Prospective Clinical and Molecular Evaluation of Potential Plasmodium ovale curtisi and wallikeri Relapses in a High-transmission Setting.

BACKGROUND: Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites. Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce. The aim of this prospective study was to characterize the reappearance patterns of ovale parasites. METHODS: P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia. Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria. RESULTS: At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri. The median duration of follow-up was 35 weeks. Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32. Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi. CONCLUSION: These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated. Interestingly, no relapse of P. ovale wallikeri was observed.

Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study.

BACKGROUND: Little is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes. METHODS AND FINDINGS: In the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%). CONCLUSIONS: No significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00811421.

Malaria in urban, semi-urban and rural areas of southern of Gabon: comparison of the Pfmdr 1 and Pfcrt genotypes from symptomatic children.

BACKGROUND: Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are first- and second-line treatments for uncomplicated Plasmodium falciparum malaria in Gabon. AL remains highly efficacious, but its widespread use has led to molecular selection of the NFD haplotype on Pfmdr1 and K76 in Pfcrt. In this study, plasmodial infection characteristics and the distribution of the Pfmdr1 and Pfcrt genotypes involved in reduced efficacy of artemisinin-based combination therapy (ACT) were investigated in four Gabonese localities. METHODS: A cross-sectional study was conducted in the paediatric units of rural (Lastourville and Fougamou), semi-urban (Koula-Moutou) and urban (Franceville) areas. Malaria was diagnosed with the rapid diagnostic test Optimal-IT(®) and confirmed by blood smear. Pfmdr1 codons 86, 184 and 1246 and Pfcrt codon 76 were genotyped by PCR-RFLP and sequencing. RESULTS: Among 1129 included children, the prevalence of plasmodial infection was 79.5 % at Lastourville, 53.6 % at Fougamou, 36.1 % at Koula-Moutou, and 21.2 % at Franceville. The prevalence was significantly higher among children over 60 months of age in both semi-urban (p = 0.01) and urban (p = 0.004) areas. The prevalence of Pfmdr1 wild-type N86 differed significantly between Lastourville (57.8 %) and Koula-Moutou (45.4 %) (p = 0.039). No difference in 184F-carrying parasites was found between Lastourville (73.8 %), Fougamou (81.6 %), Koula-Moutou (83.2 %), and Franceville (80.6 %) (p = 0.240). The prevalence of wild-type D1246 was significantly different between Lastourville (94.1 %), Koula-Moutou (85.6 %) and Franceville (87.3 %) (p = 0.01). The frequency of wild-type K76 was not significantly different across the four sites: Lastourville (16.5 %), Fougamou (27.8 %), Koula-Moutou (17.4 %), and Franceville (29.4 %) (p = 0.09). The mixed genotypes were only found in Lastourville and Franceville. The NFD, YFD and NYD haplotypes were mainly Lastourville (46.6, 25.8, 14.0 %), Fougamou (45.5, 9.1, 42.4 %), Koula-Moutou (35, 6.7, 40.4 %), and Franceville (40.0, 16.0, 32.0 %). CONCLUSION: This study shows an increase in the prevalence of childhood plasmodial infection in Gabon according to the low socio-economic level, and a high frequency of markers associated with AL treatment failure. Close monitoring of ACT use is needed.

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.