Human ascariasis: diagnostics update

Soil-transmitted helminths (STHs) infect over one billion people worldwide. Ascariasis may mimic a number of conditions, and individual clinical diagnosis often requires a thorough work-up. Kato-Katz thick smears are the standard detection method for Ascaris and, despite low sensitivity, are often used for mapping and monitoring and evaluation of national control programmes. Although increased sampling (number of stools) and diagnostic (number of examinations per stool) efforts can improve sensitivity, Kato-Katz is less sensitive than other microscopy methods such as FLOTAC®. Antibody-based diagnostics may be a sensitive diagnostic tool; however, their usefulness is limited to assessing transmission in areas aiming for elimination. Molecular diagnostics are highly sensitive and specific, but high costs limit their use to individual diagnosis, drug - efficacy studies and identification of Ascaris suum. Increased investments in research on Ascaris and other STHs are urgently required for the development of diagnostic assays to support efforts to reduce human suffering caused by these infections

Human liver flukes

Liver fluke infections occur in people worldwide. In some low-income regions, a combination of ecological, agricultural, and culinary factors leads to a very high prevalence of infection but, in higher-income regions, infections are uncommon. Infection is associated with substantial morbidity and several liver fluke species are recognised as biological carcinogens. Here, we review the epidemiology, clinical significance, and diagnostic and treatment strategies of human infection with these pathogens

Soil-transmitted helminth infections

More than a quarter of the world's population is at risk of infection with the soil-transmitted helminths Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), Trichuris trichiura, and Strongyloides stercoralis. Infected children and adults present with a range of medical and surgical conditions, and clinicians should consider the possibility of infection in individuals living in, or returning from, endemic regions. Although safe and effective drugs are donated free to endemic countries, only half of at-risk children received treatment in 2016. This Seminar describes the epidemiology, lifecycles, pathophysiology, clinical diagnosis, management, and public health control of soil-transmitted helminths. Previous work has questioned the effect of population-level deworming; however, it remains beyond doubt that treatment reduces the severe consequences of soil-transmitted helminthiasis. We highlight the need for refined diagnostic tools and effective control options to scale up public health interventions and improve clinical detection and management of these infections

The effects of subcurative praziquantel treatment on life-history traits and trade-offs in drug-resistant Schistosoma mansoni

Natural selection acts on all organisms, including parasites, to maximise reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian State-Space Models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma may be limited by life-history costs not present in susceptible counterparts. Schistosoma mansoni parasites from a praziquantel–susceptible (S), a praziquantel–resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by praziquantel treatment in the R line, could limit the spread of R parasites under praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond

A call for systems epidemiology to tackle the complexity of schistosomiasis, its control, and elimination

Ever since the first known written report of schistosomiasis in the mid-19th century, researchers have aimed to increase knowledge of the parasites, their hosts, and the mechanisms contributing to infection and disease. This knowledge generation has been paramount for the development of improved intervention strategies. Yet, despite a broad knowledge base of direct risk factors for schistosomiasis, there remains a paucity of information related to more complex, interconnected, and often hidden drivers of transmission that hamper intervention successes and sustainability. Such complex, multidirectional, non-linear, and synergistic interdependencies are best understood by looking at the integrated system as a whole. A research approach able to address this complexity and find previously neglected causal mechanisms for transmission, which include a wide variety of influencing factors, is needed. Systems epidemiology, as a holistic research approach, can integrate knowledge from classical epidemiology, with that of biology, ecology, social sciences, and other disciplines, and link this with informal, tacit knowledge from experts and affected populations. It can help to uncover wider-reaching but difficult-to-identify processes that directly or indirectly influence exposure, infection, transmission, and disease development, as well as how these interrelate and impact one another. Drawing on systems epidemiology to address persisting disease hotspots, failed intervention programmes, and systematically neglected population groups in mass drug administration programmes and research studies, can help overcome barriers in the progress towards schistosomiasis elimination. Generating a comprehensive view of the schistosomiasis system as a whole should thus be a priority research agenda towards the strategic goal of morbidity control and transmission elimination

Monitoring schistosomiasis and sanitation interventions—the potential of environmental DNA

Transmission of schistosomiasis, a human parasitic disease, is intrinsically linked to inadequate water, sanitation, and hygiene (WASH) facilities and/or their use. The mainstay of control is population‐based chemotherapy. Globally, each year, 240 million people are estimated to require this preventative treatment. However, for long‐term, sustainable control of this disease, supplementary WASH improvements are required to prevent (re)infection of humans (provision of safe water) and transmission from humans to the environment (improved sanitation). While there is established methodology for monitoring transmission in human populations, presently methods for monitoring the impact of WASH interventions, in particular sanitation, on environmental transmission are lacking. Development of such becomes paramount as integrated control programs combine drug treatments with enhanced WASH facilities and behavior change interventions, with uptake likely correlated to a reduction in fecal matter, and schistosome eggs, in the environment but any impact on infection levels in humans taking longer to become apparent. This article reports and critiques the methods currently used to monitor schistosomiasis in freshwater and soil environments and explores how environmental DNA could be used to better understand and monitor environmental contamination in relation to sanitation. Stronger evidence is required to understand how different sanitation interventions serve to limit the environmental transmission of the parasite and their relative effectiveness in preventing disease

Understanding perceptions of schistosomiasis and its control among highly endemic lakeshore communities in Mayuge, Uganda

Background: Schistosomiasis is a neglected tropical disease and a serious global-health problem with over 230 million people requiring treatment, of which the majority live in Africa. In Uganda, over 4 million people are infected. Extensive parasitological data exist on infection prevalence, intensities and the impact of repeated praziquantel mass drug administration (MDA). However, how perceptions of schistosomiasis shape prevention and treatment practices and their implications for control measures are much less well understood. Methods: Rapid ethnographic appraisals were performed for six weeks in each of three Schistosoma mansoni high endemicity communities on the shores of Lake Victoria, Mayuge District, Uganda. Data were collected between September 2017 and April 2018. Data were collected through structured observations, transect walks, and participant observation, and sixty in-depth interviews and 19 focus group discussions with purposively recruited participants. Data were analyzed thematically using iterative categorization, looking at five key areas: perceptions of 1) the symptoms of schistosomiasis; 2) the treatment of schistosomiasis; 3) how schistosomiasis is contracted; 4) how schistosomiasis is transmitted onwards and responsibilities associated with this; and 5) how people can prevent infection and/or onward transmission. Results: Observations revealed open defecation is a common practice in all communities, low latrine coverage compared to the population, and all communities largely depend on lake water and contact it on daily basis. Perceptions that a swollen stomach was a sign/symptom of ‘ekidada’ (caused by witchcraft) resulted in some people rejecting free praziquantel in favour of herbal treatment from traditional healers at a fee. Others rejected praziquantel because of its perceived side effects. People who perceived that schistosomiasis is caught from drinking unboiled lake water did not seek to minimize skin contact with infected water sources. Community members had varied perceptions about how one can catch and transmit schistosomiasis and these perceptions affect prevention and treatment practices. Open defecation and urinating in the lake were considered the main route of transmission, all communities attributed blame for transmission to the fishermen which was acknowledged by some fishermen. And, lastly, schistosomiasis was considered hard to prevent due to lack of access to safe water. Conclusion: Despite over 15 years of MDA and associated education, common misconceptions surrounding schistosomiasis exist. Perceptions people have about schistosomiasis profoundly shape not only prevention but also treatment practices, greatly reducing intervention uptake. Therefore, we advocate for a contextualized health education programme, alongside MDA, implementation of improved access to safe-water and sanitation and continued research

The impact of storage conditions on human stool 16S rRNA microbiome composition and diversity

Background: Multiple factors can influence stool sample integrity upon sample collection. Preservation of faecal samples for microbiome studies is therefore an important step, particularly in tropical regions where resources are limited and high temperatures may significantly influence microbiota profiles. Freezing is the accepted standard to preserve faecal samples however, cold chain methods are often unfeasible in fieldwork scenarios particularly in low and middle-income countries and alternatives are required. This study therefore aimed to address the impact of different preservative methods, time-to-freezing at ambient tropical temperatures, and stool heterogeneity on stool microbiome diversity and composition under real-life physical environments found in resource-limited fieldwork conditions. Methods: Inner and outer stool samples collected from one specimen obtained from three children were stored using different storage preservation methods (raw, ethanol and RNAlater) in a Ugandan field setting. Mixed stool was also stored using these techniques and frozen at different time-to-freezing intervals post-collection from 0–32 h. Metataxonomic profiling was used to profile samples, targeting the V1–V2 regions of 16S rRNA with samples run on a MiSeq platform. Reads were trimmed, combined and aligned to the Greengenes database. Microbial diversity and composition data were generated and analysed using Quantitative Insights Into Microbial Ecology and R software. Results: Child donor was the greatest predictor of microbiome variation between the stool samples, with all samples remaining identifiable to their child of origin despite the stool being stored under a variety of conditions. However, significant differences were observed in composition and diversity between preservation techniques, but intra-preservation technique variation was minimal for all preservation methods, and across the time-to-freezing range (0–32 h) used. Stool heterogeneity yielded no apparent microbiome differences. Conclusions: Stool collected in a fieldwork setting for comparative microbiome analyses should ideally be stored as consistently as possible using the same preservation method throughout

Diagnosis of helminths depends on worm fecundity and the distribution of parasites within hosts

Helminth transmission and morbidity are dependent on the number of mature parasites within a host; however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver fluke Opisthorchis viverrini, which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys (n = 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation

Harnessing technology and portability to conduct molecular epidemiology of endemic pathogens in resource-limited settings

Improvements in genetic and genomic technology have enabled field-deployable molecular laboratories and these have been deployed in a variety of epidemics that capture headlines. In this editorial, we highlight the importance of building physical and personnel capacity in low and middle income countries to deploy these technologies to improve diagnostics, understand transmission dynamics and provide feedback to endemic communities on actionable timelines. We describe our experiences with molecular field research on schistosomiasis, trypanosomiasis and rabies and urge the wider tropical medicine community to embrace these methods and help build capacity to benefit communities affected by endemic infectious diseases