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

Abstract 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. Graphical Abstrac

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