Metapopulation dynamics of SARS-CoV-2 transmission in a small-scale Amazonian society.

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we simulate and analyze the dynamics of SARS-CoV-2 infection among Amazonian forager-horticulturalists in Bolivia using a stochastic network metapopulation model parameterized with high-resolution empirical data on population structure, mobility, and contact networks. Our model suggests that relative isolation offers little protection at the population level (expected approximately 80% cumulative incidence), and more remote communities are not conferred protection via greater distance from outside sources of infection, due to common features of small-scale societies that promote rapid disease transmission such as high rates of travel and dense social networks. Neighborhood density, central household location in villages, and household size greatly increase the individual risk of infection. Simulated interventions further demonstrate that without implausibly high levels of centralized control, collective isolation is unlikely to be effective, especially if it is difficult to restrict visitation between communities as well as travel to outside areas. Finally, comparison of model results to empirical COVID-19 outcomes measured via seroassay suggest that our theoretical model is successful at predicting outbreak severity at both the population and community levels. Taken together, these findings suggest that the social organization and relative isolation from urban centers of many rural Indigenous communities offer little protection from pandemics and that standard control measures, including vaccination, are required to counteract effects of tight-knit social structures characteristic of small-scale populations.

Potential impact of doxycycline post-exposure prophylaxis prescribing strategies on incidence of bacterial sexually transmitted infections.

BACKGROUND: Doxycycline post-exposure prophylaxis (doxyPEP) reduces bacterial sexually transmitted infection (STI) incidence in people with HIV (PWH) or using HIV preexposure prophylaxis (PrEP). Given concerns about widespread antibiotic use, we identified doxyPEP prescribing strategies to minimize use while maximizing impact on STIs. METHODS: We used electronic health records of gay and bisexual men (GBM), transgender women, and non-binary people assigned male sex at birth with ≥2 STI tests (chlamydia, gonorrhea, syphilis) at an LGBTQ-focused health center during 2015-2020. We defined 10 hypothetical doxyPEP prescribing strategies based on PrEP use, HIV status, or STI history. We estimated doxyPEP use and STI diagnoses averted in counterfactual scenarios in which people meeting prescribing criteria received doxyPEP, assuming STI rates during use would have been reduced by clinical trial efficacy estimates. RESULTS: Among 10,546 individuals (94% GBM), rate of any STI was 35.9/100 person-years. Prescribing doxyPEP to all individuals would have averted 71% of STI diagnoses (number needed to treat for one year to avert one STI diagnosis, NNT = 3.9); prescribing to PrEP users/PWH (52%/12% of individuals) would have averted 60% of STI diagnoses (NNT = 2.9). Prescribing doxyPEP for 12 months after STI diagnosis would have reduced the proportion using doxyPEP to 38% and averted 39% of STI diagnoses (NNT = 2.4). Prescribing after concurrent or repeated STIs would have maximized efficiency (lowest NNTs) but prevented fewer STIs. CONCLUSIONS: Prescribing doxyPEP to individuals with STIs, particularly concurrent or repeated STIs, could avert a substantial proportion of all STI diagnoses. The most efficient prescribing strategies are based on STI history rather than HIV status or PrEP use.

Achieving the "Ending the HIV Epidemic in the U.S." incidence reduction goals among at-risk populations in the South.

INTRODUCTION: Antiretroviral medication coverage remains sub-optimal in much of the United States, particularly the Sothern region, and Non-Hispanic Black or African American persons (NHB) continue to be disproportionately impacted by the HIV epidemic. The "Ending the HIV Epidemic in the U.S." (EHE) initiative seeks to reduce HIV incidence nationally by focusing resources towards the most highly impacted localities and populations. This study evaluates the impact of hypothetical improvements in ART and PrEP coverage to estimate the levels of coverage needed to achieve EHE goals in the South. METHODS: We developed a stochastic, agent-based network model of 500,000 individuals to simulate the HIV epidemic and hypothetical improvements in ART and PrEP coverage. RESULTS: New infections declined by 78.6% at 90%/40% ART/PrEP and 94.3% at 100%/50% ART/PrEP. Declines in annual incidence rates surpassed 75% by 2025 with 90%/40% ART/PrEP and 90% by 2030 with 100%/50% ART/PrEP coverage. Increased ART coverage among NHB MSM was associated with a linear decline in incidence among all MSM. Declines in incidence among Hispanic/Latino and White/Other MSM were similar regardless of which MSM race group increased their ART coverage, while the benefit to NHB MSM was greatest when their own ART coverage increased. The incidence rate among NHB women declined by over a third when either NHB heterosexual men or NHB MSM increased their ART use respectively. Increased use of PrEP was associated with a decline in incidence for the groups using PrEP. MSM experienced the largest absolute declines in incidence with increasing PrEP coverage, followed by NHB women. CONCLUSIONS: Our analysis indicates that it is possible to reach EHE goals. The largest reductions in HIV incidence can be achieved by increasing ART coverage among MSM and all race groups benefit regardless of differences in ART initiation by race. Improving ART coverage to > 90% should be prioritized with a particular emphasis on reaching NHB MSM. Such a focus will reduce the largest number of incident cases, reduce racial HIV incidence disparities among both MSM and women, and reduce racial health disparities among persons with HIV. NHB women should also be prioritized for PrEP outreach.

Sexual Mixing by HIV Status and Pre-exposure Prophylaxis Use Among Men Who Have Sex With Men: Addressing Information Bias.

BACKGROUND: Population-level estimates of sexual network mixing for parameterizing prediction models of pre-exposure prophylaxis (PrEP) effectiveness are needed to inform prevention of HIV transmission among men who have sex with men (MSM). Estimates obtained by egocentric sampling are vulnerable to information bias due to incomplete respondent knowledge. METHODS: We estimated patterns of serosorting and PrEP sorting among MSM in the United States using data from a 2017-2019 egocentric sexual network study. Respondents served as proxies to report the HIV status and PrEP use of recent sexual partners. We contrasted results from a complete-case analysis (unknown HIV and PrEP excluded) versus a bias analysis with respondent-reported data stochastically reclassified to simulate unobserved self-reported data from sexual partners. RESULTS: We found strong evidence of preferential partnering across analytical approaches. The bias analysis showed concordance between sexual partners of HIV diagnosis and PrEP use statuses for MSM with diagnosed HIV (39%; 95% simulation interval: 31, 46), MSM who used PrEP (32%; 21, 37), and MSM who did not use PrEP (83%; 79, 87). The fraction of partners with diagnosed HIV was higher among MSM who used PrEP (11%; 9, 14) compared with MSM who did not use PrEP (4%; 3, 5). Comparatively, across all strata of respondents, the complete-case analysis overestimated the fractions of partners with diagnosed HIV or PrEP use. CONCLUSIONS: We found evidence consistent with HIV and PrEP sorting among MSM, which may decrease the population-level effectiveness of PrEP. Bias analyses can improve mixing estimates for parameterization of transmission models.

The Role of HIV Partner Services in the Modern Biomedical HIV Prevention Era: A Network Modeling Study.

BACKGROUND: HIV partner services can accelerate the use of antiretroviral-based HIV prevention tools (antiretroviral therapy [ART] and preexposure prophylaxis [PrEP]), but its population impact on long-term HIV incidence reduction is challenging to quantify with traditional partner services metrics of partner identified or HIV screened. Understanding the role of partner services within the portfolio of HIV prevention interventions, including using it to efficiently deliver antiretrovirals, is needed to achieve HIV prevention targets. METHODS: We used a stochastic network model of HIV/sexually transmitted infection transmission for men who have sex with men, calibrated to surveillance-based estimates in the Atlanta area, a jurisdiction with high HIV burden and suboptimal partner services uptake. Model scenarios varied successful delivery of partner services cascade steps (newly diagnosed "index" patient and partner identification, partner HIV screening, and linkage or reengagement of partners in PrEP or ART care) individually and jointly. RESULTS: At current levels observed in Atlanta, removal of HIV partner services had minimal impact on 10-year cumulative HIV incidence, as did improving a single partner services step while holding the others constant. These changes did not sufficiently impact overall PrEP or ART coverage to reduce HIV transmission. If all index patients and partners were identified, maximizing partner HIV screening, partner PrEP provision, partner ART linkage, and partner ART reengagement would avert 6%, 11%, 5%, and 18% of infections, respectively. Realistic improvements in partner identification and service delivery were estimated to avert 2% to 8% of infections, depending on the combination of improvements. CONCLUSIONS: Achieving optimal HIV prevention with partner services depends on pairing improvements in index patient and partner identification with maximal delivery of HIV screening, ART, and PrEP to partners if indicated. Improving the identification steps without improvement to antiretroviral service delivery steps, or vice versa, is projected to result in negligible population HIV prevention benefit.

Comparing Sexual Network Mean Active Degree Measurement Metrics Among Men Who Have Sex With Men.

BACKGROUND: Mean active degree is an important proxy measure of cross-sectional network connectivity commonly used in HIV/sexually transmitted infection epidemiology research. No current studies have compared measurement methods of mean degree using a cross-sectional study design for men who have sex with men (MSM) in the United States. We compared mean degree estimates based on reported ongoing main and casual sexual partnerships (current method) against dates of first and last sex (retrospective method). METHODS: We used data from ARTnet, a cross-sectional survey of MSM in the United States (2017-2019). ARTnet collected data on the number and types of sexual partners in the past year, limited to the 5 most recent partners (data truncation). We quantified partnerships for months 0 to 12 before the survey date (retrospective method) and compared that with ongoing partnerships on the day of survey (current method). We used linear regression to understand the impact of truncated partnership data on mean degree estimation. RESULTS: The retrospective method yielded similar degree estimates to the current for months proximate to the day of survey. The retrospective method mean degree systematically decreased as the month increased from 0 to 12 months before survey date. This was driven by data truncation: among participants with >5 partners in the past year compared with those with ≤5, the average change in main partnership degree between 12 and 0 months before survey date was -0.05 (95% confidence interval, -0.08 to -0.03) after adjusting for race/ethnicity, age, and education. The adjusted average change in casual partnership degree was -0.40 (95% confidence interval, -0.45 to -0.35). CONCLUSIONS: The retrospective method underestimates mean degree for MSM in surveys with truncated partnership data, especially for casual partnerships. The current method is less prone to bias from partner truncation when the target population has high rate of partners per year.

Effect of Screening and Treatment for Gonorrhea and Chlamydia on HIV Incidence Among Men Who Have Sex With Men in the United States: A Modeling Analysis.

BACKGROUND: Previous models have estimated the total population attributable fraction of Neisseria gonorrhoeae and Chlamydia trachomatis (NG/CT) on HIV incidence among men who have sex with men (MSM), but this does not represent realistic intervention effects. We estimated the potential impact of screening for NG/CT on downstream incidence of HIV among MSM. METHODS: Using a network model, we estimated the effects of varying coverage levels for sexually transmitted infection screening among different priority populations: all sexually active MSM regardless of HIV serostatus, MSM with multiple recent (past 6 months) sex partners regardless of serostatus, MSM without HIV, and MSM with HIV. Under the assumption that all screening events included a urethral test, we also examined the effect of increasing the proportion of screening events that include rectal screening for NG/CT on HIV incidence. RESULTS: Increasing annual NG/CT screening among sexually active MSM by 60% averted 4.9% of HIV infections over a 10-year period (interquartile range, 2.8%-6.8%). More HIV infections were averted when screening was focused on MSM with multiple recent sex partners: 60% coverage among MSM with multiple recent sex partners averted 9.8% of HIV infections (interquartile range, 8.1%-11.6%). Increased sexually transmitted infection screening among MSM without HIV averted more new HIV infections compared with the transmissions averted because of screening MSM with HIV, but fewer NG/CT tests were needed among MSM with HIV to avert a single new HIV infection. CONCLUSIONS: Screening of NG/CT among MSM is expected to lead to modest but clinically relevant reductions in HIV incidence among MSM.

A review of COVID-19 transmission dynamics and clinical outcomes on cruise ships worldwide, January to October 2020.

BackgroundCruise ships provide an ideal setting for transmission of SARS-CoV-2, given the socially dense exposure environment.AimTo provide a comprehensive review of COVID-19 outbreaks on cruise ships.MethodsPubMed was searched for COVID-19 cases associated with cruise ships between January and October 2020. A list of cruise ships with COVID-19 was cross-referenced with the United States Centers for Disease Control and Prevention's list of cruise ships associated with a COVID-19 case within 14 days of disembarkation. News articles were also searched for epidemiological information. Narratives of COVID-19 outbreaks on ships with over 100 cases are presented.ResultsSeventy-nine ships and 104 unique voyages were associated with COVID-19 cases before 1 October 2020. Nineteen ships had more than one voyage with a case of COVID-19. The median number of cases per ship was three (interquartile range (IQR): 1-17.8), with two notable outliers: the Diamond Princess and the Ruby Princess, which had 712 and 907 cases, respectively. The median attack rate for COVID-19 was 0.2% (IQR: 0.03-1.5), although this distribution was right-skewed with a mean attack rate of 3.7%; 25.9% (27/104) of voyages had at least one COVID-19-associated death. Outbreaks involving only crew occurred later than outbreaks involving guests and crew.ConclusionsIn the absence of mitigation measures, COVID-19 can spread easily on cruise ships in a susceptible population because of the confined space and high-density contact networks. This environment can create superspreader events and facilitate international spread.

Projected HIV and Bacterial Sexually Transmitted Infection Incidence Following COVID-19-Related Sexual Distancing and Clinical Service Interruption.

BACKGROUND: The global COVID-19 pandemic has the potential to indirectly impact transmission dynamics and prevention of HIV and other sexually transmitted infections (STI). It is unknown what combined impact reductions in sexual activity and interruptions in HIV/STI services will have on HIV/STI epidemic trajectories. METHODS: We adapted a model of HIV, gonorrhea, and chlamydia for a population of approximately 103 000 men who have sex with men (MSM) in the Atlanta area. Model scenarios varied the timing, overlap, and relative extent of COVID-19-related sexual distancing and service interruption within 4 service categories (HIV screening, preexposure prophylaxis, antiretroviral therapy, and STI treatment). RESULTS: A 50% relative decrease in sexual partnerships and interruption of all clinical services, both lasting 18 months, would generally offset each other for HIV (total 5-year population impact for Atlanta MSM, -227 cases), but have net protective effect for STIs (-23 800 cases). If distancing lasted only 3 months but service interruption lasted 18 months, the total 5-year population impact would be an additional 890 HIV cases and 57 500 STI cases. CONCLUSIONS: Immediate action to limit the impact of service interruptions is needed to address the indirect effects of the global COVID-19 pandemic on the HIV/STI epidemic.

Projected Impact of Concurrently Available Long-Acting Injectable and Daily-Oral Human Immunodeficiency Virus Preexposure Prophylaxis: A Mathematical Model.

BACKGROUND: Long-acting injectable (LAI) human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) is reportedly efficacious, although full trial results have not been published. We used a dynamic network model of HIV transmission among men who have sex with men to assess the population impact of LAI-PrEP when available concurrently with daily-oral (DO) PrEP. METHODS: The reference model represents the current HIV epidemiology and DO-PrEP coverage (15% among those with behavioral indications for PrEP) among men who have sex with men in the southeastern United States. Primary analyses investigated varied PrEP uptake and proportion selecting LAI-PrEP. Secondary analyses evaluated uncertainty in pharmacokinetic efficacy and LAI-PrEP persistence relative to DO-PrEP. RESULTS: Compared with the reference scenario, if 50% chose LAI-PrEP, 4.3% (95% simulation interval, -7.3% to 14.5%) of infections would be averted over 10 years. The impact of LAI-PrEP is slightly greater than that of the DO-PrEP-only regimen, based on assumptions of higher adherence and partial protection after discontinuation. If the total PrEP initiation rate doubled, 17.1% (95% simulation interval, 6.7%-26.4%) of infections would be averted. The highest population-level impact occurred when LAI-PrEP uptake and persistence improved. CONCLUSIONS: If LAI-PrEP replaces DO-PrEP, its availability will modestly improve the population impact. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage, or if persistence is greater for LAI-PrEP.

Gaps in Sexually Transmitted Infection Screening Among Men who Have Sex with Men in Pre-exposure Prophylaxis (PrEP) Care in the United States.

BACKGROUND: The US Centers for Disease Control and Prevention (CDC) recommends comprehensive sexually transmitted infection (STI) screening every 3-6 months for men who have sex with men (MSM) using human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). The gaps between these recommendations and clinical practice by region have not been quantified. METHODS: We used survey data collected from the internet-based ARTnet study between 2017 and 2019 on STI screening among MSM across the United States, stratified by current, prior, and never PrEP use. Poisson regression models with robust error variance were used to model factors, including residence in the Southeast, associated with consistent ("always" or "sometimes") exposure site-specific STI screening during PrEP care. RESULTS: Of 3259 HIV-negative MSM, 19% were currently using PrEP, 6% had used PrEP in the past, and 75% had never used PrEP. Among ever PrEP users, 87%, 78%, 57%, and 64% reported consistent screening for STIs by blood sample, urine sample or urethral swab, rectal swab, or pharyngeal swab, respectively, during PrEP care. Compared to PrEP users in all other regions, PrEP users in the Southeast were significantly less likely to be consistently screened for urogenital (adjusted prevalence ratio [aPR], 0.86; 95% confidence interval [CI], .76-.98) and rectal STIs (aPR, 0.76; 95% CI, .62-.93) during PrEP care. CONCLUSIONS: Substantial gaps exist between CDC recommendations for STI screening during PrEP care and current clinical practice, particularly for rectal and pharyngeal exposure sites that can harbor asymptomatic infections and for MSM in Southeast states where the STI burden is substantial.

HIV and Sexually Transmitted Infection Epidemic Potential of Networks of Men Who Have Sex With Men in Two Cities.

BACKGROUND: The speed with which a pathogen circulates in a sexual network is a function of network connectivity. Cross-sectional connectivity is a function of network features like momentary degree and assortative mixing. Temporal connectivity is driven by partner acquisition rates. The forward-reachable path (FRP) has been proposed as a summary measure of these two aspects of transmission potential. We use empirical data from San Francisco and Atlanta to estimate the generative parameters of the FRP and compare results to the HIV/sexually transmitted infection epidemics in each city. METHODS: We used temporal exponential random graph models to estimate the generative parameters for each city's dynamic sexual network from survey data. We then simulated stochastic dynamic networks from the fitted models and calculated the FRP for each realization, overall, and stratified by partnership type and demographics. RESULTS: The overall mean and median paths were higher in San Francisco than in Atlanta. The overall paths for each city were greater than the sum of the paths in each individual partnership network. In the casual partnership network, the mean path was highest in the youngest age group and lowest in the oldest age group, despite the fact that the youngest group had the lowest mean momentary degree and past-year partner counts. CONCLUSIONS: The FRP by age group revealed the additional utility of the measure beyond the temporal and cross-sectional network connectivity measures. Other nonnetwork factors are still necessary to infer total epidemic potential for any specific pathogen.

Rapid Review of Social Contact Patterns During the COVID-19 Pandemic.

BACKGROUND: Physical distancing measures aim to reduce person-to-person contact, a key driver of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. In response to unprecedented restrictions on human contact during the coronavirus disease 2019 (COVID-19) pandemic, studies measured social contact patterns under the implementation of physical distancing measures. This rapid review synthesizes empirical data on the changing social contact patterns during the COVID-19 pandemic. METHOD: We conducted a systematic review using PubMed, Medline, Embase, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We descriptively compared the distribution of contacts observed during the pandemic to pre-COVID data across countries to explore changes in contact patterns during physical distancing measures. RESULTS: We identified 12 studies reporting social contact patterns during the COVID-19 pandemic. Eight studies were conducted in European countries and eleven collected data during the initial mitigation period in the spring of 2020 marked by government-declared lockdowns. Some studies collected additional data after relaxation of initial mitigation. Most study settings reported a mean of between 2 and 5 contacts per person per day, a substantial reduction compared to pre-COVID rates, which ranged from 7 to 26 contacts per day. This reduction was pronounced for contacts outside of the home. Consequently, levels of assortative mixing by age substantially declined. After relaxation of initial mitigation, mean contact rates increased but did not return to pre-COVID levels. Increases in contacts post-relaxation were driven by working-age adults. CONCLUSION: Information on changes in contact patterns during physical distancing measures can guide more realistic representations of contact patterns in mathematical models for SARS-CoV-2 transmission.

A Behavioral Cascade of HIV Seroadaptation Among US Men Who Have Sex with Men in the Era of PrEP and U = U.

Seroadaptive behaviors help reduce HIV risk for some men who have sex with men (MSM), and have been well documented across MSM populations. Advancements in biomedical prevention have changed the contexts in which seroadaptive behaviors occur. We thus sought to estimate and compare the prevalence of four stages of the "seroadaptive cascade" by PrEP use in the recent era: knowledge of own serostatus, knowledge of partner serostatus; serosorting (matching by status), and condomless anal intercourse. Serosorting overall appeared to remain common, especially with casual and one-time partners. Although PrEP use did not impact status discussion, it did impact serosorting and the likelihood of having condomless anal intercourse. For respondents not diagnosed with HIV and not on PrEP, condomless anal intercourse occurred in just over half of relationships with HIV-positive partners who were not on treatment. Biomedical prevention has intertwined with rather than supplanted seroadaptive behaviors, while contexts involving neither persist.

RESUMEN: Los comportamientos seroadaptivos ayudan a reducir el riesgo de VIH en algunos hombres que tienen sexo con otros hombres (HSH) y han sido bien documentados en varias comunidades de HSH. Los avances en prevención biomédica han cambiado los contextos de los comportamientos seroadaptivos. Por ello buscamos estimar y comparar la prevalencia de cuatro fases de la 'cascada seroadaptiva' mediante el uso de PrEP en la era reciente: conocimiento del seroestatus personal, conocimiento del seroestatus del compañero, serosorting (emparejamiento por estatus) y coito anal sin condón. En general, el serosorting parece seguir siendo común especialmente con parejas casuales o de una noche. A pesar de que el uso de PrEP no impactó la discusión sobre el estatus, sí impactó el serosorting y la probabilidad de coito anal sin condón. Los encuestados no diagnosticados con VIH y sin PrEP tuvieron coito anal sin condón en la mitad de las relaciones con parejas VIH-positivo que no estaban bajo tratamiento. La prevención biomédica se ha entremezclado en lugar de suplantar los comportamientos seropositivos, mientras persisten los contextos en los que no aparece ninguno.

Is It the Timing? Short-Term Mobility and Coital Frequency in Agbogbloshie, Ghana.

Short-term mobility is often associated with increased sexual risk behavior. Mobile individuals often have higher rates of sexual risk behavior compared to non-mobile individuals, but the reasons why are not clear. Using monthly retrospective panel data from 202 men and 282 women in Agbogbloshie, Ghana, we tested whether short-term mobility was associated with changes in coital frequency, and whether the association was due to the act of travel in the given month (e.g., enabling higher risk behavior), the reason for travel, or an individual's travel propensity at other times in the year. Overnight travel specifically to visit family or friends, or for education, health, or other reasons, was associated with increased coital frequency for men. However, men with higher travel propensities had lower overall coital frequency and the act of traveling enabled more sex only for the most frequent male travelers. Men who seldom traveled had much higher coital frequency, but the act of traveling was not associated with additional sex acts. For women, travel for education, health, or other reasons increased coital frequency. Occasional female travelers had slightly more sex acts compared to non-mobile women, and the act of traveling for these women was associated with slight increases in coital frequency, supporting the enabling hypothesis. Highly mobile women had fewer sex acts per month on average. Our findings suggest that mobility characteristics measured on a broad temporal scale, as well as the reason for mobility, are important to understand the relationship between short-term mobility and sexual behavior.

Social Mixing and Clinical Features Linked With Transmission in a Network of Extensively Drug-resistant Tuberculosis Cases in KwaZulu-Natal, South Africa.

BACKGROUND: Tuberculosis (TB) is the leading infectious cause of death globally, and drug-resistant TB strains pose a serious threat to controlling the global TB epidemic. The clinical features, locations, and social factors driving transmission in settings with high incidences of drug-resistant TB are poorly understood. METHODS: We measured a network of genomic links using Mycobacterium tuberculosis whole-genome sequences. RESULTS: Patients with 2-3 months of cough or who spent time in urban locations were more likely to be linked in the network, while patients with sputum smear-positive disease were less likely to be linked than those with smear-negative disease. Associations persisted using different thresholds to define genomic links and irrespective of assumptions about the direction of transmission. CONCLUSIONS: Identifying factors that lead to many transmissions, including contact with urban areas, can suggest settings instrumental in transmission and indicate optimal locations and groups to target with interventions.

Modeling Missing Cases and Transmission Links in Networks of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.

Patterns of transmission of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases worldwide in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa, diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, missing differentially by clinical characteristics, or missing differentially by transmission (i.e., cases with many links were under- or oversampled). Under the assumption that cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases, and models provided evidence for super-spreading. To our knowledge, this is the first analysis to have assessed support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving super-spreading.

Assessment of Bias in Estimates of Sexual Network Degree using Prospective Cohort Data.

BACKGROUND: Sexual network degree, a count of ongoing partnerships, plays a critical role in the transmission dynamics of human immunodeficiency virus and other sexually transmitted infections. Researchers often quantify degree using self-reported cross-sectional data on the day of survey, which may result in bias because of uncertainty about future sexual activity. METHODS: We evaluated the bias of a cross-sectional degree measure with a prospective cohort study of men who have sex with men (MSM). At baseline, we asked men about whether recent sexual partnerships were ongoing. We confirmed the true, ongoing status of those partnerships at baseline at follow-up. With logistic regression, we estimated the partnership-level predictors of baseline measure accuracy. With Poisson regression, we estimated the longitudinally confirmed degree as a function of baseline predicted degree. RESULTS: Across partnership types, the baseline ongoing status measure was 70% accurate, with higher negative predictive value (91%) than positive predictive value (39%). Partnership exclusivity and racial pairing were associated with higher accuracy. Baseline degree generally overestimated confirmed degree. Bias, or number of ongoing partners different than predicted at baseline, was -0.28 overall, ranging from -1.91 to -0.41 for MSM with any ongoing partnerships at baseline. Comparing MSM of the same baseline degree, the level of bias was stronger for black compared with white MSM, and for younger compared with older MSM. CONCLUSIONS: Research studies may overestimate degree when it is quantified cross-sectionally. Adjustment and structured sensitivity analyses may account for bias in studies of human immunodeficiency virus or sexually transmitted infection prevention interventions.

Leveraging Modularity During Replication of High-Fidelity Models: Lessons from Replicating an Agent-Based Model for HIV Prevention.

High-fidelity models are increasingly used to predict, and guide decision making. Prior work has emphasized the importance of replication in ensuring reliable modeling, and has yielded important replication strategies. However, this work is based on relatively simple theory generating models, and its lessons might not translate to high-fidelity models used for decision support. Using NetLogo we replicate a recently published high-fidelity model examining the effects of a HIV biomedical intervention. We use a modular approach to build our model from the ground up, and provide examples of the replication process investigating the replication of two sub-modules as well as the overall simulation experiment. For the first module, we achieved numerical identity during replication, whereas we obtained distributional equivalence in replicating the second module. We achieved relational equivalence among the overall model behaviors, with a 0.98 correlation across the two implementations for our outcome measure even without strictly following the original model in the formation of the sexual network. Our results show that replication of high-fidelity models is feasible when following a set of systematic strategies that leverage the modularity, and highlight the role of replication standards, modular testing, and functional code in facilitating such strategies.

Addressing Gaps in HIV Preexposure Prophylaxis Care to Reduce Racial Disparities in HIV Incidence in the United States.

The potential for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) to reduce the racial disparities in HIV incidence in the United States might be limited by racial gaps in PrEP care. We used a network-based mathematical model of HIV transmission for younger black and white men who have sex with men (BMSM and WMSM) in the Atlanta, Georgia, area to evaluate how race-stratified transitions through the PrEP care continuum from initiation to adherence and retention could affect HIV incidence overall and disparities in incidence between races, using current empirical estimates of BMSM continuum parameters. Relative to a no-PrEP scenario, implementing PrEP according to observed BMSM parameters was projected to yield a 23% decline in HIV incidence (hazard ratio = 0.77) among BMSM at year 10. The racial disparity in incidence in this observed scenario was 4.95 per 100 person-years at risk (PYAR), a 19% decline from the 6.08 per 100 PYAR disparity in the no-PrEP scenario. If BMSM parameters were increased to WMSM values, incidence would decline by 47% (hazard ratio = 0.53), with an associated disparity of 3.30 per 100 PYAR (a 46% decline in the disparity). PrEP could simultaneously lower HIV incidence overall and reduce racial disparities despite current gaps in PrEP care. Interventions addressing these gaps will be needed to substantially decrease disparities.