Burnout level and associated factors in a sub-Saharan African medical setting: prospective cross-sectional survey.

BACKGROUND: Burnout in the hospital environment is a problem that affects care and training. Often explored in the high-income medical context, burnout is poorly studied in low and middle-income countries characterized by a precarious hospital situation and a high stake linked to the Millennium Development Goals. The aim of our study was to determine in medical practitioners, in a sub-Saharan African country's medical context, the burnout level and associated factors. METHODS: A prospective cross-sectional study by using a self-administered Likert-scale questionnaire addressed to doctors and doctoral medical students in Gabon. Maslach Burnout Inventory scale has been used. Burnout symptoms were defined by high level in at least one of the 3 dimensions. Severe burnout defined by high level in all dimensions. Explored factors: socio-demographic and psychometric. Multiple logistic regression has been performed. RESULTS: Among 104 participants, severe burnout prevailed at 1.9% (95% CI: 0.2-6.8%) and burnout symptoms at 34.6% (95% CI: 25, 6-44.6%). The associated factors with burnout symptoms: age (OR = 0.86, p = 0.004), clinical activity in a university hospital center (OR = 5.19, p = 0.006), the easy access to the hospital (OR = 0.59, p = 0.012), number of elderly dependents living with the practitioner (OR = 0.54, p = 0.012), place of residence (same borough where the hospital is located: OR = 4.09, p = 0.039) and to be favorable to traditional medicine (OR = 1.82, p = 0.087). Nagelkerke's R-squared:53.1%. CONCLUSION: In Gabon, middle-income country, almost one practitioner in two has burnout symptoms. The young age, the university hospital center, the difficulty to access to hospital and to live in the borough where the hospital is located increase the probability of burnout symptoms. These results must put question to relevant authorities regarding health and medical education, to set up: a public transport for practitioners, an optimal primary health care system, a regulation of medical tasks in hospitals, a training in clinical supervision.

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.

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.

In vitro growth of Plasmodium falciparum in neonatal blood.

BACKGROUND: Children below the age of six months suffer less often from malaria than older children in sub-Saharan Africa. This observation is commonly attributed to the persistence of foetal haemoglobin (HbF), which is considered not to permit growth of Plasmodium falciparum and therefore providing protection against malaria. Since this concept has recently been challenged, this study evaluated the effect of HbF erythrocytes and maternal plasma on in vitro parasite growth of P. falciparum in Central African Gabon. METHODS: Umbilical cord blood and peripheral maternal blood were collected at delivery at the Albert Schweitzer Hospital in Gabon. Respective erythrocyte suspension and plasma were used in parallel for in vitro culture. In vitro growth rates were compared between cultures supplemented with either maternal or cord erythrocytes. Plasma of maternal blood and cord blood was evaluated. Parasite growth rates were assessed by the standard HRP2-assay evaluating the increase of HRP2 concentration in Plasmodium culture. RESULTS: Culture of P. falciparum using foetal erythrocytes led to comparable growth rates (mean growth rate = 4.2, 95% CI: 3.5 - 5.0) as cultures with maternal red blood cells (mean growth rate =4.2, 95% CI: 3.4 - 5.0) and those from non-malaria exposed individuals (mean growth rate = 4.6, 95% CI: 3.8 - 5.5). Standard in vitro culture of P. falciparum supplemented with either maternal or foetal plasma showed both significantly lower growth rates than a positive control using non-malaria exposed donor plasma. CONCLUSIONS: These data challenge the concept of HbF serving as intrinsic inhibitor of P. falciparum growth in the first months of life. Erythrocytes containing HbF are equally permissive to P. falciparum growth in vitro. However, addition of maternal and cord plasma led to reduced in vitro growth which may translate to protection against clinical disease or show synergistic effects with HbF in vivo. Further studies are needed to elucidate the pathophysiology of innate and acquired protection against neonatal malaria.

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.

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.

Intravenous infusion of glucose 5% despite sodium mixed, is main contributor of acquired hyponatremia in adult polyvalent medicine service: Case control study.

BACKGROUND: Acquired hyponatremia is a life threatening event. Intravenous infusion of a mixture of 5% glucose and sodium solute is mainly used, but its contribution in the occurrence of acquired hyponatremia in adult, is under-investigated outside intensive care unit. OBJECTIVE: To evaluate the place of intravenous infusion of a mixture of 5% glucose and sodium in predicting acquired hyponatremia in adult polyvalent medicine service. PATIENTS AND METHODS: A case-control study have been conducted. The main exposure was intravenous infusion of a mixture of 5% glucose and sodium solute (4 grams NaCl/liter of 5% glucose). OUTCOME: Acquired hyponatremia during hospitalization. By logistic regression, the global multifactorial model predicting acquired hyponatremia, and its sub-models were established; as well as following parameters: area under the Receiving Operator Characteristic curve (AUC), maximal Youden's index with its couple of coordinates (sensibility-specificity), Nagelkerke's R-squared adjusted. RESULTS: Adjusted odds ratio (cases/controls; main exposure; outcome) ORa=2.73 (95% CI 1.40-5.32; P=0.003). Prediction of acquired hyponatremia: global multifactorial model: AUC=0.78 (95% CI 0.72-0.85; P<0.0001), Youden's index=0.34 (95% CI 0.24-0.41); sub-model (global multifactorial model without main exposure): AUC=0.72 (95% CI 0.66-0.78; P<0.0001), Youden's index=0.18 (95% CI 0.07-0.22). CONCLUSION: Intravenous infusion of a mixture of 5% glucose and sodium mainly used, highly contribute to predict acquired hyponatremia in adult polyvalent medicine service, and should be the first cause to consider for managing this acquired hyponatremia.

The baseline glomerular filtration rate, predictive of six-year survival in sub-Saharan African patients on antiretroviral therapy for HIV: Cohort study.

BACKGROUND: Recently, serious morbidity events associated with initial glomerular filtration rate (GFR) have been described during HIV infection, but this is insufficiently investigated in sub-Saharan Africa very affected by HIV. OBJECTIVE: To assess the impact of baseline GFR prevailing during the first semester of the HIV infection management on six-year survival in peoples taking antiretroviral therapy. PATIENTS AND METHODS: Closed retrospective cohort study. The death was the expected outcome, the baseline GFR (mL/min/1.73m2) in the first semester of the follow-up was the main exposure. Kaplan-Meier method, Cox regression were used for analysis. RESULTS: According to baseline GFR: <60, 60-89 and≥90, the six-year survival was 81.6%; 95.8% and 96.4% (P=0.067 Breslow). Adjusted hazard ratio for baseline GFR<60 and 60-89 (vs. ≥90) were respectively 5.4 (95%CI: 1.4-19.9; P=0.012) and 1.2 (95%CI: 0.3-4.0; P=0.754). The etiological fraction of deaths attributable to baseline GFR: GFR<60: 81% (95%CI: 0.31-0.95), GFR=60-89: 18.0% (95%CI: -0.7-0.8). Prognostic concordance index=0.84 (95%CI: 0.59-0.95) for GFR<60 and 0.55 (95%CI: 0.27-0.81) for GFR 60-89. DISCUSSION: The etiological fraction of death and prognostic concordance index associated to baseline GFR level increase significantly with decline of baseline GFR. CONCLUSION: Baseline GFR seems to predict the six-year survival in African sub-Saharan patients treated for HIV.

Urogenital schistosomiasis during pregnancy is associated with low birth weight delivery: analysis of a prospective cohort of pregnant women and their offspring in Gabon.

An estimated 40 million women of childbearing age suffer from schistosomiasis. Animal models indicate a deleterious effect of maternal schistosomiasis on pregnancy outcomes. To date there is a lack of epidemiological evidence evaluating schistosomiasis-related morbidity in pregnancy. This study was designed to describe the impact of urogenital schistosomiasis on pregnancy outcomes in a highly endemic region of central Africa. Pregnant women attending antenatal clinics in Fougamou and Lambaréné, Gabon, were consecutively screened for the presence of Schistosoma haematobium eggs in diurnal urine samples. Maternal and newborn characteristics assessed at delivery were compared between infected and uninfected mothers. The impact of maternal schistosomiasis on low birth weight and preterm delivery was assessed using logistic regression analysis. Urogenital schistosomiasis was diagnosed in 103 (9%) of 1115 pregnant women. Maternal age was inversely associated with the prevalence of urogenital schistosomiasis, with a higher burden amongst nulliparous women. Low birth weight was more common amongst infants of S. haematobium-infected mothers. This association was unaffected by controlling for demographic characteristics, gestational age and Plasmodium infection status (adjusted Odds Ratio 1.93; 95% confidence interval: 1.08-3.42). Other risk factors associated with low birth weight delivery were underweight mothers (adjusted Odds Ratio 2.34; 95% confidence interval: 1.12-4.92), peripheral or placental Plasmodium falciparum infection (adjusted Odds Ratio 2.04; 95% confidence interval: 1.18-3.53) and preterm birth (adjusted Odds Ratio 3.12; 95% confidence interval: 1.97-4.96). Preterm delivery was not associated with S. haematobium infection (adjusted Odds Ratio 1.07 95% confidence interval: 0.57-1.98). In conclusion, this study indicates that pregnant women with urogenital schistosomiasis are at an increased risk for low birth weight deliveries. Further studies evaluating targeted treatment and prevention programmes for urogenital schistosomiasis in pregnant women and their impact on delivery outcomes are warranted.

Young adolescent girls are at high risk for adverse pregnancy outcomes in sub-Saharan Africa: an observational multicountry study.

OBJECTIVES: One of Africa's most important challenges is to improve maternal and neonatal health. The identification of groups at highest risk for adverse pregnancy outcomes is important for developing and implementing targeted prevention programmes. This study assessed whether young adolescent girls constitute a group at increased risk for adverse birth outcomes among pregnant women in sub-Saharan Africa. SETTING: Data were collected prospectively as part of a large randomised controlled clinical trial evaluating intermittent preventive treatment of malaria in pregnancy (NCT00811421-Clinical Trials.gov), conducted between September 2009 and December 2013 in Benin, Gabon, Mozambique and Tanzania. PARTICIPANTS: Of 4749 participants, pregnancy outcomes were collected for 4388 deliveries with 4183 live births including 83 multiple gestations. Of 4100 mothers with a singleton live birth delivery, 24% (975/4100) were adolescents (≤19 years of age) and 6% (248/4100) were aged ≤16 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes of this predefined analysis were preterm delivery and low birth weight. RESULTS: The overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged ≤16 years showed higher risk for the delivery of a low birthweight infant (OR: 1.96; 95% CI 1.35 to 2.83). Similarly, preterm delivery was associated with young maternal age (≤16 years; OR: 2.62; 95% CI 1.59 to 4.30). In a subanalysis restricted to primiparous women: preterm delivery, OR 4.28; 95% CI 2.05 to 8.93; low birth weight, OR: 1.29; 95% CI 0.82 to 2.01. CONCLUSIONS: Young maternal age increases the risk for adverse pregnancy outcomes and it is a stronger predictor for low birth weight and preterm delivery than other established risk factors in sub-Saharan Africa. This finding highlights the need to improve adolescent reproductive health in sub-Saharan Africa. TRIAL REGISTRATION NUMBER: NCT00811421; Post-results.

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.