RESUMO
Controlled human infection model (CHIM) studies, which involve deliberate exposure of healthy human volunteers to an infectious agent, are recognised as important tools to advance vaccine development. These studies not only facilitate estimates of vaccine efficacy, but also offer an experimental approach to study disease pathogenesis and profile vaccine immunogenicity in a controlled environment, allowing correlation with clinical outcomes. Consequently, the data from CHIMs can be used to identify immunological correlates of protection (CoP), which can help accelerate vaccine development. In the case of invasive Salmonella infections, vaccination offers a potential instrument to prevent disease. Invasive Salmonella disease, caused by the enteric fever pathogens Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi A, B and C, and nontyphoidal Salmonella (iNTS), remains a significant cause of mortality and morbidity in low- and middle-income countries, resulting in over 200,000 deaths and the loss of 15 million DALYs annually. CHIM studies have contributed to the understanding of S. Typhi infection and provided invaluable insight into the development of vaccines and CoP following vaccination against S. Typhi. However, CoP are less well understood for S. Paratyphi A and iNTS. This brief review focuses on the contribution of vaccine-CHIM trials to our understanding of the immune mechanisms associated with protection following vaccines against invasive Salmonella pathogens, particularly in relation to CoP.
Assuntos
Infecções por Salmonella , Vacinas contra Salmonella , Humanos , Vacinas contra Salmonella/imunologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/prevenção & controle , Salmonella typhi/imunologia , Vacinação , Eficácia de Vacinas , Febre Tifoide/prevenção & controle , Febre Tifoide/imunologia , Salmonella/imunologiaRESUMO
An oral Controlled Human Infection Model (CHIM) with wild-type S. Typhi was re-established allowing us to explore the development of immunity. In this model, ~55% of volunteers who received the challenge reached typhoid diagnosis criteria (TD), while ~45% did not (NoTD). Intestinal macrophages are one of the first lines of defense against enteric pathogens. Most organs have self-renewing macrophages derived from tissue-resident progenitor cells seeded during the embryonic stage; however, the gut lacks these progenitors, and all intestinal macrophages are derived from circulating monocytes. After infecting gut-associated lymphoid tissues underlying microfold (M) cells, S. Typhi causes a primary bacteremia seeding organs of the reticuloendothelial system. Following days of incubation, a second bacteremia and clinical disease ensue. S. Typhi likely interacts with circulating monocytes or their progenitors in the bone marrow. We assessed changes in circulating monocytes after CHIM. The timepoints studied included 0 hours (pre-challenge) and days 1, 2, 4, 7, 9, 14, 21 and 28 after challenge. TD participants provided extra samples at the time of typhoid diagnosis, and 48-96 hours later (referred as ToD). We report changes in Classical Monocytes -CM-, Intermediate Monocytes -IM- and Non-classical Monocytes -NCM-. Changes in monocyte activation markers were identified only in TD participants and during ToD. CM and IM upregulated molecules related to interaction with bacterial antigens (TLR4, TLR5, CD36 and CD206). Of importance, CM and IM showed enhanced binding of S. Typhi. Upregulation of inflammatory molecules like TNF-α were detected, but mechanisms involved in limiting inflammation were also activated (CD163 and CD354 downregulation). CM upregulated molecules to interact/modulate cells of the adaptive immunity, including T cells (HLA-DR, CD274 and CD86) and B cells (CD257). Both CM and IM showed potential to migrate to the gut as integrin α4ß7 was upregulated. Unsupervised analysis revealed 7 dynamic cell clusters. Five of these belonged to CM showing that this is the main population activated during ToD. Overall, we provide new insights into the changes that diverse circulating monocyte subsets undergo after typhoid diagnosis, which might be important to control this disease since these cells will ultimately become intestinal macrophages once they reach the gut.
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Monócitos , Salmonella typhi , Febre Tifoide , Humanos , Febre Tifoide/diagnóstico , Febre Tifoide/imunologia , Salmonella typhi/imunologia , Monócitos/imunologia , Masculino , Adulto , Feminino , Adulto Jovem , Macrófagos/imunologiaRESUMO
Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji implemented a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of Salmonella Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (n=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017-2019. We found elevated rates of nucleotide polymorphisms in the tviD and tviE genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic S. Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12â382 S. Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same tviE mutations across the S. Typhi population, indicating that tvi selection has occurred both independently and globally. The functional impact of tvi mutations on the Vi-capsular structure and other phenotypic characteristics are not fully elucidated, yet commonly occurring tviE polymorphisms localize adjacent to predicted active site residues when overlayed against the predicted TviE protein structure. Given the central role of the Vi-polysaccharide in S. Typhi biology and vaccination, further integrated epidemiological, genomic and phenotypic surveillance is required to determine the spread and functional implications of these mutations.
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Polissacarídeos Bacterianos , Salmonella typhi , Febre Tifoide , Salmonella typhi/genética , Fiji/epidemiologia , Febre Tifoide/microbiologia , Febre Tifoide/epidemiologia , Humanos , Polissacarídeos Bacterianos/genética , Heterogeneidade Genética , Vacinas Tíficas-Paratíficas/genética , Genótipo , Mutação , Polimorfismo de Nucleotídeo Único , Cápsulas Bacterianas/genéticaAssuntos
Coinfecção , Hospitais Universitários , Malária , Febre Tifoide , Nigéria/epidemiologia , Humanos , Febre Tifoide/epidemiologia , Febre Tifoide/complicações , Estudos Retrospectivos , Coinfecção/epidemiologia , Coinfecção/parasitologia , Masculino , Feminino , Adulto , Hospitais Universitários/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Lactente , IdosoRESUMO
Background and Objectives: In the undertaken study, proteomics alterations of blood-borne XDR S. Typhi isolated from Pakistan were investigated using mass spectrometry. Materials and Methods: MDR and XDR S. Typhi total protein lysates were fractionated, digested, and processed for nanoflow LC-LTQ-Orbitrap MS analysis. Results: Among the 1267 identified proteins, 37 were differentially regulated, of which 28 were up-regulated, and 9 were down-regulated in XDR S. Typhi as compared to MDR S. Typhi. Based on the functional annotation, proteins found up-regulated are involved mainly in metabolic pathways (ManA, FadB, DacC, GpmA, AphA, PfkB, TalA, FbaB, OtsA, 16504242), the biosynthesis of secondary metabolites (ManA, FadB, GlpB, GpmA, PfkB, TalA, FbaB, OtsA), microbial metabolism in diverse environments (FadB, GpmA, PfkB, NfnB, TalA, FbaB), and ABC transporters (PstS, YbeJ, MglB, RbsB, ArtJ). Proteins found down-regulated are involved mainly in carbon metabolism (FadB, GpmA, PfkB, FalA, FbaB) and the biosynthesis of amino acids (GpmA, PfkB, TalA, FbaB). Most of the identified differential proteins were predicted to be antigenic, and matched with resistome data. Conclusions: A total of 28 proteins were up-regulated, and 9 were down-regulated in XDR S. Typhi. Further characterization of the identified proteins will help in understanding the molecular signaling involved in the emergence of XDR S. Typhi.
Assuntos
Salmonella typhi , Regulação para Cima , Salmonella typhi/efeitos dos fármacos , Paquistão , Humanos , Proteínas de Bactérias , Farmacorresistência Bacteriana Múltipla/genética , Febre Tifoide/microbiologia , Proteômica/métodosRESUMO
Despite decades of intense research, our understanding of the correlates of protection against Salmonella Typhi (S. Typhi) infection and disease remains incomplete. T follicular helper cells (TFH), an important link between cellular and humoral immunity, play an important role in the development and production of high affinity antibodies. While traditional TFH cells reside in germinal centers, circulating TFH (cTFH) (a memory subset of TFH) are present in blood. We used specimens from a typhoid controlled human infection model whereby participants were immunized with Ty21a live attenuated S. Typhi vaccine and then challenged with virulent S. Typhi. Some participants developed typhoid disease (TD) and some did not (NoTD), which allowed us to assess the association of cTFH subsets in the development and prevention of typhoid disease. Of note, the frequencies of cTFH were higher in NoTD than in TD participants, particularly 7 days after challenge. Furthermore, the frequencies of cTFH2 and cTFH17, but not cTFH1 subsets were higher in NoTD than TD participants. However, we observed that ex-vivo expression of activation and homing markers were higher in TD than in NoTD participants, particularly after challenge. Moreover, cTFH subsets produced higher levels of S. Typhi-specific responses (cytokines/chemokines) in both the immunization and challenge phases. Interestingly, unsupervised analysis revealed unique clusters with distinct signatures for each cTFH subset that may play a role in either the development or prevention of typhoid disease. Importantly, we observed associations between frequencies of defined cTFH subsets and anti-S. Typhi antibodies. Taken together, our results suggest that circulating TFH2 and TFH17 subsets might play an important role in the development or prevention of typhoid disease. The contribution of these clusters was found to be distinct in the immunization and/or challenge phases. These results have important implications for vaccines aimed at inducing long-lived protective T cell and antibody responses.
Assuntos
Salmonella typhi , Células T Auxiliares Foliculares , Febre Tifoide , Vacinas Tíficas-Paratíficas , Humanos , Salmonella typhi/imunologia , Febre Tifoide/imunologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Tíficas-Paratíficas/administração & dosagem , Células T Auxiliares Foliculares/imunologia , Masculino , Feminino , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Adulto Jovem , Polissacarídeos Bacterianos/imunologia , Imunização , Administração Oral , AdolescenteRESUMO
Background: Typhoid fever is one of the major public health concerns in developing countries, including Ethiopia. Understanding the burden and factors contributing to the transmission and development of the disease is crucial to applying appropriate preventive and therapeutic interventions. Objective: To assess the prevalence of typhoid fever and its associated factors among febrile patients visiting Arerti Primary Hospital from 1 March to 30 May 2022. Methods: A facility-based cross-sectional study was employed among 326 febrile patients visiting Arerti Primary Hospital for health services. The data were collected using laboratory procedures (widal test) and a structured interviewer-administered questionnaire. The data were entered using Epi Data version 3.1 and analyzed by SPSS version 25. Logistic regression was used to determine associations between variables. P-value < 0.05 and adjusted odds ratio with 95% confidence interval were used to measure the presence and strength of associations. Results: In this study, of the total 317 cases that participated, the majority (64.4%) of them were males with age ranges from 13 to 63 years. The overall prevalence of positive antigen tests for typhoid infection was 30.0% (95% CI: 25.0%-35.3%). About 66.9% of the study participants had good knowledge, 75.7% had favorable perception, and 42.3% had good infection prevention practice. Being unemployed [AOR = 7.57, 95% CI (1.98, 28.93)], being a farmer [AOR = 2.73, 95% CI (1.01, 7.41)], and having a body mass index (BMI) below 18.5 kg/m2 [AOR = 5.12, 95%CI (2.45, 10.68)] were significantly associated with typhoid fever infection. Conclusion: The prevalence of typhoid fever among febrile patients was high. Typhoid fever infection was significantly associated with occupational status (being unemployed and being a farmer) and lower BMI. The level of knowledge, perception, and practice of typhoid fever infection prevention were found inadequate. Therefore, behavioral change interventions are needed at the community level.
Assuntos
Febre Tifoide , Humanos , Etiópia/epidemiologia , Febre Tifoide/epidemiologia , Masculino , Feminino , Adulto , Estudos Transversais , Prevalência , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Inquéritos e Questionários , Fatores de Risco , Febre/epidemiologia , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Vaccine safety and immunogenicity data in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children are important for decision-making in HIV and typhoid co-endemic countries. In an open-label study, we recruited Malawian HEU and HIV unexposed uninfected (HUU) infants aged 9 - 11 months. HEU participants were randomized to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) at 9 months, Vi-TT at 15 months, or Vi-TT at 9 and 15 months. HUU participants received Vi-TT at 9 and 15 months. Safety outcomes included solicited and unsolicited adverse events (AE) and serious AEs (SAEs) within 7 days, 28 days, and 6 months of vaccination, respectively. Serum was collected before and at day 28 after each vaccination to measure anti-Vi IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Cohort 1 (66 participants) enrollment began 02 December 2019, and follow-up was terminated before completion due to the COVID-19 pandemic. Cohort 2 (100 participants) enrollment began 25 March 2020. Solicited AEs were mostly mild, with no significant differences between HEU and HUU participants or one- and two-dose groups. All six SAEs were unrelated to vaccination. Anti-Vi geometric mean titers (GMT) increased significantly from 4.1 to 4.6 ELISA units (EU)/mL at baseline to 2572.0 - 4117.6 EU/mL on day 28 post-vaccination, and similarly between HEU and HUU participants for both one- and two-dose schedules. All participants seroconverted (>4-fold increase in GMT) by the final study visit. Our findings of comparable safety and immunogenicity of Vi-TT in HUU and HEU children support country introductions with single-dose Vi-TT in HIV-endemic countries.
Assuntos
Anticorpos Antibacterianos , Infecções por HIV , Imunogenicidade da Vacina , Febre Tifoide , Vacinas Tíficas-Paratíficas , Vacinas Conjugadas , Humanos , Masculino , Feminino , Malaui , Lactente , Infecções por HIV/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Tíficas-Paratíficas/efeitos adversos , Vacinas Tíficas-Paratíficas/administração & dosagem , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/administração & dosagem , Anticorpos Antibacterianos/sangue , Febre Tifoide/imunologia , Febre Tifoide/prevenção & controle , Imunoglobulina G/sangue , Toxoide Tetânico/imunologia , Toxoide Tetânico/efeitos adversos , Toxoide Tetânico/administração & dosagem , Esquemas de Imunização , VacinaçãoRESUMO
Despite advancements in military medical treatment and evacuation, soldiers in austere environments remain vulnerable to disease and non-battle injury and may face prolonged evacuation before receiving definitive care. In particular, arranging care for a soldier presenting with a conditions that has a wide differential diagnosis, such as acute altered mental status (AMS), can be especially challenging. We highlight the case of an otherwise young, healthy U.S. Soldier serving in Indonesia, who presented with acute AMS concerning for undifferentiated infection. Subsequent workup at the receiving hospital following evacuation revealed Salmonella enterica infection, more commonly known as typhoid. However, even with clinical findings of typhoid encephalitis and initiation of empiric treatment, medical care proved challenging in the resource-limited local facilities, despite multiple escalations of care. Ultimately, the patient was evacuated to a tertiary facility in Singapore, where his condition improved, and 4 days after initial presentation the patient had no definitive findings of infections on lumbar puncture. This case not only highlights the threat of typhoid and other infectious diseases in modern operations but also the challenges of suboptimal medical care in both the prehospital and hospital settings when utilizing host nation facilities.
Assuntos
Militares , Febre Tifoide , Humanos , Indonésia , Febre Tifoide/diagnóstico , Febre Tifoide/terapia , Febre Tifoide/tratamento farmacológico , Masculino , Antibacterianos/uso terapêutico , Encefalite/diagnóstico , Encefalite/terapia , Diagnóstico Diferencial , Adulto , Adulto JovemRESUMO
Typbar-TCV®, a typhoid conjugate vaccine (TCV), was prequalified by the World Health Organization in 2017. We evaluated its effectiveness in a mass vaccination program targeting children 9 months to 14 years in Navi Mumbai, India, from September 2018 to July 2020. We compared laboratory-confirmed typhoid cases from six clinical sites with age-matched community controls. Of 38 cases, three (8.6%) received TCV through the campaign, compared with 53 (37%) of 140 controls. The adjusted odds ratio of typhoid fever among vaccinated children was 0.16 (95% CI: 0.05-0.55), equivalent to a vaccine effectiveness of 83.7% (95% CI: 45.0-95.3). Vaccine effectiveness of Typbar-TCV in this large public sector vaccine introduction was similar to prior randomized controlled trials, providing reassurance to policymakers that TCV effectiveness is robust in a large-scale implementation.
Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Vacinas Conjugadas , Humanos , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Tíficas-Paratíficas/administração & dosagem , Febre Tifoide/prevenção & controle , Febre Tifoide/epidemiologia , Índia/epidemiologia , Criança , Pré-Escolar , Lactente , Vacinas Conjugadas/imunologia , Adolescente , Feminino , Masculino , Eficácia de Vacinas , Salmonella typhi/imunologia , Vacinação em MassaRESUMO
INTRODUCTION: Ultrasound has proven to have great potentials in the diagnosis and work-up of patients affected by tropical diseases. Its role in the diagnosis of malaria and typhoid abounds, but its value as a triaging tool in a resource-constrained settings is indistinct. Our review aimed is aimed at assessing the utility of ultrasound in diagnosis and prognosis of malaria and typhoid. MATERIALS AND METHOD: Extensive literature search was conducted using the PubMed electronic database, for original peer reviewed articles in English language within 1964-2023. Keywords like "malaria", "typhoid", "S. Typhi", "Salmonella Typhi", "enteric fever", "ultrasound", "sonography" and "ultrasonography" were searched, using Boolean operators such as (OR, AND) applying the following filters (English, Human). A systematic synthesis of the literature was done. RESULT: Our initial search yielded 749 potentially relevant references out of which 55 were found to be eligible. Organs assessed include the liver, spleen, kidneys, intestines, mesenteric lymph nodes, among others. For malaria, pathognomonic conditions like splenic enlargement, hepatomegaly, renal abnormalities as well as mesenteric lymph nodes and intestinal wall thickening in patients with typhoid fever. CONCLUSION: Ultrasound by experienced clinicians adds significantly to the diagnosis and work-up of patients with malaria and typhoid fever. However, it is important to note that ultrasound alone may not be sufficient for definitive diagnosis as laboratory tests may still be required for confirmatory diagnosis. IMPLICATION FOR PRACTICE: This study provide information on ultrasound in diagnosis of Malaria and typhoid by evaluating the morphological changes in abdominal and other organs of the body. This can be a guide to clinicians and other healthcare providers for early diagnosis and work-up of patients in endemic areas where resources are scarce.
Assuntos
Malária , Triagem , Febre Tifoide , Ultrassonografia , Humanos , Febre Tifoide/diagnóstico por imagem , Malária/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a systemic infection that affects millions of people worldwide. S. Typhi can invade and survive within host cells, such as intestinal epithelial cells and macrophages, by modulating their immune responses. However, the immunomodulatory capability of S. Typhi in relation to TolC-facilitated efflux pump function remains unclear. The role of TolC, an outer membrane protein that facilitates efflux pump function, in the invasion and immunomodulation of S. Typhi, was studied in human intestinal epithelial cells and macrophages. The tolC deletion mutant of S. Typhi was compared with the wild-type and its complemented strain in terms of their ability to invade epithelial cells, survive and induce cytotoxicity in macrophages, and elicit proinflammatory cytokine production in macrophages. The tolC mutant, which has a defective outer membrane, was impaired in invading epithelial cells compared to the wild-type strain, but the intracellular presence of the tolC mutant exhibited greater cytotoxicity and induced higher levels of proinflammatory cytokines (IL-1ß and IL-8) in macrophages compared to the wild-type strain. These effects were reversed by complementing the tolC mutant with a functional tolC gene. Our results suggest that TolC plays a role in S. Typhi to efficiently invade epithelial cells and suppress host immune responses during infection. TolC may be a potential target for the development of novel therapeutics against typhoid fever.
Assuntos
Proteínas da Membrana Bacteriana Externa , Células Epiteliais , Macrófagos , Salmonella typhi , Febre Tifoide , Salmonella typhi/patogenicidade , Salmonella typhi/imunologia , Salmonella typhi/genética , Humanos , Macrófagos/microbiologia , Macrófagos/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas da Membrana Bacteriana Externa/imunologia , Células Epiteliais/microbiologia , Células Epiteliais/imunologia , Febre Tifoide/imunologia , Febre Tifoide/microbiologia , Imunomodulação , Citocinas/metabolismo , Citocinas/imunologia , Viabilidade Microbiana , Interleucina-8/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/imunologia , Linhagem CelularRESUMO
This study presents a reliable mathematical model to explain the spread of typhoid fever, covering stages of susceptibility, infection, carrying, and recovery, specifically in the Sheno town community. A detailed analysis is done to ensure the solutions are positive, stay within certain limits, and are stable for both situations where the disease is absent and where it is consistently present. The Routh-Hurwitz stability criterion has been used and applied for the purpose of stability analysis. Using the next-generation matrix, we determined the intrinsic potential for disease transmission. It showing that typhoid fever is spreading actively in Sheno town, with cases above a critical level. Our findings reveal the instability of the disease-free equilibrium point alongside the stability of the endemic equilibrium point. We identified two pivotal factors for transmission of the disease: the infectious rate, representing the speed of disease transmission, and the recruitment rate, indicating the rate at which new individuals enter the susceptible population. These parameters are indispensable for devising effective control measures. It is imperative to keep these parameters below specific thresholds to maintain a basic reproduction number favorable for disease control. Additionally, the study carefully examines how different factors affect the spread of typhoid fever, giving a detailed understanding of its dynamics. At the end, this study provides valuable insights and specific strategies for managing the disease in the Sheno town community.
Assuntos
Febre Tifoide , Febre Tifoide/transmissão , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Humanos , Etiópia/epidemiologia , Dinâmica não Linear , Modelos Teóricos , Número Básico de ReproduçãoRESUMO
Objective: The event-based surveillance and response report from the municipality of Buguias in the Philippines covering the period 1 January to 29 October 2022 indicated an unusual increase in the number of typhoid cases that surpassed the epidemic threshold for consecutive weeks. An investigation was conducted to confirm the existence of an outbreak, identify the source(s) of transmission and recommend prevention and control measures. Methods: The investigation employed a descriptive design. Medical records were reviewed to verify diagnoses and to identify cases that met case definitions. Key informant interviews were conducted to identify possible sources of transmission and investigate the reporting of cases in the Philippine Integrated Disease Surveillance and Response (PIDSR) system. Results: A total of 220 cases of typhoid fever were captured by the PIDSR system. Of the 208 suspected cases that were reviewed, only 15 (7.2%) met the case definition used in this investigation. Fourteen of these 15 verified cases were interviewed; five (35.7%) were farmers and 13 (92.8%) reported using springs as their main water source and source of drinking-water. Reporting of cases in the PIDSR system was largely based on the final chart diagnosis or a positive Typhidot or Tubex rapid diagnostic test result. The PIDSR case definition was not followed in the reporting of cases. Discussion: This study provides evidence of endemicity of typhoid fever in Buguias, Benguet, Philippines. However, from January to October 2022, cases were overreported by the surveillance system. Medical record reviews showed that most reported suspected cases did not meet case definition criteria. This finding emphasizes the need to improve typhoid guidelines with regards to diagnosis using rapid diagnostic tests and to investigate the cost-effectiveness of making confirmatory laboratory tests for typhoid available in the Philippines.
Assuntos
Surtos de Doenças , Febre Tifoide , Filipinas/epidemiologia , Humanos , Febre Tifoide/epidemiologia , Febre Tifoide/diagnóstico , Surtos de Doenças/prevenção & controle , Masculino , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Criança , Pré-Escolar , Vigilância da População/métodos , Adulto JovemRESUMO
OBJECTIVES: Typhoid remains a persistent contributor to childhood morbidity in communities lacking sanitation infrastructure. Typhoid conjugate vaccine (TCV) is effective in reducing disease risk in vaccinees; however, the duration of protection is unknown. This study measured the longevity of immune response to TCV in children aged under 10 years in Hyderabad, Pakistan, where an outbreak of extensively drug-resistant typhoid has been ongoing. METHODS: A subset of children who received the TCV as part of the outbreak response were enrolled purposively from March 2018 to February 2019. The participants were followed up until January 2023. Blood samples were taken at baseline, 4-6 weeks, 6 months, and annually 1-4 years after vaccination to measure anti-Vi immunoglobulin (Ig) G levels using enzyme-linked immunosorbent assay. Active phone-based surveillance was performed to identify breakthrough infections. Blood culture was offered to any child with a history of fever ≥3 days within the last 7 days. A total of 81 children received a second dose of TCV in November 2019 during a catch-up campaign organized by the Sindh government. RESULTS: Nearly all participants seroconverted (802 of 837; 95.8%) at 4-6 weeks after vaccination. A total of 4 years after vaccination, 438 of 579 (75.6%) participants remained above the seroconversion threshold. The geometric mean titer (U/mL) of anti-Vi IgG at 4-6 weeks was 832.6 (95% confidence interval [CI]: 768.0-902.6); at 4 years after vaccination, the geometric mean titers in children aged 6 months to 2 years (12.6, [95% CI: 9.8-16.3]) and >2-5 years (40.1, [95% CI: 34.4-46.6]) were lower than in children aged >5-10 years (71.1, [95% CI: 59.5-85.0]). During 4 years of follow-up, nine children had culture-confirmed Salmonella Typhi infection; these infections occurred after a median duration of 3.4 years. All enteric fever cases seroconverted at 4-6 weeks after vaccination and seven (70.0%) remained seroconverted 4 years after vaccination. CONCLUSIONS: We observed 95.8% seroconversion after a single dose of TCV. There was a decay in anti-Vi IgG titers, and, at 4 years, approximately 75.6% remained seroconverted. There was a faster decay in children aged ≤2 years. Breakthrough infections were documented after a median 3.4 years after vaccination.
Assuntos
Anticorpos Antibacterianos , Imunoglobulina G , Salmonella typhi , Febre Tifoide , Vacinas Tíficas-Paratíficas , Vacinas Conjugadas , Humanos , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Tíficas-Paratíficas/administração & dosagem , Paquistão/epidemiologia , Febre Tifoide/prevenção & controle , Febre Tifoide/imunologia , Febre Tifoide/epidemiologia , Salmonella typhi/imunologia , Pré-Escolar , Feminino , Masculino , Anticorpos Antibacterianos/sangue , Criança , Imunoglobulina G/sangue , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/administração & dosagem , Lactente , Vacinação/métodos , Surtos de Doenças/prevenção & controleRESUMO
BACKGROUND: Enteric fever is a serious public health concern. The causative agents, Salmonella enterica serovars Typhi and Paratyphi A, frequently have antimicrobial resistance (AMR), leading to limited treatment options and poorer clinical outcomes. We investigated the genomic epidemiology, resistance mechanisms, and transmission dynamics of these pathogens at three urban sites in Africa and Asia. METHODS: S Typhi and S Paratyphi A bacteria isolated from blood cultures of febrile children and adults at study sites in Dhaka (Bangladesh), Kathmandu (Nepal), and Blantyre (Malawi) during STRATAA surveillance were sequenced. Isolates were charactered in terms of their serotypes, genotypes (according to GenoTyphi and Paratype), molecular determinants of AMR, and population structure. We used phylogenomic analyses incorporating globally representative genomic data from previously published surveillance studies and ancestral state reconstruction to differentiate locally circulating from imported pathogen AMR variants. Clusters of sequences without any single-nucleotide variants in their core genome were identified and used to explore spatiotemporal patterns and transmission dynamics. FINDINGS: We sequenced 731 genomes from isolates obtained during surveillance across the three sites between Oct 1, 2016, and Aug 31, 2019 (24 months in Dhaka and Kathmandu and 34 months in Blantyre). S Paratyphi A was present in Dhaka and Kathmandu but not Blantyre. S Typhi genotype 4.3.1 (H58) was common in all sites, but with different dominant variants (4.3.1.1.EA1 in Blantyre, 4.3.1.1 in Dhaka, and 4.3.1.2 in Kathmandu). Multidrug resistance (ie, resistance to chloramphenicol, co-trimoxazole, and ampicillin) was common in Blantyre (138 [98%] of 141 cases) and Dhaka (143 [32%] of 452), but absent from Kathmandu. Quinolone-resistance mutations were common in Dhaka (451 [>99%] of 452) and Kathmandu (123 [89%] of 138), but not in Blantyre (three [2%] of 141). Azithromycin-resistance mutations in acrB were rare, appearing only in Dhaka (five [1%] of 452). Phylogenetic analyses showed that most cases derived from pre-existing, locally established pathogen variants; 702 (98%) of 713 drug-resistant infections resulted from local circulation of AMR variants, not imported variants or recent de novo emergence; and pathogen variants circulated across age groups. 479 (66%) of 731 cases clustered with others that were indistinguishable by point mutations; individual clusters included multiple age groups and persisted for up to 2·3 years, and AMR determinants were invariant within clusters. INTERPRETATION: Enteric fever was associated with locally established pathogen variants that circulate across age groups. AMR infections resulted from local transmission of resistant strains. These results form a baseline against which to monitor the impacts of control measures. FUNDING: Wellcome Trust, Bill & Melinda Gates Foundation, EU Horizon 2020, and UK National Institute for Health and Care Research.
Assuntos
Antibacterianos , Filogenia , Salmonella paratyphi A , Salmonella typhi , Febre Tifoide , Humanos , Bangladesh/epidemiologia , Nepal/epidemiologia , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Febre Tifoide/transmissão , Febre Tifoide/tratamento farmacológico , Salmonella typhi/genética , Salmonella typhi/efeitos dos fármacos , Criança , Antibacterianos/farmacologia , Adulto , Pré-Escolar , Malaui/epidemiologia , Salmonella paratyphi A/genética , Salmonella paratyphi A/efeitos dos fármacos , Masculino , Adolescente , Farmacorresistência Bacteriana/genética , Feminino , Lactente , Febre Paratifoide/epidemiologia , Febre Paratifoide/microbiologia , Febre Paratifoide/transmissão , Febre Paratifoide/tratamento farmacológico , Adulto Jovem , Genótipo , Genoma Bacteriano/genética , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , GenômicaRESUMO
BACKGROUND: In 2019, following a large outbreak of typhoid fever, the Zimbabwe Ministry of Health and Child Care conducted a typhoid conjugate vaccine (TCV) vaccination campaign in nine high-risk suburbs of Harare. We aimed to evaluate TCV vaccination coverage, vaccine perceptions, and adverse events reported after vaccination. METHODS: We conducted a two-stage cluster survey to estimate vaccination coverage in the campaign target areas among children aged 6 months-15 years and to classify coverage as either adequate (≥75 % coverage) or inadequate (<75 % coverage) among adults aged 16-45 years in one suburb. Questionnaires assessed socio-demographic factors, TCV vaccination history, reasons for receiving or not receiving TCV, adverse events following immunization, and knowledge and attitudes regarding typhoid and TCV. RESULTS: A total of 1,917 children from 951 households and 298 adults from 135 households enrolled in the survey. Weighted TCV coverage among all children aged 6 months-15 years was 85.3 % (95 % CI: 82.1 %-88.0 %); coverage was 74.8 % (95 % CI: 69.4 %-79.5 %) among children aged 6 months-4 years and 89.3 % (95 % CI: 86.2 %-91.7 %) among children aged 5-15 years. Among adults, TCV coverage was classified as inadequate with a 95 % confidence interval of 55.0 %-73.1 %. Among vaccinated persons, the most reported reason for receiving TCV (96 % across all age groups) was protection from typhoid fever; the most common reasons for non-vaccination were not being in Harare during the vaccination campaign and not being aware of the campaign. Adverse events were infrequently reported in all age groups (10 %) and no serious events were reported. CONCLUSIONS: The 2019 TCV campaign achieved high coverage among school-aged children (5-15 years). Strategies to increase vaccination coverage should be explored for younger children as part of Zimbabwe's integration of TCV into the routine immunization program, and for adults during future post-outbreak campaigns.