Birth weight, growth, nutritional status and mortality of infants from Lambaréné and Fougamou in Gabon in their first year of life.

BACKGROUND: Malnutrition and low birth weight (LBW) are two common causes of morbidity and mortality among children in sub-Saharan Africa. Both malnutrition and LBW affect early childhood development with long term consequences that may vary in their degree depending on the geographical setting. This study evaluates growth, nutritional status and mortality of infants from Lambaréné and Fougamou in Gabon from a birth cohort of a malaria in pregnancy clinical trial (NCT00811421). METHOD: A prospective longitudinal birth cohort conducted between 2009 and 2012, included infants that were followed up from birth until their first-year anniversary. The exposure of interest was low birth weight and the outcomes explored were growth represented by weight gain, the nutritional status including stunting, wasting and underweight, and the mortality. Scheduled follow-up visits were at one, nine and 12 months of age. Logistic regression was used to assess the association between low birth weight and growth and nutritional outcomes, and cox regression was used for mortality. RESULT: A total of 907 live-born infants were included in the analysis. The prevalence of LBW was 13% (115). At one month of life, out of 743 infants 10% and 4% presented with stunting and underweight, respectively, while these proportions increased at 12 months of life to 17% and 21%, respectively, out of 530 infants. The proportion of infants with wasting remained constant at 7% throughout the follow-up period. Stunting and underweight were associated with LBW, adjusted odds ratio (aOR): 2.6, 95% confidence interval (95%CI): 1.4-4.9 and aOR: 4.5, 95%CI: 2.5-8.1, respectively. Preterm birth was associated with stunting, aOR: 2.7, 95%CI: 1.2-6.3 and underweight, aOR: 5.4, 95%CI: 1.7-16.1 at one month of life. Infants with LBW were at higher hazard of death during the first year of life, adjusted hazard ratio 4.6, 95%CI: 1.2-17.0. CONCLUSION: Low birthweight infants in Gabon are at higher risks of growth and nutritional deficits and mortality during the first year of life. Tailored interventions aiming at preventing adverse pregnancy outcomes including LBW, early detection and appropriate management of growth, and nutritional deficits in infants are necessary in Gabon.

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.

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. METHODS AND FINDINGS: A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86-1.22; p=0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51-0.96]; p=0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85-0.99]; p=0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52-0.88]; p=0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78-0.95]; p=0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment. CONCLUSIONS: Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary.

Short report: premastication in rural Gabon--a cross-sectional survey.

Premastication-defined as pre-chewing of food for infants by their caregiver-is a common feeding practice in various societies. To date the impact of premastication on children's health including the potential for transmission of infectious diseases is not well understood. Since there are no epidemiologic data on premastication from resource poor regions in Central Africa, we investigated the epidemiology and demographic variables associated with premastication in Central Africa. Between 2011 and 2012, mothers were interviewed about child feeding behaviors in three rural communities in Gabon. A quarter (n = 20, 24%) of 82 participants stated to perform premastication regularly. Despite the small sample size, our study provides first baseline data for the epidemiology of premastication in Central Africa, indicating that this feeding practice is common in rural communities.

Malaria in pregnancy in rural Gabon: a cross-sectional survey on the impact of seasonality in high-risk groups.

BACKGROUND: Malaria remains one of the most important infectious diseases in pregnancy in sub-Saharan Africa. Whereas seasonal malaria chemoprevention is advocated as public health intervention for children in certain areas of highly seasonal malaria transmission, the impact of seasonality on malaria in pregnancy has not yet been investigated for stable, hyper-endemic transmission settings of Equatorial Africa. The aim of this study was to investigate the influence of seasonality on the prevalence of malaria in pregnancy in Gabon. METHODS: The study was conducted at a rural district hospital in Gabon between January 2008 and December 2011. At first antenatal care visits demographic data, parity, age, and gestational age of pregnant women were documented and thick blood smears were performed for the diagnosis of malaria. Seasonality and established risk factors were evaluated in univariate and multivariate analysis for their association with Plasmodium falciparum infection. RESULTS: 1,661 pregnant women were enrolled in this study. Participants presenting during high transmission seasons were at significantly higher risk for P. falciparum infection compared to low transmission seasons (adjusted odds ratio [AOR] 1.91, 95% confidence interval [CI] 1.39-2.63, p < 0.001). Established risk factors including parity (AOR 0.45, CI 0.30-0.69, p < 0.001 for multipara versus paucipara) and age (AOR, CI and p-value for women aged 13-17, 18-22, 23-27 and ≥ 28 years, respectively: AOR 0.59, CI 0.40-0.88; AOR 0.57, CI 0.34-0.97; AOR 0.51, CI 0.29-0.91) were significant risk factors for P. falciparum infection. High-risk groups including nulli- and primipara and younger women aged 13-17 years showed a disproportionately increased risk for malaria in high transmission seasons from 17% to 64% prevalence in low and high transmission periods, respectively. CONCLUSION: Seasonal variations lead to important differences in the risk for P. falciparum infection in pregnancy in the setting of central African regions with stable and hyper-endemic malaria transmission. The seasonal increase in malaria in pregnancy is most pronounced in high-risk groups constituted by young and pauciparous women. The evaluation of tailored seasonal prevention strategies for these high-risk populations may, therefore, be warranted.