Nafissatou Diagne

The occurrence of malaria resurgences could threaten progress toward elimination of the disease. This study investigated the impact of repeated renewal of long-lasting insecticide-treated net (LLIN) universal coverage on malaria resurgence over a period of 10 years of net implementation in Dielmo (Senegal). A longitudinal study was carried out in Dielmo between August 2007 and July 2018. In July 2008, LLINs were offered to all villagers through universal campaign distribution which was renewed in July 2011, August 2014, and May 2016. Malaria cases were treated with artemisinin-based combination therapy. Two resurgences of malaria occurred during the 10 years in which LLINs have been in use. Since the third renewal of the nets, malaria decreased significantly compared with the first year the nets were implemented (adjusted incidence rate ratio) (95% CI) = 0.35 (0.15–0.85), during the ninth year after net implementation). During the tenth year of net implementation, no cases of malaria were observed among the study population. The use of nets increased significantly after the third time the nets were renewed when compared with the year after the first and the second times the nets were renewed (P < 0.001). The third renewal of nets, which took place after 2 years instead of 3 years together with a higher use of LLINs especially among the young, probably prevented the occurrence of a third malaria upsurge in this village.

Background: Bacterial vaginosis is a very common vaginal disorder, with a gynaeco-obstetrical impact, but remains poorly understood. Current antibiotic treatment most often fails. Our objective was to exhaustively map the bacterial community present in bacterial vaginosis and normal flora, using not only a molecular approach but also a highly efficient culture approach, culturomics. Vaginal bacterial diversity was evaluated using both strategies for 24 Caucasian French women, including 7 cases of bacterial vaginosis, and 10 rural Senegalese women, including 5 cases of bacterial vaginosis. An additional 16 specimens (three cases of bacterial vaginosis and 13 normal flora) obtained during the follow-up visits of five French women with bacterial vaginosis were analysed using metagenomics.Results: The combination of culturomics and metagenomics reveals the richness and diversity of vaginal microbiota. Our data demonstrated that compared to healthy women, those with bacterial vaginosis present a shift in vaginal flora. The microbiota of the bacterial vaginosis group can be easily distinguished from that of healthy group by their increased bacterial diversity, abundance of Bacteroidales and Leptotrichiaeceae, and depletion of Proteobacteria and Lactobacillaceae species. In addition, a complex of 10 genera was associated with bacterial vaginosis: Gardnerella, Atopobium, Snethia, Aerococcus, Prevotella, Gemella, Facklamia, Porphyromonas, Mycoplasma, and Urinacoccus. Overall, the microbial population detected in bacterial vaginosis flora was largely similar to the bacterial communities found in gut microbiota. The two approaches showed a diverse vaginal microbiota that was largely non-overlapping, with only 146 common species. Furthermore, culturomics extends the repertoire of human-associated bacteria with the isolation of 27 new bacterial species.Conclusions: This study provides the most representative topology of the vaginal microbiota of normal flora and bacterial vaginosis and suggests the transplantation of gut microbiota into the vagina during bacterial vaginosis. Several sets of clinically relevant anaerobic bacteria and new species were also isolated from the human vagina, confirming that some previously “uncultivated” species may be cultivated using an appropriate strategy. Exhaustive characterisation of vaginal microbiota will enable a better understanding and management of bacterial vaginosis. Obtaining isolates will allow us to explore the bacterial interactions of the vaginal microbiota and will serve as a basis for the potential development of bacteriotherapy to prevent or treat vaginal dysbiosis.

Vaginal self-sampling and human papillomavirus (HPV) DNA testing can be useful tools for women with limited access to health care living in sub-Saharan Africa. To assess the feasibility and acceptability of vaginal self-sampling and high-risk HPV prevalence in two villages of central Senegal, women were asked to self-sample vaginal swabs for HPV detection in May, 2016. Vaginal swabs were collected from 133 women and were tested for HPV genotyping. The acceptability rate of vaginal self-sampling was 98.5%, and 99.2% of the women (133/134) used the device correctly. The quality of self-sampling was satisfactory in 100% of the samples; 10.5% of the samples were positive for HPV, including 6% with high-risk HPV types and 4% with low-risk HPV types. This preliminary study indicates that vaginal self-sampling is a valuable strategy for high-risk HPV detection and cervical cancer screening in a population of women not attending gynecologic screening in rural areas of Senegal.

The implementation of long-lasting insecticidal-treated bed nets (LLINs) has contributed to halving the mortality rate due to malaria since 2000 in sub-Saharan Africa. These tools are highly effective against indoor-feeding malaria vectors. Thus, to achieve the World Health Assembly’s new target to reduce the burden of malaria over the next 15 years by 90%, it is necessary to understand how the spatiotemporal dynamics of malaria vectors and human exposure to bites is modified in the context of scaling up global efforts to control malaria transmission. This study was conducted in Dielmo, a Senegalese village, after the introduction of LLINs and two rounds of LLINs renewals. Data analysis showed that implementation of LLINs correlated with a significant decrease in the biting densities of the main malaria vectors, Anopheles gambiae s.l. and Anopheles funestus, reducing malaria transmission. Other environment factors likely contributed to the decrease in An. funestus, but this trend was enhanced with the introduction of LLINs. The bulk of bites occurred during sleeping hours, but the residual vector populations of An. gambiae s.l. and An. funestus had an increased propensity to bite outdoors, so a risk of infectious bites remained for LLINs users. These results highlight the need to increase the level and correct use of LLINs and to combine this intervention with complementary control measures against residual exposure, such as spatial repellents and larval source management, to achieve the goal of eliminating malaria transmission.

Evaluation of local Plasmodium falciparum malaria transmission has been investigated previously using the reversible catalytic model based on prevalence of antibody responses to single antigen to estimate seroconversion rates. High correlations were observed between seroconversion rates and entomological inoculation rates (EIR). However, in this model, the effects of malaria control interventions and clinical episodes on serological measurements were not assessed. This study monitors the use of antibody responses to P. falciparum crude extracts for assessing malaria transmission, compares seroconversion rates estimated from longitudinal data to those derived from cross-sectional surveys and investigates the effects of malaria control interventions on these measures in an area of declining malaria transmission. In addition, the validity of this model was evaluated by comparison with the alternative model. Five cross-sectional surveys were carried out at the end of the wet season in Dielmo, a malaria-endemic Senegalese rural area in 2000, 2002, 2008, 2010 and 2012. Antibodies against schizonts crude extract of a local P. falciparum strain adapted to culture (Pf 07/03) were measured by ELISA. Age-specific seroprevalence model was used both for cross-sectional surveys and longitudinal data (combined data of all surveys). A total of 1504 plasma samples obtained through several years follow-up of 350 subjects was used in this study. Seroconversion rates based on P. falciparum schizonts crude extract were estimated for each cross-sectional survey and were found strongly correlated with EIR. High variability between SCRs from cross-sectional and longitudinal surveys was observed. In longitudinal studies, the alternative catalytic reversible model adjusted better with serological data than the catalytic model. Clinical malaria attacks and malaria control interventions were found to have significant effect on seroconversion. The results of the study suggested that crude extract was a good serological tool that could be used to assess the level of malaria exposure in areas where malaria transmission is declining. However, additional parameters such as clinical malaria and malaria control interventions must be taken into account for determining serological measurements for more accuracy in transmission assessment.

Mosquitoes belonging to the Anopheles gambiae complex are the main vectors of malaria in sub-Saharan Africa. Among these, An. gambiae, Anopheles coluzzii and Anopheles arabiensis are the most efficient vectors and are largely distributed in sympatric locations. However, these species present ecological and behavioural differences that impact their vectorial capacity and complicate vector-control efforts, mainly based on long-lasting insecticidal bed nets (LLINs) and indoor residual spraying (IRS). In this study, the genetic structure of these three species in a Senegalese village (Dielmo) was investigated using microsatellite data in samples collected in 2006 before implementation of LLINs, in 2008, when they were introduced, and in 2010, 2 years after the use of LLINs. In this study 611 individuals were included, namely 136 An. coluzzii, 101 An. gambiae, 6 An. coluzzii/An. gambiae hybrids and 368 An. arabiensis. According to the species, the effect of the implementation of LLINs in Dielmo is differentiated. Populations of the sister species An. coluzzii and An. gambiae regularly experienced bottleneck events, but without significant inbreeding. The Fst values suggested in 2006 a breakdown of assortative mating resulting in hybrids, but the introduction of LLINs was followed by a decrease in the number of hybrids. This suggests a decrease in mating success of hybrids, ecological maladaptation, or a lesser probability of mating between species due to a decrease in An. coluzzii population size. By contrast, the introduction of LLINs has favoured the sibling species An. arabiensis. In this study, some spatial and temporal structuration between An. arabiensis populations were detected, especially in 2008, and the higher genetic diversity observed could result from a diversifying selection. This work demonstrates the complexity of the malaria context and shows the need to study the genetic structure of Anopheles populations to evaluate the effectiveness of vector-control tools and successful management of malaria vector control.

Coordinated scaled-up malaria control interventions have substantially contributed to the dramatic decrease of malaria-related morbidity and mortality in several endemic countries, including Senegal. However, the impacts of a given malaria control intervention on vector and parasite populations, acquired immunity, and disease burden remain very poorly documented largely due to the lack of continuous surveys. This study took advantage of the sera bank established as part of the Dielmo longitudinal project to investigate the dynamics of IgG antibody responses that accompanied the epidemiological changes resulting from malaria control interventions. Schizonts crude extract of a local strain of Plasmodium falciparum (Pfsch07/03) was used in ELISA to measure and compare seroprevalence and magnitude of IgG antibody responses from 2000 to 2012. The prevalence of Pfsch07/03 IgG antibody responses progressively decreased from 97.25% in 2000 to 57.3% in 2012. The prevalence of Pfsch07/03 antibodies categorized between three different age groups (15 years) revealed increased seroprevalence with age ranging from 47.19 to 62.67 and 89.45%, respectively in (15 years) old age groups. A marked drop in seroprevalence was observed after 2008 and was significant in the younger (15 years (p = 1.00). The study revealed a substantial contribution of all malaria control interventions to the decrease of IgG antibodies responses to Pfsch07/03 throughout prevention of human-mosquitos contacts, or reduction of parasite biomass. The present study demonstrates the wider potential of sero-epidemiological analysis in monitoring changes in malaria transmission resulting from a given malaria control intervention.

Although the burden of malaria has significantly declined in recent years in sub-Saharan Africa through the widespread use of long-lasting insecticide treated bed-nets (LLINs) and artemisinin-based combination therapy, resurgence of malaria is observed in some settings after several years of LLINs use. This study aimed to assess if LLINs use remains protective against malaria during a period of resurgence of malaria morbidity in Dielmo, a rural village of Senegal. In July 2008, LLINs were offered to all villagers and lately in July 2011, LLINs were renewed. A longitudinal study was conducted between July, 2010 and December, 2011 among inhabitants of the village of Dielmo to identify all episodes of fever. Thick smears stained with Giemsa were done for every febrile villager and malaria attacks were treated with combination of Artesunate plus Amodiaquine. Cross-sectional surveys were also conducted at the end of the rainy season (October 2010 and November 2011) to assess asymptomatic carriage. A survey on LLINs use was done every quarter of the year. A random-effect logistic regression was used to assess the effect of LLINs use on the risk of having a malaria attack after adjusting for the main risk factors. The study population included 449 individuals corresponding to a total of 2140 observations. One hundred and fifteen (115) clinical malaria attacks attributed to P. falciparum (cases) have been recorded over the study period. Most of the malaria cases occurred in October-December 2010 (49/115 i.e. 43%) and among adults aged 15 years and over (50/115, i.e. 43%). During the study period, the use of LLINs was 61% among non-malaria cases and only 42% among malaria clinical cases but differenced according to age group. After adjusting on gender, age, rainfall and LLINs replacement, we found that LLINs use (AOR [95%CI] = 0.40 [0.25; 0.62], p < 0.001) remained a protective factor against malaria attacks during the study period. LLINs use remains effective to reduce malaria burden. These results highlight the need to pursue LLINs implementation in the current context of malaria elimination and to provide positive incentives to increase its use in the population.

Malaria control is mainly based on indoor residual spraying and insecticide-treated bed nets. The efficacy of these tools depends on the behaviour of mosquitoes, which varies by species. With resistance to insecticides, mosquitoes adapt their behaviour to ensure their survival and reproduction. The aim of this study was to assess the biting behaviour of Anopheles funestus after the implementation of long-lasting insecticidal nets (LLINs).