Leen Daoud, Magid Al Gunaid, Aïssatou Diawara, Mahanna Elsheik, Alison Krentel, Sami A. Al-Haidari
Trachoma remains a preventable cause of blindness in fragile and conflict-affected settings, where community-level prevention is often weak. This study examined short-term changes in community health worker capacity for trachoma prevention and referral practices, and community-reported behaviors following a capacity-strengthening intervention in Al Sabra district, Ibb, Yemen. A mixed-methods pre–post implementation design was used around an intervention delivered from 7 May to 9 July 2025. Quantitative data included CHW knowledge surveys and routine facility records of reported eye infections as a proxy indicator. Qualitative data were collected through in-depth interviews, community dialogues, and focus group discussions. Fifteen CHWs participated alongside supervisors, health staff, and community members. At endline, CHWs demonstrated high knowledge of trachoma transmission, prevention, and referral, alongside high self-reported confidence in case identification, referral, and community education. Because the baseline survey included CHWs and supervisors, whereas the endline survey included CHWs only, these findings were interpreted descriptively rather than as a direct paired comparison. Qualitative findings suggested greater awareness, less reported reliance on traditional remedies, and wider use of facial cleanliness and hygiene practices, particularly among mothers and children, and described CHWs as trusted agents of change. Routine facility data did not show a clear or sustained change in reported eye infection cases during the short follow-up period, reflecting limitations related to proxy measurement and diagnostic capacity. These exploratory findings suggest that targeted CHW capacity strengthening may support prevention behaviors and community engagement relevant to the facial cleanliness and environmental components of the SAFE strategy. The results highlight the importance of investing in community-based systems alongside biomedical interventions in fragile settings.
Dermatophytosis affects approximately 25% of the world population. Terbinafine, an antifungal medication, was historically used to treat this condition. However, the infection caused by a newer fungal species called Trichophyton indotineae has changed this situation, as it responds poorly to terbinafine. Moreover, the infection caused by this species lasts longer, returns repeatedly after treatment, and can spread over large areas of the body. This fungus was first linked to major recurrent and chronic skin infections in India and has now spread across the globe having been identified in Asia, the Middle East, Europe, and North America. The major concern is that this infection, caused by T. indotineae, may be spreading internationally, and carrying antifungal resistance, it could pose a serious global public health problem. This review discusses five main aspects of T. indotineae: taxonomic classification, epidemiology, mechanism of drug resistance, diagnostic limitations, and management challenges leading to treatment failure. The mechanism of action of terbinafine is to bind and block the fungal enzyme squalene epoxidase, which is required to produce ergosterol, a component of the cell membrane. In resistant strains, point mutations occur in the squalene epoxidase gene, particularly Leu393Phe and Phe397Leu, changing the structure of the enzyme, and terbinafine cannot bind effectively, leading to treatment failure and recurrence. Resistance to alternative drugs like itraconazole and other azoles is also increasing through the overexpression of efflux pumps. In addition, several clinical and public health problems, such as the increasing use of over-the-counter corticosteroid creams, species identification delays, household transmission, and limited public health surveillance, have also contributed to the spread and resistance of this fungal infection. There are several knowledge gaps. Addressing this threat by T. indotineae requires standardised laboratories with genetic testing to identify the species; treatment guided by susceptibility; antifungal stewardship that selects the appropriate antifungal drug, dose, and treatment duration; regulation of the use of combination drugs; international surveillance; and high-quality, multicentre RCTs to establish evidence-based dosing regimens.
Ni Made Puspawati, Iryanti Eka Suprihatin, Akshay Suthar, Ashaka Vansia, Rajesh Patel
Multidrug-resistant tuberculosis (MDR-TB) remains a major public health threat in Indonesia, which ranks second globally in tuberculosis burden. Whole-genome sequencing (WGS) studies of drug-resistant Mycobacterium tuberculosis in Indonesia have so far been analyzed largely in isolation, and no previous study has systematically compared the evolutionary conservation of classical, clinically validated resistance-associated genes with newly proposed metabolic drug targets within a single, geographically diverse Indonesian isolate collection. We compiled 444 publicly available Mycobacterium tuberculosis whole genomes from four Indonesian whole-genome sequencing studies spanning Java and Papua and analyzed them using TBProfiler for lineage assignment and genotypic drug-resistance prediction. Following exclusion of nine isolates for which an unambiguous single lineage could not be assigned, gene-level sequences for ten classical resistance-associated genes (rpoB, katG, inhA, fabG1, embB, pncA, gyrA, gyrB, rpsL, rrs) and ten emerging metabolic drug-target genes (guaA, guaB2, glnA1, gltB, dapB, folP1, bioA, panC, aroG, ilvB1) were reconstructed for 435 isolates and compared by multiple sequence alignment, variant calling, and functional annotation. (East-Asian) predominated (46.2% of isolates) and was disproportionately associated with drug-resistant genotypes (χ² = 49.07, df = 2, p < 0.001; Lineage 2 versus Lineage 4 odds ratio for any genotypic resistance 2.69, 95% CI 1.77–4.07). Overall, 28.2% of isolates were genotypically multidrug-resistant and 5.4% were pre-extensively drug-resistant, with no mutations associated with bedaquiline, linezolid, or clofazimine resistance detected. All twenty target genes were highly conserved (89.4–99.6% invariant sites), consistent with the clonal population structure of M. tuberculosis. However, the two panels differed substantially: classical resistance-associated loci were significantly less conserved than emerging targets (mean 96.47% versus 99.24%; p < 0.001), carried a significantly higher SNP density (20.70 versus 6.58 SNPs per kilobase; p = 0.002) and per-site Shannon entropy (p = 0.009), and accounted for 537 of the 670 variable sites detected across the panel despite comprising a similar total coding length. The non-synonymous-to-synonymous substitution ratio was also significantly higher among classical loci (median 1.67 versus 0.96; p = 0.033), driven by the prodrug-activating enzymes pncA (49.0) and katG (10.4) and by rpsL (6.0) and rpoB (2.08). Within the emerging panel, absolute variable-site counts were uniformly low (4–47 sites per gene) and did not support discrimination between individual candidate genes. Across a geographically diverse Indonesian Mycobacterium tuberculosis population, therapeutically unexploited metabolic drug targets are markedly more conserved and carry a substantially lower mutational burden than classical resistance-associated loci, whose elevated non-synonymous variation is concentrated in genes whose inactivation confers resistance. These findings support the emerging metabolic panel collectively as a low-variability target space for future anti-tubercular development, and establish evolutionary conservation combined with substitution-pattern analysis as a quantitative framework for target-space prioritization and genomic surveillance in high-burden tuberculosis settings.
Nzungize Lambert, Naomi A. Dyer, Umuhoza Diane, Ellie Sherrard-Smith, Mutesa Leon
In Rwanda, mosquito control interventions, relying on bed nets and insecticide spraying on household walls, remain dominant in malaria prevention. Insecticides, widely used in both public health and agriculture, are becoming less effective across the country. Resistance data collected between 2022 and 2023 showed a clear geographic distribution of insecticide resistance in mosquitoes. In seven districts, Anopheles gambiae collected during both rainy and dry seasons were tested with WHO tube assays. Pre-exposure to piperonyl butoxide (PBO) as a pyrethroid synergist significantly increased mortality after pyrethroid exposure. Still, mortality did not reach 98-100%, indicating the presence of additional resistance mechanisms, including target-site resistance, glutathione S-transferases and esterases, cuticular resistance, and behavioral resistance. These findings demonstrate that a uniform insecticide deployment plan is no longer sufficient. This policy brief recommends enhancing insecticide resistance management through routine vector molecular surveillance tools and genomic surveillance, expanding resistance monitoring to twice yearly at sentinel sites, prioritizing PBO-treated nets in high-resistance areas, and rotating alternative non-pyrethroid insecticides where appropriate.
Dhanya Dharmapalan, Madhumita Singh, Mortada El-Shabrawi, Thomas Murray, Ayebo Evawere Sadoh, Leonor Patricia Saltigeral Simental, Cyntia Ibanes-Gutiérrez, Elisavet Efstathiou, Hanan M. Fathy, Barbara Rath, Abdalla Modar Dali, Betty Nkansah Osei Mensah, Ekatherine Prokopiou, Andreas Sarantopoulos, Naveen Thacker, Joseph Haddad, Zoi Dorothea Pana
Invasive fungal diseases (IFDs) in neonates and the paediatric population pose a global challenge due to the difficult estimation of true burden, under-reported mortality rates, diagnostic difficulties and limited therapeutic options, particularly in resource-limited settings. The current state is further complicated by the rising antifungal resistance (AFR). There is also a lack of inclusivity in paediatric antifungal research trials, often resulting in extrapolation of research data obtained from adult populations, despite differences in pharmacokinetic and pharmacodynamic (PK/PD) parameters. Although this approach is not inherently inappropriate, it is not applicable in the setting of pediatric antifungal medication since disease pathophysiology and exposure–response relationships are not comparable between neonates and adults. This report synthesises the current evidence available for new antifungals in children and neonates, summarising available trial data (including PK/PD and any efficacy signals) and real-world observations to define present gaps and immediate priorities. The search strategy, eligibility criteria and data-extraction approach are set out in the Scope and Methodology section; the records identified were too few and too heterogeneous to pool, and the evidence was therefore synthesised qualitatively rather than by meta-analysis. The International Pediatric Association (IPA) Working Group proposes an urgent adoption of an ‘AMR–AFR paediatric ACCELERATE framework’, a synthesis of existing paediatric drug-development instruments adapted to antifungal agents and given defined implementation steps and measurable indicators, to guide policy, research, and regulatory strategies. This framework recommends improving awareness through the engagement of national and international stakeholders to estimate the true burden of IFD and AFR, prioritise early inclusion of paediatric populations in antifungal development, invest in child-appropriate formulations for antifungals, and increase access to diagnostic testing including resistance detection with the establishment of referral laboratories, real-world data integration, engagement of regulatory and industry stakeholders, prioritising high-burden regions for capacity building and use of modern technologies like artificial intelligence to bridge the gaps in AFR research.
