RESUMO
BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).
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Febre Paratifoide , Febre Tifoide , Humanos , Lactente , Incidência , Índia/epidemiologia , Febre Paratifoide/diagnóstico , Febre Paratifoide/epidemiologia , Vigilância da População , Estudos Prospectivos , Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia , Efeitos Psicossociais da Doença , Hemocultura , Pré-Escolar , Criança , Adolescente , População Urbana/estatística & dados numéricos , População Rural/estatística & dados numéricos , Hospitalização/estatística & dados numéricosRESUMO
Cholera was first described in the areas around the Bay of Bengal and spread globally, resulting in seven pandemics during the past two centuries. It is caused by toxigenic Vibrio cholerae O1 or O139 bacteria. Cholera is characterised by mild to potentially fatal acute watery diarrhoeal disease. Prompt rehydration therapy is the cornerstone of management. We present an overview of cholera and its pathogenesis, natural history, bacteriology, and epidemiology, while highlighting advances over the past 10 years in molecular epidemiology, immunology, and vaccine development and deployment. Since 2014, the Global Task Force on Cholera Control, a WHO coordinated network of partners, has been working with several countries to develop national cholera control strategies. The global roadmap for cholera control focuses on stopping transmission in cholera hotspots through vaccination and improved water, sanitation, and hygiene, with the aim to reduce cholera deaths by 90% and eliminate local transmission in at least 20 countries by 2030.
Assuntos
Cólera , Vibrio cholerae , Cólera/epidemiologia , Cólera/prevenção & controle , Diarreia/epidemiologia , Humanos , Epidemiologia Molecular , SaneamentoRESUMO
BACKGROUND: Cholera in Kolkata remains endemic and the Indian city is burdened with a high number of annual cases. Climate change is widely considered to exacerbate cholera, however the precise relationship between climate and cholera is highly heterogeneous in space and considerable variation can be observed even within the Indian subcontinent. To date, relatively few studies have been conducted regarding the influence of climate on cholera in Kolkata. METHODS: We considered 21 years of confirmed cholera cases from the Infectious Disease Hospital in Kolkata during the period of 1999-2019. We used Generalised Additive Modelling (GAM) to extract the non-linear relationship between cholera and different climatic factors; temperature, rainfall and sea surface temperature (SST). Peak associated lag times were identified using cross-correlation lag analysis. RESULTS: Our findings revealed a bi-annual pattern of cholera cases with two peaks coinciding with the increase in temperature in summer and the onset of monsoon rains. Variables selected as explanatory variables in the GAM model were temperature and rainfall. Temperature was the only significant factor associated with summer cholera (mean temperature of 30.3 °C associated with RR of 3.8) while rainfall was found to be the main driver of monsoon cholera (550 mm total monthly rainfall associated with RR of 3.38). Lag time analysis revealed that the association between temperature and cholera cases in the summer had a longer peak lag time compared to that between rainfall and cholera during the monsoon. We propose several mechanisms by which these relationships are mediated. CONCLUSIONS: Kolkata exhibits a dual-peak phenomenon with independent mediating factors. We suggest that the summer peak is due to increased bacterial concentration in urban water bodies, while the monsoon peak is driven by contaminated flood waters. Our results underscore the potential utility of preventative strategies tailored to these seasonal and climatic patterns, including efforts to reduce direct contact with urban water bodies in summer and to protect residents from flood waters during monsoon.
Assuntos
Cólera , Humanos , Povo Asiático , Cólera/epidemiologia , Mudança Climática , Inundações , Água , Estações do Ano , Clima , Índia/epidemiologiaRESUMO
BACKGROUND: We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting). FINDINGS: Between Nov 16, 2020, and Jan 7, 2021, we recruited 25â798 participants who were randomly assigned to receive BBV152 or placebo; 24â419 received two doses of BBV152 (n=12â221) or placebo (n=12â198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2-86·4). In the safety population (n=25â753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12â879) and placebo group (1597 [12·4%] of 12â874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths. INTERPRETATION: BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis. FUNDING: Bharat Biotech International and Indian Council of Medical Research.
Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , Eficácia de Vacinas , Vacinas de Produtos Inativados/imunologia , Adjuvantes Imunológicos , Adulto , Teste de Ácido Nucleico para COVID-19 , Método Duplo-Cego , Feminino , Humanos , Índia , MasculinoRESUMO
BACKGROUND: The Sustainable Development Goals identified universal access to water and sanitation facilities as key components for improving health. We assessed water, sanitation, and hygiene (WASH) practices and associated determinants among residents of urban slums in Kolkata, India. METHODS: Information on WASH practices was collected in 2 surveys (2018 and 2019) from participants of a prospective enteric fever surveillance conducted in 2 municipal wards of Kolkata. A composite WASH practice score was computed and a hierarchical stepwise multiple linear regression model constructed to identify key determinants of improved WASH score. RESULTS: Over 90% of households had access to piped water; 6% reported access to continuous supply. Adult women (61% in 2018; 45% in 2019) spent 20 minutes daily to fetch water. Access to improved latrines was almost universal, although 80% used shared facilities. Unhealthy disposal of children's stools was reported in both rounds. Food hygiene practices were high, with most (>90%) washing uncooked items before eating; frequent consumption of street food items was reported. CONCLUSIONS: The study area reported high WASH coverage. Unhygienic behavioral patterns predisposing to food- or water-borne diseases were also noted. Awareness building and sustainable community mobilization for food hygiene needs to be emphasized to ensure community well-being.
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Saneamento , Água , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Higiene , Índia/epidemiologia , Áreas de Pobreza , Estudos Prospectivos , Abastecimento de ÁguaRESUMO
Cholera remains a major contributor of diarrheal diseases and leads to substantial morbidity and mortality, particularly in low socioeconomic settings. Nonavailability of a national cholera control plan in India, compounded by underreporting of cholera cases and deficient accurate cholera hotspot estimates, has made cholera control a challenge. Obstacles in the programmatic introduction of oral cholera vaccine (OCV) lie within the infrastructure-stockpile, costing, distribution system, cold-chain mechanism, vaccine logistics, and lack of strengthened surveillance systems for adverse events following immunization. Sustained political commitment along with collaboration of people working in the media will also determine the policy outcome of OCV introduction in India.
Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Programas de Imunização/organização & administração , Administração Oral , Cólera/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Índia/epidemiologia , VacinaçãoRESUMO
BACKGROUND: In the densely populated slums of Kolkata, informal healthcare providers' (IHP) diarrhea-related knowledge and rationality of practices should be improved to reduce risk of adverse outcome, expenditure, and antimicrobial resistance. METHODS: A multicomponent intervention was conducted among 140 representative IHPs in the slums of 8 wards in Kolkata to assess its impact on their diarrhea-related knowledge and practice. Six intervention modules in local languages were provided (1 per month) with baseline (Nâ =â 140) and postintervention (Nâ =â 124) evaluation. RESULTS: Mean overall (61.1 to 69.3; Pâ <â .0001) and domain-specific knowledge scores for etiology/spread (5.4 to 8.1; Pâ <â .0001), management (6.4 to 7.2; Pâ <â .0001), and oral rehydration solution ([ORS] 5.7 to 6.5; Pâ <â .0001) increased significantly (at αâ =â 0.05) after intervention and were well retained. Impact on knowledge regarding etiology/spread (adjusted odds ratio [aOR]â =â 5.6; Pâ <â .0001), cholera (aORâ =â 2.0; Pâ =â .0041), management (aORâ =â 3.1; Pâ <â .0001), ORS (aORâ =â 2.3; Pâ =â .0008), and overall (aORâ =â 4.3; Pâ <â .0001) were significant. Intervention worked better for IHPs who practiced for ≥10 years (aORâ =â 3.2; Pâ <â .0001), untrained IHPs (aORâ =â 4.8; Pâ <â .0001), and pharmacists (aORâ =â 8.3; Pâ <â .0001). Irrational practices like empirical antibiotic use for every cholera case (aORâ =â 0.3; Pâ <â .0001) and investigation for every diarrhea case (aORâ =â 0.4; Pâ =â .0003) were reduced. Rationality of testing (aORâ =â 4.2; Pâ <â .0001) and antibiotic use (aORâ =â 1.8; Pâ =â .0487) improved. CONCLUSIONS: Multicomponent educational intervention resulted in sustainable improvement in diarrhea-related knowledge and practices among IHPs in slums of Kolkata. Policy implications should be advocated along with implementation and scale-up.
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Cólera , Diarreia , Conhecimentos, Atitudes e Prática em Saúde , Áreas de Pobreza , Cólera/diagnóstico , Cólera/tratamento farmacológico , Cólera/prevenção & controle , Efeitos Psicossociais da Doença , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Diarreia/prevenção & controle , Humanos , Higiene , Saneamento , Abastecimento de ÁguaRESUMO
BACKGROUND: Typhoid is known to be heterogenous in time and space, with documented spatiotemporal clustering and hotspots associated with environmental factors. This analysis evaluated spatial clustering of typhoid and modeled incidence rates of typhoid from active surveillance at 4 sites with child cohorts in India. METHODS: Among approximately 24 000 children aged 0.5-15 years followed for 2 years, typhoid was confirmed by blood culture in all children with fever >3 days. Local hotspots for incident typhoid cases were assessed using SaTScan spatial cluster detection. Incidence of typhoid was modeled with sociodemographic and water, sanitation, and hygiene-related factors in smaller grids using nonspatial and spatial regression analyses. RESULTS: Hotspot households for typhoid were identified at Vellore and Kolkata. There were 4 significant SaTScan clusters (P < .05) for typhoid in Vellore. Mean incidence of typhoid was 0.004 per child-year with the highest incidence (0.526 per child-year) in Kolkata. Unsafe water and poor sanitation were positively associated with typhoid in Kolkata and Delhi, whereas drinking untreated water was significantly associated in Vellore (P = .0342) and Delhi (P = .0188). CONCLUSIONS: Despite decades of efforts to improve water and sanitation by the Indian government, environmental factors continue to influence the incidence of typhoid. Hence, administration of the conjugate vaccine may be essential even as efforts to improve water and sanitation continue.
Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Humanos , Incidência , Lactente , Regressão Espacial , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , ÁguaRESUMO
BACKGROUND: Acute febrile illness in children is frequently treated with antibiotics. However, the inappropriate use of antibiotics has led to the emergence of multidrug-resistant pathogens. METHODS: We measured use of antibiotics for fever in 4 pediatric cohorts that were part of the Surveillance for Enteric Fever in India (SEFI) network. In this network, 24 062 children were followed up weekly, capturing information on fever and other morbidity between October 2017 and December 2019. RESULTS: An antibiotic was given in 27 183 of the 76 027 (35.8%) episodes of fever. The incidence of fever-related antibiotic use was 58.0 (95% confidence interval [CI], 57.2-58.6) per 100 child-years. The median time to initiation of antibiotics was 4 days, and in 65% of those who received an antibiotic it was initiated by the second day. Antibiotics were continued for <3 days in 24% of the episodes. Higher temperature, younger age, male sex, joint family, higher education, internet access, and availability of personal conveyance were associated with antibiotic treatment for fever. CONCLUSIONS: In developing countries where antibiotic use is not regulated, broad-spectrum antibiotics are initiated early, and often inappropriately, in febrile illness. Frequent and inappropriate use of antibiotics may increase risk of antimicrobial resistance.
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Febre Tifoide , Antibacterianos/uso terapêutico , Criança , Febre/tratamento farmacológico , Febre/epidemiologia , Humanos , Incidência , Índia/epidemiologia , Masculino , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologiaRESUMO
BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.
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Antibacterianos/uso terapêutico , Criptosporidiose/tratamento farmacológico , Cryptosporidium/patogenicidade , Diarreia/tratamento farmacológico , Escherichia coli/patogenicidade , Transtornos do Crescimento/etiologia , Shigella/patogenicidade , Estudos de Casos e Controles , Criança , Cryptosporidium/isolamento & purificação , Diarreia/epidemiologia , Diarreia/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Shigella/isolamento & purificaçãoRESUMO
Conducting population-based serosurveillance for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) will estimate and monitor the trend of infection in the adult general population, determine the socio-demographic risk factors and delineate the geographical spread of the infection. For this purpose, a serial cross-sectional survey would be conducted with a sample size of 24,000 distributed equally across four strata of districts categorized on the basis of the incidence of reported cases of COVID-19. Sixty districts will be included in the survey. Simultaneously, the survey will be done in 10 high-burden hotspot cities. ELISA-based antibody tests would be used. Data collection will be done using a mobile-based application. Prevalence from the group of districts in each of the four strata will be pooled to estimate the population prevalence of COVID-19 infection, and similarly for the hotspot cities, after adjusting for demographic characteristics and antibody test performance. The total number of reported cases in the districts and hotspot cities will be adjusted using this seroprevalence to estimate the expected number of infected individuals in the area. Such serosurveys repeated at regular intervals can also guide containment measures in respective areas. State-specific context of disease burden, priorities and resources should guide the use of multifarious surveillance options for the current COVID-19 epidemic.
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Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Vigilância da População/métodos , COVID-19 , Infecções por Coronavirus/sangue , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Pandemias , Pneumonia Viral/sangue , Prevalência , Projetos de Pesquisa , SARS-CoV-2 , Estudos SoroepidemiológicosRESUMO
In addition to improved water supply and sanitation, the 2-dose killed oral cholera vaccine (OCV) is an important tool for the prevention and control of cholera. We aimed to document the immunogenicity and protection (efficacy and effectiveness) conferred by a single OCV dose against cholera. The metaanalysis showed that an estimated 73% and 77% of individuals seroconverted to the Ogawa and Inaba serotypes, respectively, after an OCV first dose. The estimates of single-dose vaccine protection from available studies are 87% at 2 months decreasing to 33% at 2 years. Current immunologic and clinical data suggest that protection conferred by a single dose of killed OCV may be sufficient to reduce short-term risk in outbreaks or other high-risk settings, which may be especially useful when vaccine supply is limited. However, until more data suggest otherwise, a second dose should be given as soon as circumstances allow to ensure robust protection.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Imunogenicidade da Vacina , Vacinas de Produtos Inativados/imunologia , Administração Oral , Vacinas contra Cólera/administração & dosagem , Surtos de Doenças/prevenção & controle , Humanos , Esquemas de Imunização , Soroconversão , Sorogrupo , Vacinação/métodos , Potência de Vacina , Vacinas de Produtos Inativados/administração & dosagem , Vibrio cholerae/imunologiaRESUMO
BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.
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Termos de Consentimento/ética , Necessidades e Demandas de Serviços de Saúde/ética , Sujeitos da Pesquisa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Tomada de Decisões , Ética em Pesquisa , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Sujeitos da Pesquisa/estatística & dados numéricos , Inquéritos e Questionários , Adulto JovemRESUMO
The lipid composition of breast milk may have a significant impact on early infant growth and cognitive development. Comprehensive breast milk data is lacking from low-income populations in the Indian subcontinent impeding assessment of deficiencies and limiting development of maternal nutritional interventions. A single breast milk specimen was collected within 6 weeks postpartum from two low-income maternal cohorts of exclusively breastfed infants, from Dhaka, Bangladesh (n = 683) and Kolkata, India (n = 372) and assayed for percentage composition of 26 fatty acids. Mature milk (>15 days) in Dhaka (n = 99) compared to Kolkata (n = 372) was higher in total saturated fatty acid (SFA; mean 48% vs. 44%) and disproportionately lower in ω3-polyunsaturated fatty acid (PUFA), hence the ω6- and ω3-PUFA ratio in Dhaka were almost double the value in Kolkata. In both sites, after adjusting for days of lactation, increased maternal education was associated with decreased SFA and PUFA, and increasing birth order or total pregnancies was associated with decreasing ω6-PUFA or ω3-PUFA by a factor of 0.95 for each birth and pregnancy. In Dhaka, household prosperity was associated with decreased SFA and PUFA and increased ω6- and ω3-PUFA. Maternal height was associated with increased SFA and PUFA in Kolkata (1% increase per 1 cm), but body mass index showed no independent association with either ratio in either cohort. In summary, the socioeconomic factors of maternal education and household prosperity were associated with breast milk composition, although prosperity may only be important in higher cost of living communities. Associated maternal biological factors were height and infant birth order, but not adiposity. Further study is needed to elucidate the underlying mechanisms of these effects.
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Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Leite Humano/química , Fatores Socioeconômicos , População Urbana , Adulto , Bangladesh , Índice de Massa Corporal , Feminino , Humanos , Índia , Lactente , Lactação , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
INTRODUCTION: Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy. METHODS AND FINDINGS: This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5-11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%-98%) and 93% (95% CI 44%-99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses. CONCLUSIONS: These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT00289224.
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Vacinas contra Cólera/farmacologia , Cólera/prevenção & controle , Vibrio cholerae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Incidência , Índia , Lactente , Masculino , Pessoa de Meia-Idade , Risco , Adulto JovemRESUMO
Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Doenças Endêmicas , Vacinação , Administração Oral , Adolescente , Adulto , Criança , Pré-Escolar , Cólera/epidemiologia , Protocolos Clínicos , Etiópia/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Saúde Pública , Vacinas de Produtos Inativados/imunologia , Adulto JovemRESUMO
BACKGROUND: Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. METHODS: The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. FINDINGS: We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. INTERPRETATION: Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. FUNDING: The Bill & Melinda Gates Foundation.
Assuntos
Infecções Bacterianas/mortalidade , Diarreia/microbiologia , Diarreia/mortalidade , Infecções por Rotavirus/mortalidade , África Subsaariana , Ásia Ocidental/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Efeitos Psicossociais da Doença , Países em Desenvolvimento , Diarreia Infantil/microbiologia , Diarreia Infantil/mortalidade , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
BACKGROUND AND AIMS: This review aims to estimate the prevalence of undernutrition among migrants, refugees, internally displaced children, and children of migrated parents living in lower-middle-income countries. METHODS: PubMed, Scopus, Science-Direct, CINAHL-Plus, & Google Scholar were searched for peer-reviewed evidence published between January 2010 to March 2023. Two researchers independently examined the studies and retrieved the data. The internal and external validity of the studies was assessed using the NIH quality assessment tool, and a checklist adapted from Downs & Black, Bracht & Glass, and Del Siegle's guidelines. A random effect model was chosen to pool the estimates. Subgroup analysis, Meta-regression, and sensitivity analysis were done to explore the source of heterogeneity and the robustness of estimates. RESULTS: Among the 1978 records initially searched, 21 studies were selected for analysis. The pooled prevalence estimates for stunting, wasting, and underweight were estimated to be 29.39% (Confidence Interval [CI] 21.69-37.73; I2 99%; p < 0.01), 12.76% (CI 7.84-18.68; I2 99%; P < 0.01), and 24.05% (CI 16.17-32.94; I2 100%; p < 0.001) respectively. Among different WHO regions, all three undernutrition estimates were higher in LMICs belonging to the Southeast Asian region (Stunting 37.62%; wasting 14.28% and underweight 31.24%). Undernutrition among migrant Indian children was 43.55%, 18.71%, and 37.45% respectively. High heterogeneity was noted across all estimates with I2-value >90%. Sensitivity analysis across indicators showed the stability of our estimates. CONCLUSIONS: The extent of undernutrition, particularly wasting was high among migrant/refugee children living in lower-middle-income countries. Measures should be taken to strengthen the government-subsidized public food distribution system, increase healthcare outreach, and ensure public health insurance coverage among the migrant population.
Assuntos
Países em Desenvolvimento , Desnutrição , Refugiados , Migrantes , Humanos , Refugiados/estatística & dados numéricos , Prevalência , Desnutrição/epidemiologia , Países em Desenvolvimento/estatística & dados numéricos , Migrantes/estatística & dados numéricos , Criança , PaisRESUMO
BACKGROUND: Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce. METHODS: We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models. RESULTS: We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection. CONCLUSION: In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.
Assuntos
Áreas de Pobreza , Salmonella typhi , Febre Tifoide , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Humanos , Bangladesh/epidemiologia , Masculino , Feminino , Incidência , Adolescente , Criança , Adulto , Pré-Escolar , Adulto Jovem , Estudos Prospectivos , Vacinas Tíficas-Paratíficas/administração & dosagem , Análise Espaço-Temporal , Lactente , Análise por Conglomerados , Vacinação , Pessoa de Meia-Idade , População Urbana , Estudos de Casos e ControlesRESUMO
Background: Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods: We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results: Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%-64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%-75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%-64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%-48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, -26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, -3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%-81%; P < .001). Conclusions: These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.