Comprehensive Profile of Pathogens and Antimicrobial Resistance in Conjunctivitis Cases from Niger

Abdou Amza Programme Nationale de Santé Oculaire, Niamey, Niger;

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Beido Nassirou Programme Nationale de Santé Oculaire, Niamey, Niger;

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Boubacar Kadri Programme Nationale de Santé Oculaire, Niamey, Niger;

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Saley Ali Programme Nationale de Santé Oculaire, Niamey, Niger;

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Boubacar Mariama Programme Nationale de Santé Oculaire, Niamey, Niger;

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Cissé Mamadou Ibrahim Programme Nationale de Santé Oculaire, Niamey, Niger;

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Lamine Aboubacar Roufaye Programme Nationale de Santé Oculaire, Niamey, Niger;

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Elodie Lebas Francis I. Proctor Foundation, University of California, San Francisco, California;

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Emily Colby Francis I. Proctor Foundation, University of California, San Francisco, California;

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Lina Zhong Francis I. Proctor Foundation, University of California, San Francisco, California;

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Cindi Chen Francis I. Proctor Foundation, University of California, San Francisco, California;

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Kevin Ruder Francis I. Proctor Foundation, University of California, San Francisco, California;

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Danny Yu Francis I. Proctor Foundation, University of California, San Francisco, California;

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YuHeng Liu Francis I. Proctor Foundation, University of California, San Francisco, California;

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Thomas Abraham Francis I. Proctor Foundation, University of California, San Francisco, California;

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Aaron Chang Francis I. Proctor Foundation, University of California, San Francisco, California;

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Lina Mai Francis I. Proctor Foundation, University of California, San Francisco, California;

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Armin Hinterwirth Francis I. Proctor Foundation, University of California, San Francisco, California;

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Gerami D. Seitzman Francis I. Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;

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Thomas M. Lietman Francis I. Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
Department of Epidemiology and Biostatistics, University of California, San Francisco, California;
Institute for Global Health Sciences, University of California, San Francisco, California

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Thuy Doan Francis I. Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;

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on behalf of the Seasonal Conjunctivitis Outbreak Reporting for Prevention and Improved Outcomes (SCORPIO) Study Group

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.

INTRODUCTION

Conjunctivitis is a feature of many infectious disease outbreaks, and recognition of the ocular signs and symptoms is critical in minimizing the spread of the disease.1,2 In the United States and the developing world, outpatient conjunctivitis is thought to be predominantly viral in etiology.3 In this setting, the appropriate clinical management is hand hygiene, limitation of social contacts, and conservative care without antimicrobials. In other parts of the world, such as Burkina Faso, a sub-Saharan African country, the pathogen profile is more diverse and, in some cases, antimicrobials may be appropriate and even lifesaving.4 Thus, the general call to curb antibacterial treatment of acute infectious conjunctivitis to minimize antimicrobial resistance (AMR) may need to be reinterpreted within both social and geographic contexts.3,5,6

Niger is a low- to middle-income country in West Africa that borders Burkina Faso. It has a high burden of morbidity and mortality, and mass drug distributions for infectious diseases are common.79 The country has a health system to provide some essential health care, including conjunctivitis. However, because accessibility to laboratory testing is limited, the microbial characterization of pathogens associated with acute conjunctivitis is sparse for Niger. In this context, we aimed to determine 1) the signs and symptoms, and 2) the pathogen profile associated with acute infectious conjunctivitis. Furthermore, we characterized the existing AMR determinants, or resistome, in patients at the individual level, demonstrating the potential utility of pathogen detection and concurrent passive AMR surveillance.

MATERIALS AND METHODS

Study design and setting.

Study inclusion criteria included symptoms of presumed infectious conjunctivitis within 14 days. Exclusion criteria included presumed allergic, medication-related conjunctivitis or refusal to provide consent. All participating health-care personnel were trained in the swabbing protocol prior to study initiation. All patients presenting to the outpatient ophthalmology service at Niamey National Hospital who met the study criteria were enrolled, examined, and underwent sample collection during the same visit. Ethical approval from the institutional review board of the University of California, San Francisco and the ethical committee of the Niger Ministry of Health was obtained. This study adhered to the tenets of the Declaration of Helsinki. Written consent from participants 18 years and older was obtained. Guardians provided consent for children younger than 18 years of age. No incentives were offered for participating in this study.

Sample collection and management.

Sterile polyester applicators (Puritan) were used to obtain three swabs (two conjunctival swabs and one swab for both anterior nares). The swabs were then stored in DNA/RNA-Shield (Zymo Research, Irvine, CA) and transferred to a –80°C freezer until shipment back to the University of California, San Francisco for long-term storage until sample processing.4,10

Sample processing and bioinformatics.

All samples were de-identified and processed in a random manner. RNA deep sequencing (RNA-seq) library preparation, sequencing, and bioinformatics analyses for pathogen detection and AMR have been described previously.10 Briefly, 5 µL of extracted RNA from each sample was converted to complementary DNA, and sequencing libraries were prepared using the NEBNext ULTRA II RNA Library Prep Kit for Illumina (New England Biolabs, Ipswich, MA). The samples were sequenced using a NovaSeq 6000 system (Illumina, San Diego, CA) with 150-nucleotide paired-end sequencing.

Host reads were removed, with the remaining nonhost reads filtered for quality. Those nonhost reads passing the quality filter were aligned 1) to an entire National Center for Biotechnology Information nonredundant collection database for pathogen detection and 2) to the MEGARes reference antimicrobial database (version 1.0.1), using the Burrows-Wheeler Aligner with default settings.11 As bacteria colonize the nares, only viruses were considered for nasal samples to minimize overinterpretation. Matched antimicrobial genetic resistance determinants were grouped at the class level and subjected to further statistical analyses.12 Shannon alpha diversities were compared by permutation testing using R (version 3.5; R Foundation for Statistical Computing, Vienna, Austria).13 Ninety-five percent CIs (95% CI) were acquired using the adjusted Wald method. Figures were generated using Prism (version 10.0.3; GraphPad Software, Boston, MA).

RESULTS

Table 1 summarizes the demographics of the 62 patients enrolled in the 6-month period from December 2021 to May 2022. Of these patients, 33 were female (57%). The mean age was 24 ± 21 years (SD) and a mean onset of symptoms of 5 ± 3 days. Documented ocular symptoms included purulent discharge (60%; 95% CI, 47–71), itching (40%; 95% CI, 29–53), and tearing (30%; 95% CI, 19–42). On examination, bilateral subepithelial infiltrates were noted in 80% of patients (95% CI, 64–85). Coughing was the most common systemic finding (23%; 95% CI, 14–35), followed by rhinorrhea (16%; 95% CI, 9–27), and sore throat (7%; 95% CI, 2–16). Twenty-one percent of patients (95% CI, 11–36) reported having personal contact with individuals with similar signs and symptoms.

Table 1

Demographics and clinical signs and symptoms of enrolled patients

Demographic Clinical sign n* % 95% CI
Sex
 Female 33 57
 Male 25 43
Age, years ± SD 24 ± 21
Duration of symptoms, days 5 ± 3
Ocular symptoms Purulent discharge 37/62 60 47–71
Itching 25/62 40 29–53
Tearing 18/61 30 19–42
Examination findings Bilateral 47/62 80 64–85
Subepithelial infiltrates 0/60 0 0–5
Membranes 0/61 0 0–5
Preauricular lymphadenopathy 0/59 0 0–5
Systemic findings Sore throat 4/59 7 2–16
Runny nose 10/62 16 9–27
Cough 14/61 23 14–35
Contacts similarly affected Yes 9/42 21 11–36
Presented on antibiotic drop§ Yes 9/62 13 8–26

Or n/N.

Adjusted Wald method.

Sex known for 58 of 62 participants.

Antibiotic eyedrops known at presentation. An additional seven patients were on eyedrops of unknown name.

A combined 186 samples (62 nasal and 124 conjunctiva) were processed for RNA-seq. An associated pathogen was identified in 39 patients (63%; 95% CI, 50–74) and could be grouped into three categories: bacteria, DNA viruses, and RNA viruses (Figure 1A). Of those that were positive, RNA pathogens predominated and were detected in 59% of patients (23 of 39 patients; 95% CI, 43–73). Human coronaviruses (HCoVs) were detected in nine patients and included both the alpha (HCoV-229E) and beta (HCoV-OC43, HCoV-HKU1, and SARS-CoV-2) genera. Of the two patients with SARS-CoV-2–associated conjunctivitis, one 33-year-old woman presented with unilateral eye involvement with respiratory involvement (coughing and sore throat), whereas the other patient was a 13-year-old girl with bilateral eye involvement and no respiratory symptoms. Other viruses included rubella, rhinovirus A and C, rotavirus A, and human respirovirus 1.

Figure 1.
Figure 1.

Summary of pathogen profiles and genetic resistance determinants for nasal and conjunctival samples. (A) Stacked bar graph of pathogens identified for nasal samples (left) and conjunctival samples (right). (B) Heatmaps of normalized reads of genetic resistance determinants for each antibiotic class. Each row represents the reads per million matched reads (rM) for the nasal sample (left panel) and a conjunctival sample of a patient (right panel). CMV = cytomegalovirus; EBV = Epstein–Barr virus; HAdV = human adenovirus; HCoV = human coronavirus; HHV = human herpesvirus; MLS = macrolides, lincosamides, and streptogramins.

Citation: The American Journal of Tropical Medicine and Hygiene 109, 6; 10.4269/ajtmh.23-0498

The majority of the DNA viruses fell into two different pathogen types: human adenovirus (HAdV) and human herpesvirus (HHV). Unlike the United States and India, where HAdV species D is commonly associated with acute conjunctivitis, HAdV-B, -C, and -F were detected in our Nigerien patient population. Of the human herpesviruses, cytomegalovirus, Epstein–Barr virus, and HHV-8 (Kaposi sarcoma herpesvirus) were detected. Human herpesvirus 8 was detected on the conjunctiva of a 73-year-old woman who presented with a 10-day onset of bilateral conjunctivitis. She also reported having a sore throat, rhinorrhea, and coughing. Her nasal sample was positive for rotavirus A. Of the 25 patients with at least one virus identified in the nose (either DNA virus or RNA virus), 36% (95% CI, 20–55) had the same virus identified in their conjunctival samples.

Bacterial infection was identified on the conjunctiva of 18 patients (46%; 95% CI, 32–61) and included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Coinfections were documented in 14 of 39 patients (36%; 95% CI, 23–52), with both bacteria and virus identified in seven patients (18%; 95% CI, 9–32). In addition, four patients with coinfections of DNA and RNA viruses, two patients with multiple RNA viruses, and one patient with a coinfection of different DNA viruses were noted.

Figure 1B summarizes the genetic resistant determinants isolated from nasal and conjunctival swabs. Overall, normalized reads of genetic determinants of resistance to different antibiotic classes varied across each patient and were detected most commonly in the elfamycin, fluconazole, and tetracycline classes. The prevalence of at least one class of genetic resistance determinants was greater in nasal samples compared with conjunctival samples (27% [95% CI, 18–40] versus 6% [95% CI, 3–15], P = 0.003). Diversity of genetic determinants was also greater for nasal samples compared with conjunctival samples (Shannon alpha diversity, 1.12 [95% CI, 1.05–1.26] versus 1.02 [95% CI, 1.00–1.05], P = 0.01). Of the nine patients who presented on antibiotic eyedrops, none was found to have detectable AMR determinants in their conjunctival samples. However, the duration of antibiotic use was not documented as part of the clinical assessment.

DISCUSSION

Pathogens associated with conjunctivitis outbreaks are increasingly recognized as being diverse and varying geographically. The advantage of unbiased RNA-seq is the ability to identify any pathogen (bacteria, fungi, parasites, DNA and RNA viruses) in a clinical sample. Here, we used this technology with the aim of monitoring pathogens in patients with acute conjunctivitis while tracking AMR concurrently in the same samples. Overall, we found that viral and bacterial etiologies were common. We also found that the anterior nares and ocular surface are potentially easy-access, less-invasive sites for genomic surveillance of AMR at the individual level in a population undergoing routine mass drug distributions.

Human coronaviruses are a group of enveloped, positive-sense, single-stranded RNA viruses. To date, seven HCoVs have been identified, and they can be divided into two genera: alphacoronavirus and betacoronavirus.14 Of these HCoVs, HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43 generally cause mild respiratory symptoms and conjunctivitis.15,16 SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome-CoV, on the other hand, can cause severe respiratory symptoms.14 Recently, work from the Seasonal Conjunctivitis Outbreak Reporting for Prevention and Improved Outcomes (SCORPIO) study group and others10,1719 have shown that SARS-CoV-2 genomic material can be isolated directly from the conjunctiva of patients with acute conjunctivitis who presented to outpatient clinics. This demonstrates that SARS-CoV-2 can be associated with primary conjunctivitis even without associated respiratory symptoms. In our Nigerien cohort, the common human circulating coronaviruses (HCoV-229E, HCoV-HKU1, and HCoV-OC43) were detected in seven patients. Five patients had bilateral eye involvement and three patients reported respiratory symptoms (coughing, sore throat, or rhinorrhea). Of the two patients with SARS-CoV-2–associated conjunctivitis, only one patient reported respiratory symptoms. This suggests that HCoV may be an important and underappreciated pathogen class for outpatient conjunctivitis in Niger.

We identified two children, 4 and 5 years old, with rubella-associated conjunctivitis. Both children had bilateral eye involvement and coughing as a respiratory complaint. There was no evidence of corneal involvement on examination, although symptom onset at enrollment was only 3 days. Rubella is a positive-sense, single-stranded RNA virus.20,21 It is one of the leading causes of preventable birth defects and is transmitted via airborne droplets.21 Infection during the gestational period can result in birth defects, hearing loss, and blindness. The disease is mild, however, and can occur in children and adults, with the common clinical manifestations of mild fever, transient body rash, and conjunctivitis. In some patients, this initial infection can result in an indolent form of intraocular inflammation because the virus can seed intraocularly and remain in the eye—an immune-privileged site—for quite some time.22 Rubella vaccination is routine in many countries, although it is currently not a component of the childhood vaccination program in Niger.23

Human adenoviruses are nonenveloped, double-stranded DNA viruses and are one of the most frequent etiological agents for respiratory tract infections and acute viral conjunctivitis worldwide.24,25 Human adenoviruses are classified into seven species (A–G) that are subdivided further into genotypes. Conjunctivitis outbreaks are generally associated with various HAdV-D genotypes, although ocular involvement resulting from genotypes HAdV-B, HAdV-C, and HAdV-E have been detected.26 In our study, we detected multiple species (B, C, and F) associated with acute conjunctivitis. This HAdV profile appears more diverse than in neighboring Burkina Faso, although the differences may also be attributed to seasonality or small sample size.4

Various bacteria-associated etiologies of infectious conjunctivitis were also identified. Both gram-negative (H. influenza, H. aegyptius, Klebsiella pneumoniae, and Moraxella spp.) and gram-positive (S. aureus and S. pneumoniae) bacteria were detected. Haemophilus aegyptius was found to be the causative pathogen in a 3-year-old boy who presented with bilateral purulent conjunctivitis. Haemophilus aegyptius was first identified by Koch27 in Egyptian patients with conjunctivitis and was known to cause outbreaks. In the 1980s, H. aegyptius was also associated with Brazilian purpuric fever epidemics during which infected children presented with purulent conjunctivitis that progressed to systemic symptoms including fever, gastrointestinal distress, and purpura fulminans.28 Disease progression is an otherwise previously healthy child is rapid, and death can occur.28 As SCORPIO is a disease surveillance study, and follow-up visits are not included in the study design, it is unknown whether the child with H. aegyptius detected in this study developed systemic sequalae.

Patients with infectious conjunctivitis secondary to bacterial etiologies may benefit from antibiotics or close observation, particularly in children. However, from an antibiotic stewardship standpoint, there is a concern that mass antibiotic distribution may facilitate the spread of antibiotic resistance. Because viral etiology is thought to be predominant in cases of conjunctivitis in the United States, indiscriminate dispensing of antibiotic eyedrops for conjunctivitis in the United States may be inappropriate.3,29,30 However, testing for pathogen identification is not performed routinely for conjunctivitis in any location. Thus, targeted treatment toward definitively identified pathogens is rarely possible. Understanding the baseline prevalence of pathogens and of AMR profiles in these patients may improve decision workflow for patients with infectious conjunctivitis in Niger. In addition, with seasonal malaria chemoprevention during the rainy season in Niger and with the documented increase in consumption of fluoroquinolones and beta-lactams in the region, there is additional motivation to quantify local pathogen resistance patterns.3133 In our study, we found the prevalence of AMR determinants was greater in the anterior nares than in the conjunctiva. In addition, the nasal resistome was more diverse than the ocular surface resistome. One nasal sample from a 15-day-old baby boy with Moraxella catarrhalis–associated bilateral conjunctivitis harbored genetic resistance from eight classes of antibiotics (aminocoumarins, aminoglycosides, lipopeptides, macrolides, multidrug resistance, phenicol, sulfonamides, and trimethoprim). The patient did not present on antibiotic eyedrops. Thus, it may be that he was exposed to antibiotics during the gestational period or shortly thereafter. These results suggest the anterior nares may be a minimally invasive site for the detection of AMR.

The strengths of our study include the use of unbiased RNA-seq to survey comprehensively all potential pathogens associated with conjunctivitis in Niger, where phenotypic testing remains a challenge because pathogen viability for culturing purposes is hard to maintain during transportation. In addition, we were able to provide concurrent information on AMR at the individual level. Limitations of our surveillance study include a small sample size and the lack of longitudinal data to evaluate clinical outcomes. These limitations may contribute to the lack of preauricular lymphadenopathy and conjunctival membranes or pseudomembranes documented in our patient cohort. Although the detection of genetic material does not always correlate definitively with causation, clinical testing has, overall, become more reliant on molecular diagnostics such as nucleic acid amplification tests. Careful clinical correlation will always be important in the determination of causation. In particular, associated viruses detected in nasal swabs may be indicative of colonizers, and not causative pathogens, in some patients. Furthermore, it is unclear whether the resistome identified had direct phenotypic or clinical correlations. The low-biomass nature of conjunctival samples may limit the sensitivity of RNA-seq and may explain the less diverse resistome compared with the resistome of the anterior nares. Lastly, the pathogen profile as described in our study should only be interpreted in the context of Niger, because it has become increasingly clear that geography is an important factor in understanding infectious conjunctivitis.34

In summary, this study revealed that pathogens associated with acute conjunctivitis in Niger are heterogenous. Because comprehensive, unbiased pathogen-directed testing is currently impractical on an individual basis, periodic comprehensive community surveillance may be helpful in the identification of changes in disease patterns and of emerging infectious diseases.

REFERENCES

  • 1.

    Parrish RK 2nd , Stewart MW , Duncan Powers SL , 2020. Ophthalmologists are more than eye doctors: in memoriam Li Wenliang. Am J Ophthalmol 213: A1A2.

  • 2.

    Morens DM , Fauci AS , 2020. Emerging pandemic diseases: how we got to COVID-19. Cell 183: 837.

  • 3.

    Shekhawat NS , Shtein RM , Blachley TS , Stein JD , 2017. Antibiotic prescription fills for acute conjunctivitis among enrollees in a large United States managed care network. Ophthalmology 124: 10991107.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Bountogo M et al., 2023. Deep sequencing analysis of acute conjunctivitis in Burkina Faso, Africa. Int Health 15: 101103.

  • 5.

    Woodland RM , Darougar S , Thaker U , Cornell L , Siddique M , Wania J , Shah M , 1992. Causes of conjunctivitis and keratoconjunctivitis in Karachi, Pakistan. Trans R Soc Trop Med Hyg 86: 317320.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Deschenes J , Blondeau J , 2015. Besifloxacin in the management of bacterial infections of the ocular surface. Can J Ophthalmol 50: 184191.

  • 7.

    Arzika AM et al., 2022. Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger. Nat Commun 13: 976.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Keenan JD et al., 2019. Longer-term assessment of azithromycin for reducing childhood mortality in Africa. N Engl J Med 380: 22072214.

  • 9.

    O’Brien KS et al., 2020. Biannual azithromycin distribution and child mortality among malnourished children: a subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med 17: e1003285.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Prajna NV et al., 2022. Outpatient human coronavirus associated conjunctivitis in India. J Clin Virol 157: 105300.

  • 11.

    Lakin SM et al., 2017. MEGARes: an antimicrobial resistance database for high throughput sequencing. Nucl Acids Res 45: D574D580.

  • 12.

    Doan T et al., 2020. Macrolide and nonmacrolide resistance with mass azithromycin distribution. N Engl J Med 383: 19411950.

  • 13.

    Doan T et al., 2019. Macrolide resistance in MORDOR I: a cluster-randomized trial in Niger. N Engl J Med 380: 22712273.

  • 14.

    Chen B , Tian EK , He B , Tian L , Han R , Wang S , Xiang Q , Zhang S , El Arnaout T , Cheng W , 2020. Overview of lethal human coronaviruses. Signal Transduct Target Ther 5: 89.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Prill MM et al., 2012. Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls. Pediatr Infect Dis J 31: 235240.

  • 16.

    Heimdal I , Valand J , Krokstad S , Moe N , Christensen A , Risnes K , Nordbø SA , Døllner H , 2022. Hospitalized children with common human coronavirus clinical impact of codetected respiratory syncytial virus and rhinovirus. Pediatr Infect Dis J 41: e95e101.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Lalitha P et al., 2022. Deep sequencing analysis of clinical samples from patients with acute infectious conjunctivitis during the COVID-19 delta surge in Madurai, India. J Clin Virol 157: 105318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Kitazawa K , Deinhardt-Emmer S , Inomata T , Deshpande S , Sotozono C , 2021. The transmission of SARS-CoV-2 infection on the ocular surface and prevention strategies. Cells 10: 796.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Dutescu RM , Banasik P , Schildgen O , Schrage N , Uthoff D , 2021. Detection of coronavirus in tear samples of hospitalized patients with confirmed SARS-CoV-2 from oropharyngeal swabs. Cornea 40: 348350.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Smit DP , Mathew DK , Khairallah M , Yeh S , Cunningham ET Jr , 2023. A review of human ocular RNA virus infections excluding coronavirus, human T-cell lymphotropic virus, and arboviruses. Ocul Immunol Inflamm 31: 14541460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Lambert N , Strebel P , Orenstein W , Icenogle J , Poland GA , 2015. Rubella. Lancet 385: 22972307.

  • 22.

    Gonzales JA , Hinterwirth A , Shantha J , Wang K , Zhong L , Cummings SL , Qian Y , Wilson MR , Acharya NR , Doan T , 2019. Association of ocular inflammation and rubella virus persistence. JAMA Ophthalmol 137: 435438.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Peck ME , Maleghemi S , Kayembe L , Hercules M , Anyuon A , Bunga S , McFarland J , Olu O , 2023. Nationwide measles and rubella outbreaks in South Sudan, 2019. Open Forum Infect Dis 10: ofad032.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Garcia-Zalisnak D , Rapuano C , Sheppard JD , Davis AR , 2018. Adenovirus ocular infections: prevalence, pathology, pitfalls, and practical pointers. Eye Contact Lens 44 (Suppl 1 ):S1S7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Binder AM , Biggs HM , Haynes AK , Chommanard C , Lu X , Erdman DD , Watson JT , Gerber SI , 2017. Human adenovirus surveillance: United States, 2003–2016. MMWR Morb Mortal Wkly Rep 66: 10391042.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Zhang L , Zhao N , Sha J , Wang C , Jin X , Amer S , Liu S , 2016. Virology and epidemiology analyses of global adenovirus-associated conjunctivitis outbreaks, 1953–2013. Epidemiol Infect 144: 16611672.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Koch R , 1883. Bericht über die Thätigkeit der deutschen Cholerakommisionen in Aegypten und Ostindien. Wien Med Wochenschr 33: 15481551.

  • 28.

    Harrison LH , Simonsen V , Waldman EA , 2008. Emergence and disappearance of a virulent clone of Haemophilus influenzae biogroup aegyptius, cause of Brazilian purpuric fever. Clin Microbiol Rev 21: 594605.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Filleul L , Pagès F , Wan GC , Brottet E , Vilain P , 2018. Costs of conjunctivitis outbreak, Réunion Island, France. Emerg Infect Dis 24: 168170.

  • 30.

    Cho K , Kuo IC , 2023. Treatment trials for viral conjunctivitis: what we have learned and how we can improve. Cornea Open 2: e0006.

  • 31.

    Browne AJ et al., 2021. Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study. Lancet Planet Health 5: e893e904.

  • 32.

    ACCESS-SMC Partnership , 2020. Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study. Lancet 396: 18291840.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Koko DC , Maazou A , Jackou H , Eddis C , 2022. Analysis of attitudes and practices influencing adherence to seasonal malaria chemoprevention in children under 5 years of age in the Dosso Region of Niger. Malar J 21: 375.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Kaur G , Seitzman GD , Lietman TM , McLeod SD , Porco TC , Doan T , Deiner MS , 2021. Keeping an eye on pink eye: a global conjunctivitis outbreak expert survey. Int Health 14: 542544.

    • PubMed
    • Search Google Scholar
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Author Notes

Seasonal Conjunctivitis Outbreak Reporting for Prevention and Improved Outcomes (SCORPIO) study group: Lalitha Prajna, N. Venkatesh Prajna, Ramesh Gunasekaran, Sankalp Singh Sharma, and Vishnu Teja (Aravind Eye Hospital, Madurai, India); Meenu Chaudhary and Sanjeeta Sitaula (B.P. Koirala Lions Center for Ophthalmic Studies, Kathmandu, Nepal); Ali Sié, Boubacar Coulibaly, and Mamadou Bountogo (Centre de Recherche en Sante de Nouna, Burkina Faso); Thanapong Somkijrungroj and Vannarut Satitpitakul (Chulalongkorn University, Bangkok, Thailand); Huy Tran, Linh Hoàng Mai, Thảo Hạ Xuân, and Yen Tran (Hai Yen Vision Institute, Ho Chi Minh City, Vietnam); Cristhian A. Urzua, Fabian Vega, Felipe Salgado, and Loreto Cuitino (Hospital Clinico Universidad de Chile, Santiago, Chile); Fernando Pérez Pérez, Jaime Macías Martínez, and Van Charles Lansingh (Instituto Mexicano de Oftalmología, Santiago de Querétaro, Mexico); Sukhumal Thanapaisal and Wipada Laovirojjanakul (Khon Kaen University, Khon Kaen, Thailand); George McKie (National Eye Institute, Bethesda, MD); Kenia Chavez, Travis Redd, and Winston Chamberlain (Oregon Health and Science University, Portland, OR); Angel Cheng and Vivien Tham (Pacific Vision Institute of Hawaii, Honolulu, Hawaii); Wiwan Sansanayudh (Phramongkutklao Hospital, Bangkok, Thailand); Abba Kaka Hajia Yakoura, Abdoul Salam Youssoufou Souley, Adam Nouhou Diori, Ramatou Boulhassane, and Zakou Abdou (Programme National de Santé Oculaire, Niamey, Niger); Lee Goren and Ruti Sella (Rabin Medical Center, Petah Tikva, Israel); Clare Kelliher and Laura Green (Sinai Hospital, Baltimore, MD); Hon Shing Ong, Jod Mehta, and Yu-Chi Liu (Singapore Eye Research Institute); De-Kuang Hwang and Nai-Wen Fan (Taipei Veterans General Hospital, Taiwan); Hong Sheng Chiong, Javier Lacorzana, Maria Cabrera-Aguas, and Stephanie Watson (The University of Sydney, Save Sight Institute, Australia); Edmund Tsui, Nina M. Cherian, Rachel Feit-Leichman, Reginald E. Hughes Jr, Tania Onclinx, and Joseph K. Privratsky (University of California Los Angeles, Stein Eye Institute, CA); Carol Yu, Esmeralda McClean, and Iliana Molina (University of California San Diego, Shiley Eye Institute, La Jolla, CA); Michael Deiner, Travis Porco, and Stephen McLeod (University of California San Francisco, Francis I. Proctor Foundation, CA); Kuniyoshi Kanai and Meredith Whiteside (University of California Berkeley, School of Optometry, CA); Steven Yeh and Tolulope Fashina (University of Nebraska Medical Center, Truhlsen Eye Institute, Omaha, NE); James Chodosh (University of New Mexico, Albuquerque, NM); Bridgit Tarkap, Jambi N. Garap, and Magdalene Mangot (University of Papua New Guinea, School of Medicine and Health Sciences, Port Moresby, Papua New Guinea); Edwin Amel, Fasihah Taleo, Johnson Kasso, Kalbule Willie, Madopule Nanu, and Prudence Rymill (Vanuatu Eye Program, Ministry of Health, Port Vila, Vanuatu); and Anthony W. Solomon (WHO, Geneva, Switzerland).

Financial support: The research reported herein was supported by the National Eye Institute of the NIH (Award No. R01EY032041) and by a Research to Prevent Blindness unrestricted grant.

Disclosure: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Authors’ addresses: Abdou Amza, Beido Nassirou, Boubacar Kadri, Saley Ali, Boubacar Mariama, Cissé M. Ibrahim, and Lamine A. Roufaye, Programme Nationale de Santé Oculaire, Niamey, Niger, E-mails: dr.amzaabdou@gmail.com, nasbeido@yahoo.fr, boubacarkadri@gmail.com, drsaleali@gmail.com, mariekindo71@yahoo.fr, cisse_im@yahoo.fr, and rouf_lam@yahoo.fr. Elodie Lebas, Emily Colby, Lina Zhong, Cindi Chen, Kevin Ruder, Danny Yu, YuHeng Liu, Thomas Abraham, Aaron Chang, Lina Mai, and Armin Hinterwirth, Francis I. Proctor Foundation, University of California, San Francisco, CA, E-mails: elodie.lebas@ucsf.edu, emily.michele.colby@gmail.com, lina.zhong@ucsf.edu, cindi.chen@ucsf.edu, kevin.ruder@ucsf.edu, danny.yu@ucsf.edu, david.liu5@ucsf.edu, thomas.abraham@ucsf.edu, aaron.chang@ucsf.edu, lina.mai@ucsf.edu, and armin.hinterwirth@ucsf.edu. Gerami D. Seitzman and Thuy Doan, Francis I. Proctor Foundation, University of California, San Francisco, CA, and Department of Ophthalmology, University of California, San Francisco, CA, E-mails: gerami.seitzman@ucsf.edu and thuy.doan@ucsf.edu. Thomas M. Lietman, Francis I. Proctor Foundation, University of California, San Francisco, CA, Department of Ophthalmology, University of California, San Francisco, CA, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, and Institute for Global Health Sciences, University of California, San Francisco, CA, E-mail: tom.lietman@ucsf.edu.

Address correspondence to Thuy Doan, Proctor Foundation, University of California, 490 Illinois St., Floor 2, San Francisco, CA 94158. E-mail: thuy.doan@ucsf.edu
  • Figure 1.

    Summary of pathogen profiles and genetic resistance determinants for nasal and conjunctival samples. (A) Stacked bar graph of pathogens identified for nasal samples (left) and conjunctival samples (right). (B) Heatmaps of normalized reads of genetic resistance determinants for each antibiotic class. Each row represents the reads per million matched reads (rM) for the nasal sample (left panel) and a conjunctival sample of a patient (right panel). CMV = cytomegalovirus; EBV = Epstein–Barr virus; HAdV = human adenovirus; HCoV = human coronavirus; HHV = human herpesvirus; MLS = macrolides, lincosamides, and streptogramins.

  • 1.

    Parrish RK 2nd , Stewart MW , Duncan Powers SL , 2020. Ophthalmologists are more than eye doctors: in memoriam Li Wenliang. Am J Ophthalmol 213: A1A2.

  • 2.

    Morens DM , Fauci AS , 2020. Emerging pandemic diseases: how we got to COVID-19. Cell 183: 837.

  • 3.

    Shekhawat NS , Shtein RM , Blachley TS , Stein JD , 2017. Antibiotic prescription fills for acute conjunctivitis among enrollees in a large United States managed care network. Ophthalmology 124: 10991107.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Bountogo M et al., 2023. Deep sequencing analysis of acute conjunctivitis in Burkina Faso, Africa. Int Health 15: 101103.

  • 5.

    Woodland RM , Darougar S , Thaker U , Cornell L , Siddique M , Wania J , Shah M , 1992. Causes of conjunctivitis and keratoconjunctivitis in Karachi, Pakistan. Trans R Soc Trop Med Hyg 86: 317320.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Deschenes J , Blondeau J , 2015. Besifloxacin in the management of bacterial infections of the ocular surface. Can J Ophthalmol 50: 184191.

  • 7.

    Arzika AM et al., 2022. Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger. Nat Commun 13: 976.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Keenan JD et al., 2019. Longer-term assessment of azithromycin for reducing childhood mortality in Africa. N Engl J Med 380: 22072214.

  • 9.

    O’Brien KS et al., 2020. Biannual azithromycin distribution and child mortality among malnourished children: a subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med 17: e1003285.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Prajna NV et al., 2022. Outpatient human coronavirus associated conjunctivitis in India. J Clin Virol 157: 105300.

  • 11.

    Lakin SM et al., 2017. MEGARes: an antimicrobial resistance database for high throughput sequencing. Nucl Acids Res 45: D574D580.

  • 12.

    Doan T et al., 2020. Macrolide and nonmacrolide resistance with mass azithromycin distribution. N Engl J Med 383: 19411950.

  • 13.

    Doan T et al., 2019. Macrolide resistance in MORDOR I: a cluster-randomized trial in Niger. N Engl J Med 380: 22712273.

  • 14.

    Chen B , Tian EK , He B , Tian L , Han R , Wang S , Xiang Q , Zhang S , El Arnaout T , Cheng W , 2020. Overview of lethal human coronaviruses. Signal Transduct Target Ther 5: 89.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Prill MM et al., 2012. Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls. Pediatr Infect Dis J 31: 235240.

  • 16.

    Heimdal I , Valand J , Krokstad S , Moe N , Christensen A , Risnes K , Nordbø SA , Døllner H , 2022. Hospitalized children with common human coronavirus clinical impact of codetected respiratory syncytial virus and rhinovirus. Pediatr Infect Dis J 41: e95e101.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Lalitha P et al., 2022. Deep sequencing analysis of clinical samples from patients with acute infectious conjunctivitis during the COVID-19 delta surge in Madurai, India. J Clin Virol 157: 105318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Kitazawa K , Deinhardt-Emmer S , Inomata T , Deshpande S , Sotozono C , 2021. The transmission of SARS-CoV-2 infection on the ocular surface and prevention strategies. Cells 10: 796.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Dutescu RM , Banasik P , Schildgen O , Schrage N , Uthoff D , 2021. Detection of coronavirus in tear samples of hospitalized patients with confirmed SARS-CoV-2 from oropharyngeal swabs. Cornea 40: 348350.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Smit DP , Mathew DK , Khairallah M , Yeh S , Cunningham ET Jr , 2023. A review of human ocular RNA virus infections excluding coronavirus, human T-cell lymphotropic virus, and arboviruses. Ocul Immunol Inflamm 31: 14541460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Lambert N , Strebel P , Orenstein W , Icenogle J , Poland GA , 2015. Rubella. Lancet 385: 22972307.

  • 22.

    Gonzales JA , Hinterwirth A , Shantha J , Wang K , Zhong L , Cummings SL , Qian Y , Wilson MR , Acharya NR , Doan T , 2019. Association of ocular inflammation and rubella virus persistence. JAMA Ophthalmol 137: 435438.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Peck ME , Maleghemi S , Kayembe L , Hercules M , Anyuon A , Bunga S , McFarland J , Olu O , 2023. Nationwide measles and rubella outbreaks in South Sudan, 2019. Open Forum Infect Dis 10: ofad032.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Garcia-Zalisnak D , Rapuano C , Sheppard JD , Davis AR , 2018. Adenovirus ocular infections: prevalence, pathology, pitfalls, and practical pointers. Eye Contact Lens 44 (Suppl 1 ):S1S7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Binder AM , Biggs HM , Haynes AK , Chommanard C , Lu X , Erdman DD , Watson JT , Gerber SI , 2017. Human adenovirus surveillance: United States, 2003–2016. MMWR Morb Mortal Wkly Rep 66: 10391042.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Zhang L , Zhao N , Sha J , Wang C , Jin X , Amer S , Liu S , 2016. Virology and epidemiology analyses of global adenovirus-associated conjunctivitis outbreaks, 1953–2013. Epidemiol Infect 144: 16611672.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Koch R , 1883. Bericht über die Thätigkeit der deutschen Cholerakommisionen in Aegypten und Ostindien. Wien Med Wochenschr 33: 15481551.

  • 28.

    Harrison LH , Simonsen V , Waldman EA , 2008. Emergence and disappearance of a virulent clone of Haemophilus influenzae biogroup aegyptius, cause of Brazilian purpuric fever. Clin Microbiol Rev 21: 594605.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Filleul L , Pagès F , Wan GC , Brottet E , Vilain P , 2018. Costs of conjunctivitis outbreak, Réunion Island, France. Emerg Infect Dis 24: 168170.

  • 30.

    Cho K , Kuo IC , 2023. Treatment trials for viral conjunctivitis: what we have learned and how we can improve. Cornea Open 2: e0006.

  • 31.

    Browne AJ et al., 2021. Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study. Lancet Planet Health 5: e893e904.

  • 32.

    ACCESS-SMC Partnership , 2020. Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study. Lancet 396: 18291840.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Koko DC , Maazou A , Jackou H , Eddis C , 2022. Analysis of attitudes and practices influencing adherence to seasonal malaria chemoprevention in children under 5 years of age in the Dosso Region of Niger. Malar J 21: 375.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Kaur G , Seitzman GD , Lietman TM , McLeod SD , Porco TC , Doan T , Deiner MS , 2021. Keeping an eye on pink eye: a global conjunctivitis outbreak expert survey. Int Health 14: 542544.

    • PubMed
    • Search Google Scholar
    • Export Citation
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