@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 {1416, title = {Coxsackievirus A24 Causing Acute Conjunctivitis in a 2023 outbreak in Vietnam.}, journal = {Int J Infect Dis}, year = {2024}, month = {2024 Jun 12}, pages = {107133}, abstract = {

OBJECTIVES: To determine the causative pathogen during the 2023 conjunctivitis outbreak in Vietnam METHODS: RNA-sequencing was used to identify pathogens before and during the outbreak.

RESULTS: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak.

CONCLUSIONS: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

}, issn = {1878-3511}, doi = {10.1016/j.ijid.2024.107133}, author = {Tran, Huy and Hạ, Thảo and Hoang, Linh and Tran, Yen and Ruder, Kevin and Zhong, Lina and Chen, Cindi and Liu, YuHeng and Yu, Danny and Abraham, Thomas and Hinterwirth, Armin and Deiner, Michael and Porco, Travis C and Lietman, Thomas M and Doan, Thuy and Seitzman, Gerami D} } @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 {1396, title = {Human Conjunctival Transcriptome in Acanthamoeba Keratitis: An Exploratory Study.}, journal = {Cornea}, year = {2024}, month = {2024 May 21}, abstract = {

PURPOSE: The purpose of this study was to identify conjunctival transcriptome differences in patients with Acanthamoeba keratitis compared with keratitis with no known associated pathogen.

METHODS: The host conjunctival transcriptome of 9 patients with Acanthamoeba keratitis (AK) is compared with the host conjunctival transcriptome of 13 patients with pathogen-free keratitis. Culture and/or confocal confirmed Acanthamoeba in 8 of 9 participants with AK who underwent metagenomic RNA sequencing as the likely pathogen. Cultures were negative in all 13 cases where metagenomic RNA sequencing did not identify a pathogen.

RESULTS: Transcriptome analysis identified 36 genes differently expressed between patients with AK and patients with presumed sterile, or pathogen-free, keratitis. Gene enrichment analysis revealed that some of these genes participate in several biologic pathways important for cellular signaling, ion transport and homeostasis, glucose transport, and mitochondrial metabolism. Notable relatively differentially expressed genes with potential relevance to Acanthamoeba infection included CPS1, SLC35B4, STEAP2, ATP2B2, NMNAT3, and AKAP12.

CONCLUSIONS: This research suggests that the local transcriptome in Acanthamoeba keratitis may be sufficiently robust to be detected in the conjunctiva and that corneas infected with Acanthamoeba may be distinguished from the inflamed cornea where no pathogen was identified. Given the low sensitivity for corneal cultures, identification of differentially expressed genes may serve as a suggestive transcriptional signature allowing for a complementary diagnostic technique to identify this blinding parasite. Knowledge of differentially expressed genes may also direct investigation of disease pathophysiology and suggest novel pathways for therapeutic targets.

}, issn = {1536-4798}, doi = {10.1097/ICO.0000000000003545}, author = {Seitzman, Gerami D and Keenan, Jeremy D and Lietman, Thomas M and Ruder, Kevin and Zhong, Lina and Chen, Cindi and Liu, YuHeng and Yu, Danny and Abraham, Thomas and Hinterwirth, Armin and Doan, Thuy} } @article {1571, title = {Seroepidemiology of trachoma in a low prevalence region receiving annual mass azithromycin distribution in Maradi, Niger.}, journal = {PLoS Negl Trop Dis}, volume = {18}, year = {2024}, month = {2024 Dec 09}, pages = {e0012727}, abstract = {

BACKGROUND: Trachoma programs use the indicator trachomatous inflammation--follicular (TF) to monitor indication for and response to treatment for trachoma at the district level. Alternative indicators, including serologic markers, are increasingly being evaluated for trachoma surveillance. We evaluated seroprevalence of IgG antibodies to the Pgp3 antigen in two districts in Maradi, Niger thought to have low TF prevalence.

METHODS: Data were collected as part of the baseline assessment of the Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) trial in September 2021. A random sample of 80 communities was selected from Mayahi and Guidan Roumdji districts, both of which had TF prevalence <20\% at their most recent trachoma impact survey in 2018. A random sample of 50 children per community was sampled. We collected field grades, conjunctival swabs for processing PCR for ocular Chlamydia trachomatis, and dried blood spots for serologic assessment.

RESULTS: Of 3,994 children sampled in 80 communities, 49\% were female and median age was 4 years. Overall TF prevalence was 4.6\% (95\% CI 3.5 to 5.8\%) and trachomatous inflammation-intense (TI) prevalence was 0.6\% (95\% 0.3 to 0.9\%). The prevalence of ocular chlamydia was 0.03\% (95\% CI 0.08\%). Seroprevalence for Pgp3 antibodies was 6.3\% (95\% CI 5.5 to 7.1\%) in 1-9-year-olds and 3.7\% (95\% CI 2.9 to 4.4\%) in 1-5-year-olds. TF and Pgp3 seroprevalence were better correlated in 1-5-year-olds (correlation coefficient 0.29) compared to 1-9-year-olds (correlation coefficient 0.09).

CONCLUSIONS: In this low trachoma prevalence setting in Niger, seroprevalence of antibodies to Pgp3 were consistent with little ongoing transmission of C. trachomatis.

}, issn = {1935-2735}, doi = {10.1371/journal.pntd.0012727}, author = {Amza, Abdou and Kadri, Boubacar and Nassirou, Beido and Arzika, Ahmed and Gebreegziabher, Elisabeth and Hu, Huiyu and Zhong, Lina and Chen, Cindi and Yu, Danny and Abraham, Thomas and Liu, YuHeng and Wickens, Karana and Doan, Thuy and Martin, Diana and Arnold, Benjamin F and Lietman, Thomas M and Oldenburg, Catherine E} } @article {1351, title = {Comprehensive Profile of Pathogens and Antimicrobial Resistance in Conjunctivitis Cases from Niger.}, journal = {Am J Trop Med Hyg}, volume = {109}, year = {2023}, month = {2023 Dec 06}, pages = {1333-1338}, abstract = {

Infectious conjunctivitis outbreaks remain a public health burden. This study focuses on the pathogen and antimicrobial resistance (AMR) profiles identified in Niger. Sixty-two patients with acute infectious conjunctivitis who presented to health posts were enrolled from December 2021 to May 2022. Nasal and conjunctival swabs were obtained from each patient. Unbiased RNA deep sequencing (RNA-seq) was used to identify associated pathogens. A pathogen was identified in 39 patients (63\%; 95\% CI, 50-74). Of those, an RNA virus was detected in 23 patients (59\%; 95\% CI, 43-73). RNA viruses were diverse and included human coronaviruses (HCoVs): SARS-CoV-2, HCoV-229E, HCoV-HKU1, and HCoV-OC43. A DNA virus was identified in 11 patients (28\%; 95\% CI, 17-44). Of those, four patients had a coinfection with an RNA virus and two patients had a coinfection with both an RNA virus and a bacterium. DNA viruses were predominantly human herpesvirus (cytomegalovirus, Epstein-Barr virus, human herpesvirus 8) and human adenovirus species B, C, and F. Eighteen patients (46\%; 95\% CI, 32-61) had a bacteria-associated infection that included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Antimicrobial resistance determinants were detected in either the conjunctiva or nasal samples of 20 patients (32\%; 95\% CI, 22-45) and were found to be more diverse in the nose (Shannon alpha diversity, 1.12 [95\% CI, 1.05-1.26] versus 1.02 [95\% CI, 1.00-1.05], P = 0.01). These results suggest the potential utility of leveraging RNA-seq to surveil pathogens and AMR for ocular infections.

}, issn = {1476-1645}, doi = {10.4269/ajtmh.23-0498}, author = {Amza, Abdou and Nassirou, Beido and Kadri, Boubacar and Ali, Saley and Mariama, Boubacar and Ibrahim, Ciss{\'e} Mamadou and Roufaye, Lamine Aboubacar and Lebas, Elodie and Colby, Emily and Zhong, Lina and Chen, Cindi and Ruder, Kevin and Yu, Danny and Liu, YuHeng and Abraham, Thomas and Chang, Aaron and Mai, Lina and Hinterwirth, Armin and Seitzman, Gerami D and Lietman, Thomas M and Doan, Thuy} } @article {1411, title = {Pathogen Profiles of Infectious Conjunctivitis in Ho Chi Minh City, Vietnam.}, journal = {Cornea Open}, volume = {2}, year = {2023}, month = {2023 Dec}, abstract = {

PURPOSE: Conjunctivitis epidemics and pandemics remain a global burden. This study aims to comprehensively identify pathogens associated with conjunctivitis in Vietnam.

METHODS: Patients with acute conjunctivitis presented to an outpatient clinic in Ho Chi Minh City, Vietnam, were enrolled from September 2022 to March 2023. Swabs were obtained from conjunctiva and anterior nares of all patients. Unbiased RNA deep sequencing (RNA-seq) was used to identify any replicating pathogens in the samples.

RESULTS: Samples from 35 patients were analyzed. A pathogen was identified in 80\% of the patients. 72\% (95\% confidence interval: 54\% to 85\%) were infected with either HAdV-D or HAdV-B. RNA viruses detected were rhinoviruses and human coronavirus 229E. Bacteria etiologies included , , and One patient had co-infection of rhinovirus A and HAdV-B. , a fungus, was identified in one patient. Corneal sub-epithelial infiltrates, pseudomembranes, or pre-auricular lymphadenopathy were not reported in any patient.

CONCLUSIONS: Human adenoviruses are the common circulating pathogens associated with infectious conjunctivitis in Vietnam. HAdV species, however, appear to vary between geographic locations within Vietnam. Other under-recognized pathogens identified in this study, such as RNA viruses, suggest broader pathogen surveillance may be beneficial.

}, issn = {2833-6992}, doi = {10.1097/coa.0000000000000025}, author = {Tran, Huy and Hoang, Linh and Tran, Yen and Hạ, Thảo and Ruder, Kevin and Zhong, Lina and Chen, Cindi and Yu, Danny and Liu, YuHeng and Abraham, Thomas and Hinterwirth, Armin and Deiner, Michael and Porco, Travis and Lietman, Thomas M and Seitzman, Gerami D and Doan, Thuy} } @article {1356, title = {Pathogen Surveillance for Acute Infectious Conjunctivitis.}, journal = {JAMA Ophthalmol}, year = {2023}, month = {2023 Nov 02}, abstract = {

IMPORTANCE: Acute infectious conjunctivitis is a common ocular condition with major public health consequences.

OBJECTIVE: To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded.

MAIN OUTCOMES AND MEASURES: Pathogens were identified by unbiased RNA deep sequencing.

RESULTS: In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60\%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62\% (32 of 52) of patients presented with purulent discharge, while only 8\% (4 of 52) of patients had confirmed bacterial pathogens.

CONCLUSION AND RELEVANCE: In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.

}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2023.4785}, author = {Tsui, Edmund and Sella, Ruti and Tham, Vivien and Kong, Alan W and McClean, Esmeralda and Goren, Lee and Bahar, Irit and Cherian, Nina and Ramirez, Joana and Hughes, Reginald E and Privratsky, Joseph K and Onclinx, Tania and Feit-Leichman, Rachel and Cheng, Angel and Molina, Iliana and Kim, Phillip and Yu, Carol and Ruder, Kevin and Tan, Alexander and Chen, Cindi and Liu, YuHeng and Abraham, Thomas and Hinterwirth, Armin and Zhong, Lina and Porco, Travis C and Lietman, Thomas M and Seitzman, Gerami D and Doan, Thuy} }