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ObjectivesTo 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.DesignProspective cohort study.SettingA public university in California from June to August 2020.Participants2180 university students and 738 university employees.Primary outcome measuresAt 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.ResultsOver 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.ConclusionsOur 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.

IntroductionAlthough individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations.MethodsUsing an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients.ResultsOver 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4-16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27-2.88), abacavir-lamivudine-atazanavir (1.58; 1.08-2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07-1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54-0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir.ConclusionThe antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.

BackgroundMany 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.MethodsBetween 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.ResultsMost 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).ConclusionsOur 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.

BackgroundCurrently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19.MethodsWe analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality.ResultsThe data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84, and ≥85 years versus 18-39 years (adjusted risk ratios [aRRs], 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84, and ≥ 85 years versus 18-39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19).ConclusionsIn-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.

Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners.

OBJECTIVE: Examine whether glycaemic control varies according to sex and whether the latter plays a role in modifying factors associated with inadequate glycaemic control in patients with type 2 diabetes (T2D) in Brazil and Venezuela. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, nationwide survey conducted in Brazil and Venezuela from February 2006 to June 2007 to obtain information about glycaemic control and its determinants in patients with diabetes mellitus attending outpatient clinics. MAIN OUTCOME MEASURES: Haemoglobin A1c (HbA1c) level was measured by liquid chromatography, and patients with HbA1c ≥7.0% (53 mmol/mol) were considered to have inadequate glycaemic control. The association of selected variables with glycaemic control was analysed by multivariate linear regression, using HbA1c as the dependent variable. RESULTS: A total of 9418 patients with T2D were enrolled in Brazil (n=5692) and in Venezuela (n=3726). They included 6214 (66%) women and 3204 (34%) men. On average, HbA1c levels in women were 0.13 (95% CI 0.03 to 0.24; p=0.015) higher than in men, after adjusting for age, marital status, education, race, country, body mass index, duration of disease, complications, type of healthcare, adherence to diet, adherence to treatment and previous measurement of HbA1c. Sex modified the effect of some factors associated with glycaemic control in patients with T2D in our study, but had no noteworthy effect in others. CONCLUSIONS: Women with T2D had worse glycaemic control than men. Possible causes for poorer glycaemic control in women compared with men include differences in glucose homeostasis, treatment response and psychological factors. In addition, sex modified factors associated with glycaemic control, suggesting the need to develop specific treatment guidelines for men and women.

ObjectivesAbacavir's potential to cause cardiovascular disease (CVD) among people living with HIV (PLWH) is debated. We conduct a systematic review and meta-analyses to assess CVD risk from recent and cumulative abacavir exposure.MethodsWe searched Medline, Embase, Web of Science, abstracts from Conference on Retroviruses and Opportunistic Infections, and International AIDS Society/AIDS Conferences and bibliographies of review articles to identify research studies published through 2018 on CVD risk associated with abacavir exposure among PLWH. Studies assessing risk of CVD associated with recent (exposure within last 6 months) or cumulative abacavir exposure across all age-groups were eligible. Risks were quantified using fixed- and random-effects models.ResultsOf 378 unique citations, 68 full-text research articles and abstracts were reviewed. Seventeen studies assessed risk of CVD from recent or cumulative abacavir exposure. Summary relative risk (sRR) is increased for recent exposure (n=16 studies, sRR=1.61; 95% confidence interval: 1.48-1.75), higher in antiretroviral-therapy-naive population (n=5, 1.91; 1.48-2.46) and all studies reported RR>1. The sRR for recent exposure was similarly increased for the outcome of acute myocardial infarction, and for studies that adjusted for substance abuse, smoking, prior CVD, traditional CVD risk factors, and CD4 cell-count/HIV viral load. The sRR was increased for cumulative abacavir exposure (per year) (n=4, 1.12; 1.05-1.20) but no increase was seen after adjusting for recent exposure (n=5, 1.00; 0.93-1.08).ConclusionsOur findings suggest an increased risk of CVD from recent abacavir exposure. The risk remained elevated after adjusting for potential confounders. Further investigations are needed to understand CVD risk from cumulative exposure.

BackgroundThere is ongoing controversy regarding abacavir use in the treatment of HIV infection and the risk of subsequent development of cardiovascular disease. It is unclear how the risk varies as exposure accumulates.MethodsUsing an administrative health-plan dataset, risk of cardiovascular disease events (CVDe), defined as the first episode of an acute myocardial infarction or a coronary intervention procedure, associated with abacavir exposure was assessed among HIV-infected individuals receiving antiretroviral therapy across the U.S. from October 2009 through December 2014. The data were longitudinal, and analyzed using marginal structural models.ResultsOver 114,470 person-years (n = 72,733) of ART exposure, 714 CVDe occurred at an incidence rate (IR) (95% CI) of 6·23 (5·80, 6·71)/1000 person-years. Individuals exposed to abacavir had a higher IR of CVDe of 9·74 (8·24, 11·52)/1000 person-years as compared to 5·75 (5·30, 6·24)/1000 person-years for those exposed to other antiretroviral agents. The hazard (HR; 95% CI) of CVDe was increased for current (1·43; 1·18, 1·73), recent (1·41; 1·16, 1·70), and cumulative [(1·18; 1·06, 1·31) per year] exposure to abacavir. The risk for cumulative exposure followed a bell-shaped dose-response curve peaking at 24-months of exposure. Risk was similarly elevated among participants free of pre-existing heart disease or history of illicit substance use at baseline.ConclusionCurrent, recent, and cumulative use of abacavir was associated with an increased risk of CVDe. The findings were consistent irrespective of underlying cardiovascular risk factors.

ObjectivesExternal validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA.DesignMatched case-control study.SettingThirteen active surveillance sites for invasive pneumococcal disease in the USA.ParticipantsCases were identified from active surveillance and controls were age and zip code matched.Outcome measuresSocioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment.ResultsWe enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however,

Background and aimsMost studies reporting alcohol use among fatally injured victims are subject to bias, particularly those related to sample selection and to absence of injury context data. We developed a research method to estimate the prevalence of alcohol consumption and test correlates of alcohol use prior to fatal injuries.Design, setting and participantsCross-sectional study based on a probability sample of fatally injured adult victims (n = 365) autopsied in São Paulo, Brazil. Victims were sampled within systematically selected 8-hour sampling blocks, generating a representative sample of fatal injuries occurring during all hours of the day for each day of the week between June 2014 and December 2015.MeasurementsThe presence of alcohol and blood alcohol concentration (BAC) were the primary outcomes evaluated according to victims' socio-demographic, injury context data (type, day, time and injury place) and criminal history characteristics.FindingsAlcohol was detected in 30.1% [95% confidence interval (CI) = 25.6-35.1)] of the victims, with a mean blood alcohol level (BAC) level of 0.11% w/v (95% CI = 0.09-0.13) among alcohol-positive cases. Black and mixed race victims presented a higher mean BAC than white victims (P = 0.03). Fewer than one in every six suicides tested positive for alcohol, while almost half of traffic-related casualties were alcohol-positive. Having suffered traffic-related injuries, particularly those involving vehicle crashes, and injuries occurring during weekends and at night were associated significantly with alcohol use before injury (P

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however,

In 2009, in the Active Bacterial Core surveillance sites, penicillin was not commonly used to treat meningococcal disease. This is likely because of inconsistent availability of antimicrobial susceptibility testing and ease of use of third-generation cephalosporins. Consideration of current practices may inform future meningococcal disease management guidelines.

PurposeWe have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants.ParticipantsThe study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50-74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample.Findings to dateClinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare.Future plansWe will continue following this patients' cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities.Trial registration numberNCT02646943; Pre-results.

BackgroundSyndromic management of vaginal infections is known to have poor diagnostic accuracy. Logic regression is a machine-learning procedure which allows for the identification of combinations of variables to predict an outcome, such as the presence of a vaginal infection.MethodsWe used logic regression to develop predictive models for syndromic management of vaginal infection among symptomatic, reproductive-age women in south India. We assessed the positive predictive values, negative predictive values, sensitivities and specificities of the logic regression procedure and a standard WHO algorithm against laboratory-confirmed diagnoses of two conditions: metronidazole-sensitive vaginitis [bacterial vaginosis or trichomoniasis (BV/TV)], and vulvovaginal candidiasis (VVC).ResultsThe logic regression procedure created algorithms which had a mean positive predictive value of 61 % and negative predictive value of 80 % for management of BV/TV, and a mean positive predictive value of 26 % and negative predictive value of 98 % for management of VVC. The results using the WHO algorithm were similarly mixed.ConclusionsThe logic regression procedure identified the most predictive measures for management of vaginal infections from the candidate clinical and laboratory measures. However, the procedure provided further evidence as to the limits of syndromic management for vaginal infections using currently available clinical measures.

BackgroundTreatment of a multi-drug resistant tuberculosis (MDR-TB) patient is clinically challenging, requiring a minimum of 18 months of therapy. Its occurrence in a systemic lupus erythromatosus (SLE) patient may complicate management of both MDR-TB and SLE. This is the first descriptive report of MDR-TB in an SLE patient.Case presentationA 19-year old female receiving long-term prednisolone for SLE was diagnosed with MDR-TB. She was started on MDR-TB treatment regimen and prednisolone was replaced with azathioprine. After an initial response to therapy, patient experienced a flare of lupus symptoms. Imaging studies revealed avascular necrosis of right femoral head. She was then treated with intravenous methyl-prednisolone, followed by maintenance corticosteroid. Azathioprine was discontinued due to hematological toxicity and failure to control SLE. Her symptoms of lupus regressed and did not re-occur for the duration of her MDR-TB treatment. Patient was declared cured of MDR-TB after 18 months of ATT. She is currently scheduled for a total hip replacement surgery.ConclusionsThis case highlights the challenges of simultaneously managing MDR-TB and SLE in a patient due to their over-lapping signs and symptoms, drug-drug interactions, and the need for use of immunomodulatory agents in the absence of standard guidelines and documented previous experiences. Our experience underscores the importance of appropriate selection of treatment regimens for both MDR-TB and SLE.

One objective of the Emerging Infections Program (EIP) of the US Centers for Disease Control and Prevention is to provide training opportunities in infectious disease epidemiology. To determine the extent of training performed since the program's inception in 1995, we reviewed training efforts at the 10 EIP sites. By 2015, all sites hosted trainees (most were graduate public health students and physicians) who worked on a variety of infectious disease surveillance and epidemiologic projects. Trainee projects at all sites were used for graduate student theses or practicums. Numerous projects resulted in conference presentations and publications in peer-reviewed journals. Local public health and health care partners have also benefitted from EIP presentations and training. Consideration should be given to standardizing and documenting EIP training and to sharing useful training initiatives with other state and local health departments and academic institutions.

A healthy vaginal environment is predominated by certain Lactobacillus species, which lead to the prevention of infections of the reproductive tract. This study examined the characteristics of cultivable Lactobacillus species in both healthy women and women with bacterial vaginosis (BV). Between November 2011 and September 2013, 139 women attending a women's clinic in Mysore, India, were evaluated for BV in a cross-sectional study. BV was diagnosed using Amsel's criteria: homogeneous vaginal discharge, vaginal pH >4.5, production of amines, and presence of "clue" cells. Those with three or more of the characteristics were considered to have BV. Vaginal swabs were then cultured in Rogosa agar and de Man-Rogosa-Sharpe broth. Gram-positive lactobacilli generating 600-800 bp amplicons by 16 sRNA were further characterized by sequencing. Cultivable vaginal samples were obtained from 132 women (94.9%). According to the Amsel criteria, 83 women (62.1%) were healthy, and 49 (37.1%) had BV. Eleven different Lactobacillus species were isolated from 47 women. The common lactobacilli species found in this sample included L. crispatus (39.6%), L. gasseri (45.8%), and L. jensenii (14.6%). Lactobacilli were isolated from 39 healthy women and eight with BV. L. gasseri was cultured from 18.8% of healthy women and 6.1% with BV. The presence of L. reuteri was significantly associated with normal vaginal microbiota (P-value = 0.026). These results further our understanding of vaginal lactobacilli colonization and richness in this particular population. Our findings showed that lactobacilli species present in the vaginas of healthy women in India do not differ from those reported from other countries.

The aim of this study was to assess risk factors associated with low levels of HIV testing among MSM recruited through respondent driven sampling (RDS) in Brazil. Of 3,617 participants, 48.4% had never tested previously for HIV. A logistic model indicated that younger age, lower socioeconomic class, education, poor HIV/AIDS knowledge, no history of cruising, and having been tested during the study were characteristics independently associated with low levels of previous HIV testing. The HIV testing rate among MSM in Brazil is still low in spite of the availability of a large number services providing universal and free access to HIV/AIDS diagnosis and treatment. To respond to low utilization, the authors propose a higher priority for testing for key populations such as MSM, expanded education, expanding testing sites and a welcoming and nonjudgmental environment in health services.

Lactobacillus species play an integral part in the health of the vaginal microbiota. We compared vaginal Lactobacillus species in women from India and the USA with and without bacterial vaginosis (BV). Between July 2009 and November 2010, a cross-sectional study was conducted among 40 women attending a women's health clinic in Mysore, India, and a sexually transmitted diseases clinic in San Francisco, USA. Women were diagnosed with BV using Amsel's criteria and the Nugent score. Lactobacillus 16S rDNA was sequenced to speciate the cultured isolates. Ten Indian and 10 US women without BV were compared with an equal number of women with BV. Lactobacilli were isolated from all healthy women, but from only 10% of Indian and 50% of US women with BV. 16S rDNA from 164 Lactobacillus colonies was sequenced from healthy women (126 colonies) and women with BV (38 colonies). Seven cultivable Lactobacillus species were isolated from 11 Indian women and nine species from 15 US women. The majority of Lactobacillus species among Indian women were L. crispatus (25.0%), L. jensenii (25.0%) and L. reuteri (16.7%). Among US women, L. crispatus (32.0%), L. jensenii (20.0%) and L. coleohominis (12.0%) predominated. L. jensenii and L. crispatus dominated the vaginal flora of healthy Indian and US women. Indian women appeared to have a higher percentage of obligate heterofermentative species, suggesting the need for a larger degree of metabolic flexibility and a more challenging vaginal environment.

To determine the role of primary antifungal prophylaxis in the prevention of cryptococcal meningitis and all-cause mortality in advanced HIV infection. This was a systematic review and meta-analysis of randomized trials and observational studies. Google Scholar™, PubMed and Embase databases were searched for relevant studies. Quality was assessed using different criteria, depending on study type. Publication bias was assessed and subgroup and sensitivity analyses were performed. When the results of the meta-analysis were homogeneous, the fixed-effects model was used; when the results of the meta-analysis were heterogenous, the random effects model was used. Primary prophylaxis prevented cryptococcal meningitis but did not confer protection against overall mortality, although there was evidence of a reduction in cryptococcal-specific mortality in resource-limited settings. Primary antifungal prophylaxis should be recommended in patients with advanced HIV infection in resource-limited settings with a high incidence of cryptococcal meningitis.

UnlabelledThe efficiency of hepatitis C virus (HCV) transmission by sexual activity remains controversial. We conducted a cross-sectional study of HCV-positive subjects and their partners to estimate the risk for HCV infection among monogamous heterosexual couples. A total of 500 anti-HCV-positive, human immunodeficiency virus-negative index subjects and their long-term heterosexual partners were studied. Couples were interviewed separately for lifetime risk factors for HCV infection, within-couple sexual practices, and sharing of personal grooming items. Blood samples were tested for anti-HCV, HCV RNA, and HCV genotype and serotype. Sequencing and phylogenetic analysis determined the relatedness of virus isolates among genotype-concordant couples. The majority of HCV-positive index subjects were non-Hispanic white, with a median age of 49 years (range, 26-79 years) and median of 15 years (range, 2-52 years) of sexual activity with their partners. Overall, HCV prevalence among partners was 4% (n=20), and nine couples had concordant genotype/serotype. Viral isolates in three couples (0.6%) were highly related, consistent with transmission of virus within the couple. Based on 8,377 person-years of follow-up, the maximum incidence rate of HCV transmission by sex was 0.07% per year (95% confidence interval, 0.01-0.13) or approximately one per 190,000 sexual contacts. No specific sexual practices were related to HCV positivity among couples.ConclusionThe results of this study provide quantifiable risk information for counseling long-term monogamous heterosexual couples in which one partner has chronic HCV infection. In addition to the extremely low estimated risk for HCV infection in sexual partners, the lack of association with specific sexual practices provides unambiguous and reassuring counseling messages.

The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19-35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001-2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001-2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ≥1 dose increased from 38% to 97%. Case-control VE for ≥1 dose was estimated as 75% against all-serotype IPD (annual range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the screening method, the overall VE was 86% for ≥1 dose (annual range: -240-70%) against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs.

Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (

BackgroundJails are an important venue of HIV care and a place for identification, treatment and referral for care. HIV infected inmates in the San Francisco County jail are offered antiretroviral treatment (ART), which many take only while in jail. We evaluated the effect of ART administration in a cohort of jail inmates going in and out of jail over a nine year period.Methodology/principal findingsIn this retrospective study, we examined inmates with HIV going in and out of jail. Inmates were categorized by patterns of ART use: continuous ART - ART both in and out of jail, intermittent ART - ART only in jail; never on ART - eligible by national guidelines, but refused ART. CD4 and HIV viral load (VL) were compared over time in these groups. Over a 9 year period, 512 inmates were studied: 388 (76%) on intermittent ART, 79 (15%) on continuous ART and 45(9%) never-on ART. In a linear mixed model analysis, inmates on intermittent ART were 1.43; 95%CI (1.03, 1.99) times and those never on ART were 2.89; 95%CI (1.71, 4.87) times more likely to have higher VL than inmates on continuous ART. Furthermore, Inmates on intermittent ART and never-on ART lost 1.60; 95%CI (1.06, 2.13) and 1.97; 95%CI (0.96, 3.00) more CD4 cells per month, respectively, compared to continuously treated inmates. The continuous ART inmates gained 0.67CD4 cells/month.Conclusions/significanceContinuous ART therapy in jail inmate's benefits CD4 cell counts and control of VL especially compared to those who never took ART. Although jail inmates on intermittent ART were more likely to lose CD4 cells and experience higher VL over time than those on continuous ART, CD4 cell loss was slower in these inmates as compared to inmates never on ART. Further studies are needed to evaluate whether or not intermittent ART provides some benefit in outcome if continuous ART is not possible or likely.

BackgroundPolysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population. The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil.MethodsA case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview.ResultsAfter adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI:

BackgroundOral fluid-based rapid tests are promising for improving HIV diagnosis and screening. However, recent reports from the United States of false-positive results with the oral OraQuick ADVANCE HIV1/2 test have raised concerns about their performance in routine practice. We report a field evaluation of the diagnostic accuracy, client preference, and feasibility for the oral fluid-based OraQuick Rapid HIV1/2 test in a rural hospital in India.Methodology/principal findingsA cross-sectional, hospital-based study was conducted in 450 consenting participants with suspected HIV infection in rural India. The objectives were to evaluate performance, client preference and feasibility of the OraQuick Rapid HIV-1/2 tests. Two Oraquick Rapid HIV1/2 tests (oral fluid and finger stick) were administered in parallel with confirmatory ELISA/Western Blot (reference standard). Pre- and post-test counseling and face to face interviews were conducted to determine client preference. Of the 450 participants, 146 were deemed to be HIV sero-positive using the reference standard (seropositivity rate of 32% (95% confidence interval [CI] 28%, 37%)). The OraQuick test on oral fluid specimens had better performance with a sensitivity of 100% (95% CI 98, 100) and a specificity of 100% (95% CI 99, 100), as compared to the OraQuick test on finger stick specimens with a sensitivity of 100% (95% CI 98, 100), and a specificity of 99.7% (95% CI 98.4, 99.9). The OraQuick oral fluid-based test was preferred by 87% of the participants for first time testing and 60% of the participants for repeat testing.Conclusion/significanceIn a rural Indian hospital setting, the OraQuick Rapid- HIV1/2 test was found to be highly accurate. The oral fluid-based test performed marginally better than the finger stick test. The oral OraQuick test was highly preferred by participants. In the context of global efforts to scale-up HIV testing, our data suggest that oral fluid-based rapid HIV testing may work well in rural, resource-limited settings.

BackgroundOral fluid-based rapid tests are promising for improving HIV diagnosis and screening. However, recent reports from the United States of false-positive results with the oral OraQuick ADVANCE HIV1/2 test have raised concerns about their performance in routine practice. We report a field evaluation of the diagnostic accuracy, client preference, and feasibility for the oral fluid-based OraQuick Rapid HIV1/2 test in a rural hospital in India.Methodology/principal findingsA cross-sectional, hospital-based study was conducted in 450 consenting participants with suspected HIV infection in rural India. The objectives were to evaluate performance, client preference and feasibility of the OraQuick Rapid HIV-1/2 tests. Two Oraquick Rapid HIV1/2 tests (oral fluid and finger stick) were administered in parallel with confirmatory ELISA/Western Blot (reference standard). Pre- and post-test counseling and face to face interviews were conducted to determine client preference. Of the 450 participants, 146 were deemed to be HIV sero-positive using the reference standard (seropositivity rate of 32% (95% confidence interval [CI] 28%, 37%)). The OraQuick test on oral fluid specimens had better performance with a sensitivity of 100% (95% CI 98, 100) and a specificity of 100% (95% CI 99, 100), as compared to the OraQuick test on finger stick specimens with a sensitivity of 100% (95% CI 98, 100), and a specificity of 99.7% (95% CI 98.4, 99.9). The OraQuick oral fluid-based test was preferred by 87% of the participants for first time testing and 60% of the participants for repeat testing.Conclusion/significanceIn a rural Indian hospital setting, the OraQuick Rapid- HIV1/2 test was found to be highly accurate. The oral fluid-based test performed marginally better than the finger stick test. The oral OraQuick test was highly preferred by participants. In the context of global efforts to scale-up HIV testing, our data suggest that oral fluid-based rapid HIV testing may work well in rural, resource-limited settings.

BackgroundThe risk of transmission of Mycobacterium tuberculosis from patients to health-care workers (HCWs) is a neglected problem in many low- and middle-income countries (LMICs). Most health-care facilities in these countries lack resources to prevent nosocomial transmission of tuberculosis (TB).Methods and findingsWe conducted a systematic review to summarize the evidence on the incidence and prevalence of latent TB infection (LTBI) and disease among HCWs in LMICs, and to evaluate the impact of various preventive strategies that have been attempted. To identify relevant studies, we searched electronic databases and journals, and contacted experts in the field. We identified 42 articles, consisting of 51 studies, and extracted data on incidence, prevalence, and risk factors for LTBI and disease among HCWs. The prevalence of LTBI among HCWs was, on average, 54% (range 33% to 79%). Estimates of the annual risk of LTBI ranged from 0.5% to 14.3%, and the annual incidence of TB disease in HCWs ranged from 69 to 5,780 per 100,000. The attributable risk for TB disease in HCWs, compared to the risk in the general population, ranged from 25 to 5,361 per 100,000 per year. A higher risk of acquiring TB disease was associated with certain work locations (inpatient TB facility, laboratory, internal medicine, and emergency facilities) and occupational categories (radiology technicians, patient attendants, nurses, ward attendants, paramedics, and clinical officers).ConclusionsIn summary, our review demonstrates that TB is a significant occupational problem among HCWs in LMICs. Available evidence reinforces the need to design and implement simple, effective, and affordable TB infection-control programs in health-care facilities in these countries.

Background: Sputum microscopy, the most important conventional test for tuberculosis, is specific in settings with high burden of tuberculosis and low prevalence of non tuberculous mycobacteria. However, the test lacks sensitivity. Although bacteriophage-based tests for tuberculosis have shown promising results, their overall accuracy has not been systematically evaluated.Methods: We did a systematic review and meta-analysis of published studies to evaluate the accuracy of phage-based tests for the direct detection of M. tuberculosis in clinical specimens. To identify studies, we searched Medline, EMBASE, Web of science and BIOSIS, and contacted authors, experts and test manufacturers. Thirteen studies, all based on phage amplification method, met our inclusion criteria. Overall accuracy was evaluated using forest plots, summary receiver operating (SROC) curves, and subgroup analyses.Results: The data suggest that phage-based assays have high specificity (range 0.83 to 1.00), but modest and variable sensitivity (range 0.21 to 0.88). The sensitivity ranged between 0.29 and 0.87 among smear-positive, and 0.13 to 0.78 among smear-negative specimens. The specificity ranged between 0.60 and 0.88 among smear-positive and 0.89 to 0.99 among smear-negative specimens. SROC analyses suggest that overall accuracy of phage-based assays is slightly higher than smear microscopy in direct head-to-head comparisons.Conclusion: Phage-based assays have high specificity but lower and variable sensitivity. Their performance characteristics are similar to sputum microscopy. Phage assays cannot replace conventional diagnostic tests such as microscopy and culture at this time. Further research is required to identify methods that can enhance the sensitivity of phage-based assays without compromising the high specificity.

In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.

Countywide antibiotic resistance patterns may provide additional information from that obtained from national sampling or individual hospitals. We reviewed susceptibility patterns of selected bacterial strains isolated from blood in San Francisco County from January 1996 to March 1999. We found substantial hospital-to-hospital variability in proportional resistance to antibiotics in multiple organisms. This variability was not correlated with hospital indices such as number of intensive care unit or total beds, annual admissions, or average length of stay. We also found a significant increase in methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and proportional resistance to multiple antipseudomonal antibiotics. We describe the utility, difficulties, and limitations of countywide surveillance.