61 results found
Whittaker C, Ratmann O, Dye C, et al., 2021, Altered demographic profile of hospitalizations during the second COVID-19 wave in Amazonas, Brazil, The Lancet Regional Health - Americas, Vol: 2, ISSN: 2667-193X
Bezemer D, Blenkinsop A, Hall M, et al., 2021, In-country acquisition of HIV-1 non-B infection within the Netherlands is frequent, but results in limited onward transmission, AIDS, ISSN: 0269-9370
Objective To investigate introductions and spread of different HIV-1 subtypes in the Netherlands. Design We identified distinct HIV-1 transmission chains in the Netherlands within the global epidemic context through viral phylogenetic analysis of partial HIV-1 polymerase sequences from individuals enrolled in the ATHENA national HIV cohort of all persons in care since 1996, and publicly available international background sequences. Methods Viral lineages circulating in the Netherlands were identified through maximum parsimony phylogeographic analysis. The proportion of HIV-1 infections acquired in-country among heterosexuals and men having sex with men (MSM) was estimated from phylogenetically observed, national transmission chains using a branching process model that accounts for incomplete sampling. Results As of January 1st 2019, 2,589 (24%) of 10,971 (41%) HIV-1 sequenced individuals in ATHENA had non-B subtypes (A1, C, D, F, G) or circulating recombinant forms (CRF01AE, CRF02AG, CRF06-cpx). The 1,588 heterosexuals were in 1,224, and 536 MSM in 270 phylogenetically observed transmission chains. After adjustments for incomplete sampling, most heterosexual (75%) and MSM (76%) transmission chains were estimated to include only the individual introducing the virus (size=1). Onward transmission occurred mostly in chains size 2-5 amongst heterosexuals (62%) and in chains size ≥10 amongst MSM (64%). Considering some chains originated in-country from other risk-groups, 40% (95%CI: 36-44%) of non-B-infected heterosexuals and 62% (95%CI: 49%-73%) of MSM acquired infection in-country. Conclusions Whilst most HIV-1 non-B introductions showed no or very little onward transmission, a considerable proportion of non-B infections amongst both heterosexuals and MSM in the Netherlands have been acquired in-country.
Hillis S, Blenkinsop A, Villaveces A, et al., 2021, COVID-19-associated orphanhood and caregiver death in the United States, Pediatrics, ISSN: 0031-4005
Background: Most COVID-19 deaths occur among adults, not children, and attention has focused on mitigating COVID-19 burden among adults. However, a tragic consequence of adult deaths is that high numbers of children might lose their parents and caregivers to COVID-19-associated deaths.Methods: We quantified COVID-19-associated caregiver loss and orphanhood in the US and for each state using fertility and excess and COVID-19 mortality data. We assessed burden and rates of COVID-19-associated orphanhood and deaths of custodial and co-residing grandparents, overall and by race/ethnicity. We further examined variations in COVID-19-associated orphanhood by race/ethnicity for each state. Results: We found that from April 1, 2020 through June 30, 2021, over 140,000 children in the US experienced the death of a parent or grandparent caregiver. The risk of such loss was 1.1 to 4.5 times higher among children of racial and ethnic minorities, compared to Non-Hispanic White children. The highest burden of COVID-19-associated death of parents and caregivers occurred in Southern border states for Hispanic children, Southeastern states for Black children, and in states with tribal areas for American Indian/Alaska Native populations.Conclusions: We found substantial disparities in distributions of COVID-19-associated death of parents and caregivers across racial and ethnic groups. Children losing caregivers to COVID-19 need care and safe, stable, and nurturing families with economic support, quality childcare and evidence-based parenting support programs. There is an urgent need to mount an evidence-based comprehensive response focused on those children at greatest risk, in the states most affected.
Cabras S, Castellanos ME, Ratmann O, 2021, Goodness of fit for models with intractable likelihood, Test, Vol: 30, Pages: 713-736, ISSN: 1133-0686
Routine goodness-of-fit analyses of complex models with intractable likelihoods are hampered by a lack of computationally tractable diagnostic measures with well-understood frequency properties, that is, with a known sampling distribution. This frustrates the ability to assess the extremity of the data relative to fitted simulation models in terms of pre-specified test statistics, an essential requirement for model improvement. Given an Approximate Bayesian Computation setting for a posited model with an intractable likelihood for which it is possible to simulate from them, we present a general and computationally inexpensive Monte Carlo framework for obtaining p-valuesthat are asymptotically uniformly distributed in [0, 1] under the posited model when assumptions about the asymptotic equivalence between the conditional statistic and the maximum likelihood estimator hold. The proposed framework follows almost directly from the conditional predictive p-value proposed in the Bayesian literature. Numerical investigations demonstrate favorable power properties in detecting actual model discrepancies relative to other diagnostic approaches. We illustrate the technique on analytically tractable examples and on a complex tuberculosis transmission model.
Mishra S, Mindermann S, Sharma M, et al., 2021, Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England., EClinicalMedicine, Vol: 39
Background: Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. Methods: We examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021. Findings: Across data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May. Interpretation: The outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts. Funding: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open
Ratmann O, Bhatt S, Flaxman S, 2021, Implications of a highly transmissible variant of SARS-CoV-2 for children, Archives of Disease in Childhood, Vol: 106, Pages: 1-1, ISSN: 0003-9888
Mishra S, Scott JA, Laydon DJ, et al., 2021, Comparing the responses of the UK, Sweden and Denmark to COVID-19 using counterfactual modelling, SCIENTIFIC REPORTS, Vol: 11, Pages: 1-9, ISSN: 2045-2322
The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others’ policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country’s first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.
Hillis S, Unwin H, Chen Y, et al., 2021, Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study, The Lancet, Vol: 398, Pages: 391-402, ISSN: 0140-6736
Background: The COVID-19 pandemic response has focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalization. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation.Methods: We use mortality and fertility data to model minimum estimates and rates of COVID-19-associated orphanhood (death of 1 or both parents) and deaths of custodial and co-residing grandparents for 21 countries. We use these estimates to model global extrapolations for the number of children experiencing COVID-19-associated deaths of parents and grandparents ages 60-84.Results: Globally, from March 1, 2020-March 31, 2021, we estimate 974,000 children experienced death of primary caregivers, including parents or custodial grandparents; >1.3 million experienced death of primary caregivers and co-residing grandparents (or kin). Countries with rates of primary caregiver deaths >1/1000 children included Peru, South Africa, Mexico, Colombia, Brazil, I.R. Iran, U.S.A., and Russia (range, 1.0-8.5/1000). Numbers of children orphaned exceeded numbers of deaths among those aged 15 – 44; 2 – 5 times more children had deceased fathers than deceased mothers. Conclusions: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families nurture children bereft of caregivers and help ensure institutionalization is avoided. These data demonstrate the need for an additional pillar of our response: prevent, detect, respond, and care for children.
Meyerowitz-Katz G, Bhatt S, Ratmann O, et al., 2021, Is the cure really worse than the disease? The health impacts of lockdowns during COVID-19, BMJ Global Health, Vol: 6, Pages: 1-6, ISSN: 2059-7908
Mousa A, Winskill P, Watson OJ, et al., 2021, Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys., medRxiv
Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).
Bogers SJ, Schim van der Loeff MF, Davidovich U, et al., 2021, Promoting HIV indicator condition-guided testing in hospital settings (PROTEST 2.0): study protocol for a multicentre interventional study, BMC Infectious Diseases, Vol: 21, ISSN: 1471-2334
BACKGROUND: Late presentation remains a key barrier towards controlling the HIV epidemic. Indicator conditions (ICs) are those that are AIDS-defining, associated with a prevalence of undiagnosed HIV > 0.1%, or whose clinical management would be impeded if an HIV infection were undiagnosed. IC-guided HIV testing is an effective strategy in identifying undiagnosed HIV, but opportunities for earlier HIV diagnosis through IC-guided testing are being missed. We present a protocol for an interventional study to improve awareness of IC-guided testing and increase HIV testing in patients presenting with ICs in a hospital setting. METHODS: We designed a multicentre interventional study to be implemented at five hospitals in the region of Amsterdam, the Netherlands. Seven ICs were selected for which HIV test ratios (proportion of patients with an IC tested for HIV) will be measured: tuberculosis, cervical/vulvar cancer or high-grade cervical/vulvar dysplasia, malignant lymphoma, hepatitis B and C, and peripheral neuropathy. Prior to the intervention, a baseline assessment of HIV test ratios across ICs will be performed in eligible patients (IC diagnosed January 2015 through May 2020, ≥18 years, not known HIV positive) and an assessment of barriers and facilitators for HIV testing amongst relevant specialties will be conducted using qualitative (interviews) and quantitative methods (questionnaires). The intervention phase will consist of an educational intervention, including presentation of baseline results as competitive graphical audit and feedback combined with discussion on implementation and opportunities for improvement. The effect of the intervention will be assessed by comparing HIV test ratios of the pre-intervention and post-intervention periods. The primary endpoint is the HIV test ratio within ±3 months of IC diagnosis. Secondary endpoints are the HIV test ratio within ±6 months of diagnosis, ratio ever tested f
Dijkstra M, van Rooijen MS, Hillebregt MM, et al., 2021, Decreased Time to Viral Suppression After Implementation of Targeted Testing and Immediate Initiation of Treatment of Acute Human Immunodeficiency Virus Infection Among Men Who Have Sex With Men in Amsterdam, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: 1952-1960, ISSN: 1058-4838
Faria NR, Mellan TA, Whittaker C, et al., 2021, Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil, SCIENCE, Vol: 372, Pages: 815-+, ISSN: 0036-8075
Mishra S, Mindermann S, Sharma M, et al., 2021, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Publisher: Imperial College London, 44
Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when, whether, and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. This is particularly true for England, which has high coverage from vaccines that are likely more protective against B.1.1.7 than some other VOCs. We examine trends in B.1.1.7’s prevalence in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. Our results suggest shifts in the composition of SARS-CoV-2 lineages driving transmission in England between March and April 2021. Local transmission of non-B.1.1.7 VOCs may be increasing; this warrants urgent further investigation.
Volz E, Mishra S, Chand M, et al., 2021, Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England, Nature, Vol: 593, Pages: 266-269, ISSN: 0028-0836
The SARS-CoV-2 lineage B.1.1.7, designated a Variant of Concern 202012/01 (VOC) by Public Health England1, originated in the UK in late Summer to early Autumn 20202. Whole genome SARS-CoV-2 sequence data collected from community-based diagnostic testing shows an unprecedentedly rapid expansion of the B.1.1.7 lineage during Autumn 2020, suggesting a selective advantage. We find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Time-varying reproduction numbers for the VOC and cocirculating lineages were estimated using SGTF and genomic data. The best supported models did not indicate a substantial difference in VOC transmissibility among different age groups. There is a consensus among all analyses that the VOC has a substantial transmission advantage with a 50% to 100% higher reproduction number.
Unwin H, Mishra S, Bradley V, et al., 2020, State-level tracking of COVID-19 in the United States, Nature Communications, Vol: 11, Pages: 1-9, ISSN: 2041-1723
As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.
Novitsky V, Zahralban-Steele M, Moyo S, et al., 2020, Mapping of HIV-1C Transmission Networks Reveals Extensive Spread of Viral Lineages Across Villages in Botswana Treatment-as-Prevention Trial, JOURNAL OF INFECTIOUS DISEASES, Vol: 222, Pages: 1670-1680, ISSN: 0022-1899
Monod M, Blenkinsop A, Xi X, et al., 2020, Report 32: Targeting interventions to age groups that sustain COVID-19 transmission in the United States, Pages: 1-32
Following inial declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementaon of non-pharmaceucal inter-venons, it is sll not known how they are impacted by changing contact paerns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of intervenons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-speciﬁc mobility trends from more than 10 million individuals and link these mechaniscally to age-speciﬁc COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age speciﬁc contact paerns and use this rich relaonship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we ﬁnd lile support for age-shis in contact and transmission dynamics over me. We esmate that, unl August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infecons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with connued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 aributable deaths over a 90-day period. These ﬁndings indicate that targeng intervenons to adults aged 20-49 are an important con-sideraon in halng resurgent epidemics, and prevenng COVID-19-aributable deaths when kindergartens and elementary schools reopen.
Hanke K, Fiedler S, Grumann C, et al., 2020, A recent human immunodeficiency virus outbreak among people who inject drugs in Munich, Germany, is associated with consumption of synthetic cathinones, Open Forum Infectious Diseases, Vol: 7, Pages: ofaa192-ofaa192, ISSN: 2328-8957
Background: Needle and syringe sharing among people who inject drugs (PWID) can result in a rapid regional spread of a human immunodeficiency virus (HIV) variant. Such outbreaks have been identified recently in several countries and have raised public health attention because of an association with new psychoactive substances (NPS). Methods: Dried serum spots from approximately 60% of newly diagnosed HIV cases in Germany in 2013-2018 were received together with statutory notification data. Samples were sequenced in the pol-region, genotyped, and viral phylogenies were analyzed. For selected samples, the hepatitis C virus (HCV) status and the presence of NPS were determined. Results: An outbreak of closely related 27 subtype C infections with a core of 11 cases with almost identical sequences was identified using phylogenetic analyses. The first case of the outbreak was diagnosed in 2015, and the last one was in 2018. With exception of 3 infections, all were reported from Munich, the capital of the federal state of Bavaria. Of 26 analyzed outbreak members, 24 (92.3%) had a resolved or viremic HCV coinfection. In 8 of 18 (44%) cases, α-pyrrolidinopentiothiophenone and/or the related substance α-pyrrolidinoheptiophenone was identified. Conclusions: Despite harm reduction services in place, HIV outbreaks of considerable size can occur in PWID. The establishment of a real-time molecular surveillance is advised to rapidly identify outbreaks and target prevention measures.
Mellan T, Hoeltgebaum H, Mishra S, et al., 2020, Report 21: Estimating COVID-19 cases and reproduction number in Brazil
Brazil is an epicentre for COVID-19 in Latin America. In this report we describe the Brazilian epidemicusing three epidemiological measures: the number of infections, the number of deaths and the reproduction number. Our modelling framework requires sufficient death data to estimate trends, and wetherefore limit our analysis to 16 states that have experienced a total of more than fifty deaths. Thedistribution of deaths among states is highly heterogeneous, with 5 states—São Paulo, Rio de Janeiro,Ceará, Pernambuco and Amazonas—accounting for 81% of deaths reported to date. In these states, weestimate that the percentage of people that have been infected with SARS-CoV-2 ranges from 3.3% (95%CI: 2.8%-3.7%) in São Paulo to 10.6% (95% CI: 8.8%-12.1%) in Amazonas. The reproduction number (ameasure of transmission intensity) at the start of the epidemic meant that an infected individual wouldinfect three or four others on average. Following non-pharmaceutical interventions such as school closures and decreases in population mobility, we show that the reproduction number has dropped substantially in each state. However, for all 16 states we study, we estimate with high confidence that thereproduction number remains above 1. A reproduction number above 1 means that the epidemic isnot yet controlled and will continue to grow. These trends are in stark contrast to other major COVID19 epidemics in Europe and Asia where enforced lockdowns have successfully driven the reproductionnumber below 1. While the Brazilian epidemic is still relatively nascent on a national scale, our resultssuggest that further action is needed to limit spread and prevent health system overload.
Vollmer M, Mishra S, Unwin H, et al., 2020, Report 20: A sub-national analysis of the rate of transmission of Covid-19 in Italy
Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28; 238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a
Hoornenborg E, Coyer L, Boyd A, et al., 2020, High incidence of HCV in HIV-negative men who have sex with men using pre-exposure prophylaxis, JOURNAL OF HEPATOLOGY, Vol: 72, Pages: 855-864, ISSN: 0168-8278
Bbosa N, Ssemwanga D, Ssekagiri A, et al., 2020, Phylogenetic and demographic characterization of directed HIV-1 transmission using deep sequences from high-risk and general population cohorts/groups in Uganda, Viruses, Vol: 12, ISSN: 1999-4915
Across sub-Saharan Africa, key populations with elevated HIV-1 incidence and/or prevalence have been identified, but their contribution to disease spread remains unclear. We performed viral deep-sequence phylogenetic analyses to quantify transmission dynamics between the general population (GP), fisherfolk communities (FF), and women at high risk of infection and their clients (WHR) in central and southwestern Uganda. Between August 2014 and August 2017, 6185 HIV-1 positive individuals were enrolled in 3 GP and 10 FF communities, 3 WHR enrollment sites. A total of 2531 antiretroviral therapy (ART) naïve participants with plasma viral load >1000 copies/mL were deep-sequenced. One hundred and twenty-three transmission networks were reconstructed, including 105 phylogenetically highly supported source-recipient pairs. Only one pair involved a WHR and male participant, suggesting that improved population sampling is needed to assess empirically the role of WHR to the transmission dynamics. More transmissions were observed from the GP communities to FF communities than vice versa, with an estimated flow ratio of 1.56 (95% CrI 0.68-3.72), indicating that fishing communities on Lake Victoria are not a net source of transmission flow to neighboring communities further inland. Men contributed disproportionally to HIV-1 transmission flow regardless of age, suggesting that prevention efforts need to better aid men to engage with and stay in care.
Capoferri AA, Lamers SL, Grabowski MK, et al., 2020, Recombination analysis of near full-length HIV-1 sequences and the identification of a potential new circulating recombinant form from Rakai, Uganda., AIDS Research and Human Retroviruses, ISSN: 0889-2229
The Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium has been vital in the generation and examination of near full-length HIV-1 sequences generated from Sub-Saharan Africa. In this study, we examined a subset (n = 275) of sequences from Rakai, Uganda, collected between August 2011 and January 2015. Sequences were initially screened with COMET for subtyping and then evaluated using bootscanning and phylogenetic inference. Among 275 sequences, 38.6% were subtype D, 19.3% were subtype A, 2.9% were subtype C, and 39.3% were recombinant. The recombinants were structurally diverse in the number of breakpoints observed, the location of recombinant segments, and represented subtypes, with AD recombinants accounting for the majority of all recombinants (29.8%). Within the AD subpopulation, we identified a potential new circulating recombinant form in five individuals where the polymerase gene was subtype D and most of env was subtype A (D-A junctures at HXB2 6760 and 8709). While the breakpoints were identical for the viruses from these individuals, the viral fragments did not cluster together. These results suggest selection for a viral strain where properties of the subtype A and subtype D portions of the virus confer a survival advantage. The continued study of recombinants will increase our breadth of knowledge for the genetic diversity and evolution of HIV-1, which can further contribute to our understanding toward a universal HIV-1 vaccine.
Ratmann O, Kagaayi J, Hall M, et al., 2020, Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda, The Lancet HIV, Vol: 7, Pages: e173-e183, ISSN: 2352-3018
BackgroundInternational and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda.MethodsWe did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population.FindingsBetween Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4–7·3) of transmissions occurred within lakeside areas, 89·2% (86·0–91·
Grant HE, Hodcroft EB, Ssemwanga D, et al., 2020, Pervasive and non-random recombination in near full-length HIV genomes from Uganda., Virus Evol, Vol: 6, Pages: 1-12, ISSN: 2057-1577
Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (n = 9); A1/C/D (n = 13), and 33 complex types). K-means clustering of the recombinant A1/D genomes revealed a section of envelope (C2gp120-TMgp41) is often inherited intact, whilst a generalized linear model was used to demonstrate significantly fewer breakpoints in the gag-pol and envelope C2-TM regions compared with accessory gene regions. Despite similar recombination patterns in many recombinants, no clearly supported circulating recombinant form (CRF) was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93 per cent) of the A1/D recombinants appear to be unique recombinant forms. Thus, recombination is pervasive with clear biases in breakpoint location, but CRFs are not a significant feature, characteristic of a complex, and diverse epidemic.
Chatzilena A, van Leeuwen E, Ratmann O, et al., 2019, Contemporary statistical inference for infectious disease models using Stan, Epidemics: the journal of infectious disease dynamics, Vol: 29, ISSN: 1755-4365
This paper is concerned with the application of recent statistical advances to inference of infectious disease dynamics. We describe the fitting of a class of epidemic models using Hamiltonian Monte Carlo and variational inference as implemented in the freely available Stan software. We apply the two methods to real data from outbreaks as well as routinely collected observations. Our results suggest that both inference methods are computationally feasible in this context, and show a trade-off between statistical efficiency versus computational speed. The latter appears particularly relevant for real-time applications.
Le Vu S, Ratmann O, Delpech V, et al., 2019, HIV-1 transmission patterns in men who have sex with men: insights from genetic source attribution analysis, AIDS Research and Human Retroviruses, Vol: 39, Pages: 805-813, ISSN: 0889-2229
BACKGROUND: Near 60% of new HIV infections in the United Kingdom are estimated to occur in men who have sex with men (MSM). Age-disassortative partnerships in MSM have been suggested to spread the HIV epidemics in many Western developed countries and to contribute to ethnic disparities in infection rates. Understanding these mixing patterns in transmission can help to determine which groups are at a greater risk and guide public health interventions. METHODS: We analyzed combined epidemiologic data and viral sequences from MSM diagnosed with HIV at the national level. We applied a phylodynamic source attribution model to infer patterns of transmission between groups of patients. RESULTS: From pair probabilities of transmission between 14 603 MSM patients, we found that potential transmitters of HIV subtype B were on average 8 months older than recipients. We also found a moderate overall assortativity of transmission by ethnic group and a stronger assortativity by region. CONCLUSIONS: Our findings suggest that there is only a modest net flow of transmissions from older to young MSM in subtype B epidemics and that young MSM, both for Black or White groups, are more likely to be infected by one another than expected in a sexual network with random mixing.
Le Vu S, Ratmann O, Delpech V, et al., 2019, HIV-1 Transmission Patterns in Men Who Have Sex with Men: Insights from Genetic Source Attribution Analysis, AIDS Research and Human Retroviruses, ISSN: 0889-2229
Abeler-Dorner L, Grabowski MK, Rambaut A, et al., 2019, PANGEA-HIV 2: Phylogenetics and networks for generalised epidemics in Africa, Current Opinion in HIV and AIDS, Vol: 14, Pages: 173-180, ISSN: 1746-630X
Purpose of review The HIV epidemic in sub-Saharan Africa is far from being under control and the ambitious UNAIDS targets are unlikely to be met by 2020 as declines in per-capita incidence being largely offset by demographic trends. There is an increasing number of proven and specific HIV prevention tools, but little consensus on how best to deploy them.Recent findings Traditionally, phylogenetics has been used in HIV research to reconstruct the history of the epidemic and date zoonotic infections, whereas more recent publications focus on HIV diversity and drug resistance. However, it is also the most powerful method of source attribution available for the study of HIV transmission. The PANGEA (Phylogenetics And Networks for Generalized Epidemics in Africa) consortium has generated over 18 000 NGS HIV sequences from five countries in sub-Saharan Africa. Using phylogenetic methods, we will identify characteristics of individuals or groups, which are most likely to be at risk of infection or at risk of infecting others.Summary Combining phylogenetics, phylodynamics and epidemiology will allow PANGEA to highlight where prevention efforts should be focussed to reduce the HIV epidemic most effectively. To maximise the public health benefit of the data, PANGEA offers accreditation to external researchers, allowing them to access the data and join the consortium. We also welcome submissions of other HIV sequences from sub-Saharan Africa to the database.
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