zithromax and Parasitemia

We present two cases of Babesia-induced splenic injury at a single institution. In the late summer, two patients presented with left-sided abdominal pain radiating to the shoulder. They were both found to have hemolytic anemia, thrombocytopenia, and acute splenic infarction on imaging. Blood smears showed intracellular ring forms consistent with Babesia spp. and low parasitemia (<1%). Diagnosis was confirmed by PCR for Babesia microti. Both patients improved with azithromycin and atovaquone, without blood products or surgical intervention. Several weeks following treatment, repeat blood smears revealed no parasites. Splenic infarct and hemorrhage have been previously reported as rare complications of babesiosis. However, given the steady rise in Babesia microti cases in the USA, even these rare complications will become more prevalent. We review both the diagnosis and management of Babesia-induced splenic complications, which can be challenging in patients with low-level parasitemia. Clinicians should consider babesiosis as a cause of atraumatic splenic injury.

Topics: Azithromycin; Babesia microti; Babesiosis; Humans; Parasitemia

Several experimental models have been used in order to evaluate the in vivo efficacy of azithromycin against numerous human pathogenic bacteria and parasites, including comparison between azithromycin and other antibiotics belonging or not to the macrolide family. Using the experimental models, three major objectives can be distinguished: the comparative studies of the efficacy dose 50 (ED50) of azithromycin compared to other orally given antibiotics, the azithromycin efficacy in animal infected with intracellular multiplying micro-organisms, and the demonstration of the specific azithromycin accumulation in tissues in direct relationship with the local recruitment of phagocytic cells at the infectious foci. The ED50 of azithromycin has been compared with those of erythromycin or cefaclor in varying acute murine infections. Evidence was given of a similar efficacy for the three tested antibiotics. Nevertheless a marked advantage for azithromycin was observed in experimental local infections and with infections due to Gram-negative bacteria (Haemophilus influenzae, Branhamella catarrhalis). The second objective was to confirm in vivo the preferential efficacy of azithromycin in models using intracellular multiplying microorganisms, due to its great capacity to accumulate inside of professional phagocytes. Several models have been used, such as those performed with Listeria monocytogenes, Legionella pneumophila, S. typhimurium, Brucella melitensis, M. avium and C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cefaclor; Disease Models, Animal; Erythromycin; Legionnaires' Disease; Listeriosis; Lung Diseases; Mice; Mycobacterium avium; Parasitemia; Salmonella Infections, Animal; Tuberculosis

Maternal malaria and infections during pregnancy are risk factors for fetal growth restriction. We assessed the impact of preventive treatment in pregnancy on maternal malaria and fetal growth. Between 2003 and 2006, we enrolled 1,320 pregnant Malawian women, 14-26 gestation weeks, in a randomized trial and treated them with two doses of sulfadoxine-pyrimethamine (SP, control) at enrollment and between 28-34 gestation weeks; with monthly SP from enrollment until 37 gestation weeks; or with monthly SP and azithromycin twice, at enrollment and between 28 and 34 gestation weeks (AZI-SP). Participants were seen at 4-week intervals until 36 completed gestation weeks and weekly thereafter. At each visit, we collected dried blood spots for real-time polymerase chain reaction diagnosing of malaria parasitemia and, in a random subgroup of 341 women, we measured fetal biparietal diameter and femur length with ultrasound. For the monthly SP versus the control group, the odds ratios (OR) (95% CI) of malaria parasitemia during the second, third, and both trimesters combined were 0.79 (0.46-1.37), 0.58 (0.37-0.92), and 0.64 (0.42-0.98), respectively. The corresponding ORs for the AZI-SP versus control group were 0.47 (0.26-0.84), 0.51 (0.32-0.81), and 0.50 (0.32-0.76), respectively. Differences between the AZI-SP and the monthly SP groups were not statistically significant. The interventions did not affect fetal biparietal diameter and femur length growth velocity. The results suggest that preventive maternal treatment with monthly SP reduced malaria parasitemia during pregnancy in Malawi and that the addition of azithromycin did not provide much additional antimalarial effect.

Topics: Antimalarials; Azithromycin; Drug Combinations; Female; Fetal Development; Humans; Malaria; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine

Azithromycin has recently been shown to reduce all-cause childhood mortality in sub-Saharan Africa. One potential mechanism of this effect is via the anti-malarial effect of azithromycin, which may help treat or prevent malaria infection. This study evaluated short- and longer-term effects of azithromycin on malaria outcomes in children.. Children aged 8 days to 59 months were randomized in a 1:1 fashion to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Children were evaluated for malaria via thin and thick smear and rapid diagnostic test (for those with tympanic temperature ≥ 37.5 °C) at baseline and 14 days and 6 months after treatment. Malaria outcomes in children receiving azithromycin versus placebo were compared at each follow-up timepoint separately.. Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. Children were a median of 26 months and 51% were female, and 17% were positive for malaria parasitaemia at baseline. There was no evidence of a difference in malaria parasitaemia at 14 days or 6 months after treatment. In the azithromycin arm, 20% of children were positive for parasitaemia at 14 days compared to 17% in the placebo arm (P = 0.43) and 7.6% vs. 5.6% in the azithromycin compared to placebo arms at 6 months (P = 0.47).. Azithromycin did not affect malaria outcomes in this study, possibly due to the individually randomized nature of the trial. Trial registration This study is registered at clinicaltrials.gov (NCT03676751; registered 19 September 2018).

Topics: Administration, Oral; Antimalarials; Azithromycin; Female; Humans; Infant; Infant, Newborn; Malaria; Male; Parasitemia

Antibiotics are recommended by the WHO as part of the management of uncomplicated severe acute malnutrition in children. We evaluated whether azithromycin, an antibiotic with antimalarial properties, improved malarial parasitemia outcomes in children with severe acute malnutrition compared with amoxicillin, an antibiotic commonly used for severe acute malnutrition that does not have antimalarial properties. Total of 301 children were randomized (1:1) to a single oral dose of azithromycin or a 7-day course of amoxicillin and followed for 8 weeks. We found no significant evidence that children receiving azithromycin had improved parasitemia outcomes relative to amoxicillin. Although azithromycin may have advantages over amoxicillin in terms of dosing and administration for uncomplicated severe acute malnutrition, it may not yield additional benefit for malaria outcomes.

Topics: Amoxicillin; Anti-Infective Agents; Azithromycin; Burkina Faso; Child Nutrition Disorders; Child, Preschool; Humans; Infant; Infant Nutrition Disorders; Malaria; Parasitemia; Treatment Outcome

Reductions in malaria morbidity have been reported following azithromycin mass drug administration (MDA) for trachoma. The recent Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin MDA. Here, we investigate the effects of azithromycin MDA on malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and azithromycin or placebo syrup was distributed to children aged 1-59 months for a total of four biannual distributions. At baseline, 12-month, and 24-month follow-up visits, a random sample of 1,200 children was assessed for malaria with thick and thin blood smears and hemoglobin measurement. In the community-level analysis, there was no difference in the prevalence of parasitemia (1.0% lower in azithromycin-treated communities; 95% CI: -8.2 to 6.1), gametocytemia (0.7% lower in azithromycin-treated communities; 95% CI: -2.8 to 1.5), or anemia (1.7% lower in azithromycin-treated communities; 95% CI: -8.1 to 4.6) between placebo and azithromycin communities. Further interrogation of the data at the individual level, both per-protocol (including only those who received treatment 6 months previously) and by intention-to-treat, did not identify differences in parasitemia between treatment arms. In contrast to several previous reports, this study did not show an effect of azithromycin MDA on malaria parasitemia at the community or individual levels.

Topics: Anemia; Anti-Bacterial Agents; Azithromycin; Child Mortality; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Malaria; Male; Mass Drug Administration; Parasitemia; Prevalence

Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. A total of 122 women (median gestation, 26 weeks [range, 14 to 32 weeks]) were randomized 1:1 to three daily doses of 1 g AZ plus 960 mg PQ tetraphosphate or single-dose SP (4,500 mg sulfadoxine plus 225 mg pyrimethamine), based on computer-generated block randomization. Tolerability was assessed to day 7, and efficacy was assessed to day 42 (when participants were returned to usual care) and at delivery. Data for 119 participants (AZ-PQ,

Topics: Adult; Antimalarials; Asymptomatic Diseases; Azithromycin; Chemoprevention; Drug Combinations; Erythrocytes; Female; Gestational Age; Humans; Live Birth; Malaria, Falciparum; Malaria, Vivax; Papua New Guinea; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Pregnancy; Pyrimethamine; Quinolines; Random Allocation; Severity of Illness Index; Stillbirth; Sulfadoxine

Malaria and human immunodeficiency virus (HIV) infections in pregnancy are important and major contributing factors to maternal morbidity and mortality in sub-Saharan Africa. Prevention of malaria in HIV-positive pregnant woman will reduce the burden of malaria-HIV comorbidity. The objective of this study was to compare effects and safety of azithromycin (AZ) with sulphadoxine-pyrimethamine (SP) for intermittent preventive therapy for malaria in HIV-positive pregnant women.. We performed a randomized, controlled, open-label pregnancy trial of 140 HIV-positive pregnant patients attending antenatal clinics at the University College Hospital and Adeoyo Maternity Teaching Hospital, Ibadan, Nigeria. Participants were enrolled from a gestational age of 16 weeks and randomized to receive AZ or SP. The primary outcome was peripheral parasitaemia at delivery. Secondary outcomes were drug tolerability, foetal outcome and birthweight. The χ2 test (or Fisher's exact test, as appropriate) and Student's t test were used in the per-protocol analysis. The level of statistical significance was p<0.05.. A total of 123 participants (87.9%) completed the study: 60 participants received AZ and 63 received SP. The incidence of malaria parasitaemia at delivery in the AZ group was 6 (10.0%), compared with 7 (11.1%) in the SP group (relative risk 0.89 [95% confidence interval 0.28 to 2.82], p=0.84). Placental parasitization was demonstrated in 1 (1.6%) participant in the SP group compared with 3 (5.0%) in the AZ group (p=0.36).. The findings suggest that AZ is comparable to SP in malaria prevention and safety in HIV-positive pregnant women.

Topics: Adult; Anti-Bacterial Agents; Antimalarials; Azithromycin; Drug Combinations; Drug Therapy, Combination; Female; HIV Seropositivity; Humans; Malaria; Nigeria; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine

Mass azithromycin distributions have been shown to reduce mortality in preschool children, although the factors mediating this mortality reduction are not clear. This study was performed to determine whether mass distribution of azithromycin, which has modest antimalarial activity, reduces the community burden of malaria.. In a cluster-randomized trial conducted from 23 November 2014 until 31 July 2017, 30 rural communities in Niger were randomized to 2 years of biannual mass distributions of either azithromycin (20 mg/kg oral suspension) or placebo to children aged 1 to 59 months. Participants, field staff, and investigators were masked to treatment allocation. The primary malaria outcome was the community prevalence of parasitemia on thick blood smear, assessed in a random sample of children from each community at study visits 12 and 24 months after randomization. Analyses were performed in an intention-to-treat fashion. At the baseline visit, a total of 1,695 children were enumerated in the 15 azithromycin communities, and 3,029 children were enumerated in the 15 placebo communities. No communities were lost to follow-up. The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI 5.1%-15.7%; 52 of 552 children across all communities) in the azithromycin-treated group and 6.7% (95% CI 4.0%-12.6%; 36 of 542 children across all communities) in the placebo-treated group. In the prespecified primary analysis, parasitemia was lower in the azithromycin-treated group at month 12 (mean prevalence 8.8%, 95% CI 5.1%-14.3%; 51 of 551 children across all communities) and month 24 (mean 3.5%, 95% CI 1.9%-5.5%; 21 of 567 children across all communities) than it was in the placebo-treated group at month 12 (mean 15.3%, 95% CI 10.8%-20.6%; 81 of 548 children across all communities) and month 24 (mean 4.8%, 95% CI 3.3%-6.4%; 28 of 592 children across all communities) (P = 0.02). Communities treated with azithromycin had approximately half the odds of parasitemia compared to those treated with placebo (odds ratio [OR] 0.54, 95% CI 0.30 to 0.97). Parasite density was lower in the azithromycin group than the placebo group at 12 and 24 months (square root-transformed outcome; density estimates were 7,540 parasites/μl lower [95% CI -350 to -12,550 parasites/μl; P = 0.02] at a mean parasite density of 17,000, as was observed in the placebo arm). No significant difference in hemoglobin was observed between the 2 treatment groups at 12 and 24 months (mean 0.34 g/dL higher in the azithromycin arm, 95% CI -0.06 to 0.75 g/dL; P = 0.10). No serious adverse events were reported in either group, and among children aged 1 to 5 months, the most commonly reported nonserious adverse events (i.e., diarrhea, vomiting, and rash) were less common in the azithromycin-treated communities. Limitation. Mass azithromycin distributions were associated with a reduced prevalence of malaria parasitemia in this trial, suggesting one possible mechanism for the mortality benefit observed with this intervention.. The trial was registered on ClinicalTrials.gov (NCT02048007).

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Cluster Analysis; Female; Humans; Infant; Malaria; Male; Mass Drug Administration; Niger; Parasitemia; Time Factors

Azithromycin has modest efficacy against malaria, and previous cluster randomized trials have suggested that mass azithromycin distribution for trachoma control may play a role in malaria control. We evaluated the effect of annual versus biannual mass azithromycin distribution over a 3-year period on malaria prevalence during the peak transmission season in a region with seasonal malaria transmission in Niger.. Twenty-four communities in Matameye, Niger, were randomized to annual mass azithromycin distribution (3 distributions to the entire community during the peak transmission season) or biannual-targeted azithromycin distribution (6 distributions to children <12 years of age, including 3 in the peak transmission season and 3 in the low transmission season). Malaria indices were evaluated at 36 months during the high transmission season.. Parasitemia prevalence was 42.6% (95% confidence interval: 31.7%-53.6%) in the biannual distribution arm compared with 50.6% (95% confidence interval: 40.3%-60.8%) in the annual distribution arm (P = 0.29). There was no difference in parasite density or hemoglobin concentration in the 2 treatment arms.. Additional rounds of mass azithromycin distribution during low transmission may not have a significant impact on malaria parasitemia measured during the peak transmission season.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Cluster Analysis; Female; Humans; Infant; Malaria; Male; Mass Drug Administration; Niger; Parasitemia; Prevalence; Seasons; Trachoma

Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years. The 12 communities randomized to annual azithromycin received three treatments during the high-transmission season, and the 12 communities randomized to biannual azithromycin received a total of six treatments: three during the high-transmission season and three during the low-transmission season. Blood samples were taken to assess malariometric indices among children in all study communities at a single time point during the high-transmission season after 3 years of the intervention. No significant differences were identified in malaria parasitemia, parasite density, or hemoglobin concentration between the annual and biannual treatment arms. When compared with annual mass azithromycin alone, additional mass azithromycin distributions given during the low-transmission season did not significantly reduce the subsequent prevalence of malaria parasitemia or parasite density after 3 years, as measured during the high-transmission season.

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Infant; Malaria; Male; Niger; Parasitemia; Trachoma

Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority.. This was an open-label, non-comparative study (NCT01103713) in 5 countries in East and sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) to assess parasitological response and drug concentrations of a single, 3-day course of four tablets of a fixed-dose combination of azithromycin-chloroquine (AZCQ) 250/155 mg given during the second or third trimester to women with asymptomatic Plasmodium falciparum parasitemia in their first or second pregnancy. Parasitemia was determined by microscopy and molecular genotyping was performed to characterize parasites relative to the baseline infection. Weekly follow-up visits took place until day 42 after first dose and additional follow-up occurred after delivery. Systemic concentrations of azithromycin (AZ), chloroquine (CQ), and the CQ metabolite, desethyl CQ (DECQ) were evaluated at Day 0 (pre-dose), at Day 2 (pre-dose, 2 and 8 hours) and randomly at Days 7 and 14. Systemic concentrations of CQ and DECQ were also measured randomly at Day 21 and Day 28. In total, 404 women were screened for eligibility and 168 were treated, 155 of whom completed the study. PCR-adjusted parasitological response in the modified intent-to-treat population at day 28 (the primary efficacy endpoint) was estimated by the Kaplan-Meier method as 99.35% (95% confidence interval [CI]: 97.76, 100.00). PCR-adjusted parasitological response remained high at day 42 (95.19%; 95% CI: 91.35, 99.03). In general, the mean concentrations of serum AZ, plasma CQ, and plasma DECQ showed large CV% values (ranges of 33-156%, 42-228%, and 57-109%, respectively). There were 157 live births, three stillbirths, and eight pregnancies of unknown outcome: 7 due to withdrawal of participant consent and 1 lost to follow-up. The most frequent treatment-emergent adverse events were vomiting (20.8%) and dizziness (19.6%).. These results suggest that a 3-day course of AZCQ can lead to an adequate 28-day parasitological response.

Topics: Adolescent; Adult; Africa South of the Sahara; Asymptomatic Diseases; Azithromycin; Chloroquine; Drug Combinations; Drug Resistance; Female; Humans; Kaplan-Meier Estimate; Malaria, Falciparum; Parasite Load; Parasitemia; Plasmodium falciparum; Pregnancy; Treatment Outcome; Young Adult

We assessed the effect of mass azithromycin treatment on malaria parasitemia in a trachoma trial in Niger. Twenty-four study communities received treatment during the wet, high-transmission season. Twelve of the 24 communities were randomized to receive an additional treatment during the dry, low-transmission season. Outcome measurements were conducted at the community-level in children < 1-72 months of age in May-June 2011. Parasitemia was higher in the 12 once-treated communities (29.8%, 95% confidence interval [CI] = 21.5-40.0%) than in the 12 twice-treated communities (19.5%, 95% CI = 13.0-26.5%, P = 0.03). Parasite density was higher in once-treated communities (354 parasites/μL, 95% CI = 117-528 parasites/μL) than in twice-treated communities (74 parasites/μL, 95% CI = 41-202 parasites/μL, P = 0.03). Mass distribution of azithromycin reduced malaria parasitemia 4-5 months after the intervention. The results suggest that drugs with antimalaria activity can have long-lasting impacts on malaria during periods of low transmission.

Topics: Azithromycin; Child; Child, Preschool; Cluster Analysis; DNA, Protozoan; Female; Humans; Infant; Logistic Models; Malaria; Male; Niger; Parasitemia; Prevalence; Seasons; Treatment Outcome

Given increasing rates of resistance to existing therapy, new options for treatment and prophylaxis of malaria are needed.. Two randomised, comparative, non-inferiority studies were conducted in Africa, one double-blinded and one open-label. Adults with fever, a positive peripheral blood smear, and a positive rapid diagnostic test for Plasmodium falciparum were randomised in both studies to either azithromycin (AZ) 1,000 mg plus chloroquine (CQ) 600-mg base (AZCQ 1,000 mg) once daily for three days or mefloquine hydrochloride (MQ) 1,250 mg (split dose). In the first study, an additional regimen of AZ 500 mg plus CQ 600-mg base (AZCQ 500 mg) once daily for three days was included. All study participants were hospitalised until three consecutive daily blood smears were negative for asexual P. falciparum parasitaemia. Study participants were evaluated weekly for 42 days, with Day 28 polymerase chain reaction (PCR)-corrected parasitological clearance rate as primary endpoint.. A total of 467 subjects were randomised in the two studies. At 28 days' follow-up, PCR-corrected parasitological clearance rates in the per protocol population in the first study were 101/103 (98%) with AZCQ 1,000 mg compared with 102/103 (99%) with MQ (95% confidence interval [CI]: -5.2, 3.3). The AZCQ 500-mg regimen was stopped during an interim study review (six [86%] clearance of seven evaluable; two lost to follow-up). In the second study, clearance rates were similar: AZCQ 1,000 mg 107/107 (100%) vs MQ 111/112 (99%; 95% CI: -1.8, 3.6). Among the participating countries, in vitro CQ resistance based on pfcrt mutation frequency in the baseline isolates across both studies ranged from 20.8% (Zambia) to 96.1% (Uganda). Serious adverse events (AEs; all causality) were observed more frequently with MQ compared with AZCQ (four vs one, respectively), though discontinuations for AEs were similar (four vs three, respectively). Common AEs in the AZ-containing arms included pruritus, vomiting, dizziness, and headache.. Among adults with symptomatic uncomplicated falciparum malaria in Africa, the combination of AZ 1,000 mg and CQ 600-mg base once daily for three days resulted in Day 28 PCR-corrected parasitological clearance rates of ≥98% and was non-inferior to treatment with MQ. AZCQ was well tolerated.. ClinicalTrials.gov identifiers NCT00082576 and NCT00367653.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials; Azithromycin; Chloroquine; Drug Therapy, Combination; Female; Humans; Malaria, Falciparum; Male; Mefloquine; Middle Aged; Parasitemia; Plasmodium falciparum; Polymerase Chain Reaction; Treatment Outcome; Uganda; Young Adult; Zambia

In recent studies, the combination of azithromycin and artesunate has proven to be a promising alternative for the treatment of uncomplicated falciparum malaria.. We conducted a randomized, controlled clinical trial assessing the efficacy of azithromycin-artesunate combination therapy. The study was conducted involving 228 patients aged 8-65 years. Patients were randomized to 1 of 2 cohorts at a ratio of 2:1, receiving either azithromycin-artesunate once daily for 3 days (30 mg/kg per day of azithromycin plus 4 mg/kg per day of artesunate) or an adult dose of 80 mg of artemether plus 960 mg of lumefantrine (4 tablets Coartem or the equivalent for children weighing <35 kg) twice daily for 3 days.. The 42-day cure rate by Kaplan-Meier analysis was 94.6% (95% confidence interval [CI], 89.38%-97.44%) in the azithromycin-artesunate arm and 97.0% (95% CI, 89.45%-99.40%) in the control arm. Fever clearance times and parasite clearance times did not show any differences between the 2 arms (P=.59 and .95, respectively). No serious adverse events were seen, but the percentage of patients who developed any adverse event was higher in the control group (P=.03).. Our data suggest that azithromycin-artesunate is an efficacious and well-tolerated treatment for patients with uncomplicated falciparum malaria in Bangladesh.

Topics: Adolescent; Adult; Aged; Animals; Antimalarials; Artemether; Artemisinins; Artesunate; Azithromycin; Bangladesh; Child; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Humans; Lumefantrine; Malaria, Falciparum; Male; Middle Aged; Parasitemia; Time Factors; Treatment Outcome; Young Adult

Azithromycin, the most potent antimalarial macrolide antibiotic, is synergistic with quinine against Plasmodium falciparum in vitro. We assessed combinations of azithromycin and quinine against uncomplicated P. falciparum malaria at the Armed Forces Research Institute of Medical Sciences-Kwai River Clinical Center along the Thailand-Myanmar border, an area with a high prevalence of multidrug-resistant P. falciparum. Four regimens were assessed in an open-label dose-ranging design involving 61 volunteers. All received oral quinine (Q; 30 mg/kg/day divided every 8 hours for 3 days) with oral azithromycin (Az; 500 mg twice a day for 3 days, 500 mg twice a day for 5 days, or 500 mg three times a day for 3 days). A comparator group received quinine and doxycycline (Dx; 100 mg twice a day for 7 days). Study observation was 28 days per protocol. Sixty volunteers completed the study. Seven days of QDx cured 100% of the volunteers. One failure occurred in the lowest QAz regimen (on day 28) and none occurred in either of the two higher Az regimens. Cinchonism occurred in nearly all subjects. Overall, the azithromycin regimens were well tolerated, and no volunteers discontinued therapy. Three- and five-day azithromycin-quinine combination therapy appears safe, well tolerated, and effective in curing drug-resistant P. falciparum malaria. Further evaluation, especially in pediatric and obstetric populations, is warranted.

Topics: Administration, Oral; Adult; Animals; Antimalarials; Azithromycin; Cohort Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Malaria, Falciparum; Male; Middle Aged; Parasitemia; Plasmodium falciparum; Quinine

We assessed the prophylactic efficacy of azithromycin (250 mg/day) against malaria in 276 adults in western Thailand in a randomized, double-blind, placebo-controlled trial. After antimalarial suppressive treatment, volunteers were randomized in a 2:1 ratio to either the azithromycin or placebo, respectively. Study medication was given for an average of 74 days. The azithromycin group (n = 179) had five endpoint parasitemias (1 Plasmodium vivax and 4 P. falciparum), and the placebo group (n = 97) had 28 endpoint parasitemias (21 P. vivax, 5 P. falciparum, and 2 mixed infections). Adverse events and compliance and withdrawal rates were similar in both groups. The protective efficacy (PE) of azithromycin was 98% for P. vivax (95% confidence interval [CI] = 88-100%). There were too few cases to reliably estimate the efficacy of azithromycin for P. falciparum (PE =71%, 95% C =-14-94%). We conclude that daily azithromycin was safe, well-tolerated, and had a high efficacy for the prevention of P. vivax malaria.

Topics: Adult; Animals; Antimalarials; Azithromycin; Chemoprevention; Double-Blind Method; Female; Humans; Malaria, Vivax; Male; Parasitemia; Plasmodium vivax; Thailand; Treatment Outcome

Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.

Topics: Adult; Aged; Animals; Antimalarials; Azithromycin; Chloroquine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Malaria, Vivax; Male; Middle Aged; Parasitemia; Plasmodium vivax; Primaquine; Treatment Outcome

New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.

Topics: Adolescent; Adult; Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antimalarials; Azithromycin; Double-Blind Method; Doxycycline; Female; Humans; Indonesia; Malaria, Falciparum; Malaria, Vivax; Male; Middle Aged; Parasitemia; Treatment Outcome

To determine whether azithromycin, 250 mg/d, is effective prophylaxis for liver infection or for both liver and subsequent blood infection with Plasmodium falciparum.. Controlled phase II trial with two cohorts entered sequentially.. Clinical trials center of Walter Reed Army Institute of Research, Washington, D.C.. Each of the two cohorts consisted of 12 normal adult volunteers who had not had malaria during the previous 2 years: 10 who received azithromycin prophylaxis and 2 controls who did not received treatment.. For cohort 1, prophylactic efficacy against liver infection alone during the initial 7 days of the infection was determined by loading participants with azithromycin before challenge with P. falciparum-infected mosquitoes on day 0 and by then giving the drug for 7 days after the challenge. The regimen was 500 mg on day 14 before the challenge, followed by 250 mg/d from day 13 before the challenge through day 7 after the challenge. For cohort 2, prophylactic efficacy against both the liver infection and the subsequent blood infection was determined by continuing drug administration for 28 days after the challenge.. Plasmodium falciparum infection was diagnosed through peripheral blood smears obtained up to 70 days after challenge. Malarial symptoms and adverse drug reactions were also monitored.. In cohort 1, 4 of 10 volunteers who received azithromycin prophylaxis (40%) did not develop parasitemia. In cohort 2, none of the 10 volunteers receiving azithromycin prophylaxis (100%) developed parasitemia. For each cohort, both control volunteers became parasitemic on days 9 through 13 after the challenge. Adverse drug reactions were few and mild.. In this model, prophylaxis with azithromycin (250 mg/d) was partially effective against liver parasites and completely successful against the combination of liver and blood parasites. These data suggest that azithromycin has the potential to be an effective, well-tolerated clinical prophylactic agent for P. falciparum malaria.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antimalarials; Azithromycin; Drug Administration Schedule; Female; Humans; Liver Diseases, Parasitic; Malaria, Falciparum; Male; Middle Aged; Parasitemia

BACKGROUND Babesia species are intraerythrocytic parasitic protozoa that are endemic to the Northeast and north Midwest of the United States. Babesia microti is the most common cause of babesiosis in North America and causes a malaria-like tick-borne parasitosis. Babesia is commonly transmitted through the bite of Ixodes species ticks, often concomitantly with other tick-borne organisms such as Borrelia burgdorferi, Ehrlichia, Rickettsia rickettsii, and Anaplasma phagocytophilum. In the Midwest, Lyme disease is the most common tick-borne illness, and other organisms can sometimes be overlooked. The risk of tick-borne parasitic or bacterial infection is increased in patients after splenectomy. CASE REPORT An 89-year-old man with asplenia and multiple other comorbidities presented to the Emergency Department after a fall at home preceded by 2 to 3 days of fever and loss of appetite and 1 week of generalized weakness. The patient had thrombocytopenia, leukocytosis with neutrophilia, transaminitis, hyperbilirubinemia, and elevated creatine kinase level consistent with tick-borne illness. Laboratory testing revealed Borrelia and Babesia co-infection and other culprits were ruled out via high sensitivity PCR. Owing to the patient's asplenic status, the babesiosis was slow to resolve with appropriate treatment. After an extended 8-week treatment with azithromycin and atovaquone, the patient demonstrated clinical resolution of babesiosis with a negative blood smear. CONCLUSIONS First-line treatment with azithromycin and atovaquone is effective in treating babesiosis even in complicated patients, such as this elderly, asplenic patient. However, in cases such as this, an extended course of a first-line treatment regimen is still appropriate.

Topics: Aged; Aged, 80 and over; Atovaquone; Azithromycin; Babesia; Babesiosis; Humans; Male; Parasitemia; Trust; United States

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Atovaquone; Azithromycin; Babesiosis; BNT162 Vaccine; COVID-19; COVID-19 Drug Treatment; Fever; Humans; Leukemia, Myeloid, Acute; Male; Parasitemia; Remission Induction; SARS-CoV-2; Splenectomy

The relationship between malaria and malnutrition is complicated, and existence of one may predispose or exacerbate the other. We evaluated the relationship between malaria parasitemia and nutritional status in children living in communities participating in a cluster-randomized trial of biannual azithromycin compared with placebo for prevention of childhood mortality. Data were collected during the low malaria transmission and low food insecurity season. Parasitemia was not associated with weight-for-height

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Female; Humans; Infant; Malaria; Male; Mass Drug Administration; Niger; Nutritional Status; Parasitemia; Seasons

Neonatal tick bites place infants at risk for acquiring infections that have rarely or never been documented in this age group. We describe 2 rare cases of tickborne infection in neonates. The first patient presented with multiple erythema migrans and fever, leading to a diagnosis of early disseminated Lyme disease. The second patient presented with irritability, fever, and worsening anemia due to babesiosis. Both infants had been bitten by arthropods fitting the description of ticks before the onset of symptoms. Our cases demonstrate the clinical course of 2 common tickborne infections occurring at an atypical age, opening the door to new, complex questions for which little guiding data exists. As tickborne infections become more prevalent, we expect other clinicians will be faced with similarly challenging neonatal cases. Providers must use past experience and a keen eye to identify neonates with tickborne infections and sort through their optimal diagnosis and management. In this article, we raise some of the questions we faced and discuss our conclusions.

Topics: Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Atovaquone; Azithromycin; Babesiosis; Ceftriaxone; Erythema Chronicum Migrans; Exanthema; Female; Humans; Infant, Newborn; Parasitemia; Tick Bites

Mass administration of azithromycin for trachoma control led to a sustained reduction in all-cause mortality among Ethiopian children. Whether the addition of azithromycin to the monthly sulfadoxine-pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention could reduce mortality and morbidity among African children was unclear.. We randomly assigned children 3 to 59 months of age, according to household, to receive either azithromycin or placebo, together with sulfadoxine-pyrimethamine plus amodiaquine, during the annual malaria-transmission season in Burkina Faso and Mali. The drug combinations were administered in four 3-day cycles, at monthly intervals, for three successive seasons. The primary end point was death or hospital admission for at least 24 hours that was not due to trauma or elective surgery. Data were recorded by means of active and passive surveillance.. In July 2014, a total of 19,578 children were randomly assigned to receive seasonal malaria chemoprevention plus either azithromycin (9735 children) or placebo (9843 children); each year, children who reached 5 years of age exited the trial and new children were enrolled. In the intention-to-treat analysis, the overall number of deaths and hospital admissions during three malaria-transmission seasons was 250 in the azithromycin group and 238 in the placebo group (events per 1000 child-years at risk, 24.8 vs. 23.5; incidence rate ratio, 1.1; 95% confidence interval [CI], 0.88 to 1.3). Results were similar in the per-protocol analysis. The following events occurred less frequently with azithromycin than with placebo: gastrointestinal infections (1647 vs. 1985 episodes; incidence rate ratio, 0.85; 95% CI, 0.79 to 0.91), upper respiratory tract infections (4893 vs. 5763 episodes; incidence rate ratio, 0.85; 95% CI, 0.81 to 0.90), and nonmalarial febrile illnesses (1122 vs. 1424 episodes; incidence rate ratio, 0.79; 95% CI, 0.73 to 0.87). The prevalence of malaria parasitemia and incidence of adverse events were similar in the two groups.. Among children in Burkina Faso and Mali, the addition of azithromycin to the antimalarial agents used for seasonal malaria chemoprevention did not result in a lower incidence of death or hospital admission that was not due to trauma or surgery than antimalarial agents plus placebo, although a lower disease burden was noted with azithromycin than with placebo. (Funded by the Joint Global Health Trials scheme; ClinicalTrials.gov number, NCT02211729.).

Topics: Amodiaquine; Anti-Bacterial Agents; Antimalarials; Azithromycin; Burkina Faso; Child Mortality; Child, Preschool; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Hospitalization; Humans; Incidence; Infant; Infant Mortality; Malaria; Male; Mali; Mass Drug Administration; Parasitemia; Pyrimethamine; Sulfadoxine

Human African trypanosomosis (HAT) and animal African trypanosomosis (AAT) are diseases of economic importance in humans and animals that affect more than 36 African countries. The currently available trypanocidal drugs are associated with side effects, and the parasites are continually developing resistance. Thus, effective and safe drugs are needed for the treatment of HAT and AAT. This study aimed to evaluate the effects of azithromycin (AZM) on Trypanosoma brucei brucei-infected mice. Mice were randomly divided into 7 groups consisting of a vehicle control group, 5 test groups and a diminazene aceturate (DA)-treated group. Mice were treated orally for 7 and 28 days, as short-term and long-term treatments, respectively. Short-term AZM treatment cured 23% (16 of 70) of the overall treated mice whereas long-term treatment resulted in the survival of 70% of the mice in the groups that received AZM at doses of 300 and 400 mg/kg. Trypanosomes treated in vitro with 25 μg/mL of AZM were subjected to transmission electron microscopy, which revealed the presence of increased numbers of glycosomes and acidocalcisomes in comparison to the vehicle group. The current study showed the trypanocidal effect of AZM on T. b. brucei in vivo. The demonstrated efficacy increased with an increase in treatment period and an increased concentration of AZM.

Topics: Administration, Oral; Animals; Anti-Infective Agents; Azithromycin; Body Weight; Female; Inhibitory Concentration 50; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Parasitemia; Random Allocation; Survival Rate; Time Factors; Trypanosoma brucei brucei; Trypanosomiasis, African

Piroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml.. Fifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity.. Before treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result.. IMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.

Topics: Animals; Antiprotozoal Agents; Atovaquone; Azithromycin; Babesia microti; Babesiosis; Dog Diseases; Dogs; Drug Therapy, Combination; Europe; Female; Imidocarb; Male; Naphthoquinones; Parasitemia; Polymerase Chain Reaction

Topics: Animals; Anti-Bacterial Agents; Antimalarials; Atovaquone; Azithromycin; Babesia; Babesiosis; Drug Resistance; Drug Therapy, Combination; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Parasitemia; Stem Cell Transplantation

Despite major efforts over the past 50 years to develop a malaria vaccine, no product has been licensed yet. Irradiated sporozoites are the benchmark for an experimental live-attenuated malaria vaccine that induces potent protection against re-infection in humans and animal models. Lasting protection can also be elicited by parasite attenuation via tailored genetic modification or drug cover leading to renewed interest in whole-organism vaccination strategies. In this study, we systematically compared the protective efficacy of different whole-organism vaccination approaches in the Plasmodium berghei/C57bl/6 rodent malaria model. We applied blood stage parasitemia and quantitative RT-PCR of liver parasite loads as two complementary primary endpoints of a malaria challenge infection. We were able to demonstrate similar potency of genetic attenuation, i.e., uis3(-) and p36p(-) parasites, and prophylactic drug cover, i.e., azithromycin, pyrimethamine, primaquine and chloroquine, during sporozoite exposure in comparison to irradiated sporozoites. Importantly, when animals were covered with the antibiotic azithromycin during sporozoite exposure we observed superior protection. On the other end, immunizations with heat-killed and over-irradiated sporozoites failed to confer any detectable protection. Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy.

Topics: Animals; Azithromycin; CD8-Positive T-Lymphocytes; Chloroquine; Erythrocytes; Female; Liver; Malaria; Malaria Vaccines; Mice; Mice, Inbred C57BL; Parasite Load; Parasitemia; Plasmodium berghei; Sporozoites; Vaccination; Vaccines, Attenuated

Babesiosis is an emerging tickborne malaria-like infection principally caused by Babesia microti. This infection typically resolves either spontaneously or after administration of a 7-10-day course of azithromycin plus atovaquone or clindamycin plus quinine. Although certain highly immunocompromised patients may respond suboptimally to these drug regimens, unlike the situation with malaria there has been no reported evidence that the cause of treatment failure is infection with drug-resistant strains of B. microti.. Emergence of drug resistance in B. microti was defined as the development of a microbiologic relapse (recurrent parasitemia or a marked increase in parasitemia) in association with both clinical and laboratory abnormalities indicative of active babesiosis in a patient after 28 days of uninterrupted antibabesia drug therapy and while still receiving treatment.. The clinical case histories of 3 highly immunocompromised patients who received a subcurative course of azithromycin-atovaquone associated with the eventual development of resistance to this drug regimen are described. One of the 3 patients died of complications related to babesiosis.. B. microti may become resistant to azithromycin-atovaquone during the treatment of babesiosis with this combined drug regimen in highly immunocompromised patients. Although research is needed to determine the optimal therapy for highly immunocompromised patients with babesiosis, reducing the level of immunosuppression when possible would appear to be a desirable strategy.

Topics: Aged, 80 and over; Animals; Antiprotozoal Agents; Atovaquone; Azithromycin; Babesia microti; Babesiosis; Drug Resistance; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Male; Middle Aged; Parasitemia

Babesia gibsoni is a protozoan parasite of dogs worldwide yet both an effective treatment and a reliable method for detecting subclinical cases of this emerging infection remain elusive. Experimental B. gibsoni infections were established in vivo to investigate the efficacy of combined atovaquone and azithromycin drug therapy and to determine the detection limits of a nested-PCR, IFAT and microscopy during various stages of infection. While atovaquone and azithromycin produced a reduction in parasitaemia, it did not eliminate the parasite and drug resistance appeared to develop in one dog. Polymerase chain reaction was found to be most useful in detecting infection in the pre-acute and acute stages, while IFAT was most reliable during chronic infections. Microscopy is suggested to be only effective for detecting acute stage infections. This study also describes the detection of B. gibsoni in tissue samples during chronic infections for the first time, suggesting possible sequestration of this parasite.

Topics: Acute Disease; Animals; Anti-Infective Agents; Antibodies, Protozoan; Atovaquone; Azithromycin; Babesia; Babesiosis; Chronic Disease; DNA, Protozoan; Dog Diseases; Dogs; Drug Resistance; Female; Fluorescent Antibody Technique; Parasitemia; Polymerase Chain Reaction

Many different drug-resistant lines of rodent malaria are available as screening models. It is obligatory to screen new compounds for antimalarial activity against a series of resistant lines in order to identify a compound with potential for the treatment of multi-drug resistant (MDR) malaria infections. Instead of using a battery of resistant lines, a single MDR Plasmodium yoelii nigeriensis strain that shows a wide spectrum of drug resistance to high doses of chloroquine, mepacrine, amodiaquine, mefloquine, quinine, quinidine, halofantrine as well as tetracyclines, fluoroquinolines and erythromycin, was used to assess the blood schizontocidal efficacy of a new macrolide azithromycin and other antibiotics. The present study shows that only azithromycin has the potential to control an MDR P. y. nigeriensis infection in Swiss mice, provided the treatment with a dose of 50-100 mg/kg/day by oral route is continued for a period of 7 days. Tetracycline, oxytetracycline, doxycyline, erythromycin, ciprofloxacin and norfloxacin, although active in vitro, failed to protect the mice. Tetracycline, ciprofloxacin and norfloxacin combinations with chloroquine did not control the infection. Additionally, the antimalarial efficacy of azithromycin can be potentiated with the addition of arteether, which is an ethyl ether derivative of artemisinin. A total (100%) curative effect has been obtained with a shorter regimen of 4 days only.

Topics: Animals; Antimalarials; Artemisinins; Azithromycin; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Therapy, Combination; Mice; Parasitemia; Plasmodium yoelii

The spectrum of antimalarial activity of the new macrolide antibiotic azithromycin was evaluated against blood- and sporozoite-induced infections with a chloroquine-resistant strain of Plasmodium yoelii nigeriensis (N-67) in Swiss mice and with simian parasite Plasmodium cynomolgi B in rhesus monkeys. Against experimental rodent malaria, a 70 mg/kg/day dose showed curative blood-schizontocidal activity in a four-dose regimen administered orally from day 0 to day 3 or from day 2 to day 5 to mice harboring established infection. The curative response was also obtained with a 40 mg/kg/day dose administered in an extended seven-dose (days 0-6) regimen. Azithromycin was also effective in the causal prophylactic test, since a 50 mg/kg dose from day -1 to day +2 protected mice against P. y. nigeriensis (N-67) sporozoite challenge. In comparison, erythromycin did not show either of the above activities up to a 405 mg/kg/day dose in identical regimens. Comparison of the ED(90) values showed that azithromycin was 31-fold more effective than erythromycin as a blood schizontocide. In the simian model, trophozoite-induced infections of P. cynomolgi B were cured with 25 mg/kg/day azithromycin administered for 7 days. In the causal prophylactic test, the prepatent period was significantly extended in monkeys challenged with P. cynomolgi B sporozoites, presumably because of the growth inhibition of preerythrocytic schizonts in hepatocytes. Azithromycin did not exhibit any hypnozoitocidal (dormant exoerythrocytic stages) activity at 25 mg/kg/day in a seven-dose regimen.

Topics: Animals; Anti-Bacterial Agents; Antimalarials; Azithromycin; Chloroquine; Doxycycline; Erythromycin; Female; Macaca mulatta; Malaria; Male; Mice; Parasitemia; Plasmodium cynomolgi; Plasmodium yoelii; Primaquine; Pyrimethamine

Babesiosis is a malaria-like, tick-transmitted zoonosis caused by protozoa of the family Piroplasmorida, which includes Babesia and Theileria species. In the United States, the infection is endemic in the Northeast and upper Midwest, although cases have recently been described in Northern California and Washington State. We report a case of babesiosis in a patient infected with HIV who presented with a prolonged fever of unknown origin; the patient had not undergone splenectomy. Parasitemia persisted despite initial clinical improvement after treatment with quinine and clindamycin. Babesiosis was controlled with a maintenance regimen consisting of clindamycin, doxycycline, and high-dose azithromycin, but the infection was not eradicated. Babesiosis should be considered in the differential diagnosis of HIV-infected patients with fevers and/or anemia in areas where the infection is endemic. HIV-infected patients who are severely immunosuppressed, even those without a history of splenectomy, may present with severe manifestations of babesiosis and develop a chronic infection, which may require therapy to prevent relapse of disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; Azithromycin; Babesiosis; Chronic Disease; Clindamycin; Doxycycline; Drug Therapy, Combination; Fever of Unknown Origin; Humans; Male; Parasitemia; Quinine

The traditional therapy for the treatment of human Babesia microti infections has been the combination of clindamycin and quinine. However, in recent years, it has become apparent that some patients have not responded to this regimen. We became involved in the treatment of several cases of babesiosis in which atovaquone was used to treat this infection. Therefore, using the hamster model, we determined the efficacy of atovaquone alone as well as atovaquone plus azithromycin for the treatment of experimental babesiosis. Atovaquone (100 mg/kg/day) and atovaquone (100 mg/kg/day) with azithromycin (150 mg/kg/day) were effective agents for the treatment of experimental babesiosis in hamsters. When atovaquone was used as monotherapy recrudescences occurred. Organisms obtained from recrudescent animals, when inoculated into uninfected animals, proved to be unresponsive to atovaquone therapy, suggesting the emergence of drug resistance. Resistant organisms did not emerge in hamsters treated with the combination of atovaquone and azithromycin. Atovaquone should be considered in the therapeutic regimen of patients with babesiosis who have either failed standard therapy or have become intolerant to such therapy.

Topics: Animals; Anti-Bacterial Agents; Antimalarials; Antiprotozoal Agents; Artemisinins; Atovaquone; Azithromycin; Babesiosis; Cricetinae; Disease Models, Animal; Drug Therapy, Combination; Naphthoquinones; Parasitemia; Recurrence; Sesquiterpenes

We compared the efficacy of azithromycin to the clinical antimalarial doxycycline in Plasmodium berghei-infected mice and in P. falciparum-infected Aotus monkeys. When mice were administered drug orally twice a day for three days, the minimum total dose of azithromycin that cured all mice was 768 mg/kg. Doxycycline at a dose of 1,536 mg/kg cured no mice. The efficacy of fast-acting blood schizonticides (quinine, halofantrine, artemisinin) against P. berghei was augmented by azithromycin. In monkey experiments in which there were two animals per experimental group, azithromycin (100 mg/kg/day for seven days) eliminated parasitemia; azithromycin (30 mg/kg/day) initially cleared 99.8-100% of the parasites with recrudescence in the one completely cleared case. Doxycycline (30 mg/kg/day) cleared 100% of the parasites with recrudescence in both cleared cases. Since azithromycin can be clinically administered at a somewhat higher daily dosage than doxycycline, the data suggest that it may be possible to replace drugs of the tetracycline class with azithromycin in combination with fast-acting blood schizonticides for the treatment of P. falciparum infection.

Topics: Administration, Oral; Animals; Antimalarials; Aotus trivirgatus; Artemisinins; Azithromycin; Disease Models, Animal; Doxycycline; Drug Therapy, Combination; Humans; Injections, Subcutaneous; Malaria; Malaria, Falciparum; Mice; Parasitemia; Phenanthrenes; Plasmodium berghei; Quinine; Sesquiterpenes