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1.
EClinicalMedicine ; 43: 101253, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34977517

RESUMO

The availability and use of vaccines for the coronavirus disease 2019 (COVID-19) in low and middle-income countries (L/MICs) lags far behind more affluent countries, and vaccines currently used in L/MICs are predominantly of lower efficacy. As vaccines continue to be rolled out in L/MICs, successful control of COVID-19 by vaccines requires monitoring both of vaccine protection of vaccinees (effectiveness) and of the entire targeted populations, including vaccine herd protection of non-vaccinees (impact). To be of greatest relevance to L/MICs, there is the need to address the distinctive medical and demographic features of populations, health systems, and demography that may greatly affect vaccine performance in these settings. We identified 58 published studies that included 85 evaluations of the effectiveness of different COVID-19 vaccines globally. Only three were done in L/MICs, and no impact studies were identified in these settings. Post-deployment studies of the protection by COVID-19 vaccines rolled out in L/MICs constitute an important but currently neglected global priority.

2.
Pathogens ; 10(11)2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34832637

RESUMO

Rickettsiae may cause febrile infections in humans in tropical and subtropical regions. From Madagascar, no molecular data on the role of rickettsioses in febrile patients are available. Blood samples from patients presenting with fever in the area of the capital Antananarivo were screened for the presence of rickettsial DNA. EDTA (ethylenediaminetetraacetic acid) blood from 1020 patients presenting with pyrexia > 38.5 °C was analyzed by gltA-specific qPCR. Positive samples were confirmed by ompB-specific qPCR. From confirmed samples, the gltA amplicons were sequenced and subjected to phylogenetic analysis. From five gltA-reactive samples, two were confirmed by ompB-specific qPCR. The gltA sequence in the sample taken from a 38-year-old female showed 100% homology with R. typhi. The other sample taken from a 1.5-year-old infant was 100% homologous to R. felis. Tick-borne rickettsiae were not identified. The overall rate of febrile patients with molecular evidence for a rickettsial infection from the Madagascan study site was 0.2% (2/1020 patients). Flea-borne rickettsiosis is a rare but neglected cause of infection in Madagascar. Accurate diagnosis may prompt adequate antimicrobial treatment.

3.
Emerg Infect Dis ; 27(12): 3163-3165, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34808080

RESUMO

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic.


Assuntos
COVID-19 , Perfuração Intestinal , Febre Tifoide , Humanos , Perfuração Intestinal/epidemiologia , Perfuração Intestinal/etiologia , Madagáscar/epidemiologia , SARS-CoV-2 , Febre Tifoide/epidemiologia
4.
Am J Trop Med Hyg ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749309

RESUMO

Quantitative polymerase chain reaction (qPCR) of dried blood spots (DBS) for pathogen detection is a potentially convenient method for infectious disease diagnosis. This study tested 115 DBS samples paired with whole blood specimens of children and adolescent from Burkina Faso, Sudan, and Madagascar by qPCR for a wide range of pathogens, including protozoans, helminths, fungi, bacteria, and viruses. Plasmodium spp. was consistently detected from DBS but yielded a mean cycle threshold (Ct) 5.72 ± 1.6 higher than that from whole blood samples. A DBS qPCR Ct cutoff of 27 yielded 94.1% sensitivity and 95.1% specificity against the whole blood qPCR cutoff of 21 that has been previously suggested for malaria diagnosis. For other pathogens investigated, DBS testing yielded a sensitivity of only 8.5% but a specificity of 98.6% compared with whole blood qPCR. In sum, direct PCR of DBS had reasonable performance for Plasmodium but requires further investigation for the other pathogens assessed in this study.

5.
J Med Virol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709664

RESUMO

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

6.
Vaccine ; 39(40): 5876-5882, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34454788

RESUMO

BACKGROUND: Vaccine herd protection assessed in a cluster-randomized trial (CRT) may be masked by disease transmission into the cluster from outside. However, herd effects can be unmasked using a 'fried-egg' approach whereby the analysis, restricted to the innermost households of clusters, 'yolk', creates an insulating 'egg-white' periphery. This approach has been demonstrated to unmask vaccine herd protection in reanalyses of cholera and typhoid vaccine CRTs. We applied this approach to an earlier CRT in Bangladesh of rotavirus vaccine (RV) whose overall analysis had failed to detect herd protection. Herein we present the results of this analysis. METHODS: In the study area, infants in 142 villages were randomized to receive two doses of RV with routine EPI vaccines (RV villages) or only EPI vaccines (non-RV villages). We analyzed RV protection against acute rotavirus diarrhoea for the entire cluster (P100) and P75, P50, P25 clusters, representing 75%, 50% and 25% of the innermost households for each cluster, respectively. RESULTS: During 2 years of follow-up, there was evidence of 27% overall (95 %CI: 7, 43) and 42% total protection (95 %CI: 23, 56) in the P100 cluster, but it did not increase when moved in smaller yolks. There was no evidence of indirect vaccine protection in the yolks at any cluster size. CONCLUSION: Our reanalysis of the CRT using the fried- egg approach did not detect RV herd protection. Whether these findings reflect a true inability of the RV to confer herd protection in this setting, or are due to limitations of the approach, requires further study.


Assuntos
Cólera , Vacinas contra Rotavirus , Rotavirus , Bangladesh/epidemiologia , Humanos , Imunidade Coletiva , Lactente
7.
Lancet Infect Dis ; 21(10): 1407-1414, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34146473

RESUMO

BACKGROUND: Killed whole-cell oral cholera vaccines (OCVs) are widely used for prevention of cholera in developing countries. However, few studies have evaluated the protection conferred by internationally recommended OCVs for durations beyond 2 years of follow-up. METHODS: In this study, we followed up the participants of a cluster-randomised controlled trial for 2 years after the end of the original trial. Originally, we had randomised 90 geographical clusters in Dhaka slums in Bangladesh in equal numbers (1:1:1) to a two-dose regimen of OCV alone (targeted to people aged 1 year or older), a two-dose regimen of OCV plus a water-sanitation-hygiene (WASH) intervention, or no intervention. There was no masking of group assignment. The WASH intervention conferred little additional protection to OCV and was discontinued at 2 years of follow-up. Surveillance for severe cholera was continued for 4 years. Because of the short duration and effect of the WASH intervention, we combined the two OCV intervention groups. The primary outcomes were OCV overall protection (protection of all members of the intervention clusters) and total protection (protection of individuals who got vaccinated in the intervention clusters) against severe cholera, which we assessed by multivariable survival models appropriate for cluster-randomised trials. This trial is registered on ClinicalTrials.gov, NCT01339845. FINDINGS: The study was done between April 17, 2011, and Nov 1, 2015. 268 896 participants were present at the time of the first dose, with 188 206 in the intervention group and 80 690 in the control group. OCV coverage of the two groups receiving OCV was 66% (123 659 of 187 214 participants). During 4 years of follow-up, 441 first episodes of severe cholera were detected (243 episodes in the vaccinated groups and as 198 episodes in the unvaccinated group). Overall OCV protection was 36% (95% CI 19 to 49%) and total OCV protection was 46% (95% CI 32 to 58). Cumulative total vaccine protection was notably lower for people vaccinated before the age of 5 years (24%; -30 to 56) than for people vaccinated at age 5 years or older (49%; 35 to 60), although the differences in protection for the two age groups were not significant (p=0·3308). Total vaccine protection dropped notably (p=0·0115) after 3 years in children vaccinated at 1-4 years of age. INTERPRETATION: These findings provide further evidence of long-term effectiveness of killed whole-cell OCV, and therefore further support for the use of killed whole-cell OCVs to control endemic cholera, but indicate that protection is shorter-lived in children vaccinated before the age of 5 years than in people vaccinated at the age of 5 years or older. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the Bengali translation of the abstract see Supplementary Materials section.


Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Vibrio cholerae/imunologia , Administração Oral , Adolescente , Bangladesh/epidemiologia , Criança , Pré-Escolar , Cólera/economia , Cólera/microbiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Áreas de Pobreza , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vibrio cholerae/genética , Adulto Jovem
8.
BMC Infect Dis ; 21(1): 529, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090380

RESUMO

BACKGROUND: Invasive non-typhoidal Salmonella (iNTS) is a growing health-concern in many parts of sub-Saharan Africa. iNTS is associated with fatal diseases such as HIV and malaria. Despite high case fatality rates, the disease has not been given much attention. The limited number of population-based surveillance studies hampers accurate estimation of global disease burden. Given the lack of available evidence on the disease, it is critical to identify high risk areas for future surveillance and to improve our understanding of iNTS endemicity. METHODS: Considering that population-based surveillance data were sparse, a composite index called the iNTS risk factor (iNRF) index was constructed based on risk factors that commonly exist across countries. Four risk factors associated with the prevalence of iNTS were considered: malaria, HIV, malnutrition, and safe water. The iNRF index was first generated based on the four risk factors which were collected within a 50 km radius of existing surveillance sites. Pearson product-moment correlation was used to test statistical associations between the iNRF index and the prevalence of iNTS observed in the surveillance sites. The index was then further estimated at the subnational boundary level across selected countries and used to identify high risk areas for iNTS. RESULTS: While the iNRF index in some countries was generally low (i.e. Rwanda) or high (i.e. Cote d'Ivoire), the risk-level of iNTS was variable not only by country but also within a country. At the provincial-level, the highest risk area was identified in Maniema, the Democratic Republic of Congo, whereas Dakar in Senegal was at the lowest risk. CONCLUSIONS: The iNRF index can be a useful tool to understand the geographically varying risk-level of iNTS. Given that conducting a population-based surveillance study requires extensive human and financial resources, identifying high risk areas for iNTS prior to a study implementation can facilitate an appropriate site-selection process in the future.


Assuntos
Infecções por HIV/epidemiologia , Malária/epidemiologia , Desnutrição/epidemiologia , Infecções por Salmonella/epidemiologia , África ao Sul do Saara/epidemiologia , Índice de Massa Corporal , Água Potável , Infecções por HIV/complicações , Humanos , Malária/complicações , Desnutrição/complicações , Modelos Biológicos , Vigilância da População , Fatores de Risco , Salmonella , Infecções por Salmonella/complicações
9.
Nat Commun ; 12(1): 2879, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001879

RESUMO

As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/prevenção & controle , Proteínas de Bactérias/genética , Genoma Bacteriano/genética , Genômica/métodos , Genótipo , Geografia , Humanos , Malaui , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana/métodos , Mutação , Salmonella typhi/genética , Salmonella typhi/fisiologia , Tanzânia , Febre Tifoide/microbiologia
10.
Clin Infect Dis ; 73(8): 1338-1345, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33822011

RESUMO

BACKGROUND: The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood. METHODS: Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid Fever Surveillance in Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral, and parasitic pathogens. Clinical metadata were also assessed. RESULTS: A total of 615 blood samples available for analysis originated from Burkina Faso (n = 53), Madagascar (n = 364), and Sudan (n = 198) and were taken from participants ranging in age from 0-19 years. Through the TaqMan-Array Card, at least 1 pathogen was detected in 62% (33 of 53), 24% (86 of 364), and 60% (118 of 198) of specimens from Burkina Faso, Madagascar, and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp., accounting for 47% (25 of 53), 2.2% (8 of 364), and 45% (90 of 198) of AFI at the respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357 of 516) of patients with clinical diagnoses of malaria, respiratory infection, or gastrointestinal infection were prescribed a World Health Organization guideline-recommended empiric antibiotic, whereas only 45% (106 of 237) of patients with pathogens detected were treated with an antibiotic exerting likely activity. CONCLUSIONS: A PCR approach for identifying multiple bacterial, viral, and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome.


Assuntos
Doenças Transmissíveis , Febre , Adolescente , Adulto , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Febre/epidemiologia , Febre/etiologia , Humanos , Lactente , Recém-Nascido , Madagáscar/epidemiologia , Sudão , Adulto Jovem
11.
Vaccines (Basel) ; 9(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808924

RESUMO

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).

12.
Artigo em Inglês | MEDLINE | ID: mdl-33579043

RESUMO

Nearly 59,000 human deaths worldwide are attributable to rabies annually, of which more than a third occur in Africa. In recent years, progress has been made in both action and collaboration including implementation of surveillance and prevention measures. In this review we assess the scale of surveillance, preventive, and control efforts of canine-transmitted human rabies in African countries. We reviewed literature published from 2014 to 2018, retrieved from electronic databases including MEDLINE, Global Index Medicus, BIOSIS, Science Citation Index, and EMBASE. WHO reports, national disease control program reports, and conference proceedings were also reviewed. The database search was conducted using keywords including rabies, control, and prevention. In forty countries (40/54), some level of rabies control and prevention strategy was available while in fourteen (14/54) countries, no specific national control and prevention strategy for human rabies could be retrieved. Thirty-four (34/54) countries utilized the Stepwise Approach towards Rabies Elimination (SARE) tool to monitor the national rabies control efforts-five of these countries were at the lowest tier (0/5) of the SARE scoring system while no country had achieved the highest score (5/5). High burden countries need to step up the implementation of context specific national rabies control, prevention, and monitoring strategies. As a zoonosis, rabies control and elimination require coordination between human and veterinarian health sectors under the "One Health" umbrella and with national master plans on the prevention and control of neglected tropical diseases ending in 2020, the time to act is now.


Assuntos
Doenças do Cão , Vacinas Antirrábicas , Raiva , África/epidemiologia , Animais , Erradicação de Doenças , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Cães , Humanos , Políticas , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária
13.
Nat Med ; 27(2): 205-211, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33469205

RESUMO

After the recent announcement of COVID-19 vaccine efficacy in clinical trials by several manufacturers for protection against severe disease, a comprehensive post-efficacy strategy for the next steps to ensure vaccination of the global population is now required. These considerations should include how to manufacture billions of doses of high-quality vaccines, support for vaccine purchase, coordination of supply, the equitable distribution of vaccines and the logistics of global vaccine delivery, all of which are a prelude to a massive vaccination campaign targeting people of all ages. Furthermore, additional scientific questions about the vaccines remain that should be answered to improve vaccine efficacy, including questions regarding the optimization of vaccination regimens, booster doses, the correlates of protection, vaccine effectiveness, safety and enhanced surveillance. The timely and coordinated execution of these post-efficacy tasks will bring the pandemic to an effective, and efficient, close.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Ensaios Clínicos Fase III como Assunto , SARS-CoV-2/fisiologia , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Imunidade Coletiva , Vacinação
14.
Clin Infect Dis ; 72(11): e720-e726, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964216

RESUMO

BACKGROUND: Sustained investments in water, sanitation, and hygiene (WASH) have lagged in resource-poor settings; incremental WASH improvements may, nonetheless, prevent diseases such as typhoid in disease-endemic populations. METHODS: Using prospective data from a large cohort in urban Kolkata, India, we evaluated whether baseline WASH variables predicted typhoid risk in a training subpopulation (n = 28 470). We applied a machine learning algorithm to the training subset to create a composite, dichotomous (good, not good) WASH variable based on 4 variables, and evaluated sensitivity and specificity of this variable in a validation subset (n = 28 470). We evaluated in Cox regression models whether residents of "good" WASH households experienced a lower typhoid risk after controlling for potential confounders. We constructed virtual clusters (radius 50 m) surrounding each household to evaluate whether a prevalence of good WASH practices modified the typhoid risk in central household members. RESULTS: Good WASH practices were associated with protection in analyses of all households (hazard ratio [HR] = 0.57; 95% confidence interval [CI], .37-.90; P = .015). This protection was evident in persons ≥5 years old at baseline (HR = 0.47; 95% CI, .34-.93; P = .005) and was suggestive, though not statistically significant, in younger age groups (HR = 0.61; 95% CI, .27-1.38; P = .235). The level of surrounding household good WASH coverage was also associated with protection (HR = 0.988; 95% CI, .979-.996; P = .004, for each percent coverage increase). However, collinearity between household WASH and WASH coverage prevented an assessment of their independent predictive contributions. CONCLUSIONS: In this typhoid-endemic setting, natural variation in household WASH was associated with typhoid risk. If replicated elsewhere, these findings suggest that WASH improvements may enhance typhoid control, short of major infrastructural investments.


Assuntos
Saneamento , Febre Tifoide , Pré-Escolar , Humanos , Higiene , Índia , Áreas de Pobreza , Estudos Prospectivos , Febre Tifoide/epidemiologia , Água
15.
Sci Rep ; 10(1): 21168, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273605

RESUMO

A better understanding of disease-specific biomarker profiles during acute infections could guide the development of innovative diagnostic methods to differentiate between malaria and alternative causes of fever. We investigated autoantibody (AAb) profiles in febrile children (≤ 5 years) admitted to a hospital in rural Ghana. Serum samples from 30 children with a bacterial bloodstream infection and 35 children with Plasmodium falciparum malaria were analyzed using protein microarrays (Protoplex Immune Response Assay, ThermoFisher). A variable selection algorithm was applied to identify the smallest set of AAbs showing the best performance to classify malaria and bacteremia patients. The selection procedure identified 8 AAbs of which IFNGR2 and FBXW5 were selected in repeated model run. The classification error was 22%, which was mainly due to non-Typhi Salmonella (NTS) diagnoses being misclassified as malaria. Likewise, a cluster analysis grouped patients with NTS and malaria together, but separated malaria from non-NTS infections. Both current and recent malaria are a risk factor for NTS, therefore, a better understanding about the function of AAb in disease-specific immune responses is required in order to support their application for diagnostic purposes.


Assuntos
Autoanticorpos/imunologia , Biomarcadores/metabolismo , Malária Falciparum/imunologia , Sepse/classificação , Sepse/imunologia , Algoritmos , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Masculino
16.
PLoS Negl Trop Dis ; 14(8): e0008530, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804950

RESUMO

We evaluated the protection conferred by a first documented visit for clinical care of typhoid fever against recurrent typhoid fever prompting a visit. This study takes advantage of multi-year follow-up of a population with endemic typhoid participating in a cluster-randomized control trial of Vi capsular polysaccharide typhoid vaccine in Kolkata, India. A population of 70,566 individuals, of whom 37,673 were vaccinated with one dose of either Vi vaccine or a control (Hepatitis A) vaccine, were observed for four years. Surveillance detected 315 first typhoid visits, among whom 4 developed subsequent typhoid, 3 due to reinfection, defined using genomic criteria and corresponding to -124% (95% CI: -599, 28) protection by the initial illness. Point estimates of protection conferred by an initial illness were negative or negligible in both vaccinated and non-vaccinated subjects, though confidence intervals around the point estimates were wide. These data provide little support for a protective immunizing effect of clinically treated typhoid illness, though modest levels of protection cannot be excluded.


Assuntos
Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/administração & dosagem , Anticorpos Antibacterianos , Humanos , Índia/epidemiologia , Salmonella typhi/imunologia , Febre Tifoide/imunologia , Vacinas Tíficas-Paratíficas/uso terapêutico , Vacinação
17.
Expert Rev Vaccines ; 19(8): 691-698, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32838605

RESUMO

INTRODUCTION: The world is currently fighting a COVID-19 pandemic, perhaps the most disruptive infectious disease outbreak since the 1918 Spanish influenza. Governments have taken drastic measures to curb the spread of SARS-CoV-2, and the development of safe and efficacious vaccine candidates is being accelerated. The possibility of vaccine-mediated disease enhancement with coronavirus vaccines has been flagged as a potential safety concern, and, despite the urgent need, should be thoroughly assessed as vaccines against SARS-CoV-2 are being tested. AREA COVERED: We review the in vivo evidence suggesting a theoretical risk of disease enhancement after vaccination with SARS-CoV and MERS-CoV vaccine candidates. We also identify knowledge gaps that need to be filled to maximize the chance of developing a safe vaccine and minimize the risk of encountering disease enhancement in vaccinated individuals after exposure to SARS-CoV-2. EXPERT OPINION: We compile and propose avenues to investigate the risk of vaccine-mediated disease enhancement both during pre-clinical and early clinical development. While the pressing need for a vaccine against COVID-19 (and future epidemic coronaviruses) cannot be ignored, we advocate to keep safety at the center of the debate. Protecting individuals with effective and safe vaccines should be a priority, even during extraordinary times like the COVID-19 pandemic.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/administração & dosagem , Animais , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , SARS-CoV-2 , Vacinação/efeitos adversos , Vacinação/métodos , Vacinas Virais/efeitos adversos
18.
Heliyon ; 6(7): e04389, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32695907

RESUMO

Background: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. Methods: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). Results: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. Conclusion: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place.

19.
Front Immunol ; 11: 1246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636844

RESUMO

Recent advances in systems biology have shifted vaccine development from a largely trial-and-error approach to an approach that promote rational design through the search for immune signatures and predictive correlates of protection. These advances will doubtlessly accelerate the development of a vaccine for schistosomiasis, a neglected tropical disease that currently affects over 250 million people. For over 15 years and with contributions of over 120 people, we have endeavored to test and optimize Sm-p80-based vaccines in the non-human primate model of schistosomiasis. Using RNA-sequencing on eight different Sm-p80-based vaccine strategies, we sought to elucidate immune signatures correlated with experimental protective efficacy. Furthermore, we aimed to explore the role of antibodies through in vivo passive transfer of IgG obtained from immunized baboons and in vitro killing of schistosomula using Sm-p80-specific antibodies. We report that passive transfer of IgG from Sm-p80-immunized baboons led to significant worm burden reduction, egg reduction in liver, and reduced egg hatching percentages from tissues in mice compared to controls. In addition, we observed that sera from Sm-p80-immunized baboons were able to kill a significant percent of schistosomula and that this effect was complement-dependent. While we did not find a universal signature of immunity, the large datasets generated by this study will serve as a substantial resource for further efforts to develop vaccine or therapeutics for schistosomiasis.


Assuntos
Anticorpos Anti-Helmínticos/farmacologia , Antígenos de Helmintos/imunologia , Helmintíase Animal/prevenção & controle , Imunização Passiva , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Modelos Animais de Doenças , Helmintíase Animal/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Papio , Schistosoma mansoni , Esquistossomose mansoni
20.
Clin Infect Dis ; 71(Suppl 2): S102-S110, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32725221

RESUMO

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.


Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , África ao Sul do Saara/epidemiologia , Ásia/epidemiologia , Humanos , Índia/epidemiologia , Salmonella typhi , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle
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