Review from JAMA — Efficacy of Current Drugs Against Soil-Transmitted Helminth Infections — Systematic Review and Meta-analysis

SUMMARY: An estimated 750 million people are at risk of infections with food-borne trematodes, which comprise liver flukes ( Clonorchis sinensis , Fasciola gigantica , Fasciola hepatica , Opisthorchis felineus , and Opisthorchis viverrini ), lung flukes ( Paragonimus spp.), and intestinal flukes (e.g., Echinostoma spp., Fasciolopsis buski , and the heterophyids). Food-borne trematodiases pose a significant public health and economic problem, yet these diseases are often neglected. In this review, we summarize the taxonomy, morphology, and life cycle of food-borne trematodes. Estimates of the at-risk population and number of infections, geographic distribution, history, and ecological features of the major food-borne trematodes are reviewed. We summarize clinical manifestations, patterns of infection, and current means of diagnosis, treatment, and other control options. The changing epidemiological pattern and the rapid growth of aquaculture and food distribution networks are highlighted, as these developments might be associated with an elevated risk of transmission of food-borne trematodiases. Current research needs are emphasized.

Foodborne trematodiasis is an emerging public health problem, particularly in Southeast Asia and the Western Pacific region. We summarize the complex life cycle of foodborne trematodes and discuss its contextual determinants. Currently, 601.0, 293.8, 91.1, and 79.8 million people are at risk for infection with Clonorchis sinensis, Paragonimus spp., Fasciola spp., and Opisthorchis spp., respectively. The relationship between diseases caused by trematodes and proximity of human habitation to suitable freshwater bodies is examined. Residents living near freshwater bodies have a 2.15-fold higher risk (95% confidence interval 1.38–3.36) for infections than persons living farther from the water. Exponential growth of aquaculture may be the most important risk factor for the emergence of foodborne trematodiasis. This is supported by reviewing aquaculture development in countries endemic for foodborne trematodiasis over the past 10–50 years. Future and sustainable control of foodborne trematodiasis is discussed.

Objective To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. Design Systematic review and network meta-analysis. Data Sources PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016. Study selection Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against Ascaris lumbricoides, hookworm (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura. The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models. Results 55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against A lumbricoides. Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against T trichiura, with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against T trichiura: by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027). Conclusions All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against T trichiura. The decrease in efficacy of albendazole against T trichiura over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against T trichiura.

Malaria not only remains a leading cause of morbidity and mortality, but it also impedes socioeconomic development, particularly in sub-Saharan Africa. Rapid and unprecedented urbanization, going hand-in-hand with often declining economies, might have profound implications for the epidemiology and control of malaria, as the relative disease burden increases among urban dwellers. Reviewing the literature and using a modeling approach, we find that entomologic inoculation rates in cities range from 0 to 54 per year, depending on the degree of urbanization, the spatial location within a city, and overall living conditions. Using the latest United Nations figures on urbanization prospects, nighttime light remotely sensed images, and the “Mapping Malaria Risk in Africa” results on climate suitability for stable malaria transmission, we estimate that 200 million people (24.6% of the total African population) currently live in urban settings where they are at risk of contracting the disease. Importantly, the estimated total surface area covered by these urban settings is only approximately 1.1–1.6% of the total African surface. Considering different plausible scenarios, we estimate an annual incidence of 24.8–103.2 million cases of clinical malaria attacks among urban dwellers in Africa. These figures translate to 6–28% of the estimated global annual disease incidence. Against this background, basic health care delivery systems providing early diagnosis and early treatment and preventive actions through mother and child health programs and the promotion of insecticide-treated bed nets for the rapidly growing numbers of the urban poor must be improved alongside well-tailored and integrated malaria control strategies. We propose environmental management and larviciding within well-specified productive sites as a main feature for such an integrated control approach. Mitigation of the current burden of malaria in urban African settings, in turn, is a necessity for stimulating environmentally and socially sustainable development.

Human-made ecologic transformations have occurred at an unprecedented rate over the past 50 years. Prominent among them are water resource development projects. An estimated 40,000 large dams and 800,000 small dams have been built, and 272 million hectares of land are currently under irrigation worldwide. The establishment and operation of water projects has had a history of facilitating a change in the frequency and transmission dynamics of malaria, but analyses of these environmental risk factors are sparse. Here, we present a comprehensive review of studies that assessed the impact of irrigation and dam building on malaria prevalence or incidence, stratified by the World Health Organization’s (WHO) sub-regions of the world, and link these studies with the latest statistics on disability adjusted life years, irrigated agriculture, and large dams. We also present estimates of the population at risk due to proximity to irrigation schemes and large dam reservoirs. In WHO sub-regions 1 and 2, which have 87.9% of the current global malaria burden, only 9.4 million people are estimated to live near large dams and irrigation schemes. In contrast, the remaining sub-regions concentrate an estimated 15.3 million people near large dams and up to 845 million near irrigation sites, while here only 12.1% of the global malaria burden is concentrated. Whether an individual water project triggers an increase in malaria transmission depends on the contextual determinants of malaria, including the epidemiologic setting, socioeconomic factors, vector management, and health seeking behavior. We conclude that in unstable malaria endemic areas, integrated malaria control measures, coupled with sound water management, are mandatory to mitigate the current burden of malaria in locations near irrigation or dam sites.