Nicholas M. Douglas

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection first described in the early 1900s that predominantly affects severely immunocompromised individuals. Historically, popul...

Objectives: Kiribati has one of the highest rates of leprosy worldwide. A nationwide screening and chemoprophylaxis program for household leprosy contacts was introduced in 2018. In 2022, population‐wide screening and rifamycin‐based treatment or chemoprophylaxis for leprosy and tuberculosis was introduced as part of the PEARL and COMBINE studies. Largescale rifamycin use theoretically risks selection of resistant Mycobacterium leprae strains. This study aimed to elucidate the baseline antimicrobial resistance (AMR) profile of M. leprae isolates in Kiribati using a novel molecular method. Methods: Mycobacterium leprae genomes from skin biopsies of patients clinically diagnosed with leprosy in Kiribati between 2017 and 2024 were analysed. We used an M. leprae specific repetitive element (RLEP) PCR to confirm the presence of M. leprae DNA. Samples with sufficient DNA (cycle threshold (CT) value < 30) proceeded for resistance testing. A combination of nested and heminested PCR assays was used to amplify the drug resistance determining regions (DRDR's) for dapsone ( folP1 ), rifampicin ( rpoB ) and fluoroquinolones ( gyrA ) followed by DNA Sanger sequencing. Results: 216 skin biopsies (multibacillary [MB], n = 155, paucibacillary [PB], n = 61) underwent confirmatory testing. 192/216 (89%) samples were PCR positive (median Ct value 24.5 [range 12.0–44.4]), including 145 MB cases (median CT 21.1 [range 12.0–42.0]) and 47 PB cases (median CT 34.0 [range 14.8–37.0]). Twenty‐four (11%) samples were PCR negative and 21 of these underwent histopathological testing, with 12 (57%) showing changes consistent with leprosy. 116 (60%) positive samples proceeded to AMR testing (MB, n = 106; PB, n = 10). In 10 cases (9%), dapsone resistance‐conferring mutations were identified in the folP1 region. No mutations were identified in the rpoB or gyrA genes. Conclusion: Molecular analysis of skin biopsies revealed moderate‐level dapsone resistance but no rifampicin resistance in Kiribati. Establishing this baseline AMR profile will enable a before‐versus‐after intervention analysis of antimicrobial resistance in M. leprae isolates in Kiribati.

Unique patient identification is necessary for detecting malaria recurrence and facilitates individualised treatment. Reliable patient identification in se

In 2021, the World Health Organization (WHO) recommended scaling up leprosy prevention activities, including chemoprophylaxis, as one of the pillars of their ‘Towards Zero Leprosy’ strategy. This recommendation was primarily based on a 57% overall reduction in leprosy incidence among contacts who received chemoprophylaxis in the COLEP study conducted in Bangladesh. Since this landmark study, further research on the efficacy, feasibility, and implementation of leprosy chemoprophylaxis has been conducted. Additionally, concerns have been raised regarding the strength of evidence supporting the overall benefit of chemoprophylaxis and the potential for propagation of drug resistance in M. leprae strains. This literature review presents the current evidence for the efficacy and safety of rifamycin-based chemoprophylaxis in preventing clinical disease, and the feasibility of implementing chemoprophylaxis programmes. Post-exposure prophylaxis (PEP) has a reported efficacy of 45–80%, depending on the degree of case contact, the classification of the index case, the selected chemoprophylaxis regimen, the geographical setting, childhood BCG coverage and the implementation approach. As an intervention, it appears to be feasible, cost-effective, and acceptable to patients, contacts, and healthcare staff, with minimal harm. Implementation strategies need to be tailored to specific epidemiological and sociocultural settings for maximal benefit. Further research is required to optimise PEP regimens and strategies in various epidemiological settings and to assess the impact of these programmes on the susceptibility profile of local M. leprae strains.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, an SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases retrospectively (2010–2017) and prospectively (2018–2022). We conducted a retrospective audit to determine the comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,641 household contacts were identified (9791 in the retrospective and 3850 in the prospective cohort). In the retrospective cohort, 1044 (11%) contacts were absent, 403 (4%) were ineligible for SDR, and 42 new cases were detected (0.4%) Overall, SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR, and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were 23 SDR refusals. The median time to SDR administration was 220 days (IQR 162–468) and 120 days (IQR 36–283) for the retrospective and prospective cohorts, respectively. SDR was readily accepted in both cohorts. The new case detection rate (0.5%) is consistent with that in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single dose rifampicin post exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, a SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases both retrospectively (2010-2017) and prospectively (2018 onwards). We conducted a retrospective audit to determine comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,643 household contacts were identified (9,791 in the retrospective and 3,850 in the prospective cohort). In the retrospective cohort, 1,044 (11%) contacts were absent, 403 (4%) were ineligible for SDR and 42 new cases were detected (0.4%) Overall SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were a total of 23 SDR refusals. The median time to SDR ad-ministration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts respectively. SDR was readily accepted in both cohorts. The new case detec-tion rate (0.5%) is consistent with that seen in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

: Primaquine (PQ) kills Plasmodium vivax hypnozoites but can cause severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We conducted two systematic reviews. The first used data from clinical trials to determine the variety of definitions and frequency of hematological serious adverse events (SAEs) related to PQ treatment of vivax malaria. The second used data from prospective studies and case reports to describe the clinical presentation, management, and outcome of severe PQ-associated hemolysis necessitating hospitalization. In the first review, SAEs were reported in 70 of 249 clinical trials. There were 34 hematological SAEs among 9,824 patients with P. vivax malaria treated with PQ, nine of which necessitated hospitalization or blood transfusion. Criteria used to define SAEs were diverse. In the second review, 21 of 8,487 articles screened reported 163 patients hospitalized after PQ radical cure; 79.9% of whom (123 of 154) were prescribed PQ at ≥ 0.5 mg/kg/day. Overall, 101 patients were categorized as having probable or possible severe PQ-associated hemolysis, 96.8% of whom were G6PD deficient (< 30% activity). The first symptoms of hemolysis were reported primarily on day 2 or 3 (45.5%), and all patients were hospitalized within 7 days of PQ commencement. A total of 57.9% of patients (77 of 133) had blood transfusion. Seven patients (6.9%) with probable or possible hemolysis died. Even when G6PD testing is available, enhanced monitoring for hemolysis is warranted after PQ treatment. Clinical review within the first 5 days of treatment may facilitate early detection and management of hemolysis. More robust definitions of severe PQ-associated hemolysis are required.

Introduction Progress towards leprosy elimination is threatened by increasing incidence in ‘hot-spot’ areas where more effective control strategies are urgently required. In these areas, active case finding and leprosy prevention limited to known contacts is insufficient for control. Population-wide active case-finding together with universal prevention through mass drug administration (MDA) has been shown to be effective in ‘hot-spot’ areas, but is logistically challenging and expensive. Combining leprosy screening and MDA with other population-wide screening activities such as for tuberculosis may increase programme efficiency. There has been limited evaluation of the feasibility and effectiveness of combined screening and MDA interventions. The COMBINE study aims to bridge this knowledge gap. Methods and analysis This implementation study will assess the feasibility and effectiveness of active leprosy case-finding and treatment, combined with MDA using either single-dose rifampicin or rifamycin-containing tuberculosis preventive or curative treatment, for reducing leprosy incidence in Kiribati. The leprosy programme will run over 2022–2025 in concert with population-wide tuberculosis screening-and-treatment in South Tarawa. The primary research question is to what extent the intervention reduces the annual leprosy new case detection rate (NCDR) in adults and children compared with routine screening and postexposure prophylaxis (PEP) among close contacts (baseline leprosy control activities). Comparisons will be made with (1) the preintervention NCDR separably among adults and children in South Tarawa (before–after study) and (2) the corresponding NCDRs in the rest of the country. Additionally, the postintervention prevalence of leprosy obtained from a survey of a ‘hot-spot’ sub-population will be compared with prevalence documented during the intervention. The intervention will be implemented in collaboration with the Kiribati National Leprosy Programme. Ethics and dissemination Approval has been obtained from the Kiribati Ministry of Health and Medical Services (MHMS), the University of Otago (H22/111) and the University of Sydney (2021/127) Human Research Ethics Committees. Findings will be shared with the MHMS, local communities and internationally through publication.