Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study.

BACKGROUND: Mass drug administration (MDA) program of albendazole to at-risk populations as preventive chemotherapy is the core public health intervention to control soil-transmitted helminths (STHs). Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing reinfection. We assessed the efficacy of albendazole against STH parasite infection and reinfection status after cure. METHODS: A total of 984 schoolchildren infected with at least one type of STH parasite (hookworm, Ascaris lumbricoides, Trichuris trichiura) in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March 2019. Stool exams at week-4 and at week-8 of post-MDA were done using Kato Katz technique. The primary outcome was efficacy assessed by cure rate (CR) and fecal egg reduction rates (ERRs) at four weeks of post-MDA. The secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of post-MDA. Group comparisons in CR and related factors were assessed with chi-square or Fisher's exact tests. Predictors of CR were examined through univariate and multivariate regression analyses. RESULTS: The overall CR and ERR for hookworm infection were 97.2% (95% CI 94.6-99.4) and 97.02%, respectively. The overall CR and ERR for A. lumbricoides were 71.5% (95% CI 68.3-74.6) and 84.5% respectively. The overall CR and ERR and for T. trichiura were 49.5% (95% CI 44.8-54.2) and 68.3%, respectively. The CR among moderate T. trichiura infection intensity was 28.6%. Among children cured of hookworm, A. lumbricoides and T. trichiura at week 4 post-MDA, 4.6%, 18.3% and 52.4% became reinfected at week-8 post-MDA, respectively. Significantly lower CR (36.6%) and higher reinfection after cure (60.6%) among A. lumbricoides and T. trichiura coinfected children than A. lumbricoides only (CR = 69.6%, reinfection rate = 15.1%) or T. trichiura only infected children (CR = 55.6%, reinfection rate = 47.1%) was observed. Pre-treatment coinfection with ≥ two types of STH parasites was significantly associated with re-infection after cure. CONCLUSION: Albendazole MDA is efficacious against hookworm but has reduced efficacy against A. lumbricoides and is not effective against T. trichiura. The low drug efficacy and high reinfection rate after cure underscore the need for alternative treatment and integration of other preventive measures to achieve the target of eliminating STHs as a public health problem by 2030.

Efficacy and safety of praziquantel preventive chemotherapy in Schistosoma mansoni infected school children in Southern Ethiopia: A prospective cohort study.

Background: The World Health Organization recommends efficacy and safety surveillance of anti-helminths used in mass drug administration campaigns. We evaluated the effectiveness of single-dose praziquantel against Schistosoma mansoni infection, and the safety of praziquantel plus albendazole preventive chemotherapy (PC) in Schistosoma mansoni infected school children (n = 512) in Southern Ethiopia. Method: Stool examinations were done using thick smear Kato-Katz at baseline, week-4, and week-8 of post-Mass drug administration (MDA) to assess praziquantel efficacy. Participants were followed for MDA-associated adverse events up to day 7 of post-MDA. The primary and secondary study outcomes were praziquantel efficacy (parasitological cure and egg reduction rates) and MDA-associated adverse events (AEs), respectively. Result: The overall cure rates at week-4 and week-8 were 89.1% (95%CI = 86.1-91.7) and 87.5% (95%CI = 83.6-90.8), respectively. Cure rates among moderate-to-heavily infected children were significantly lower (p = 0.001) compared to those with light infection at week-4 (84.4% vs. 91.1%, p = 0.03) and week-8 (78.6% vs. 91.9%, respectively). Older children had a higher cure rate than younger ones at week-8 (90.1% vs. 79.5%, p = 0.01). Among those who were Schistosoma egg-free (cured) at week 4, 7.8% became egg-positive at week 8. The overall egg reduction rate (ERR) at week-4 and week-8 were 93.5% and 91.3%, respectively, being lower among the 5-9 years old age groups (p = 0.01) at week-8. The proportion of children who remained schistosoma egg-positive throughout the study follow-up period was 4.6%, and their ERR at week-4 and week-8 was 50% and 51%, respectively, which is below the 90% World Health Organization threshold for efficacy. The incidence of experiencing at least one type of MDA-associated AEs were 17.0% (95%CI = 13.8%-20.5%); abdominal pain, headache, and vomiting were the most common. The proportion of mild, moderate, and severe AEs was 63.2%, 26.3%, and 10.5%, respectively. Females experienced more AEs than males (p = 0.03). Conclusion: Single-dose praziquantel is still effective for the treatment of intestinal schistosomiasis. Praziquantel and albendazole preventive chemotherapy is safe and tolerable, and associated AEs are mostly mild-to-moderate and transient. However, the reduced PZQ effectiveness in moderate-to-heavy infection and observed AEs in about one-fifth of infected children underscores the need for better treatment strategies and surveillance for early detection of parasite resistance and management of AEs.

Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring.

Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5−15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5−14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ2 = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas.

Prevalence, Intensity, and Correlates of Schistosomiasis and Soil-Transmitted Helminth Infections after Five Rounds of Preventive Chemotherapy among School Children in Southern Ethiopia.

Preventive chemotherapy (PC) is a WHO-recommended strategy to control and eliminate schistosomiasis and soil-transmitted helminths (STHs). We assessed the prevalence, intensity, and correlates of schistosomiasis and STH infection after five rounds of PC in southern Ethiopia. A total of 3162 school children from four schools in Wondo Gennet and Hawella Tula districts were screened for Schistosoma mansoni and STHs infection. The overall prevalence of S. mansoni infection was 25.8% (range between schools 11.6% to 54.1%), with light (19.1%), moderate (5.3%), and heavy (1.4%) infection intensities. A total of 61.6% S. mansoni-infected children were STH co-infected. The overall prevalence of STHs infection was 54.7% (range between schools 30.6-71.0%), with moderate-to-heavy intensity infections being 16.3%. Ascaris lumbricoides was the most prevalent 45% (95% CI, 43.5-47) followed by Trichuris trichiura 25.3% (95% CI, 23.8-26.9) and hookworm 6.1% (95% CI, 5.3-7). A total of 33.7% of STHs-infected children had A. lumbricoides and T. trichiura co-infections. S. mansoni infection was significantly associated with school and STHs co-infection (p < 0.001). STH infection was correlated with school and younger age (p < 0.001). Despite repeated PC, S. mansoni and STH infection remain significant health problems, and the WHO target to control schistosomiasis and eliminate STH by 2020 may not be achieved. Intensified control and prevention measures, including drug efficacy surveillance, is recommended.