WHO's LF elimination program is not enough

by William G. Gilroy

Haiti Program MDA Haiti Program MDA

More than 1 billion people in tropical and subtropical countries are at risk for lymphatic filariasis (LF), also known as elephantiasis. The World Health Organization has set a goal to eliminate LF in vulnerable countries through mass drug administrations, an effort that has seen dramatic results. However, a new study suggests that WHO’s recommendations for elimination are not enough.

Recently listed on the World Health Organization’s list of top neglected tropical diseases, LF is an attack on a person’s lymph system that leaves parts of the body grotesquely deformed. Tiny thread-worms colonize lymph vessels and prevent them from fighting bacterial and fungal infections, resulting in pain, fever, scarring, swelling, and oozing abscesses, usually in the legs, arms, scrotum and the breast. The disfigured person is unable to work and is typically shunned by society.

Researchers from the University of Notre Dame’s Eck Institute for Global Health believe that a combination of mass drug administration (MDA) and mosquito control, tailored to local conditions, is the best approach to eventually eliminate LF.

Edwin Michael, an epidemiologist in Notre Dame’s Department of Biological Sciences who led the research effort, pointed out that mathematical models offer valuable tools for understanding epidemiological patterns and for developing and evaluating strategies for the effective control of these complex diseases.

Michael’s group applied mathematical models to field data assembled from several sites worldwide where LF is endemic. The results showed that due to geographical differences, parasite transmission and extinction dynamics vary from place to place. Consequently, the effectiveness of MDAs to eliminate LF also varied significantly.

“The intervention simulations we carried out in the paper showed that timelines to parasite elimination due to current mass drug administration and other various proposed MDA options, with and without inclusion of mosquito control, also differed significantly between the study sites,” Michael said. “This is a major finding and is in contrast to WHO’s recommendation that applying four to six years of annual MDA commonly everywhere will bring about LF elimination globally.”

Another key finding of the research efforts is that including mosquito control into MDA programs markedly reduced the amount of time required to achieve elimination, as well as decreased the risk of recurrence of infection once MDA programs stopped.

“Such an approach also reduced the variance in the durations of interventions required to achieve LF elimination across sites, suggesting that this strategy could represent an option that is also robust to the effects of local transmission heterogeneities,” Michael said.

The research provided the first numerical estimates of transmission breakpoints — the point in treatment below which it is unlikely for the parasite to persist — for all the various transmission and infection variables that may serve as extinction targets for LF. A significant finding is that the predicted values of these breakpoint thresholds are strikingly much lower than the comparatively higher values set by WHO as targets indicative of interrupted LF transmission.

“This is another major result from this work as it suggests that using the current WHO thresholds will not only overestimate the likelihood of having achieved parasite elimination, but it will also result in high risk for recurrence of infection, if interventions are stopped once these thresholds are crossed.”

What this research means for the global LF elimination program is that the current strategy of using MDAs to fight infection is not enough. Until MDAs are combined with mosquito control, and mathematical modelling is used to make better sense of how local infection in a community will respond to these efforts, LF elimination is unlikely to be successfully accomplished in all endemic settings.

“In particular, our results show that the duration and frequency of mass treatments will differ between sites as a result of geographic variations in baseline endemicity levels as well as breakpoint thresholds, and will be strongly affected by the capacity of programs to achieve high drug coverage,” Michael said. “These complexities imply that more flexible management approaches that adapt specific interventions to local transmission patterns in different geographic settings will be needed if we are to successfully accomplish the goal of global LF eradication. In this regard, we have shown that including vector control to mass drug treatments, or more frequent mass drug administrations if inclusion of vector control proves infeasible, will be required if the effects of site to site transmission heterogeneities are to be overcome, and elimination of LF everywhere is to be achieved within a reasonable timeframe.”

Brajendra Singh, a senior research scientist and mathematical ecologist, and graduate students Benjamin Mayala and Morgan Smith from Michael’s lab also participated in the research. Funding from the National Institutes of Health, the Melinda and Bill Gates Foundation and the Eck Institute supported the research.

The paper in the journal Parasites and Vectors can be found here: www.parasitesandvectors.com/content/8/1/522.

Contact: Edwin Michael, 574-631-2234, emichael@nd.edu