Sensitivity of IFN-γ Release Assay to Detect Latent Tuberculosis Infection Is Retained in HIV-Infected Patients but Dependent on HIV/AIDS Progression

Background

Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV.

Objective

To assess the validity of a newly developed in-house ELISPOT interferon-γ release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST).

Methodology/Principal Findings

ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain.

Conclusion

Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals.     

Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial

Background

The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.

Methodology/Principal Findings

A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18–55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 µg/AS02A 0.25 mL or FMP2.1 50 µg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.

Conclusion/Significance

The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00308061","term_id":"NCT00308061"}}NCT00308061     

Genetic and Environmental Factors Associated with Laboratory Rearing Affect Survival and Assortative Mating but Not Overall Mating Success in Anopheles gambiae Sensu Stricto

Anopheles gambiae sensu stricto, the main vector of malaria in Africa, is characterized by its vast geographical range and complex population structure. Assortative mating amongst the reproductively isolated cryptic forms that co-occur in many areas poses unique challenges for programs aiming to decrease malaria incidence via the release of sterile or genetically-modified mosquitoes. Importantly, whether laboratory-rearing affects the ability of An. gambiae individuals of a given cryptic taxa to successfully mate with individuals of their own form in field conditions is still unknown and yet crucial for mosquito-releases. Here, the independent effects of genetic and environmental factors associated with laboratory rearing on male and female survival, mating success and assortative mating were evaluated in the Mopti form of An. gambiae over 2010 and 2011. In semi-field enclosures experiments and despite strong variation between years, the overall survival and mating success of male and female progeny from a laboratory strain was not found to be significantly lower than those of the progeny of field females from the same population. Adult progeny from field-caught females reared at the larval stage in the laboratory and from laboratory females reared outdoors exhibited a significant decrease in survival but not in mating success. Importantly, laboratory individuals reared as larvae indoors were unable to mate assortatively as adults, whilst field progeny reared either outdoors or in the laboratory, as well as laboratory progeny reared outdoors all mated significantly assortatively. These results highlight the importance of genetic and environment interactions for the development of An. gambiae''s full mating behavioral repertoire and the challenges this creates for mosquito rearing and release-based control strategies.     

Groundfish assemblages diversity in upwelling ecosystems: insights from the Mauritanian Exclusive Economic Zone

Upwelling ecosystems exhibit strong spatio-temporal variations of environmental conditions that drive the dynamics of marine diversity and ressources. Yet little is known in these ecosystems concerning the diversity of groundfishes. We studied the effects of environment (sea surface temperature, chlorophyll a concentration and bathymetric strata) and fishing pressure on this variability in the Mauritanian Exclusive Economic Zone (MEEZ), based on abundance data collected from 2158 hauls from scientific surveys performed on the continental shelf (15–200 m) between 1997 and 2010. First, for each haul (i.e. alpha-diversity), Species richness S and Berger Parker dominance D_bp were used as proxies of two complementary groups of nine indices, belonging to three main components of diversity (species number, evenness and taxonomic diversity), identified by a principal component analysis based on Spearman correlation coefficient. Thus the set of diversity indices used in this work suggests that a single component of diversity cannot represent the biodiversity of MEEZ groundfish. Second, generalized linear models (GLM) highlighted the stability of both indices for environmental variables, fishing effort and time, while, as shown by a previous study in the MEEZ, these variables influence species composition (i.e. beta-diversity). A longitudinal gradient of S and D_bp was highlighted, with coastal strata being richer in species and abundances more evenly distributed among species than offshore strata. Overall, this study provides a baseline of groundfish diversity in the MEEZ, that is also useful for comparison to other upwelling ecosystems, and essential for monitoring its potential shifts faced to climate change.

     

Chromosomal inversions and ecotypic differentiation in Anopheles gambiae: the perspective from whole‐genome sequencing

The molecular mechanisms and genetic architecture that facilitate adaptive radiation of lineages remain elusive. Polymorphic chromosomal inversions, due to their recombination‐reducing effect, are proposed instruments of ecotypic differentiation. Here, we study an ecologically diversifying lineage of Anopheles gambiae, known as the Bamako chromosomal form based on its unique complement of three chromosomal inversions, to explore the impact of these inversions on ecotypic differentiation. We used pooled and individual genome sequencing of Bamako, typical (non‐Bamako) An. gambiae and the sister species Anopheles coluzzii to investigate evolutionary relationships and genomewide patterns of nucleotide diversity and differentiation among lineages. Despite extensive shared polymorphism and limited differentiation from the other taxa, Bamako clusters apart from the other taxa, and forms a maximally supported clade in neighbour‐joining trees based on whole‐genome data (including inversions) or solely on collinear regions. Nevertheless, F_ST outlier analysis reveals that the majority of differentiated regions between Bamako and typical An. gambiae are located inside chromosomal inversions, consistent with their role in the ecological isolation of Bamako. Exceptionally differentiated genomic regions were enriched for genes implicated in nervous system development and signalling. Candidate genes associated with a selective sweep unique to Bamako contain substitutions not observed in sympatric samples of the other taxa, and several insecticide resistance gene alleles shared between Bamako and other taxa segregate at sharply different frequencies in these samples. Bamako represents a useful window into the initial stages of ecological and genomic differentiation from sympatric populations in this important group of malaria vectors.     

Comparison of macrofauna communities in sediments of the beds of vertical flow constructed wetlands planted with Panicum maximum (Jacq.) treating domestic wastewater

To improve our understanding of the ecological functioning of constructed wetlands, the macrofauna structure in the sediments of a constructed wetland planted with Panicum maximum treating domestic wastewater was studied. Two beds were planted with young P. maximum and two unplanted beds were used as controls. After 150 days of wastewater treatment on the beds, macrofauna was collected by taking five cores of sediment samples at the corners and the centre of each bed following three layers in the vertical profile. Globally, the planted beds removed COD, NH₄⁺, and PO₄^3? more (p < 0.05) than the control. Eleven taxa belonging to 6 classes and 11 orders were recorded. Macrofauna was significantly more diversified (Mann–Whitney test: p < 0.05) in terms of Shannon index of diversity in the planted beds (0.25–0.44 bits/ind.) than in the control (0.08–0.23 bits/ind.). But macrofauna settlement presents a relative homogeneity between the beds (index Jaccard = 0.63). Its abundance was three times higher in the planted bed than in the control. From the surface to the bottom of the beds, macrofauna diversity and abundance decreased and were heavily dominated by Annelida. The significant relationships were only observed between Insecta and Myriapoda in the control.     

Bidirectional Introgressive Hybridization between a Cattle and Human Schistosome Species

Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions, caused by parasitic flatworms of the genus Schistosoma (subclass Digenea). Following major water development schemes in the 1980s, schistosomiasis has become an important parasitic disease of children living in the Senegal River Basin (SRB). During molecular parasitological surveys, nuclear and mitochondrial markers revealed unexpected natural interactions between a bovine and human Schistosoma species: S. bovis and S. haematobium, respectively. Hybrid schistosomes recovered from the urine and faeces of children and the intermediate snail hosts of both parental species, Bulinus truncatus and B. globosus, presented a nuclear ITS rRNA sequence identical to S. haematobium, while the partial mitochondrial cox1 sequence was identified as S. bovis. Molecular data suggest that the hybrids are not 1st generation and are a result of parental and/or hybrid backcrosses, indicating a stable hybrid zone. Larval stages with the reverse genetic profile were also found and are suggested to be F1 progeny. The data provide indisputable evidence for the occurrence of bidirectional introgressive hybridization between a bovine and a human Schistosoma species. Hybrid species have been found infecting B. truncatus, a snail species that is now very abundant throughout the SRB. The recent increase in urinary schistosomiasis in the villages along the SRB could therefore be a direct effect of the increased transmission through B. truncatus. Hybridization between schistosomes under laboratory conditions has been shown to result in heterosis (higher fecundity, faster maturation time, wider intermediate host spectrum), having important implications on disease prevalence, pathology and treatment. If this new hybrid exhibits the same hybrid vigour, it could develop into an emerging pathogen, necessitating further control strategies in zones where both parental species overlap.     

Where Do We Go from Here? Prevalence of Trachoma Three Years after Stopping Mass Distribution of Antibiotics in the Regions of Kayes and Koulikoro,Mali

Objectives

A national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were launched in the regions of Kayes and Koulikoro in 2003. MDA was discontinued after three annual rounds in 2006, and an impact survey conducted. We resurveyed all districts in Kayes and Koulikoro in 2009 to reassess trachoma prevalence and determine intervention objectives for the future. In this paper we present findings from both the 2006 and 2009 surveys.

Methods

Population-based cluster surveys were conducted in each of the nine districts in Koulikoro in 2006 and 2009, whilst in Kayes, four of seven districts in 2006 and all seven districts in 2009 were surveyed. Household members present were examined for clinical signs of trachoma.

Results

Overall, 29,179 persons from 2,528 compounds, in 260 clusters were examined in 2006 and 32,918 from 7,533 households in 320 clusters in 2009. The prevalence of TF in children aged 1–9 years in Kayes and Koulikoro was 3.9% (95%CI 2.9–5.0%, range by district 1.2–5.4%) and 2.7% (95%CI 2.3–3.1%, range by district 0.1–5.0%) respectively in 2006. In 2009 TF prevalence was 7.26% (95%CI 6.2–8.2%, range by district 2.5–15.4%) in Kayes and 8.19% (95%CI 7.3–9.1%, range by district 1.7–17.2%) in Koulikoro among children of the same age group. TT in adults 15 years of age and older was 2.37% (95%CI 1.66–3.07%, range by district 0.30–3.54%) in 2006 and 1.37% (95%CI 1.02–1.72%, range by district 0.37–1.87%) in 2009 in Kayes and 1.75% (95%CI 1.31–2.23%, range by district 1.06–2.49%) in 2006 and 1.08% (95%CI 0.86–1.30%, range by district 0.34–1.78%) in 2009 in Koulikoro.

Conclusions

Using WHO guidelines for decision making, four districts, Bafoulabe in Kayes Region; and Banamba, Kolokani and Koulikoro in Koulikoro Region, still meet criteria for district-wide implementation of the full SAFE strategy as TF in children exceeds 10%. A community-by-community approach to trachoma control may now be required in the other twelve districts. Trichiasis surgery provision remains a need in all districts and should be enhanced in six districts in Kayes and five in Koulikoro where the prevalence exceeded 1.0% in adults. Since 1997 great progress has been observed in the fight against blinding trachoma; however, greater effort is required to meet the elimination target of 2015.     

Bottlenecks for High Coverage of Intermittent Preventive Treatment in Pregnancy: The Case of Adolescent Pregnancies in Rural Burkina Faso

Background

While IPTp-SP is currently being scaled up in sub-Saharan Africa (SSA), the coverage with the required ≥2 doses of SP remains considerably short of the Roll Back Malaria (RBM) goal of 80%, not to mention of the recently advocated universal coverage.

Methods

The study triangulates quantitative data from a health center randomized community-based trial on IPTp-SP effectiveness and the additional benefit of a promotional campaign with qualitative data from focused ethnography.

Findings

In rural Burkina Faso, despite the significantly higher risk of malaria infection among adolescent primigravidae (PG) (OR 2.44 95%CI 1.81–3.28, p<0.001), making them primary target beneficiaries of IPTp-SP, adolescents adhered to the required three or more ANC visits significantly less (PG: 46.6%; SG 43.7%) than adults (PG: 61.9%; SG 54.9%) and had lower SP uptake during the malaria transmission season, further showing the difficulty of reaching this age group. Adolescents'' structural constraints (such as their social position and household labor requirements) and needs (such as anonymity in the health encounter) leave them highly vulnerable during their pregnancies and, especially, during the high malaria transmission season.

Conclusion

Our study shows that adolescents need to be targeted specifically, prior to their first pregnancy and with measures adapted to their social context, addressing their structural constraints and needs and going beyond standard health promotion campaigns. Unless such specific measures are taken, adolescents'' social vulnerability will present a serious bottleneck for the effectiveness of IPTi-SP.