@article {1596, title = {Comparison of antimicrobial resistance genes on the ocular surface of patients with corneal infections in California and Malawi.}, journal = {Int Health}, year = {2025}, month = {2025 Apr 29}, abstract = {

BACKGROUND: Antimicrobial resistance (AMR) determinants on the ocular surface may contribute to poor treatment responses.

METHODS: An exploratory comparative analysis of ocular surface AMR determinants, as determined by RNA-sequencing (RNA-seq), on patients presenting with corneal infections at the Proctor Medical Clinic at the University of California San Francisco in San Francisco, CA, USA, and the Queen Elizabeth Central Hospital at the Department of Ophthalmology of Kamuzu College of Health Sciences in Blantyre, Malawi, was conducted. All patients underwent swabbing of three sites on the ocular surface: cornea, ipsilateral conjunctiva, and contralateral conjunctiva.

RESULTS: Mutations conferring macrolide resistance were present on the ocular surface in 58\% (95\% CI 44 to 71\%) of the participants in Malawi and 32\% (95\% CI 20 to 46\%) of the participants in San Francisco. Aminoglycosides resistance genes were also common on the ocular surface with 58\% (95\% CI 44 to 71\%) prevalence in Malawi and 21\% (95\% CI 12 to 35\%) in San Francisco. AMR was associated with poorer visual outcomes in a subset of patients.

CONCLUSIONS: As determined by RNA-seq, ocular surface AMR gene mutations are common in patients with infectious keratitis. Surveillance may be important for infectious keratitis treatment selection as well as providing guidance for antibiotic stewardship.

}, issn = {1876-3405}, doi = {10.1093/inthealth/ihaf042}, author = {Seitzman, Gerami D and Kalua, Khumbo and Misanjo, Esther S and Chen, Cindi and Ouimette, Kevin and Zhong, Lina and Liu, YuHeng and Yu, Danny and Abraham, Thomas and Wu, Nathaniel and Yan, Daisy and Lietman, Thomas M and Hinterwirth, Armin and Doan, Thuy} } @article {1456, title = {Association of weather variables with pathogens contributing to conjunctivitis worldwide.}, journal = {Clin Infect Dis}, year = {2024}, month = {2024 Aug 19}, abstract = {

PURPOSE: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally.

METHODS: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus).

RESULTS: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95\% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95\% CI: 0.46 to 0.82, P\<0.001). Relative humidity (\%) was associated with increased odds of RNA virus infections (OR=2.64, 95\% CI: 1.51 to 4.61, P\<0.001), and fungal infections (OR=2.35, 95\% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95\%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95\% CI: 0.25 to 0.71, P\<0.001). Temperature ({\textdegree}C) was not associated with ocular infections for any pathogen type.

CONCLUSIONS: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

}, issn = {1537-6591}, doi = {10.1093/cid/ciae417}, author = {Yan, Daisy and Prajna, N Venkatesh and Lalitha, Prajna and Sansanayudh, Wiwan and Satitpitakul, Vannarut and Laovirojjanakul, Wipada and Chaudhary, Meenu and Bountogo, Mamadou and Sie, Ali and Coulibaly, Boubacar and Amza, Abdou and Nassirou, Beido and Almou, Ibrahim and Tran, Huy and Tran, Yen and Tsui, Edmund and Onclinx, Tania and Sella, Ruti and Goren, Lee and McClean, Esmeralda and Tham, Vivien and Chen, Cindi and Ruder, Kevin and Zhong, Lina and Liu, YuHeng and Yu, Danny and Abraham, Thomas and Lebas, Elodie and Arnold, Benjamin F and McLeod, Stephen D and Deiner, Michael S and Porco, Travis C and Seitzman, Gerami D and Lietman, Thomas M and Shantha, Jessica and Hinterwirth, Armin and Doan, Thuy} } @article {1436, title = {Etiologies of Infectious Keratitis in Malawi.}, journal = {Am J Trop Med Hyg}, year = {2024}, month = {2024 Jul 16}, abstract = {

Infectious keratitis is a leading cause of corneal blindness worldwide with little information known about causative etiologies in Malawi, Africa. This area is resource-limited with ophthalmologist and microbiology services. The Department of Ophthalmology at the Kamuzu College of Health Sciences in Blantyre, Malawi, is a participating site of an international corneal ulcer consortium, capriCORN (Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory-markers in the CORNea). In this study, 50 patients with corneal ulcers were swabbed for pathogen identification using RNA-sequencing. Corneal trauma was reported in 41\% and 19\% of the patients worked in agriculture. A pathogen was identified in 58\% of the cases. Fungal pathogens predominated, followed by viruses and bacteria. Aspergillus, Fusarium, HSV-1, and Gardnerella were the most common pathogens detected. 50\% of patients reported treatment with an antibiotic before presentation. Pathogens unusual for infectious keratitis, such as Subramaniula asteroids, Aureobasidium pullulans, and Gardnerella vaginalis, were also detected.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.24-0149}, author = {Kalua, Khumbo and Misanjo, Esther S and Lietman, Thomas M and Ruder, Kevin and Zhong, Lina and Chen, Cindi and Liu, YuHeng and Yu, Danny and Abraham, Thomas and Wu, Nathaniel and Yan, Daisy and Hinterwirth, Armin and Doan, Thuy and Seitzman, Gerami D} } @article {1381, title = {Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).}, journal = {PLoS Med}, volume = {21}, year = {2024}, month = {2024 May}, pages = {e1004386}, abstract = {

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting.

METHODS AND FINDINGS: The Macrolide Oraux pour R{\'e}duire les D{\'e}c{\`e}s avec un Oeil sur la R{\'e}sistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95\% CI 1.5 to 3.51, Punadj \< 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95\% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95\% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability.

CONCLUSIONS: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored.

TRIAL REGISTRATION: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

}, keywords = {Anti-Bacterial Agents, Azithromycin, Child Mortality, Child, Preschool, Drug Resistance, Bacterial, Female, Humans, Infant, Macrolides, Male, Mass Drug Administration, Niger}, issn = {1549-1676}, doi = {10.1371/journal.pmed.1004386}, author = {Arzika, Ahmed M and Abdou, Amza and Maliki, Ramatou and Beido, Nassirou and Kadri, Boubacar and Harouna, Abdoul N and Galo, Abdoul N and Alio, Mankara K and Lebas, Elodie and Oldenburg, Catherine E and O{\textquoteright}Brien, Kieran S and Chen, Cindi and Zhong, Lina and Zhou, Zhaoxia and Yan, Daisy and Hinterwirth, Armin and Keenan, Jeremy D and Porco, Travis C and Lietman, Thomas M and Doan, Thuy} }