Enhanced Understanding of Infectious Diseases by Fusing Multiple Datasets: A Case Study on Malaria in the Western Brazilian Amazon Region

BACKGROUND: A common challenge to the study of several infectious diseases consists in combining limited cross-sectional survey data, collected with a more sensitive detection method, with a more extensive (but biased) syndromic sentinel surveillance data, collected with a less sensitive method. Our article describes a novel modeling framework that overcomes this challenge, resulting in enhanced understanding of malaria in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 486 individuals was monitored using four cross-sectional surveys, where all participants were sampled regardless of symptoms (aggressive-active case detection), resulting in 1,383 microscopy and 1,400 polymerase chain reaction tests. Data on the same individuals were also obtained from the local surveillance facility (i.e., passive and active case detection), totaling 1,694 microscopy tests. Our model accommodates these multiple pathogen and case detection methods. This model is shown to outperform logistic regression in terms of interpretability of its parameters, ability to recover the true parameter values, and predictive performance. We reveal that the main infection determinant was the extent of forest, particularly during the rainy season and in close proximity to water bodies, and participation on forest activities. We find that time residing in Acrelandia (as a proxy for past malaria exposure) decreases infection risk but surprisingly increases the likelihood of reporting symptoms once infected, possibly because non-naïve settlers are only susceptible to more virulent Plasmodium strains. We suggest that the search for asymptomatic carriers should focus on those at greater risk of being infected but lower risk of reporting symptoms once infected. CONCLUSIONS/SIGNIFICANCE: The modeling framework presented here combines cross-sectional survey data and syndromic sentinel surveillance data to shed light on several aspects of malaria that are critical for public health policy. This framework can be adapted to enhance inference on infectious diseases whenever asymptomatic carriers are important and multiple datasets are available

The Risk of Stable Partnerships: Associations between Partnership Characteristics and Unprotected Anal Intercourse among ...

Background Partnership type is an important factor associated with unprotected anal intercourse (UAI) and subsequent risk for HIV and sexually transmitted infections (STI). We examined the association of partnership type with UAI among men who have sex with men (MSM) and male-to-female transgender women (TGW) in Lima, Peru, recently diagnosed with HIV and/or STI. Methods We report data from a cross-sectional analysis of MSM and TGW recently diagnosed with HIV and/or STI in Lima, Peru between 2011 and 2012. We surveyed participants regarding UAI with up to their three most recent sexual partners according to partner type. Multivariable Generalized Estimate Equating (GEE) models with Poisson distribution were used to estimate prevalence ratios (PR) for UAI according to partner type. Results Among 339 MSM and TGW recently diagnosed with HIV and/or STI (mean age: 30.6 years, SD 9.0), 65.5% self-identified as homosexual/gay, 16.0% as bisexual, 15.2% as male-to-female transgender, and 3.3% as heterosexual. Participants provided information on 893 recent male or TGW partners with whom they had engaged in insertive or receptive anal intercourse: 28.9% stable partners, 56.4% non-stable/non-transactional partners (i.e. casual or anonymous), and 14.7% transactional partners (i.e. transactional sex client or sex worker). Unprotected anal intercourse was reported with 41.3% of all partners. In multivariable analysis, factors associated with UAI included partnership type (non-stable/non-transactional partner APR 0.73, [95% CI 0.59–0.91], transactional partner APR 0.53 [0.36–0.78], p 10 encounters APR 1.43 [1.06–1.92], p < 0.05. Conclusion UAI was more commonly reported for stable partners and in partnerships with > 10 sexual encounters, suggesting UAI is more prevalent in partnerships with a greater degree of interpersonal commitment. Further research assessing partner-level factors and behavior is critical for improving HIV and/or STI prevention efforts among Peruvian MSM and TGW

Anticipated Notification of Sexual Partners following STD Diagnosis among Men Who Have Sex with Men and Transgender Women in Lima, Peru: A Mixed Methods Analysis

Background: New strategies to support partner notification (PN) are critical for STD control and require detailed understanding of how specific individual and partnership characteristics guide notification decisions. Methods: From 2011 to 2012, 397 MSM and TW recently diagnosed with HIV, syphilis, or another STD completed a survey on anticipated notification of recent sexual partners and associated factors. Qualitative interviews were conducted with a subset of participants to provide further depth to quantitative findings. Prevalence ratios and generalized estimating equation (GEE) models were used to analyze participant- and partner-level factors associated with anticipated PN. Results: Among all partners reported, 52.5% were described as “Very Likely” or “Somewhat Likely” to be notified. Anticipated notification was more likely for main partners than casual (adjusted Prevalence Ratio [aPR], 95% CI: 0.63, 0.54–0.75) or commercial (aPR, 95% CI: 0.44, 0.31–0.62) partners. Other factors associated with likely notification included perception of the partner as an STD source (aPR, 95% CI: 1.27, 1.10–1.48) and anticipated future sexual contact with the partner (aPR, 95% CI: 1.30, 1.11–1.52). An HIV diagnosis was associated with a lower likelihood of notification than non-HIV STDs (aPR: 0.68, 0.55–0.86). Qualitative discussion of the barriers and incentives to PN reflected a similar differentiation of anticipated notification according to partnership type and type of HIV/STD diagnosis. Discussion: Detailed attention to how partnership characteristics guide notification outcomes is essential to the development of new PN strategies. By accurately and thoroughly assessing the diversity of partnership interactions among individuals with HIV/STD, new notification techniques can be tailored to partner-specific circumstances

Anti-Retroviral Treatment Outcomes among Older Adults in Zomba District, Malawi

BACKGROUND: There are approximately 3 million people aged 50 and older in sub-Saharan Africa who are HIV-positive. Despite this, little is known about the characteristics of older adults who are on treatment and their treatment outcomes. METHODS: A retrospective cohort analysis was performed using routinely collected data with Malawi Ministry of Health monitoring tools from facilities providing antiretroviral therapy services in Zomba district. Patients aged 25 years and older initiated on treatment from July 2005 to June 2010 were included. Differences in survival, by age group, were determined using Kaplan-Meier survival plots and Cox proportional hazards regression models. RESULTS: There were 10,888 patients aged 25 and older. Patients aged 50 and older (N = 1419) were more likely to be male (P<0.0001) and located in rural areas (P = 0.003) than those aged 25-49. Crude survival estimates among those aged 50-59 were not statistically different from those aged 25-49 (P = 0.925). However, survival among those aged 60 and older (N = 345) was worse (P = 0.019) than among those 25-59. In the proportional hazards model, after controlling for sex and stage at initiation, survival in those aged 50-59 did not differ significantly from those aged 25-49 (hazard ratio 1.00 (95% CI: 0.79 to 1.27; P = 0.998) but the hazard ratio was 1.46 (95% CI: 1.03 to 2.06; P = 0.032) for those aged 60 and older compared to those aged 25-49. CONCLUSIONS: Treatment outcomes of those aged 50-59 are similar to those aged 25-49. A better understanding of how older adults present for and respond to treatment is critical to improving HIV services

Can Male Circumcision Have an Impact on the HIV Epidemic in Men Who Have Sex with Men?

Background: Three trials have demonstrated the prophylactic effect of male circumcision (MC) for HIV acquisition among heterosexuals, and MC interventions are underway throughout sub-Saharan Africa. Similar efforts for men who have sex with men (MSM) are stymied by the potential for circumcised MSM to acquire HIV easily through receptive sex and transmit easily through insertive sex. Existing work suggests that MC for MSM should reach its maximum potential in settings where sexual role segregation is historically high and relatively stable across the lifecourse; HIV incidence among MSM is high; reported willingness for prophylactic circumcision is high; and pre-existing circumcision rates are low. We aim to identify the likely public health impact that MC interventions among MSM would have in one setting that fulfills these conditions—Peru—as a theoretical upper bound for their effectiveness among MSM generally. Methods and Findings: We use a dynamic, stochastic sexual network model based in exponential-family random graph modeling and parameterized from multiple behavioral surveys of Peruvian MSM. We consider three enrollment criteria (insertive during 100%, >80% or >60% of UAI) and two levels of uptake (25% and 50% of eligible men); we explore sexual role proportions from two studies and different frequencies of switching among role categories. Each scenario is simulated 10 times. We estimate that efficiency could reach one case averted per 6 circumcisions. However, the population-level impact of an optimistic MSM-MC intervention in this setting would likely be at most ∼5–10% incidence and prevalence reductions over 25 years. Conclusions: Roll-out of MC for MSM in Peru would not result in a substantial reduction in new HIV infections, despite characteristics in this population that could maximize such effects. Additional studies are needed to confirm these results for other MSM populations, and providers may consider the individual health benefits of offering MC to their MSM patients

What Drives the US and Peruvian HIV Epidemics in Men Who Have Sex with Men (MSM)?

In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4–5% (Model 1) or 22–29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80–81% and 49%, respectively) stem from chronic-stage partners and the remainder (14–16% and 27–35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24–31%), diagnosed but untreated (36–46%), and currently being treated (30–36%). Roughly one-third of infections (32–39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru

Traditional and Web-Based Technologies to Improve Partner Notification Following Syphilis Diagnosis Among Men Who Have Sex With Men in Lima, Peru: Pilot Randomized Controlled Trial

Background: Patient-initiated partner notification (PN) following the diagnosis of a sexually transmitted infection is a critical component of disease control in men who have sex with men (MSM) sexual networks. Both printed and internet-based technologies offer potential tools to enhance traditional partner notification approaches among MSM in resource-limited settings. Objective: This randomized controlled trial aimed to evaluate the effect of 2 different PN technologies on notification outcomes following syphilis diagnosis among MSM in Peru: A Web-based notification system and patient-delivered partner referral cards. Methods: During 2012-2014, we screened 1625 MSM from Lima, Peru, for syphilis infection and enrolled 370 MSM with symptomatic primary or secondary syphilis (n=58) or asymptomatic latent syphilis diagnosed by serology (rapid plasma reagin, RPR, and Microhemagglutination assay for Treponema pallidum antibody; n=312). Prior to enrollment, potential participants used a computer-based self-interviewing system to enumerate their recent sexual partnerships and provide details of their 3 most recent partners. Eligible participants were randomly assigned to one of 4 intervention arms: (1) counseling and patient-initiated Web-based PN (n=95), (2) counseling with Web-based partner notification and partner referral cards (n=84), (3) counseling and partner referral cards (n=97), and (4) simple partner notification counseling (control; n=94). Self-reported partner notification was assessed after 14 days among 354 participants who returned for the follow-up assessment. Results: The median age of enrolled participants was 27 (interquartile range, IQR 23-34) years, with a median of 2 partners (IQR 1-5) reported in the past month. Compared with those who received only counseling (arm 4), MSM provided with access to Web-based partner notification (arms 1 and 2) or printed partner referral cards (arms 2 and 3) were more likely to have notified one or more of their sexual partners (odds ratio, OR, 2.18, 95% CI 1.30-3.66; P=.003 and OR 1.68, 95% CI 1.01-2.79; P=.045, respectively). The proportion of partners notified was also higher in both Web-based partner notification (241/421, 57.2%; P<.001) and referral card (240/467, 51.4%; P=.006) arms than in the control arm (82/232, 35.3%). Conclusions: Both new Web-based technologies and traditional printed materials support patient-directed notification and improve self-reported outcomes among MSM with syphilis. Additional research is needed to refine the use of these partner notification tools in specific partnership contexts.Revisión por paresRevisión por pare

Homophobia and heteronormativity as dimensions of stigma that influence sexual risk behaviors among men who have sex with men (MSM) and women (MSMW) in Lima, Peru: a mixed-methods analysis

Background Stigma differentially influences HIV and STI care among MSM, especially regarding partner notification practices. Recognizing the heterogeneous behaviors/identities within the category “MSM,” we used mixed-methods to assess sexual risk behaviors among men who have sex with men only (MSMO) and behaviorally bisexual MSM (MSMW) with HIV and/or other STIs. Methods MSMO/MSMW recently diagnosed (< 30 days) with HIV, syphilis, urethritis, or proctitis completed a cross-sectional survey assessing sexual risk behaviors, anticipated disclosure, and sexual partnership characteristics (n = 332). Multivariable generalized estimating equation models assessed characteristics associated with female compared to male partners in the last three partnerships. Follow-up qualitative interviews (n = 30) probed partner-specific experiences (e.g., acts and disclosure). Results Among all participants, 13.9% (n = 46) described at least one of their last three sex partners as female (MSMW). MSMW (mean age of 31.8) reported a mean of 3.5 partners (SD = 4.5) in the past 3 months and MSMO (mean age 30.6) reported a mean of 4.6 partners (SD = 9.7) in the past 3 months. MSMW were more likely to report unprotected insertive anal sex (77.9%) than MSMO (43.1%; p < 0.01). Cisgender female partners were associated with condomless insertive sex in the last 3 months (aPR: 3.97, 95%CI: 1.98–8.00) and classification as a “primary” partnership (2.10, 1.34–3.31), and with lower prevalence of recent HIV diagnosis (0.26, 0.11–0.61). Planned notification of HIV/STI diagnoses was less common for female than for male partners (0.52, 0.31–0.85). Narratives illustrate internal (e.g., women as ‘true’ partners) and community-level processes (e.g., discrimination due to exposure of same-sex behavior) that position homosexual behavior and bisexual identity as divergent processes of deviance and generate vulnerability within sexual networks. Conclusions MSMW recently diagnosed with HIV/STI in Peru report varying partnership characteristics, with different partner-specific risk contexts and prevention needs. Descriptions highlight how behaviorally bisexual partnerships cut across traditional risk group boundaries and suggest that HIV/STI prevention strategies must address diverse, partnership-specific risks

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120