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OBJECTIVE: To examine the risk of preterm birth (PTB) and small for gestational age (SGA) among women with HIV compared to women without HIV. Secondary objectives were to explore the role of maternal immune activation (IA) and effect of cART timing on these outcomes. DESIGN: Prospective observational cohort. SETTING: Urban government-run clinic at Chawama Hospital in Lusaka, Zambia. PARTICIPANTS: A total of 1481 women with and without HIV with singleton pregnancies enrolled before 26 weeks' gestation by ultrasound dating. METHODS: From August 2019 to November 2022, pregnant women were enrolled in a 1â:â1 ratio of HIV infection. Maternal baseline clinical factors were collected, as well as CD4 + , viral load and CD8 + T-cell IA in women with HIV. Birth outcomes were also collected. The association of HIV-exposure and cART timing on outcomes was assessed by multivariable logistic regression. The independent role of IA was determined by mediation analysis. MAIN OUTCOME MEASURES: PTB (<37âweeks) and SGA. RESULTS: There were 38 fetal deaths and 1230 singleton live births. Maternal HIV infection was associated with PTB [adjusted odds ratio (AOR) 1.60, 95% confidence interval (CI) 1.11-2.32] and to a lesser extent SGA (AOR 1.29, 95% CI 0.98-1.70). Maternal cART timing impacted these associations, with highest risk in women who started cART after conception (PTB AOR 1.77, 95% CI 1.09-2.87, SGA AOR 1.52, 95% CI 1.04-2.22). Maternal IA was not associated with PTB independent of HIV infection. CONCLUSIONS: HIV is associated with PTB. Risk of PTB and SGA was highest in women with HIV who started cART in pregnancy, a modifiable risk factor.
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Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Nacimiento Prematuro/epidemiología , Adulto , Estudios Prospectivos , Zambia/epidemiología , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Adulto Joven , Carga Viral , Atención Preconceptiva , Factores de Riesgo , Fármacos Anti-VIH/uso terapéuticoRESUMEN
INTRODUCTION: There have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening. METHODS: Between August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma. RESULTS: Of the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants. CONCLUSION: Use of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.
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Complicaciones Infecciosas del Embarazo , Serodiagnóstico de la Sífilis , Sífilis , Humanos , Femenino , Sífilis/diagnóstico , Sífilis/sangre , Sífilis/epidemiología , Embarazo , Adulto , Serodiagnóstico de la Sífilis/métodos , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Zambia/epidemiología , Treponema pallidum/inmunología , Adulto Joven , Tamizaje Masivo/métodosRESUMEN
BACKGROUND: Although cannabis use incidence, societal acceptance, and legislation all trend positively, cannabis remains federally illegal in the USA. Prior studies have revealed that patients are reluctant to disclose their cannabis use history in the healthcare system, which can negatively impact patient care. This study reports the frequency of cannabis use disclosure with special considerations for stigmatization. To better understand the limitations, providers face in providing collaborative, comprehensive, and informed care, this study evaluated four domains of stigma: perceived, anticipated, enacted, and internalized. METHODS: This study used a descriptive exploratory design. Data collection occurred using an anonymous, online national survey with a convenience sample in the USA. Recruitment relied on electronic media and occurred between July and December 2022. Participants were adults older than 21 years and self-identified as having used cannabis and accessed the healthcare system within the last five years. The survey measured demographic characteristics, cannabis use, and disclosure patterns. Stigma was measured using the Stigma Use Stigma Mechanism Scale (SU-SMS) and Substance Abuse Use Self-Stigma Scale (SASSS) with language modifications for cannabis. Ordinal logistic regression models were performed to evaluate associations between the frequency of cannabis use disclosure patterns and each stigma category. Associations were assessed using Chi-squared or Fisher's exact tests. RESULTS: Data were available for 249 respondents. Most participants (57.1%) reported initiating a conversation about cannabis with their healthcare provider; 27.8% of the time, cannabis is never discussed, and healthcare providers initiate only 15.1% of related discussions. Anticipated stigma [95% CI 1.045-1.164] and total stigma [95% CI 1.001-1.039] had statistically significant associations with nondisclosure. Annual household income (p = .04), chronicity of cannabis use (p = .03), frequency of cannabis use (p = .02), and a known amount of CBD in products consumed (p = .01) had statistically significant associations with the frequency of cannabis use disclosure. CONCLUSIONS: Patients who use cannabis experience stigmatization in the healthcare setting that may limit disclosure of cannabis use history. Future studies would be well served to explore anticipated stigma more deeply. Healthcare providers should be knowledgeable to lead such conversations relating to cannabis while maintaining an unbiased perspective.
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Cannabis , Adulto , Humanos , Estigma Social , Estereotipo , Revelación , Encuestas y CuestionariosRESUMEN
Introduction: Associative connections have previously been identified between nasopharyngeal infections and infant mortality. The nasopharyngeal microbiome may potentially influence the severity of these infections. Methods: We conducted an analysis of a longitudinal prospective cohort study of 1,981 infants who underwent nasopharyngeal sampling from 1 week through 14 weeks of age at 2-3-week intervals. In all, 27 microbiome samples from 9 of the infants in the cohort who developed fatal acute febrile illness (fAFI) were analyzed in pooled comparisons with 69 samples from 10 healthy comparator infants. We completed 16S rRNA amplicon gene sequencing all infant NP samples and characterized the maturation of the infant NP microbiome among the fAFI(+) and fAFI(-) infant cohorts. Results: Beta diversity measures of fAFI(-) infants were markedly higher than those of fAFI(+) infants. The fAFI(+) infant NP microbiome was marked by higher abundances of Escherichia, Pseudomonas, Leuconostoc, and Weissella, with low relative presence of Alkalibacterium, Dolosigranulum, Moraxella, and Streptococcus. Conclusions: Our results suggest that nasopharyngeal microbiome dysbiosis precedes fAFI in young infants. Early dysbiosis, involving microbes such as Escherichia, may play a role in the causal pathway leading to fAFI or could be a marker of other pathogenic forces that directly lead to fAFI.
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Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Zambia/epidemiología , Entierro , PandemiasRESUMEN
Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care to 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia during 2015. Our Southern Africa Mother Infant Pertussis Study (SAMIPS) prospectively monitored a cohort of mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for respiratory syncytial virus (RSV) and Bordetella pertussis. Our retrospective analysis of the SAMIPS cohort found that symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.
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Virus Sincitial Respiratorio Humano , Tos Ferina , Femenino , Humanos , Lactante , Niño , Tos Ferina/diagnóstico , Estudios Retrospectivos , Zambia/epidemiología , Antibacterianos/uso terapéutico , Bordetella pertussis , PenicilinasRESUMEN
BACKGROUND: There is very little information on the beliefs and perceptions of mothers about SIDS and its related risk factors in Africa. To better understand parental decisions about infant sleep practices and other risk factors for SIDS, we conducted focus group discussions (FGDs) with mothers of infants in Lusaka, Zambia. METHODS: FGDs involved 35 purposively sampled mothers aged 18-49 years. FGDs were conducted using a semi-structured interview guide in the local language, Nyanja. These were translated, transcribed verbatim into English, and then coded and analyzed using thematic analysis in NVivo 12. RESULTS: Six FGDs were conducted with 35 mothers in April-May 2021 across two study sites. FGD Participants were generally aware of sudden unexplained infant deaths, with several describing stories of apparent SIDS in the community. The side sleeping position was preferred and perceived to be safer for the infant with most believing the supine position posed an aspiration or choking risk to the infant. Bedsharing was also preferred and perceived to be convenient for breastfeeding and monitoring of the infant. Experienced family members such as grandmothers and mothers-in-law, and health care workers were frequently cited as sources of information on infant sleep position. A heightened awareness of the infant's sleeping environment was suggested as a mechanism to prevent SIDS and smothering. CONCLUSIONS: Decisions about bedsharing and infant sleep position were guided by maternal beliefs and perceptions about what is convenient for breastfeeding and safer for the infant. These concerns are vital to designing tailored interventions to address sleep-related sudden infant losses in Zambia. Public health campaigns with tailored messages that address these concerns are likely to be effective at ensuring optimal uptake of safe sleep recommendations.
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Madres , Muerte Súbita del Lactante , Femenino , Lactante , Humanos , Muerte Súbita del Lactante/epidemiología , Muerte Súbita del Lactante/etiología , Muerte Súbita del Lactante/prevención & control , Zambia , Factores de Riesgo , Sueño , Posición PronaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and lower respiratory tract infections in children in their first year of life, disproportionately affecting infants in developing countries. Previous studies have found that the nasopharyngeal (NP) microbiome of infants with RSV infection has specific characteristics that correlate with disease severity, including lower biodiversity, perturbations of the microbiota and differences in relative abundance. These studies have focused on infants seen in clinical or hospital settings, predominantly in developed countries. METHODS: We conducted a nested case control study within a random sample of 50 deceased RSV+ infants with age at death ranging from 4 days to 6 months and 50 matched deceased RSV- infants who were all previously enrolled in the Zambia Pertussis and RSV Infant Mortality Estimation (ZPRIME) study. All infants died within the community or within 48 hours of facility admittance. As part of the ZPRIME study procedures, all decedents underwent one-time, postmortem NP sampling. The current analysis explored the differences between the NP microbiome profiles of RSV+ and RSV- decedents using the 16S ribosomal DNA sequencing. RESULTS: We found that Moraxella was more abundant in the NP microbiome of RSV+ decedents than in the RSV- decedents. Additionally, Gemella and Staphylococcus were less abundant in RSV+ decedents than in the RSV- decedents. CONCLUSIONS: These results support previously reported findings of the association between the NP microbiome and RSV and suggest that changes in the abundance of these microbes are likely specific to RSV and may correlate with mortality associated with the disease.
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Enfermedades Transmisibles , Microbiota , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Niño , Humanos , Lactante , Zambia/epidemiología , Estudios de Casos y Controles , HospitalizaciónRESUMEN
BACKGROUND: Having infants sleep with their parents and sleeping face down or on their sides are the two most proximate and modifiable risk factors for sudden infant death syndrome (SIDS). Little is known about the burden of SIDS or the prevalence of these risk factors in Africa. Our primary objective was to determine the prevalence of modifiable risk factors of SIDS in Lusaka, Zambia. METHODS: We conducted cross-sectional surveys with recent mothers of infants aged < 1 year across two busy urban clinic sites in Lusaka, Zambia. We used log-binomial regression analysis to identify factors predictive of bedsharing and prone sleeping. RESULTS: Surveys were conducted with 478 mothers between April-May 2021. The sleep-related risk factors, bedsharing and side sleeping, were widely prevalent. 89.5% of respondents indicated that they share a bed with the infant during sleep, 73.0% preferred putting their baby on its side, and 19.9% preferred the prone position. Only 6.7% of respondents described using the safer, supine position. Age of infant was the only factor which was predictive of prone sleeping. Infants > 2 months old were twice as likely to be put to sleep in a prone position compared to infants aged less than 2 months old. Mothers reported that they rarely (24.1%) received advice from medical caregivers to use the supine position. Maternal use of alcohol (12.0%) and tobacco (0.8%) during pregnancy were uncommon. CONCLUSIONS: Bedsharing and placing the infant to sleep on the side were commonly reported among the mothers we interviewed. Whether this represents an opportunity to reduce SIDS in Zambia is unclear since accurate data on the burden of SIDS in Zambia is not available. There is a need for increased awareness of SIDS and more prospective data collection on its burden and related risk factors in these African populations.
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Muerte Súbita del Lactante , Lactante , Femenino , Embarazo , Humanos , Muerte Súbita del Lactante/epidemiología , Muerte Súbita del Lactante/etiología , Estudios Transversales , Zambia/epidemiología , Factores de Riesgo , Sueño , Prevalencia , Posición PronaRESUMEN
BACKGROUND: The Mobile Continuing Medical Education (mCME) 2.0 project was a randomized controlled trial that found that a 6-month text message-based CME intervention improved both the use of online medical training resources and medical knowledge among a cadre of HIV clinicians in Vietnam. This companion study analyzed intervention costs and cost-effectiveness. METHODS: We conducted (1) a financial analysis based on costs incurred during the trial's planning and implementation; (2) an economic analysis to consider resource utilization; and (3) cost-effectiveness analyses to estimate cost inputs relative to impact: increase in self-study (measured by visits to online courses) and increase in knowledge (measured by exam score improvement) (in 2016 US$). Finally, we estimated the economic cost of a 9-month national program and a 10-year scaled-up model (in 2021 US$). RESULTS: The total financial cost of the intervention was US$49,552; the main cost drivers were personnel time (71.4%) and technology inputs (14.9%). The total economic cost was estimated at US$92,212, with the same key cost inputs (representing 77.7% and 8.0%, respectively, of total costs). The financial cost per 10% increase in accessing online courses was US$923, while the cost of improving knowledge, measured by a 10% improvement in mean exam score across the study population, was US$32,057 (US$605 per intervention clinician). The comparable total economic cost of each improvement, respectively, was US$1,770 and US$61,452 (US$1,159 per intervention clinician). A future 9-month national program was estimated to cost US$37,403, while the full 10-year scaled-up program was estimated at US$196,446. CONCLUSIONS: This analysis indicates that leveraging mobile technology could be a feasible way to provide distance learning to health professions across Vietnam at a relatively low cost. Given the need for practical ways to expand CME in resource-constrained regions of the world, this approach warrants further study and possible adoption.
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Infecciones por VIH , Envío de Mensajes de Texto , Análisis Costo-Beneficio , Educación Médica Continua , Infecciones por VIH/prevención & control , Humanos , VietnamRESUMEN
At our university based high throughput screening program, we test all members of our community weekly using RT-qPCR. RT-qPCR cycle threshold (CT) values are inversely proportional to the amount of viral RNA in a sample and are a proxy for viral load. We hypothesized that CT values would be higher, and thus the viral loads at the time of diagnosis would be lower, in individuals who were infected with the virus but remained asymptomatic throughout the course of the infection. We collected the N1 and N2 target gene CT values from 1633 SARS-CoV-2 positive RT-qPCR tests of individuals sampled between August 7, 2020, and March 18, 2021, at the BU Clinical Testing Laboratory. We matched this data with symptom reporting data from our clinical team. We found that asymptomatic patients had CT values significantly higher than symptomatic individuals on the day of diagnosis. Symptoms were followed by the clinical team for 10 days post the first positive test. Within the entire population, 78.1% experienced at least one symptom during surveillance by the clinical team (n = 1276/1633). Of those experiencing symptoms, the most common symptoms were nasal congestion (73%, n = 932/1276), cough (60.0%, n = 761/1276), fatigue (59.0%, n = 753/1276), and sore throat (53.1%, n = 678/1276). The least common symptoms were diarrhea (12.5%, n = 160/1276), dyspnea on exertion (DOE) (6.9%, n = 88/1276), foot or skin changes (including rash) (4.2%, n = 53/1276), and vomiting (2.1%, n = 27/1276). Presymptomatic individuals, those who were not symptomatic on the day of diagnosis but became symptomatic over the following 10 days, had CT values higher for both N1 (median = 27.1, IQR 20.2-32.9) and N2 (median = 26.6, IQR 20.1-32.8) than the symptomatic group N1 (median = 21.8, IQR 17.2-29.4) and N2 (median = 21.4, IQR 17.3-28.9) but lower than the asymptomatic group N1 (median = 29.9, IQR 23.6-35.5) and N2 (median = 30.0, IQR 23.1-35.7). This study supports the hypothesis that viral load in the anterior nares on the day of diagnosis is a measure of disease intensity at that time.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , SARS-CoV-2/genética , Tomografía Computarizada por Rayos X , Universidades , Carga ViralRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Niño , Preescolar , Costo de Enfermedad , Salud Global , Mortalidad Hospitalaria , Hospitalización , Humanos , Lactante , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and a key driver of childhood mortality. Previous RSV burden of disease estimates used hospital-based surveillance data and modelled, rather than directly measured, community deaths. Given this uncertainty, we conducted a 3-year post-mortem prevalence study among young infants at a busy morgue in Lusaka, Zambia-the Zambia Pertussis RSV Infant Mortality Estimation (ZPRIME) study. METHODS: Infants were eligible for inclusion if they were aged between 4 days and less than 6 months and were enrolled within 48 h of death. Enrolment occurred mainly at the University Teaching Hospital of the University of Zambia Medical School (Lusaka, Zambia), the largest teaching hospital in Zambia. We extracted demographic and clinical data from medical charts and official death certificates, and we conducted verbal autopsies with the guardian or next of kin. RSV was identified using reverse transcriptase quantitative PCR and stratified by age, time of year, and setting (community vs facility deaths). By combining the PCR prevalence data with syndromic presentation, we estimated the proportion of all infant deaths that were due to RSV. FINDINGS: The ZPRIME study ran from Aug 31, 2017, to Aug 31, 2020, except for from April 1 to May 6, 2020, during which data were not collected due to restrictions on human research at this time (linked to COVID-19). We enrolled 2286 deceased infants, representing 79% of total infant deaths in Lusaka. RSV was detected in 162 (7%) of 2286 deceased infants. RSV was detected in 102 (9%) of 1176 community deaths, compared with 10 (4%) of 236 early facility deaths (<48 h from admission) and 36 (5%) of 737 late facility deaths (≥48 h from admission). RSV deaths were concentrated in infants younger than 3 months (116 [72%] of 162 infants), and were clustered in the first half of each year and in the poorest and most densely populated Lusaka townships. RSV caused at least 2·8% (95% CI 1·0-4·6) of all infant deaths and 4·7% (1·3-8·1) of community deaths. INTERPRETATION: RSV was a major seasonal cause of overall infant mortality, particularly among infants younger than 3 months of age. Because most RSV deaths occurred in the community and would have been missed through hospital-based surveillance, the global burden of fatal RSV has probably been underestimated. FUNDING: Bill & Melinda Gates Foundation.
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Infecciones por Virus Sincitial Respiratorio/mortalidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Vigilancia en Salud Pública/métodos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitial Respiratorio Humano , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Zambia/epidemiologíaRESUMEN
OBJECTIVES: To determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia. DESIGN: A systematic, postmortem prevalence study. SETTING: A busy, inner-city morgue in Lusaka. PARTICIPANTS: We sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies. INTERVENTIONS: Not applicable-this was an observational study. PRIMARY OUTCOMES: Prevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time. SECONDARY OUTCOMES: Shifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates. RESULTS: From 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed 'probably due to COVID-19', and weakest among children, with an age-dependent increase in PCR signal intensity. CONCLUSIONS: COVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years.
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COVID-19 , Niño , Humanos , COVID-19/diagnóstico , COVID-19/epidemiología , Zambia/epidemiología , Prevalencia , SARS-CoV-2 , Reacción en Cadena de la Polimerasa , Prueba de COVID-19RESUMEN
Background: Infants suffering from lower respiratory tract infections (LRTIs) have distinct nasopharyngeal (NP) microbiome profiles that correlate with severity of disease. Whether these profiles precede the infection or are a consequence of it, is unknown. In order to answer this question, longitudinal studies are needed. Methods: We conducted a retrospective analysis of NP samples collected in a longitudinal birth cohort study of Zambian mother-infant pairs. Samples were collected every two weeks from 1-week through 14-weeks of age. Ten of the infants in the cohort who developed LRTI were matched 1:3 with healthy comparators. We completed 16S rRNA gene sequencing on the samples each of these infants contributed and compared the NP microbiome of the healthy infants to infants who developed LRTI. Results: The infant NP microbiome maturation was characterized by transitioning from Staphylococcus dominant to respiratory-genera dominant profiles during the first three months of life, similar to what is described in the literature. Interestingly, infants who developed LRTI had distinct NP microbiome characteristics before infection, in most cases as early as the first week of life. Their NP microbiome was characterized by the presence of Novosphingobium, Delftia, high relative abundance of Anaerobacillus, Bacillus, and low relative abundance of Dolosigranulum, compared to the healthy controls. Mothers of infants with LRTI also had low relative abundance of Dolosigranulum in their baseline samples compared to mothers of infants that did not develop an LRTI. Conclusions: Our results suggest that specific characteristics of the NP microbiome precede LRTI in young infants and may be present in their mothers as well. Early dysbiosis may play a role in the causal pathway leading to LRTI or could be a marker of underlying immunological, environmental, or genetic characteristics that predispose to LRTI.
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Disbiosis , Nasofaringe , Infecciones del Sistema Respiratorio , Humanos , Estudios Longitudinales , Disbiosis/microbiología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/epidemiología , Nasofaringe/microbiología , Lactante , Femenino , Masculino , Recién Nacido , Estudios Retrospectivos , ARN Ribosómico 16S/genética , Microbiota , Estudios de Cohortes , Cohorte de NacimientoRESUMEN
BACKGROUND: Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. METHODS: We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. RESULTS: From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40-64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected. CONCLUSIONS: Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19.
Asunto(s)
COVID-19 , Adulto , Autopsia , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Síndrome , Zambia/epidemiologíaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology in low- and middle-income countries is poorly understood. Risk factors associated with RSV-associated infant deaths that occur in community settings are incompletely known. METHODS: Community deaths for infants aged 4 days to 6 months were identified during a 3-year postmortem RSV prevalence study at the main city morgue in Lusaka, Zambia, where 80% of deaths are registered. This analysis focuses on the subset of deaths for which an abbreviated verbal autopsy was available and intended to sort deaths into respiratory or nonrespiratory causes by clinical adjudication. Posterior nasopharyngeal swab samples were collected within 48 hours of death and tested for RSV using quantitative reverse-transcription polymerase chain reaction. Associations between potential risk factors were determined as relative risks with 95% confidence intervals (CIs). RESULTS: We prospectively enrolled 798 community infant deaths with verbal autopsies and RSV laboratory results, of which 62 results were positive. The mean age of the infants was 10 weeks, and 41.4% of them were male. Of all deaths, 44% were attributed to respiratory causes. RSV was detected in 7.8% of the community infants and was significantly associated with respiratory deaths (risk ratio, 4.0 [95% CI, 2.2-7.1]). Compared with older infants, those aged 0-8 weeks had a 2.83 (95% CI, 1.30-6.15) increased risk of dying with RSV. The risk of RSV for the 0-8-week age group increased to 5.24 (1.56-33.14) with adjustment for demographics, parental education, and geography. RSV deaths were increased with domiciliary overcrowding and were concentrated in poor and dense neighborhoods in Lusaka (risk ratio, 2.00 [95% CI, 1.22-3.27]). CONCLUSION: RSV is a significant contributor to community respiratory deaths in this population, particularly in the first 3 months of life and in the more poor and dense parts of Lusaka.