MDA helminth control: more questions than answers

Soil transmitted helminths (STH) and schistosomiasis (SCH) have been recognised as important diseases for decades. Diagnostics, treatments and understanding were accrued throughout the 20th century, and reached the point where control and elimination appeared to be primarily a matter of implementation of mass drug administration (MDA) programmes [1]. However, in 2015, both STH and SCH remain global health problems, so perhaps we do not have the right tools, or we are not applying them effectively. To our knowledge, MDA for STH and SCH has never been demonstrated to eliminate infection without concomitant economic development. What are we missing?


MDA helminth control: more questions than answers
Soil-transmitted helminths (STH) and schistosomiasis have been recognised as important diseases. Diagnostics, treatments, and understanding of these were accrued throughout the 20th century, and reached the point that control and elimination seemed to be mostly a matter of implementation of mass drug administration (MDA) programmes. 1 However, in 2015, both STH and schistosomiasis are global health problems, so perhaps we do not have the right methods or they are not being eff ectively applied. To our knowledge, MDA for STH and schistosomiasis has never been reported to eliminate infection without concomitant economic development. What are we missing?
Most understanding about infection and disease is from longitudinal intervention studies completed in the 1980s and 1990s, [2][3][4][5] which are now ageing and rarely benefi ted from modern techniques, such as nextgeneration sequencing. Very surprising is how much is not fully understood about these infections-eg, the biological or ecological basis of predisposition to high worm burdens, the importance of household-based transmission, the causes and resulting eff ects of coinfection with many parasites, and how to measure the burden of disease.
Measurement of the burden of disease is particularly vexing. Cochrane reviews, published in 2012 6 and 2015 7 , have emphasised the paucity of information (only 42 and 45 papers were included, respectively) and reported that little evidence was available for any benefi cial eff ect of deworming, even though people in the fi eld were convinced that these result in a great eff ect on physical and mental health. 8 By contrast, evidence of the eff ects in livestock and wildlife is accruing. 9 More than 1 billion children worldwide live at risk of helminth infection, 10 and yet the eff ect on their health and development still cannot be quantifi ed.
In The Lancet Global Health, Nathan Lo and colleagues 11 introduce two advances that should be highlighted. First is the inclusion of fi ve diff erent parasites in the same study, which is sensible, in view of the substantial overlap in diagnostic procedures and treatments for the diff erent species. Second, the authors 11 worked with detailed data in one setting (Côte d'Ivoire) and made comparisons between diff erent communities within that setting; such linkage between consistent local data and models is rare. Helminth infection and disease can be very diff erent in diff erent communities, but well validated models in many settings might allow for the extrapolation to others. We would like to think that this paper 11 marks the demise for universal studies of single helminth species.
Lo and colleagues 11 also add to the evidence that MDA might need to be widened beyond school-aged children (5-14 years). Diff erent frequencies of treatment are known to be needed for communities with diff erent intensities of infection, but less appreciated is that diff erent age groups need to be treated for diff erent circumstances, particularly with the aim to stop transmission of infections. 12 Lo and colleagues' results 11 suggest that widening coverage to additional age groups could be highly cost eff ective in terms of disability-adjusted life-years averted, motivating wider treatment programmes for eff ect rather than purely for the aim of local elimination.
Generally, we need interventions that are sustainable in the face of social, economic, and ecological heterogeneities. Models need to guide intervention programmes in terms of what to measure and how to use this information to manage the intervention. However, this task is diffi cult for modellers to provide because detailed data from many settings do not exist; or in settings where data do exist, the mechanisms to share these are not available in a way that provides useful results for both individual countries and wider policy formulation.
Lo and colleagues' study 11 emphasises the need for additional longitudinal studies of infection and disease-with longer follow-up time than have been done previously, especially if the negative sequelae of infection in children starts while they are very young and lasts for decades. Such future studies need a broadening of research approaches, particularly to include multiparasitism, the concepts of parasite tolerance (ie, that some individuals can harbour high burdens with relatively little eff ect on their health), social dimensions (ie, people with the highest burdens are less likely to be included in interventions and research studies, possibly because of their high burden, than those with low burdens), and potential reservoirs of transmission (ie, the role of households and environmental