Prevalence of trachoma in Somali region, Ethiopia: results from trachoma impact surveys in 50 woredas.

BACKGROUND: Following interventions to eliminate trachoma in Somali region, Ethiopia, we aimed to re-estimate the prevalence of trachomatous trichiasis (TT) and trachomatous inflammation-follicular (TF) at woreda level and identify the factors associated with the disease. METHODS: We implemented cross-sectional community-based surveys in 50 trachoma-endemic woredas, using a standardized survey. Households were the secondary sampling unit. Surveys were undertaken through a combination of interviews of household heads and direct inspection of water, sanitation and hygiene (WASH) access, plus clinical evaluation of eligible household members for TT and TF. RESULTS: Overall, 41 (82%) of the 50 woredas had met the WHO-recommended active trachoma elimination threshold (prevalence of TF <5% in 1-9-y-olds) and 42 (84%) had met the TT threshold (prevalence of TT unknown to the health system <0.2% in ≥15-y-olds). Only 18% of households had access to an improved drinking water source within a 30-min trip and only 25% had an improved latrine. CONCLUSIONS: Additional rounds of antibiotic mass drug administration, plus interventions to enhance facial cleanliness and improve the environment, are required in nine woredas. TT surgical campaigns are needed in eight woredas. Greater access to WASH is required across all the woredas that were surveyed.

Twenty-Three Population-Based Trachoma Prevalence Surveys in the Central and Northern Regions of Benin, 2018-2022.

PURPOSE: Trachoma is an infectious eye disease caused by Chlamydia trachomatis. Infection causes conjunctival inflammation, which can be manifested by the sign known as trachomatous inflammation-follicular (TF). Repeated inflammation leads to eyelid scarring, which in susceptible individuals can cause in-turning of the eyelashes, referred to as trachomatous trichiasis (TT). This article describes 23 population-based surveys conducted in northern and central Benin to determine TF and/or TT prevalence for trachoma elimination purposes. METHODS: A total of 18 surveys estimated the prevalence of both TF and TT: two baseline surveys, eight impact surveys after implementation of interventions against trachoma, and eight surveillance surveys. Five other evaluation units (EUs) were surveyed for TT only. To estimate the TF prevalence, a target sample size of 1701 (baseline) and 1164 1-9-year-olds (impact and surveillance) was required, whereas 2818 ≥ 15-year-olds were required to estimate the less prevalent TT. In each EU, individuals were selected by two-stage cluster sampling and examined by certified graders for TF and/or TT. RESULTS: A total of 68,613 people were examined. TF prevalence estimates were under the 5% elimination threshold in all surveys. TT prevalence estimates were above the 0.2% elimination threshold in all five TT-only surveys and in four impact surveys, ranging from 0.2-0.57. CONCLUSION: TF prevalence in Benin is low, but TT was above 0.2% in nine districts. Increased case-finding and continuing efforts to improve surgery accessibility will be needed to reduce the burden of TT in Benin.

Longitudinal changes in tear cytokines and antimicrobial proteins in trachomatous disease.

BACKGROUND: Trachoma is a neglected tropical disease caused by ocular infection with Chlamydia trachomatis, where repeated infections and chronic inflammation can ultimately result in scarring, trichiasis and blindness. While scarring is thought to be mediated by a dysregulated immune response, the kinetics of cytokines and antimicrobial proteins in the tear film have not yet been characterised. METHODOLOGY: Pooled tears from a Gambian cohort and Tanzanian cohort were semi-quantitatively screened using a Proteome Profiler Array to identify cytokines differentially regulated in disease. Based on this screen and previous literature, ten cytokines (CXCL1, IP-10, IFN-γ, IL-1ß, IL-8, IL-10, IL-12 p40, IL-1RA, IL-1α and PDGF), lysozyme and lactoferrin were assayed in the Tanzanian cohort by multiplex cytokine assay and ELISA. Finally, CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled in the Gambian cohort by multiplex cytokine assay and ELISA. RESULTS: In the Tanzanian cohort, IL-8 was significantly increased in those with clinically inapparent infection (p = 0.0086). Lysozyme, IL-10 and chemokines CXCL1 and IL-8 were increased in scarring (p = 0.016, 0.046, 0.016, and 0.037). CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled over the course of infection in a Gambian cohort study, with evidence of an inflammatory response both before, during and after detectable infection. CXCL1, IL-8 and IP-10 were higher in the second infection episode relative to the first (p = 0.0012, 0.044, and 0.04). CONCLUSIONS: These findings suggest that the ocular immune system responds prior to and continues to respond after detectable C. trachomatis infection, possibly due to a positive feedback loop inducing immune activation. Levels of CXC chemokines in successive infection episodes were increased, which may offer an explanation as to why repeated infections are a risk factor for scarring.

Baseline, Impact and Surveillance Trachoma Prevalence Surveys in Burundi, 2018-2021.

PURPOSE: Trachoma is an eye disease caused by the bacterium Chlamydia trachomatis (Ct). It can lead to permanent vision loss. Since 2007, Burundi has included trachoma elimination as part of its fight against neglected tropical diseases and blindness. This study presents the results of trachoma baseline, impact and surveillance surveys conducted in Burundi between 2018 and 2021. METHODS: Areas were grouped into evaluation units (EU) with resident populations of between 100,000 and 250,000 people. Baseline surveys were conducted in 15 EUs, impact surveys in 2 EUs and surveillance surveys in 5 EUs; in each survey, 23 clusters of about 30 households were included. Consenting residents of those households were screened for clinical signs of trachoma. Access to water, sanitation and hygiene (WASH) was recorded. RESULTS: A total of 63,800 individuals were examined. The prevalence of TF in 1-9-year-olds was above the elimination threshold of 5% in a single EU at baseline, but fell below the threshold in subsequent impact and surveillance surveys. The prevalence of TT was below the 0.2% elimination threshold in ≥15-year-olds in all EUs surveyed. A high proportion (83%) of households had access to safe drinking water, while only a minority (~8%) had access to improved latrines. CONCLUSION: Burundi has demonstrated the prevalence levels necessary for trachoma elimination status. With continued effort and the maintenance of existing management plans, trachoma elimination in Burundi is within reach.

The Gambia Trachomatous Trichiasis Surveys: Results from Five Evaluation Units Confirm Attainment of Trachoma Elimination Thresholds.

INTRODUCTION: Trichiasis is present when in-turned eyelashes touch the eyeball. It may result in permanent vision loss. Trachomatous trichiasis (TT) is caused by multiple rounds of inflammation associated with conjunctival Chlamydia trachomatis infection. Surveys have been designed to estimate the prevalence of TT in evaluation units (EUs) of trachoma-endemic countries in order to help develop appropriate programme-level plans. In this study, TT-only surveys were conducted in five EUs of The Gambia to determine whether further intensive programmatic action was required. METHODS: Two-stage cluster sampling was used to select 27 villages per EU and ~25 households per village. Graders assessed the TT status of individuals aged ≥15 years in each selected household, including the presence or absence of conjunctival scarring in those with TT. RESULTS: From February to March 2019, 11595 people aged ≥15 years were examined. A total of 34 cases of TT were identified. All five EUs had an age- and gender-adjusted prevalence of TT unknown to the health system <0.2%. Three of five EUs had a prevalence of 0.0%. CONCLUSION: Using these and other previously collected data, in 2021, The Gambia was validated as having achieved national elimination of trachoma as a public health problem. Trachoma is still present in the population, but as its prevalence is low, it is unlikely that today's youth will experience the exposure to C. trachomatis required to precipitate TT. The Gambia demonstrates that with political will and consistent application of human and financial resources, trachoma can be eliminated as a public health problem.

The Prevalence of Trachomatous Trichiasis in People Aged 15 Years and Over in Six Evaluation Units of Gaoual, Labé, Dalaba and Beyla Districts, Guinea.

PURPOSE: Trachoma is a public health problem in 42 countries. Inflammation associated with repeated ocular infection with Chlamydia trachomatis can cause the eyelid to scar and turn inwards, resulting in the eyelashes rubbing against the eyeball, known as trachomatous trichiasis (TT). In Guinea, baseline surveys conducted in 2013 reported inflammatory trachoma prevalences below the World Health Organization (WHO) threshold for elimination, but TT prevalences above threshold. Given this epidemiological context and time since baseline survey, TT-only surveys were conducted in selected districts to determine current TT prevalence. The results of this study provide critical data for assessing Guinea's achievement of trachoma elimination targets. METHODS: Four health districts, consisting of six evaluation units (EU), were surveyed. In each EU, field teams visited 29 clusters with a minimum 30 households included in each. Participants aged≥15 years were examined by certified graders trained to identify TT and determine whether management had been offered. RESULTS: A total of 22,476 people were examined, with 48 TT cases across the six EUs identified. Five of six EUs had an age-and-gender adjusted TT-prevalence unknown to the health system less than 0.2%, whereas one EU, Beyla 2, had an adjusted TT prevalence of 0.24%. CONCLUSION: These TT-only surveys, along with findings from other trachoma interventions, suggest that Guinea is close to achieving elimination of trachoma as a public health problem. This study demonstrates the value of undertaking TT-only surveys in settings where baseline surveys indicated active trachoma prevalences below WHO elimination threshold, but TT prevalences above it.

A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma.

Background: Ocular infections with Chlamydia trachomatis serovars A-C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection. Methods: Sera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. trachomatis antigens and three serovars [elementary bodies and major outer membrane protein (MOMP), serovars A-C], IgG responses towards five MOMP peptides (serovars A-C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected. Results: The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p < 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%). Conclusions: Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG.

Monitoring SARS-CoV-2 incidence and seroconversion among university students and employees: a longitudinal cohort study in California, June-August 2020.

OBJECTIVES: To identify incident SARS-CoV-2 infections and inform effective mitigation strategies in university settings, we piloted an integrated symptom and exposure monitoring and testing system among a cohort of university students and employees. DESIGN: Prospective cohort study. SETTING: A public university in California from June to August 2020. PARTICIPANTS: 2180 university students and 738 university employees. PRIMARY OUTCOME MEASURES: At baseline and endline, we tested participants for active SARS-CoV-2 infection via quantitative PCR (qPCR) test and collected blood samples for antibody testing. Participants received notifications to complete additional qPCR tests throughout the study if they reported symptoms or exposures in daily surveys or were selected for surveillance testing. Viral whole genome sequencing was performed on positive qPCR samples, and phylogenetic trees were constructed with these genomes and external genomes. RESULTS: Over the study period, 57 students (2.6%) and 3 employees (0.4%) were diagnosed with SARS-CoV-2 infection via qPCR test. Phylogenetic analyses revealed that a super-spreader event among undergraduates in congregate housing accounted for at least 48% of cases among study participants but did not spread beyond campus. Test positivity was higher among participants who self-reported symptoms (incidence rate ratio (IRR) 12.7; 95% CI 7.4 to 21.8) or had household exposures (IRR 10.3; 95% CI 4.8 to 22.0) that triggered notifications to test. Most (91%) participants with newly identified antibodies at endline had been diagnosed with incident infection via qPCR test during the study. CONCLUSIONS: Our findings suggest that integrated monitoring systems can successfully identify and link at-risk students to SARS-CoV-2 testing. As the study took place before the evolution of highly transmissible variants and widespread availability of vaccines and rapid antigen tests, further research is necessary to adapt and evaluate similar systems in the present context.

Sequence based HLA-DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in The Gambia.

Class II HLA loci DRB1, DQB1 and DPB1 were typed for a total of 939 Gambian participants by locus-specific amplicon sequencing. Participants were from multiple regions of The Gambia and drawn from two studies: a family study aiming to identify associations between host genotype and trachomatous scarring (N = 796) and a cohort study aiming to identify correlates of immunity to trachoma (N = 143). All loci deviated from Hardy-Weinberg equilibrium, likely due to the family-based nature of the study: 608 participants had at least one other family member included in the study population. The most common alleles for HLA-DRB1, DQB1 and DPB1 respectively were DRB1*13:04 (18.8 %), DQB1*03:19 (27.9 %) and DPB1*01:01 (25.4 %). Participants belonged to a variety of ethnicities, including the Mandinka, Fula, Wolof and Jola ethnic groups.

HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 allele frequencies of North Tanzanian Maasai.

Locus-specific amplicon sequencing was used to HLA type 336 participants of Maasai ethnicity at the HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci. Participants were recruited from three study villages in North Tanzania, for the purpose of investigating risk factors for trachomatous scarring in children. Other than HLA-A, all loci significantly deviated from Hardy-Weinberg equilibrium, possibly due to high relatedness between individuals: 238 individuals shared a house with at least one another participant. The most frequent allele for each locus were A*68:02 (14.3 %), B*53:01 (8.4 %), C*06:02 (19.2 %), DRB1*13:02 (17.7 %), DQB1*02:01 (16.9 %) and DPB1*01:01 (15.7 %), while the most common inferred haplotype was A*68:02 âˆ¼ B*18:01 âˆ¼ C*07:04 âˆ¼ DRB1*08:04 âˆ¼ DQB1*04:02 âˆ¼ DPB1*04:01 (1.3 %).

Feasibility and effectiveness of daily temperature screening to detect COVID-19 in a prospective cohort at a large public university.

BACKGROUND: Many persons with active SARS-CoV-2 infection experience mild or no symptoms, presenting barriers to COVID-19 prevention. Regular temperature screening is nonetheless used in some settings, including university campuses, to reduce transmission potential. We evaluated the potential impact of this strategy using a prospective university-affiliated cohort. METHODS: Between June and August 2020, 2912 participants were enrolled and tested for SARS-CoV-2 by PCR at least once (median: 3, range: 1-9). Participants reported temperature and symptoms daily via electronic survey using a previously owned or study-provided thermometer. We assessed feasibility and acceptability of daily temperature monitoring, calculated sensitivity and specificity of various fever-based strategies for restricting campus access to reduce transmission, and estimated the association between measured temperature and SARS-CoV-2 test positivity using a longitudinal binomial mixed model. RESULTS: Most participants (70.2%) did not initially have a thermometer for taking their temperature daily. Across 5481 total person months, the average daily completion rate of temperature values was 61.6% (median: 67.6%, IQR: 41.8-86.2%). Sensitivity for SARS-CoV-2 ranged from 0% (95% CI 0-9.7%) to 40.5% (95% CI 25.6-56.7%) across all strategies for self-report of possible COVID-19 symptoms on day of specimen collection, with corresponding specificity of 99.9% (95% CI 99.8-100%) to 95.3% (95% CI 94.7-95.9%). An increase of 0.1 °F in individual mean body temperature on the same day as specimen collection was associated with 1.11 increased odds of SARS-CoV-2 positivity (95% CI 1.06-1.17). CONCLUSIONS: Our study is the first, to our knowledge, that examines the feasibility, acceptability, and effectiveness of daily temperature screening in a prospective cohort during an infectious disease outbreak, and the only study to assess these strategies in a university population. Daily temperature monitoring was feasible and acceptable; however, the majority of potentially infectious individuals were not detected by temperature monitoring, suggesting that temperature screening is insufficient as a primary means of detection to reduce transmission of SARS-CoV-2.

Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus.

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

Piloting an integrated SARS-CoV-2 testing and data system for outbreak containment among college students: A prospective cohort study.

BACKGROUND: Colleges and universities across the country are struggling to develop strategies for effective control of COVID-19 transmission as students return to campus. METHODS AND FINDINGS: We conducted a prospective cohort study with students living on or near the UC Berkeley campus from June 1st through August 18th, 2020 with the goal of providing guidance for campus reopening in the safest possible manner. In this cohort, we piloted an alternative testing model to provide access to low-barrier, high-touch testing and augment student-driven testing with data-driven adaptive surveillance that targets higher-risk students and triggers testing notifications based on reported symptoms, exposures, or other relevant information. A total of 2,180 students enrolled in the study, 51% of them undergraduates. Overall, 6,247 PCR tests were administered to 2,178 students over the two-month period. Overall test positivity rate was 0.9%; 2.6% of students tested positive. Uptake and acceptability of regular symptom and exposure surveys was high; 98% of students completed at least one survey, and average completion rate was 67% (Median: 74%, IQR: 39%) for daily reporting of symptoms and 68% (Median: 75%, IQR: 40%) for weekly reporting of exposures. Of symptom-triggered tests, 5% were PCR-positive; of exposure-triggered tests, 10% were PCR-positive. The integrated study database augmented traditional contact tracing during an outbreak; 17 potentially exposed students were contacted the following day and sent testing notifications. At study end, 81% of students selected their desire "to contribute to UC Berkeley's response to COVID-19" as a reason for their participation in the Safe Campus study. CONCLUSIONS: Our results illustrate the synergy created by bringing together a student-friendly, harm reduction approach to COVID-19 testing with an integrated data system and analytics. We recommend the use of a confidential, consequence-free, incentive-based daily symptom and exposure reporting system, coupled with low-barrier, easy access, no stigma testing. Testing should be implemented alongside a system that integrates multiple data sources to effectively trigger testing notifications to those at higher risk of infection and encourages students to come in for low-barrier testing when needed.

Five subfamilies of ß-defensin genes are present in salmonids: Evolutionary insights and expression analysis in Atlantic salmon Salmo salar.

ß-defensins (BD) are the largest family of vertebrate defensins with potent antimicrobial, chemotactic and immune-regulatory activities. Four BD genes (BD1-4) have been cloned previously in rainbow trout but none have been reported in other salmonids. In this study seven BD genes (BD1a-b, 2-4, 5a-b) are characterised in Atlantic salmon and additional BD genes (BD1b and BD5) in rainbow trout. Bioinformatic analysis revealed up to seven BD genes in the genomes of other salmonids that belong to five subfamilies (BD1-5) due to whole genome duplications. BD1-2 and BD4-5 are also present in basal teleosts but only BD1 and/or BD5 are present in advanced teleosts due to loss of one chromosomal locus. BD3 is salmonid specific. Fish BD have a unique three-coding exon structure. Fish BD are highly divergent between subfamilies but conserved within each subfamily. Atlantic salmon BD genes are differentially expressed in tissues, often with low level expression in systemic immune organs (head kidney and spleen) yet with at least one BD gene highly expressed in mucosal tissues, heart, blood and liver. This suggests an important role of these BD genes in innate immunity in mucosa, liver and blood in Atlantic salmon.

Factors influencing the long-term dynamics of larval sea lice density at east and west coast locations in Scotland.

Sea lice (Copepoda: Caligidae) are marine copepods that parasitize finfish, and in cases of high infestation can result in severe epithelial damage and mortality. In Scotland, 2 species of sea louse, Lepeophtheirus salmonis and Caligus elongatus, pose a significant economic burden to the marine Atlantic salmon aquaculture industry and potentially impact wild salmonids. The purpose of this study was to determine how the density of pelagic sea lice is affected by external variables, in order to improve our understanding of sea lice dynamics. Long-term data from 2 sampling sites on the east and west coasts of Scotland were modelled independently in conjunction with environmental and anthropogenic variables. Statistical analysis identified that at the east coast site, the most influential factor affecting lice density was salinity. On the west coast, salinity, rainfall and farmed salmon production year were most influential. Molecular and morphological techniques also showed that the individuals recorded on the east coast were C. elongatus, a generalist copepod parasite, whereas only the salmonid-specific L. salmonis were found on the west. These results reiterate the role of environmental factors in influencing sea lice dynamics, and that salmonids are the primary hosts of sea lice on the west coast, but there could be non-salmonid host species as well as salmonid species influencing east coast sea lice densities.