Appropriateness of the current parasitological control target for hookworm morbidity: A statistical analysis of individual-level data.

BACKGROUND: Soil-transmitted helminths affect almost 2 billion people globally. Hookworm species contribute to most of the related morbidity. Hookworms mainly cause anaemia, due to blood loss at the site of the attachment of the adult worms to the human intestinal mucosa. The World Health Organization (WHO) aims to eliminate hookworm morbidity by 2030 through achieving a prevalence of moderate and heavy intensity (M&HI) infections below 2%. In this paper, we aim to assess the suitability of this threshold to reflect hookworm-attributable morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We developed a hierarchical statistical model to simulate individual haemoglobin concentrations in association with hookworm burdens, accounting for low haemoglobin values attributable to other causes. The model was fitted to individual-level data within a Bayesian framework. Then, we generated different endemicity settings corresponding to infection prevalence ranging from 10% to 90% (0% to 55% M&HI prevalence), using 1, 2 or 4 Kato-Katz slides. For each scenario, we estimated the prevalence of anaemia due to hookworm. Our results showed that on average, haemoglobin falls below the WHO threshold for anaemia when intensities are above 2000 eggs per gram of faeces. For the different simulated scenarios, the estimated prevalence of anaemia attributable to hookworm ranges from 0% to 30% (95%-PI: 24% - 36%) being mainly associated to the prevalence of M&HI infections. Simulations show that a 2% prevalence of M&HI infections in adults corresponds to a prevalence of hookworm-attributable anaemia lower than 1%. CONCLUSIONS/SIGNIFICANCE: Our results support the use of the current WHO thresholds of 2% prevalence of M&HI as a proxy for hookworm morbidity. A single Kato-Katz slide may be sufficient to assess the achievement of the morbidity target. Further studies are needed to elucidate haemoglobin dynamics pre- and post- control, ideally using longitudinal data in adults and children.

Impact of Key Assumptions About the Population Biology of Soil-Transmitted Helminths on the Sustainable Control of Morbidity.

The design and evaluation of control programs for soil-transmitted helminths (STHs) is based on surveillance data recording measurements of egg counts in the stool of infected individuals, which underpin estimates of the prevalence and average intensity of infection. There is considerable uncertainty around these measurements and their interpretation. The uncertainty is composed of several sources of measurement error and the limit of detection of fecal smear tests on the one hand, and key assumptions on STH biology on the other hand, including assumptions on the aggregation of worms within hosts and on the impact of density-dependent influences on worm reproduction. Using 2 independently developed models of STH transmission we show how different aspects of STH biology and human behavior impact on STH surveillance and control programs and how accounting for uncertainty can help to develop optimal and sustainable control strategies to meet the World Health Organization (WHO) morbidity target for STHs.

Deworming women of reproductive age during adolescence and pregnancy: what is the impact on morbidity from soil-transmitted helminths infection?

BACKGROUND: Soil-transmitted helminths (STHs) are a major cause of poor health in low- and middle-income countries. In particular, hookworm is known to cause anaemia in children and women of reproductive age (WRA). One goal of the World Health Organization's (WHO) 2030 roadmap for neglected tropical diseases is to reduce STH-related morbidity in WRA. As a minimal intervention, the WHO recommends deworming adolescent girls annually during human papilloma virus vaccination programmes and WRA during pregnancy and lactation. These routine interventions are low cost and can be implemented even by the most basic health services in endemic countries. In this study we use a cohort model to investigate the potential impact on STH-related morbidity in WRA. RESULTS: Annual deworming treatment of adolescent girls reduces the prevalence of moderate- and heavy-intensity infections in this age group by up to 60% in moderate transmission settings and by 12-27% in high transmission settings. Treatment of WRA during pregnancy and lactation on its own has a small (< 20%) but significant effect on morbidity although it does not lead to the achievement of the morbidity target (< 2% moderate- to high-intensity infections) in this age group. However, depending on the age-intensity profile of infection, which may vary geographically, and assumptions on the density-dependence of egg production by fertilised female worms, continued school-based treatment may be able to reduce the force of infection acting on WRA, both through an indirect effect on the overall population-based force of infection and via reducing the burden of infection as children age and move into the WRA age classes. As a result, morbidity in WRA may be eliminated. CONCLUSION: While deworming during pregnancy and lactation does not lead to the achievement of the morbidity target in WRA and its efficacy may vary by setting, it is still expected to be beneficial for maternity and child health. Monitoring of any WRA-based intervention is recommended to evaluate its effectiveness.

Modelling the impact of COVID-19-related control programme interruptions on progress towards the WHO 2030 target for soil-transmitted helminths.

BACKGROUND: On 1 April 2020, the WHO recommended an interruption of all activities for the control of neglected tropical diseases, including soil-transmitted helminths (STH), in response to the COVID-19 pandemic. This paper investigates the impact of this disruption on the progress towards the WHO 2030 target for STH. METHODS: We used two stochastic individual-based models to simulate the impact of missing one or more preventive chemotherapy (PC) rounds in different endemicity settings. We also investigated the extent to which this impact can be lessened by mitigation strategies, such as semiannual or community-wide PC. RESULTS: Both models show that without a mitigation strategy, control programmes will catch up by 2030, assuming that coverage is maintained. The catch-up time can be up to 4.5 y after the start of the interruption. Mitigation strategies may reduce this time by up to 2 y and increase the probability of achieving the 2030 target. CONCLUSIONS: Although a PC interruption will only temporarily impact the progress towards the WHO 2030 target, programmes are encouraged to restart as soon as possible to minimise the impact on morbidity. The implementation of suitable mitigation strategies can turn the interruption into an opportunity to accelerate progress towards reaching the target.

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.

Impact of Different Sampling Schemes for Decision Making in Soil-Transmitted Helminthiasis Control Programs.

Starting and stopping preventive chemotherapy (PC) for soil-transmitted helminthiasis is typically based on the prevalence of infection as measured by Kato-Katz (KK) fecal smears. Kato-Katz-based egg counts can vary highly over repeated stool samples and smears. Consequentially, the sensitivity of KK-based surveys depends on the number of stool samples per person and the number of smears per sample. Given finite resources, collecting multiple samples and/or smears means screening fewer individuals, thereby lowering the statistical precision of prevalence estimates. Using population-level data from various epidemiological settings, we assessed the performance of different sampling schemes executed within the confines of the same budget. We recommend the use of single-slide KK for determining prevalence of moderate-to-heavy intensity infection and policy decisions for starting and continuing PC; more sensitive sampling schemes may be required for policy decisions involving stopping PC. Our findings highlight that guidelines should include specific guidance on sampling schemes.