Population Pharmacokinetics of Mefloquine Intermittent Preventive Treatment for Malaria in Pregnancy in Gabon.

Mefloquine was evaluated as an alternative for intermittent preventive treatment of malaria in pregnancy (IPTp) due to increasing resistance against the first-line drug sulfadoxine-pyrimethamine (SP). This study determined the pharmacokinetic characteristics of the mefloquine stereoisomers and the metabolite carboxymefloquine (CMQ) when given as IPTp in pregnant women. Also, the relationship between plasma concentrations of the three analytes and cord samples was evaluated, and potential covariates influencing the pharmacokinetic properties were assessed. A population pharmacokinetic analysis was performed with 264 pregnant women from a randomized controlled trial evaluating a single and a split-dose regimen of two 15-mg/kg mefloquine doses at least 1 month apart versus SP-IPTp. Both enantiomers of mefloquine and its carboxy-metabolite (CMQ), measured in plasma and cord samples, were applied for pharmacokinetic modelling using NONMEM 7.3. Both enantiomers and CMQ were described simultaneously by two-compartment models. In the split-dose group, mefloquine bioavailability was significantly increased by 5%. CMQ induced its own metabolism significantly. Maternal and cord blood concentrations were significantly correlated (r2 = 0.84) at delivery. With the dosing regimens investigated, prophylactic levels are not constantly achieved. A modeling tool for simulation of the pharmacokinetics of alternative mefloquine regimens is presented. This first pharmacokinetic characterization of mefloquine IPTp indicates adequate exposure in both mefloquine regimens; however, concentrations at delivery were below previously suggested threshold levels. Our model can serve as a valuable tool for researchers and clinicians to develop and optimize alternative dosing regimens for IPTp in pregnant women.

Epidemiology of Human Herpes Virus 8 in Pregnant Women and their Newborns--A cross-sectional delivery survey in Central Gabon.

OBJECTIVES: On the background of a high prevalence of HHV-8 infection in pre-pubertal Central African children, this study investigated the potential for in utero transmission of HHV-8. PATIENTS: Gabonese pregnant women were invited to provide peripheral and cord blood samples for serological and PCR diagnostics of HHV-8 infection at delivery for this cross-sectional survey. RESULTS: Out of 344 participants 120 (35%, 95% CI: 30-40%) were serologically positive for HHV-8. 31% (95% CI: 22-40%) of cord blood samples of seropositive women had detectable IgG antibodies. Among all seropositive participants HHV-8 was detected by PCR in one maternal peripheral blood sample at delivery (1%, 95% CI: 0.2-7%) and in none of cord blood samples. There was no association between demographic characteristics and infection status. Similarly, there was no difference in risk for premature delivery, low birth weight, and maternal anaemia in HHV-8 seropositive women. DISCUSSION: These data suggest a high seroprevalence of HHV-8 infection in pregnant women, however viraemia at delivery does not commonly occur in Central Africa. Based on these observations it may be speculated that infection of children may occur more commonly either antepartum or later on in infancy and childhood.

Evaluation of intermittent preventive treatment of malaria against group B Streptococcus colonization in pregnant women: a nested analysis of a randomized controlled clinical trial of sulfadoxine/pyrimethamine versus mefloquine.

OBJECTIVES: Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine-the current intermittent preventive treatment of malaria in pregnancy (IPTp)-has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine-an antimalarial without in vitro activity against GBS-was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp. METHODS: Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth outcome analyses were computed. RESULTS: Among 549 participants, 106 were positive for GBS colonization at delivery (19%; 95% CI = 16%-23%). Prevalence of maternal GBS colonization showed no significant difference between the two IPTp regimens (mefloquine-IPTp: 67 of 366 women = 18%; 95% CI = 14%-22%; sulfadoxine/pyrimethamine-IPTp: 39 of 183 women = 21%; 95% CI = 15%-27%). Risk factor analysis for GBS colonization demonstrated a significant association with illiteracy (adjusted OR = 2.03; 95% CI = 1.25-3.30). GBS colonization had no impact on birth outcome, anaemia at delivery, gestational age and birth weight. CONCLUSIONS: Sulfadoxine/pyrimethamine did not reduce colonization rates when used as the IPTp drug during pregnancy. Illiteracy was associated with GBS colonization.

Efficacy of mefloquine intermittent preventive treatment in pregnancy against Schistosoma haematobium infection in Gabon: a nested randomized controlled assessor-blinded clinical trial.

BACKGROUND: Urogenital schistosomiasis is a major public health problem in sub-Saharan Africa, and routine programs for screening and treatment of pregnant women are not established. Mefloquine-currently evaluated as a potential alternative to sulfadoxine-pyrimethamine as intermittent preventive treatment against malaria in pregnancy (IPTp)-is known to exhibit activity against Schistosoma haematobium. In this study we evaluated the efficacy of mefloquine IPTp against S. haematobium infection in pregnant women. METHODS: Pregnant women with S. haematobium infection presenting at 2 antenatal health care centers in rural Gabon were invited to participate in this nested randomized controlled, assessor-blinded clinical trial comparing sulfadoxine-pyrimethamine with mefloquine IPTp. Study drugs were administered twice during pregnancy with a 1- month interval after completion of the first trimester. RESULTS: Sixty-five pregnant women were included in this study. Schistosoma haematobium egg excretion rates showed a median reduction of 98% (interquartile range [IQR], 70%-100%) in the mefloquine group compared to an increase of 20% (IQR, -186% to 75%) in the comparator group. More than 80% of patients showed at least 50% reduction of egg excretion and overall cure rate was 47% (IQR, 36%-70%) 6 weeks after the second administration of mefloquine IPTp. CONCLUSION: When used as IPTp for the prevention of malaria, mefloquine shows promising activity against concomitant S. haematobium infection leading to an important reduction of egg excretion in pregnant women. Provided that further studies confirm these findings, the use of mefloquine may transform future IPTp programs into a 2-pronged intervention addressing 2 of the most virulent parasitic infections in pregnant women in sub-Saharan Africa. CLINICAL TRIALS REGISTRATION: NCT01132248; ATMR2010020001429343.

Prospective evaluation of artemether-lumefantrine for the treatment of non-falciparum and mixed-species malaria in Gabon.

BACKGROUND: The recommendation of artemisinin combination therapy (ACT) as first-line treatment for uncomplicated falciparum malaria is supported by a plethora of high quality clinical trials. However, their recommendation for the treatment of mixed-species malaria and the large-scale use for the treatment of non-falciparum malaria in endemic regions is based on anecdotal rather than systematic clinical evidence. METHODS: This study prospectively observed the efficacy of artemether-lumefantrine for the treatment of uncomplicated non-falciparum or mixed-species malaria in two routine district hospitals in the Central African country of Gabon. RESULTS: Forty patients suffering from uncomplicated Plasmodium malariae, Plasmodium ovale or mixed-species malaria (including Plasmodium falciparum) presenting at the hospital received artemether-lumefantrine treatment and were followed up. All evaluable patients (n=38) showed an adequate clinical and parasitological response on Day 28 after oral treatment with artemether-lumefantrine (95% confidence interval: 0.91,1). All adverse events were of mild to moderate intensity and completely resolved by the end of study. CONCLUSIONS: This first systematic assessment of artemether-lumefantrine treatment for P. malariae, P. ovale and mixed-species malaria demonstrated a high cure rate of 100% and a favourable tolerability profile, and thus lends support to the practice of treating non-falciparum or mixed-species malaria, or all cases of malaria without definite species differentiation, with artemether-lumefantrine in Gabon. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00725777.