trimethoprim--sulfamethoxazole-drug-combination and Parasitemia

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 In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials..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

 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

The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children.. Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Ugandan children, ages 6 months to 2 years, who were treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine.. Population pharmacokinetics for lumefantrine used a 2-compartment open model with first-order absorption. Age had a significant positive correlation with bioavailability in a model that included allometric scaling. Children not receiving trimethoprim-sulfamethoxazole with capillary whole blood concentrations <200 ng/mL had a 3-fold higher hazard of 28-day recurrent parasitemia, compared with those with concentrations >200 ng/mL (P = .0007). However, for children receiving trimethoprim-sulfamethoxazole, the risk of recurrent parasitemia did not differ significantly on the basis of this threshold. Day 3 concentrations were a stronger predictor of 28-day recurrence than day 7 concentrations.. We demonstrate that age, in addition to weight, is a determinant of lumefantrine exposure, and in the absence of trimethoprim-sulfamethoxazole, lumefantrine exposure is a determinant of recurrent parasitemia. Exposure levels in children aged 6 months to 2 years was generally lower than levels published for older children and adults. Further refinement of artemether-lumefantrine dosing to improve exposure in infants and very young children may be warranted.

Topics: Antimalarials; Artemether; Artemisinins; Black People; Child, Preschool; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Humans; Infant; Lumefantrine; Malaria, Falciparum; Male; Parasitemia; Plasmodium falciparum; Recurrence; Treatment Outcome; 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

Artemisinin-based combination therapies (ACTs) and trimethoprim-sulfamethoxazole (TS) prophylaxis are important tools for malaria control, but there are concerns about their effect on gametocytes, the stage of the parasite responsible for transmission. We conducted a longitudinal clinical trial in a cohort of HIV-infected and uninfected children living in an area of high malaria transmission intensity in Uganda. Study participants were randomized to artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) for all treatments of uncomplicated malaria (N = 4,380) as well as TS prophylaxis for different durations. The risks of gametocytemia detected by microscopy in the 28 days after antimalarial therapy were compared using multivariate analyses. The risk of gametocyte detection was significantly higher in patients treated with DP compared with AL (adjusted relative risk = 1.85, P < 0.001) and among children prescribed TS prophylaxis (adjusted relative risk = 1.76, P < 0.001). The risk of gametocytemia and its potential for increasing transmission should be considered when evaluating different ACTs and TS prophylaxis for malaria control.

Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluorenes; HIV Infections; Humans; Infant; Longitudinal Studies; Malaria, Falciparum; Multivariate Analysis; Parasitemia; Plasmodium falciparum; Post-Exposure Prophylaxis; Prevalence; Proportional Hazards Models; Quinolines; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Trophozoites; Uganda

It has been proposed that polymorphisms of the Merozoite Surface Protein 1 and 2 (MSP1 and MSP2) and the Glutamate Rich Protein (GLURP) genes can be considered as genetic markers for the genotyping of field populations of Plasmodium falciparum. During a field study on in vivo drug resistance against chloroquine, sulphadoxine/pyrimethamine (S/P) and cotrimoxazole in West Uganda, sensitive and resistant isolates were collected from patients by fingerprick for genotyping. 59 (72.8%) of the 81 P. falciparum samples isolated at day 0 showed multiclonal infection with 2-7 clones. Among the isolates we investigated, presence of the allelic family MAD20 of MSP1 at day 0 was significantly (P = 0.0041) associated with decreased resistance to antimalarials. Use of this method in a field study on in vivo drug resistance demonstrates another potential application of genotyping as a tool for epidemiological investigations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antigens, Protozoan; Antimalarials; Child; Child, Preschool; Chloroquine; Drug Combinations; Drug Resistance; Female; Genotype; Humans; Infant; Malaria, Falciparum; Male; Merozoite Surface Protein 1; Middle Aged; Parasitemia; Plasmodium falciparum; Protozoan Proteins; Pyrimethamine; Sulfadoxine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

The level of blood filariasis parasitaemia as well as the frequency of and the relationship between cotrimoxazole prophylaxis (CTX-P), antiretroviral therapy (ART) intake and CD4 cell count among people living with human immunodeficiency virus (PLHIV) in rural areas of Gabon were being studied.. Sociodemographic data and recent biological tests of PLHIV and HIV-negative participants were collected. Loa loa and Mansonella perstans microfilaria were detected by direct microscopy examination and leucoconcentration.. Overall, 209 HIV-positive and 148 HIV-negative subjects were enrolled. The overall prevalence of microfilaria was comparable between PLHIV (19.9% [n=41/206]) and HIV-negative participants (14.8% [n=22/148]) (p=0.2). The L. loa infection rate was comparable between HIV-positive (9.2%) and HIV-negative participants (6.8%) (p=0.2), while the M. perstans infection rate was 14-fold higher among PLHIV (p<0.01). L. loa parasitaemia was 6-fold lower in PLHIV receiving CTX-P (median 150 mf/mL [interquartile range {IQR} 125-350]) than in patients without (900 [550-2225]) (p<0.01). Among subjects with a CD4 cell count <200 cells/μL, the prevalence of M. perstans was 7-fold higher than that of L. loa (20.6% vs 2.9%).. This study suggests a similar exposure to L. loa infection of PLHIV and HIV-negative patients while M. perstans is more frequently found in HIV-positive individuals, notably those with a CD4 count <200 cells/μL.

Topics: Adult; Animals; Filariasis; Gabon; HIV Infections; Humans; Loiasis; Parasitemia; Pilot Projects; Prevalence; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Human immunodeficiency virus (HIV) infection and Plasmodium falciparum malaria are 2 of the gravest health threats in sub-Saharan Africa. Multiple repeat infections with the malaria parasite as seen in endemic areas are necessary to develop specific malaria immunity. HIV is an immunosuppressive virus and in children aged <5 years, development of malaria-specific immunity may be impaired and malaria parasite clearance in theory will be delayed; hence the predisposition to increased incidence of asymptomatic malaria or severe malaria. This cross-sectional study was carried out to examine associations between immunosuppression and asymptomatic malaria parasitemia (ASMP) in HIV-infected children aged <5 years in Benin City.. One hundred seventy-nine asymptomatic HIV-1-positive and 179 age- and sex-matched HIV-1-negative children aged <5 years were recruited. The malaria parasite was determined by Giemsa-stained blood film by certified microscopy while concomitant CD4(+) count was estimated in the HIV-infected children.. The prevalence of ASMP in those who were HIV-infected of 34.1% was significantly higher than 17.3% in the HIV uninfected (P = .001). The prevalence of ASMP was highest (59.3%) among subjects who were severely immunosuppressed (CDC immunologic category 3). The prevalence of ASMP significantly increased with advanced immune disease in the subjects (P = .011). Severe (World Health Organization) clinical staging was also significantly associated with increased prevalence of ASMP (P = .031). The prevalence of ASMP is significantly higher among subjects not receiving cotrimoxazole, associated with threefold risk of having ASMP (P = .003: odds ratio = 3.5).. ASMP is more common in HIV-positive children aged <5 years and is significantly associated with declining CD4(+) T-cell count and severe clinical disease. There is a need for integration of HIV- and malaria-control programs for stronger case management. Malaria-control programs may consider malaria prevention interventions and cotrimoxazole prophylaxis for preschool children who are HIV-infected and living in malaria-endemic regions.

Topics: Antimalarials; Asymptomatic Infections; Chemoprevention; Child, Preschool; Coinfection; Cross-Sectional Studies; Female; HIV Seropositivity; HIV-1; Humans; Immune Tolerance; Immunocompromised Host; Infant; Infant, Newborn; Malaria, Falciparum; Male; Nigeria; Odds Ratio; Parasitemia; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

To determine the prevalence of malaria parasitemia and other common illnesses among drug store clients in one rural community, with a view to the potential role of specialist drug stores in expanding coverage of effective malaria treatment to households in highly endemic areas.. Follow-back study of 2466 client visits selected from all 10 drug stores operating in the town of Ikwiriri between May 30 and August 31 2004. Of these, 521 (21.2%) were made by or on behalf of persons ill with fever or malaria. Two hundred and ninety three were eligible as residents of the surrounding nine villages and all agreed to participate in the study. Each patient was evaluated by a clinical officer and provided a blood sample for malaria on the day of the shop visit, either at the shop or at home.. Only 50 (17.1%) visits by or on behalf of febrile patients resulted in the purchase of an antimalarial drug, while an antipyretic medication was obtained at 226 visits (77.1%). Clinicians diagnosed malaria in 63.8% of patients. Malaria parasites were identified in blood film samples from 24.2% (95% CI: 19.6, 29.5). This is double the parasite prevalence rate of 10.7% (95% CI: 8.6, 13.1) obtained from a household survey of 1004 healthy individuals selected from these villages at the same time. It is not significantly lower than the prevalence observed among 880 clients presenting with fever at health facilities in the district: 29.7% (95% CI: 23.0, 37.3). The prevalence of malaria parasitemia among children younger than 5 years whose families sought fever treatment from drug stores (42.1%; 95% CI: 31.4, 53.5) was equal to that of children presenting with fever at health facilities (42.5%; 95% CI: 25.0, 62.2).. Currently, drug store clients do not obtain malaria-specific treatment in the majority of cases where it might be warranted. Parasitological findings indicate that drug store clients, especially children, are as likely to be infected with malaria as patients seeking care for similar illnesses at health facilities. Drug stores may be attractive partners for policy makers eager to engage the private retail sector in expanding coverage of malaria treatment.

Topics: Adult; Amodiaquine; Analgesics, Non-Narcotic; Anemia; Antimalarials; Child, Preschool; Drug Combinations; Endemic Diseases; Female; Fever; Humans; Malaria, Falciparum; Male; Parasitemia; Patient Acceptance of Health Care; Pharmacies; Prevalence; Pyrimethamine; Rural Health; Sulfadoxine; Tanzania; Trimethoprim, Sulfamethoxazole Drug Combination

In many African countries, trimethoprim-sulfamethoxazole (TS) is recommended for the treatment of children with malaria and pneumonia - in accordance with the guidelines for the integrated management of childhood illness (IMCI) - and, in some settings, for the home management of febrile illnesses. There have been few studies, however, of the risk of failure of treatment with this drug combination in children with acute, Plasmodium falciparum malaria. The factors that identify children at risk of treatment failure after being given TS were therefore evaluated in 101 children with acute, symptomatic, uncomplicated, P. falciparum malaria, in a hyper-endemic area of south-western Nigeria. Overall, 11% of the children failed treatment by day 14. In a multivariate analysis, two factors were found to be independent predictors of the failure of treatment with TS: an age of <3 years (adjusted odds ratio=0.1; 95% confidence interval=0.02-0.53; P=0.007); and a body temperature of >or=38 degrees C 2 days after the commencement of treatment (adjusted odds ratio=4.9; 95% confidence interval=1.2-21.3; P=0.03). These findings may have implications for control efforts in some sub-Saharan African countries, where TS is recommended for the management of malaria in children, with or without pneumonia.

Topics: Antimalarials; Child; Child, Preschool; Endemic Diseases; Female; Humans; Infant; Malaria, Falciparum; Male; Parasitemia; Risk Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

The apicomplexan parasite Plasmodium gallinaceum has not been much studied from the veterinary standpoint. Although it causes malaria in domesticated chickens, no effective drugs appear to be commercially available. A mixture of trimethoprim and sulphaquinoxaline (TMP/SQX, ratio 1:3), with a wide spectrum of activity against bacteria and coccidia, is here shown to be also efficacious against blood-induced P. gallinaceum malaria when administered therapeutically in the feed of chickens for 5-day periods, beginning on the day before infection, or on the day of infection, or up to four days after infection. Chickens were protected against mortality and reduction of weight gain. Three other criteria of efficacy, which showed good correlation with each other and also with the two commercial performance criteria, were the production of green diarrhoea (due to biliverdin), parasitaemia and reduced haematocrit values. When TMP/SQX treatments were initiated sooner than five days after infection, parasites were almost entirely eliminated from the blood, whereas treatments initiated later than four days after infection failed to protect birds against clinical disease. Birds protected by TMP/SQX against primary infection with P. gallinaceum were immune to clinical malaria when exposed to a severe blood-induced challenge of P. gallinaceum 28 days later.

Topics: Animals; Antimalarials; Chickens; Diarrhea; Hematocrit; Malaria, Avian; Male; Parasitemia; Plasmodium gallinaceum; Poultry Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

A five-year-old female dog was presented with a four-week history of inappetence, weight loss, and skin and gait abnormalities. Physical examination revealed weakness, depression, incoordination of the posterior limbs, emaciation, skin and hair coat alterations, peripheral lymphadenopathy, pale mucous membranes and fever. Laboratory analysis of samples revealed abnormalities which included anaemia, neutrophilic leucocytosis, thrombocytopenia, low serum glucose and albumin concentrations, and increased serum alkaline phosphatase activity. The diagnosis was confirmed microscopically, by demonstrating the presence of Hepatozoon canis gametocytes within neutrophils in Giemsa-stained peripheral blood smears. Treatment consisting of toltrazuril and a trimethoprim-sulfamethoxazole combination was effective in relieving the clinical signs and clearing the blood of H. canis gametocytes. To the authors' knowledge, this is the first detailed clinical description of H. canis infection in a dog in Turkey.

Topics: Animals; Coccidiosis; Coccidiostats; Dog Diseases; Dogs; Eucoccidiida; Female; Parasitemia; Treatment Outcome; Triazines; Trimethoprim, Sulfamethoxazole Drug Combination; Turkey

The clinical characteristics and the responses to oral antimalarial therapy of 104 children presenting consecutively with or without Plasmodium falciparum hyperparasitaemia (HP) were investigated in an endemic area. At presentation, although the 52 children with HP were significantly younger and had significantly higher heart rates than the 52 without, there were no significant differences between the two groups in their symptoms or in any other clinical feature of their malaria. Responses to oral antimalarial drugs were similar in both groups. Analysis of the disposition kinetics of parasitaemia, using a non-compartmental model similar to that used in characterizing drug disposition, showed that the two groups had similar half-lives of parasitaemia (t1/2pd), volumes of blood completely cleared of parasites per unit time (CLBpd), and parasite-clearance-time:t1/2pd ratios. Three children in the HP group, all aged < 3 years, progressed to cerebral malaria within 8 h of presentation, and another HP child presented with isolated trunkal ataxia, indicative of cerebellar involvement. No child in the non-HP group had any of the features of severe malaria. Although the clinical characteristics and responses to oral therapy of children with and without HP are therefore very similar, young children with HP appear to have an increased risk of developing other features of severe malaria.

Topics: Adolescent; Age Factors; Analysis of Variance; Antimalarials; Child; Child, Preschool; Chloroquine; Drug Therapy, Combination; Endemic Diseases; Female; Heart Rate; Humans; Infant; Malaria, Falciparum; Male; Nigeria; Parasitemia; Prospective Studies; Pyrimethamine; Sulfadoxine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination