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American gadfly : the intellectual odyssey of Paul Fussell
\"American cultural historian, literary and social critic and college professor Paul Fussell (1924-2012) wrote and edited 21 books on a wide variety of topics, ranging from 18th century British literature to works on World War II to sardonic takes on American culture. This book offers a thorough introduction to his writings and thought, constructing an argument for Fussell's continued importance and relevancy. Covering Fussell's traumatic experience in World War II and the important influence it had on his life and outlook, this intellectual biography puts in context Fussell's perspectives on ethics, the human experience and literature as an evaluative and critical endeavor.\"-Provided by publisher\"-- Provided by publisher.
Book
Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda
Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence and lockdown and a severe lake flooding event, both of which occurred in 2020.
We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda. The data were collected both prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence and a severe flooding event. Households impacted by flooding were identified via drone data and through consulting village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-differences statistical modeling approach.
A total of 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. After the COVID-19 pandemic and lockdown, we observed a decline in HIV-associated risk behaviors: transactional sex declined from 29.4% to 24.8% (p = 0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p = 0.021). ART coverage increased from 91.6% to 97.2% (p<0.001). There was 17% decline in transactional sex (aPR = 0.83, 95% CI: 0.75-0.92) and 28% decline in the overall HIV risk score (aPR = 0.83, 95% CI: 0.75-0.92) among HIV-seronegative participants. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes when comparing those affected by floods to those not affected by floods, in the periods before and after COVID-19, based on difference-in-differences analyses.
Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and/or population resilience. Understanding exactly what HIV programs and personal or community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events.
Journal Article
The Effects of Circumcision on the Penis Microbiome
Circumcision is associated with significant reductions in HIV, HSV-2 and HPV infections among men and significant reductions in bacterial vaginosis among their female partners.
We assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3-V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significant decrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families-Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)-were uniquely abundant before circumcision. Within these families we identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp.
The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.
Journal Article
Male Circumcision for HIV and STI Prevention: A Reflection
The majority of procedures are performed in infancy or childhood, but in some cultures circumcision is part of initiation rituals marking the transition from adolescence to adulthood (e.g., Xhosa of South Africa). Since the 1990s, the Rakai Health Sciences Program has worked on male circumcision for prevention of HIV and other sexually transmitted infections (STIs) through a series of studies conducted in rural Rakai district of south-central Uganda. [...]the observational data were considered suggestive, but not conclusive, and insufficient to warrant WHO and Joint United Nations Program on HIV/AIDS (UNAIDS) recommending the procedure for HIV control. [...]circumcision presented a new paradigm because a surgical procedure had never been used to prevent an infectious disease. [...]the only way to resolve the question of whether circumcision could prevent HIV acquisition was to conduct randomized trials. All 3 trials were stopped early owing to evidence of significant efficacy, with risk ratios ranging from 0.41 to 0.43. [...]the trial results were similar to a metaanalysis of observational studies, which estimated a risk ratio of 0.42 (10).
Journal Article
Rates of HIV-1 Transmission per Coital Act, by Stage of HIV-1 Infection, in Rakai, Uganda
BackgroundWe estimated rates of human immunodeficiency virus (HIV)–1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner MethodsWe retrospectively identified 235 monogamous, HIV-discordant couples in a Ugandan population-based cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner’s stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression ResultsThe average rate of HIV transmission was 0.0082/coital act (95% confidence interval [CI], 0.0039–0.0150) within ∼2.5 months after seroconversion of the index partner; 0.0015/coital act within 6–15 months after seroconversion of the index partner (95% CI, 0.0002–0.0055); 0.0007/coital act (95% CI, 0.0005–0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015–0.0041) 6–25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission ConclusionsThe rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission
Journal Article
HIV Prevention Efforts and Incidence of HIV in Uganda
Preventing HIV infection is a global priority. In this article, the association of the scale-up of male circumcision, HIV treatment, and behavioral interventions on the incidence of HIV infection was assessed in Rakai, Uganda.
Journal Article
Evaluating the biomedical and behavioral drivers of HIV incidence decline in adolescent girls and young women in Uganda: A mathematical modeling study
HIV incidence among adolescent girls and young women (AGYW) in eastern and southern Africa has declined substantially over the past two decades. These declines are often attributed to biomedical HIV prevention strategies, though concurrent changes in sexual behavior may also contribute. We evaluated the contributions of biomedical and behavioral drivers to historical incidence decline in AGYW and projected their impact on incidence trajectories over the next 30 years.
We conducted a mathematical modeling study using data from the Rakai Community Cohort Study (RCCS), an open, population-based cohort of adults aged 15-49 years in 30 communities in Rakai, Uganda. We used an agent-based HIV-1 transmission model calibrated to cohort data to estimate HIV incidence trends among AGYW, aged 15-24, and to quantify the independent and combined effects of antiretroviral therapy (ART), voluntary medical male circumcision (VMMC), and changes in age at first sex (AFS). HIV incidence among women aged 15-24 declined by 71% between 2000 and 2019, from 1.57 to 0.45 per 100 person-years, representing the largest decline across female age groups in the cohort. Increasing AFS over the study period (by approximately 3 years in women and 2 years in men) was the largest contributor to incidence declines among adolescent women aged 15-19, averting 17% of cumulative infections between 2000 and 2020 and 37% between 2000 and 2050. Among women aged 20-24, ART scale-up had the greatest impact, averting 13% of infections by 2020 and 43% by 2050. VMMC contributed modestly to historical declines but had larger projected effects over longer time horizons. ART, VMMC, and delays in AFS acted additively to reduce HIV incidence among AGYW. Study limitations include reliance on self-reported sexual behavior and the use of a mathematical model that cannot capture all real-world sexual network dynamics.
Both biomedical HIV interventions and broader behavioral changes contributed to declines in HIV incidence among AGYW. Sustaining continued incidence declines in young women will require maintaining both the protective changes in sexual behaviors and effective biomedical interventions.
Journal Article
The Role of Viral Introductions in Sustaining Community-Based HIV Epidemics in Rural Uganda: Evidence from Spatial Clustering, Phylogenetics, and Egocentric Transmission Models
It is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. The aim of this study was to determine the extent to which continued HIV transmission in rural communities--home to two-thirds of the African population--is driven by intra-community sexual networks versus viral introductions from outside of communities.
We analyzed the spatial dynamics of HIV transmission in rural Rakai District, Uganda, using data from a cohort of 14,594 individuals within 46 communities. We applied spatial clustering statistics, viral phylogenetics, and probabilistic transmission models to quantify the relative contribution of viral introductions into communities versus community- and household-based transmission to HIV incidence. Individuals living in households with HIV-incident (n = 189) or HIV-prevalent (n = 1,597) persons were 3.2 (95% CI: 2.7-3.7) times more likely to be HIV infected themselves compared to the population in general, but spatial clustering outside of households was relatively weak and was confined to distances <500 m. Phylogenetic analyses of gag and env genes suggest that chains of transmission frequently cross community boundaries. A total of 95 phylogenetic clusters were identified, of which 44% (42/95) were two individuals sharing a household. Among the remaining clusters, 72% (38/53) crossed community boundaries. Using the locations of self-reported sexual partners, we estimate that 39% (95% CI: 34%-42%) of new viral transmissions occur within stable household partnerships, and that among those infected by extra-household sexual partners, 62% (95% CI: 55%-70%) are infected by sexual partners from outside their community. These results rely on the representativeness of the sample and the quality of self-reported partnership data and may not reflect HIV transmission patterns outside of Rakai.
Our findings suggest that HIV introductions into communities are common and account for a significant proportion of new HIV infections acquired outside of households in rural Uganda, though the extent to which this is true elsewhere in Africa remains unknown. Our results also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and should target key populations likely responsible for introductions into communities.
Journal Article
Effect of Peer Health Workers on AIDS Care in Rakai, Uganda: A Cluster-Randomized Trial
Human resource limitations are a challenge to the delivery of antiretroviral therapy (ART) in low-resource settings. We conducted a cluster randomized trial to assess the effect of community-based peer health workers (PHW) on AIDS care of adults in Rakai, Uganda.
15 AIDS clinics were randomized 2:1 to receive the PHW intervention (n = 10) or control (n = 5). PHW tasks included clinic and home-based provision of counseling, clinical, adherence to ART, and social support. Primary outcomes were adherence and cumulative risk of virologic failure (>400 copies/mL). Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART. Analysis was by intention to treat. From May 2006 to July 2008, 1336 patients were followed. 444 (33%) of these patients were already on ART at the start of the study. No significant differences were found in lack of adherence (<95% pill count adherence risk ratio [RR] 0.55, 95% confidence interval [CI] 0.23-1.35; <100% adherence RR 1.10, 95% CI 0.94-1.30), cumulative risk of virologic failure (RR 0.81, 95% CI 0.61-1.08) or in shorter-term virologic outcomes (24 week virologic failure RR 0.93, 95% CI 0.65-1.32; 48 week, RR 0.83, 95% CI 0.47-1.48; 72 week, RR 0.81, 95% CI 0.44-1.49). However, virologic failure rates >or=96 weeks into ART were significantly decreased in the intervention arm compared to the control arm (96 week failure RR 0.50, 95% CI 0.31-0.81; 120 week, RR 0.59, 95% CI 0.22-1.60; 144 week, RR 0.39, 95% CI 0.16-0.95; 168 week, RR 0.30, 95% CI 0.097-0.92; 192 week, RR 0.067, 95% CI 0.0065-0.71).
A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART, but did not affect cumulative risk of virologic failure, adherence measures, or shorter-term virologic outcomes. PHWs may be an effective intervention to sustain long-term ART in low-resource settings.
ClinicalTrials.gov NCT00675389.
Journal Article