Post-deployment effectiveness of malaria control interventions on Plasmodium infections in Madagascar: a comprehensive phase IV assessment

Additional file 1. Definition of variables

Modèles contre maladies infectieuses par Gauthier Sallet. Le paludisme fait de la résistance, entretien avec Christophe Rogier, propos recueillis par Dominique Chouchan.

National audienceComment enrayer les ravages d'une maladie telle que le paludisme ? Les modèles numériques devraient au moins offrir un outil de compréhension de sa diffusion et de l'émergence des résistances aux médicaments

Outcome of life-threatening malaria in African children requiring endotracheal intubation

BACKGROUND: Little is known about children undergoing critical care for malaria. The purpose of this survey was to evaluate the outcome in African children requiring endotracheal intubation for life-threatening malaria. METHODS: All children with a primary diagnosis of severe malaria (2000 WHO definition) requiring endotracheal intubation, hospitalised over a five-year period, within a tertiary-care hospital in Dakar, Senegal, were enrolled in a retrospective cohort study. RESULTS: 83 consecutive patients were included (median PRISM h(24 )score: 14; IQR: 10–19, multiple organ dysfunctions: 91.5%). The median duration of ventilation was 36 hrs (IQR: 4–72). Indications for intubation were deep coma (Glasgow score ≤7, n = 16), overt cortical or diencephalic injury, i.e, status epilepticus/decorticate posturing (n = 20), severe brainstem involvement, i.e., decerebrate posturing/opisthotonus (n = 15), shock (n = 15), cardiac arrest (n = 13) or acute lung injury (ALI) (PaO(2)/FiO(2 )<300 Torr, n = 4). Death occurred in 50 cases (case fatality rate (CFR), 60%) and was associated with multiple organ dysfunctions (median PELOD(h24 )scores: 12.5 among non-survivors versus 11 among survivors, p = 0.02). Median PRISM(h24 )score was significantly lower when testing deep coma against other indications (10 vs 15, p < 0.001), ditto for PELOD(h24 )score (2.5 vs 13, p = 0.02). Multivariate analysis identified deep coma as having a better outcome than other indications (CFR, 12.5% vs 40.0 to 93.3%, p < 0.0001). Decerebrate posturing/opisthotonus (CFR 73.3%, adjusted relative risk (aRR) 10.7, 95% CI 2.3–49.5) were associated with a far worse prognosis than status epilepticus/decorticate posturing (CFR 40.0%, aRR 5.7, 95% CI 1.2–27.1). Thrombocytopaenia (platelet counts <100,000/mm(3)) was associated with death (aRR 2.6, 95% CI 1.2–5.8) and second-line anticonvulsant use (clonazepam or thiopental) with survival (aRR 0.4, 95% CI 0.2–0.9). Complications, mostly nosocomial infections (n = 20), ALI/ARDS (n = 9) or sub-glottic stenosis (n = 3), had no significant prognostic value. CONCLUSION: In this study, the outcome of children requiring intubation for malaria depends more on clinical presentation and progression towards organ failures than on critical care complications per se. In sub-Saharan Africa, mechanical ventilation for life-threatening childhood malaria is feasible, but seems unlikely to dramatically improve the prognosis

New protective battle-dress impregnated against mosquito vector bites

<p>Abstract</p> <p>Background</p> <p>Mixing repellent and organophosphate (OP) insecticides to better control pyrethroid resistant mosquito vectors is a promising strategy developed for bed net impregnation. Here, we investigated the opportunity to adapt this strategy to personal protection in the form of impregnated clothes.</p> <p>Methods</p> <p>We compared standard permethrin impregnated uniforms with uniforms manually impregnated with the repellent KBR3023 alone and in combination with an organophosphate, Pirimiphos-Methyl (PM). Tests were carried out with <it>Aedes aegypti</it>, the dengue fever vector, at dusk in experimental huts.</p> <p>Results</p> <p>Results showed that the personal protection provided by repellent KBR3023-impregnated uniforms is equal to permethrin treated uniforms and that KBR3023/PM-impregnated uniforms are more protective.</p> <p>Conclusion</p> <p>The use of repellents alone or combined with OP on clothes could be promising for personal protection of military troops and travellers if residual activity of the repellents is extended and safety is verified.</p

Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

Background: The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag (R) system associated with the atmospheric generators for capnophilic bacteria Genbag CO2 (R) was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. Methods: The susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine) by the standard 42-hour H-3-hypoxanthine uptake inhibition method using the Genbag CO2 (R) system and compared to controlled incubator conditions (5% CO2 and 10% O-2). Results: The counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O-2) were significantly higher than those of Genbag (R) conditions (2738 cpm vs 2282 cpm, p < 0.0001). The geometric mean IC50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine. To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag (R) conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O-2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine (vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM). Conclusions: The atmospheric generators for capnophilic bacteria Genbag CO2 (R) is an appropriate technology that can be transferred to the field for epidemiological surveys of drug-resistant malaria. The present data suggest the importance of the gas mixture on in vitro microtest results for anti-malarial drugs and the importance of determining the microtest conditions before comparing and analysing the data from different laboratories and concluding on malaria resistance

Social and environmental malaria risk factors in urban areas of Ouagadougou, Burkina Faso

<p>Abstract</p> <p>Background</p> <p>Despite low endemicity, malaria remains a major health problem in urban areas where a high proportion of fevers are presumptively treated using anti-malarial drugs. Low acquired malaria immunity, behaviour of city-dwellers, access to health care and preventive interventions, and heterogenic suitability of urban ecosystems for malaria transmission contribute to the complexity of the malaria epidemiology in urban areas.</p> <p>Methods</p> <p>The study was designed to identify the determinants of malaria transmission estimated by the prevalence of anti-circumsporozoite (CSP) antibodies, the prevalence and density of <it>Plasmodium falciparum </it>infection, and the prevalence of malarial disease in areas of Ouagadougou, Burkina-Faso. Thick blood smears, dried blood spots and clinical status have been collected from 3,354 randomly chosen children aged 6 months to 12 years using two cross-sectional surveys (during the dry and rainy seasons) in eight areas from four ecological strata defined according to building density and land tenure (regular versus irregular). Demographic characteristics, socio-economic information, and sanitary and environmental data concerning the children or their households were simultaneously collected. Dependent variables were analysed using mixed multivariable models with random effects, taking into account the clustering of participants within compounds and areas.</p> <p>Results</p> <p>Overall prevalences of CSP-antibodies and <it>P. falciparum </it>infections were 7.7% and 16.6% during the dry season, and 12.4% and 26.1% during the rainy season, respectively, with significant differences according to ecological strata. Malaria risk was significantly higher among children who i) lived in households with lower economic or education levels, iii) near the hydrographic network, iv) in sparsely built-up areas, v) in irregularly built areas, vi) who did not use a bed net, vii) were sampled during the rainy season or ii) had traveled outside of Ouagadougou.</p> <p>Conclusion</p> <p>Malaria control should be focused in areas which are irregularly or sparsely built-up or near the hydrographic network. Furthermore, urban children would benefit from preventive interventions (e.g. anti-vectorial devices or chemoprophylaxis) aimed at reducing malaria risk during and after travel in rural areas.</p

Implication of haematophagous arthropod salivary proteins in host-vector interactions

The saliva of haematophagous arthropods contains an array of anti-haemostatic, anti-inflammatory and immunomodulatory molecules that contribute to the success of the blood meal. The saliva of haematophagous arthropods is also involved in the transmission and the establishment of pathogens in the host and in allergic responses. This survey provides a comprehensive overview of the pharmacological activity and immunogenic properties of the main salivary proteins characterised in various haematophagous arthropod species. The potential biological and epidemiological applications of these immunogenic salivary molecules will be discussed with an emphasis on their use as biomarkers of exposure to haematophagous arthropod bites or vaccine candidates that are liable to improve host protection against vector-borne diseases