Salmonella enterica serovar Paratyphi A-induced immune response in Caenorhabditis elegans depends on MAPK pathways and DAF-16.

Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is a pathogen that can cause enteric fever. According to the recent epidemic trends of typhoid fever, S. Paratyphi A has been the major important causative factor in paratyphoid fever. An effective vaccine for S. Paratyphi A has not been developed, which made it a tricky public health concern. Until now, how S. Paratyphi A interacts with organisms remain unknown. Here using lifespan assay, we found that S. Paratyphi A could infect Caenorhabditis elegans (C. elegans) at 25°C, and attenuate thermotolerance. The immune response of C. elegans was mediated by tir-1, nsy-1, sek-1, pmk-1, mpk-1, skn-1, daf-2 and daf-16, suggesting that S. Paratyphi A could regulate the MAPK and insulin pathways. Furthermore, we observed several phenotypical changes when C. elegans were fed S. 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 S. Paratyphi A requires living bacteria and is not mediated by secreting toxin. Using hydrogen peroxide analysis and quantitative RT-PCR, we discovered that S. Paratyphi A could increase oxidative stress and regulate the immune response in C. elegans. Our results sheds light on the infection mechanisms of S. Paratyphi A and lays a foundation for drugs and vaccine development.

Invasive Non-Typhoidal Salmonella Lineage Biofilm Formation and Gallbladder Colonization Vary But Do Not Correlate Directly with Known Biofilm-Related Mutations.

Non-typhoidal Salmonella (NTS) serovars have a broad host range and cause gastroenteritis in humans. However, invasive NTS (iNTS) bloodstream infections have increased in the last decade, causing 60,000 deaths annually. Human-specific typhoidal Salmonella colonizes and forms biofilms on gallstones, resulting in chronic, asymptomatic infection. iNTS lineages are undergoing genomic reduction and may have adapted to person-to-person transmission via mutations in virulence, bile resistance, and biofilm formation. As such, we sought to determine the capacity of iNTS lineages for biofilm formation and the development of chronic infections in the gallbladder in our mouse model. Of the lineages tested (L1, L2, L3 and UK), only L2 and UK were defective for the rough, dry and red (RDAR) morphotype, correlating with the known bcsG (cellulose) mutation but not with csgD (curli) gene mutations. Biofilm-forming ability was assessed in vitro, which revealed a biofilm formation hierarchy of L3 > ST19 > UK > L1 = L2, which did not correlate directly with either the bcsG or the csgD mutation. By confocal microscopy, biofilms of L2 and UK had significantly less curli and cellulose, while L1 biofilms had significantly lower cellulose. All iNTS strains were able to colonize the mouse gallbladder, liver, and spleen in a similar manner, while L3 had a significantly higher bacterial load in the gallbladder and increased lethality. While there was iNTS lineage variability in biofilm formation, gallbladder colonization, and virulence in a chronic mouse model, all tested lineages were capable of colonization despite possessing biofilm-related mutations. Thus, iNTS strains may be unrecognized chronic pathogens in endemic settings.

Immunisation used for offensive and defensive purposes during the Second World War.

The best defence against natural or intentional biological agents during armed conflict is usually immunisation, as with typhoid fever, but exceptional circumstances are informative. A large iatrogenic epidemic of hepatitis B occurred in 1942 due to contaminated lots of yellow fever (YF) vaccine used in the US military, even though there was no natural risk of infection. YF vaccine was intended to protect against Japanese Army's use of YF as a biowarfare agent, which did not eventuate. Salmonella typhi was used to infect German soldiers in a Paris café during Christmas 1941 in the knowledge that the café staff but not the soldiers were likely to be immunised against typhoid fever. German Army use of the Weil-Felix reaction to eliminate civilians likely to be typhus infected was subverted by Polish medical officers. They immunised civilians with locally produced Proteus antigens to create false-positive Weil-Felix reactions in order to exempt men from forced labour schemes. Immunisation against biowarfare agents has a mixed record, indicating that vaccines rarely cover well for intelligence gaps.

Validation of the Nelwan Score as a screening tool for the diagnosis of typhoid fever in adults in Indonesia.

INTRODUCTION: Typhoid fever diagnosis is challenging for clinicians in areas with limited laboratory facilities. Scoring methods based on signs and symptoms are useful for screening for probable cases of typhoid fever. The Nelwan Score variables are derived from the clinical signs and symptoms of patients with suspected typhoid. We validated the Nelwan Score compared to laboratory tests as the gold standard. METHODS: This cross-sectional study was conducted between July 2017 and January 2018 in five hospitals and two primary health care centers in Jakarta and Tangerang, Indonesia. Patients with fever for 3-14 days and gastrointestinal symptoms were evaluated using the Nelwan Score. Blood cultures, samples for polymerase chain reaction testing, and additional rectal swab cultures were collected simultaneously to confirm the diagnosis of typhoid. Data were analyzed using a contingency table to measure sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and the optimal cut-off of the Nelwan Score for typhoid diagnosis was determined using a receiver-operating characteristic curve. RESULT: Typhoid was confirmed in 11 of the 233 patients (4.7%) with suspected typhoid. Among laboratory-confirmed typhoid cases, the median Nelwan Score was 11 (range: 9-13) and the optimal cut-off value was 10, with an area under the curve of 71.3%, sensitivity of 81.8%, specificity of 60.8%, PPV of 9.3%, and NPV of 98.5%. CONCLUSION: A Nelwan Score of 10 is the best cut-off value for screening for typhoid fever. It is useful as screening tool for typhoid fever, where laboratory resources are limited, and could help to decrease irrational antibiotic use.

[Epidemiological characteristics of typhoid fever and paratyphoid fever in China, 2004-2020].

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Spatial heterogeneity of socio-economic determinants of typhoid/paratyphoid fever in one province in central China from 2015 to 2019.

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.

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.

Malaria and typhoid fever among patients presenting with febrile illnesses in Ga West Municipality, Ghana.

BACKGROUND: Clinicians in areas where malaria and typhoid fever are co-endemic often treat infected patients irrationally, which may lead to the emergence of drug resistance and extra cost to patients. This study determined the proportion of febrile conditions attributable to either malaria and/or typhoid fever and the susceptibility patterns of Salmonella spp. isolates to commonly used antimicrobial agents in Ghana. METHODS: One hundred and fifty-seven (157) febrile patients attending the Ga West Municipal Hospital, Ghana, from February to May 2017 were sampled. Blood samples were collected for cultivation of pathogenic bacteria and the susceptibility of the Salmonella isolates to antimicrobial agents was performed using the Kirby-Bauer disk diffusion method with antibiotic discs on Müller Hinton agar plates. For each sample, conventional Widal test for the detection of Salmonella spp was done as well as blood film preparation for detection of Plasmodium spp. Data on the socio-demographic and clinical characteristics of the study participants were collected using an android technology software kobo-collect by interview. RESULTS: Of the total number of patients aged 2-37 years (median age = 6 years, IQR 3-11), 82 (52.2%) were females. The proportion of febrile patients with falciparum malaria was 57/157 (36.3%), while Salmonella typhi O and H antigens were detected in 23/157 (14.6%) of the samples. The detection rate of Salmonella spp in febrile patients was 10/157 (6.4%). Malaria and typhoid fever coinfection using Widal test and blood culture was 9 (5.7%) and 3 (1.9%), respectively. The isolates were highly susceptible to cefotaxime, ceftriaxone, ciprofloxacin, and amikacin but resistant to ampicillin, tetracycline, co-trimoxazole, gentamicin, cefuroxime, chloramphenicol, and meropenem. CONCLUSION: Plasmodium falciparum and Salmonella spp coinfections were only up to 1.9%, while malaria and typhoid fever, individually, were responsible for 36.3% and 6.4%, respectively. Treatment of febrile conditions must be based on laboratory findings in order not to expose patients to unnecessary side effects of antibiotics and reduce the emergence and spread of drug resistance against antibiotics.

Immune responses in children after vaccination with a typhoid Vi-tetanus toxoid conjugate vaccine in Bangladesh.

A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection.

Burden of Typhoid and Paratyphoid Fever in India.

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. Salmonella enterica 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.).

Genomic analysis unveils genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages.

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.

Prevalence of Salmonella in Stool During the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. METHODS: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. RESULTS: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites. CONCLUSIONS: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa.

Ceftriaxone resistant Salmonella enterica serovar Paratyphi A identified in a case of enteric fever: first case report from Pakistan.

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.

Tropical infections as occupational diseases among young volunteers in social projects.

PURPOSE: The trend of volunteering overseas has increased tremendously over the last decade. Volunteers often go to regions where they are exposed to the risk of tropical infections like malaria, dengue, typhoid fever and schistosomiasis. Health assessments have shown a high occurrence of tropical infections among young volunteers. Such tropical infections are notifiable in Germany, as they are covered by a separate branch of the social insurance system. However, there is still limited data on systematical improvement of medical prevention and health care for volunteers. METHODS: This retrospective study included 457 cases with a diagnosis for a tropical infection or typhoid fever from January 2016 to December 2019. Data sets were anonymised and then analysed with descriptive statistics first. Cases of volunteers sent abroad by "Weltwärts" were compared to cases of aid workers sent to non-industrial countries. RESULTS: A high occurrence of tropical infections as occupational diseases has been shown for volunteers compared to other (mostly older) aid workers being sent to tropical regions. The risk of acquiring a tropical infection was significantly higher in Africa compared to other tropical regions. Cases of malaria were reported significantly more often among the group of volunteers than among aid workers during the period under review. Medical check-ups after travel were rare among volunteers. CONCLUSIONS: Data imply a disproportionate risk for malaria in Africa with a higher risk of acquiring malaria tropica in Sub-Saharan regions. Region-specific risks need to be addressed in training seminars in order to raise awareness among young volunteers before travel. Medical examinations after travel should be mandatory and specific to a particular region.

Screening of lipid-A related genes and development of low-endotoxicity live-attenuated Salmonella gallinarum by arnT deletion that elicits immune responses and protection against fowl typhoid in chickens.

In the present study, lipid-A gene mutants of Salmonella gallinarum (SG) were screened, and the arnT mutant exhibited optimal acidic and oxidative-stress and macrophage-survival. Modifying lipid-A by arnT-deletion resulted in significantly reduced endotoxicity, virulence, and mortality. Therefore, the arnT-deleted vaccine-candidate strain JOL2841 was constructed and demonstrated to be safe due to appropriate clearance by the chicken immune system. The reduced-endotoxicity of JOL2841 was evident from the downregulation of TNFα and IL-1ß inflammatory cytokines, no inflammatory signs in organ gross-examination, and histopathological analysis. The IgY and IgA antibody titres, CD4, and CD8 T-cell population improvements, and IL-4, IL-2, and INFγ expression decipher the profound Th2 and Th1 immunogenicity. Consequently, JOL2841 exhibited prominent protection against wild-type SG challenge, as revealed by organ pathogen-load determination, organ gross-examination, and histopathological examination. Overall, the study represented the first report of arnT deficient SG resulted in negligible endotoxicity, low-virulence, safety and coordinated elicitation of humoral and cell-mediated immune response in chickens.

Genomic Characterization and Genetic Profiles of Salmonella Gallinarum Strains Isolated from Layers with Fowl Typhoid in Colombia.

Salmonella Gallinarum (SG) is the causative agent of fowl typhoid (FT), a disease that is harmful to the poultry industry. Despite sanitation and prophylactic measures, this pathogen is associated with frequent disease outbreaks in developing countries, causing high morbidity and mortality. We characterized the complete genome sequence of Colombian SG strains and then performed a comparative genome analysis with other SG strains found in different regions worldwide. Eight field strains of SG plus a 9R-derived vaccine were subjected to whole-genome sequencing (WGS) and bioinformatics analysis, and the results were used for subsequent molecular typing; virulome, resistome, and mobilome characterization; and a comparative genome study. We identified 26 chromosome-located resistance genes that mostly encode efflux pumps, and point mutations were found in gyrase genes (gyrA and gyrB), with the gyrB mutation S464T frequently found in the Colombian strains. Moreover, we detected 135 virulence genes, mainly in 15 different Salmonella pathogenicity islands (SPIs). We generated an SPI profile for SG, including C63PI, CS54, ssaD, SPI-1, SPI-2, SPI-3, SPI-4, SPI-5, SPI-6, SPI-9, SPI-10, SPI-11, SPI-12, SPI-13, and SPI-14. Regarding mobile genetic elements, we found the plasmids Col(pHAD28) and IncFII(S) in most of the strains and 13 different prophage sequences, indicating a frequently obtained profile that included the complete phage Gifsy_2 and incomplete phage sequences resembling Escher_500465_2, Shigel_SfIV, Entero_mEp237, and Salmon_SJ46. This study presents, for the first time, the genomic content of Colombian SG strains and a profile of the genetic elements frequently found in SG, which can be further studied to clarify the pathogenicity and evolutionary characteristics of this serotype.

Retrobulbar Optic Neuritis Post Typhoid fever: Atypical Case Report.

Purpose: Post typhoid autoimmune-mediated simultaneous retrobulbar optic neuritis (RBN) involving both eyes is a rare complication requiring early diagnosis and prompt treatment. Case presentation: We present a case of bilateral RBN in a six-year-old male who came to our department with a chief complaint of sudden onset painless profound loss of vision in both eyes, after an episode of high-grade fever 2 weeks earlier. Perception of light was doubtful in right eye (RE) and vision was hand movement in left eye (LE). On ocular examination, anterior segment and fundoscopy of both eye were normal. Blood investigation was normal except for raised ESR. CT of brain and orbit was normal. MRI of brain and orbit revealed bilateral thickening and restriction of optic nerve suggestive of ON. He was initiated with intravenous methyl-prednisolone for three consecutive days after which tapering doses of oral corticosteroid was given. Results: A rapid and marked improvement in Uncorrected Visual Acuity (UCVA) was observed with UCVA improving to 6/ 12 RE and 6/ 9 LE post 1 month. The pupillary reaction also became normal in both eyes. Moreover, there was a significant reduction in the Widal titre of the patient post 2 weeks of treatment. Discussion: Paediatric ON has rare and unique characteristics, which differentiates it from adult ON. No clinical trials have been performed for paediatric ON, so current clinical practice follows the evidence drawn from the Optic Neuritis Treatment Trial (ONTT). Conclusion: Paediatric ON is uncommon. Despite having clinically severe bilateral vision loss, retrobulbar optic neuritis in children post typhoid fever has excellent response to steroid therapy if early diagnosed and treated. Abbreviations: RBN = Retrobulbar Optic Neuritis, MRI = Magnetic Resonance Imaging, CT = Computerized Tomography, UCVA = Uncorrected Visual Acuity, RE = Right eye, LE = Left eye, ON = Optic neuritis, ONTT = Optic Neuritis Treatment Trial.

Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses.

Introduction: Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood. Methods and results: Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV. Discussion: Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.