Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 35 Records) |
Query Trace: Tobias J[original query] |
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COVID-19 vaccination site accessibility, United States, December 11, 2020-March 29, 2022
Yee R , Carranza D , Kim C , Trinidad JP , Tobias JL , Bhatkoti R , Kuwabara S . Emerg Infect Dis 2024 30 (5) 947-955 During December 11, 2020-March 29, 2022, the US government delivered ≈700 million doses of COVID-19 vaccine to vaccination sites, resulting in vaccination of ≈75% of US adults during that period. We evaluated accessibility of vaccination sites. Sites were accessible by walking within 15 minutes by 46.6% of persons, 30 minutes by 74.8%, 45 minutes by 82.8%, and 60 minutes by 86.7%. When limited to populations in counties with high social vulnerability, accessibility by walking was 55.3%, 81.1%, 86.7%, and 89.4%, respectively. By driving, lowest accessibility was 96.5% at 15 minutes. For urban/rural categories, the 15-minute walking accessibility between noncore and large central metropolitan areas ranged from 27.2% to 65.1%; driving accessibility was 79.9% to 99.5%. By 30 minutes driving accessibility for all urban/rural categories was >95.9%. Walking time variations across jurisdictions and between urban/rural areas indicate that potential gains could have been made by improving walkability or making transportation more readily available. |
High-resolution characterization of recent tuberculosis transmission in Botswana using geospatial and genomic data - the Kopanyo Study (preprint)
Baker CR , Barilar I , de Araujo LS , Rimoin AW , Parker DM , Boyd R , Tobias JL , Moonan PK , Click ES , Finlay A , Oeltmann JE , Minin VN , Modongo C , Zetola NM , Niemann S , Shin SS . medRxiv 2022 18 Introduction. Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis (Mtb) transmission in high tuberculosis burden settings. Methods. We performed whole genome sequencing (WGS) on Mtb DNA extracted from sputum cultures from a population-based tuberculosis study conducted in 2012-2016 in Gaborone, Botswana. We used kernel density estimation, spatial K-functions, and created spatial distributions of phylogenetic trees. WGS-based clusters of isolates <5 single nucleotide polymorphisms were considered recent transmission, and large WGS-based clusters (>10 members) were considered outbreaks. Results. We analyzed data from 1449 participants with culture-confirmed TB. Among these, 946 (65%) participants had both molecular and geospatial data. A total of 62 belonged to five large outbreaks (10-19 participants each). Geospatial clustering was detected in two of the five large outbreaks, suggesting heterogeneous spatial patterns within the community. Conclusions. Integration of genomic and geospatial data identified distinct patterns of tuberculosis transmission in a high-tuberculosis burden setting. Targeted interventions in these smaller geographies may interrupt on-going transmission. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Reaching youth through faith leaders: Evaluation of the Faith Matters! Initiative
Kanagasabai U , Aholou T , Chevalier MS , Tobias JL , Okuku J , Shiraishi RW , Sheneberger R , Pande YC , Chifuwe C , Mamane LE , Njika G , Obongo C , Thorsen VC . AIDS Educ Prev 2023 35 82-99 Faith leaders can be uniquely positioned to guide and support young people on health issues, particularly HIV/AIDS and sexual violence. Faith Matters!, a 2-day training workshop for faith leaders, was delivered in September 2021 in Zambia. Sixty-six faith leaders completed a questionnaire at baseline, 64 at posttraining, and 59 at 3-month follow-up. Participants' knowledge, beliefs, and comfort communicating about HIV/AIDS and sexual violence were assessed. More faith leaders accurately identified common places where sexual violence occurs at the 3-month point compared to baseline: at church (2 vs. 22, p = .000), the fields (16 vs. 29, p = .004), parties (22 vs. 36, p = .001), and clubs (24 vs. 35, p = .034). More faith leaders stated that they engaged in conversations that supported people living with HIV (48 at baseline vs. 53, p = .049 at 3-month follow-up). These findings can inform future HIV/AIDS initiatives focusing on increasing the capacity among communities of faith. |
Use of high-resolution geospatial and genomic data to characterize recent tuberculosis transmission, Botswana
Baker CR , Barilar I , de Araujo LS , Rimoin AW , Parker DM , Boyd R , Tobias JL , Moonan PK , Click ES , Finlay A , Oeltmann JE , Minin VN , Modongo C , Zetola NM , Niemann S , Shin SS . Emerg Infect Dis 2023 29 (5) 977-987 ![]() Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks. |
Retaining patients with drug-resistant tuberculosis on treatment during the COVID-19 pandemic - Dharavi, Mumbai, India, 2020-2022
Gomare MD , Bhide S , Deshmukh R , Kaipilyawar S , Puri V , Moonan PK , Khetade DK , Nyendak M , Yeldandi V , Smith JP , Tobias JL , Date A , Joshi R , Kumar R , Ho CS . MMWR Morb Mortal Wkly Rep 2023 72 (12) 304-308 Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum(†); historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies. |
Characterizing tuberculosis transmission dynamics in high-burden urban and rural settings.
Smith JP , Oeltmann JE , Hill AN , Tobias JL , Boyd R , Click ES , Finlay A , Mondongo C , Zetola NM , Moonan PK . Sci Rep 2022 12 (1) 6780 ![]() ![]() Mycobacterium tuberculosis transmission dynamics in high-burden settings are poorly understood. Growing evidence suggests transmission may be characterized by extensive individual heterogeneity in secondary cases (i.e., superspreading), yet the degree and influence of such heterogeneity is largely unknown and unmeasured in high burden-settings. We conducted a prospective, population-based molecular epidemiology study of TB transmission in both an urban and rural setting of Botswana, one of the highest TB burden countries in the world. We used these empirical data to fit two mathematical models (urban and rural) that jointly quantified both the effective reproductive number, [Formula: see text], and the propensity for superspreading in each population. We found both urban and rural populations were characterized by a high degree of individual heterogeneity, however such heterogeneity disproportionately impacted the rural population: 99% of secondary transmission was attributed to only 19% of infectious cases in the rural population compared to 60% in the urban population and the median number of incident cases until the first outbreak of 30 cases was only 32 for the rural model compared to 791 in the urban model. These findings suggest individual heterogeneity plays a critical role shaping local TB epidemiology within subpopulations. |
Zambia assessment of tuberculosis (TB) and HIV in the mines (ZATHIM): implications for programs and policies
Podewils LJ , Long EF , Fuller TJ , Mwakazanga D , Kapungu K , Tembo M , Mwanza S , Curran KG , Smith JP , Tobias JL , Kasongo W . BMC Public Health 2022 22 (1) 791 BACKGROUND: Mineworkers in Southern Africa have the highest rates of tuberculosis (TB) among working populations in the world (The World Bank, Benefits and costs associated with reducing tuberculosis among Southern Africa's mineworkers, 2014), making mineworkers a key population for TB program efforts. The current evaluation aimed to characterize mineworkers and former (ex-) mineworkers, and assess knowledge, attitudes and practices related to TB and HIV care among mineworkers and healthcare workers (HCWs) in Zambia. METHODS: A mixed-methods evaluation of current and former (ex-) mineworkers and HCWs was conducted in the Copperbelt and North-Western provinces, Zambia. Knowledge, attitudes and practices (KAPs) related to TB care and policies were assessed using a structured survey. Focus Group Discussions (FGDs) were conducted with current and ex-mineworkers to understand perceptions, practices, and barriers related to accessing healthcare for TB. RESULTS: Overall, 2,792 mineworkers and 94 HCWs completed the KAP survey, and 206 (171 current, 71 ex-) mineworkers participated in FGDs. Mineworkers and ex-mineworkers were knowledgeable about TB symptoms (cough; 94%), transmission (81.7%) and treatment (99.2%). Yet, barriers to seeking care were evident with 30% of mineworkers experiencing cough, and 19% reporting 2 or more TB symptoms at the time of the survey. The majority of mineworkers (70.9%) were aware of policies barring persons from working after a diagnosis of TB, and themes from FGDs and HCW comments (n = 32/62; 51.6%) recognized fear of job loss as a critical barrier to providing timely screening and appropriate care for TB among mineworkers. The majority (76.9%) of mineworkers indicated they would not disclose their TB status to their supervisor, but would be willing to share their diagnosis with their spouse (73.8%). CONCLUSION: Fear of job loss, driven by governmental policy and mistrust in mining companies, is a major barrier to healthcare access for TB among mineworkers in Zambia. As a result of these findings, the government policy prohibiting persons from working in the mines following TB disease is being repealed. However, major reforms are urgently needed to mitigate TB among mineworkers, including ensuring the rights of mineworkers and their communities to healthy living and working environments, improved social responsibility of mining companies, and facilitating choice and access to affordable, timely, and high-quality healthcare services. |
Tuberculosis attributed to transmission within healthcare facilities, Botswana-The Kopanyo Study.
Smith JP , Modongo C , Moonan PK , Dima M , Matsiri O , Fane O , Click ES , Boyd R , Finlay A , Surie D , Tobias JL , Zetola NM , Oeltmann JE . Infect Control Hosp Epidemiol 2022 43 (11) 1-7 ![]() OBJECTIVE: Healthcare facilities are a well-known high-risk environment for transmission of M. tuberculosis, the etiologic agent of tuberculosis (TB) disease. However, the link between M. tuberculosis transmission in healthcare facilities and its role in the general TB epidemic is unknown. We estimated the proportion of overall TB transmission in the general population attributable to healthcare facilities. METHODS: We combined data from a prospective, population-based molecular epidemiologic study with a universal electronic medical record (EMR) covering all healthcare facilities in Botswana to identify biologically plausible transmission events occurring at the healthcare facility. Patients with M. tuberculosis isolates of the same genotype visiting the same facility concurrently were considered an overlapping event. We then used TB diagnosis and treatment data to categorize overlapping events into biologically plausible definitions. We calculated the proportion of overall TB cases in the cohort that could be attributable to healthcare facilities. RESULTS: In total, 1,881 participants had TB genotypic and EMR data suitable for analysis, resulting in 46,853 clinical encounters at 338 healthcare facilities. We identified 326 unique overlapping events involving 370 individual patients; 91 (5%) had biologic plausibility for transmission occurring at a healthcare facility. A sensitivity analysis estimated that 3%-8% of transmission may be attributable to healthcare facilities. CONCLUSIONS: Although effective interventions are critical in reducing individual risk for healthcare workers and patients at healthcare facilities, our findings suggest that development of targeted interventions aimed at community transmission may have a larger impact in reducing TB. |
Antiretroviral therapy initiation and retention among clients who received peer-delivered linkage case management and standard linkage services, Eswatini, 2016-2020: retrospective comparative cohort study
MacKellar D , Hlophe T , Ujamaa D , Pals S , Dlamini M , Dube L , Suraratdecha C , Williams D , Byrd J , Tobias J , Mndzebele P , Behel S , Pathmanathan I , Mazibuko S , Tilahun E , Ryan C . Arch Public Health 2022 80 (1) 74 BACKGROUND: Persons living with HIV infection (PLHIV) who are diagnosed in community settings in sub-Saharan Africa are particularly vulnerable to barriers to care that prevent or delay many from obtaining antiretroviral therapy (ART). METHODS: We conducted a retrospective cohort study to assess if a package of peer-delivered linkage case management and treatment navigation services (CommLink) was more effective than peer-delivered counseling, referral, and telephone follow-up (standard linkage services, SLS) in initiating and retaining PLHIV on ART after diagnosis in community settings in Eswatini. HIV-test records of 773 CommLink and 769 SLS clients aged15years diagnosed between March 2016 and March 2018, matched by urban and rural settings of diagnosis, were selected for the study. CommLink counselors recorded resolved and unresolved barriers to care (e.g., perceived wellbeing, fear of partner response, stigmatization) during a median of 52days (interquartile range: 35-69) of case management. RESULTS: Twice as many CommLink than SLS clients initiated ART by 90days of diagnosis overall (88.4% vs. 37.9%, adjusted relative risk (aRR): 2.33, 95% confidence interval (CI): 1.97, 2.77) and during test and treat when all PLHIV were eligible for ART (96.2% vs. 37.1%, aRR: 2.59, 95% CI: 2.20, 3.04). By 18months of diagnosis, 54% more CommLink than SLS clients were initiated and retained on ART (76.3% vs. 49.5%, aRR: 1.54, 95% CI: 1.33, 1.79). Peer counselors helped resolve 896 (65%) of 1372 identified barriers of CommLink clients. Compared with clients with3 unresolved barriers to care, 42% (aRR: 1.42, 95% CI: 1.19, 1.68) more clients with 1-2 unresolved barriers, 44% (aRR: 1.44, 95% CI: 1.25, 1.66) more clients with all barriers resolved, and 54% (aRR: 1.54, 95% CI: 1.30, 1.81) more clients who had no identified barriers were initiated and retained on ART by 18months of diagnosis. CONCLUSIONS: To improve early ART initiation and retention among PLHIV diagnosed in community settings, HIV prevention programs should consider providing a package of peer-delivered linkage case management and treatment navigation services. Clients with multiple unresolved barriers to care measured as part of that package should be triaged for differentiated linkage and retention services. |
Geospatial transmission hotspots of recent HIV infection - Malawi, October 2019-March 2020
Telford CT , Tessema Z , Msukwa M , Arons MM , Theu J , Bangara FF , Ernst A , Welty S , O'Malley G , Dobbs T , Shanmugam V , Kabaghe A , Dale H , Wadonda-Kabondo N , Gugsa S , Kim A , Bello G , Eaton JW , Jahn A , Nyirenda R , Parekh BS , Shiraishi RW , Kim E , Tobias JL , Curran KG , Payne D , Auld AF . MMWR Morb Mortal Wkly Rep 2022 71 (9) 329-334 Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection.(†) The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)(§) and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission. |
Geographic and demographic heterogeneity of SARS-CoV-2 diagnostic testing in Illinois, USA, March to December 2020.
Holden TM , Richardson RAK , Arevalo P , Duffus WA , Runge M , Whitney E , Wise L , Ezike NO , Patrick S , Cobey S , Gerardin J . BMC Public Health 2021 21 (1) 1105 BACKGROUND: Availability of SARS-CoV-2 testing in the United States (U.S.) has fluctuated through the course of the COVID-19 pandemic, including in the U.S. state of Illinois. Despite substantial ramp-up in test volume, access to SARS-CoV-2 testing remains limited, heterogeneous, and insufficient to control spread. METHODS: We compared SARS-CoV-2 testing rates across geographic regions, over time, and by demographic characteristics (i.e., age and racial/ethnic groups) in Illinois during March through December 2020. We compared age-matched case fatality ratios and infection fatality ratios through time to estimate the fraction of SARS-CoV-2 infections that have been detected through diagnostic testing. RESULTS: By the end of 2020, initial geographic differences in testing rates had closed substantially. Case fatality ratios were higher in non-Hispanic Black and Hispanic/Latino populations in Illinois relative to non-Hispanic White populations, suggesting that tests were insufficient to accurately capture the true burden of COVID-19 disease in the minority populations during the initial epidemic wave. While testing disparities decreased during 2020, Hispanic/Latino populations consistently remained the least tested at 1.87 tests per 1000 population per day compared with 2.58 and 2.87 for non-Hispanic Black and non-Hispanic White populations, respectively, at the end of 2020. Despite a large expansion in testing since the beginning of the first wave of the epidemic, we estimated that over half (50-80%) of all SARS-CoV-2 infections were not detected by diagnostic testing and continued to evade surveillance. CONCLUSIONS: Systematic methods for identifying relatively under-tested geographic regions and demographic groups may enable policymakers to regularly monitor and evaluate the shifting landscape of diagnostic testing, allowing officials to prioritize allocation of testing resources to reduce disparities in COVID-19 burden and eventually reduce SARS-CoV-2 transmission. |
Where Are the Newly Diagnosed HIV Positives in Kenya Time to Consider Geo-Spatially Guided Targeting at a Finer Scale to Reach the "First 90"
Waruru A , Wamicwe J , Mwangi J , Achia TNO , Zielinski-Gutierrez E , Ng'ang'a L , Miruka F , Yegon P , Kimanga D , Tobias JL , Young PW , De Cock KM , Tylleskär T . Front Public Health 2021 9 503555 Background: The UNAIDS 90-90-90 Fast-Track targets provide a framework for assessing coverage of HIV testing services (HTS) and awareness of HIV status - the "first 90." In Kenya, the bulk of HIV testing targets are aligned to the five highest HIV-burden counties. However, we do not know if most of the new HIV diagnoses are in these five highest-burden counties or elsewhere. Methods: We analyzed facility-level HTS data in Kenya from 1 October 2015 to 30 September 2016 to assess the spatial distribution of newly diagnosed HIV-positives. We used the Moran's Index (Moran's I) to assess global and local spatial auto-correlation of newly diagnosed HIV-positive tests and Kulldorff spatial scan statistics to detect hotspots of newly diagnosed HIV-positive tests. For aggregated data, we used Kruskal-Wallis equality-of-populations non-parametric rank test to compare absolute numbers across classes. Results: Out of 4,021 HTS sites, 3,969 (98.7%) had geocodes available. Most facilities (3,034, 76.4%), were not spatially autocorrelated for the number of newly diagnosed HIV-positives. For the rest, clustering occurred as follows; 438 (11.0%) were HH, 66 (1.7%) HL, 275 (6.9%) LH, and 156 (3.9%) LL. Of the HH sites, 301 (68.7%) were in high HIV-burden counties. Over half of 123 clusters with a significantly high number of newly diagnosed HIV-infected persons, 73(59.3%) were not in the five highest HIV-burden counties. Clusters with a high number of newly diagnosed persons had twice the number of positives per 1,000,000 tests than clusters with lower numbers (29,856 vs. 14,172). Conclusions: Although high HIV-burden counties contain clusters of sites with a high number of newly diagnosed HIV-infected persons, we detected many such clusters in low-burden counties as well. To expand HTS where most needed and reach the "first 90" targets, geospatial analyses and mapping make it easier to identify and describe localized epidemic patterns in a spatially dispersed epidemic like Kenya's, and consequently, reorient and prioritize HTS strategies. |
COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program - Kentucky, March 2021.
Cavanaugh AM , Fortier S , Lewis P , Arora V , Johnson M , George K , Tobias J , Lunn S , Miller T , Thoroughman D , Spicer KB . MMWR Morb Mortal Wkly Rep 2021 70 (17) 639-643 ![]() ![]() Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. The Kentucky Department for Public Health (KDPH) and a local health department investigated a COVID-19 outbreak in a SNF that occurred after all residents and health care personnel (HCP) had been offered vaccination. Among 83 residents and 116 HCP, 75 (90.4%) and 61 (52.6%), respectively, received 2 vaccine doses. Twenty-six residents and 20 HCP received positive test results for SARS-CoV-2, the virus that causes COVID-19, including 18 residents and four HCP who had received their second vaccine dose >14 days before the outbreak began. An R.1 lineage variant was detected with whole genome sequencing (WGS). Although the R.1 variant has multiple spike protein mutations, vaccinated residents and HCP were 87% less likely to have symptomatic COVID-19 compared with those who were unvaccinated. Vaccination of SNF populations, including HCP, is critical to reduce the risk for SARS-CoV-2 introduction, transmission, and severe outcomes in SNFs. An ongoing focus on infection prevention and control practices is also essential. |
Population-based geospatial and molecular epidemiologic study of tuberculosis transmission dynamics, Botswana, 2012-2016
Zetola NM , Moonan PK , Click E , Oeltmann JE , Basotli J , Wen XJ , Boyd R , Tobias JL , Finlay A , Modongo C . Emerg Infect Dis 2021 27 (3) 835-844 Tuberculosis (TB) elimination requires interrupting transmission of Mycobacterium tuberculosis. We used a multidisciplinary approach to describe TB transmission in 2 sociodemographically distinct districts in Botswana (Kopanyo Study). During August 2012-March 2016, all patients who had TB were enrolled, their sputum samples were cultured, and M. tuberculosis isolates were genotyped by using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats. Of 5,515 TB patients, 4,331 (79%) were enrolled. Annualized TB incidence varied by geography (range 66-1,140 TB patients/100,000 persons). A total of 1,796 patient isolates had valid genotyping results and residential geocoordinates; 780 (41%) patients were involved in a localized TB transmission event. Residence in areas with a high burden of TB, age <24 years, being a current smoker, and unemployment were factors associated with localized transmission events. Patients with known HIV-positive status had lower odds of being involved in localized transmission. |
Possible transmission mechanisms of mixed Mycobacterium tuberculosis infection in high HIV prevalence country, Botswana
Baik Y , Modongo C , Moonan PK , Click ES , Tobias JL , Boyd R , Finlay A , Oeltmann JE , Shin SS , Zetola NM . Emerg Infect Dis 2020 26 (5) 953-960 Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains (i.e., mixed infection) challenges clinical and epidemiologic paradigms. We explored possible transmission mechanisms of mixed infection in a population-based, molecular epidemiology study in Botswana during 2012-2016. We defined mixed infection as multiple repeats of alleles at >2 loci within a discrete mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) result. We compared mixed infection MIRU-VNTR results with all study MIRU-VNTR results by considering all permutations at each multiple allele locus; matched MIRU-VNTR results were considered evidence of recently acquired strains and nonmatched to any other results were considered evidence of remotely acquired strains. Among 2,051 patients, 34 (1.7%) had mixed infection, of which 23 (68%) had recently and remotely acquired strains. This finding might support the mixed infection mechanism of recent transmission and simultaneous remote reactivation. Further exploration is needed to determine proportions of transmission mechanisms in settings where mixed infections are prevalent. |
A neighbor-based approach to identify tuberculosis exposure, the Kopanyo Study
Moonan PK , Zetola NM , Tobias JL , Basotli J , Boyd R , Click ES , Dima M , Fane O , Finlay AM , Ogopotse M , Wen XJ , Modongo C , Oeltmann JE . Emerg Infect Dis 2020 26 (5) 1010-1013 Contact investigation is one public health measure used to prevent tuberculosis by identifying and treating persons exposed to Mycobacterium tuberculosis. Contact investigations are a major tenet of global tuberculosis elimination efforts, but for many reasons remain ineffective. We describe a novel neighbor-based approach to reframe contact investigations. |
The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa.
Park SE , Pham DT , Boinett C , Wong VK , Pak GD , Panzner U , Espinoza LMC , von Kalckreuth V , Im J , Schutt-Gerowitt H , Crump JA , Breiman RF , Adu-Sarkodie Y , Owusu-Dabo E , Rakotozandrindrainy R , Soura AB , Aseffa A , Gasmelseed N , Keddy KH , May J , Sow AG , Aaby P , Biggs HM , Hertz JT , Montgomery JM , Cosmas L , Fields B , Sarpong N , Razafindrabe TJL , Raminosoa TM , Kabore LP , Sampo E , Teferi M , Yeshitela B , El Tayeb MA , Sooka A , Meyer CG , Krumkamp R , Dekker DM , Jaeger A , Poppert S , Tall A , Niang A , Bjerregaard-Andersen M , Valborg Løfberg S , Seo HJ , Jeon HJ , Deerin JF , Park J , Konings F , Ali M , Clemens JD , Hughes P , Sendagala JN , Vudriko T , Downing R , Ikumapayi UN , Mackenzie GA , Obaro S , Argimon S , Aanensen DM , Page A , Keane JA , Duchene S , Dyson Z , Holt KE , Dougan G , Marks F , Baker S . Nat Commun 2018 9 (1) 5094 ![]() ![]() There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa. |
Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17
Jeddy Z , Tobias JH , Taylor EV , Northstone K , Flanders WD , Hartman TJ . Arch Osteoporos 2018 13 (1) 84 Prenatal exposures to perfluoroalkyl substances (PFAS) have been associated with developmental outcomes in offspring. We found that prenatal concentrations of some PFAS may be associated with reduced bone mass and size in 17-year-old British girls, although it is not clear whether these associations are driven by body size. PURPOSE: PFAS are used to make protective coatings on common household products. Prenatal exposures have been associated with developmental outcomes in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between prenatal concentrations of PFAS and bone health in girls at 17 years of age and whether body composition can explain any associations. METHODS: We measured concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) in maternal serum samples collected during pregnancy. We obtained bone health outcomes in the girls, such as bone mineral density, bone mineral content, bone area, and area-adjusted bone mineral content from whole-body dual-energy X-ray absorptiometry (DXA) scans. We used multivariable linear regression to explore associations between each PFAS and each bone health outcome with adjustment for important confounders such as girls' age at clinic visit, maternal education, and gestational age at sample collection. We also controlled for girls' height and lean mass to explore the role body composition had on observed associations. RESULTS: Prenatal PFOS, PFOA, PFHxS, and PFNA concentrations were associated with inverse effects on bone size and mass after adjusting for important confounders. Conversely, PFNA was positively associated with area-adjusted bone mineral content. However, most significant associations attenuated after additional controlling for height and lean mass. CONCLUSIONS: Prenatal concentrations of some PFAS may be associated with reduced bone mass and size in adolescent girls, although it is not clear whether these associations are driven by body size. |
Spatial-temporal trend for mother-to-child transmission of HIV up to infancy and during pre-Option B+ in western Kenya, 2007-13
Waruru A , Achia TNO , Muttai H , Ng'ang'a L , Zielinski-Gutierrez E , Ochanda B , Katana A , Young PW , Tobias JL , Juma P , De Cock KM , Tylleskär T . PeerJ 2018 2018 (3) e4427 ![]() Introduction: Using spatial-temporal analyses to understand coverage and trends in elimination of mother-to-child transmission of HIV (e-MTCT) efforts may be helpful in ensuring timely services are delivered to the right place. We present spatial-temporal analysis of seven years of HIV early infant diagnosis (EID) data collected from 12 districts in western Kenya from January 2007 to November 2013, during pre-Option B+ use. Methods: We included in the analysis infants up to one year old. We performed trend analysis using extended Cochran-Mantel-Haenszel stratified test and logistic regression models to examine trends and associations of infant HIV status at first diagnosis with: early diagnosis ( < 8 weeks after birth), age at specimen collection, infant ever having breastfed, use of single dose nevirapine, and maternal antiretroviral therapy status. We examined these covariates and fitted spatial and spatial-temporal semiparametric Poisson regression models to explain HIVinfection rates using R-integrated nested Laplace approximation package. We calculated new infections per 100,000 live births and used Quantum GIS to map fitted MTCT estimates for each district in Nyanza region. Results: Median age was two months, interquartile range 1.5-5.8 months. Unadjusted pooled positive rate was 11.8% in the seven-years period and declined from 19.7% in 2007 to 7.0% in 2013, p < 0.01. Uptake of testing ≤ 8 weeks after birth was under 50% in 2007 and increased to 64.1% by 2013, p < 0.01. By 2013, the overall standardized MTCTrate was 447 infections per 100,000 live births. Based on Bayesian deviance information criterion comparisons, the spatial-temporal model with maternal and infant covariates was best in explaining geographical variation in MTCT. Discussion: Improved EID uptake and reduced MTCT rates are indicators of progress towards e-MTCT. Cojoined analysis of time and covariates in a spatial context provides a robust approach for explaining differences in programmatic impact over time. Conclusion: During this pre-Option B+ period, the prevention of mother to child transmission program in this region has not achieved e-MTCT target of ≤ 50 infections per 100,000 live births. Geographical disparities in program achievements may signify gaps in spatial distribution of e-MTCT efforts and could indicate areas needing further resources and interventions. |
Finding hidden HIV clusters to support geographic-oriented HIV interventions in Kenya
Waruru A , Achia TNO , Tobias JL , Ng'ang'a J , Mwangi M , Wamicwe J , Zielinski-Gutierrez E , Oluoch T , Muthama E , Tylleskar T . J Acquir Immune Defic Syndr 2018 78 (2) 144-154 BACKGROUND: In a spatially well-known and dispersed HIV epidemic, identifying geographic clusters with significantly higher HIV-prevalence is important for focusing interventions for people living with HIV (PLHIV). METHODS: We used Kulldorff spatial-scan Poisson model to identify clusters with high numbers of HIV-infected persons 15-64 years old. We classified PLHIV as belonging to either higher or lower prevalence (HP/LP) clusters, then assessed distributions of socio-demographic and bio-behavioral HIV risk factors and associations with clustering. RESULTS: About half of survey locations, 112/238 (47%) had high rates of HIV (HP clusters), with 1.1-4.6 times greater PLHIV adults observed than expected. Richer persons compared to respondents in lowest wealth index had higher odds of belonging to a HP cluster, adjusted odds ratio (aOR), 1.61(95% CI: 1.13-2.3), aOR 1.66(95% CI: 1.09-2.53), aOR 3.2(95% CI: 1.82-5.65), aOR 2.28(95% CI: 1.09-4.78) in second, middle, fourth and highest quintiles respectively. Respondents who perceived themselves to have greater HIV risk or were already HIV-infected had higher odds of belonging to a HP cluster, aOR 1.96(95% CI: 1.13-3.4) and aOR 5.51(95% CI: 2.42-12.55) respectively; compared to perceived low risk. Men who had ever been clients of FSW had higher odds of belonging to a HP cluster than those who had never been, aOR 1.47(95% CI: 1.04-2.08); and uncircumcised men vs circumcised, aOR 3.2, (95% CI: 1.74-5.8). CONCLUSION: HIV infection in Kenya exhibits localized geographic clustering associated with socio-demographic and behavioral factors, suggesting disproportionate exposure to higher HIV-risk. Identification of these clusters reveals the right places for targeting priority-tailored HIV interventions. |
Molecular, Spatial, and Field Epidemiology Suggesting TB Transmission in Community, Not Hospital, Gaborone, Botswana.
Surie D , Fane O , Finlay A , Ogopotse M , Tobias JL , Click ES , Modongo C , Zetola NM , Moonan PK , Oeltmann JE . Emerg Infect Dis 2017 23 (3) 487-490 ![]() During 2012-2015, 10 of 24 patients infected with matching genotypes of Mycobacterium tuberculosis received care at the same hospital in Gaborone, Botswana. Nosocomial transmission was initially suspected, but we discovered plausible sites of community transmission for 20 (95%) of 21 interviewed patients. Active case-finding at these sites could halt ongoing transmission. |
Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution.
Rutledge GG , Bohme U , Sanders M , Reid AJ , Cotton JA , Maiga-Ascofare O , Djimde AA , Apinjoh TO , Amenga-Etego L , Manske M , Barnwell JW , Renaud F , Ollomo B , Prugnolle F , Anstey NM , Auburn S , Price RN , McCarthy JS , Kwiatkowski DP , Newbold CI , Berriman M , Otto TD . Nature 2017 542 (7639) 101-104 ![]() Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri). These species are prevalent across most regions in which malaria is endemic and are often undetectable by light microscopy, rendering their study in human populations difficult. The exact evolutionary relationship of these species to the other human-infective species has been contested. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole. |
Prevalence and correlates of genital infections among newly diagnosed human immunodeficiency virus-infected adults entering human immunodeficiency virus care in Windhoek, Namibia
Djomand G , Schlefer M , Gutreuter S , Tobias S , Patel R , Deluca N , Hood J , Sawadogo S , Chen C , Muadinohamba A , Lowrance DW , Bock N . Sex Transm Dis 2016 43 (11) 698-705 Background Identifying and treating genital infections, including sexually transmitted infections (STI), among newly diagnosed human immunodeficiency virus (HIV)-infected individuals may benefit both public and individual health. We assessed prevalence of genital infections and their correlates among newly diagnosed HIV-infected individuals enrolling in HIV care services in Namibia. Methods Newly diagnosed HIV-infected adults entering HIV care at 2 health facilities in Windhoek, Namibia, were recruited from December 2012 to March 2014. Participants provided behavioral and clinical data including CD4+ T lymphocyte counts. Genital and blood specimens were tested for gonorrhea, Chlamydia, trichomoniasis, Mycoplasma genitalium, syphilis, bacterial vaginosis, and vulvovaginal candidiasis. Results Among 599 adults, 56% were women and 15% reported consistent use of condoms in the past 6 months. The most common infections were bacterial vaginosis (37.2%), trichomoniasis (34.6%) and Chlamydia (14.6%) in women and M. genitalium (11.4%) in men. Correlates for trichomoniasis included being female (adjusted relative risk, [aRR], 7.18; 95% confidence interval [CI], 4.07-12.65), higher education (aRR, 0.58; 95% CI, 0.38-0.89), and lower CD4 cell count (aRR, 1.61; 95% CI, 1.08-2.40). Being female (aRR, 2.39; 95% CI, 1.27-4.50), nonmarried (aRR, 2.30; (95% CI, 1.28-4.14), and having condomless sex (aRR, 2.72; 95% CI, 1.06-7.00) were independently associated with chlamydial infection. Across all infections, female (aRR, 2.31; 95% CI, 1.79-2.98), nonmarried participants (aRR, 1.29; 95% CI, 1.06-1.59), had higher risk to present with any STI, whereas pregnant women (aRR, 1.16, 95% CI 1.03-1.31) were at increased risk of any STI or reproductive tract infection. |
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Machiela MJ , Zhou W , Karlins E , Sampson JN , Freedman ND , Yang Q , Hicks B , Dagnall C , Hautman C , Jacobs KB , Abnet CC , Aldrich MC , Amos C , Amundadottir LT , Arslan AA , Beane-Freeman LE , Berndt SI , Black A , Blot WJ , Bock CH , Bracci PM , Brinton LA , Bueno-de-Mesquita HB , Burdett L , Buring JE , Butler MA , Canzian F , Carreon T , Chaffee KG , Chang IS , Chatterjee N , Chen C , Chen C , Chen K , Chung CC , Cook LS , Crous Bou M , Cullen M , Davis FG , De Vivo I , Ding T , Doherty J , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF , Friedenreich CM , Fuchs CS , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Gaudet MM , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Henriksson R , Holly EA , Hong YC , Hoover RN , Hsiung CA , Hu N , Hu W , Hunter DJ , Hutchinson A , Jenab M , Johansen C , Khaw KT , Kim HN , Kim YH , Kim YT , Klein AP , Klein R , Koh WP , Kolonel LN , Kooperberg C , Kraft P , Krogh V , Kurtz RC , LaCroix A , Lan Q , Landi MT , Marchand LL , Li D , Liang X , Liao LM , Lin D , Liu J , Lissowska J , Lu L , Magliocco AM , Malats N , Matsuo K , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Moore L , Olson SH , Orlow I , Park JY , Patino-Garcia A , Peplonska B , Peters U , Petersen GM , Pooler L , Prescott J , Prokunina-Olsson L , Purdue MP , Qiao YL , Rajaraman P , Real FX , Riboli E , Risch HA , Rodriguez-Santiago B , Ruder AM , Savage SA , Schumacher F , Schwartz AG , Schwartz KL , Seow A , Wendy Setiawan V , Severi G , Shen H , Sheng X , Shin MH , Shu XO , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Van Den Berg D , Visvanathan K , Wacholder S , Wang JC , Wang Z , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolpin BM , Wong MP , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xia L , Yang HP , Yang PC , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Ziegler RG , Perez-Jurado LA , Caporaso NE , Rothman N , Tucker M , Dean MC , Yeager M , Chanock SJ . Nat Commun 2016 7 11843 ![]() To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. |
Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk.
Inzaule SC , Weidle PJ , Yang C , Ndiege K , Hamers RL , Rinke de Wit TF , Thomas T , Zeh C . J Antimicrob Chemother 2016 71 (6) 1619-26 ![]() BACKGROUND: K65R is a relatively rare drug resistance mutation (DRM) selected by the NRTIs tenofovir, didanosine, abacavir and stavudine and confers cross-resistance to all NRTIs except zidovudine. Selection by other NRTIs is uncommon. OBJECTIVES: In this study we investigated the frequency of emergence of the K65R mutation and factors associated with it in HIV-1-infected infants exposed to low doses of maternal lamivudine, zidovudine and either nevirapine or nelfinavir ingested through breast milk, using specimens collected from the Kisumu Breastfeeding Study. METHODS: Plasma specimens with viral load ≥1000 copies/mL collected from HIV-infected infants at 0-1, 2, 6, 14, 24 and 36 weeks of age and maternal samples at delivery were tested for HIV drug resistance using Sanger sequencing of the polymerase gene. Factors associated with K65R emergence were assessed using Fisher's exact test and the Wilcoxon rank-sum test. RESULTS: K65R was detected in samples from 6 of the 24 infants (25%) who acquired HIV-1 infection by the age of 6 months. K65R emerged in half of the infants by 6 weeks and in the rest by 14 weeks of age. None of the mothers at delivery or the infants with a positive genotype at first time of positivity had the K65R mutation. Infants with K65R had low baseline CD4 cell counts (P = 0.014), were more likely to have DRMs earlier (≤6 weeks versus ≥14 weeks, P = 0.007) and were more likely to have multiclass drug resistance (P = 0.035). M184V was the most common mutation associated with K65R emergence. K65R had reverted by 3 months after cessation of breastfeeding. CONCLUSIONS: A high rate of K65R emergence may suggest that ingesting low doses of lamivudine via breast milk could select for this mutation. The presence of this mutation may have a negative impact on future responses to NRTI-based ART. More in vitro studies are, however, needed to establish the molecular mechanism for this selection. |
Amoebic meningoencephalitis and disseminated infection caused by Balamuthia mandrillaris in a Western lowland gorilla (Gorilla gorilla gorilla)
Gjeltema JL , Troan B , Muehlenbachs A , Liu L , Da Silva AJ , Qvarnstrom Y , Tobias JR , Loomis MR , De Voe RS . J Am Vet Med Assoc 2016 248 (3) 315-21 CASE DESCRIPTION: A 22-year-old male gorilla (Gorilla gorilla gorilla) housed in a zoo was evaluated for signs of lethargy, head-holding, and cervical stiffness followed by development of neurologic abnormalities including signs of depression, lip droop, and tremors. CLINICAL FINDINGS: Physical examination under general anesthesia revealed a tooth root abscess and suboptimal body condition. A CBC and serum biochemical analysis revealed mild anemia, neutrophilia and eosinopenia consistent with a stress leukogram, and signs consistent with dehydration. Subsequent CSF analysis revealed lymphocytic pleocytosis and markedly increased total protein concentration. TREATMENT AND OUTCOME: Despite treatment with antimicrobials, steroids, and additional supportive care measures, the gorilla's condition progressed to an obtunded mentation with grand mal seizures over the course of 10 days. Therefore, the animal was euthanized and necropsy was performed. Multifocal areas of malacia and hemorrhage were scattered throughout the brain; on histologic examination, these areas consisted of necrosis and hemorrhage associated with mixed inflammation, vascular necrosis, and intralesional amoebic trophozoites. Tan foci were also present in the kidneys and pancreas. Immunohistochemical testing positively labeled free-living amoebae within the brain, kidneys, eyes, pancreas, heart, and pulmonary capillaries. Subsequent PCR assay of CSF and frozen kidney samples identified the organism as Balamuthia mandrillaris, confirming a diagnosis of amoebic meningoencephalitis. CLINICAL RELEVANCE: Infection with B mandrillaris has been reported to account for 2.8% of captive gorilla deaths in North America over the past 19 years. Clinicians working with gorillas should have a high index of suspicion for this diagnosis when evaluating and treating animals with signs of centrally localized neurologic disease. |
HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.
Rhee SY , Jordan MR , Raizes E , Chua A , Parkin N , Kantor R , Van Zyl GU , Mukui I , Hosseinipour MC , Frenkel LM , Ndembi N , Hamers RL , Rinke de Wit TF , Wallis CL , Gupta RK , Fokam J , Zeh C , Schapiro JM , Carmona S , Katzenstein D , Tang M , Aghokeng AF , De Oliveira T , Wensing AM , Gallant JE , Wainberg MA , Richman DD , Fitzgibbon JE , Schito M , Bertagnolio S , Yang C , Shafer RW . PLoS One 2015 10 (12) e0145772 ![]() The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naive individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naive individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy. |
Investments in blood safety improve the availability of blood to underserved areas in a sub-Saharan African country
Pitman JP , Wilkinson R , Basavaraju SV , von Finckenstein B , Sibinga CS , Marfin AA , Postma MJ , Mataranyika M , Tobias J , Lowrance DW . ISBT Sci Ser 2014 9 (2) 325-333 BACKGROUND AND OBJECTIVES: Since 2004, several African countries, including Namibia, have received assistance from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Gains have been documented in the safety and number of collected units in these countries, but the distribution of blood has not been described. MATERIALS AND METHODS: Nine years of data on blood requests and issues from Namibia were stratified by region to describe temporal and spatial changes in the number and type of blood components issued to Namibian healthcare facilities nationally. RESULTS: Between 2004 and 2007 (early years of PEPFAR support) and 2008-2011 (peak years of PEPFAR support), the average number of red cell units issued annually increased by 23.5% in seven densely populated but less-developed regions in northern Namibia; by 30% in two regions with urban centres; and by 35.1% in four sparsely populated rural regions. CONCLUSION: Investments in blood safety and a policy decision to emphasize distribution of blood to underserved regions improved blood availability in remote rural areas and increased the proportion of units distributed as components. However, disparities persist in the distribution of blood between Namibia's urban and rural regions. |
Good laboratory practice for clinical next-generation sequencing informatics pipelines.
Gargis AS , Kalman L , Bick DP , da Silva C , Dimmock DP , Funke BH , Gowrisankar S , Hegde MR , Kulkarni S , Mason CE , Nagarajan R , Voelkerding KV , Worthey EA , Aziz N , Barnes J , Bennett SF , Bisht H , Church DM , Dimitrova Z , Gargis SR , Hafez N , Hambuch T , Hyland FC , Luna RA , MacCannell D , Mann T , McCluskey MR , McDaniel TK , Ganova-Raeva LM , Rehm HL , Reid J , Campo DS , Resnick RB , Ridge PG , Salit ML , Skums P , Wong LJ , Zehnbauer BA , Zook JM , Lubin IM . Nat Biotechnol 2015 33 (7) 689-93 ![]() We report principles and guidelines (Supplementary Note) that were developed by the Next-Generation Sequencing: Standardization of Clinical Testing II (Nex-StoCT II) informatics workgroup, which was first convened on October 11–12, 2012, in Atlanta, Georgia, by the US Centers for Disease Control and Prevention (CDC; Atlanta, GA). We present here recommendations for the design, optimization and implementation of an informatics pipeline for clinical next-generation sequencing (NGS) to detect germline sequence variants in compliance with existing regulatory and professional quality standards1. The workgroup, which included informatics experts, clinical and research laboratory professionals, physicians with experience in interpreting NGS results, NGS test platform and software developers and participants from US government agencies and professional organizations, also discussed the use of NGS in testing for cancer and infectious disease. A typical NGS analytical process and selected workgroup recommendations are summarized in Table 1, and detailed in the guidelines presented in the Supplementary Note. |
Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.
Rhee SY , Blanco JL , Jordan MR , Taylor J , Lemey P , Varghese V , Hamers RL , Bertagnolio S , de Wit TF , Aghokeng AF , Albert J , Avi R , Avila-Rios S , Bessong PO , Brooks JI , Boucher CA , Brumme ZL , Busch MP , Bussmann H , Chaix ML , Chin BS , D'Aquin TT , De Gascun CF , Derache A , Descamps D , Deshpande AK , Djoko CF , Eshleman SH , Fleury H , Frange P , Fujisaki S , Harrigan PR , Hattori J , Holguin A , Hunt GM , Ichimura H , Kaleebu P , Katzenstein D , Kiertiburanakul S , Kim JH , Kim SS , Li Y , Lutsar I , Morris L , Ndembi N , Ng KP , Paranjape RS , Peeters M , Poljak M , Price MA , Ragonnet-Cronin ML , Reyes-Teran G , Rolland M , Sirivichayakul S , Smith DM , Soares MA , Soriano VV , Ssemwanga D , Stanojevic M , Stefani MA , Sugiura W , Sungkanuparph S , Tanuri A , Tee KK , Truong HH , van de Vijver DA , Vidal N , Yang C , Yang R , Yebra G , Ioannidis JP , Vandamme AM , Shafer RW . PLoS Med 2015 12 (4) e1001810 ![]() BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naive individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions-a proxy for recent infection-yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs-K101E, K103N, Y181C, and G190A-accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen. |
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