Adjusting Incidence Estimates with Laboratory Test Performances: A Pragmatic Maximum Likelihood Estimation-Based Approach.

Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings.

Association of protective behaviors with SARS-CoV-2 infection: results from a longitudinal cohort study of adults in the San Francisco Bay Area.

PURPOSE: In an effort to decrease transmission during the first years of the COVID-19 pandemic, public health officials encouraged masking, social distancing, and working from home, and restricted travel. However, many studies of the effectiveness of these measures had significant methodologic limitations. In this analysis, we used data from the TrackCOVID study, a longitudinal cohort study of a population-based sample of 3846 adults in the San Francisco Bay Area, to evaluate the association between self-reported protective behaviors and incidence of SARS-CoV-2 infection. METHODS: Participants without SARS-CoV2 infection were enrolled from August to December 2020 and followed monthly with testing and surveys (median of four visits). RESULTS: A total of 118 incident infections occurred (3.0% of participants). At baseline, 80.0% reported always wearing a mask; 56.0% avoided contact with nonhousehold members some/most of the time; 9.6% traveled outside the state; and 16.0% worked 20 or more hours per week outside the home. Factors associated with incident infection included being Black or Latinx, having less than a college education, and having more household residents. The only behavioral factor associated with incident infection was working outside the home (adjusted hazard ratio 1.62, 95% confidence interval 1.02-2.59). CONCLUSIONS: Focusing on protecting people who cannot work from home could help prevent infections during future waves of COVID-19, or future pandemics from respiratory viruses. This focus must be balanced with the known importance of directing resources toward those at risk of severe infections.

Identifying Paucisymptomatic or Asymptomatic and Unrecognized Ebola Virus Disease Among Close Contacts Based on Exposure Risk Assessments and Screening Algorithms.

BACKGROUND: There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for paucisymptomatic or asymptomatic Ebola virus (EBOV) infection and unrecognized EBOV disease (EVD). METHODS: We used serostatus and self-reported postexposure symptoms from a cohort study to classify contact-participants as having no infection, paucisymptomatic or asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, or high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with or without rapid diagnostic testing (RDT) or exposure assessments. RESULTS: This analysis included 990 EVD survivors and 1909 contacts, of whom 115 (6%) had paucisymptomatic or asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (adjusted odds ratio, 3.5 [95% confidence interval, 2.4-4.9]). To identify contacts with unrecognized EVD who test negative by the WHO case definition, the sensitivity was 96% with RDT (95% confidence interval, 91%-99%), 87% with high-risk exposure (82%-92%), and 97% with intermediate- to high-risk exposures (93%-99%). The proportion of false-positives was 2% with RDT and 53%-93% with intermediate- and/or high-risk exposures. CONCLUSION: We demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD.

Design of a population-based longitudinal cohort study of SARS-CoV-2 incidence and prevalence among adults in the San Francisco Bay Area.

PURPOSE: We describe the design of a longitudinal cohort study to determine SARS-CoV-2 incidence and prevalence among a population-based sample of adults living in six San Francisco Bay Area counties. METHODS: Using an address-based sample, we stratified households by county and by census-tract risk. Risk strata were determined by using regression models to predict infections by geographic area using census-level sociodemographic and health characteristics. We disproportionately sampled high and medium risk strata, which had smaller population sizes, to improve precision of estimates, and calculated a desired sample size of 3400. Participants were primarily recruited by mail and were followed monthly with PCR testing of nasopharyngeal swabs, testing of venous blood samples for antibodies to SARS-CoV-2 spike and nucleocapsid antigens, and testing of the presence of neutralizing antibodies, with completion of questionnaires about socio-demographics and behavior. Estimates of incidence and prevalence will be weighted by county, risk strata and sociodemographic characteristics of non-responders, and will take into account laboratory test performance. RESULTS: We enrolled 3842 adults from August to December 2020, and completed follow-up March 31, 2021. We reached target sample sizes within most strata. CONCLUSIONS: Our stratified random sampling design will allow us to recruit a robust general population cohort of adults to determine the incidence of SARS-CoV-2 infection. Identifying risk strata was unique to the design and will help ensure precise estimates, and high-performance testing for presence of virus and antibodies will enable accurate ascertainment of infections.

Food Insecurity as a Risk Factor for Outcomes Related to Ebola Virus Disease in Kono District, Sierra Leone: A Cross-Sectional Study.

Studies have shown that people suffering from food insecurity are at higher risk for infectious and noncommunicable diseases and have poorer health outcomes. No study, however, has examined the association between food insecurity and outcomes related to Ebola virus disease (EVD). We conducted a cross-sectional study in two Ebola-affected communities in Kono district, Sierra Leone, from November 2015 to September 2016. We enrolled persons who were determined to have been exposed to Ebola virus. We assessed the association of food insecurity, using an adapted version of the Household Food Insecurity Access Scale, a nine-item scale well validated across Africa, with having been diagnosed with EVD and having died of EVD, using logistic regression models with cluster-adjusted standard errors. We interviewed 326 persons who were exposed to Ebola virus; 61 (19%) were diagnosed with EVD and 45/61 (74%) died. We found high levels (87%) of food insecurity, but there was no association between food insecurity and having been diagnosed with EVD. Among EVD cases, those who were food insecure had 18.3 times the adjusted odds of death than those who were food secure (P = 0.03). This is the first study to demonstrate a potential relationship between food insecurity and having died of EVD, although larger prospective studies are needed to confirm these findings.

Characterization of HIV Recent Infection Among High-Risk Men at Public STI Clinics in Mumbai.

We examined associations with HIV recent infection and estimated transmitted drug resistance (TDR) prevalence among 3345 men at sexually transmitted infection clinics in Mumbai (2002-2005). HIV seroincidence was 7.92% by the BED-CEIA and was higher at a clinic located near brothels (12.39%) than at a hospital-based clinic (3.94%). HIV recent infection was associated with a lifetime history of female sex worker (FSW) partners, HSV-2, genital warts, and gonorrhea. TDR prevalence among recent infection cases was 5.7%. HIV testing services near sex venues may enhance case detection among high-risk men who represent a bridging population between FSWs and the men's other sexual partners.

Anatomy of a Hotspot: Chain and Seroepidemiology of Ebola Virus Transmission, Sukudu, Sierra Leone, 2015-16.

Studies have yet to include minimally symptomatic Ebola virus (EBOV) infections and unrecognized Ebola virus disease (EVD) in Ebola-related transmission chains and epidemiologic risk estimates. We conducted a cross-sectional, sero-epidemiological survey from October 2015 to January 2016 among 221 individuals living in quarantined households from November 2014 to February 2015 during the Ebola outbreak in the village of Sukudu, Sierra Leone. Of 48 EBOV-infected persons, 25% (95% confidence interval [CI], 14%-40%) had minimally symptomatic EBOV infections and 4% (95% CI, 1%-14%) were unrecognized EVD cases. The pattern of minimally symptomatic EBOV infections in the transmission chain was nonrandom (P < .001, permutation test). Not having lived in the same house as an EVD case was significantly associated with minimally symptomatic infection. This is the first study to investigate a chain of EBOV transmission inclusive of minimally symptomatic EBOV infections and unrecognized EVD. Our findings provide new insights into Ebola transmission dynamics and quarantine practices.

Symptoms of Depression in People Living with HIV in Ho Chi Minh City, Vietnam: Prevalence and Associated Factors.

This cross-sectional study investigated the prevalence and correlates of symptoms of depression among 400 people living with HIV/AIDS (PLHIV) from two HIV clinics in Ho Chi Minh City, Vietnam. Based on the Center for Epidemiologic Studies-Depression scale, 36.5% of participants were classified as likely to be clinically depressed. Factors independently associated with symptoms of depression included self-report of poor or fair health (aOR 2.16, 95% CI 1.33-3.51), having a low body mass index (aOR 1.85, 95% CI 1.13-3.04), reporting recent problems with family (aOR 1.97, 95% CI 1.21-3.19), feeling shame about being HIV-infected (aOR 1.90, 95% CI 1.20-3.00), and reporting conflict with a partner (aOR 2.21, 95% CI 1.14-4.26). Participants who lived with family (aOR 0.48, 95% CI 0.25-0.90) or who received emotional support from their families or supportive HIV networks (aOR 0.45, 95% CI 0.25-0.80) were less likely to experience symptoms of depression. Screening for and treatment of depression among Vietnamese PLHIV are needed.

High-risk motorcycle taxi drivers in the HIV/AIDS era: a respondent-driven sampling survey in Kampala, Uganda.

We evaluated motorcycle taxi ('boda-boda') drivers in Kampala for the prevalence of HIV/sexually transmitted infections. We used respondent-driven sampling to recruit a cross-sectional sample of boda-boda drivers. We collected data through audio computer-assisted self-administered interviews. Men were tested for HIV, syphilis serology using Rapid Plasma Reagin and enzyme immunoassay, and Chlamydia and gonorrhoea using urine polymerase chain reaction. We recruited 683 men. Median age was 26 years; 59.4% were single. The prevalence of HIV was 7.5% (95% CI 5.2-10.0), of positive syphilis serology was 6.1% (95% CI 4.3-8.1), of Chlamydia was 1.1% (95% CI 0.4-2.0), and of gonorrhoea was 1.2% (95% CI 0.1-1.2). Many men (67.8%) had both casual and regular partners, sex with other men (8.7%), and commercial sex (33.1%). Factors associated with having HIV included reporting a genital ulcer (odds ratio [OR] =2.4, 95% CI 1.4-4.4), drinking alcohol during last sex (OR 2.0, 95% CI 1.1-3.7), having 4-6 lifetime partners (OR 2.2, 95% CI 1.0-4.8), and having one's last female partner be >24 years of age (OR 2.8, 95% CI 1.2-6.6). Independent predictors of HIV included age ≥31 (adjusted OR (aOR) 5.8, 95% CI 1.5-48.5), having 4-6 partners (aOR 2.2, 95%CI 1.0-5.1), and self-report of a genital ulcer (OR 2.3, 95% CI 1.2-4.1). Only 39.2% of men were circumcised, and 36.9% had been HIV tested in the past. Male boda-boda drivers have a higher prevalence of HIV than the general population, and low frequency of preventive behaviours, such as circumcision and HIV testing. Targeted and intensified interventions for this group are warranted.

University students and the risk of HIV and other sexually transmitted infections in Uganda: the Crane survey.

Adolescents and young adults are at high risk of human immunodeficiency virus (HIV) infection in sub-Saharan Africa. Previous reports have found that university students in Africa comprise a sexually active population, although the prevalence of HIV or sexually transmitted infections (STI) has not been measured. We conducted a cross-sectional survey of students from five large universities in Kampala, Uganda, using respondent-driven sampling. We asked students to complete behavioral questionnaires and provide biological samples to test for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and bacterial vaginosis. We enrolled 649 students and obtained interpretable data from 640. Around 50% of the respondents were male, and the mean age was 22 years. An estimated 0.8% (95% CI 0.0-2.0) of male students had Chlamydia infection, approximately 4.3% (95% CI 2.0-7.0) had syphilis, 0.4% (95% CI 0.0-0.9) had HIV, and none had gonorrhea. An estimated 32.6% (95% CI 22.4-40.8) of women had bacterial vaginosis, 2.5% (95% CI 0.7-6.3) had Chlamydia infection, 1.7% (95% CI 0.5-3.6) had syphilis, 1.0% (95% CI 0.0-2.4) had gonorrhea, 0.9% (95% CI 0.0-4.2) had trichomoniasis, and 0.9% (95% CI 0.0-1.8) had HIV. We found no significant risk factors for HIV or other STI among males. We also found that not using a condom during the latest sexual intercourse was significantly associated with HIV infection, other STI, or bacterial vaginosis (OR 2.16; 95% 1.26-3.78) among females. We conclude that while university students are sexually active and there is substantial risk for syphilis, there is little evidence of substantially increased HIV risk among them.

Virological surveillance of influenza-like illness among children in Ghana, 2008-2010.

BACKGROUND: The global annual attack rate for influenza is estimated to be 10%-20% in children, although limited information exists for Africa. In 2007, Ghana initiated influenza surveillance by routine monitoring of acute respiratory illness to obtain data on circulating strains. We describe influenza surveillance in children <11 years old who had influenza-like illness (ILI) from January 2008 to December 2010. METHODS: Oropharyngeal swabs from pediatric outpatients with ILI attending any of 22 health facilities across the country were submitted. We tested swabs for influenza virus using molecular assays, virus isolation, and hemagglutination assays. RESULTS: Of the 2810 swabs, 636 (23%) were positive for influenza virus. The percentage of positives by gender was similar. The proportion of ILI cases positive for influenza increased with age from 11% (31/275) in infants (aged 0-1 years) to 31% (377/1219) among children aged 5-10 years (P < .001). The majority of cases were influenza A (90%), of which 60% were influenza A(H1N1)pdm09. In all 3 years, influenza activity appeared slightly higher during May through July. CONCLUSIONS: During the 3 years of influenza surveillance in Ghana, children aged <11 years bore a high burden of influenza-associated ILI.

Sexual behavior among men who have sex with women, men, and Hijras in Mumbai, India--multiple sexual risks.

We describe the same-sex partnerships and sexual risk behavior of men attending sexually transmitted infection (STI) clinics in Mumbai, India. The HIV prevalence among 2,381 men sampled was 14%; 62% had a documented STI. Almost all men reported sex with women; additionally, 13% also reported having sex with other men, 13% reported sex with Hijras (male-to-female transgenders), and 11% had sex with all 3 genders. Men who had sex with men and/or Hijras as well as women, reported having greater numbers of partners, including female sex workers (FSW), and were more likely to engage in insertive anal and oral sex with women. The prevalence of HIV was higher among men having sex with Hijras (14%) or with all 3 genders (13%) than among men having sex with men and women (8%). A high proportion of men who attend STI clinics in Mumbai are behaviorally bi- or tri-sexual and have multiple partners with whom they engage in risky sex. STI/HIV prevention programs should not assume that men only have sex with women.

Changes in high-risk behaviors over time among young drug users in South Vietnam: a three-province study.

Vietnam is in the midst of an expanding HIV epidemic, primarily driven by an increase in injection drug use in young people. This study was conducted to understand the patterns and initiation of drug use, and the sexual risk behavior among youth in three provinces in southern Vietnam. A cross-sectional survey was conducted among male and female drug users under age 25 recruited from drug treatment centers (N = 560) and the community (N = 240) in Ho Chi Minh City, Dong Nai and Ba Ria-Vung Tau. The majority of those surveyed (82%) began by smoking heroin; after a year, 57% were injecting heroin and/or opium. Initiation of drug use frequently occurred in entertainment venues. Among injectors, 23% shared needles; 71% of all users were sexually active of whom 77% had unprotected sex. More than half of those recruited from treatment centers had previously been in drug treatment. Public health programs to prevent and treat the dual epidemics of HIV and drug abuse must be able to access and respond to the needs of youth, many of whom are unemployed and exposed to drug traffic.

An archived lot of coccidioidin induces specific coccidioidal delayed-type hypersensitivity and correlates with in vitro assays of coccidioidal cellular immune response.

No test for assessing cellular immune response in coccidioidomycosis is currently available in the United States. In the present study, we tested 49 healthy subjects living in the coccidioidal endemic region with a 1:55.8 dilution of a single lot of coccidioidin archived since the 1970s. In this group, 23 evaluable subjects demonstrated >/=5 mm of induration at 24, 48 or 72 h, with a mean+/-SEM maximum induration of 18.4+/-4.0 mm. The induration results among 14 subjects reactive at 24 h were compared to those from 179 individuals in an historical cohort studied in the 1980s using a reference lot of coccidioidin. Results were within 5% and not significantly different (P=0.924). The maximum induration response of all evaluable subjects correlated significantly with the results of in vitro tests of coccidioidal cellular immunity using supernatant interferon-gamma concentration and CD69 expression on T cells (Spearman rank correlation coefficients 0.69 and 0.68, respectively; P<0.01 for both). These data suggest that archived coccidioidin retains its potency and specificity and that in vitro test of coccidioidal immunity may have utility in the measurement of coccidioidal cellular immunity.

Alcohol use by men is a risk factor for the acquisition of sexually transmitted infections and human immunodeficiency virus from female sex workers in Mumbai, India.

OBJECTIVE: We investigated whether men who were under the influence of alcohol when visiting female sex workers (FSW) were at greater risk for sexually transmitted infections (STI) and human immunodeficiency virus (HIV). STUDY: A cross-sectional analysis using baseline data from a randomized controlled trial of an HIV prevention intervention for high-risk men in Mumbai, India. RESULTS: The overall HIV prevalence among 1741 men sampled was 14%; 64% had either a confirmed STI or HIV; 92% reported sex with an FSW, of whom 66% reported having sex while under the influence of alcohol (SUI). SUI was associated with unprotected sex (odds ratio [OR]: 3.1; 95% confidence interval [CI], 2.3-4.1), anal sex (OR: 1.5; 1.1-2.0), and more than10 FSW partners (OR: 2.2; 1.8-2.7). SUI was independently associated with having either an STI or HIV (OR: 1.5; 1.2-1.9). CONCLUSION: Men who drink alcohol when visiting FSWs engage in riskier behavior and are more likely to have HIV and STIs. Prevention programs in India need to raise awareness of this relationship.

Incidence of coccidioides infection among dogs residing in a region in which the organism is endemic.

OBJECTIVE: To determine the incidence of Coccidioides infection among dogs residing in a region in which the organism is endemic (Pima and Maricopa counties, Arizona) and estimate the rate of clinical illness. DESIGN: Community-based longitudinal and cross-sectional studies. ANIMALS: 124 healthy 4- to 6-month-old seronegative puppies (longitudinal study) and 381 4- to 18-month-old dogs with unknown serostatus (cross-sectional study). PROCEDURE: Dogs in the longitudinal study were tested at 6-month intervals for at least 1 year for anticoccidioidal antibodies. Dogs that became ill were evaluated for coccidioidomycosis. Dogs in the cross-sectional study were tested for anticoccidioidal antibodies once, and clinical abnormalities were recorded. RESULTS: 28 of the 104 (27%) dogs that completed the longitudinal study developed anticoccidioidal antibodies. Thirty-two of the 381 (8%) dogs in the cross-sectional study had anticoccidioidal antibodies. Five seropositive dogs in the longitudinal study and 13 seropositive dogs in the cross-sectional study had clinical signs of disease. The remaining seropositive dogs were otherwise healthy and were classified as subclinically infected. Survival analysis indicated that the cumulative probability of infection by 2 years of age was 28%, and the cumulative probability of clinical infection by 2 years of age was 6%. Titers for clinically and subclinically infected dogs overlapped. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that young dogs living in the study area had a high likelihood of becoming infected with Coccidioides spp, but few developed clinical illness. Serologic testing alone was insufficient for a diagnosis of clinical disease because of the overlap in titers between clinically and subclinically infected dogs.