How geographic access to care shapes disease burden: the current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar

Background: Post-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning. Methodology & principal findings: We use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790–1120), with PEP averting an additional 800 deaths (95% PI: 640–970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust. Conclusions & significance: PEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths

Chemical composition of essential oils from bark and leaves of individual trees of Ravensara aromatica Sonnerat

International audienceThe chemical composition of essential oils obtained by hydrodistillation of leaves and bark (taken individually, tree by tree) of Ravensara aromatica Sonnerat of Madagascar was investigated by gas chromatography and gas chromatography coupled with mass spectrometry. Results were treated by principal component analysis. Four chemotypes highlighted about leaves in an earlier work were confirmed: chemotype 1 (> 90% methyl chavicol), chemotype 2 (72-80% methyl eugenol), chemotype 3 (25-28% α-terpinene) and chemotype 4 (25-34% sabinene). The chemical composition of R. aromatica bark is in all cases characterized by a high amount of methyl chavicol (83-98%), whatever the chemotype. One can conclude that the bark oil of R. aromatica corresponds to the oil described previously under the name "oil of R anisata.

Composition and antimicrobial activity of essential oils of Cinnamosma fragrans

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Bark Essential Oil of Cedrelopsis grevei from Madagascar: Investigation of Steam-Distillation Conditions.

International audienceThe effect of the distillation time on the yield and chemical composition of the bark essential oil of Cedrelopsis grevei Baill. was investigated. Distillation kinetics were determined for three batches of bark sampled from two sites, i.e., Itampolo (batches IT1 and IT2) and Salary (SAL), located in a region in the south of Madagascar with characteristically large populations of C. grevei. The bark samples were subjected to steam distillation, and the essential oil was collected at 3-h intervals. The total yield (calculated after 14 h of distillation) varied from 0.9 to 1.7%, according to the batch tested. Moreover, the essential oils obtained were characterized by GC-FID and GC/MS analyses. During the course of the distillation, the relative percentages of the most volatile components (monoterpenes and sesquiterpene hydrocarbons) diminished progressively, whereas the least volatile ones (oxygenated derivatives) increased at a consistent rate. Principal component analysis (PCA) and agglomerative hierarchical clustering analysis (AHC) of the results, performed on 13 principal components, allowed distinguishing three chemical groups, corresponding to the three batches, irrespective of the distillation time. This indicated that the chemical variability currently observed with commercial samples is not mainly linked to the experimental conditions of the extraction process, as the distillation time did not significantly alter the chemical composition of the essential oils

Healthcare utilization, provisioning of post-exposure prophylaxis, and estimation of human rabies burden in Madagascar

International audienceIn Madagascar, dog-mediated rabies has been endemic for over a century, however there is little data on its incidence or impact. We collected data over a 16-month period on provisioning of post-exposure pro-phylaxis (PEP) at a focal clinic in the Moramanga District and determined the rabies status of biting animals using clinical and laboratory diagnosis. We find that animal rabies cases are widespread, and clinic-based triage and investigation are effective ways to increase detection of rabies exposures and to rule out non-cases. A high proportion of rabies-exposed persons from Moramanga sought (84%) and completed PEP (90% of those that initiated PEP), likely reflecting the access and free provisioning of PEP in the district. Current clinic vial sharing practices demonstrate the potential for intradermal administration of PEP in endemic African settings, reducing vaccine use by 50% in comparison to intramuscular administration. A high proportion of PEP demand was attributed to rabies cases, with approximately 20% of PEP administered to probable rabies exposures and an additional 20% to low-to-no risk contacts with confirmed/ probable animal or human cases. Using a simplified decision tree and our data on rabies exposure status and health-seeking behavior, we estimated an annual incidence of 42-110 rabies exposures and 1-3 deaths per 100,000 persons annually. Extrapolating to Madagascar, we estimate an annual burden of 282-745 human rabies deaths with current PEP provisioning averting 1499-3958 deaths each year. Data from other clinics and districts are needed to improve these estimates, particularly given that PEP availability is currently limited to only 31 clinics in the country. A combined strategy of mass dog vaccination , enhanced surveillance, and expanded access to PEP along with more judicious guidelines for administration could effectively reduce and eventually eliminate the burden of rabies in Madagascar