BACKGROUND
Bedaquiline (BDQ) resistance presents a critical challenge in the fight against tuberculosis (TB), particularly multidrug-resistant (MDR) strains. The emergence of resistance to BDQ, a key drug in treating MDR-TB, poses significant threats to TB treatment effectiveness.
METHODS
The National Institute of Tuberculosis and Respiratory Diseases in Delhi and the Médecins Sans Frontières clinic in Mumbai provide BDQ, delamanid, and carbapenem-based regimens for patients with suspected or confirmed treatment failure. BDQ phenotypic drug-susceptibility testing (DST) was performed for all BDQ-exposed patients. Treatment regimens were individualized based on exposure history, comorbidities, drug interactions, prior adverse drug reactions, and DST results.
RESULTS
Of 117 BDQ-exposed patients from December 2020–December 2022, 42 (36%) exhibited a BDQ-resistant strain. Median (IQR) age was 24 (22–32) years, with 63 (54%) females and 94% with pulmonary TB. Patients with a BDQ-resistant strain were older (median age: 27 vs 23 years; P = .04), more likely to have lung cavities (risk ratio [RR]: 1.8; 95%-CI: 1.1–3.1; P = .02), and be resistant to clofazimine (RR: 2.3; 95%-CI: 1.5–3.6; P = .001). Overall, 102 patients initiated treatment. Patients with BDQ-resistance had higher risk of unfavorable outcomes compared with BDQ-susceptible patients (RR:2.1; 95%-CI: 1.5–2.8; P < .001). Overall, 87% (33/38) of patients with BDQ-resistance experienced unfavorable treatment outcomes: 15 (40%) died, 15 (40%) had treatment failure, and 3 (8%) were lost-to-follow-up.
CONCLUSIONS
The study highlights a concerning rate of BDQ-resistance among previously treated patients, resulting in poor treatment outcomes. To prevent treatment failure, we recommend implementing BDQ-DST, developing affordable and accurate rapid tests for BDQ-resistance, and intensifying research and development efforts for newer TB drugs.
OBJECTIVES
The main objective of this study was to implement an online pediatric case‐based POCUS course in low‐resource medical settings and examine learning outcomes and feasibility.
METHODS
This was a multicenter prospective cohort study conducted in a convenience sample of clinicians affiliated with Médecins Sans Frontières (MSF) training sites. MSF POCUS trainers provided the standard hands‐on, on‐site POCUS training and supplemented this with access to a web‐based course. Participants provided diagnoses for 400 image‐based POCUS cases from four common pediatric POCUS applications until they achieved the mastery learning standard of 90% accuracy, sensitivity (cases with pathology), and specificity (cases without pathology). Each participant also completed a course evaluation.
RESULTS
From 10 MSF sites, 110 clinicians completed 82,206 cases. There were significant learning gains across the POCUS applications with respect to accuracy (delta 14.2%; 95% CI 13.1, 15.2), sensitivity (delta 13.2%; 95% CI 12.1, 14.2), and specificity (delta 13.8%; 95% CI 12.7, 15.0). Furthermore, 90 (81.8%) achieved the mastery learning standard in at least one application, and 69 (62.7%) completed a course evaluation on at least one application for a total of 231 evaluations. Of these, 206 (89.2%) agreed/strongly agreed that the experience had relevance to their practice, met expectations, and had a positive user design. However, 59/110 (53.6%) clinicians reported a lack of protected time, and 54/110 (49.0%) identified challenges with accessing internet/hardware.
CONCLUSIONS
In resource‐limited MSF settings, implementing web‐based POCUS case practice demonstrated successful learning outcomes despite approximately half of the participants encountering significant technical challenges.
In 2021 in response to an outbreak of hepatitis E in Bentiu internally displaced persons camp the South Sudanese Ministry of Health with support from Médecins Sans Frontières implemented the first-ever mass reactive vaccination campaign with HEV239 (Hecolin; Innovax, Xiamen, China). We conducted qualitative research to assess knowledge, attitudes, and practices related to hepatitis E and the hepatitis E vaccine. We conducted 8 focus group discussions (FGDs) with community leaders, the general population of vaccine-eligible adults, vaccine-eligible pregnant women (vaccinated and non-vaccinated), and healthcare workers. FGDs were separate by gender and were audio recorded, transcribed, and translated to English. Two coders used inductive thematic analysis to organize emergent themes. Data were collected in November 2022. Most participants had experiences with hepatitis E (e.g., infected themselves or knowing someone that had been infected) and viewed hepatitis E as a dangerous disease. Participants believed children, pregnant women, and older persons were the highest risk groups and frequently made requests for additional hepatitis E vaccination campaigns and expanded eligibility criteria for vaccination. Knowledge of the negative impacts of hepatitis E and trusted relationships with the organizations offering the vaccine were key facilitators of vaccine acceptance. The primary barriers to vaccination were practical issues related to being away from the camp during the campaign or not knowing about the campaign, but participants shared that some in the community were unvaccinated due to fears about injections, social pressure, misinformation, and concerns about why some groups were eligible for vaccination and not others (e.g., young children). Personal experiences with hepatitis E illness, perceived severity of illness, and confidence in organizations recommending the vaccine were drivers of high demand for hepatitis E vaccines in the first-ever use of the vaccine in an outbreak setting. Addressing practical issues related to population mobility can improve coverage in future campaigns.
The COVID-19 pandemic accelerated the development of AI-driven tools to improve public health surveillance and outbreak management. While AI programs have shown promise in disease surveillance, they also present issues such as data privacy, prejudice, and human-AI interactions. This sixth session of the of the WHO Pandemic and Epidemic Intelligence Innovation Forum examines the use of Artificial Intelligence (AI) in public health by collecting the experience of key global health organizations, such the Boston Children's Hospital, the Global South AI for Pandemic & Epidemic Preparedness & Response (AI4PEP) network, Medicines Sans Frontières (MSF), and the University of Sydney. AI's utility in clinical care, particularly in diagnostics, medication discovery, and data processing, has resulted in improvements that may also benefit public health surveillance. However, the use of AI in global health necessitates careful consideration of ethical issues, particularly those involving data use and algorithmic bias. As AI advances, particularly with large language models, public health officials must develop governance frameworks that stress openness, accountability, and fairness. These systems should address worldwide differences in data access and ensure that AI technologies are tailored to specific local needs. Ultimately, AI's ability to improve healthcare efficiency and equity is dependent on multidisciplinary collaboration, community involvement, and inclusive AI designs in ensuring equitable healthcare outcomes to fit the unique demands of global communities.
The incidence and mortality of kala-azar (KA, visceral leishmaniasis) in India have fallen drastically in the past few years, and in 2023 the reported KA incidence reached the threshold for elimination as a public health problem (<1 case/10 000 of population at subdistrict level). One of the strategies adopted by India's kala-azar elimination program (KAEP) was the regular independent assessment of the program implementation by teams of experts. We present the findings of assessments undertaken in 2019, 2021 and 2023, when the KAEP was in the last mile of elimination. Factors that contributed to its success were political commitment, intensified implementation, a strong network of KA partners and committed donors. Bottlenecks were observed in disease surveillance, data utilization, vector-control operations and program management at implementation. To sustain the gains and achieve validation of elimination, the KAEP should continue the following minimal essential services: optimized active and passive case detection and management of KA, post-KA dermal leishmaniasis, KA-HIV coinfection and relapse supported by vector-control interventions. Long-term measures that will sustain elimination are overall socioeconomic development, including improved living conditions, parallel with efficient surveillance and operational research that is aligned with the changing epidemiology of the disease.
BACKGROUND
Antibiotics are indispensable to modern healthcare, yet their equitable access remains a pressing global challenge. Factors contributing to inequities include insufficient evidence for optimal clinical use, limited registration, pricing for Reserve antibiotics, and supply chain challenges. These issues disproportionately affect low- and middle-income countries, exacerbating antimicrobial resistance burdens.
OBJECTIVES
This paper explores the multifaceted dimensions of inequitable antibiotic access and proposes a comprehensive framework to address the crisis.
SOURCES
Published articles, grey literature analysis, and the authors' own expertise contributed to this article.
CONTENT
While much attention has been paid to push-and-pull incentives for antibiotic development, these interventions are inadequate to reach sustainable and equitable access to antibiotics. Improving equitable antibiotic access requires an ecosystem approach, involving multiple stakeholders and including public–private partnerships. The paper advocates for initiatives spanning research and development, regulatory pathways, procurement strategies, and financing mechanisms and suggests concrete interventions in each of these areas. The specific interventions and mix of public and private actors may vary according to antibiotic, market, and health system context, but must be designed to meet public health needs while also supporting a market that will sustain quality-assured production and delivery of antibiotics.
IMPLICATIONS
Addressing the challenge of equitable antibiotic access requires coordinated efforts across sectors and regions. By embracing an ecosystem approach centred on public health priorities, stakeholders can pave the way for a sustainable supply of antibiotics, and equitable access, safeguarding the future of global healthcare amidst the growing threat of antimicrobial resistance.
BACKGROUND
Visceral leishmaniasis (VL) is a vector-borne disease caused by Leishmania parasites and transmitted by sand fly bites, targeted for elimination in India. VL primarily affects rural, low-income populations with limited health care access. In South Asia, few studies have explored patients’ perspectives, diagnoses, and treatment experiences; particularly lacking an understanding about the patients’ life experiences outside of clinical research settings.
METHODOLOGY/PRINCIPAL FINDINGS
A qualitative study was conducted in Bihar, India, using moderator-facilitated, protocol-defined discussion. Eighteen adult patients and 12 caregivers of children diagnosed with and treated for VL within the last 12 months were identified by self-report. Mean time from symptom onset to diagnosis was 13.8 days. Challenges of the early patient life experience included lack of urgency by health care professionals, delayed diagnosis, and no guarantee of treatment at the location of their VL diagnosis (63% had to switch to a different center for treatment, at times delaying treatment). Key barriers identified in previous studies that were re-confirmed in this study include out-of-pocket financial burden, absence from work/home duties, and long-distance travel to hospitals. Patients and caregivers (n = 29/30) expressed a preference for a potential oral treatment that could be taken close to home.
CONCLUSIONS/SIGNIFICANCE
This study reveals new insights about the patient life experience and reconfirms previous research indicating that access to care for patients with VL in the Bihar area remains a challenge. Although most patients with VL seek care early, diagnosis often requires multiple visits to a health care facility. Despite access to therapy in public hospitals, some patients reported a preference for private care. Even if diagnosis takes place in a government-funded public setting, some patients reported needing to move from the location of diagnosis to another center to receive therapy, creating an additional burden for patients. As a potential alternative to current parenteral treatment, adult patients and caregivers of pediatric patients expressed interest in a potential oral therapy because it may reduce barriers to access care.
BACKGROUND
Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.
METHODS
In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points.
RESULTS
A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.
CONCLUSIONS
A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.
Cholera is a bacterial water-borne diarrheal disease transmitted via the fecal-oral route that causes high morbidity in sub-Saharan Africa and Asia. It is preventable with vaccination, and Water, Sanitation, and Hygiene (WASH) improvements. However, the impact of vaccination in endemic settings remains unclear. Cholera is endemic in the city of Kalemie, on the shore of Lake Tanganyika, in the Democratic Republic of Congo, where both seasonal mobility and the lake, a potential environmental reservoir, may promote transmission. Kalemie received a vaccination campaign and WASH improvements in 2013–2016. We assessed the impact of this intervention to inform future control strategies in endemic settings. We fit compartmental models considering seasonal mobility and environmentally-based transmission. We estimated the number of cases the intervention avoided, and the relative contributions of the elements promoting local cholera transmission. We estimated the intervention avoided 5,259 cases (95% credible interval: 1,576.6–11,337.8) over 118 weeks. Transmission did not rely on seasonal mobility and was primarily environmentally-driven. Removing environmental exposure or contamination could control local transmission. Repeated environmental exposure could maintain high population immunity and decrease the impact of vaccination in similar endemic areas. Addressing environmental exposure and contamination should be the primary target of interventions in such settings.
BACKGROUND
Only 63% of patients initiating multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment in 2020 were treated successfully. 24-Week all-oral bedaquiline, pretomanid, and linezolid (BPaL)–based regimens have demonstrated higher rates of treatment success and have been recommended by the World Health Organization. Operational research is urgently required to evaluate these regimens in non-trial settings.
METHODS
This was a prospective cohort study of patients with microbiologically confirmed MDR/RR-TB and pre–extensively drug-resistant TB (pre-XDR-TB) initiated on BPaL-based regimens in Belarus and Uzbekistan (February 2022–June 2023). All clinical care and research procedures were delivered by treating physicians. After treatment completion, patients were followed up at 6 and 12 months, including collecting sputum to ascertain recurrence. The primary objective was to estimate the effectiveness (cured or treatment completed) and safety (the occurrence of serious adverse events) of BPaL-based regimens.
RESULTS
A total of 677 patients initiated treatment with BPaL-based regimens during the study. We documented successful treatment outcomes in 95.3% (427/448) of patients with MDR/RR-TB treated with BPaL plus moxifloxacin and 90.4% (207/229) of patients with pre–XDR-TB treated with BPaL plus clofazimine. 10.2% (69/677) experienced serious adverse events including 24 deaths (3.5%), 11 of which occurred during treatment. 83.3% (20/24) of deaths were not related to TB or TB treatment. Of patients who were successfully treated and completed 12-month follow-up, 0.5% (2/383) had recurrence.
CONCLUSIONS
BPaL-based regimens for MDR/RR-TB and pre–XDR-TB are safe and highly effective in non-trial settings. These regimens should be considered for widespread implementation globally, and further research is needed to evaluate their performance in other key populations.