Protocol, rationale and design of BE-PEOPLE (Bedaquiline enhanced exposure prophylaxis for LEprosy in the Comoros): a cluster randomized trial on effectiveness of rifampicin and bedaquiline as post-exposure prophylaxis of leprosy contacts.

BACKGROUND: Leprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP. METHODS: BE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150-600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial. DISCUSSION: The COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone. TRIAL REGISTRATION: NCT05597280. Protocol version 5.0 on 28 October 2022.

Costs and Outcomes of Integrated Human African Trypanosomiasis Surveillance System Using Rapid Diagnostic Tests, Democratic Republic of the Congo.

We integrated sleeping sickness case detection into the primary healthcare system in 2 health districts in the Democratic Republic of the Congo. We replaced a less field-friendly serologic test with a rapid diagnostic test, which was followed up by human African trypanosomiasis microscopic testing, and used a mixed costing methodology to estimate costs from a healthcare provider perspective. We screened a total of 18,225 persons and identified 27 new cases. Average financial cost (i.e., actual expenditures) was US $6.70/person screened and $4,464/case diagnosed and treated. Average economic cost (i.e., value of resources foregone that could have been used for other purposes) was $9.40/person screened and $6,138/case diagnosed and treated. Our study shows that integrating sleeping sickness surveillance into the primary healthcare system is feasible and highlights challenges in completing the diagnostic referral process and developing a context-adapted diagnostic algorithm for the large-scale implementation of this strategy in a sustainable and low-cost manner.

Use of the Lung Flute ECO to assist in sputum collection for tuberculosis testing: a randomised crossover trial.

The Lung Flute ECO, a self-powered, low-cost oscillatory positive expiratory pressure device, assisted people with presumptive tuberculosis to produce an adequate sputum volume for diagnostic testing and was well tolerated https://bit.ly/47sDq8W.

Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.

BACKGROUND: Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP. METHODS: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed. FINDINGS: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline. INTERPRETATION: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission. FUNDING: European and Developing Countries Clinical Trials Partnership. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Cost of a new method of active screening for human African trypanosomiasis in the Democratic Republic of the Congo.

BACKGROUND: Human African trypanosomiases caused by the Trypanosoma brucei gambiense parasite is a lethal disease targeted for eradication. One of the main disease control strategies is active case-finding through outreach campaigns. In 2014, a new method for active screening was developed with mini, motorcycle-based, teams. This study compares the cost of two active case-finding approaches, namely the traditional mobile teams and mini mobile teams, in the two health districts of the Democratic Republic of the Congo. METHODS: The financial and economic costs of both approaches were estimated from a health care provider perspective. Cost and operational data were collected for 12 months for 1 traditional team and 3 mini teams. The cost per person screened and diagnosed was calculated and univariate sensitivity analysis was conducted to identify the main cost drivers. RESULTS: During the study period in total 264,630 people were screened, and 23 HAT cases detected. The cost per person screened was lower for a mini team than for a traditional team in the study setting (US$1.86 versus US$2.08). A comparable result was found in a scenario analysis, assuming both teams would operate in a similar setting, with the cost per person screened by a mini team 15% lower than the cost per person screened by a traditional team (1.86 $ vs 2.14$). The main explanations for this lower cost are that mini teams work with fewer human resources, cheaper means of transportation and do not perform the Capillary Tube Centrifugation test or card agglutination test dilutions. DISCUSSION: Active HAT screening with mini mobile teams has a lower cost and could be a cost-effective alternative for active case-finding. Further research is needed to determine if mini mobile teams have similar or better yields than traditional mobile teams in terms of detections and cases successfully treated.