427, 346, 549 patients were admitted in 2005, 2006, 2007, respectively. Mortality dropped from 26.46% in 2005 to 18.76% in 2007 (p-value 0.003), due to the significant reduction in rainy season mortality (death/discharge ratio: 0.79, 0.55 and 0.26 in 2005, 2006 and 2007 respectively; p-value 0.001) while dry season mortality remained constant (0.39, 0.37 and 0.32; p-value 0.647). Costs of malaria prevention were limited: 2€/person. No drop-outs were observed. Health education attendance was 96-99%.. Malaria prevention in African tertiary care hospitals seems feasible with limited costs. Vector control, personal protection and cotrimoxazole prophylaxis seem to reduce mortality in severely ill TB patients. Prospective randomized trials are needed to confirm our findings in similar settings.

Topics: Adolescent; Adult; Animals; Antimalarials; Chemoprevention; Female; Guinea-Bissau; Hospitals; Humans; Insecticide-Treated Bednets; Insecticides; Malaria; Male; Middle Aged; Mosquito Control; Permethrin; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Young Adult

Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV).. Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect Plasmodium falciparum antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months.. Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic P. falciparum antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months.. In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. falciparum antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.

Topics: Adult; Anti-HIV Agents; Antigens, Protozoan; Antimalarials; Antiretroviral Therapy, Highly Active; Chemoprevention; Cohort Studies; Cross-Sectional Studies; Female; HIV Infections; Humans; Malaria; Male; Plasmodium falciparum; Prevalence; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Urban Population

We report a case of apparent malaria infection presented with a syndrome of painless, generalized lymphadenopathy without granulomas shortly after exposure to fresh water in rural West Africa. Residual infection with Massilia timonae was diagnosed and successfully treated with co-trimoxazole.

Topics: Anti-Infective Agents; Antimalarials; Bacterial Infections; Belgium; Fever of Unknown Origin; Humans; Lymphatic Diseases; Malaria; Male; Middle Aged; Nigeria; Oxalobacteraceae; Travel; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa South of the Sahara; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Bacterial Infections; CD4 Lymphocyte Count; Drug Therapy, Combination; HIV Infections; Humans; Malaria; Mycoses; Protozoan Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Opportunistic infections are the leading cause of mortality among HIV-infected people. Several simple interventions prevent illness, prolong life, or prevent HIV transmission from HIV-infected people in Africa. These include: cotrimoxazole prophylaxis; insecticide-treated bed nets; supplies for household water treatment and safe storage; materials promoting family voluntary counselling and testing (VCT); and condoms. We provided these interventions to adults and children with HIV who were members of the AIDS Support Organization in Uganda. To evaluate use of this basic care and prevention package, we surveyed a representative sample of 112 clients of TASO in their homes. Among respondents, 95% reported taking cotrimoxazole everyday, 89% said they had slept under a bednet the night before, 65% reported current treatment of household drinking water, 89% of sexually active respondents reported using condoms, and 96% reported family use of VCT. Household observations verified that use of cotrimoxazole, bednets, and water treatment products were consistent with reported use. This evaluation suggests successful distribution and use of basic care and prevention services at an AIDS organization in Uganda.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bedding and Linens; Condoms; Counseling; Delivery of Health Care; Female; Humans; Insecticides; Malaria; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Water Purification

Topics: Adult; Antimalarials; Antiretroviral Therapy, Highly Active; Bedding and Linens; Child; Cost-Benefit Analysis; HIV Infections; Home Care Services; Humans; Insecticides; Malaria; Rural Health Services; Rural Population; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Chemoprevention; Humans; Malaria; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

Studies in developed countries have shown highly active antiretroviral therapy (HAART) decreases incidence of severe opportunistic diseases (ODs) in HIV-infected patients beyond that which is expected from changes in CD4+ T-cell count.. To estimate the independent impact of HAART on reducing ODs and mortality in Côte d'Ivoire.. Within two longitudinal studies of HIV-infected adults (1996-2003), we identified time on 'cotrimoxazole alone' and 'HAART plus cotrimoxazole' WHO stage 3-4 defining events and severe malaria were divided into those preventable and not preventable with cotrimoxazole. Incidence of ODs by CD4 count stratum was estimated using incidence density analysis. CD4+ T-cell count at time of OD was estimated using linear interpolation. Using Poisson regression, we estimated the effect of HAART on OD incidence and mortality by CD4 count stratum.. Totals of 446 and 135 adults were followed during 6,216 and 3,412 person-months in the cotrimoxazole alone and HAART plus cotrimoxazole periods, respectively. There was a CD4+ T-cell-independent risk reduction for ODs and mortality during the HAART plus cotrimoxazole period compared with cotrimoxazole alone, which varied by time on HAART, CD4 count stratum and OD type. It was mainly seen after 6 months on HAART and for ODs not preventable by cotrimoxazole. The HAART effect differed significantly by CD4 count stratum (P=0.02), but was significant in all strata after 6 months on HAART.. In these sub-Saharan African adults, HAART initiation reduced ODs and mortality beyond that which was expected through the HAART-induced CD4+ T-cell increase. Further studies should examine practical implications of this independent 'HAART effect' on clinical outcomes in patients on HAART.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Bacterial Infections; CD4 Lymphocyte Count; Cote d'Ivoire; Drug Therapy, Combination; HIV Infections; Humans; Incidence; Malaria; Mycoses; Poisson Distribution; Severity of Illness Index; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis and insecticide-treated bednets reduce malaria risk among HIV-infected adults. The efficacy of TMP/SMX may be diminished where antifolate resistance to malaria is high. We evaluated the efficacy of these interventions for malaria prevention among Ugandan children.. We concurrently followed 300 HIV-infected children aged 1-10 years and a community-based cohort of 561 healthy children aged 1-11 years over 11 months in Kampala, Uganda. The HIV-infected children received TMP/SMX prophylaxis and insecticide treated bednets. In the community cohort, insecticide-treated bednets were introduced during the observation period. Children from both cohorts were followed using a standardized protocol to measure the incidence of malaria.. Only nine episodes of malaria were diagnosed among HIV-infected children (incidence = 0.07/person-year) in comparison with 440 episodes among children from the community (incidence = 0.90/person-year; P < 0.0001). The use of insecticide-treated bednets was associated with a 43% reduction in malaria incidence (P < 0.001), and a combination of TMP/SMX and use of insecticide-treated bednets with a 97% reduction in malaria incidence (P < 0.001). The prevalence of five mutations associated with antifolate resistance was high among malaria cases detected in both the HIV (100%) and community cohorts (75%). Malaria accounted for only 4% of febrile episodes in the HIV cohort in comparison with 33% in the community-based cohort (P < 0.0001).. In a malaria endemic area with a high level of molecular markers of antifolate resistance, the combined use of TMP/SMX prophylaxis and insecticide-treated bednets was associated with a dramatic reduction in malaria incidence among HIV-infected children.

Topics: Antimalarials; Bedding and Linens; Case-Control Studies; Child; Child, Preschool; Female; HIV Infections; Humans; Incidence; Infant; Insecticides; Longitudinal Studies; Malaria; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets.. In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season.. 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056).. A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Topics: Adult; Anti-Retroviral Agents; Antimalarials; Bedding and Linens; Female; HIV Infections; HIV-1; Humans; Incidence; Insecticides; Malaria; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antimalarials; Child; Child, Preschool; Drug Combinations; Drug Eruptions; Female; Humans; Infant; Infant, Newborn; Malaria; Malawi; Male; Middle Aged; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Severity of Illness Index; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination

The threat for opportunistic diseases in HIV-infected adults in sub-Saharan Africa is characterized by a higher frequency of tuberculosis and invasive bacterial diseases than in Europe and by the presence of malaria. Since these three infections may occur early after the onset of immuno-deficiency, HIV-infected patients with less than 200 CD4/mm3 are more likely to develop an infectious episode with severe morbidity in sub-Saharan Africa than in Europe. For this reason the WHO now recommends starting cotrimoxazole prophylaxis at 350 and even 500 CD4/mml in sub-Saharan Africa. The question of whether antiretroviral treatment should also be initiated "earlier" in sub-Saharan Africa than in Europe has also been raised.

Topics: Africa South of the Sahara; Anti-Infective Agents; Antitubercular Agents; Bacterial Infections; HIV Infections; Humans; Malaria; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis

To characterize availability of fever and malaria medicines within the retail sector in rural Tanzania, assess the likely public health implications, and identify opportunities for policy interventions to increase the coverage of effective treatment.. A census of retailers selling drugs was undertaken in the areas under demographic surveillance in four Tanzanian districts, using a structured questionnaire.. Drugs were stocked by two types of retailer: a large number of general retailers (n = 675) and a relatively small number of drug shops (n = 43). Almost all outlets stocked antipyretics/painkillers. One-third of general retailers stocking drugs had antimalarials, usually chloroquine alone. Almost all drug shops stocked antimalarials (98%): nearly all had chloroquine, 42% stocked quinine, 37% sulphadoxine-pyrimethamine and 30% amodiaquine. A large number of antimalarial brands were available. Population ratios indicate the relative accessibility of retail drug providers compared with health facilities. Drug shop staff generally travelled long distances to buy from drugs wholesalers or pharmacies. General retailers bought mainly from local general wholesalers, with a few general wholesalers accounting for a high proportion of all sources cited.. Drugs were widely available from a large number of retail outlets. Potential negative implications include provision of ineffective drugs, confusion over brand names, uncontrolled use of antimalarials, and the availability of components of potential combination therapy regimens as monotherapies. On the other hand, this active and highly accessible retail market provides opportunities for improving the coverage of effective antimalarial treatment. Interventions targeted at all drug retailers are likely to be costly to deliver and difficult to sustain, but two promising points for targeted intervention are drug shops and selected general wholesalers. Retail quality may also be improved through consumer education, and modification of the chemical quality, packaging and price of products entering the retail distribution chain.

Topics: Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antimalarials; Chloroquine; Commerce; Dosage Forms; Health Services Accessibility; Humans; Malaria; Private Sector; Quinine; Rural Health; Tanzania; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Africa; Animals; Antimalarials; Drug Resistance, Multiple; HIV Seropositivity; Humans; Malaria; Plasmodium falciparum; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Comorbidity; HIV Infections; HIV-1; Humans; Immunocompromised Host; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

The seeking of healthcare for childhood illnesses was studied in three rural Nigerian communities of approximately 10,000 population each. The aim was to provide a baseline understanding of illness behaviour on which to build a programme for the promotion of prepackaged chloroquine and cotrimoxazole for early and appropriate treatment of childhood fevers at the community level. A total of 3117 parents of children who had been ill during the 2 weeks prior to interview responded to questions about the nature of the illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illnesses were 'hot body' (43.9 per cent), malaria, known as iba (17.7 per cent), and cough (7.4 per cent). The most common form of first-line treatment was drugs from a patent medicine vendor or drug hawker (49.6 per cent). Only 3.6 per cent did nothing. Most who sought care (77.5 per cent) were satisfied with their first line of action, and did not seek further treatment. The average cost of an illness episode was less than US$2.00 with a median of US$1.00. Specifically, chloroquine tablets cost an average of US 29 cents per course. Analysis found a configuration of signs and symptoms associated with chloroquine use, to include perception of the child having malaria, high temperature and loss of appetite. The configuration positively associated with antibiotic use consisted of cough and difficult breathing. The ability of the child's care-givers, both parental and professional, to make these distinctions in medication use will provide the foundation for health education in the promotion of appropriate early treatment of childhood fevers in the three study sites.

Topics: Anti-Bacterial Agents; Antimalarials; Child; Child, Preschool; Chloroquine; Cough; Female; Fever; Health Surveys; Humans; Infant; Malaria; Male; Medicine, African Traditional; Nigeria; Rural Health; Trimethoprim, Sulfamethoxazole Drug Combination

An attempt was made to estimate the risk of severe cutaneous adverse reactions (SCARs) to Fansidar (sulfadoxine plus pyrimethamine). Cases were identified through a spontaneous reporting system. Persons exposed were estimated using sales data of 27 countries reporting one SCAR case for either Fansidar or a related product, Bactrim (cotrimoxazole; sulfamethoxazole plus trimethoprim). Between 1974 and 1989, 126 cases were notified for Fansidar: 87 cases of erythema multiforme or Stevens-Johnson syndrome, and 39 cases of toxic epidermic necrolysis. 86% of cases were reported in Europe or North America. In 116 cases with use known, prophylaxis was the reason in 103, and treatment in 13. Toxic epidermolysis and erythema multiforme/Stevens-Johnson syndrome had case fatalities of 36 (95% confidence intervals 21 to 53%) and 9% (4 to 18%), respectively. Fansidar users were estimated at 117 million, and the overall SCAR risk to be 1.1 (0.9 to 1.3) per million. For developing countries with mainly single dose use, the risk was estimated to 0.1 (0.0 to 0.1) per million. For Europe and North America with mainly prophylactic use, the risk was 10 (8 to 12) and 36 (23 to 48) per million, respectively. Prophylactic use had a 40 times higher risk than single dose therapeutic use. The aggregated risk peaked in 1984-1985, with global and North American SCAR frequencies of 3.4 (2.4 to 4.3) and 72 (41 to 102) per million, respectively. After 1985, North America reported only one further case despite continued use by an estimated 0.3 million persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adverse Drug Reaction Reporting Systems; Antimalarials; Drug Combinations; Drug Eruptions; Drug Utilization; Erythema Multiforme; Humans; Malaria; Pyrimethamine; Risk Factors; Stevens-Johnson Syndrome; Sulfadoxine; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child, Preschool; Humans; Infant; Malaria; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amebiasis; Aminoquinolines; Antiprotozoal Agents; Humans; Malaria; Metronidazole; Pneumonia, Pneumocystis; Pyrimethamine; Quinine; Suramin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Trypanosomiasis

6 out of 7 patients with severe neutropenia associated with the use of amodiaquine for malaria prophylaxis amodiaquine (400 mg weekly) plus proguanil (200 mg daily); 1 of these patients had also taken cotrimoxazole and another had taken sulphaguanidine. The 7th patient had taken amodiaquine alone, but at a higher dose. A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000.

Topics: Acute Disease; Adult; Agranulocytosis; Amodiaquine; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leukocyte Count; Malaria; Male; Middle Aged; Neutropenia; Proguanil; Retrospective Studies; Sulfaguanidine; Sulfamethoxazole; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Antimalarials; Drug Combinations; Humans; Malaria; Male; Plasmodium falciparum; Plasmodium vivax; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Humans; Malaria; Psoriasis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antimalarials; Drug Combinations; Hemolysis; Humans; Infant; Infant, Newborn; Malaria; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child; Drug Combinations; Female; Humans; Malaria; Male; Middle Aged; Plasmodium falciparum; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with enteric fever confirmed by isolation of Salmonella species from blood culture, were treated with the combination of trimethoprim-sulphamethoxazole (co-trimoxazole). All 133 patients responded well to treatment. The mean defervescence was 2.74 days. No serious side effects were noticed and relapses occurred in the patients during the period of follow up.

Topics: Adolescent; Adult; Drug Combinations; Female; Humans; Jaundice; Malaria; Male; Middle Aged; Sudan; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever