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BACKGROUND: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients. METHODS: SPECTRA participants at 8 study sites in the Philippines who developed real-time reverse transcriptase-polymerase chain reaction (rRT-PCR)-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for 3 weeks using rRT-PCR and anti-SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections. RESULTS: One hundred fifty-four eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: .15-3.90%) if the index case was an SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20-10.8%) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: -28% to 97%). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28-97%). The impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7-96%) or asymptomatic (n = 24; RRR = 100%; 90% CI: -76% to 100%) was measurable but the low numbers undermine the clinical significance. CONCLUSIONS: In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether or not index cases were symptomatic.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Estudos Prospectivos , Filipinas/epidemiologia , Vacinação , Anticorpos AntiviraisRESUMO
BACKGROUND: Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. OBJECTIVE: The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. PATIENTS AND METHOD: In this case-control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. RESULTS: Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). CONCLUSION: This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.
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Pré-Eclâmpsia , Deficiência de Vitamina D , Feminino , Humanos , Gravidez , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Pré-Eclâmpsia/genética , Estudos de Casos e Controles , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética , Genótipo , Predisposição Genética para DoençaRESUMO
BACKGROUND: The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. METHODS: We conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9-13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. RESULTS: A single fIPV dose at age 9-13 months yielded 75% (95% confidence interval [CI], 6%-82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%-97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion. CONCLUSIONS: Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic. CLINICAL TRIAL REGISTRATION: NCT03890497.
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Poliomielite , Poliovirus , Idoso , Anticorpos Antivirais , Bangladesh , Humanos , Esquemas de Imunização , Lactente , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Vacinação/métodosRESUMO
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.
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Febre Tifoide , Vacinas Tíficas-Paratíficas , Humanos , Criança , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Vacinas Conjugadas , Saneamento , Água , Bangladesh/epidemiologia , HigieneRESUMO
Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV2-related Sabin 2 transmission in rural Matlab, Bangladesh based on stool samples collected from infants and their household contacts during an mOPV2 clinical trial. Sabin 2 transmission following the mOPV2 clinical trial was replicated by specifying multiple, heterogeneous contact rates based on household and community membership. Once calibrated, the model generated Matlab-specific insights regarding poliovirus transmission following an accidental point importation or mass vaccination event. We also show that assuming homogeneous contact rates (mass action), as is common of poliovirus forecast models, does not accurately represent the clinical trial and risks overestimating forecasted poliovirus outbreak probability. Our study identifies household and community structure as an important source of transmission heterogeneity when assessing OPV-related transmission risk and provides a calibratable framework for expanding these analyses to other populations. Trial Registration: ClinicalTrials.gov This trial is registered with clinicaltrials.gov, NCT02477046.
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Vacinação em Massa/estatística & dados numéricos , Modelos Estatísticos , Poliomielite , Vacina Antipólio Oral , Poliovirus , Bangladesh , Humanos , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Poliomielite/virologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
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Diarreia/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus , Rotavirus , Bangladesh , Humanos , Lactente , Rotavirus/imunologia , Eficácia de VacinasRESUMO
Studying the evolution of catalytically promiscuous enzymes like those from the N-succinylamino acid racemase/ o-succinylbenzoate synthase (NSAR/OSBS) subfamily can reveal mechanisms by which new functions evolve. Some enzymes in this subfamily have only OSBS activity, while others catalyze OSBS and NSAR reactions. We characterized several NSAR/OSBS subfamily enzymes as a step toward determining the structural basis for evolving NSAR activity. Three enzymes were promiscuous, like most other characterized NSAR/OSBS subfamily enzymes. However, Alicyclobacillus acidocaldarius OSBS (AaOSBS) efficiently catalyzes OSBS activity but lacks detectable NSAR activity. Competitive inhibition and molecular modeling show that AaOSBS binds N-succinylphenylglycine with moderate affinity in a site that overlaps its normal substrate. On the basis of possible steric conflicts identified by molecular modeling and sequence conservation within the NSAR/OSBS subfamily, we identified one mutation, Y299I, that increased NSAR activity from undetectable to 1.2 × 102 M-1 s-1 without affecting OSBS activity. This mutation does not appear to affect binding affinity but instead affects kcat, by reorienting the substrate or modifying conformational changes to allow both catalytic lysines to access the proton that is moved during the reaction. This is the first site known to affect reaction specificity in the NSAR/OSBS subfamily. However, this gain of activity was obliterated by a second mutation, M18F. Epistatic interference by M18F was unexpected because a phenylalanine at this position is important in another NSAR/OSBS enzyme. Together, modest NSAR activity of Y299I AaOSBS and epistasis between sites 18 and 299 indicate that additional sites influenced the evolution of NSAR reaction specificity in the NSAR/OSBS subfamily.
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Alicyclobacillus/enzimologia , Isomerases de Aminoácido/metabolismo , Carbono-Carbono Liases/metabolismo , Alicyclobacillus/química , Alicyclobacillus/genética , Alicyclobacillus/metabolismo , Isomerases de Aminoácido/química , Isomerases de Aminoácido/genética , Carbono-Carbono Liases/química , Carbono-Carbono Liases/genética , Domínio Catalítico , Cristalografia por Raios X , Evolução Molecular , Modelos Moleculares , Filogenia , Conformação Proteica , Especificidade por SubstratoRESUMO
BACKGROUND: Telosma mosaic virus (TelMV, Potyvirus, Potyviridae) is an emerging viral pathogen that threatens passion fruit plantations worldwide. However, an efficient strategy for controlling such a virus is not yet available. Cross protection is a phenomenon in which pre-infection of a plant with one mild strain prevents or delays subsequent infection by the same or closely related virus. HC-Pro is the potyviral encoded multifunctional protein involved in several steps of viral infection, including multiplication, movement, transmission and RNA silencing suppression. In this study, we tested whether it is possible to generate attenuated viral strains capable of conferring protection against severe TelMV infection by manipulating the HC-Pro gene. RESULTS: By introducing point mutation into the conserved motif FRNK of HC-Pro that is essential for RNA silencing suppression, we have successfully obtained three attenuated mutants of TelMV (R181K, R181D, and R181E, respectively). These attenuated TelMV mutants could systemically infect passion fruit plants without noticeable symptoms. Pre-inoculation of one of these attenuated mutants confers efficient protection against subsequent infection by severe TelMV strain. Moreover, we demonstrated that the HC-Pros harbored by the attenuated mutants exhibit reduced RNA silencing suppression activity in Nicotiana benthamiana leaves. CONCLUSION: The attenuated TelMV mutants developed in this study that are suitable for cross protection offer a practical, powerful tool to fight against TelMV for sustainable passion fruit production. © 2024 Society of Chemical Industry.
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BACKGROUND: Vaccination constitutes an attractive control measure for hepatitis E virus (HEV), a major cause of maternal and perinatal mortality globally. Analysis of pregnant participants in an effectiveness trial of the HEV vaccine HEV239 showed possible HEV239-associated fetal losses. We aimed to conduct a detailed analysis of this safety signal. METHODS: In a double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomly allocated (1:1) to two vaccine groups, in which non-pregnant women aged 16-39 years received either HEV239 (HEV239 group) or Hepa-B (a hepatitis B vaccine; control group). We implemented weekly surveillance for pregnancy detection, and follow-up of pregnancies once every 2 weeks, using physician-confirmed diagnoses to evaluate fetal loss outcomes (miscarriage [spontaneous abortion], stillbirth, and elective termination). Data from a parallel system of reproductive health surveillance in Matlab were used to clarify study diagnoses when necessary. Miscarriage was assessed only among participants whose first positive pregnancy test and vaccination date (for whichever dose was closest to the date of last menstrual period [LMP]) were before 20 weeks' gestation. We defined the following analysis periods of interest: from 90 days before the LMP until the pregnancy outcome (the proximal period); from the LMP date until the pregnancy outcome (the pregnancy period); from 90 days before the LMP until the LMP date (90 days pre-LMP period); and from enrolment until 90 days before the LMP (the distal period). Both Poisson and Cox regression models were used to assess the associations between receipt of HEV239 and fetal loss outcomes. The trial was registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Among the 19â460 non-pregnant participants enrolled in the trial, 5011 were identified as having pregnancies within 2 years following vaccination and met the criteria for analysis (2407 in the HEV239 group and 2604 in the control group). Among participants vaccinated in the proximal period and evaluated for miscarriage, miscarriage occurred in 54 (8·9%) of 607 in the HEV239 group and 32 (4·5%) of 719 in the control group (adjusted relative risk [aRR] 2·0 [95% CI 1·3-3·1], p=0·0009). Similarly, the risk of miscarriages was increased in the HEV239 group versus the control group among participants inadvertently vaccinated during pregnancy (22 [10·5%] miscarriages among 209 participants in the HEV239 group vs 14 [5·3%] of 266 in the control group; aRR 2·1 [95% CI 1·1-4·1], p=0·036) and among those vaccinated within 90 days pre-LMP (32 [8·0%] of 398 vs 18 [4·0%] of 453; 1·9 [1·1-3·2], p=0·013). No increased risk of miscarriage was observed in those who received HEV239 in the distal period (93 [5·6%] of 1647 vs 80 [4·5%] of 1773; 1·3 [0·8-1·9], p=0·295). Stillbirth and elective termination showed no increased risk among women administered HEV239 versus those administered Hepa-B in any of the analysis periods. INTERPRETATION: HEV239 given shortly before or during pregnancy was associated with an elevated risk of miscarriage. This association poses a possible safety concern for programmatic use of HEV239 in women of childbearing age. FUNDING: Research Council of Norway and Innovax.
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Aborto Espontâneo , Hepatite E , Vacinas contra Hepatite Viral , Humanos , Feminino , Bangladesh/epidemiologia , Gravidez , Adulto , Método Duplo-Cego , Adulto Jovem , Vacinas contra Hepatite Viral/administração & dosagem , Adolescente , Hepatite E/epidemiologia , Hepatite E/prevenção & controle , Aborto Espontâneo/epidemiologia , População Rural/estatística & dados numéricos , Vírus da Hepatite E/imunologia , Morte FetalRESUMO
In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May-August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = -3% [90% confidence interval: -6 - 0.4%]; type 3 difference: -3% [-6 to -0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule.
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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.
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BACKGROUND: Hepatitis E virus (HEV) leads to high mortality in pregnant women in low-income countries. We aimed to evaluate the safety of a HEV vaccine and its effectiveness in preventing hepatitis E during pregnancy. METHODS: In this phase 4, double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomised 1:1 to receive HEV239 (a recombinant HEV vaccine) or a control vaccine (Hepa-B, a hepatitis B vaccine), using block randomisation with random number tables and blocks of size eight, stratified by cluster population size. Eligible non-pregnant women (aged 16-39 years) were vaccinated intramuscularly on day 0, at 1 month, and at 6 months, and followed up for 2 years after the last immunisation. The primary endpoint was hepatitis E in the pregnant, per-protocol population (those who received all three doses within 2 days of the scheduled dates), while safety was a secondary endpoint, assessed in the intention-to-treat (ITT) population (participants who received at least one dose). Solicited adverse events were recorded for the first 7 days after each dose, and unsolicited events until 2 years after a participant's final dose. Pregnancy-related safety outcomes were assessed in the pregnant ITT population. This study is registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Between Oct 2, 2017, and Feb 28, 2019, 19â460 participants were enrolled and received either HEV239 (9478 [48·7%] participants, 33 clusters) or Hepa-B (9982 [51·3%] participants, 34 clusters), of whom 17â937 (92·2%) participants received three doses and 17â613 (90·5%) were vaccinated according to protocol (8524 [48·4%] in the HEV239 group and 9089 [51·6%] in the control group). No pregnant participants were confirmed to have hepatitis E in either treatment group. HEV239 showed a mild safety profile, similar to Hepa-B, with no difference in the proportion of solicited adverse events between groups and no severe solicited events. Pain was the most common local symptom (1215 [12·8%] HEV239 recipients and 1218 [12·2%] Hepa-B recipients) and fever the most common systemic symptom (141 [1·5%] HEV239 recipients and 145 [1·5%] Hepa-B recipients). None of the serious adverse events or deaths were vaccine related. Among pregnant participants, the HEV239 group had a higher risk of miscarriage (136 [5·7%] of 2407 pregnant participants) compared with the control group (102 [3·9%] of 2604; adjusted odds ratio 1·54 [95% CI 1·15-2·08]). INTERPRETATION: The effectiveness of HEV239 in pregnant women remains uncertain. HEV239 was safe and well tolerated in non-pregnant women, but findings regarding miscarriage warrant further investigation. FUNDING: Research Council of Norway; Innovax.
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Hepatite E , População Rural , Vacinas contra Hepatite Viral , Humanos , Feminino , Bangladesh/epidemiologia , Adulto , Método Duplo-Cego , Hepatite E/prevenção & controle , Hepatite E/epidemiologia , Gravidez , Adulto Jovem , Adolescente , Vacinas contra Hepatite Viral/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vírus da Hepatite E/imunologia , Complicações Infecciosas na Gravidez/prevenção & controleRESUMO
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.
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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
SARS-CoV-2 serological testing is useful to determine seroprevalence, epidemiological trends, and the extent of transmission. The collection and transport of serum samples can be logistically challenging, especially in remote underserved areas. Dried blood spots (DBSs) would allow easier sample collection and logistical handling compared with standard serum collection, particularly for extensive and repeated SARS-CoV-2 serosurveys. We evaluated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IgG ELISA (Wantai, Beijing, China) using DBSs against sera for the quantitative detection of SARS-CoV-2 IgG antibody. The IgG ELISA was used to test paired sera and DBSs obtained from individuals with recent virologically confirmed COVID-19 illness and banked paired sera and DBSs collected before the COVID-19 pandemic. We found that 100/100 (100%) seropositive samples were positive using DBSs, and 193/194 (99%) seronegative samples were negative using DBSs. Compared with sera, the DBS method had a 100% sensitivity, 99% specificity, 99% PPV, and 100% NPV. Use of DBSs for SARS-CoV-2 household or population serosurveys may be considered in situations with limitations in sample collection, shipment, and storage.
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Anticorpos Antivirais , Teste Sorológico para COVID-19 , COVID-19 , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , SARS-CoV-2 , Sensibilidade e Especificidade , Humanos , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/sangue , COVID-19/imunologia , Teste Sorológico para COVID-19/métodos , Teste em Amostras de Sangue Seco/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Estudos Soroepidemiológicos , Manejo de EspécimesRESUMO
Context: The COVID-19 epidemic has had a substantial influence on the mental health of chronic disease patients. However, there is a scarcity of research on them in Bangladesh. Aims: This study aims to explore the prevalence of and identify the risk factors for depression, anxiety, and stress symptoms during the COVID-19 pandemic among people with chronic diseases in Bangladesh. Materials and Methods: This cross-sectional study involving face-to-face and telephone interviews was carried out among Bangladeshi people diagnosed with chronic diseases between September and November 2020. The total sample size was 878, and a convenient sampling technique was used. Logistic regression analysis was performed to investigate potential influencing factors for depression, anxiety, and stress. Results: The mean age of respondents was 50.10 years. Among them, 35.0%, 36.0%, and 29.0% suffered from depression, anxiety, and stress symptoms, respectively. In multivariable logistic regression, depression had a significant positive association with higher age (≥60 years), lower income, rural residency, and loss of close family members due to COVID-19. Anxiety had a significant positive association with higher age (≥40 years), lower education, lower income, rural residency, and loss of close family members due to COVID-19. Stress had a significant positive association with higher age (≥40 years), no income, rural residency, and loss of close family members due to COVID-19. Conclusion: It is urgent to consider the risk of developing mental health distress among chronic disease patients, especially aged people, by health service providers and generate effective programs for emergency situations.
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BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide and it contributes to considerable maternal and neonatal mortality and morbidity in many low-income countries like Bangladesh. A three-dose regimen of a vaccine against HEV (HEV 239) has shown promising results in China. The effects and safety of this vaccine in other populations and with different dosing regimens remains uncertain. OBJECTIVES: Investigate the immune response and safety of a two-dose regimen with the HEV 239 vaccine among healthy adults. Examine the feasibility of conducting a larger HEV 239 vaccine trial in rural Bangladesh. METHODS: One-hundred healthy men and non-pregnant women 16-39 years old were randomized in a 1:1 ratio to receive two doses of either the study (HEV) or control (Hepatitis B virus, HBV) vaccine (at 0, 1 month). Blood samples were collected at day 0, day 60 and 2 years after vaccination. The primary endpoints were the proportion and severity of adverse events up to 2 months after dose one and the longitudinal shift in anti-HEV IgG levels from day 0 to day 60 and 2 years after vaccination. RESULTS: Adverse events to HEV 239 were comparable to the control vaccine, mild in severity and resolved within one to nine days. All participants in the study group seroconverted and achieved high levels of HEV IgG antibodies that remained positive for two years in all but one. A T-cell response was detected one month after HEV 239 vaccination. CONCLUSION: Our results show that two doses of the HEV 239 vaccine produces broad and likely functional immune responses against HEV that remain for at least two years. The safety profile was acceptable and a phase four study of HEV 239 in rural Bangladesh is feasible. CLINICALTRIALS: gov Identifier: NCT02759991.
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Vírus da Hepatite E , Vacinas , Masculino , Feminino , Recém-Nascido , Humanos , Adulto , Adolescente , Adulto Jovem , Bangladesh , Projetos Piloto , Anticorpos Anti-Hepatite , Imunoglobulina G , Método Duplo-Cego , Imunogenicidade da Vacina , Anticorpos AntiviraisRESUMO
OBJECTIVES: To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. METHODS: This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. RESULTS: We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). CONCLUSION: Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.
RESUMO
BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention.
Assuntos
Imunidade nas Mucosas , Poliomielite , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Humanos , Lactente , Bangladesh , Poliovirus , Vacina Antipólio de Vírus Inativado/efeitos adversos , Estados Unidos , Poliomielite/prevenção & controleRESUMO
The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic.
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Vacinas contra Cólera , Cólera , Humanos , Cólera/prevenção & controle , Cólera/epidemiologia , Água , Bangladesh , Saneamento , Vacinação , Higiene , Administração OralRESUMO
BACKGROUND: Typhoid fever, or enteric fever, is a highly fatal infectious disease that affects over 9 million people worldwide each year, resulting in more than 110,000 deaths. Reduction in the burden of typhoid in low-income countries is crucial for public health and requires the implementation of feasible water, sanitation, and hygiene (WASH) interventions, especially in densely populated urban slums. OBJECTIVE: In this study, conducted in Mirpur, Bangladesh, we aimed to assess the association between household WASH status and typhoid risk in a training subpopulation of a large prospective cohort (n=98,087), and to evaluate the performance of a machine learning algorithm in creating a composite WASH variable. Further, we investigated the protection associated with living in households with improved WASH facilities and in clusters with increasing prevalence of such facilities during a 2-year follow-up period. METHODS: We used a machine learning algorithm to create a dichotomous composite variable ("Better" and "Not Better") based on 3 WASH variables: private toilet facility, safe drinking water source, and presence of water filter. The algorithm was trained using data from the training subpopulation and then validated in a distinct subpopulation (n=65,286) to assess its sensitivity and specificity. Cox regression models were used to evaluate the protective effect of living in "Better" WASH households and in clusters with increasing levels of "Better" WASH prevalence. RESULTS: We found that residence in households with improved WASH facilities was associated with a 38% reduction in typhoid risk (adjusted hazard ratio=0.62, 95% CI 0.49-0.78; P<.001). This reduction was particularly pronounced in individuals younger than 10 years at the first census participation, with an adjusted hazard ratio of 0.49 (95% CI 0.36-0.66; P<.001). Furthermore, we observed an inverse relationship between the prevalence of "Better" WASH facilities in clusters and the incidence of typhoid, although this association was not statistically significant in the multivariable model. Specifically, the adjusted hazard of typhoid decreased by 0.996 (95% CI 0.986-1.006) for each percent increase in the prevalence of "Better" WASH in the cluster (P=.39). CONCLUSIONS: Our findings demonstrate that existing variations in household WASH are associated with differences in the risk of typhoid in densely populated urban slums. This suggests that attainable improvements in WASH facilities can contribute to enhanced typhoid control, especially in settings where major infrastructural improvements are challenging. These findings underscore the importance of implementing and promoting comprehensive WASH interventions in low-income countries as a means to reduce the burden of typhoid and improve public health outcomes in vulnerable populations.