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Hepatitis E should be considered a neglected tropical disease

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Andrew S. Azman, Iza Ciglenecki, Joseph F. Wamala, Julia Lynch, Rakesh Aggarwal, Mahmudur Rahman, Sid Wong, Micaela Serafini, Ali M. Moussa, Harry R. Dalton, Ananta Shrestha, Rajendra Pant, Emily S. Gurley

Hepatitis E virus (HEV) is a major cause of acute jaundice worldwide, with a case fatality risk (CFR) as high as 30% among symptomatic pregnant women. Human HEV includes four genotypes; the nonepidemic, zoonotic genotypes (typically 3 and 4) have gained increasing recognition in North America and Europe over the past decade because of the potential risk of transmission through food, blood transfusions, and organ donation. However, relatively little attention and few resources have been invested into genotypes 1 and 2 (g1/g2), which cause outbreaks among the world’s most vulnerable populations living with poor access to safe water and sanitation infrastructure. Here, we argue that the burden of this disease, combined with the neglect by the public health, research, and clinical communities and limited options for treatment and control, make it a serious candidate for classification as a neglected tropical disease (NTD).

HEV g1/g2 are transmitted through the fecal–oral route, so large water and sanitation interventions have been implemented during outbreaks to reduce transmission. The few studies that have looked into intervention impact during outbreaks provide little evidence of major intervention-related reductions in risk, especially during outbreaks in Africa. However, studying the effects of these interventions is difficult because of the long incubation period of the disease and relatively imprecise diagnostics and clinical case definitions. There are no therapeutics known to reduce morbidity and mortality from acute hepatitis E in the general population, although antivirals may provide some hope in the future. Fortunately, there is a vaccine licensed for use in China, Hecolin (Xiamen Innovax Biotech, China), that has demonstrated high efficacy in a large randomized trial. However, this vaccine is not approved for purchase by United Nations organizations (World Health Organization [WHO] prequalified), nor has it been used in routine public health interventions.

The classification as an NTD by WHO can bring additional dedicated public health and research resources to a disease, in addition to increasing general awareness in the health community and beyond. Recent additions to this list include chromoblastomycosis and other deep mycoses, scabies and other ectoparasites, and snake bite envenoming. The WHO Strategic and Technical Advisory Group for Neglected Tropical Diseases currently lists 20 recognized NTDs and has set out the criteria that should be met for future additions to the list. These criteria are as follows: (1) the condition disproportionately affects populations living in poverty and causes important morbidity and mortality in such populations, justifying a global response; (2) the condition primarily affects populations living in tropical and subtropical areas; (3) the condition is immediately amenable to broad control, elimination, or eradication by applying one or more of the five public health strategies adopted by the (WHO) Department for Control of NTDs; and/or (4) the condition is relatively neglected by research when it comes to developing new diagnostics, medicines, and other control tools. Here, we review these four criteria with respect to hepatitis E caused by epidemic HEV (primarily g1/g2) and provide the evidence to support its inclusion as an NTD.