Background
The WHO 2016 guidelines for stopping ivermectin mass drug administration and verifying elimination of human onchocerciasis imply, and in one case specify explicitly, that the procedures have to be applied to transmission zones. The WHO guidelines
follow the APOC 2010 "Conceptual and Operational Framework of Onchocerciasis Elimination with Ivermectin Treatment" in defining a transmission zone (or "endemic focus" or "transmission focus") as "A geographical area where transmission of Onchocerca volvulus occurs by locally breeding vectors and which can be regarded as a natural ecological and epidemiological unit for interventions". In Africa, onchocerciasis endemic areas are vast with widely differing pre-control endemicities requiring programme managers
to decide which areas belong to a transmission zone. However, the WHO guidelines do not provide any guidance and evidence-based methods for delineation are currently not available.
In a number of onchocerciasis endemic areas under long-term MDA (community-directed treatment with ivermectin, CDTI), parasites with low susceptibility to ivermectin's embryostatic effect have been identified and are frequently referred to as "suboptimal
responders" (SOR). The progeny of such parasites could be preferentially transmitted, increasing the time to transmission suppression, decreasing the decline in the adult worm population and ultimately jeopardizing achieving elimination of transmission
of O. volvulus. Some authors have proposed that SOR indicate emerging resistance of O. volvulus to ivermectin. Recent data suggest that SOR may reflect previously underestimated variation in parasite response to ivermectin
and that this response is a polygenic, quantitative trait mediated by quantitative trait loci (QTL) subject to soft sweeps. Consequently, an increase in prevalence of parasites with low susceptibility to ivermectin cannot be excluded and countries
would benefit from tools allowing to monitor the susceptibility of parasites to ivermectin (and potentially later to moxidectin). Currently, identification of SORs requires either serial skin snips or extirpation of subcutaneous nodules and histological
evaluation of the macrofilariae, methods not suitable for monitoring.
The WHO and the Global Programme to Eliminate Lymphatic Filariasis (GPELF) currently target the elimination of LF as a public health problem through MDA with albendazole with diethylcarbamazine or, in onchocerciasis co-endemic areas, ivermectin.
The WHO 2011 manual for national elimination programmes on "Monitoring and epidemiological assessment of mass drug administration in the global programme to eliminate lymphatic filariasis" recommends implementation of the "Transmission
Assessment Surveys" (TAS) to determine whether MDA can be stopped or not in "evaluation units" (EU) selected by the LF programme managers. EUs can comprise one Implementation Unit (IU, i.e. areas qualifying for MDA), part of
an IU or multiple IUs. In some areas where MDA was stopped, the resurgence has been observed several years later, raising the question of the origin of this resurgence (parasites from within the EU or from outside the EU) and thus possibly about the
appropriateness of the EU selected. Countries would benefit from tools for the investigation of the likely sources of apparent post-MDA resurgence of parasite transmission and tools to delineate EUs as areas across which the parasite is transmitted
via vector or human movements.
Current activities for onchocerciasis control and elimination
TDR is funding research to exploit population genomics and modelling to
- Identify genetic markers that allow to determine the extent to which the parasites, as well as the vectors, in different endemic locations, are related to each other. This relatedness is an indicator of the extent of historical interbreeding and thus
transmission of the parasite between different locations. The targeted outcome is an easy-to-use tool for country NTD managers to delineate "transmission zones" as areas with defined levels of parasite interbreeding. The genetic markers would
also allow determining where parasites caught during the post-treatment and/or post-elimination surveillance are coming from, i.e. whether they belong to the original parasite population or were imported through vector or human migration from
other endemic areas.
- Expand the EpiOncho O. volvulus transmission model to allow modelling the effect of parasite movement (via vectors and/or humans) between areas with different endemicity and control treatment history. The targeted outcome is a model with
an interface that country NTD managers can use to e.g. estimate the risk and time frame for a resurgence if CDTI was discontinued in one area because it meets WHO guideline criteria for stopping CDTI when parasites are being introduced via human
or vector movement from (an) other areas (s) not yet meeting criteria for stopping CDTI;
- Develop a method for determining the number of male and/or female macrofilariae that contributed to a sample of O. volvulus obtained in vectors caught for WHO guideline recommended pool-screening or in skin snips. The targeted outcome is
a tool for country NTD managers to estimate the minimum number of reproductively active adult parasites to aid in predicting the number of additional years of CDTI required to interrupt transmission
- Identify genetic markers of O. volvulus response to ivermectin that could be incorporated into the tool for delineating "transmission zones" and used by country NTD managers to monitor the prevalence of parasites with a genotype conferring
a SOR phenotype.
