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Open Forum Infectious Diseases May 2023serovar Paratyphi A, the causative agent of paratyphoid fever, is a neglected tropical disease with a high burden and mortality in low- and middle-income countries....
serovar Paratyphi A, the causative agent of paratyphoid fever, is a neglected tropical disease with a high burden and mortality in low- and middle-income countries. Limited information is available regarding its genomic diversity, especially from South Asian countries that are collectively responsible for >80% of all paratyphoid cases. At the 2021 International Conference on Typhoid and Other Salmonelloses, researchers from the around the globe presented their work on Paratyphi A genomics. Presentations described recent genomic data from South Asia and the development of , an open-access single-nucleotide polymorphism-based genotyping scheme, to segregate Paratyphi A genomes in a systematic and sustainable manner. In this review, we attempt to summarize the progress made thus far on Paratyphi A genomics and discuss the questions that remain to better understand the pathogen and develop interventions to fight it.
PubMed: 37274527
DOI: 10.1093/ofid/ofad077 -
BMJ Open May 2023This is the first efficacy study of an oral live attenuated vaccine against Paratyphi A using a human challenge model of paratyphoid infection. . Paratyphi A is...
Accelerating clinical development of a live attenuated vaccine against Paratyphi A (VASP): study protocol for an observer-participant-blind randomised control trial of a novel oral vaccine using a human challenge model of Paratyphi A infection in healthy adult volunteers.
INTRODUCTION
This is the first efficacy study of an oral live attenuated vaccine against Paratyphi A using a human challenge model of paratyphoid infection. . Paratyphi A is responsible for 3.3 million cases of enteric fever every year, with over 19 000 deaths. Although improvements to sanitation and access to clean water are vital to reduce the burden of this condition, vaccination offers a cost-effective, medium-term solution. Efficacy trials of potential . Paratyphi vaccine candidates in the field are unlikely to be feasible given the large number of participants required. Human challenge models therefore offer a unique, cost-effective solution to test efficacy of such vaccines.
METHODS AND ANALYSIS
This is an observer-blind, randomised, placebo-controlled trial phase I/II of the oral live-attenuated vaccine against . Paratyphi A, CVD 1902. Volunteers will be randomised 1:1 to receive two doses of CVD 1902 or placebo, 14 days apart. One month following second vaccination all volunteers will ingest . Paratyphi A bacteria with a bicarbonate buffer solution. They will be reviewed daily in the following 14 days and diagnosed with paratyphoid infection if the predefined microbiological or clinical diagnostic criteria are met. All participants will be treated with antibiotics on diagnosis, or at day 14 postchallenge if not diagnosed. The vaccine efficacy will be determined by comparing the relative attack rate, that is, the proportion of those diagnosed with paratyphoid infection, in the vaccine and placebo groups.
ETHICS AND DISSEMINATION
Ethical approval for this study has been obtained from the Berkshire Medical Research Ethics Committee (REC ref 21/SC/0330). The results will be disseminated via publication in a peer-reviewed journal and presentation at international conferences.
TRIAL REGISTRATION NUMBER
ISRCTN15485902.
Topics: Humans; Adult; Vaccines, Attenuated; Salmonella paratyphi A; Healthy Volunteers; Volunteers; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Clinical Trials, Phase I as Topic
PubMed: 37225278
DOI: 10.1136/bmjopen-2022-068966 -
Zhonghua Liu Xing Bing Xue Za Zhi =... May 2023To analyze the incidence trend and epidemiological characteristics of typhoid fever and paratyphoid fever in China from 2004 to 2020, understand the high-incidence...
To analyze the incidence trend and epidemiological characteristics of typhoid fever and paratyphoid fever in China from 2004 to 2020, understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. The descriptive epidemiological method and spatial analysis method were applied to analyze the epidemiological characteristics of typhoid fever and paratyphoid fever in China during this period by using the surveillance data collected from the National Notifiable Infectious Disease Reporting System of Chinese Center for Disease Control and Prevention. A total of 202 991 cases of typhoid fever were reported in China from 2004 to 2020. More cases occurred in men than in women (sex ratio: 1.18∶1). Most cases were reported in adults aged 20-59 years (53.60%). The incidence rate of typhoid fever decreased from 2.54/100 000 in 2004 to 0.38/100 000 in 2020. The highest incidence rate was reported in young children aged <3 years after 2011, ranging from 1.13/100 000 to 2.78/100 000, and during this period the proportion of cases in this age group increased from 3.48% to 15.59%. The proportion of the cases in the elderly aged ≥60 years increased from 6.46% in 2004 to 19.34% in 2020. The hotspot areas existed in Yunnan, Guizhou, Guangxi and Sichuan Provinces and expanded to Guangdong, Hunan, Jiangxi, and Fujian Provinces. A total of 86 226 paratyphoid fever cases were reported from 2004 to 2020, the male to female ratio of the cases was 1.21∶1. Most cases were reported in adults aged 20-59 years (59.80%). The incidence rate of paratyphoid fever decreased from 1.26/100 000 in 2004 to 0.12/100 000 in 2020. The highest incidence rate of paratyphoid fever was in young children aged <3 years after 2007, ranging from 0.57/100 000 to 1.19/100 000, and during this period the proportion of the cases in this age group increased from 1.48% to 30.92%. The proportion of the cases in the elderly aged ≥60 years increased from 4.52% in 2004 to 22.28% in 2020. The hotspot areas expanded to the east, including Guangdong, Hunan and Jiangxi Provinces, from Yunnan, Guizhou, Sichuan, and Guangxi Provinces. The results showed a low level of incidence of typhoid fever and paratyphoid fever in China with a trend of decreasing per year. The hotspots were mainly in the of Yunnan, Guizhou, Guangxi and Sichuan Provinces, with an expanding trend to eastern China. It is necessary to strengthen the typhoid fever and paratyphoid fever prevention and control in southwestern China, among young children aged <3 years and the elderly aged ≥60 years.
Topics: Adult; Aged; Child, Preschool; Female; Humans; Male; China; Paratyphoid Fever; Sex Ratio; Typhoid Fever; Young Adult; Middle Aged
PubMed: 37221062
DOI: 10.3760/cma.j.cn112338-20221116-00977 -
BMC Public Health May 2023Typhoid fever and paratyphoid fever are one of the most criticial public health issues worldwide, especially in developing countries. The incidence of this disease may...
BACKGROUND
Typhoid fever and paratyphoid fever are one of the most criticial public health issues worldwide, especially in developing countries. The incidence of this disease may be closely related to socio-economic factors, but there is a lack of research on the spatial level of relevant determinants of typhoid fever and paratyphoid fever.
METHODS
In this study, we took Hunan Province in central China as an example and collected the data on typhoid and paratyphoid incidence and socio-economic factors in 2015-2019. Firstly spatial mapping was made on the disease prevalence, and again using geographical probe model to explore the critical influencing factors of typhoid and paratyphoid, finally employing MGWR model to analysis the spatial heterogeneity of these factors.
RESULTS
The results showed that the incidence of typhoid and paratyphoid fever was seasonal and periodic and frequently occurred in summer. In the case of total typhoid and paratyphoid fever, Yongzhou was the most popular, followed by Xiangxi Tujia and Miao Autonomous Prefecture, Huaihua and Chenzhou generally focused on the south and west. And Yueyang, Changde and Loudi had a slight increase trend year by year from 2015 to 2019. Moreover, the significant effects on the incidence of typhoid and paratyphoid fever from strong to weak were as follows: gender ratio(q = 0.4589), students in ordinary institutions of higher learning(q = 0.2040), per capita disposable income of all residents(q = 0.1777), number of foreign tourists received(q = 0.1697), per capita GDP(q = 0.1589), and the P values for these factors were less than 0.001. According to the MGWR model, gender ratio, per capita disposable income of all residents and Number of foreign tourists received had a positive effect on the incidence of typhoid and paratyphoid fever. In contrast, students in ordinary institutions of higher learning had a negative impact, and per capita GDP shows a bipolar change.
CONCLUSIONS
The incidence of typhoid and paratyphoid fever in Hunan Province from 2015 to 2019 was a marked seasonality, concentrated in the south and west of Hunan Province. Attention should be paid to the prevention and control of critical periods and concentrated areas. Different socio-economic factors may show other directions and degrees of action in other prefecture-level cities. To summarize, health education, entry-exit epidemic prevention and control can be strengthened. This study may be beneficial to carry out targeted, hierarchical and focused prevention and control of typhoid fever and paratyphoid fever, and provide scientific reference for related theoretical research.
Topics: Humans; Typhoid Fever; Paratyphoid Fever; Seasons; China; Incidence; Socioeconomic Factors
PubMed: 37217879
DOI: 10.1186/s12889-023-15738-0 -
Human Vaccines & Immunotherapeutics Dec 2023Typhoid remains one of the major serious health concerns for children in developing countries. With extremely drug-resistant cases emerging, preventative measures like... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, observer-blind, controlled phase III clinical trial assessing safety and immunological non-inferiority of Vi-diphtheria toxoid versus Vi-tetanus toxoid typhoid conjugate vaccine in healthy volunteers in eastern Nepal.
Typhoid remains one of the major serious health concerns for children in developing countries. With extremely drug-resistant cases emerging, preventative measures like sanitation and vaccination, including typhoid conjugate vaccines (TCV) remain the mainstay in its prevention and control. Different types of TCVs are being developed to meet the global demand. This report outlines the results from a study done to assess the immunogenicity and safety of Vi-Diphtheria toxoid (Vi-DT) TCV in Nepal. The study was a randomized, active-controlled, immunological non-inferiority and safety study. Eligible participants from Sunsari and Morang districts of eastern Nepal were randomized into 4 study groups (A-D) within 3 age strata (6 months to <2 years, 2 to <18 years, and 18 to 45 years). Groups A to C received a single dose (25 μg) of Vi-DT test vaccine from any of the 3 lots, while group D received the comparator, Typbar-TCV®, Vi-tetanus toxoid (Vi-TT) vaccine (25 μg) in 1:1:1:1 ratio and evaluated at 4 weeks postvaccination with 6 months follow-up. Amongst 400 randomized participants, anti-Vi-IgG seroconversion rates for all age strata in Vi-DT pooled groups (A+B+C) were 100.00% (97.5% CI 98.34-100.00) vs 98.99% (97.5% CI 93.99-99.85) in Vi-TT group (D) at 4 weeks. Comparable safety events were reported between the groups. Three serious adverse events (1 in Vi-DT; 2 in Vi-TT group) were reported during the 6 months follow-up, none being related to the investigational product. Thus, Vi-DT vaccine is safe, immunogenic, and immunologically non-inferior to Vi-TT when analyzed at 4 weeks postvaccination.
Topics: Child; Humans; Infant; Child, Preschool; Typhoid Fever; Vaccines, Conjugate; Tetanus Toxoid; Nepal; Healthy Volunteers; Diphtheria Toxoid; Typhoid-Paratyphoid Vaccines; Antibodies, Bacterial
PubMed: 37128723
DOI: 10.1080/21645515.2023.2203634 -
Frontiers in Immunology 2023serovar Paratyphi A (. Paratyphi A) is a pathogen that can cause enteric fever. According to the recent epidemic trends of typhoid fever, . Paratyphi A has been the...
serovar Paratyphi A (. Paratyphi A) is a pathogen that can cause enteric fever. According to the recent epidemic trends of typhoid fever, . Paratyphi A has been the major important causative factor in paratyphoid fever. An effective vaccine for . Paratyphi A has not been developed, which made it a tricky public health concern. Until now, how . Paratyphi A interacts with organisms remain unknown. Here using lifespan assay, we found that . Paratyphi A could infect () at 25°C, and attenuate thermotolerance. The immune response of was mediated by , , , , , , and , suggesting that . Paratyphi A could regulate the MAPK and insulin pathways. Furthermore, we observed several phenotypical changes when were fed . Paratyphi A, including an accelerated decline in body movement, reduced the reproductive capacity, shortened spawning cycle, strong preference for OP50, arrested pharyngeal pumping and colonization of the intestinal lumen. The virulence of . Paratyphi A requires living bacteria and is not mediated by secreting toxin. Using hydrogen peroxide analysis and quantitative RT-PCR, we discovered that . Paratyphi A could increase oxidative stress and regulate the immune response in . . Our results sheds light on the infection mechanisms of . Paratyphi A and lays a foundation for drugs and vaccine development.
Topics: Animals; Salmonella paratyphi A; Caenorhabditis elegans; Typhoid-Paratyphoid Vaccines; Typhoid Fever; Immunity; Caenorhabditis elegans Proteins; Forkhead Transcription Factors
PubMed: 37122724
DOI: 10.3389/fimmu.2023.1118003 -
PLoS Pathogens Apr 2023Paratyphoid fever caused by S. Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S. Paratyphi A has...
Paratyphoid fever caused by S. Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis highlights that the genome degradation events and gene acquisitions or losses are key molecular events in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 hypothetically disrupted coding sequences (HDCS) or pseudogenes-forming mutations possibly associated with the emergence of lineages were identified. The pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We have identified six characteristic missense mutations associated with lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A, however, these mutations confer only a low structural impact and possibly have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human-restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and monitoring by means of genomic surveillance would be constantly needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.
Topics: Humans; Typhoid Fever; Salmonella typhi; Phylogeny; Salmonella paratyphi A; Anti-Bacterial Agents; Genomics
PubMed: 37115804
DOI: 10.1371/journal.ppat.1010650 -
JMIR Public Health and Surveillance Apr 2023China is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic...
BACKGROUND
China is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic triggered the initiation of the China Information System for Disease Control and Prevention (CISDCP). Since then, numerous studies have investigated the epidemiological features and trends of individual infectious diseases in China; however, few considered the changing spatiotemporal trends and seasonality of these infectious diseases over time.
OBJECTIVE
This study aims to systematically review the spatiotemporal trends and seasonal characteristics of class A and class B notifiable infectious diseases in China during 2005-2020.
METHODS
We extracted the incidence and mortality data of 8 types (27 diseases) of notifiable infectious diseases from the CISDCP. We used the Mann-Kendall and Sen's methods to investigate the diseases' temporal trends, Moran I statistic for their geographical distribution, and circular distribution analysis for their seasonality.
RESULTS
Between January 2005 and December 2020, 51,028,733 incident cases and 261,851 attributable deaths were recorded. Pertussis (P=.03), dengue fever (P=.01), brucellosis (P=.001), scarlet fever (P=.02), AIDS (P<.001), syphilis (P<.001), hepatitis C (P<.001) and hepatitis E (P=.04) exhibited significant upward trends. Furthermore, measles (P<.001), bacillary and amebic dysentery (P<.001), malaria (P=.04), dengue fever (P=.006), brucellosis (P=.03), and tuberculosis (P=.003) exhibited significant seasonal patterns. We observed marked disease burden-related geographic disparities and heterogeneities. Notably, high-risk areas for various infectious diseases have remained relatively unchanged since 2005. In particular, hemorrhagic fever and brucellosis were largely concentrated in Northeast China; neonatal tetanus, typhoid and paratyphoid, Japanese encephalitis, leptospirosis, and AIDS in Southwest China; BAD in North China; schistosomiasis in Central China; anthrax, tuberculosis, and hepatitis A in Northwest China; rabies in South China; and gonorrhea in East China. However, the geographical distribution of syphilis, scarlet fever, and hepatitis E drifted from coastal to inland provinces during 2005-2020.
CONCLUSIONS
The overall infectious disease burden in China is declining; however, hepatitis C and E, bacterial infections, and sexually transmitted infections continue to multiply, many of which have spread from coastal to inland provinces.
Topics: Infant, Newborn; Humans; Scarlet Fever; Syphilis; Hepatitis E; Retrospective Studies; Seasons; Acquired Immunodeficiency Syndrome; Communicable Diseases; Tuberculosis; Brucellosis; Dengue; Hepatitis C
PubMed: 37103994
DOI: 10.2196/42820 -
BMC Infectious Diseases Apr 2023Enteric fever is an acute systemic infectious disease associated with substantial morbidity and mortality in low- and middle-income countries (LMIC), with a global...
BACKGROUND
Enteric fever is an acute systemic infectious disease associated with substantial morbidity and mortality in low- and middle-income countries (LMIC), with a global burden of 14.3 million cases. Cases of enteric fever or paratyphoid fever, caused by Salmonella enterica serovar Paratyphi A (S. Para A) have been found to rise in many endemic and non-endemic countries. Drug resistance is relatively uncommon in S. Para A. Here we report a case of paratyphoid fever caused by ceftriaxone resistant S. Para A from Pakistan.
CASE PRESENTATION
A 29-year-old female presented with a history of fever, headache, and shivering. Her blood culture revealed a S. Para A isolate (S7), which was resistant to ceftriaxone, cefixime, ampicillin and ciprofloxacin. She was prescribed oral Azithromycin for 10 days, which resulted in resolution of her symptoms. Two other isolates of S. Para A (S1 and S4), resistant to fluoroquinolone were also selected for comparison. DST and whole genome sequencing was performed for all three isolates. Sequence analysis was performed for identification of drug resistance and phylogeny. Whole Genome Sequencing (WGS) of S7 revealed the presence of plasmids, IncX4 and IncFIB(K). blaCTX-M-15 and qnrS1 genes were found on IncFIB(K). The gyrA S83F mutation conferring fluoroquinolone resistance was also found present. Multi-locus sequence typing (MLST) showed the S7 isolate to belong to ST129. S1 and S4 had the gyrA S83Y and S83F mutations respectively.
CONCLUSIONS
We highlight the occurrence of plasmid-mediated ceftriaxone resistant strain of S. Para A. This is of significance as ceftriaxone is commonly used to treat paratyphoid fever and resistance in S. Para A is not known. Continuous epidemiological surveillance is required to monitor the transmission and spread of antimicrobial resistance (AMR) among Typhoidal Salmonellae. This will guide treatment options and preventive measures including the need for vaccination against S. Para A in the region.
Topics: Humans; Female; Adult; Typhoid Fever; Ceftriaxone; Anti-Bacterial Agents; Salmonella paratyphi A; Multilocus Sequence Typing; Paratyphoid Fever; Salmonella typhi; Pakistan; Fluoroquinolones; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 37101111
DOI: 10.1186/s12879-023-08152-9 -
The New England Journal of Medicine Apr 2023In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is...
BACKGROUND
In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection.
METHODS
From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community.
RESULTS
A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age.
CONCLUSIONS
The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).
Topics: Humans; Infant; Incidence; India; Paratyphoid Fever; Population Surveillance; Prospective Studies; Typhoid Fever; Cost of Illness; Blood Culture; Child, Preschool; Child; Adolescent; Urban Population; Rural Population; Hospitalization
PubMed: 37075141
DOI: 10.1056/NEJMoa2209449