Malaria Morbidity in High and Seasonal Malaria Transmission Area of Burkina Faso

Background

Malariometric parameters are often primary endpoints of efficacy trials of malaria vaccine candidates. This study aims to describe the epidemiology of malaria prior to the conduct of a series of drug and vaccine trials in a rural area of Burkina Faso.

Methods

Malaria incidence was prospectively evaluated over one year follow-up among two cohorts of children aged 0–5 years living in the Saponé health district. The parents of 1089 children comprising a passive case detection cohort were encouraged to seek care from the local health clinic at any time their child felt sick. Among this cohort, 555 children were randomly selected for inclusion in an active surveillance sub-cohort evaluated for clinical malaria during twice weekly home visits. Malaria prevalence was evaluated by cross-sectional survey during the low and high transmission seasons.

Results

Number of episodes per child ranged from 0 to 6 per year. Cumulative incidence was 67.4% in the passive and 86.2% in the active cohort and was highest among children 0–1 years. Clinical malaria prevalence was 9.8% in the low and 13.0% in the high season (p>0.05). Median days to first malaria episode ranged from 187 (95% CI 180–193) among children 0–1 years to 228 (95% CI 212, 242) among children 4–5 years. The alternative parasite thresholds for the malaria case definition that achieved optimal sensitivity and specificity (70–80%) were 3150 parasites/µl in the high and 1350 parasites/µl in the low season.

Conclusion

Clinical malaria burden was highest among the youngest age group children, who may represent the most appropriate target population for malaria vaccine candidate development. The pyrogenic threshold of parasitaemia varied markedly by season, suggesting a value for alternative parasitaemia levels in the malaria case defintion. Regional epidemiology of malaria described, Sapone area field centers are positioned for future conduct of malaria vaccine trials.     

Community screening and treatment of asymptomatic carriers of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis

Background

Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area.

Methods

Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions.

Results

The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention.

Conclusions

Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.

     

Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick

Tick saliva contains potent antihemostatic molecules that help ticks obtain their enormous blood meal during prolonged feeding. We isolated thrombin inhibitors present in the salivary gland extract from partially fed female Amblyomma variegatum, the tropical bont tick, and characterized the most potent, variegin, one of the smallest (32 residues) thrombin inhibitors found in nature. Full-length variegin and two truncated variants were chemically synthesized. Despite its small size and flexible structure, variegin binds thrombin with strong affinity (K(i) approximately 10.4 pM) and high specificity. Results using the truncated variants indicated that the seven residues at the N terminus affected the binding kinetics; when removed, the binding characteristics changed from fast to slow. Further, the thrombin active site binding moiety of variegin is in the region of residues 8-14, and the exosite-I binding moiety is within residues 15-32. Our results show that variegin is structurally and functionally similar to the rationally designed thrombin inhibitor, hirulog. However, compared with hirulog, variegin is a more potent inhibitor, and its inhibitory activity is largely retained after cleavage by thrombin.     

Variation in soil carbon stocks and their determinants across a precipitation gradient in West Africa

We examine the influence of climate, soil properties and vegetation characteristics on soil organic carbon (SOC) along a transect of West African ecosystems sampled across a precipitation gradient on contrasting soil types stretching from Ghana (15°N) to Mali (7°N). Our findings derive from a total of 1108 soil cores sampled over 14 permanent plots. The observed pattern in SOC stocks reflects the very different climatic conditions and contrasting soil properties existing along the latitudinal transect. The combined effects of these factors strongly influence vegetation structure. SOC stocks in the first 2 m of soil ranged from 20 Mg C ha^?1 for a Sahelian savanna in Mali to over 120 Mg C ha^?1 for a transitional forest in Ghana. The degree of interdependence between soil bulk density (SBD) and soil properties is highlighted by the strong negative relationships observed between SBD and SOC (r² > 0.84). A simple predictive function capable of encompassing the effect of climate, soil properties and vegetation type on SOC stocks showed that available water and sand content taken together could explain 0.84 and 0.86 of the total variability in SOC stocks observed to 0.3 and 1.0 m depth respectively. Used in combination with a suitable climatic parameter, sand content is a good predictor of SOC stored in highly weathered dry tropical ecosystems with arguably less confounding effects than provided by clay content. There was an increased contribution of resistant SOC to the total SOC pool for lower rainfall soils, this likely being the result of more frequent fire events in the grassier savannas of the more arid regions. This work provides new insights into the mechanisms determining the distribution of carbon storage in tropical soils and should contribute significantly to the development of robust predictive models of biogeochemical cycling and vegetation dynamics in tropical regions.     

Diversity assessment of benthic macroinvertebrate communities in Banco National Park (Banco Stream,Côte d'Ivoire)

In the present study, a first inventory of benthic macroinvertebrates in the Banco Stream, Côte d'Ivoire, and the correlations between environmental variables and taxonomic richness were analysed. Seven stations were sampled monthly over a 1‐year period, using a hand net (10 × 10 cm, 250 μm mesh, 50 cm length). One hundred and thirty‐two macroinvertebrate taxa were recorded. These taxa were distributed among 74 families and 15 orders belonging to Insecta (118 taxa; 89% of total richness), Oligochaeta (seven taxa), Crustacea (five taxa) and Mollusca (two taxa). Kruskal–Wallis test revealed significant difference (at least P < 0.05) in macroinvertebrate richness between upstream stations (S1 and S2) and stations S4, S5 and S6. Chironominae and Tanypodinae (Insecta) were the two very frequent taxa in all the stations. Lumbriculidae (Oligochaeta), Desmocaris trispinosa (Crustacea) and Eurymetra sp. (Insecta) were frequently found in the samples. Hierarchical cluster analysis revealed three groups of sampling stations according to taxonomic similarity. Taxonomic richness was significantly and negatively correlated with conductivity, while it was significantly and positively correlated with substrate types (woody debris and gravel). Due to the fact that Banco stream is the locality type of an endemic shrimp species (Macrobrachium thysi), this basin is of high conservation priority.     

Broad Adaptive Immune Responses to M. tuberculosis Antigens Precede TST Conversion in Tuberculosis Exposed Household Contacts in a TB-Endemic Setting

Background

The identification of Mycobacterium^-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN–γ release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN–γ may help to define markers of early Mtb infection.

Methods

We assessed the TST status of Mtb^-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST⁺); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST⁻). We assessed their short^- and long^-term immune responses to PPD and ESAT–6/CFP–10 (EC) via IFN–γ ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages.

Results

After 1 and 6 days stimulation with EC, 12 cytokines (IFN–γ, IL–2, IP–10, TNF–α, IL–13, IL–17, IL–10, GMCSF, MIP–1β, MCP–3, IL–2RA and IL–1A) were not different in TSTC compared to TST⁺ suggesting that robust adaptive Mtb^-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN–γ ELISPOT to EC in combination with TST results revealed that IP–10 and IL–17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection.

Conclusion

We describe a detailed analysis of Mtb^-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for ‘at^-risk’ populations beyond TST and IGRA.     

Association of Antibody Responses to the Conserved Plasmodium falciparum Merozoite Surface Protein 5 with Protection against Clinical Malaria

Background

Plasmodium falciparum merozoite surface protein 5 (PfMSP5) is an attractive blood stage vaccine candidate because it is both exposed to the immune system and well conserved. To evaluate its interest, we investigated the association of anti-PfMSP5 IgG levels, in the context of responses to two other conserved Ags PfMSP1p19 and R23, with protection from clinical episodes of malaria in cross-sectional prospective studies in two different transmission settings.

Methods

Ndiop (mesoendemic) and Dielmo (holoendemic) are two Senegalese villages participating in an on-going long-term observational study of natural immunity to malaria. Blood samples were taken before the transmission season (Ndiop) or before peak transmission (Dielmo) and active clinical surveillance was carried out during the ensuing 5.5-month follow-up. IgG responses to recombinant PfMSP5, PfMSP1p19 and R23 were quantified by ELISA in samples from surveys carried out in Dielmo (186 subjects) and Ndiop (221 subjects) in 2002, and Ndiop in 2000 (204 subjects). In addition, 236 sera from the Dielmo and Ndiop-2002 surveys were analyzed for relationships between the magnitude of anti-PfMSP5 response and neutrophil antibody dependent respiratory burst (ADRB) activity.

Results

Anti-PfMSP5 antibodies predominantly IgG1 were detected in 60–74% of villagers, with generally higher levels in older age groups. PfMSP5 IgG responses were relatively stable for Ndiop subjects sampled both in 2000 and 2002. ADRB activity correlated with age and anti-PfMSP5 IgG levels. Importantly, PfMSP5 antibody levels were significantly associated with reduced incidence of clinical malaria in all three cohorts. Inclusion of IgG to PfMSP1p19 in the poisson regression model did not substantially modify results.

Conclusion

These results indicate that MSP5 is recognized by naturally acquired Ab. The large seroprevalence and association with protection against clinical malaria in two settings with differing transmission conditions and stability over time demonstrated in Ndiop argue for further evaluation of baculovirus PfMSP5 as a vaccine candidate.