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1.
Clin Infect Dis ; 78(1): 31-39, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-37633257

RESUMO

BACKGROUND: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. METHODS: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. RESULTS: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. CONCLUSIONS: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.


Assuntos
Bacteriemia , Infecção Hospitalar , Infecções por Klebsiella , Sepse , Humanos , Klebsiella pneumoniae , Infecção Hospitalar/epidemiologia , Mortalidade Hospitalar , Bacteriemia/microbiologia , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Sepse/tratamento farmacológico , Genômica
2.
Epidemiol Infect ; 152: e52, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497497

RESUMO

Hepatitis E virus (HEV) is a major cause of acute jaundice in South Asia. Gaps in our understanding of transmission are driven by non-specific symptoms and scarcity of diagnostics, impeding rational control strategies. In this context, serological data can provide important proxy measures of infection. We enrolled a population-representative serological cohort of 2,337 individuals in Sitakunda, Bangladesh. We estimated the annual risks of HEV infection and seroreversion both using serostatus changes between paired serum samples collected 9 months apart, and by fitting catalytic models to the age-stratified cross-sectional seroprevalence. At baseline, 15% (95 CI: 14-17%) of people were seropositive, with seroprevalence highest in the relatively urban south. During the study, 27 individuals seroreverted (annual seroreversion risk: 15%, 95 CI: 10-21%), and 38 seroconverted (annual infection risk: 3%, 95CI: 2-5%). Relying on cross-sectional seroprevalence data alone, and ignoring seroreversion, underestimated the annual infection risk five-fold (0.6%, 95 CrI: 0.5-0.6%). When we accounted for the observed seroreversion in a reversible catalytic model, infection risk was more consistent with measured seroincidence. Our results quantify HEV infection risk in Sitakunda and highlight the importance of accounting for seroreversion when estimating infection incidence from cross-sectional seroprevalence data.


Assuntos
Vírus da Hepatite E , Hepatite E , Humanos , Bangladesh/epidemiologia , Estudos Soroepidemiológicos , Estudos Transversais , Anticorpos Anti-Hepatite
3.
Clin Microbiol Rev ; 35(3): e0021121, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-35726607

RESUMO

Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million cases and 143,000 deaths each year due to cholera. The disease is transmitted fecally-orally via contaminated food or water. Severe dehydrating cholera can progress to hypovolemic shock due to the rapid loss of fluids and electrolytes, which requires a rapid infusion of intravenous (i.v.) fluids. The case fatality rate exceeds 50% without proper clinical management but can be less than 1% with prompt rehydration and antibiotics. Oral cholera vaccines (OCVs) serve as a major component of an integrated control package during outbreaks or within zones of endemicity. Water, sanitation, and hygiene (WaSH); health education; and prophylactic antibiotic treatment are additional components of the prevention and control of cholera. The World Health Organization (WHO) and the Global Task Force for Cholera Control (GTFCC) have set an ambitious goal of eliminating cholera by 2030 in high-risk areas.


Assuntos
Vacinas contra Cólera , Cólera , Antibacterianos , Cólera/diagnóstico , Cólera/epidemiologia , Cólera/prevenção & controle , Surtos de Doenças/prevenção & controle , Humanos , Água
4.
Clin Infect Dis ; 76(2): 263-270, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36136760

RESUMO

BACKGROUND: Cholera remains a public health threat for low- and middle-income countries, particularly in Asia and Africa. Shanchol™, an inactivated oral cholera vaccine (OCV) is currently in use globally. OCV and oral poliovirus vaccines (OPV) could be administered concomitantly, but the immunogenicity and safety of coadministration among children aged 1-3 years is unknown. METHODS: We undertook an open-label, randomized, controlled, inequality trial in Dhaka city, Bangladesh. Healthy children aged 1-3 years were randomly assigned to 1 of 3 groups: bivalent OPV (bOPV)-alone, OCV-alone, or combined bOPV + OCV and received vaccines on the day of enrollment and 28 days later. Blood samples were collected on the day of enrollment, day 28, and day 56. Serum poliovirus neutralizing antibodies and vibriocidal antibodies against Vibrio cholerae O1 were assessed using microneutralization assays. RESULTS: A total of 579 children aged 1‒3 years were recruited, 193 children per group. More than 90% of the children completed visits at day 56. Few adverse events following immunization were recorded and were equivalent among study arms. On day 28, 60% (90% confidence interval: 53%-67%) and 54% (46%-61%) of participants with co-administration of bOPV + OCV responded to polioviruses type 1 and 3, respectively, compared to 55% (47%-62%) and 46% (38%-53%) in the bOPV-only group. Additionally, >50% of participants showed a ≥4-fold increase in vibriocidal antibody titer responses on day 28, comparable to the responses observed in OCV-only arm. CONCLUSIONS: Co-administration of bOPV and OCV is safe and effective in children aged 1-3 years and can be cost-beneficial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03581734).


Assuntos
Vacinas contra Cólera , Cólera , Poliomielite , Poliovirus , Humanos , Criança , Lactente , Pré-Escolar , Bangladesh , Cólera/prevenção & controle , Vacina Antipólio Oral , Vacinas de Produtos Inativados , Administração Oral , Poliomielite/prevenção & controle
5.
PLoS Med ; 20(9): e1004286, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37708235

RESUMO

BACKGROUND: Cholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity. METHODS AND FINDINGS: We conducted a systematic review of studies that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR, and/or a rapid diagnostic test. We searched PubMed, Embase, Scopus, and Google Scholar for studies that sampled at least one suspected case between January 1, 2000 and April 19, 2023, to reflect contemporary patterns in V. cholerae positivity. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated V. cholerae positivity using a random-effects meta-analysis, adjusting for test performance. We included 119 studies from 30 countries. V. cholerae positivity was lower in studies with representative sampling and in studies that set minimum ages in suspected case definitions. After adjusting for test performance, on average, 52% (95% credible interval (CrI): 24%, 80%) of suspected cases represented true V. cholerae infections. After adjusting for test performance and study methodology, the odds of a suspected case having a true infection were 5.71 (odds ratio 95% CrI: 1.53, 15.43) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings. Variation across studies was high, and a limitation of our approach was that we were unable to explain all the heterogeneity with study-level attributes, including diagnostic test used, setting, and case definitions. CONCLUSIONS: In this study, we found that burden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera by 2-fold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased cholera burden estimates. Given the substantial variability in positivity between settings, extrapolations from suspected to confirmed cases, which is necessary to estimate cholera incidence rates without exhaustive testing, should be based on local data.


Assuntos
Cólera , Vibrio cholerae , Humanos , Cólera/diagnóstico , Cólera/epidemiologia , Vibrio cholerae/genética , Surtos de Doenças , Diarreia/epidemiologia , Reação em Cadeia da Polimerase
6.
Epidemiol Infect ; 151: e204, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38031480

RESUMO

Current evidence suggests that recent acute respiratory infections and seasonal influenza may precipitate acute myocardial infarction (AMI). This study examined the potential link between recent clinical respiratory illness (CRI) and influenza, and AMI in Bangladesh. Conducted during the 2018 influenza season at a Dhaka tertiary-level cardiovascular (CV) hospital, it included 150 AMI cases and two control groups: 44 hospitalized cardiac patients without AMI and 90 healthy individuals. Participants were matched by gender and age groups. The study focused on self-reported CRI and laboratory-confirmed influenza ascertained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) within the preceding week, analyzed using multivariable logistic regression. Results showed that cases reported CRI, significantly more frequently than healthy controls (27.3% vs. 13.3%, adjusted odds ratio (aOR): 2.21; 95% confidence interval (CI): 1.05-4.06), although this was not significantly different from all controls (27.3% vs. 22.4%; aOR: 1.19; 95% CI: 0.65-2.18). Influenza rates were insignificantly higher among cases than controls. The study suggests that recent respiratory illnesses may precede AMI onset among Bangladeshi patients. Infection prevention and control practices, as well as the uptake of the influenza vaccine, may be advocated for patients at high risk of acute CV events.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infarto do Miocárdio , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Influenza Humana/tratamento farmacológico , Vacinas contra Influenza/uso terapêutico , Estudos de Casos e Controles , Bangladesh/epidemiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico
8.
Biotechnol Appl Biochem ; 70(3): 1057-1071, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36417773

RESUMO

Cellulases are used in textile, pulp and paper, brewery and wine, sugars, and ethanol industries. Four fungal isolates obtained from organic municipal solid wastes (OMSW) were selected based on their cellulolytic activity on carboxymethyl cellulose (CMC) agar medium. Based on the internal transcribed spacer (ITS) sequence of the ribosomal DNA, the four cellulolytic isolates were identified as Aspergillus fumigatus AKAL1, Aspergillus oryzae AKAL4, Aspergillus flavus AKAL8, and Aspergillus flavus AKAL9. After 9 days of fermentation at 30°C and pH 6.5 under 110 rpm agitation, these isolates produced the maximum amount of cellulase. The cellulase showed optimum activity at temperature 35-40°C and pH 6.0-7.0 and was stable for 1 h at 25-45°C and pH 5.0-7.0. The Mg2+ and Zn2+ significantly increased but Hg2+ , K+ , and Ca2+ severely repressed the cellulase activity. Degradation of filter papers and bio-stoning of denim was successfully done with the crude cellulase. An endo-ß-1,4-glucanase was isolated and characterized from Aspergillus isolates. Genome-wide analysis revealed that the genomes of A. oryzae, A. fumigatus, and A. flavus, the pertinent species of the fungal isolates, had 23, 25, and 22 cellulase genes, respectively. Phylogenetic analysis revealed that the cellulases in these fungal species were divided into three major groups, and the isolated endo-ß-1,4-glucanase clustered to Group II. Ten different motifs are present in cellulases of the three species. Results herein provide a valuable resource for understanding cellulase genes in Aspergillus species and potential application of cellulase in textile and fermentable sugars production industries.


Assuntos
Aspergillus oryzae , Celulase , Celulases , Celulase/genética , Celulase/metabolismo , Filogenia , Celulases/genética , Açúcares , Concentração de Íons de Hidrogênio
9.
J Clin Lab Anal ; 37(13-14): e24948, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37496432

RESUMO

BACKGROUND: Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients. METHODS: The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test. RESULTS: The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test. CONCLUSION: TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.


Assuntos
Bactérias , Febre Tifoide , Humanos , Estudos Transversais , Bangladesh/epidemiologia , Febre/diagnóstico , Febre Tifoide/diagnóstico
10.
Proc Natl Acad Sci U S A ; 117(46): 29055-29062, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33139570

RESUMO

The enterotoxigenic Escherichia coli (ETEC) are among the most common causes of diarrheal illness and death due to diarrhea among young children in low-/middle-income countries (LMICs). ETEC have also been associated with important sequelae including malnutrition and stunting, placing children at further risk of death from diarrhea and other infections. Our understanding of the molecular pathogenesis of acute diarrheal disease as well as the sequelae linked to ETEC are still evolving. It has long been known that ETEC heat-labile toxin (LT) activates production of cAMP in the cell, signaling the modulation of cellular ion channels that results in a net efflux of salt and water into the intestinal lumen, culminating in watery diarrhea. However, as LT also promotes ETEC adhesion to intestinal epithelial cells, we postulated that increases in cAMP, a critical cellular "second messenger," may be linked to changes in cellular architecture that favor pathogen-host interactions. Indeed, here we show that ETEC use LT to up-regulate carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs) on the surface of small intestinal epithelia, where they serve as critical bacterial receptors. Moreover, we show that bacteria are specifically recruited to areas of CEACAM expression, in particular CEACAM6, and that deletion of this CEACAM abrogates both bacterial adhesion and toxin delivery. Collectively, these results provide a paradigm for the molecular pathogenesis of ETEC in which the bacteria use toxin to drive up-regulation of cellular targets that enhances subsequent pathogen-host interactions.


Assuntos
Antígenos CD/metabolismo , Moléculas de Adesão Celular/metabolismo , Escherichia coli Enterotoxigênica/metabolismo , Infecções por Escherichia coli/metabolismo , Adesinas Bacterianas/metabolismo , Antígenos CD/genética , Toxinas Bacterianas/metabolismo , Células CACO-2 , Moléculas de Adesão Celular/genética , Diarreia/microbiologia , Células Epiteliais/metabolismo , Infecções por Escherichia coli/microbiologia , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Mucosa Intestinal/metabolismo , Transcriptoma
11.
Medicina (Kaunas) ; 59(7)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37512091

RESUMO

Background and Objectives: The morbidity and mortality associated with COVID-19 have burdened worldwide healthcare systems beyond their capacities, forcing them to promptly investigate the virus characteristics and its associated outcomes. This clinical analysis aimed to explore the key factors related to the fatal outcome of severe COVID-19 cases. Materials and Methods: Thirty-five adult severe COVID-19 patients were enrolled from two COVID-19 hospitals in Dhaka, Bangladesh. Clinical manifestation, comorbid conditions, medications, SARS-CoV-2 RT-PCR related cycle threshold (CT) value, hematology, biochemical parameters with SARS-CoV-2 specific IgG and IgM responses at enrollment were compared between the survivors and deceased participants. Results: Total 27 patients survived and 8 patients died within 3 months of disease onset. Deceased patients suffered longer from shortness of breath than the survived (p = 0.049). Among the severe cases, 62% of the deceased patients had multiple comorbid condition compared to 48% of those who survived. Interestingly, the anti-viral was initiated earlier among the deceased patients [median day of 1 (IQR: 0, 1.5) versus 6.5 (IQR: 6.25, 6.75)]. Most of the survivors (55%) received a combination of anticoagulant (p = 0.034). Liver enzymes, creatinine kinase, and procalcitonin were higher among the deceased patients during enrollment. The median CT value among the deceased was significantly lower than the survivors (p = 0.025). A significant difference for initial IgG (p = 0.013) and IgM (p = 0.030) responses was found between the survivor and the deceased groups. Conclusions: The factors including older age, male gender, early onset of respiratory distress, multiple comorbidities, low CT value, and poor antibody response may contribute to the fatal outcome in severe COVID-19 patients. Early initiation of anti-viral and a combination of anticoagulant treatment may prevent or lower the fatality among severe COVID-19 cases.


Assuntos
COVID-19 , Adulto , Humanos , Masculino , SARS-CoV-2 , Estudos Prospectivos , Bangladesh/epidemiologia , Antivirais , Anticoagulantes , Imunoglobulina G , Imunoglobulina M
12.
Infect Immun ; 90(8): e0016122, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35862704

RESUMO

Cholera is an acute watery, diarrheal disease that causes high rates of morbidity and mortality without treatment. Early detection of the etiologic agent of toxigenic Vibrio cholerae is important to mobilize treatment and mitigate outbreaks. Monoclonal antibody (mAb) based rapid diagnostic tests (RDTs) enable early detection in settings without laboratory capacity. However, the odds of an RDT testing positive are reduced by nearly 90% when the common virulent bacteriophage ICP1 is present. We hypothesize that adding a mAb for the common, and specific, virulent bacteriophage ICP1 as a proxy for V. cholerae to an RDT will increase diagnostic sensitivity when virulent ICP1 phage is present. In this study, we used an in-silico approach to identify immunogenic ICP1 protein targets that were conserved across disparate time periods and locations. Specificity of targets to cholera patients with known ICP1 was determined, and specific targets were used to produce mAbs in a murine model. Candidate mAbs to the head protein demonstrated specificity to ICP1 by Enzyme linked immunosorbent assay (ELISA) and an ICP1 phage neutralization assay. The limit of detection of the final mAb candidate for ICP1 phage particles spiked into cholera stool matrix was 8 × 105 PFU by Western blotting analysis. This mAb will be incorporated into a RDT prototype for evaluation in a future diagnostic study to test the guiding hypothesis behind this study.


Assuntos
Bacteriófagos , Cólera , Vibrio cholerae , Doença Aguda , Animais , Anticorpos Monoclonais/metabolismo , Cólera/diagnóstico , Cólera/epidemiologia , Diarreia , Fezes , Humanos , Camundongos
13.
Clin Infect Dis ; 75(10): 1681-1687, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-35412603

RESUMO

BACKGROUND: Typhoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid. METHODS: A total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture-confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models. RESULTS: The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval [CI], 43%-65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%-48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%-80%; P < .001). CONCLUSIONS: Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk. CLINICAL TRIALS REGISTRATION: ISRCTN11643110.


Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Humanos , Criança , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Vacinas Conjugadas , Saneamento , Água , Bangladesh/epidemiologia , Higiene
14.
Emerg Infect Dis ; 28(2): 429-431, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35076007

RESUMO

A March-June 2021 representative serosurvey among Sitakunda subdistrict (Chattogram, Bangladesh) residents found an adjusted prevalence of severe acute respiratory syndrome coronavirus 2 antibodies of 64.1% (95% credible interval 60.0%-68.1%). Before the Delta variant surge, most residents had been infected, although cumulative confirmed coronavirus disease incidence was low.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Bangladesh/epidemiologia , Humanos , Estudos Soroepidemiológicos
15.
Lancet ; 398(10301): 675-684, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34384540

RESUMO

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.


Assuntos
Polissacarídeos Bacterianos/administração & dosagem , Toxoide Tetânico/uso terapêutico , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/administração & dosagem , Vacinação , Vacinas Conjugadas/administração & dosagem , Adolescente , Bangladesh/epidemiologia , Criança , Pré-Escolar , Países em Desenvolvimento , Encefalite Japonesa/epidemiologia , Feminino , Humanos , Lactente , Vacinas contra Encefalite Japonesa/administração & dosagem , Masculino , Salmonella typhi/imunologia , Toxoide Tetânico/imunologia , Febre Tifoide/epidemiologia , Febre Tifoide/imunologia
16.
J Infect Dis ; 224(12 Suppl 2): S749-S753, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34549784

RESUMO

Bangladesh is entering from low-income to lower-middle-income status in 2020, and this will be completed in the next 5 years. With gross national income growing, vaccines will need to be procured through private market for the Expanded Program on Immunization. A cost-benefit analysis is needed to evaluate vaccine demand in different socioeconomic groups in the country, to inform this procurement. Moreover, disease burden studies and awareness of importance of specific vaccines are needed as we move forward. A life-course approach to vaccination may enable whole society to realize the full potential of vaccination and address most significant threats to its success over time.


Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Desenvolvimento Sustentável , Vacinação , Bangladesh , Doenças Transmissíveis Emergentes/prevenção & controle , Humanos , Programas de Imunização
17.
J Infect Dis ; 224(12 Suppl 2): S821-S828, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34550392

RESUMO

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of mortality and morbidity in children in low-income countries. We have tested an oral ETEC vaccine, ETVAX, consisting of inactivated E coli overexpressing the most prevalent colonization factors and a toxoid, LCTBA, administered together with a mucosal adjuvant, double-mutant heat-labile toxin (dmLT), for capacity to induce mucosal immune responses and immunological memory against the primary vaccine antigens, ie, colonization factors, heat-labile toxin B-subunit and O antigen. The studies show that ETVAX could induce strong intestine-derived and/or fecal immune responses in a majority of vaccinated Swedish adults and in different age groups, including infants, in Bangladesh.


Assuntos
Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli , Vacinas contra Escherichia coli/administração & dosagem , Imunidade nas Mucosas , Adolescente , Adulto , Anticorpos Antibacterianos , Criança , Enterotoxinas , Humanos , Lactente , Pessoa de Meia-Idade
18.
J Infect Dis ; 224(12 Suppl 2): S801-S804, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34528671

RESUMO

Safe and effective rotavirus vaccines (RVs) are needed to reduce the enormous public health burden of rotavirus illness in developing countries. Vaccination is critical for effective control of rotavirus infection since it cannot be prevented with improvements in water and sanitation. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) has completed several groundbreaking RV trials (Phase I-Phase IV). The safety, immunogenicity, efficacy, and effectiveness of different RVs were evaluated among both urban and rural populations. In this study, we present the results, policy implications, and lessons learned for successful implementation of these trials as well as future directions for rotavirus vaccination in Bangladesh.


Assuntos
Diarreia/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus , Rotavirus , Bangladesh , Humanos , Lactente , Rotavirus/imunologia , Eficácia de Vacinas
19.
J Infect Dis ; 224(12 Suppl 2): S910-S914, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668553

RESUMO

Informal slums are growing exponentially in the developing world and these will serve as the breeding ground for a future global pandemic. Virtually every sustainable development goal is unmet in slums around the globe thus we must act now to divert a global humanitarian crisis.


Assuntos
Doenças Transmissíveis , Pandemias , Áreas de Pobreza , Previsões , Humanos , População Urbana
20.
J Infect Dis ; 224(12 Suppl 2): S805-S812, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34549775

RESUMO

BACKGROUND: Hepatitis E virus (HEV) genotypes 1 and 2 are a major cause of avoidable morbidity and mortality in South Asia. Despite the high risk of death among infected pregnant women, scarce incidence data has been a contributing factor to global policy recommendations against the introduction of licensed hepatitis E vaccines, one of the only effective prevention tools. METHODS: We tested serum from a nationally representative serosurvey in Bangladesh for anti-HEV immunoglobulin G and estimated seroprevalence. We used Bayesian geostatistical models to generate high-resolution maps of seropositivity and examined variability in seropositivity by individual-level, household-level, and community-level risk factors using spatial logistic regression. RESULTS: We tested serum samples from 2924 individuals from 70 communities representing all divisions of Bangladesh and estimated a national seroprevalence of 20% (95% confidence interval [CI], 17%-24%). Seropositivity increased with age and male sex (odds ratio, 2.2 male vs female; 95% CI, 1.8-2.8). Community-level seroprevalence ranged widely (0-78%) with higher seroprevalence in urban areas, including Dhaka, with a 3.0-fold (95% credible interval, 2.3-3.7) higher seroprevalence than the rest of the country. CONCLUSIONS: Hepatitis E infections are common throughout Bangladesh. Strengthening surveillance for hepatitis E, especially in urban areas, can provide additional evidence to appropriately target interventions.


Assuntos
Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/epidemiologia , Imunoglobulina G/sangue , Adolescente , Bangladesh/epidemiologia , Teorema de Bayes , Criança , Pré-Escolar , Feminino , Hepatite E/sangue , Hepatite E/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Vigilância da População , Gravidez , Estudos Soroepidemiológicos
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