Defining stopping criteria for ending randomized clinical trials that investigate the interruption of transmission of soil-transmitted helminths employing mass drug administration

Autor: Werkman, M, Toor, J, Vegvari, C, Wright, JE, Truscott, JE, Ásbjörnsdóttir, KH, Means, A, Walson, JL, Anderson, RM
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Ascaris Lumbricoides
Drug Administration
Nematoda
IMPACT
RC955-962
Helminthiasis
MATHEMATICAL-MODELS
Drug Therapy
Tropical Medicine
Arctic medicine. Tropical medicine
Helminths
Disease Transmission
Infectious
Medicine and Health Sciences
Parasitic Diseases
Humans
Animals
Intestinal Diseases
Parasitic
Randomized Controlled Trials as Topic
Anthelmintics
Science & Technology
Pharmaceutics
Ascaris
Organisms
Biology and Life Sciences
Eukaryota
11 Medical And Health Sciences
06 Biological Sciences
Models
Theoretical
Tropical Diseases
Invertebrates
Health Care
Infectious Diseases
Treatment Outcome
Soil-Transmitted Helminthiases
INFECTIONS
Hookworms
Helminth Infections
Mass Drug Administration
Parasitology
Female
Public aspects of medicine
RA1-1270
Health Statistics
Morbidity
Life Sciences & Biomedicine
Research Article
Neglected Tropical Diseases
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 12, Iss 10, p e0006864 (2018)
Popis: The current World Health Organization strategy to address soil-transmitted helminth (STH) infections in children is based on morbidity control through routine deworming of school and pre-school aged children. However, given that transmission continues to occur as a result of persistent reservoirs of infection in untreated individuals (including adults) and in the environment, in many settings such a strategy will need to be continued for very extended periods of time, or until social, economic and environmental conditions result in interruption of transmission. As a result, there is currently much discussion surrounding the possibility of accelerating the interruption of transmission using alternative strategies of mass drug administration (MDA). However, the feasibility of achieving transmission interruption using MDA remains uncertain due to challenges in sustaining high MDA coverage levels across entire communities. The DeWorm3 trial, designed to test the feasibility of interrupting STH transmission, is currently ongoing. In DeWorm3, three years of high treatment coverage—indicated by mathematical models as necessary for breaking transmission—will be followed by two years of surveillance. Given the fast reinfection (bounce-back) rates of STH, a two year no treatment period is regarded as adequate to assess whether bounce-back or transmission interruption have occurred in a given location. In this study, we investigate if criteria to determine whether transmission interruption is unlikely can be defined at earlier timepoints. A stochastic, individual-based simulation model is employed to simulate core aspects of the DeWorm3 community-based cluster-randomized trial. This trial compares a control arm (annual treatment of children alone with MDA) with an intervention arm (community-wide biannual treatment with MDA). Simulations were run for each scenario for both Ascaris lumbricoides and hookworm (Necator americanus). A range of threshold prevalences measured at six months after the last round of MDA and the impact of MDA coverage levels were evaluated to see if the likelihood of bounce-back or elimination could reliably be assessed at that point, rather than after two years of subsequent surveillance. The analyses suggest that all clusters should be assessed for transmission interruption after two years of surveillance, unless transmission interruption can be effectively ruled out through evidence of low treatment coverage. Models suggest a tight range of homogenous prevalence estimates following high coverage MDA across clusters which do not allow for discrimination between bounce back or transmission interruption within 24 months following cessation of MDA.
Author summary Soil-transmitted helminths (STH) remain prevalent in many African, South American and Asian countries. The WHO recommends treating pre-school aged children (pre-SAC) and school-aged children (SAC) in areas with endemic STH infections. However, treating pre-SAC and SAC only is unlikely to achieve STH transmission interruption, as adults remain infected and contribute to re-infection in the community, particularly with hookworm. Treating the entire community with high-coverage and high-frequency mass drug administration (MDA) may achieve transmission interruption and ongoing community-based clinical trials are investigating the feasibility and impact of such an approach. Since large-scale trials are costly and STH prevalence may bounce back quickly to pre-treatment levels when MDA ceases, it may be more efficient to stop the trial when interruption of transmission can be ruled out. In these circumstances it may be necessary to investigate why transmission interruption was not achieved to inform necessary improvements in future community-wide treatment programmes. Factors that may affect the likelihood of transmission interruption include water, sanitation and hygiene (WASH), sociodemographic, migration and environmental factors. These factors should be investigated in cases where interruption of transmission is not achieved. In this study, we investigate the stopping criteria required to determine whether transmission interruption has occurred following multiple rounds of MDA.
Databáze: OpenAIRE
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