Jeremy David Keenan

Trachoma is the leading infectious cause of blindness worldwide and is targeted for global elimination as a public health problem by 2030. As we approach this target, defining when population-level trachoma control interventions can be stopped, and determining how post-intervention surveillance should be performed, are becoming increasingly important. Molecular diagnosis of ocular Chlamydia trachomatis (Ct) using polymerase chain reaction (PCR) provides a highly sensitive and specific indicator of infection, yet there are currently no programmatic guidelines based on Ct infection. We assembled 86 cross-sectional surveys of ocular Ct infection from 13 countries, representing data from 46,914 children aged 1-5 years. Our analyses suggest that infection prevalence of 0.81% in this age group corresponds to a threshold below which population-level interventions can be stopped with at least 90% confidence. Correspondingly, with confidence exceeding 90%, we propose that interventions should continue when infection prevalence is greater than 1.99%. Interpretation of infection surveillance data is a generalisable challenge in low-prevalence settings for many infectious diseases. This study proposes a robust framework for how Ct infection surveillance could support accurate population-level assessments of trachoma endemicity and could allow a step-change in decision-making precision for programmes as we approach the endgame for trachoma elimination.

Purpose: To review recent advances in the diagnosis and management of acanthamoeba keratitis (AK), emphasizing clinically relevant developments from the past 5 years. Methods: A scoping review of PubMed and ClinicalTrials.gov was conducted for studies published between July 2020 and December 2025 using the terms “acanthamoeba AND (diag* OR test* OR treatment).” Clinical studies and studies of human AK specimens were prioritized. A total of 814 publications and 11 clinical trial listings were screened, with 128 full-text articles reviewed. Results: Recent diagnostic advances included artificial intelligence models developed for in vivo confocal microscopy images and anterior segment photographs. Polymerase chain reaction (PCR) assays demonstrated sensitivity similar to or greater than culture while maintaining high specificity. Emerging modalities included next-generation sequencing, viability PCR assays, and antibody-based diagnostics. Recent studies on acanthamoeba treatment include the Orphan Drug for Acanthamoeba Keratitis (ODAK) trial, which randomized eyes to polyhexamethylene biguanide (PHMB) 0.08% monotherapy or PHMB 0.02% plus propamidine 0.1% combination therapy, and found similar 12-month cure rates and visual outcomes in the two groups, and better-than-expected outcomes using a standardized protocol. Adjunctive therapies including topical voriconazole, Rose Bengal Photodynamic Antimicrobial Therapy, miltefosine, and povidone-iodine showed potential benefit, although evidence was limited primarily to observational studies and small clinical trials. Surgical management strategies, including penetrating and lamellar keratoplasty, demonstrated variable recurrence rates, and the optimal timing of keratoplasty remains uncertain. Conclusions: New diagnostic technologies and standardized PHMB-based treatment protocols may improve outcomes for AK. Evidence is more limited for a range of other potential therapies.

The aim of this study was to determine the antiamoebic efficacy of povidone-iodine when used as an adjunct to topical biguanide therapy for Acanthamoeba keratitis. Patients with smear- or culture-positive Acanthamoeba keratitis received topical chlorhexidine 0.04%, half-hourly for 2 days, then hourly for days 3–6, then eight times per day for days 7–28. Participants were randomized in a 1:1 ratio to receive either adjunctive topical povidone-iodine at the same frequency as chlorhexidine or no additional therapy (i.e., control group). Povidone-iodine was initially administered as a 2.5% solution but was reduced to a 1% solution after several reports of intolerance. The primary outcome was Acanthamoeba growth from the culture of corneal scrapings at 1, 2, and 4 weeks after randomization, as assessed by laboratory staff masked to treatment allocation. Of 49 patients enrolled, 25 were randomized to adjunctive povidone-iodine (mean age 48 [SD 16] years; 32% female) and 24 to control (mean age 43 [15] years; 33% female). Four (16%) participants discontinued 2.5% povidone-iodine prematurely due to intolerance. The proportion of participants with a positive culture during the initial 4 weeks of antiamoebic treatment was not significantly different in the povidone-iodine group (6/18 [33%] at 4 weeks) and control group (5/16 [31%] at 4 weeks) (RR 0.90, 95%CI: 0.35–2.29; P = 0.82). When used as an adjunctive to standard biguanide therapy, povidone-iodine did not markedly accelerate the clearance of Acanthamoeba organisms from the corneal surface over the initial month of therapy. This study is registered with ClinicalTrials.gov as NCT03484507 .

Programmatic decisions regarding surveillance and intervention for trachoma are made at the district level, reflecting an implicit assumption that transmission within districts is sufficiently homogeneous. However, as trachoma transmission declines, residual pockets of transmission may become spatially heterogeneous at sub-district scales. Using cluster-level data from 12 districts in Amhara, Ethiopia (2019–2023), we assess the spatial structure of Pgp3 antibody responses, a sensitive measure of infection transmission. Spatial clustering was evident in higher prevalence districts but diminished as populations approach elimination. We show that as districts approach elimination sub-district heterogeneity disappears, and district-level summaries are likely sufficient to guide decision-making.

The spread of antibiotic resistance is a major concern in the setting of azithromycin mass drug distribution for childhood mortality. We performed long-read whole-genome sequencing and phenotypic resistance analysis on Streptococcus pneumoniae isolated from the nasopharynx of Nigerien children from communities treated with either six twice-yearly azithromycin distributions or placebo. Here, we showed that co-selection for macrolide, tetracycline, and trimethoprim-sulfamethoxazole genetic resistance was detected with repeated azithromycin mass drug distributions. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT02047981 .

Large-scale, placebo-controlled, cluster-randomized trials in high-mortality settings in sub-Saharan Africa demonstrated a 14–18% reduction in childhood mortality following twice-annual mass drug administration (MDA) of azithromycin among children aged 1–59 months. Azithromycin MDA also selected for antimicrobial resistance (AMR), particularly macrolide resistance. It is unknown whether the AMR from azithromycin MDA could spill over to neighboring untreated populations. If present, such geographic spillover effects could lead trials to underestimate AMR risks. We assess between-village geographic spillover effects of genotypic macrolide resistance using metagenomic deep sequencing in rectal swabs collected from 300 children in 30 monitoring villages in Niger after two years of MDA in 594 surrounding villages. Conditional permutation tests assess associations between proximal azithromycin treatment intensity and resistance gene abundance. We find no evidence of geographic spillover of macrolide resistance in untreated villages, as the genetic load of AMR remains at baseline levels in placebo-treated villages regardless of surrounding azithromycin treatment intensity (Spearman ρ = −0.05, P = 0.83). Sensitivity analyses confirm robustness across metrics, and no spillover effects are detected for other antibiotic classes. Azithromycin MDA-induced macrolide resistance appears localized to treated villages, mitigating some concerns about geographic spillover of AMR to nearby untreated villages at 24 months.

: The community-randomized, placebo-controlled Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial revealed that biannual mass azithromycin distributions to preschool children reduced child mortality in sub-Saharan Africa. Other benefits may also be possible. Surveillance of local health post records was assessed from the Niger study site from 2014 to 2016. Community-level data on all clinic visits, diagnoses, and antibiotic prescriptions recorded in the health post logbooks were retrospectively extracted for the period spanning from 12 months before baseline to 12 months after baseline. During the 12-month period after the communities were randomized in the MORDOR trial, a total of 5,229 clinic visits were documented in the azithromycin group, compared with 7,647 in the placebo group (incidence rate ratio [IRR]: 0.82; 95% CI: 0.79–0.85); 2,011 malaria diagnoses were documented in the azithromycin group, compared with 3,366 in the placebo group (IRR: 0.71; 95% CI: 0.46–1.39); and 2,218 courses of antibiotics were documented in the azithromycin group, compared with 3,297 in the placebo group (IRR: 0.81; 95% CI: 0.77–0.85). The reduction in clinic visits and clinic-prescribed antibiotics is consistent with a reduction in infectious diseases in the azithromycin-treated communities.