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Purpose: The prevalence of trichiasis is higher in females and increases markedly with age. Surveys carried out in the daytime, particularly in developing countries, are prone to find older individuals and females at home at the time of the survey. Population-level trichiasis estimates should adjust sample proportions to reflect the demographic breakdown of the population, although the most accurate method of doing this is unclear. Methods: Having obtained data from 162 surveys carried out in Ethiopia as part of the Global Trachoma Mapping Project from 2012 to 2015, we used internal validation with both Brier and Logarithmic forecast scoring to test stratification models to identify those models with the highest predictive accuracy. Selection of partitions was undertaken by both simple random sampling (SRS) and cluster sampling (CS) over 8192 selections. Results: A total of 4529 (1.9%) cases of trichiasis were identified from 241,139 individuals aged ≥15 years from a total of 4210 kebeles and 122,090 households visited. Overall, the binning method using 5-year bands from age 15 to 69 years, with coarser binning in 20-year age-bands above this age, provided the best predictive accuracy, in both SRS and CS methodologies and for both the Brier and Logarithmic scoring rules. Conclusion: The greatest predictive accuracy for trichiasis estimates was found by adjusting for sex and in 5-year age-bands from the age of 15 to 69 years and in 20-year age-bands in those aged 70 years and greater. Trichiasis surveys attempting to make population-level inferences should use this method to optimise surgery backlog estimates.

The aim of this study was to assess the accuracy of blood glucose monitors (BGMs) from studies reported in the medical literature. A literature review was performed of publications between 2010 and 2017 that presented data about the accuracy of BGMs using ISO 15197 2003 and/or ISO 15197 2013 as target standards. We found 58 publications describing the performance of 143 unique BGM systems, 59 of which were Food and Drug Administration (FDA) cleared. When compared with non-FDA-cleared BGMs, FDA-cleared BGMs were significantly more likely to pass both ISO 15197 2003 (OR = 2.39, CI 1.45-3.92, P 0.01) and ISO 15197 2013 standards (OR = 2.20, CI 1.51-3.27, P 0.01). Newer meters were more likely to pass both ISO 15197 2003 and ISO 15197 2013 standards. Many of the studies were supported by BGM manufacturers, and when compared with independent studies, an FDA-cleared BGM was significantly more likely to pass in a manufacturer-supported study for both ISO 15197 2003 (OR = 22.4, CI 8.73-21.57, P 0.001) and ISO 15197 2013 (OR = 23.08, CI 10.16-60.03, P 0.001). BGM accuracy should be assessed independently following regulatory clearance to ensure accurate performance. Failure to meet performance levels mandated by standards can result in deleterious clinical and economic effects.

BACKGROUND: Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality. METHODS: In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression. RESULTS: Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported. CONCLUSIONS: This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

Mathematical models predict that the community-level incidence of a controlled infectious disease across a region approaches a geometric distribution. This could hold over larger regions, if new cases remain proportional to existing cases. Leprosy has been disappearing for centuries, making an excellent candidate for testing this hypothesis. Here, we show the annual new case detection rate of leprosy in Indian districts to be consistent with a geometric distribution. For 2008–2013, goodness-of-fit testing was unable to exclude the geometric, and the shape parameter of the best fit negative binomial distribution was close to unity (0.95, 95% CI 0.87–1.03). Ramifications include that a district-level cross-sectional survey may reveal whether an infectious disease is headed towards elimination, that apparent outliers are expected and not necessarily representative of program failure, and that proportion 1/e of a small geographical unit may not meet a control threshold even when a larger area has. Keywords: Leprosy, Geometric distribution, Elimination, Mathematical model

Objective To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. Methods Study Participants : Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). Intervention : Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. Main Outcome Measures : TPK button culture positivity. Results A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90–0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32–4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16–51.70; P = .003). Conclusions There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

Purpose To study the correlation between corneal and scleral intraocular pressure (IOP) by pneumatonometry in pediatric patients. Design Cross-sectional study. Participants Patients (age range, 0–15 years) undergoing an eye examination under anesthesia or eye surgery were recruited at the University of California, San Francisco, Benioff Children's Hospital between July 2015 and April 2016. Methods Intraocular pressure measurements were obtained by pneumatonometry on the central cornea and the inferonasal and inferotemporal sclera in a random order. Spearman correlations between corneal versus inferonasal scleral IOP and corneal versus inferotemporal scleral IOP were calculated. A linear mixed-effect model was used to derive a predictive equation for corneal IOP from scleral IOP and to perform covariate analysis for age, axial length, central corneal thickness, and lens status. The standard deviation of the predicted corneal IOP was determined by bootstrap mixed-effect regression analysis. Main Outcome Measures The predictive model of corneal IOP from scleral IOP. Results Seventy-five eyes from 40 patients were included in the study. Spearman correlation coefficient for corneal versus inferotemporal scleral IOP was 0.79 ( P P P = 0.07), lens status ( P = 0.4), age ( P = 0.33), and axial length ( P = 0.15) did not affect significantly the relationship between corneal and scleral IOP in the multivariate regression analysis. The standard deviation of predicted corneal IOP was less than 1.2 mmHg within an inferotemporal scleral IOP range of 10 to 35 mmHg. Conclusions In children, corneal and scleral IOP are correlated significantly when measured by pneumatonometry. Measurements obtained from the inferotemporal sclera are better predictors of corneal IOP than those obtained from inferonasal sclera. Pneumatonometry on the inferotemporal sclera may be an alternative method to estimate IOP for pediatric patients from whom corneal IOP measurement is difficult to obtain.

Acute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted (P < 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.

Purpose: We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers. Methods: Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]). Results: In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR −0.39, 95% CI: −0.61, −0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR −0.18, 95% CI: −0.30, −0.05) compared to topical voriconazole. Conclusions: The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.

Macrolide Antimicrobial Resistance in MORDOR I In MORDOR I, azithromycin decreased mortality in children in Niger. In this report, it is shown that azithromycin also increased antimicrobial resista...

IMPORTANCE: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. OBJECTIVE: To evaluate changes in antifungal resistance over time. DESIGN, SETTING, AND PARTICIPANTS: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. INTERVENTIONS: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. MAIN OUTCOMES AND MEASURES: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. RESULTS: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P

Purpose To describe the characteristics of MAK -related retinal degeneration using optical coherence tomography angiography (OCTA) and adaptive optics scanning laser ophthalmoscopy (AOSLO). Design Cross-sectional study. Methods Six patients with rod-cone degeneration and disease-causing mutations in MAK were evaluated with visual acuity, spectral-domain OCT, confocal AOSLO, and OCTA. Foveal avascular zone (FAZ) area, vessel densities, and perfusion densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the central macula in all 6 patients were compared with 5 normal subjects. Cone spacing was measured in 4 patients from AOSLO images and compared with 37 normal subjects. Results Patients ranged from 25 to 81 years of age (mean, 52 years). Visual acuity varied from 20/13 to 20/40 +2 , except in 1 patient with cystoid macular edema whose vision was 20/60 − and 20/70 +1 . The SCP ( P = .012) and DCP ( P = .013) vessel density and perfusion density ( P =.015 and .013, respectively) were significantly lower in patients compared to normal subjects in the parafoveal region 1.0–3.0 mm from the fovea, but were similar to normal subjects within 1.0 mm of the fovea. The FAZ area was not significantly different from normal (all P ≥ .24). Cone spacing was normal at almost all locations in 2 patients with early disease and increased in 2 patients with advanced disease. Conclusions Although retinal vascular densities are reduced and cone spacing is increased in advanced disease, central foveal structure is maintained until late stages of disease, which may contribute to preservation of foveal vision in eyes with MAK -related retinal degeneration.

Background Substantial heterogeneity in measles outbreak sizes may be due to genotype-specific transmissibility. Using a branching process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number R among postelimination California measles cases during 2000-2015 (400 cases, 165 outbreaks). Methods Assuming a negative binomial secondary case distribution, we fit a branching process model to the distribution of outbreak sizes using maximum likelihood and estimated the reproduction number R for a multigenotype model. Results Genotype B3 is found to be significantly more transmissible than other genotypes (P = .01) with an R of 0.64 (95% confidence interval [CI], .48-.71), while the R for all other genotypes combined is 0.43 (95% CI, .28-.54). This result is robust to excluding the 2014-2015 outbreak linked to Disneyland theme parks (referred to as "outbreak A" for conciseness and clarity) (P = .04) and modeling genotype as a random effect (P = .004 including outbreak A and P = .02 excluding outbreak A). This result was not accounted for by season of introduction, age of index case, or vaccination of the index case. The R for outbreaks with a school-aged index case is 0.69 (95% CI, .52-.78), while the R for outbreaks with a non-school-aged index case is 0.28 (95% CI, .19-.35), but this cannot account for differences between genotypes. Conclusions Variability in measles transmissibility may have important implications for measles control; the vaccination threshold required for elimination may not be the same for all genotypes or age groups.

BACKGROUND Despite continued reductions in the number of HIV cases reported among San Francisco men who have sex with men (MSM) and the HIV-prevention potential offered by pharmaceutical tools such as pre-exposure prophylaxis (PrEP), there are uncertainties, particularly given reported decreases in consistent condom use. A key uncertainty is what groups of MSM should be targeted. This study estimates the distribution of behavioral patterns before infection among San Francisco MSM newly infected with HIV in 2014. METHODS We used a novel modeling approach. The approach uses estimates from the National HIV Behavioral Surveillance System for MSM, the Medical Monitoring Project, 2 trials of PrEP, and a meta-analysis of per-act risks of HIV infection. RESULTS The modeling study suggests that 76% of newly HIV-infected MSM in 2014 were individuals with no discernible strategy in the 6 months before infection: that is, they had condomless receptive anal intercourse with one or more partners not perceived to be HIV uninfected. An estimated 7% of newly infected MSM were serosorters before infection. CONCLUSIONS Prevention efforts in San Francisco must reach HIV-uninfected MSM with no discernible behavioral strategy, a group that constitutes 8% of HIV-uninfected MSM in the city. Our study suggests that if all HIV-uninfected, San Francisco MSM with no discernible strategy had been on PrEP in 2014, there would have been 70% fewer HIV infections among San Francisco MSM. Uncertainty analysis suggests that PrEP's impact may be maximized by encouraging PrEP persistence and concomitant reductions in sexual risk behaviors.

OBJECTIVE: To analyze the incidence rate of herpes zoster ophthalmicus (HZO) and differences by age, sex, race and region from 1994 to 2018. DESIGN: Retrospective, observational cohort study. SUBJECTS: Patients with a new International Classification of Disease (ICD) 9(th) or 10(th) code for herpes zoster (HZ) and HZO from January 1, 1994 to December 31, 2018 in the OptumLabs ® Data Warehouse. METHODS: OLDW, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record (EHR) data, was used to identify enrollees with continuous enrollment in the database for ≥365 days. Patients with no history of HZ or HZO and a new code for HZ and HZO were counted as incident cases. The incidence rate of HZO was calculated by year, 10-year age groups, sex, race, and geographic region. MAIN OUTCOME MEASURES: Differences in incidence rate from 1994 to 2018, by 10-year age groups and sex. RESULTS: From 1994 to 2018, 633,474 cases of HZ were reported with 49,745 (7.9%) having HZO. The incidence of HZO increased from 1994 to 2018 by an estimated 1.1 cases per 100,000 person-years annually (95% CI 1.0 to 1.3, P

The 2019-nCoV outbreak has raised concern of global spread. While person-to-person transmission within the Wuhan district has led to a large outbreak, the transmission potential outside of the region remains unclear. Here we present a simple approach for determining whether the upper limit of the confidence interval for the reproduction number exceeds one for transmission in the United States, which would allow endemic transmission. As of February 7, 2020, the number of cases in the United states support subcritical transmission, rather than ongoing transmission. However, this conclusion can change if pre-symptomatic cases resulting from human-to-human transmission have not yet been identified.

IntroductionCytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons.Methods and analysisThe Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host’s immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment.Ethics and disseminationThe University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication.Trial registration numberNCT03576898.

Objective:In the present study, we aimed to compare anthropometric indicators as predictors of mortality in a community-based setting.Design:We conducted a population-based longitudinal study nested in a cluster-randomized trial. We assessed weight, height and mid-upper arm circumference (MUAC) on children 12 months after the trial began and used the trial’s annual census and monitoring visits to assess mortality over 2 years.Setting:Niger.Participants:Children aged 6–60 months during the study.Results:Of 1023 children included in the study at baseline, height-for-age Z-score, weight-for-age Z-score, weight-for-height Z-score and MUAC classified 777 (76·0 %), 630 (61·6 %), 131 (12·9 %) and eighty (7·8 %) children as moderately to severely malnourished, respectively. Over the 2-year study period, fifty-eight children (5·7 %) died. MUAC had the greatest AUC (0·68, 95 % CI 0·61, 0·75) and had the strongest association with mortality in this sample (hazard ratio = 2·21, 95 % CI 1·26, 3·89, P = 0·006).Conclusions:MUAC appears to be a better predictor of mortality than other anthropometric indicators in this community-based, high-malnutrition setting in Niger.

To analyze the incidence rate (IR) of herpes zoster ophthalmicus (HZO) and differences by age, gender, race, and region from 1994 through 2018.Retrospective, observational cohort study.Patients with a new International Classification of Diseases, Ninth or Tenth Edition, codes for herpes zoster (HZ) and HZO from January 1, 1994, through December 31, 2018, in the OptumLabs Data Warehouse (OptumLabs, Cambridge, MA).OptumLabs Data Warehouse, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data, was used to identify enrollees with continuous enrollment in the database for 365 days or more. Patients with no history of HZ or HZO and a new code for HZ and HZO were counted as incident cases. The IR of HZO was calculated by year, 10-year age groups, gender, race, and region.Differences in IR from 1994 through 2018 by 10-year age groups and gender.From 1994 through 2018, 633 474 cases of HZ were reported, with 49 745 (7.9%) having HZO. The incidence of HZO increased from 1994 through 2018 by an estimated 1.1 cases per 100 000 person-years annually (95% confidence interval [CI], 1.0-1.3; P0.001). The estimated relative increase was 3.6% annually (95% CI, 3.0%-4.1%). HZO IR increased in all ages over 10 years until 2007, then began declining in individuals younger than 21 and older than 60, stabilizing in individuals 21 to 30 years old, and increasing more slowly among individuals 31 to 60 years old. Men showed an HZO incidence rate ratio (IRR) of 0.74 compared with women. Compared with white patients, the IRRs were 0.70, 0.75, and 0.64 for Asians, black patients, and Hispanics, respectively.The incidence of HZO has increased 3.6% per year from 1994 to 2018 in the United States. Since 2008, HZO incidence declined in individuals younger than 21 years and older than 60 years while increasing at a lower rate in middle-aged adults. Given the continued increase, greater efforts should be made to vaccinate eligible adults 50 years of age and older. More research on earlier vaccination is warranted.

Background As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. Methods For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. Results During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. Conclusions Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges., Author summary As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has been reported, and in which EVD cases and their contacts have been difficult for health workers to reach. We used an ensemble of models to estimate EVD transmission rates and to forecast the short- and long-term course of the outbreak. Our models project that a final size of roughly up to 300 additional cases is most likely, and estimate that transmission rates are higher than would be seen under optimal levels of contact tracing and vaccination. While a catastrophic outbreak is not projected, is it not ruled out, and prevention and vigilance are warranted.

Purpose: The clinical sign trachomatous inflammation - follicular (TF) is used to monitor indication for and response to mass azithromycin distribution in trachoma-endemic communities. Here, we assess the relationship between TF, trachomatous inflammation - intense (TI), and infection with ocular Chlamydia trachomatis over time during annual mass azithromycin distribution. Methods: We used data from a cluster-randomized trial of mass azithromycin distribution for trachoma control in a mesoendemic region of Niger. This study includes 24 communities that received 3 years of annual mass azithromycin distribution. TF, TI, and ocular chlamydia infection were monitored among children aged 0-5 years. We assessed the correlation between the prevalence of ocular chlamydia infection and 1) TF and 2) TI prevalence over time. Results: At baseline, ocular chlamydia prevalence was 21.2% (95% CI 14.3-28.1%), TF prevalence was 27.7% (95% CI 21.2-34.2%), and TI prevalence was 8.3% (95% CI 5.2-11.5%). The prevalence of all three measures decreased significantly over time (P < 0.001). At baseline, ocular chlamydia infection prevalence was strongly correlated with both TF (rho = 0.78, P < 0.0001) and TI (rho = 0.76, P < 0.0001). The correlation between ocular chlamydia infection and both TF and TI was weak at months 12 and 24. At 36 months, when TF prevalence had dropped below 10%, ocular chlamydia infection and TF were moderately correlated (rho = 0.70, P= 0.0002). Conclusions: Both TF and TI are good indicators of infection prevalence prior to mass azithromycin distribution. However, this relationship may be affected by repeated rounds of mass azithromycin distribution.

BACKGROUND: Herpes zoster (HZ) and herpes zoster ophthalmicus (HZO) are common and debilitating diseases. There is no consensus in the literature whether HZ and HZO exhibit seasonal patterns. OBJECTIVES: To determine whether HZ and HZO are seasonal. STUDY DESIGN: All patients in the OptumLabs® Data Warehouse (OLDW), a longitudinal, insurance claims database with de-identified lives between January 1, 2006 and December 31, 2017 with 365 days or more of continuous enrollment were considered in the study. The database was queried for patients reporting a new ICD-9/ICD-10 code for HZ or HZO and monthly counts of each administrative code were modeled using Morelet wavelets and analyzed for annual periodicity using Fisher’s g test. RESULTS: There were a total of 513,911 new cases of HZ during this time period; 40,166 cases (7.8%) were reported as HZO. Administrative coding for new cases of HZ exhibited annual periodicity (P

Background Biannual mass azithromycin administration to preschool children reduces all-cause mortality, but the mechanism for the effect is not understood. Azithromycin has activity against malaria parasites, and malaria is a leading cause of child mortality in the Sahel. The effect of biannual versus annual azithromycin distribution for trachoma control on serological response to merozoite surface protein 1 (MSP-119), a surrogate for malaria incidence, was evaluated among children in Niger. Methods Markers of malaria exposure were measured in two arms of a factorial randomized controlled trial designed to evaluate targeted biannual azithromycin distribution to children under 12 years of age compared to annual azithromycin to the entire community for trachoma control (N = 12 communities per arm). Communities were treated for 36 months (6 versus 3 distributions). Dried blood spots were collected at 36 months among children ages 1–5 years, and MSP-119 antibody levels were assessed using a bead-based multiplex assay to measure malaria seroprevalence. Results Antibody results were available for 991 children. MSP-119 seropositivity was 62.7% in the biannual distribution arm compared to 68.7% in the annual arm (prevalence ratio 0.91, 95% CI 0.83 to 1.00). Mean semi-quantitative antibody levels were lower in the biannual distribution arm compared to the annual arm (mean difference − 0.39, 95% CI − 0.05 to − 0.72). Conclusions Targeted biannual azithromycin distribution was associated with lower malaria seroprevalence compared to that in a population that received annual distribution. Trial Registration Clinicaltrials.gov NCT00792922

Author(s): Bensinger, Ethan; Rinella, Nicholas; Saud, Asma; Loumou, Panagiota; Ratnam, Kavitha; Griffin, Shane; Qin, Jia; Porco, Travis C; Roorda, Austin; Duncan, Jacque L | Abstract: PurposeTo assess the relationship between cone spacing and visual acuity in eyes with rod-cone degeneration (RCD) followed longitudinally.MethodsHigh-resolution images of the retina were obtained using adaptive optics scanning laser ophthalmoscopy from 13 eyes of nine RCD patients and 13 eyes of eight healthy subjects at two sessions separated by 10 or more months (mean 765 days, range 311-1935 days). Cone spacing Z-score measured as close as possible (average l0.25°) to the preferred retinal locus was compared with visual acuity (letters read on the Early Treatment of Diabetic Retinopathy Study [ETDRS] chart and logMAR) and foveal sensitivity.ResultsCone spacing was significantly correlated with ETDRS letters read (ρ = -0.47, 95%CI -0.67 to -0.24), logMAR (ρ = 0.46, 95%CI 0.24 to 0.66), and foveal sensitivity (ρ = -0.30, 95%CI -0.52 to -0.018). There was a small but significant increase in mean cone spacing Z-score during follow-up of +0.97 (95%CI 0.57 to 1.4) in RCD patients, but not in healthy eyes, and there was no significant change in any measure of visual acuity.ConclusionsCone spacing was correlated with visual acuity and foveal sensitivity. In RCD patients, cone spacing increased during follow-up, while visual acuity did not change significantly. Cone spacing Z-score may be a more sensitive measure of cone loss at the fovea than visual acuity in patients with RCD.

IMPORTANCE This is the first study to compare the efficacy and safety of endocyclophotocoagulation (ECP) via pars plana (ECP-plus) with ECP via limbus (anterior ECP) for treating glaucoma. BACKGROUND There is no direct comparison of treatment outcomes between ECP-plus and anterior ECP. DESIGN Retrospective study. PARTICIPANTS Fifty-four consecutive patients. METHODS Fifty-eight eyes from 54 consecutive patients underwent anterior ECP (33 eyes) or ECP-plus (25 eyes) with 2-year follow-up. Linear mixed model was used to analyse the surgical outcomes. MAIN OUTCOME MEASURES Intraocular Pressure (IOP) was the primary outcome. Secondary outcomes were best-corrected visual acuity, number of glaucoma medications, complications and success rate. RESULTS Compared to anterior ECP, patients in the ECP-plus group had lower IOP (estimate of effect size [EES] = -3.7 mmHg, P = 0.023) and used fewer number of glaucoma medications (EES = -1.11, P = 0.003), after adjusting for degrees of treatment, preoperative IOP, and presence of combined ECP and phacoemulsification procedure. Patients with ECP-plus achieved a higher success rate at 2 years postoperatively (80% vs 33.3%, P

OBJECTIVE. To determine the precision of new and established methods for estimating duration of HIV infection. DESIGN. A retrospective analysis of HIV testing results from serial samples in commercially-available panels, taking advantage of extensive testing previously conducted on 53 seroconverters. METHODS. We initially investigated four methods for estimating infection timing: 1) “Fiebig stages” based on test results from a single specimen; 2) an updated “4(th) gen” method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; 3) modeling of “viral ramp-up” dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and 4) using detailed clinical testing history to define a plausible interval and best estimate of infection time. We then investigated a “two-step method” using data from both methods 3 and 4, allowing for test results to have come from specimens collected on different days. RESULTS. Fiebig and “4(th) gen” staging method estimates of time since detectable viremia had similar and modest correlation with observed data. Correlation of estimates from both new methods (3 and 4), and from a combination of these two (“2-step method”) was markedly improved and variability significantly reduced when compared with Fiebig estimates on the same specimens. CONCLUSIONS. The new “two-step” method more accurately estimates timing of infection and is intended to be generalizable to more situations in clinical medicine, research, and surveillance than previous methods. An online tool is now available that enables researchers/clinicians to input data related to method 4, and generate estimated dates of detectable infection.

Background To examine the effect of mitomycin c (MMC) and 5-flurouracil (5-FU) on treatment outcomes following Ahmed glaucoma valve (AGV) implantation. Design Retrospective consecutive case series. Participants Fifty patients who received AGV implantation from 1999–2013 in the San Francisco VA hospital. Methods The + INJECTION group received intraoperative MMC followed by postoperative injections of MMC and/or 5-FU whereas the -INJECTION group did not. Main Outcome Measures Primary outcome was treatment success at one year post-implantation. Intraocular pressure (IOP), the presence of a hypertensive phase (HP), and the number of glaucoma medications were examined at time points up to one year. Results Twenty-six patients/eyes in the + INJECTION group and 24 patients/eyes in the -INJECTION group were included. Treatment success was higher in the + INJECTION compared to the -INJECTION group (86% versus 58%; p = 0.04). IOP was lower in the + INJECTION compared to the -INJECTION group at 1, 3, 6, and 12 months (p

PurposeTo investigate the association between ultrasound energy, expressed as cumulative dissipated energy (CDE), and changes in intraocular pressure (IOP) after uncomplicated cataract surgery by phacoemulsification.MethodsIn this prospective study, nonglaucomatous subjects underwent cataract surgery by phacoemulsification. IOP was compared by clustered linear regression at 4 separate time-points: preoperative, 1 day, 1 month, and 3 months after cataract surgery. Changes in the IOP were evaluated as a function of CDE using univariate and multivariate clustered linear regression models, which adjusted for sex, ethnicity, age, axial length, spherical equivalent, mean preoperative Shaffer gonioscopy grade of all 4 quadrants, cataract grade, preoperative IOP, central corneal thickness, and use of both eyes in the same subject.ResultsOne hundred sixty-one eyes (89 Asian, 49 white, 12 African, and 11 Hispanic) from 116 nonglaucomatous subjects were analyzed. The 161 eyes included 81 right and 80 left eyes. The 89 Asian eyes included 46 Chinese, 35 Filipino, and 8 Vietnamese. Preoperative IOP was 14.9±3.2 mm Hg. Postoperative IOP significantly increased to 16.0±4.9 mm Hg at 1 day (P=0.037) and decreased to 12.4±3.1 and 12.3±3.0 mm Hg at 1 and 3 months, respectively (both P0.05).ConclusionsThe amount of ultrasound energy delivered to the eye during phacoemulsification, expressed as CDE, was not associated with postoperative changes in IOP.

Author(s): Hiep, Nguyen Xuan; Ngondi, Jeremiah M; Anh, Vu Tuan; Dat, Tran Minh; An, Tran Van; Dung, Nguyen Chi; Thang, Nguyen Duy; Chu, Brian K; Willis, Rebecca; Bakhtiari, Ana; Pavluck, Alexandre L; Johnson, James; Sidwell, Joshua; Brady, Molly; Henry, Rob; Mosher, Aryc; Porco, Travis C; Lietman, Thomas M; Rotondo, Lisa A; Lewallen, Susan; Courtright, Paul; Solomon, Anthony W; Global Trachoma Mapping Project | Abstract: PurposeFollowing interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation-follicular (TF) and trichiasis.MethodsA population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9nyears and adults aged ≥50nyears) were examined for trachoma.ResultsA total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Ha Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50nyears, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50nyears, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages.ConclusionFindings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Ha Giang Province, further investigations will be undertaken.

Purpose/Aim: To evaluate the best formula to predict intraocular pressure (IOP) reduction after cataract surgery.Materials and methods: In this prospective longitudinal study, we included consecuti...

BackgroundMass azithromycin distributions are effective for clearing ocular strains of Chlamydia trachomatis, yet infection frequently returns in areas with hyperendemic trachoma. A better understanding of the factors associated with chlamydial reinfection could be helpful to plan trachoma elimination strategies.MethodsThis was a prospective cohort study conducted in a trachoma-hyperendemic region of Ethiopia in 2003. As part of a larger cluster-randomized trial, 21 villages were treated with a single mass azithromycin distribution and all children 5years and younger were monitored for ocular chlamydia and clinically active trachoma at baseline and at 2 and 6months following the treatment.ResultsIn 20 villages with available data, azithromycin treatment coverage was 88.7% (95% confidence interval [CI] 85.7-91.8%). In total, 1005 children tested negative for ocular chlamydia at the 2-month visit, of whom 41 became infected by 6months (1.0 incident chlamydia infections per 100 person-months, 95%CI 0.7-1.4). The presence of intense trachomatous inflammation (TI) at baseline was associated with incident infection at 6months (incidence rate ratio 1.91, 95%CI 1.03-3.55). Ocular chlamydia infections clustered more within households than communities: (intraclass correlation coefficient 0.01 for communities and 0.29 for households six months posttreatment). Younger children were more likely to have persistent clinically active trachoma (P=0.03).ConclusionsMore intensive antibiotic distributions may be warranted for younger children, for children with TI, and for households containing children with ocular chlamydia infections.

Mass drug administration (MDA) with azithromycin may reduce under-5 child mortality (U5M) in sub-Saharan Africa. Here, we conducted a pooled analysis of all published cluster-randomized trials evaluating the effect of azithromycin MDA on child mortality. We pooled data from cluster-randomized trials randomizing communities to azithromycin MDA versus control. We calculated mortality rates in the azithromycin and control arms in each study, and by country for multisite studies including multiple countries. We conducted a two-stage individual community data meta-analysis to estimate the effect of azithromycin for prevention of child mortality. Three randomized controlled trials in four countries (Ethiopia, Malawi, Niger, and Tanzania) were identified. The overall pooled mortality rate was 15.9 per 1,000 person-years (95% confidence interval [CI]: 15.5–16.3). The pooled mortality rate was lower in azithromycin-treated communities than in placebo-treated communities (14.7 deaths per 1,000 person-years, 95% CI: 14.2–15.3 versus 17.2 deaths per 1,000 person-years, 95% CI: 16.5–17.8). There was a 14.4% reduction in all-cause child mortality in communities receiving azithromycin MDA (95% CI: 6.3–21.7% reduction, P = 0.0007). All-cause U5M was lower in communities receiving azithromycin MDA than in control communities, suggesting that azithromycin MDA could be a new tool to reduce child mortality in sub-Saharan Africa. However, heterogeneity in effect estimates suggests that the magnitude of the effect may vary in time and space and is currently not predictable.

Background: Violence can impact Ebola virus disease (EVD) transmission in the current outbreak in the eastern Democratic Republic of the Congo (DRC). We hypothesized that violent events targeted against the Ebola response will be associated with more EVD transmission than untargeted events. Methods: We used a dynamic cohort of individuals who lived in Ebola-affected and unaffected health zones in DRC from April 2018 to August 2019. The time-varying exposure was the number of violent events, as defined by the Armed Conflict Location & Event Data Project (ACLED) database, that occurred in each health zone over a series of days. These violent events were categorized into "Ebola-targeted" vs. "Ebola-untargeted", and further sub-categorized by "civilians," "military or politics," or "protests." The outcome variable was the estimated daily reproduction number (Rest) by health zone, which was estimated from daily EVD case counts (from DRC Ministry of Health) by the Wallinga-Teunis method. We fit a linear time-series regression to model the relationship of violent events and R comparing EVD-affected and unaffected health zones. Findings: The average Rest was 1.06 (95% confidence interval [CI]: 1.02-1.11). We found an overall change in R of 0.035 (95% CI: 0.020-0.050) among Ebola-affected compared to unaffected health zones. Violent events targeting the Ebola response were associated with an increase in Rest of 0.098 (95% CI: 0.064-0.132) while untargeted, violent events had a smaller effect (0.022, 95% CI: 0.005-0.038). Additional analyses showed the increase in Rest was primarily driven by Ebola-targeted civilian events and, to a lesser extent, by Ebola-untargeted military, political, or protest events. Interpretation: These findings suggest that civilian acts of violence directly targeted against the Ebola response efforts had the largest impact on EVD transmission. To a lesser extent, untargeted military, political, or protest events also had an impact. Funding Statement: This work was supported by National Institute of Allergy and Infectious Disease (K08 grant number AI139361 to ETR; K23 grant number AI135037 to JDK) and National Institute of General Medical Sciences (R01 grant number GM130900 to TCP, JDK, and ETR). Declaration of Interests: The authors stated: "None to declare." Ethics Approval Statement: The authors stated: "Data were publicly available and de-identified, so ethics committee approval was not needed."

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.

There is too much going on around us to see everything at once, or to simultaneously process all the information in our field of view. Instead, we normally direct our gaze to parts of the scene that are particularly meaningful or important. Yet, even when we think that we are keeping our eyes still on an object of interest, our eyes remain in continuous motion. This chapter reviews the different kinds of “fixational” eye movements (the eye movements that occur when our gaze is “fixed” on an object or a point in space). We also discuss the effects that fixational eye movements have on vision and perception, their potential adaptive advantages, and their generation mechanisms. After reading this chapter, you will be able to articulate the importance of fixational eye movements in facilitating and influencing visual perception (for instance, in helping us to see the world and assisting us as we perform specific tasks). You will be able to explain the role of microsaccades (the largest of these small fixational eye movements) in counteracting neural adaptation and visual fading (the perceptual vanishing of an unchanging stimulus). You will also be able to outline the neural generation of microsaccades. In addition, this chapter will help you understand the relationship between fixational eye movements and shifts of attention. Finally, you will be able to describe, in general terms, the potential relevance of fixational eye movements to the diagnosis of neurological disorders.

Author(s): Qin, Jia; Rinella, Nicholas; Zhang, Qinqin; Zhou, Hao; Wong, Jessica; Deiner, Michael; Roorda, Austin; Porco, Travis C; Wang, Ruikang K; Schwartz, Daniel M; Duncan, Jacque L | Abstract: PurposeTo compare cone spacing and choriocapillaris (CC) perfusion adjacent to geographic atrophy (GA) in patients with age-related macular degeneration (AMD) and age-similar normal eyes.MethodsSubjects were imaged using adaptive optics scanning laser ophthalmoscopy (AOSLO), fundus autofluorescence (FAF), and swept-source optical coherence tomography angiography. The GA border was identified using FAF images; CC flow void was analyzed in 1° regions extending from the GA border. A grader masked to CC perfusion selected regions of interest (ROIs) with unambiguous cone mosaics in AOSLO images. At each ROI, cone spacing and CC flow void were converted to Z-scores (standard deviations from the mean of 12 normal eyes aged 50 to 81 years for cone spacing, and 60 normal eyes age 51 to 88 years for CC flow void).ResultsExcluding regions of GA and drusen, CC flow void in eight eyes of six patients with AMD was significantly greater than in four age-similar normal eyes (exact permutation test, P = 0.024). CC flow void was negatively correlated with distance from the GA margin (r = -0.35; 95% confidence interval [CI], -0.53 to -0.12). Increased cone spacing was significantly correlated with CC flow void (r = 0.33; 95% CI, 0.12 to 0.59). Cone spacing was increased in 39% of ROIs, while CC flow void was increased in 96% of ROIs.ConclusionsIn eyes with GA due to AMD, CC hypoperfusion was significantly correlated with, and more extensive than, cone photoreceptor loss. The results suggest that reduced CC perfusion contributes to the development of GA.

BackgroundAs of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak with case-count time series from prior outbreaks to project the short-term and long-term course of the outbreak.MethodsFor short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts.ResultsDuring validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone.ConclusionsOur projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.Author summaryAs of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has been reported, and in which EVD cases and their contacts have been difficult for health workers to reach. We used an ensemble of models to estimate EVD transmission rates and to forecast the short- and long-term course of the outbreak. Our models project that a final size of roughly up to 300 additional cases is most likely, and estimate that transmission rates are higher than would be seen under optimal levels of contact tracing and vaccination. While a catastrophic outbreak is not projected, is it not ruled out, and prevention and vigilance are warranted.

Background Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met. Methods A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1–5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation—follicular [TF] and trachomatous inflammation—intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level. Results Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children. Conclusion Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger. Trial registration ClinicalTrials.gov NCT00792922., Author summary Trachoma programs currently use the clinical sign of trachomatous inflammation-follicular (TF) to guide community treatment decisions and evaluate response to mass drug administration with azithromycin. These programs rely on clinical grading that poorly correlates with infection with the causative agent of trachoma, Chlamydia trachomatis (Ct), in low prevalence areas. Serologic measures of Ct may provide additional information about exposure and transmission patterns. Here, we evaluated the relationship between serologic markers of Ct, infection, and TF at the individual and community levels to evaluate the utility of serology for measuring trachoma in a mesoendemic region of Niger. We found that serologic markers correlated with both infection and TF, indicating that inclusion of serologic markers may be useful to guide trachoma decision making.

Background In many infectious diseases, a core group of individuals plays a disproportionate role in transmission. If these individuals were effectively prevented from transmitting infection, for example with a perfect vaccine, then the disease would disappear in the remainder of the community. No vaccine has yet proven effective against the ocular strains of chlamydia that cause trachoma. However, repeated treatment with oral azithromycin may be able to prevent individuals from effectively transmitting trachoma. Methodology/Principal findings Here we assess several methods for identifying a core group for trachoma, assuming varying degrees of knowledge about the transmission process. We determine the minimal core group from a completely specified model, fitted to results from a large Ethiopian trial. We compare this benchmark to a core group that could actually be identified from information available to trachoma programs. For example, determined from the rate of return of infection in a community after mass treatments, or from the equilibrium prevalence of infection. Conclusions/Significance Sufficient groups are relatively easy for programs to identify, but will likely be larger than the theoretical minimum., Author summary Public health programs can in theory target treatment to a core group of individuals responsible for a disproportionate amount of transmission. The smallest group of individuals who need to be vaccinated to eventually eliminate an infectious disease is easy to find in theory, but not in practice. While no vaccine has proven effective for trachoma, intensive periodic treatment may be able to effectively prevent individuals from transmitting infection. Here we use a variety of methods to find a core group for trachoma transmission, including methods that use information available to trachoma programs. We show that the rate that infection returns into a community after mass treatment, or the pre-treatment prevalence of an infectious disease should work, but will include more individuals than the theoretical minimum core group.

PURPOSE AND OBJECTIVE: Epidemic and seasonal infectious conjunctivitis outbreaks can adversely impact education, workforce and economy. Yet conjunctivitis is typically not a reportable disease, potentially delaying mitigating intervention. Our study objective was to determine if conjunctivitis epidemics could be identified using Google Trends search data. DESIGN: Search data for conjunctivitis-related and control search terms from 5 years and countries worldwide were obtained. Country and term were masked. Temporal scan statistics were applied to identify candidate epidemics. Candidates were then assessed for geotemporal concordance with an a priori defined collection of known reported conjunctivitis outbreaks, as a measure of sensitivity. PARTICIPANTS: Populations by country that searched Google’s search engine using our study terms. MAIN OUTCOME MEASURES: Percent of known conjunctivitis outbreaks also found in the same country and time period by our candidate epidemics, identified from conjunctivitis-related searches RESULTS: We identified 135 candidate conjunctivitis epidemic periods from 77 countries. Compared to our a priori defined collection of known reported outbreaks, candidate conjunctivitis epidemics identified 18 out of 26 (69% sensitivity) of the reported country-wide and/or island nation-wide outbreaks, 9 out of 20 (45% sensitivity) of the reported region and/or district-wide outbreaks, but far fewer nosocomial and reported smaller outbreaks. Similar overall and individual sensitivity, as well as specificity, was found on a country-level basis. We also found that 83% of our candidate epidemics had start dates prior (of those, 20% were over 12 weeks prior) to their concurrent reported outbreak’s report issuance date. Permutation tests provided evidence that on average conjunctivitis candidate epidemics occurred geotemporally closer to outbreak reports than chance alone would suggest (P