No Difference in the Incidence of Malaria in Human-Landing Mosquito Catch Collectors and Non-Collectors in a Senegalese Village with Endemic Malaria

BackgroundThe human landing catches is the gold standard method used to study the vectors of malaria and to estimate their aggressiveness. However, this method has raised safety concerns due to a possible increased risk of malaria or other mosquito-borne diseases among the mosquito collectors. The aim of this study was to evaluate the incidence of malaria attacks among mosquito collectors and to compare these results with those of non-collectors in a Senegalese village.MethodsFrom July 1990 to December 2011, a longitudinal malaria study involving mosquito collectors and non-collectors was performed in Dielmo village, Senegal. During the study period, 4 drugs were successively used to treat clinical malaria, and long-lasting insecticide-treated nets were offered to all villagers in July 2008. No malaria chemoprophylaxis was given to mosquito collectors. Incidence of uncomplicated clinical malaria and asymptomatic malaria infection were analyzed among these two groups while controlling for confounding factors associated with malaria risk in random effects negative binomial and logistic regression models, respectively.ResultsA total of 3,812 person-trimester observations of 199 adults at least 15 years of age were analyzed. Clinical malaria attacks accounted for 6.3% both in collectors and non-collectors, and asymptomatic malaria infections accounted for 21% and 20% in collectors and non-collectors, respectively. A non-significant lower risk of malaria was observed in the collector group in comparison with the non-collector group after adjusting for other risk factors of malaria and endemicity level (Clinical malaria: adjusted incidence rate ratio = 0.89; 95% confidence interval = 0.65-1.22; p= 0.47).ConclusionBeing a mosquito collector in Dielmo was not significantly associated with an increased risk of malaria both under holoendemic, mesoendemic and hypoendemic conditions of malaria epidemiology. This result supports the view that HLC, the most accurate method for evaluating malaria transmission, may be used without health concerns in Dielmo.     

Spatial swarm segregation and reproductive isolation between the molecular forms of Anopheles gambiae

Anopheles gambiae, the major malaria vector in Africa, can be divided into two subgroups based on genetic and ecological criteria. These two subgroups, termed the M and S molecular forms, are believed to be incipient species. Although they display differences in the ecological niches they occupy in the field, they are often sympatric and readily hybridize in the laboratory to produce viable and fertile offspring. Evidence for assortative mating in the field was recently reported, but the underlying mechanisms awaited discovery. We studied swarming behaviour of the molecular forms and investigated the role of swarm segregation in mediating assortative mating. Molecular identification of 1145 males collected from 68 swarms in Donéguébougou, Mali, over 2 years revealed a strict pattern of spatial segregation, resulting in almost exclusively monotypic swarms with respect to molecular form. We found evidence of clustering of swarms composed of individuals of a single molecular form within the village. Tethered M and S females were introduced into natural swarms of the M form to verify the existence of possible mate recognition operating within-swarm. Both M and S females were inseminated regardless of their form under these conditions, suggesting no within-mate recognition. We argue that our results provide evidence that swarm spatial segregation strongly contributes to reproductive isolation between the molecular forms in Mali. However this does not exclude the possibility of additional mate recognition operating across the range distribution of the forms. We discuss the importance of spatial segregation in the context of possible geographic variation in mechanisms of reproductive isolation.     

Betacyanins and phenolic compounds from Amaranthus spinosus L. and Boerhavia erecta L

Stem bark extracts of Boerhavia erecta L. (erect spiderling) and Amaranthus spinosus L. (spiny amaranth), two wild growing weed plants used in traditional African medicine, were characterized with respect to their phenolic profile including the betalains. While the main betalains in A. spinosus were identified as amaranthine and isoamaranthine, the major betacyanins in B. erecta were betanin, isobetanin together with neobetanin. The latter showed higher betalain concentrations amounting to 186 mg/100 g, while the former contained 24 mg betacyanins in 100 g of the ground plant material. Extracts of A. spinosus were found to contain hydroxycinnamates, quercetin and kaempferol glycosides, whereas catechins, procyanidins and quercetin, kaempferol and isorhamnetin glycosides were detected in B. erecta. The amounts of these compounds ranged from 305 mg/100 g for A. spinosus to 329 mg/100 g for B. erecta.     

Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old,Health District of Sokone,Senegal, 2010–2013

Introduction

Malaria is a leading cause of morbidity and mortality in sub-Saharan Africa. Detailed characterization of the risks for malaria, among populations living in areas where the disease is endemic, is an important priority, especially for planning and evaluating future malaria-control tools. A prospective cohort study was implemented in children under ten years living in rural areas with high Plasmodium falciparum transmission in Senegal.

Methods

Malaria incidence was prospectively evaluated over three year follow-up among a cohort of children aged less than 10 years old living in eight villages of the Sokone health district. The parents of 1316 children comprising a passive case detection cohort were encouraged to seek care from the study health centers at any time their child felt sick. In the event of reported history of fever within 24 hours or measured axillary temperature ≥ 37.5°C, a Rapid Diagnostic Test (RDT) was performed.

Results

From November 2010 to October 2013, among the 1468 reported febrile episodes, 264 were confirmed malaria episodes. Over the 3 years, 218 (16.9%) children experienced at least one clinical malaria episode. Cumulative malaria incidence was 7.3 episodes per 100 children-year at risk, with remarkably heterogeneous rates from 2.5 to 10.5 episodes per 100 children-year at risk. Clinical malaria prevalence ranged from 11.5 to 28.4% in the high transmission season versus from 9.6 to 21.2% in the low transmission season.

Conclusion

This longitudinal community-based study shows that occurrence of clinical malaria was not evenly distributed among all the cohort children in the eight villages. It demonstrates the complexity of spatial distribution of malaria incidence at a local level, even in a region of vegetation and altitudinal homogeneity.     

A Spatio-temporal Model of African Animal Trypanosomosis Risk

Background

African animal trypanosomosis (AAT) is a major constraint to sustainable development of cattle farming in sub-Saharan Africa. The habitat of the tsetse fly vector is increasingly fragmented owing to demographic pressure and shifts in climate, which leads to heterogeneous risk of cyclical transmission both in space and time. In Burkina Faso and Ghana, the most important vectors are riverine species, namely Glossina palpalis gambiensis and G. tachinoides, which are more resilient to human-induced changes than the savannah and forest species. Although many authors studied the distribution of AAT risk both in space and time, spatio-temporal models allowing predictions of it are lacking.

Methodology/Principal Findings

We used datasets generated by various projects, including two baseline surveys conducted in Burkina Faso and Ghana within PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign) national initiatives. We computed the entomological inoculation rate (EIR) or tsetse challenge using a range of environmental data. The tsetse apparent density and their infection rate were separately estimated and subsequently combined to derive the EIR using a “one layer-one model” approach. The estimated EIR was then projected into suitable habitat. This risk index was finally validated against data on bovine trypanosomosis. It allowed a good prediction of the parasitological status (r² = 67%), showed a positive correlation but less predictive power with serological status (r² = 22%) aggregated at the village level but was not related to the illness status (r² = 2%).

Conclusions/Significance

The presented spatio-temporal model provides a fine-scale picture of the dynamics of AAT risk in sub-humid areas of West Africa. The estimated EIR was high in the proximity of rivers during the dry season and more widespread during the rainy season. The present analysis is a first step in a broader framework for an efficient risk management of climate-sensitive vector-borne diseases.     

Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3

Background

Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates.

Methods and Findings

We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved.

Conclusions

Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.     

Predicting alpha diversity of African rain forests: models based on climate and satellite‐derived data do not perform better than a purely spatial model

Aim Our aim was to evaluate the extent to which we can predict and map tree alpha diversity across broad spatial scales either by using climate and remote sensing data or by exploiting spatial autocorrelation patterns. Location Tropical rain forest, West Africa and Atlantic Central Africa. Methods Alpha diversity estimates were compiled for trees with diameter at breast height ≥ 10 cm in 573 inventory plots. Linear regression (ordinary least squares, OLS) and random forest (RF) statistical techniques were used to project alpha diversity estimates at unsampled locations using climate data and remote sensing data [Moderate Resolution Imaging Spectroradiometer (MODIS), normalized difference vegetation index (NDVI), Quick Scatterometer (QSCAT), tree cover, elevation]. The prediction reliabilities of OLS and RF models were evaluated using a novel approach and compared to that of a kriging model based on geographic location alone. Results The predictive power of the kriging model was comparable to that of OLS and RF models based on climatic and remote sensing data. The three models provided congruent predictions of alpha diversity in well‐sampled areas but not in poorly inventoried locations. The reliability of the predictions of all three models declined markedly with distance from points with inventory data, becoming very low at distances > 50 km. According to inventory data, Atlantic Central African forests display a higher mean alpha diversity than do West African forests. Main conclusions The lower tree alpha diversity in West Africa than in Atlantic Central Africa may reflect a richer regional species pool in the latter. Our results emphasize and illustrate the need to test model predictions in a spatially explicit manner. Good OLS or RF model predictions from inventory data at short distance largely result from the strong spatial autocorrelation displayed by both the alpha diversity and the predictive variables rather than necessarily from causal relationships. Our results suggest that alpha diversity is driven by history rather than by the contemporary environment. Given the low predictive power of models, we call for a major effort to broaden the geographical extent and intensity of forest assessments to expand our knowledge of African rain forest diversity.     

Signaling of the neurotrophin receptor p75 in relation to Alzheimer’s disease

The cellular mechanism of neuronal apoptosis in Alzheimer’s disease (AD) is poorly understood. Many hypotheses have been put fourth to explain the underlying reason for neuro-degeneration in AD. Here, it is demonstrated that all neurotrophins that activated p75, without co-activation of the relevant Trk co-receptor, mediated apoptosis in hippocampal neurons. Thus, proneurotrophins and amyloid β peptides (Aβ) can induce p75-mediated apoptosis in hippocampal neurons since they do not bind or activate Trk receptors. Based on the combined effects of aging, proneurotrophins, neurotrophins, and Aβ, a novel model of pathogenesis in AD is proposed. This mini-review explores the ligand and cell type based signaling pathways of the neurotrophin receptor p75 relating to Alzheimer’s disease.     

Significantly reduced intensity of infection but persistent prevalence of schistosomiasis in a highly endemic region in mali after repeated treatment

Background

Preventive chemotherapy against schistosomiasis has been implemented since 2005 in Mali, targeting school-age children and adults at high risk. A cross-sectional survey was conducted in 2010 to evaluate the impact of repeated treatment among school-age children in the highly-endemic region of Segou.

Methodology/Principal Findings

The survey was conducted in six sentinel schools in three highly-endemic districts, and 640 school children aged 7–14 years were examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Overall prevalence of S. haematobium infection was 61.7%, a significant reduction of 30% from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni infection was 12.7% which was not significantly different from the baseline. Overall mean intensity of S. haematobium and S. mansoni infection was 180.4 eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2 eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of 81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both significantly (p<0.01). Mathematical modelling suggests that the observed results were in line with the expected changes.

Conclusions/Significance

Significant reduction in intensity of infection on both infections and modest but significant reduction in S. haematobium prevalence were achieved in highly-endemic Segou region after repeated chemotherapy. However, persistent prevalence of both infections and relatively high level of intensity of S. mansoni infection suggest that more intensified control measures be implemented in order to achieve the goal of schistosomiasis elimination. In addition, closer monitoring and evaluation activities are needed in the programme to monitor the drug tolerance and to adjust treatment focus.