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Trichuris trichiura, a soil-transmitted helminth (STH), often persists after a single dose of anthelminthic treatment. To overcome limited efficacy against T. trichiura of benzimidazoles (albendazole or mebendazole), the primary drugs used in mass drug administration (MDA) campaigns, the World Health Organization endorses the use of a combination of ivermectin and albendazole as a more effective treatment to be used for preventive chemotherapy. Given observed considerable differences in efficacy of the combination therapy over albendazole monotherapy, between different settings, it is necessary to evaluate the performance of the combination before introducing it on a larger scale. This open-label, randomized controlled superiority trial in two Ugandan primary schools enrolled eligible 6- to 12-year-olds positive for T. trichiura. Participants were randomized 1:1 to receive either a single dose of albendazole alone or co-administered albendazole and ivermectin. Adverse events were monitored at three and 24h post-treatment. Follow-up samples were collected 14 to 21 days post-treatment for efficacy assessment. The combination of albendazole with ivermectin showed superior efficacy against T. trichiura compared to albendazole alone, both in terms of cure rates (31.3% versus 12.3%, difference 18.9%-points, 95% CI 6.2–31.2, p < 0.004) and in terms of egg reduction rates (ERRs; 91.4% versus 52.7%). A higher cure rate against co-infecting Ascaris lumbricoides was observed in the combination compared to the albendazole monotherapy arm (100% versus 83.9%). Both therapies showed an excellent safety profile with few and only mild and transient treatment emergent adverse events observed in the albendazole monotherapy and albendazole plus ivermectin arm (total of 22 and 19 events, respectively). In conclusion, the efficacy of the combination therapy against T. trichiura in Uganda is superior to that of albendazole alone. Given the high ERRs observed albendazole-ivermectin might aid in eliminating morbidity, an important target of STH control programs. Trial registration (clinicaltrials.gov): NCT06037876. Author summary: Despite several decades of preventive chemotherapy with single-dose albendazole distribution to at-risk populations, soil-transmitted helminth infections remain of public health concern in Uganda. The Ministry of Health has stated interest in the introduction of potentially more efficacious treatment strategies against T. trichiura such as the use of a combination of the two deworming drugs (ivermectin and albendazole) instead of only albendazole as currently used. Given significant differences in efficacy between the combination therapy compared to albendazole monotherapy against T. trichiura in different settings, we conducted a randomized clinical trial in two Ugandan primary schools to assess whether in Uganda the combination is more efficacious than albendazole alone. The findings of our study confirmed higher efficacy against T. trichiura in the study area. Both treatment regimens were well tolerated. In conclusion, we conceive that the introduction of the combination therapy is advantageous and its introduction into the existing STH control programme should now be evaluated from a recipient and provider perspective. [ABSTRACT FROM AUTHOR]

Background: Manual screening of a Kato-Katz (KK) thick stool smear remains the current standard to monitor the impact of large-scale deworming programs against soil-transmitted helminths (STHs). To improve this diagnostic standard, we recently designed an artificial intelligence based digital pathology system (AI-DP) for digital image capture and analysis of KK thick smears. Preliminary results of its diagnostic performance are encouraging, and a comprehensive evaluation of this technology as a cost-efficient end-to-end diagnostic to inform STH control programs against the target product profiles (TPP) of the World Health Organisation (WHO) is the next step for validation. Methods: Here, we describe the study protocol for a comprehensive evaluation of the AI-DP based on its (i) diagnostic performance, (ii) repeatability/reproducibility, (iii) time-to-result, (iv) cost-efficiency to inform large-scale deworming programs, and (v) usability in both laboratory and field settings. For each of these five attributes, we designed separate experiments with sufficient power to verify the non-inferiority of the AI-DP (KK2.0) over the manual screening of the KK stool thick smears (KK1.0). These experiments will be conducted in two STH endemic countries with national deworming programs (Ethiopia and Uganda), focussing on school-age children only. Discussion: This comprehensive study will provide the necessary data to make an evidence-based decision on whether the technology is indeed performant and a cost-efficient end-to-end diagnostic to inform large-scale deworming programs against STHs. Following the protocolized collection of high-quality data we will seek approval by WHO. Through the dissemination of our methodology and statistics, we hope to support additional developments in AI-DP technologies for other neglected tropical diseases in resource-limited settings. Trial registration: The trial was registered on September 29, 2023 Clinicaltrials.gov (ID: NCT06055530). [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminth (STH) infections, commonly caused by roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Necator americanus and Ancylostoma duodenale), were widespread among Ugandan schoolchildren in the late 1990s and early 2000s. Since 2003, the Ugandan Ministry of Health has administered biannual preventive chemotherapy to children aged 1–14 years to control these infections. Twenty years after the program's inception, there is scant data to show the long-term impact of these national deworming efforts. Methods: To estimate the prevalence and intensity of STH infections among 10–14-year-old primary school children, school-based, cross-sectional surveys were conducted in November 2023 across five districts (Kamwenge, Sheema, Adjumani, Lamwo, and Zombo). Sixty-five children from five schools per district were selected for inclusion. Fecal egg counts were determined using the Kato-Katz microscopy technique, performed in duplicate by trained laboratory technicians. Results: The survey findings revealed a high prevalence of any STH infection in Kamwenge District (21.2%, 95% confidence limits (CL): 5.7%, 36.6%), while the remaining four districts exhibited lower prevalences, ranging from 0.4% (95% CL: 0.0%, 1.2%) in Adjumani District to 5.6% (95% CL: 0.0%, 11.4%) in Sheema District. The prevalence of moderate-to-heavy-intensity infections was below 1% across all districts. A. lumbricoides was identified infrequently. Hookworm infections were primarily identified in the western districts of Kamwenge and Sheema, while T. trichiura infections were common only in Kamwenge District. Hookworm and T. trichiura infections were uncommon in the northern districts of Adjumani, Lamwo, and Zombo. Conclusions: These surveys suggest that morbidity due to STH infections among schoolchildren may be well controlled in these five districts, as evidenced by low moderate-to-heavy-intensity infection prevalence. However, the prevalence of any intensity infection remains elevated in some districts, indicating the need for continued preventive chemotherapy distribution. A reduction from biannual treatment may be warranted in four districts, per World Health Organization recommendations. Author summary: Intestinal worm infections, also known as soil-transmitted helminth (STH) infections, are a significant public health concern that can impair physical growth, lead to anemia, and affect cognitive development among children. Initial surveys in Uganda between 1998 and 2005 showed a high prevalence of STH infections, with over 50% of school-aged children affected in many districts. In response, the Ugandan Ministry of Health initiated biannual deworming campaigns targeting school-aged children, along with health education programs. Our follow-up surveys in November 2023 across five districts aimed to evaluate the impact of these deworming campaigns on the prevalence of STH infections. We found a substantial decrease in STH prevalence in four districts, suggesting that the national deworming program has been effective and could potentially reduce the frequency of deworming campaigns in these areas. However, in Kamwenge District, the STH prevalence remained elevated, indicating a need for further investigation to understand the persistence of infections and to enhance control measures to meet World Health Organization targets. [ABSTRACT FROM AUTHOR]