Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal

Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positives samples (n = 352) were collected from children under 5 years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)–ELISA. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) was stable between years at < 10% in the control group (P = 0.69), while it rose significantly in the IPTi/c group from 2% in 2010 to 20% in 2011 (P = 0.008). The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41% to 65% in 2011 (P = 0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6% to 28.6% (P = 0.07) and from 66.7% to 47.5% (P = 0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. Combined with Pfdhfr, there was a weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr + Pfdhps 437G) in both groups (P = 0.15 and P = 0.34). During the two cross-sectional surveys, some significant changes were observed in the SP-resistance-related genes. However, since these changes were observed in the two groups, the IPTi/c strategy does only seem to have limited impact on resistance development and other factors as well. However, continuous monitoring will be needed, due to the up-scaling of the IPTi/c strategy in Senegal according to WHO recommendations.     

High Prevalence of Severe Food Insecurity and Malnutrition among HIV-Infected Adults in Senegal,West Africa

Background

Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes.

Methods

We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review.

Results

One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01).

Conclusions

Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population.     

High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio)

The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum), yaws (ssp. pertenue), and endemic syphilis (ssp. endemicum) in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papio papio) at Parc National Niokolo Koba in south eastern Senegal for the presence of anti-T. pallidum antibodies. Since T. pallidum infection in this species was identified 50 years ago, and there has been no attempt to treat non-human primates for infection, it was hypothesized that a large number of West African baboons are still infected with simian strains of the yaws-bacterium. All animals were without clinical signs of treponematoses, but 18 of 20 (90%) baboons tested positive for antibodies against T. pallidum based on treponemal tests. Yet, Guinea baboons seem to develop no clinical symptoms, though it must be assumed that infection is chronic or comparable to the latent stage in human yaws infection. The non-active character is supported by the low anti-T. pallidum serum titers in Guinea baboons (median = 1:2,560) versus serum titers that are found in genital-ulcerated olive baboons with active infection in Tanzania (range of medians among the groups of initial, moderate, and severe infected animals = 1:15,360 to 1:2.097e+7). Our findings provide evidence for simian infection with T. pallidum in wild Senegalese baboons. Potentially, Guinea baboons in West Africa serve as a natural reservoir for human infection, as the West African simian strain has been shown to cause sustainable yaws infection when inoculated into humans. The present study pinpoints an area where further research is needed to support the currently on-going second WHO led yaws eradication campaign with its goal to eradicate yaws by 2020.     

Comparison of heterologous neutralizing antibody responses of human immunodeficiency virus type 1 (HIV-1)- and HIV-2-infected Senegalese patients: distinct patterns of breadth and magnitude distinguish HIV-1 and HIV-2 infections

Neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections were compared, and their relationships with established clinical markers of progression were examined. Neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated HIV-1-infected subjects and 35 untreated HIV-2-infected subjects using a pseudotyped reporter virus assay. The breadth of the neutralizing response, defined as the proportion of panel viruses positively neutralized by patient plasma, was significantly greater among HIV-2-infected subjects than among HIV-1-infected subjects. Notably, for fully one-third of HIV-2 subjects, all viruses were effectively neutralized in our panel. Magnitudes of responses, defined as reciprocal 50% inhibitory concentration (IC(50)) titers for positive reactions, were significantly greater among HIV-1-infected subjects than among HIV-2-infected subjects. When plasma samples from HIV-1 patients were tested for cross-neutralization of HIV-2 and vice versa, we found that these intertype responses are very rare and their prevalences comparable in both HIV-1 and HIV-2 infection. The significantly higher magnitude of heterologous responses for HIV-1 compared to HIV-2 prompted us to examine associations with viremia, which is known to be significantly higher in HIV-1 infection. Importantly, there was a significant positive correlation between the IC(50) titer and viral load within both the HIV-1 and HIV-2 groups, suggesting heterologous antibodies may be driven by viral replication. We conclude that HIV-2 infection is characterized by a broad, low-magnitude intratype neutralization response, while HIV-1 is characterized by a narrower but higher-magnitude intratype response and that a significant positive association between the IC(50) titer and viremia is common to both HIV-1 and HIV-2 infections.     

High variation reduces the value of feather stable isotope ratios in identifying new wintering areas for aquatic warblers Acrocephalus paludicola in West Africa

Stable isotope analysis of feathers can be useful in the study of seasonal interactions and migratory connectivity in birds. For the Palaearctic–African migration system, however, the lack of isotope data from feathers of known origin in Africa renders the geographic assignment of birds captured on European breeding grounds to potential wintering areas problematic. Rectrices of the threatened aquatic warbler Acrocephalus paludicola grown in Africa were sampled across six European countries to assess whether birds in different breeding populations shared similar isotopic signatures and so were likely to have wintered in the same region in Africa. Freshly grown feathers of aquatic warblers collected at the only known wintering site in Senegal showed high variation in carbon, nitrogen, and hydrogen isotope ratios. Due to similarly high variation in isotope ratios of African‐grown feathers within all breeding populations, it was not possible to determine whether different populations wintered in different regions. However, isotope signatures of 20% of birds captured on European breeding grounds fell outside the range of those captured in Senegal, suggesting a wider wintering distribution than is currently known. We therefore assessed whether the origin of these feathers could be estimated by trying to establish isotopic gradients across sub‐Saharan West Africa. Feathers of three ecologically similar surrogate species were sampled from wetlands across a 3000 km east‐west and a 2000 km north–south transect. Within‐site variation in feather isotope ratios was frequently larger than the difference predicted by gradients across West Africa. Thus, predicting the origin of individual feathers using single‐isotope gradients was not reliable. The large within‐site variability of feather isotope ratios of a habitat specialist species like the aquatic warbler indicates that using feather isotope ratios will require large sample sizes from many locations, and may thus not be an efficient tool in identifying wintering areas of Palaearctic–African migrants.     

Lésions des organes génitaux externes par arme a feu: a propos de six observations

Patients and Methods

This is a retrospective study of patients admitted with gunshot injuries to the external genital organs to the urology departments of Aristide Le Dantec Hospital, Grand Yoff General Hospital and Dakar Principal Hospital, between January 1998 and January 2003. The following parameters were studied: patients’ age and gender, interval between accident and admission, clinical features, complementary investigations and treatment, and early and late outcomes.

Results

Only males were observed and the mean age of these patients was 37.7 years (range: 22–52 years). Lesions were accidental in five cases. Two cases of testicular wounds, two cases of corpus cavernosum injuries, two cases of urethral injury, and one case of perineal wound were observed. After excision of the lesions, complementary procedures consisted of: orchidectomy in two cases, corpus cavernosum — albuginea suture in two cases and end-to-end urethral suture in one case. Perineoscrotal wounds were sutured three days after debridement. All patients received antibiotics and antitetanus serum. No death was observed during the immediate follow-up. No case of urethral stricture or erectile dysfunction was observed with a follow-up of 18 months. Semen analysis was normal in the two cases of orchidectomy.     

Results of an action-research on epilepsy in rural mali

Purpose

To evaluate the RARE (Réseau Action-Recherche sur l’Epilepsie) program, a model of managing and treating people with epilepsy (PWE) at a primary health-care level in rural areas of Mali, we assessed treatment efficacy and compliance of patients who underwent the first year follow-up.

Methods

A network of rural general practitioners (GPs) settled in six rural districts of the regions of Koulikoro, Segou and Sikasso, was involved in the diagnosis, evaluation and monitoring of all the identified PWE and in the distribution of phenobarbital (PB). All the participants were included in a prospective database and followed-up by GPs at 4 months intervals during the first year. Seizure frequency, treatment doses and appearance of adverse events (AEs) were systematically recorded. Efficacy was evaluated in terms of reduction of seizures frequency while noncompliance in terms of time to study withdrawal for any cause.

Key findings

596 patients treated with PB were included in the analysis. Of these, 74.0% completed the first year follow-up. At the final visit, 59.6% were seizure-free: 31.0% for 12 months, 10.2% for 8 months and 18.4% for 4 months. Adults and patients with convulsive seizures were the most drug-resistant (p<0.002). Few AEs were recorded. The multivariate analysis showed that being a woman, presenting convulsive seizures, having more than 5 seizures/month and had never be treated were predictors of withdrawal (p≤0.05) at 12 months.

Significance

This study showed a good response and compliance to the treatment and allowed the identification of some factors associated with failure of management in a setting very near to clinical practice. Awareness campaigns are needed to assure a broader accessibility to treatment and to improve the compliance and continuity with treatment programs.     

Background Rates of Adverse Pregnancy Outcomes for Assessing the Safety of Maternal Vaccine Trials in Sub-Saharan Africa

Background

Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa.

Methods

We developed a mathematical model that calculates a clinical trial''s expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed.

Findings

Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6–73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9–16.4) or premature (median 15.4%, IQR: 10.6–19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5–17.6), with the musculoskeletal system comprising 30%.

Interpretation

Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of adverse pregnancy outcomes will improve safety assessment of interventions during pregnancy.     

Global Stability of Reversible Enzymatic Metabolic Chains

We consider metabolic networks with reversible enzymatic reactions. The model is written as a system of ordinary differential equations, possibly with inputs and outputs. We prove the global stability of the equilibrium (if it exists), using techniques of monotone systems and compartmental matrices. We show that the equilibrium does not always exist. Finally, we consider a metabolic system coupled with a genetic network, and we study the dependence of the metabolic equilibrium (if it exists) with respect to concentrations of enzymes. We give some conclusions concerning the dynamical behavior of coupled genetic/metabolic systems.     

Stem Nodulation in Legumes: Diversity,Mechanisms, and Unusual Characteristics

Rhizobia can establish a nitrogen-fixing symbiosis with plants of the Leguminosae family. They elicit on their host plant the formation of new organs, called nodules, which develop on the roots. A few aquatic legumes, however, can form nodules on their stem at dormant root primordia. The stem-nodulating legumes described so far are all members of the genera Aeschynomene, Sesbania, Neptunia, and Discolobium. Their rhizobial symbionts belong to four genera already described: Rhizobium, Bradyrhizobium, Sinorhizobium, and Azorhizobium. This review summarizes our current knowledge on most aspects of stem nodulation in legumes, the infection process and nodule development, the characterization and unusual features of the associated bacteria, and the molecular genetics of nodulation. Potential use as green manure in lowland rice of these stem-nodulating legumes, giving them agronomical importance, is also discussed.