Saba Maria Lambert

Background: Dosing guidance for children with leprosy remains operationally challenging. For children under 10 years of age, current WHO recommendations rely on mg/kg dosing of the three separate components of leprosy multidrug therapy, which are difficult to implement in routine care and may result in inconsistent drug exposures. Weight-banded dosing offers a pragmatic alternative that better aligns with pharmacokinetic principles and existing drug formulations. Methodology: A pharmacokinetic simulation study was conducted to develop harmonized weight-banded dosing regimens for rifampicin, clofazimine, and dapsone in children aged 2 to <10 years. Using the WHO dosing tool, drug exposures across harmonized weight bands were simulated and adult-equivalent systemic exposure (80-125% of adult area under the concentration-time curve) targeted. Predicted exposures were contextualized against safety reference regimens used in tuberculosis meningitis, multidrug-resistant tuberculosis, and leprosy. An iterative review process involving the WHO Technical Working Group on leprosy in children ensured clinical and operational feasibility. Results: Proposed weight-banded multidrug therapy regimens achieved adult-equivalent exposures across most weight bands. Predicted exposures modestly exceeded 125% of adult levels at the lower end of selected weight bands but remained well below safety benchmarks, namely exposures associated with daily rifampicin therapy for tuberculosis meningitis and clofazimine regimens for multidrug-resistant tuberculosis. Dapsone exposures were comparable to those achieved with current leprosy dosing. The existing 10-14-year-old child MDT blister pack could be used without modification in children weighing 25-39.9 kg and with limited tablet or gel capsule removal in children weighing 6-24.9 kg. Conclusions: A harmonized weight-banded dosing strategy was developed that enables effective, practical dosing of leprosy multidrug therapy in children under 10 years using existing free-of-charge blister packs provided through WHO. This approach improves dosing consistency, supports programmatic implementation, and provides a rational interim solution while child-friendly formulations are being developed.

Little is known about the stigma and discrimination children with leprosy are subject to and the subsequent impact on their psychological well-being. The aim of this study is to systematically review the literature for evidence that closes this knowledge gap and informs practice. In line with a PRISMA-P Protocol (PROSPERO CRD420251089128), we conducted a systematic review, underpinned by an extensive search strategy. There was no inclusion restriction on methodology, time period, country, or language. Data extraction was completed through a double-review process, which was guided by a deductive theoretical framework and shaped by inductive coding. This was followed by a data synthesis and double-blinded quality appraisal. The search strategy identified 914 items. Following a double-blind review with conflict mediation, we included 48 items. The review found evidence for nine domains of discrimination, 16 stigma types, and seven individual-level mental health responses. Social/interpersonal stigma and affective/cognitive mental health responses were the most prevalent findings. Fourteen moderating factors were identified, with disease awareness/knowledge the most frequent. Children affected by leprosy are subject to multiple stigma types and discrimination in numerous life domains, which adversely affects their mental health. Policy and practice recommendations include a multisectoral response including community engagement, public health and education sectors, a whole-family approach including all family members directly/indirectly affected by leprosy, and recognition of the inter-relationships between moderating factors. Despite the novel findings this review presents, there are limitations stemming from the dataset and from methodological choices. Given the gaps in primary academic research and the identified limitations, the topic deserves substantial future attention.

In Ethiopia, the incidence of cutaneous leishmaniasis (CL) is estimated to range from 20, 000–30, 000 new cases due to Leishmania aethiopica . Children and young adults, in rural communities with limited access to health care are most affected. The current standard of care, pentavalent sodium stibogluconate is only administered in specialist centres, has limited effectiveness and is associated with severe adverse effects. Cryotherapy is recommended in national guidelines at the primary care level to treat uncomplicated CL, but is rarely available due to limited numbers of trained clinicians and lack of resources. We co-developed and evaluated a decentralised intervention, administered at a rural health centre, using carbon dioxide (CO ₂ ) cryotherapy, which is available for the treatment of cervical dysplasia. A pragmatic clinical trial design was used, providing training at the health centre that combined theoretical instruction with direct patient assessment. Study clinicians recruited patients with suspected CL who had a slit-skin smear performed with confirmation by expert microscopists. The diagnostic accuracy of trained clinical and laboratory staff at a rural health centre were compared to experts. Individuals aged ≥12 years with parasitologically confirmed uncomplicated CL received CO ₂ cryotherapy. Participants were followed until Day 90. Cure was defined as complete re-epithelialization of the index lesion. The study was registered in the Pan African Clinical Trials Registry with trial number PACTR202605616785682. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=41111 . We trained seven clinicians and laboratory professionals at Keteteya Health Centre. Of 331 individuals who attended the clinic with skin disease, 158 (47.7%) were clinically diagnosed by trained clinical staff with CL. Overall 123 (78%) had laboratory confirmed CL and of these 85 (53.8%) received CO ₂ cryotherapy. By Day 90, 68 of 77 (88.3% (95% CI: 78.5–94.1%)) were cured. Adverse events were mild and transient, with no individual discontinuing treatment. Trained health centre clinical and laboratory staff were able to accurately diagnose CL. CO ₂ cryotherapy was safe and efficacious when administered by trained staff. A training programme to facilitate CO ₂ cryotherapy appears to be a feasible approach to decentralizing CL diagnosis and treatment to primary healthcare facilities in endemic areas of Ethiopia.

BACKGROUND: Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy associated with disability, morbidity and mortality. Impairment of health-related quality of life (HRQoL) in ENL has been reported using the Dermatology Life Quality Index (DLQI) and the 36-Item Short Form Health Survey (SF-36), the latter validated in people affected by leprosy. Understanding the correlation between these measures is important to determine whether the shorter dermatology-specific DLQI provides a valid and practical measure of HRQoL in ENL. OBJECTIVES: To examine the relationship between DLQI and SF-36 scores in individuals with ENL using data from the Methotrexate and Prednisolone study in ENL (MaPs in ENL). METHODS: A post-hoc analysis of prospectively collected HRQoL data from the trial sites in India, Indonesia, and Nepal of the MaPs in ENL multicentre randomised clinical trial was performed. HRQoL was assessed using the DLQI and SF-36 at enrolment and at weeks 24, 48 and 60. Associations between DLQI and SF-36 physical (PCS) and mental (MCS) component summary scores were evaluated using correlation analyses and multivariable linear regression at enrolment, and linear mixed-effects models during follow-up adjusted for age, sex, recruiting centre and enrolment SF-36 scores. RESULTS: A total of 383 paired HRQoL assessments from 129 participants were analysed. At enrolment, HRQoL impairment was substantial (median DLQI 19, IQR 15–21; mean PCS 30.3 ±7.3; mean MCS 33.3 ±8.4). DLQI scores improved markedly during follow-up. Across all timepoints, DLQI was strongly inversely correlated with PCS (r = −0.848) and MCS (r = −0.806) (both p<0.001). In adjusted analyses, higher DLQI scores were consistently associated with lower PCS and MCS. At enrolment, each 1-point increase in DLQI was associated with a 0.66-point reduction in PCS and a 0.51-point reduction in MCS (both p<0.001). These associations remained strong during follow-up, with no evidence that they varied over time. CONCLUSIONS: DLQI scores were strongly and consistently associated with SF-36 physical and mental health scores. These findings support the use of the DLQI as a practical patient reported outcome measure to assess the HRQoL associated with ENL and its change following treatment. What is already known about this topic?: ENL is associated with substantial morbidity and impaired quality of life. Dermatology-specific and generic HRQoL instruments have been used in leprosy. Comparative data between DLQI and SF-36 in ENL are scarce and limited. What does this study add?: The DLQI strongly inversely correlated with with the SF-36 measures in ENL. Dermatology-specific impairment reflects broader physical and mental health burden in ENL. The DLQI may be a practical outcome measure for ENL clinical studies and routine clinical assessment.

Background: Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in additional to prednisolone reduces the need for additional prednisolone in adults with severe ENL. Methods and Findings: We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18–60 years with severe ENL were randomised to receive oral methotrexate and prednisolone, or matching placebo and prednisolone. All participants received an identical prednisolone regime over 20 weeks and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62–1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62–1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov ( NCT03775460 ). Conclusions: Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL. Author’s Summary: Why was this study done?: Erythema nodosum leprosum (ENL) is a painful, relapsing inflammatory complication of leprosy that often requires prolonged courses of oral corticosteroids. Long-term corticosteroids can cause serious adverse effects including mortality in some settings Thalidomide is effective but is not accessible in many endemic countries. Methotrexate treatment is inexpensive and widely available, but high-quality evidence for its use in ENL is lacking. What did the researchers do and find?: We conducted an international, multicentre, double-blind randomised trial in four countries, enrolling 137 adults with severe ENL. Participants received either weekly oral methotrexate or identical placebo tablets, and 20-week course of oral prednisolone Methotrexate did not reduce the likelihood of ENL flares needing additional prednisolone at 24 or 48 weeks, nor did it reduce flare severity or overall flare burden. Quality of life improved markedly but with no clear difference between treatment groups. Methotrexate was generally well tolerated What do these findings mean?: Adding methotrexate to prednisolone does not provide clinically meaningful corticosteroid-sparing benefit for severe ENL. New therapies for severe ENL are required because even with high quality care corticosteroids are required at high doses for prolonged periods in most people

Background: Cutaneous leishmaniasis (CL) is a major public health concern, particularly in Ethiopia, where about 40 000 new cases occur annually, predominantly caused by Leishmania aethiopica. Clinical phenotypes include localized CL (LCL), mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL). Despite the high disease burden, treatment options and high-quality data on treatment outcomes are limited. Objectives: To evaluate the effectiveness of standard treatments in Ethiopia to inform future clinical trials. Methods: We conducted an observational cohort study of patients with parasitologically confirmed cutaneous leishmaniasis at two specialized dermatology referral hospitals. Clinical- and patient-reported outcomes were assessed at baseline and at standardized times during follow-up. The primary clinical outcome measure (‘cure’) was complete re-epithelialization or flattening of the index lesion at day 90. Patient-reported outcomes were assessed using skin-specific and general quality-of-life scores. Results: We enrolled 666 participants from April 2022 to October 2023. Median patient age was 20 years (interquartile range 14–35) and 405 patients were male (60.8%). More than half (n = 372; 55.9%) had previously received traditional treatment for CL. Most participants had LCL (n = 390; 58.6%) or MCL (n = 261; 39.1%). Intramuscular sodium stibogluconate 20 mg kg–1 daily was the most frequently used systemic therapy, either alone or in combination with lesion-directed therapy (cryotherapy or intralesional sodium stibogluconate). At day 90, 28.3% (n = 83/293) of participants with LCL, 23.5% (v = 47/200) with MCL and 8% (n = 1/12) with DCL were deemed cured. By day 90, all patient-reported outcomes of skin health improved for those with LCL or MCL, but skin and CL-related quality-of-life scores did not improve for those with DCL. Most participants (n = 522/641; 81.4%) experienced at least one clinical adverse event and 7.2% (n = 46/641) had abnormal laboratory findings during treatment. Conclusions: Current treatment strategies have low cure rates in Ethiopia. Well-designed randomized controlled trials are urgently needed to improve management of CL caused by L. aethiopica.

Background: Skin diseases are associated with reduced health‐related quality of life (HRQoL) of children and their families. The Children’s Dermatology Life Quality Index (CDLQI) questionnaire is a skin disease‐specific measure of HRQoL in children. Our study aimed to translate the CDLQI into Amharic, culturally adapt, and evaluate the validity and reliability of the translation. Methods: This study was embedded within a larger hospital‐based cohort study of cutaneous leishmaniasis (CL). Forward–backward translation procedures were conducted, followed by assessment of content and face validity. The psychometric properties were evaluated through reliability (internal consistency and interrater reliability), construct validity (including known‐group, convergent, and discriminant validity), and responsiveness to change. Cronbach’s alpha, intraclass correlation coefficient (ICC), Mann–Whitney U test, Kruskal–Wallis test, confirmatory factor analysis (CFA), and Wilcoxon paired rank test were used to assess internal consistency, interrater reliability, known‐group validity, construct validity, and responsiveness to change validity, respectively. Results: The CDLQI showed acceptable content validity with a modified kappa between 0.7 and 0.9. In a pilot testing, children reported that the items in the translated Amharic version of the CDLQI were unambiguous. Among 188 enrolled participants, 129 (68.62%) were diagnosed with CL and 59 (31.38%) with other skin conditions. The median CDLQI score was 7 (IQR = 10). The overall Cronbach’s alpha and ICC were 0.82 and 0.92, respectively. The median CDLQI score showed statistically significant differences between “mild” vs. “severe” and “moderate” vs. “severe” CL cases ( p < 0.001), as well as between the number of lesions (single vs. multiple) ( p = 0.034) and lesion size (< 40 mm vs. ≥ 40 mm) ( p < 0.001). CFA showed acceptable convergent validity with most items loading strongly (0.50–0.74), and Heterotrait–Monotrait ratio values ranging from 0.614 to 0.744. The CDLQI median score significantly decreased from Day 1 (median = 9) to Day 90 (median = 4; p < 0.001). Conclusions: Our Amharic version of the CDLQI showed acceptable validity and reliability, supporting its use in clinical practice and research to assess the HRQoL of Amharic‐speaking children with skin conditions in Ethiopia.

Localised cutaneous leishmaniasis (LCL) is a common neglected tropical disease in Ethiopia, which is mainly treated with intralesional (IL) pentavalent antimonial such as sodium stibogluconate (SSG) and/or cryotherapy. Both treatments are painful, and studies are lacking on the pain associated with these or affected individuals’ experiences of them. A cross-sectional, observational study was conducted at ALERT Comprehensive Specialized Hospital, Addis Ababa/Ethiopia. The socio-demographic and clinical data of individuals affected by LCL receiving IL SSG and/or cryotherapy was gathered, and their treatment was observed. Participants quantified their treatment-associated pain using the Wong–Baker Pain Scale. Health-related quality of life was measured using the (Children’s) Dermatology Life Quality Index. Adverse effects, participant experiences with local therapies, and dermatologists’ experiences and opinions of local LCL treatment were assessed using structured questionnaires. Of the thirty-six individuals with LCL included (64% male, 14% children), 52% reported a treatment-associated pain score ≥ 8. Cryotherapy administered with a cotton bud was associated with lower pain scores ≤ 6 (odds ratio: 0.15, 95% confidence interval: 0.03–0.89) compared to a cryotherapy spray device. There was wide variation in treatment administration. Local LCL treatment is painful, and most individuals experience significant pain. This study highlights the need for less painful but effective treatments, structured training, and clear standard operating procedures.

Introduction Cutaneous leishmaniasis (CL) remains a major public health challenge, especially in endemic regions like Ethiopia, where an estimated 40,000 new cases occur annually. Effective treatment evaluation for CL relies on consistent clinical assessments, yet variability in lesion descriptions can complicate reliable outcome measures. Methods We conducted an inter-reliability study of clinicians’ evaluations of CL lesion morphology and size at ALERT Hospital, Addis Ababa. Twelve clinicians independently examined 12 patients with parasitologically confirmed CL, each clinician assessing lesion morphology, size, and severity. Results We found high consistency in reporting major morphological categories (e.g., plaques) but significant variability in secondary features like dyspigmentation and scale, as well as mucosal involvement. Lesion size measurements showed limited variability, suggesting its reliability as a potential measure for future clinical trials. Disparities in severity assessments highlight the need for a standardized scoring system in CL. Discussion Our findings underscore the importance of training for consistent, high-quality clinical evaluations of CL and suggests that lesion size could be a reproducible outcome measure in treatment efficacy trials.

Introduction Cutaneous leishmaniasis (CL) remains a major public health challenge, especially in endemic regions like Ethiopia, where an estimated 40,000 new cases occur annually. Effective treatment evaluation for CL relies on consistent clinical assessments, yet variability in lesion descriptions can complicate reliable outcome measures. Methods We conducted an inter-reliability study of clinicians’ evaluations of CL lesion morphology and size at ALERT Hospital, Addis Ababa. Twelve clinicians independently examined 12 patients with parasitologically confirmed CL, each clinician assessing lesion morphology, size, and severity. Results We found high consistency in reporting major morphological categories (e.g., plaques) but significant variability in secondary features like dyspigmentation and scale, as well as mucosal involvement. Lesion size measurements showed limited variability, suggesting its reliability as a potential measure for future clinical trials. Disparities in severity assessments highlight the need for a standardized scoring system in CL. Discussion Our findings underscore the importance of training for consistent, high-quality clinical evaluations of CL and suggests that lesion size could be a reproducible outcome measure in treatment efficacy trials.