The impact of community-wide, mass drug administration on aggregation of soil-transmitted helminth infection in human host populations

Abstract

Background: Soil-transmitted helminths (STH) are intestinal parasites estimated to infect over 1.5 billion people. Current treatment programmes are aimed at morbidity control through school-based deworming programmes (targeting school-aged children, SAC) and treating women of reproductive age (WRA), as these two groups are believed to record the highest morbidity. More recently, however, the potential for interrupting transmission by treating entire communities has been receiving greater emphasis and the feasibility of such programmes are now under investigation in randomised clinical trials through the Bill & Melinda Gates Foundation funded DeWorm3 studies. Helminth parasites are known to be highly aggregated within human populations, with a small minority of individuals harbouring most worms. Empirical evidence from the TUMIKIA project in Kenya suggests that aggregation may increase significantly after anthelminthic treatment. Methods: A stochastic, age-structured, individual-based simulation model of parasite transmission is employed to better understand the factors that might induce this pattern. A simple probabilistic model based on compounded negative binomial distributions caused by age-dependencies in both treatment coverage and exposure to infection is also employed to further this understanding. Results: Both approaches confirm helminth aggregation is likely to increase post-mass drug administration as measured by a decrease in the value of the negative binomial aggregation parameter, k. Simple analytical models of distribution compounding describe the observed patterns well. Conclusions: The helminth aggregation that was observed in the field was replicated with our stochastic individualbased model. Further work is required to generalise the probabilistic model to take account of the respective sensitivities of different diagnostics on the presence or absence of infection.

Patterns of individual non-treatment during multiple rounds of mass drug administration for control of soil-transmitted helminths in the TUMIKIA trial, Kenya: a secondary longitudinal analysis

“…Modelling studies have suggested that soil-transmitted helminth infections in endemic communities become increasingly clustered as disease prevalence drops, determined in part by patterns of individual participation during MDA, with important consequences for the probability of achieving transmission interruption. 32 , 33 Developing a stronger empirical understanding of the effects of systematic non-treatment on transmission of soil-transmitted helminths and other neglected tropical diseases, and the identification of new approaches to ensure treatment of identified subgroups, remain urgent priorities.…”

Schistosomiasis, soil transmitted helminthiasis, and malaria co-infections among women of reproductive age in rural communities of Kwale County, coastal Kenya

“…The prevalence of S. haematobium in Kwale (similar study site to the current study) among adults was 18.2% in 2010 [ 11 ] and 15.07% in 2018 among people of all age groups and gender [ 12 ]. Three major STH infections are caused by roundworms ( Ascaris lumbricoides ), whipworms ( Trichuris trichiura ), and the hookworms ( Ancylostoma duodenale and/or Necator americanus ) [ 13 – 15 ]. Generally a combination of factors have been implicated in STH infections which include poverty, lack of sanitation, and inadequate hygiene [ 15 – 17 ].…”

Probability distributions of helminth parasite burdens within the human host population following repeated rounds of mass drug administration and their impact on the transmission breakpoint

“…What has not been appreciated, however, is that repeated rounds of MDA, the favoured control option for human helminth infections, tend to drive parasite aggregation to higher and higher levels (very small k values) [9]. Very recent studies point to persistent non-adherence to treatment being the causative mechanism [10,11].…”

“…Typically, diagnostics measure the intensity of infection using eggs counts from urine, stool or blood samples or DNA detection (qPCR) methods. However, information is beginning to emerge from large scale trials of how best to conduct deworming programmes, such as TUMIKIA and DeWorm3, that suggest under repeated rounds of treatment the degree of worm aggregation in the targeted communities rises steeply [7][8][9]. The generative mechanism or mechanisms are poorly understood at present, but non-compliance to treatment in a small proportion of the population looks to be one of great importance [10,11].…”