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

Abstract

In 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 prophylaxis (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.

Keywords: Canine rabies; Contact tracing; Disease burden; Intradermal; Post-exposure treatment; Rabies surveillance.

Fig. 1. Adapted decision tree framework to estimate burden of human rabies deaths and deaths averted by PEP.

We considered that some proportion of total bites in the population (expected bites annually, dark red box) are genuine rabies exposures (Bites × prabid = Rabies exposures), and non-exposures ((1 - prabid) × Bites) do not contribute to rabies deaths or averted deaths. Of the genuine rabies exposures, a fraction present to an ARMC and all of these persons receive PEP (Rabies exposures × preport = Reported exposures). Some of these exposed persons would otherwise have become infected and died if they had not received PEP (Reported exposures × pinfect = Deaths averted by PEP). Of the unreported exposures, a proportion will die due to rabies infection (Unreported exposures × pinfect = Deaths due to rabies). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2. PEP administration and vaccine use.

(A) Distribution of observed daily patient presentations (i.e. the number of days with N patients reporting to the ARMC) and (B) calculation of the minimum volume of vaccine (mL) used under current practice with PEP administered according to the updated TRC regimen or according to the latest WHO recommendations with the abridged 1-week ID regimen. Use of 4 × 0.1 mL per 0.5 mL vial (current practice) vs. 5 × 0.1 mL injections per 0.5 mL vial were also compared. The red dashed line corresponds to vaccine use under IM administration, assuming 1 vial per IM injection and the same level of compliance (i.e. under the Essen 4-dose or Zagreb regimen). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3. Rabies in the Moramanga District.

(A) Average monthly reported bite incidence (blue shading) per commune and total numbers of probable or confirmed cases (dark red circles). A red × indicates if at least one animal case was confirmed in the commune. All coordinates are the commune centroid, and the inset shows the district (in blue) in relation to the other districts (polygons) and ARMC (grey points) in Madagascar. (B) Time series of probable and confirmed animal cases and human cases (bars), as well as total confirmed/probable rabies exposures (dashed line) from September 2016 to December 2017. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4. Patients reporting to the ARMC.

(A) Monthly time series of patients reporting to the ARMC by their exposure status; the blue line indicates when systematic triaging of patients at the clinic began. (B) Number of contacts per probable case and the rabies status of the case (one bovine case tested negative after sample submission). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)