Vector competence and filariasis transmission in Mali

Lymphatic filariasis (LF) is a public health problem in 73 countries and is associated with marked morbidity and disability. It is unique because of its transmission by five main genera of mosquitoes, including Culex, Aedes, Anopheles, Mansonia and Ochlerotatus. In Mali, LF endemicity mapping in 2004 found all eight administrative regions to be endemic for LF. Prior to the National LF Elimination Programme (NPELF), six pilot sentinel villages were selected for baseline research studies to inform the most appropriate strategy for monitoring the impact of the proposed elimination programme based on treatment with ivermectin in combination with albendazole. The following three objectives form the basis of my PhD studies:(i) investigate LF vector population and associated transmission patterns before, during and after the initiation of mass drug administration (MDA) (ii) assess efficacy of new entomological trapping tools for LF post-MDA xenomonitoring and (iii) determine transmission potential in a urban environment in Mali. The overall design is a descriptive study including cross sectional entomological surveys along with longitudinal human surveys to assess the MDA impact. I used standard infection status assessment methods as well as recently developed methods; including the antibody test for Wb123. I conducted these studies in both rural (Sikasso and Kolondieba districts) and urban areas (Bamako, the capital city). My thesis is the first report of the outcome of up to five years post-MDA annual assessment of W. bancrofti transmission using both entomological and parasitological data in an Anopheles transmission area where albendazole plus ivermectin is the recommended drug regimen and Anopheles gambiae s.l the main vector for LF transmission. These features are found mainly in the Western part of Africa. In the pilot sentinel sites in Mali, made of six neighbouring villages, seven MDA rounds with the albendazole plus ivermectin were successful not only at stopping LF transmission (infection rates within 6-7 years old children <2%) in the short term, but also at sustaining it for up to five years after the last MDA. In contrast, impact assessment in another hyper endemic area (two neighbouring villages treated by the NPELF in the district of Kolondieba) did not demonstrate interruption of transmission after the sixth and seventh MDA rounds. The reasons of these different outcomes of MDA implementation in the different areas are discussed. Of note, the failure in the latter villages was detected using only the ICT card, a method that has been found to overestimate the infection rate in children when compared to the circulating filarial antigen test (Og4C3 ELISA) and the Wb123 antibody test in the pilot sentinel area. In Anopheles transmission areas, it has been observed that focal low-level transmission can exist without being a real threat for re-emergence of transmission, due to lower capacity of the vector to transmit when parasite density is low. Nevertheless, in areas that fail the Transmission Assessment Survey (TAS), adult populations should be checked in addition to the recommended 6-7 year-old age group. Additionally, this thesis showed very promising results for using the Ifakara tent trap type C (ITTC), a human baited trap alternative to the human landing catch. Anopheles yields and infection rates using ITTC were strongly correlated with results using human landing catch (HLC) overall, as well as monthly, in two villages with significantly different Anopheles densities. Finally, it appears that the current version of the TAS needs more tools and additional directions for human infection status determination especially when the baseline endemicity level is high. Further evaluation the ITTC after reducing its bulkiness is required to confirm its usefulness for LF entomological studies in Anopheles transmission areas. From the 6,174 Culex spp and the 16 Anopheles gambiae s.l processed and 1,002 volunteers tested, there was no evidence of LF transmission in the urban environment of Bamako in Mali

First report of HIV-related oral manifestations in Mali

Introduction: In 2004, the sudden availability of free antiretroviral therapy (ART in Mali, within the context of an already overburdened health care&nbsp; system created gaps in individual patient quality of care. The objective of this study was to determine the prevalence of HIV-related oral manifestations (OM) during the first month of ART therapy in a Malian health facility. Methods: Medical records of adult patients who initiated ART regimens at the Gabriel Tour&eacute; Hospital, Mali (2001 to 2008) were randomly identified. Multiple logistic regression models were used to evaluate the relationship between the presence of OM during the first month of ART and selected variables, including CD4 counts and WHO clinical staging at ART initiation. Results: Out of 205 patients on ART (mean age 39 &plusmn; 10 years), 71.0% were females and 36.1% had no formal education. 40.6% were in WHO clinical stage III. OM prevalence during the first month of HIV care was 31.4%, being oral candidiasis the commonest lesion. 73.2% and 82.5% of the patients with OM had CD4 count &lt; 200 cells/mm3 and were classified as WHO clinical stage III or IV. WHO clinical stage III and VI patients had 5.4-fold increased odds of having any OM (both p&lt; 0.01) when controlling for age, ethnicity, gender, marital status, and CD4 counts. Conclusion: OM detected in people with low CD4 count and WHO clinical stage III and IV at ART initiation suggested that they were very immune- compromised when initiating HIV care. Early identification of OM could improve the quality of care and guarantee the benefits of ART

Successful field trial of attractive toxic sugar bait (ATSB) plant-spraying methods against malaria vectors in the Anopheles gambiae complex in Mali, West Africa

<p>Abstract</p> <p>Background</p> <p>Based on highly successful demonstrations in Israel that attractive toxic sugar bait (ATSB) methods can decimate local populations of mosquitoes, this study determined the effectiveness of ATSB methods for malaria vector control in the semi-arid Bandiagara District of Mali, West Africa.</p> <p>Methods</p> <p>Control and treatment sites, selected along a road that connects villages, contained man-made ponds that were the primary larval habitats of <it>Anopheles gambiae </it>and <it>Anopheles arabiensis</it>. Guava and honey melons, two local fruits shown to be attractive to <it>An. gambiae </it>s.l., were used to prepare solutions of Attractive Sugar Bait (ASB) and ATSB that additionally contained boric acid as an oral insecticide. Both included a color dye marker to facilitate determination of mosquitoes feeding on the solutions. The trial was conducted over a 38-day period, using CDC light traps to monitor mosquito populations. On day 8, ASB solution in the control site and ATSB solution in the treatment site were sprayed using a hand-pump on patches of vegetation. Samples of female mosquitoes were age-graded to determine the impact of ATSB treatment on vector longevity.</p> <p>Results</p> <p>Immediately after spraying ATSB in the treatment site, the relative abundance of female and male <it>An. gambiae </it>s.l. declined about 90% from pre-treatment levels and remained low. In the treatment site, most females remaining after ATSB treatment had not completed a single gonotrophic cycle, and only 6% had completed three or more gonotrophic cycles compared with 37% pre-treatment. In the control site sprayed with ASB (without toxin), the proportion of females completing three or more gonotrophic cycles increased from 28.5% pre-treatment to 47.5% post-treatment. In the control site, detection of dye marker in over half of the females and males provided direct evidence that the mosquitoes were feeding on the sprayed solutions.</p> <p>Conclusion</p> <p>This study in Mali shows that even a single application of ATSB can substantially decrease malaria vector population densities and longevity. It is likely that ATSB methods can be used as a new powerful tool for the control of malaria vectors, particularly since this approach is highly effective for mosquito control, technologically simple, inexpensive, and environmentally safe.</p

Implementing Preventive Chemotherapy through an Integrated National Neglected Tropical Disease Control Program in Mali

Neglected tropical diseases (NTDs) are a group of chronic infections that affect the poorest group of the populations in the world. There are currently five major NTDs targeted through mass drug treatment in the affected communities. The drug delivery can be integrated to deliver different drug packages as these NTDs often overlap in distribution. Mali is endemic with all five major NTDs. The integrated national NTD control program was implemented through the primary health care system using the community health center workers and the community drug distributors aiming at long-term sustainability. After a pilot start in three regions in 2007 without prior examples to follow on integrated mass drug administration, treatment for the five targeted NTDs was gradually scaled up and reached all endemic districts by 2009, and annual drug coverage in the targeted population has since been maintained at a high level for each of the five NTDs. Around 10 million people received one or more drug treatments each year since 2009. The country is on the way to meet the national objectives of elimination or control of these diseases. The successes and lessons learned in Mali are valuable assets to other countries looking to start similar programs

The Wolbachia endosymbiont as an anti-filarial nematode target

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Connaissances, attitudes et pratiques face aux IST VIH-SIDA chez les lycéens de Gao (Nord-Mali Afrique de l’Ouest).

La prévalence du VIH a augmenté de 0,6 à 1,1 % entre 2001 et 2006 dans la région de Gao. En Afrique, la pandémie du VIH/SIDA affecte surtout les jeunes et se transmet en grande partie par voie sexuelle. Nous avons menée une étude transversale chez les lycéens de la ville de Gao pour évaluer leur connaissances attitudes et pratiques par rapport à l’infection par le VIH. L’inclusion des sujets s’est faite de façon exhaustive ou par un échantillonnage aléatoire selon la taille de l’effectif des écoles. Un questionnaire individuel et anonyme a été rempli par les élèves après obtention de leur consentement éclairé. Nous avons interviewé 446 élèves. La moyenne d’âge était de 16,6±1,4 ans, la majorité était des hommes (66,5%), 6,1% était marié et 5,2% avait déjà eu un enfant. Quarante et huit pourcent des élèves avaient déjà eu des relations sexuelles. La proportion de garçons qui avait déjà eu une relation sexuelle était significativement plus élevée que celle des filles (56,6% vs 30,8%) (p<10-3 ). La moyenne d’âge à la première relation sexuelle était significativement plus basse chez les garçons (13,4±2,5 vs 15,5±1,8 ans) (p<10-3 ). Soixante et huit pourcent des élèves on dit avoir déjà entendu parler des IST; 87,4% ont estimé connaitre le VIH, Mais la proportion des élèves qui connaissait les différents modes de transmission du VIH était plus faible: 78,7 % pour la transmission sexuelle; 71,3% pour la transmission sanguine et seulement 30,8 % pour la transmission mère enfant. Comme source d’information sur le VIH, la télévision a été la plus fréquemment citée (82,1%); suivi de la radio (66,4%); et des discussions avec les amis (48%) ou les parents (23,3%). La proportion des filles qui parlait avec leurs parents était significativement plus élevée que celle des garçons (29,5% vs 20,2%: p=0,028). La lute contre le SIDA et les IST doit se baser sur la prévention en donnant les informations appropriées aux jeunes avant qu’ils ne commencent l’activité sexuelle et l’école est un lieu indiqué pour acquérir les connaissances correctes et les pratique sures