Effectiveness of insecticidal nets on uncomplicated clinical malaria : a case-control study for operational evaluation

Background: In a context of large-scale implementation of malaria vector control tools, such as the distribution of long-lasting insecticide nets (LLIN), it is necessary to regularly assess whether strategies are progressing as expected and then evaluate their effectiveness. The present study used the case-control approach to evaluate the effectiveness of LLIN 42 months after national wide distribution. This study design offers an alternative to cohort study and randomized control trial as it permits to avoid many ethical issues inherent to them. Methods: From April to August 2011, a case-control study was conducted in two health districts in Benin; Ouidah-Kpomasse-Tori (OKT) in the south and Djougou-Copargo-Ouake (DCO) in the north. Children aged 0-60 months randomly selected from community were included. Cases were children with a high axillary temperature (>= 37.5 degrees C) or a reported history of fever during the last 48 h with a positive rapid diagnostic test (RDT). Controls were children with neither fever nor signs suggesting malaria with a negative RDT. The necessary sample size was at least 396 cases and 1188 controls from each site. The main exposure variable was "sleeping every night under an LLIN for the 2 weeks before the survey" (SL). The protective effectiveness (PE) of LLIN was calculated as PE = 1 - odds ratio. Results: The declared SL range was low, with 17.0 and 27.5 % in cases and controls in the OKT area, and 44.9 and 56.5 % in cases and controls, in the DCO area, respectively. The declared SL conferred 40.5 % (95 % CI 22.2-54.5 %) and 55.5 % (95 % CI 28.2-72.4 %) protection against uncomplicated malaria in the OKT and the DCO areas, respectively. Significant differences in PE were observed according to the mother's education level. Conclusion: In the context of a mass distribution of LLIN, their use still conferred protection in up to 55 % against the occurrence of clinical malaria cases in children. Social factors, the poor use and the poor condition of an LLIN can be in disfavour with its effectiveness. In areas, where LLIN coverage is assumed to be universal or targeted at high-risk populations, case-control studies should be regularly conducted to monitor the effectiveness of LLIN. The findings will help National Malaria Control Programme and their partners to improve the quality of malaria control according to the particularity of each area or region as far as possible

Heterologous prime-boost vaccination using an ASO3B-adjuvanted influenza A(H5N1) vaccine in infants and children <3 years of age

Presented in part: Options for the Control of Influenza VIII Conference, Cape Town, South Africa, 5–10 September 2013BACKGROUND: Protecting young children from pandemic influenza should also reduce transmission to susceptible adults, including pregnant women. METHODS: An open study assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005(H5N1)-AS03B (AS03B is an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion [5.93 mg tocopherol]) in infants and children aged 6 to <36 months that was given 6 months following 2-dose primary vaccination with A/Indonesia/05/2005(H5N1)-AS03B. Vaccines contained 1.9 µg of hemagglutinin antigen and AS03B. Hemagglutinin inhibition (HI) responses, microneutralization titers, and antineuraminidase antibody levels were assessed for 6 months following the booster vaccination. RESULTS: For each age stratum (defined on the basis of the subject's age at first vaccination as 6 to <12 months, 12 to <24 months, and 24 to <36 months) and overall (n=113), European influenza vaccine licensure criteria were fulfilled for responses to A/turkey/Turkey/1/2005(H5N1) 10 days following the booster vaccination. Local pain and fever increased with consecutive doses. Anamnestic immune responses were demonstrated for HI, neutralizing, and antineuraminidase antibodies against vaccine-homologous/heterologous strains. Antibody responses to vaccine-homologous/heterologous strains persisted in all children 6 months following the booster vaccination. CONCLUSIONS: Prevaccination of young children with a clade 2 strain influenza A(H5N1) AS03-adjuvanted vaccine followed by heterologous booster vaccination boosted immune responses to the homologous strain and a related clade, with persistence for at least 6 months. The results support a prime-boost vaccination approach in young children for pandemic influenza preparedness. CLINICAL TRIALS REGISTRATION: NCT01323946.Terry Nolan, Patricia Izurieta, Bee-Wah Lee, Poh Chong Chan, Helen Marshall, Robert Booy, Mamadou Drame, and David W. Vaugh

Rapid cognitive decline, one-year institutional admission and one-year mortality: Analysis of the ability to predict and inter-tool agreement of four validated clinical frailty indexes in the safes cohort

Objectives: To evaluate the predictive ability of four clinical frailty indexes as regards one-year rapid cognitive decline (RCD — defined as the loss of at least 3 points on the MMSE score), and one-year institutional admission (IA) and mortality respectively; and to measure their agreement for identifying groups at risk of these severe outcomes. Design: One-year follow-up and multicentre study of old patients participating in the SAFEs cohort study. Setting: Nine university hospitals in France. Participants: 1,306 patients aged 75 or older (mean age 85±6 years; 65% female) hospitalized in medical divisions through an Emergency department. Measurements: Four frailty indexes (Winograd; Rockwood; Donini; and Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an ordinal scoring system able to discriminate different grades of frailty, and constructed based on the accumulation of identified deficits after comprehensive geriatric assessment conducted during the first week of hospital stay, were used to categorize participants into three different grades of frailty: Gl — not frail; G2 — moderately frail; and G3 — severely frail. Comparisons between groups were performed using Fisher's exact test. Agreement between indexes was evaluated using Cohen's Kappa coefficient. Results: All patients were classified as frail by at least one of the four indexes. The Winograd and Rockwood indexes mainly classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and 1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD, 377 (36%) were admitted into an institutional setting, and 445 (34%) had died With the Rockwood index, all subjects who expenenced RCD were classified in G2; and in G2 and G3 when the Donini and Schoevaerdts indexes were used No significant difference was found between frailty grade and RCD, whereas frailty grade was significantly associated with an increased risk of IA and death, whatever the frailty index considered. Agreement between the different indexes of frailty was poor with Kappa coefficients ranging from −0.02 to 0.15. Conclusion: These findings confirm the poor clinimetric properties of these current indexes to measure frailty, underlining the fact that further work is needed to develop a better and more widely-accepted definition of frailty and therefore a better understanding of its pathophysiolog

IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal

<p>Abstract</p> <p>Background</p> <p>Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific <it>Anopheles </it>gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to <it>Anopheles </it>bites. The aim of this study was to use this biomarker to evaluate the human exposure to <it>Anopheles </it>mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where <it>Anopheles </it>biting rates and malaria transmission are supposed to be low.</p> <p>Methods</p> <p>One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district.</p> <p>Results</p> <p>Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to <it>Anopheles gambiae </it>bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and <it>Anopheles </it>mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to <it>Anopheles </it>bites between different exposure groups of districts.</p> <p>Conclusions</p> <p>Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to <it>Anopheles </it>bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings.</p

Variable selection: current practice in epidemiological studies

Selection of covariates is among the most controversial and difficult tasks in epidemiologic analysis. Correct variable selection addresses the problem of confounding in etiologic research and allows unbiased estimation of probabilities in prognostic studies. The aim of this commentary is to assess how often different variable selection techniques were applied in contemporary epidemiologic analysis. It was of particular interest to see whether modern methods such as shrinkage or penalized regression were used in recent publications. Stepwise selection methods remained the predominant method for variable selection in publications in epidemiological journals in 2008. Shrinkage methods were not used in any of the reviewed articles. Editors, reviewers and authors have insufficiently promoted the new, less controversial approaches of variable selection in the biomedical literature, whereas statisticians may not have adequately addressed the method’s feasibility

IgG Responses to Anopheles gambiae Salivary Antigen gSG6 Detect Variation in Exposure to Malaria Vectors and Disease Risk

Assessment of exposure to malaria vectors is important to our understanding of spatial and temporal variations in disease transmission and facilitates the targeting and evaluation of control efforts. Recently, an immunogenic Anopheles gambiae salivary protein (gSG6) was identified and proposed as the basis of an immuno-assay determining exposure to Afrotropical malaria vectors. In the present study, IgG responses to gSG6 and 6 malaria antigens (CSP, AMA-1, MSP-1, MSP-3, GLURP R1, and GLURP R2) were compared to Anopheles exposure and malaria incidence in a cohort of children from Korogwe district, Tanzania, an area of moderate and heterogeneous malaria transmission. Anti-gSG6 responses above the threshold for seropositivity were detected in 15% (96/636) of the children, and were positively associated with geographical variations in Anopheles exposure (OR 1.25, CI 1.01–1.54, p = 0.04). Additionally, IgG responses to gSG6 in individual children showed a strong positive association with household level mosquito exposure. IgG levels for all antigens except AMA-1 were associated with the frequency of malaria episodes following sampling. gSG6 seropositivity was strongly positively associated with subsequent malaria incidence (test for trend p = 0.004), comparable to malaria antigens MSP-1 and GLURP R2. Our results show that the gSG6 assay is sensitive to micro-epidemiological variations in exposure to Anopheles mosquitoes, and provides a correlate of malaria risk that is unrelated to immune protection. While the technique requires further evaluation in a range of malaria endemic settings, our findings suggest that the gSG6 assay may have a role in the evaluation and planning of targeted and preventative anti-malaria interventions

Snake Envenoming: A Disease of Poverty

Every year snake envenoming kills more people in the tropics than some of the world's recognised neglected tropical diseases (NTDs), including schistosomiasis and leishmaniasis. While lacking the epidemic potential of an infectious/vector-borne disease, snake envenoming in rural tropical communities has as great a medical mortality, if not morbidity, as the NTDs. The recent categorisation of snake envenoming as an NTD is an important advance that hopefully will result in the wider recognition and allocation of resources, particularly since death from snake envenoming is preventable; antivenom is very effective when the appropriate antivenom is correctly administered. Snake envenoming urgently requires international support to instigate the epidemiological, health education, and effective treatment initiatives that proved so potent in addressing the medical burden of NTDs such as leprosy and dracunculosis. All the global estimates of snake envenoming and deaths from snakebite indicate that mortality is highest in the world's tropical countries. Here we examined associations between the globally available data on (i) snakebite-induced mortality and (ii) socioeconomic markers of poverty. Our data unequivocally establishes that snake envenoming is globally associated with poverty, a distinctive characteristic of the neglected tropical diseases

“But the moment they find out that you are MSM…”: a qualitative investigation of HIV prevention experiences among men who have sex with men (MSM) in Ghana’s health care system

Abstract: The prevalence of HIV in Ghana is 1.3%, compared to 17% among men who have sex with men (MSM). There is limited empirical data on the current health care climate and its impact on HIV prevention services for Ghanaian MSM. The purposes of this study were to investigate (1) MSM’s experiences using HIV prevention resources, (2) what factors, including health care climate factors, influenced MSM’s use of prevention resources and (3) MSM self-identified strategies for improving HIV/sexually transmitted infection (STI) prevention among MSM in Ghanaian communities. Methods: We conducted 22 focus groups (n = 137) with peer social networks of MSM drawn from three geographic communities in Ghana (Accra, Kumasi, Manya Krobo). The data were examined using qualitative content analysis. Interviews with individual health care providers were also conducted to supplement the analysis of focus group findings to provide more nuanced illuminations of the experiences reported by MSM..

Evaluation of the Human IgG Antibody Response to Aedes albopictus Saliva as a New Specific Biomarker of Exposure to Vector Bites

Aedes-borne viruses like dengue and chikungunya are a major problem in Reunion Island. Assessing exposure to Aedes bites is crucial to estimating the risk of pathogen transmission. Currently, the exposure of populations to Aedes albopictus bites is mainly evaluated by entomological methods which are indirect and difficult to apply on a large scale. Recent findings suggest that evaluation of human antibody responses against arthropod salivary proteins could be useful in assessing exposure to mosquito bites. The results indicate that 88% of the studied population produce IgG to Ae. albopictus saliva antigens in Reunion Island and show that this biomarker can detect different levels of individual exposure. In addition, little cross-reactivity is observed with Aedes aegypti saliva, suggesting that this could be a specific marker for exposure to Aedes albopictus bites. Taken together, these results suggest that antibody responses to saliva could constitute a powerful immuno-epidemiological tool for evaluating exposure to Aedes albopictus and therefore the risk of arbovirus infection