A novel phospholipase A2 is a core component of the typhoid toxin genetic islet.

Salmonella Typhi, the cause of typhoid fever, is a bacterial pathogen of substantial global importance. Typhoid toxin is a secreted AB-type toxin that is a key S. Typhi virulence factor encoded within a 5-gene genetic islet. Four genes in this islet have well-defined roles in typhoid toxin biology; however, the function of the fifth gene is unknown. Here, we investigate the function of this gene, which we name ttaP. We show that ttaP is cotranscribed with the typhoid toxin subunit cdtB, and we perform genomic analyses that indicate that TtaP is very highly conserved in typhoid toxin islets found in diverse salmonellae. We show that TtaP is a distant homolog of group XIV secreted phospholipase A2 (PLA2) enzymes, and experimentally demonstrate that TtaP is a bona fide PLA2. Sequence and structural analyses indicate that TtaP differs substantially from characterized PLA2s, and thus represents a novel class of PLA2. Secretion assays revealed that TtaP is neither cosecreted with typhoid toxin, nor is it required for toxin secretion. Although TtaP is a phospholipase that remains associated with the S. Typhi cell, assays that probed for altered cell envelope integrity failed to identify any differences between WT S. Typhi and a ttaP deletion strain. Collectively, this study identifies a biochemical activity for the lone uncharacterized typhoid toxin islet gene and lays the groundwork for exploring how this gene factors into S. Typhi pathogenesis. This study further identifies a novel class of PLA2, enzymes that have a wide range of industrial applications.

Environmental Surveillance for Salmonella Typhi and its Association With Typhoid Fever Incidence in India and Malawi.

BACKGROUND: Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever. METHODS: We developed standardized protocols for typhoid ES, including sampling site selection, validation, characterization; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG, and tviB) and a marker of human fecal contamination (HF183). ES was implemented over 12 months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022. RESULTS: S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%; 95% confidence interval [CI], 4.4%-12.4%) vs 11/533 (2.1%; 95% CI, 1.1%-4.0%) in grab and 79/517 (15.3%; 95% CI, 9.8%-23.0%) vs 23/594 (3.9%; 95% CI, 1.9%-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES. CONCLUSIONS: ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility.

Detecting Residual Chronic Salmonella Typhi Carriers on the Road to Typhoid Elimination in Santiago, Chile, 2017-2019.

BACKGROUND: In Santiago, Chile, where typhoid had been hyperendemic (1977-1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring during 2017-2019. METHODS: Culture-confirmed cases were classified as autochthonous (domestically acquired) versus travel/immigration related. Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers. Whole genome sequences of acute cases and their epidemiologically linked chronic carrier isolates were compared. RESULTS: Five of 16 autochthonous typhoid cases (31.3%) were linked to 4 chronic carriers in case households; 2 cases (onsets 23 months apart) were linked to the same carrier. Carriers were women aged 69-79 years with gallbladder dysfunction and Typhi fecal excretion; 3 had highly elevated serum anti-Vi titers. Genomic analyses revealed close identity (≤11 core genome single-nucleotide polymorphism [SNP] differences) between case and epidemiologically linked carrier isolates; all were genotypes prevalent in 1980s Santiago. A cluster of 4 additional autochthonous cases unlinked to a carrier was identified based on genomic identity (0-1 SNPs). Travel/immigration isolate genotypes were typical for the countries of travel/immigration. CONCLUSIONS: Although autochthonous typhoid cases in Santiago are currently rare, 5 of 16 such cases (31.3%) were linked to elderly chronic carriers identified among household contacts of cases.

Malaria and typhoid fever co-infection: a retrospective analysis of University Hospital records in Nigeria.

BACKGROUND: Studies have long documented the presence of malaria and typhoid fever in sub-Saharan Africa (SSA). However, studies on these diseases have primarily concentrated on rural settings, neglecting the potential impact on urban areas. This knowledge gap hinders effective surveillance and intervention strategies. To bridge this gap, this study investigated the prevalence of malaria and typhoid co-infections in an urban environment. METHODS: This study, conducted at Lead City University Hospital in Ibadan, Nigeria (West Africa's largest metropolis), analysed medical records of over 3195 patients seen between April and June 2023. Descriptive statistics and chi-square tests were used to understand how these co-infections were distributed across different age and gender groups. RESULTS: The prevalence of co-infection peaked in May (9.7%), followed by June (8.9%) and April (5.7%). Notably, children aged 6-12 years exhibited the highest co-infection rate (18.5%), while those under five had the lowest (6.3%). Gender analysis indicated a slight difference, with 8.8% of females and 7.1% of males co-infected. Malaria prevalence was highest at the beginning of the rainy season and significantly decreased over time. Conversely, typhoid fever displayed the opposite trend, increasing with the rainy season. Children under five years old were most susceptible to malaria, while typhoid fever predominantly affected adults over 25 years old, with prevalence decreasing significantly with age. CONCLUSION: This study sheds light on the previously overlooked risk of malaria and typhoid co-infections in urban settings. These findings highlight the need for enhanced surveillance and targeted public health interventions, particularly for vulnerable groups like young children during peak transmission seasons.

Prevalence of Salmonella Typhi, its associated factors and antimicrobial susceptibility profile among patients attending Hawassa University Comprehensive Specialized Hospital, Hawassa, Ethiopia.

INTRODUCTION: Salmonella Typhi infections cause significant morbidity and mortality worldwide, especially in developing countries including Ethiopia. This study aimed to determine the prevalence of Salmonella Typhi, its associated factors and antibiotic susceptibility profile among suspected typhoid patients. METHODS: A cross-sectional study was conducted on 270 typhoid fever suspected patients at Hawassa University Comprehensive Specialized Hospital from June 2022 to September 2022. Data were collected using questionnaires by face-to-face interview. Stool samples for microbiological culture, blood samples for S. Typhi IgM/Entero-check WB rapid test and isolates for antimicrobial susceptibility tests were used through standard procedures and according to the reagents manufactures' instructions. Hygiene implementation of patients was also assessed using interview. Sociodemographic and clinical characteristics of the patient's were considered. Descriptive statistics were used to summarize the data, and logistic regression model analysis was performed to assess associations between S. Typhi infection and the associated sociodemographic and clinical factors. RESULTS: The prevalence of S. Typhi IgM/Entero-check WB rapid test and stool culture results were 3.3%; (95% CI: 1.5-5.6) and 3.7%; (95% CI: 1.9-6.3) respectively. Not washing hands after latrine [AOR = 0.85, 95% CI (0.15-4.79), p = 0.05] is not significant but, not washing hands before meal [AOR = 0.053, 95% CI (0.08-0.36), p = 0.03], eating raw vegetables [AOR = 0.024, 95% CI (0.001-0.48), p = 0.015] and drinking water from a stream [AOR = 0.12, 95% CI (0.19-0.70), p = 0.001] were significantly associated with S. Typhi infection, but in terms of AOR, all are preventive. Susceptibility of isolates was 9/10 (90%), 8/10 (80%), and 8/10 (80%) to ciprofloxacin, ceftriaxone, and chloramphenicol, respectively. The majorities 100% and 80% of the isolates were resistant to ampicillin and cotrimoxazole, respectively. About 40% of the isolates were MDR. CONCLUSION: The prevalence of Salmonella Typhi with MDR has been observed. Therefore, health programmers and stakeholders should make efforts to improve the habit of sanitation, strengthen the capacity of laboratory diagnostic methods and increase awareness of the misprescription and misuse of antibiotics to reduce the impact of MDR bacteria.

Large outbreak of typhoid fever on a river cruise ship used as accommodation for asylum seekers, the Netherlands, 2022.

On 6 April 2022, the Public Health Service of Kennemerland, the Netherlands, was notified about an outbreak of fever and abdominal complaints on a retired river cruise ship, used as shelter for asylum seekers. The diagnosis typhoid fever was confirmed on 7 April. An extensive outbreak investigation was performed. Within 47 days, 72 typhoid fever cases were identified among asylum seekers (n = 52) and staff (n = 20), of which 25 were hospitalised. All recovered after treatment. Consumption of food and tap water on the ship was associated with developing typhoid fever. The freshwater and wastewater tanks shared a common wall with severe corrosion and perforations, enabling wastewater to leak into the freshwater tank at high filling levels. Salmonella Typhi was cultured from the wastewater tank, matching the patient isolates. In the freshwater tank, Salmonella species DNA was detected by PCR, suggesting the presence of the bacterium and supporting the conclusion of contaminated freshwater as the probable source of the outbreak. Outbreaks of uncommon infections may occur if persons from endemic countries are accommodated in crowded conditions. Especially when accommodating migrants on ships, strict supervision on water quality and technical installations are indispensable to guarantee the health and safety of the residents.

Typhoid Fever Presenting with Ileal Perforation and Gastric Perforation.

Typhoid fever is caused by Salmonella typhi and Salmonella paratyphi. It is a disease of developing countries and is seen among people of low socio-economic status. Patients can develop complications like typhoid intestinal perforation which is associated with higher mortality. A 15-year-old female presented to the emergency pediatric unit with fever, abdominal pain and abdominal distension. She was septic, in respiratory distress, and had marked generalized abdominal tenderness with guarding. An assessment of generalized peritonitis secondary to typhoid intestinal perforation was made. She had exploratory laparotomy with intra-operative findings of ileal perforation and gastric perforation. She had repair of the intestinal and gastric perforations. Our patient presented late with concurrent use of NSAIDs and overwhelming sepsis which likely contributed to the gastric perforation as this is not a usual finding in patients with typhoid intestinal perforation. Gastric perforation is an unusual finding in patients with typhoid intestinal perforation. Typhoid fever and its complications can be easily prevented by the provision of safe water, proper facilities for sanitation, and practicing good hygiene.

La fièvre typhoïde est causée par Salmonella typhi et Salmonella paratyphi. C'est une maladie des pays en développement et elle est observée chez les personnes de bas niveau socio-économique. Les patients peuvent développer des complications telles que la perforation intestinale typhoïdique, associée à une mortalité plus élevée. Une adolescente de 15 ans s'est présentée à l'unité de pédiatrie d'urgence avec de la fièvre, des douleurs abdominales et une distension abdominale. Elle était septique, en détresse respiratoire, et présentait une sensibilité abdominale généralisée marquée avec une défense. Une évaluation d'une péritonite généralisée secondaire à une perforation intestinale typhoïdique a été réalisée. Elle a subi une laparotomie exploratrice révélant une perforation iléale et une perforation gastrique. Des réparations ont été effectuées sur les perforations intestinales et gastriques. Notre patiente s'est présentée tardivement avec une utilisation concomitante d'AINS et une septicémie sévère, ce qui a probablement contribué à la perforation gastrique, car cela n'est pas une découverte habituelle chez les patients atteints de perforation intestinale typhoïdique. La perforation gastrique est une découverte inhabituelle chez les patients atteints de perforation intestinale typhoïdique. La fièvre typhoïde et ses complications peuvent être facilement prévenues par la fourniture d'eau potable, d'installations sanitaires adéquates et en pratiquant une bonne hygiène MOTS-CLÉS: fièvre typhoïde, perforation intestinale, perforation gastrique.

Extensively drug-resistant Salmonella typhi Infection in Adults; Experience from A Tertiary Care Hospital.

Objectives: This study aimed to determine the epidemiology, clinical features, and complications of extensively drug-resistant Salmonella typhi (XDR S. typhi) infection in adults. Method: This cross-sectional study enrolled adults with culture-proven XDR S. typhi admitted to Hayatabad Medical Complex, Peshawar from 1st March to 10th September 2022. Their demographic characteristics, clinical features, treatment, and complications were recorded. Results: Out of 84 patients, 68 (80.9%) were male. The mean age of enrolled patients was 25.2 ± 11.3 years. The mean duration of fever at the time of admission was 13.6 ± 8.2 days, respectively. The most common symptom was loose stools (n=25, 29.8%). Most of the patients (n=69, 82.1%) had received empirical treatment before hospitalization. The majority of the patients (n=42, 50%) received meropenem and a combination of meropenem and azithromycin (n=35, 41.7%) during the study. The time to defervescence for both regimens was similar. Five patients (6%) developed complications of enteric fever. There was no mortality among the participants. Conclusions: Diarrhea was the most common associated clinical feature in XDR typhoid fever. Most of the patients received meropenem alone or in combination with azithromycin with a comparable time to defervescence. The majority of the patients recovered uneventfully and there was no mortality among the study participants.

Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India.

BACKGROUND: The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level. METHODS: We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression. RESULTS: Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities. CONCLUSIONS: Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.

Case of Carbapenem-Resistant Salmonella Typhi Infection, Pakistan, 2022.

Salmonella Typhi infection in a patient in Pakistan initially responded to standard treatment but failed to respond to subsequent treatment. The first strain was susceptible to carbapenems and azithromycin; subsequent strains harbored the NDM-5 gene. Treatment with a combination of intravenous meropenem and colistin was successful. Carbapenem-resistant Salmonella Typhi emergence will hinder treatment.

Cost-effectiveness analysis of typhoid conjugate vaccines in an outbreak setting: a modeling study.

BACKGROUND: Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks. METHODOLOGY: We developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak. RESULTS: Assuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred. CONCLUSIONS: Countries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy.

Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda.

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

Associations of water, sanitation, and hygiene with typhoid fever in case-control studies: a systematic review and meta-analysis.

BACKGROUND: Water, sanitation, and hygiene (WASH) play a pivotal role in controlling typhoid fever, as it is primarily transmitted through oral-fecal pathways. Given our constrained resources, staying current with the most recent research is crucial. This ensures we remain informed about practical insights regarding effective typhoid fever control strategies across various WASH components. We conducted a systematic review and meta-analysis of case-control studies to estimate the associations of water, sanitation, and hygiene exposures with typhoid fever. METHODS: We updated the previous review conducted by Brockett et al. We included new findings published between June 2018 and October 2022 in Web of Science, Embase, and PubMed. We used the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for risk of bias (ROB) assessment. We classified WASH exposures according to the classification provided by the WHO/UNICEF Joint Monitoring Programme for Water Supply, Sanitation, and Hygiene (JMP) update in 2015. We conducted the meta-analyses by only including studies that did not have a critical ROB in both Bayesian and frequentist random-effects models. RESULTS: We identified 8 new studies and analyzed 27 studies in total. Our analyses showed that while the general insights on the protective (or harmful) impact of improved (or unimproved) WASH remain the same, the pooled estimates of OR differed. Pooled estimates of limited hygiene (OR = 2.26, 95% CrI: 1.38 to 3.64), untreated water (OR = 1.96, 95% CrI: 1.28 to 3.27) and surface water (OR = 2.14, 95% CrI: 1.03 to 4.06) showed 3% increase, 18% decrease, and 16% increase, respectively, from the existing estimates. On the other hand, improved WASH reduced the odds of typhoid fever with pooled estimates for improved water source (OR = 0.54, 95% CrI: 0.31 to 1.08), basic hygiene (OR = 0.6, 95% CrI: 0.38 to 0.97) and treated water (OR = 0.54, 95% CrI: 0.36 to 0.8) showing 26% decrease, 15% increase, and 8% decrease, respectively, from the existing estimates. CONCLUSIONS: The updated pooled estimates of ORs for the association of WASH with typhoid fever showed clear changes from the existing estimates. Our study affirms that relatively low-cost WASH strategies such as basic hygiene or water treatment can be an effective tool to provide protection against typhoid fever in addition to other resource-intensive ways to improve WASH. TRIAL REGISTRATION: PROSPERO 2021 CRD42021271881.

Deciphering Target Protein Cascade in Salmonella typhi Biofilm using Genomic Data Mining, and Protein-protein Interaction.

Background: Salmonella typhi biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the S. typhi outbreak has turned into a fatal disease typhoid. S. typhi infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of S. typhi. Objective: The study aimed to identify a cascade of target proteins in S. typhi biofilm condition with the help of genomic data mining and protein-protein interaction analysis. Methods: The goal of this study was to notice some important pharmacological targets in S. typhi. using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease. Results: In this study, we identified 15 potential target proteins that are critical for S. typhi biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of S. typhi. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence. Conclusion: All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in S. typhi is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.

Recent advances in the diagnosis and management of typhoid fever in Africa: A review.

Typhoid fever, a classical disease of enteric origin caused by Salmonella species of bacteria, is among the most important diseases threatening public health in Africa. The African continent is a marker for both low resources within the healthcare system and poor disease control policy formulations in managing endemic infectious diseases. Since the colonial era, the Widal serological test has been used to confirm typhoid fever in Africa, however recent studies recommend blood culture, and when blood culture cannot be obtained, clinical findings, laboratory Widal test confirmation, and ruling out other febrile illnesses as confirmatory pathway to diagnose typhoid fever in Africa. Managing typhoid fever relies on antimicrobials. In 1980s chloramphenicol was the medication of choice. Years later, amoxicillin and co-trimoxazole were adopted. However, the instantaneous rise of resistant strains of Salmonella enterica confers an important challenge to treat the burdensome enteric fever. The current treatment algorithm of typhoid fever in Africa relies significantly on the use of fluoroquinolones, macrolides, and cephalosporins. Developed nations have successfully addressed and controlled typhoid fever via improvement in accessing safe water and food, better sanitary and hygienic behaviours, and vaccines development. Nevertheless, there is significant evidence to infer improvement in the diagnosis management of typhoid fever over the last few decades, and efforts are underway to control the disease spread in Africa. This review aims to provide an overview of the latest developments in typhoid fever diagnosis and management in Africa and provide key recommendations for a coordinated approach to mitigate typhoid in the continent.

Pan Drug-Resistant Salmonella Serovar Typhi Septicaemia In A Child: A Case Report.

Typhoid fever, caused by Salmonella enterica serovar Typhi, is a common cause of febrile illness, especially in lower middle-income countries. The only known reservoirs of this infection are humans, and it is prevalent in areas with limited availability of clean drinking water and sanitary conditions. Lately, extensively drug-resistant Salmonella ser. Typhi (XDR S. Typhi) has emerged as one of Pakistan's most challenging public health concerns. Here, we report a case of relapsed typhoid fever in a child, in whom the isolate was found to be resistant to meropenem and azithromycin.

Complicated multi-drug resistant typhoid fever with cerebral oedema, diffuse encephalitis and fungal infection of the oral cavity: A case report.

Enteric fever is a highly fatal infectious disease that can present with extensive symptoms that renders diagnosis quite risky. Multi-drug resistant Salmonella typhi infection has become endemic in third world countries and has been routinely associated with catastrophic complications and even death, with diagnostic and therapeutic impedance. Typhoid fever is known to cause life-threatening cerebral complications. We report the case of a 16-year-old male who presented to us with a high-grade fever, watery diarrhoea, altered level of consciousness, and a mixed dark-coloured crusted oral lesion. Blood workup showed neutropenia, lymphocytopenia, thrombocytopenia, transaminitis, and hyponatraemia. Blood culture grew multi-drug resistant Salmonella Typhi. CT scan of the brain showed diffuse cerebral oedema, while EEG was consistent with the diagnosis of diffuse encephalitis. The patient responded well to culture-sensitive antibiotics, while the oral lesion showed a dramatic response to presumptive antifungal treatment. We discuss the compositions available to date on typhoid-associated encephalitis and the connection of fungal infection in this specific case attempting to promote awareness regarding possible unorthodox presentations of enteric fever.

Extensively drug-resistant typhoid fever; it's not that simple: a case report.

Multi-drug resistant strains of Salmonella typhi (S. typhi) has remained endemic in developing countries for the last two decades. With irrational use of antibiotics, an extensively drug-resistant (XDR) strain of S. typhi, sensitive only to Carbapenems and Azithromycin, has evolved which was first reported in Sindh, Pakistan, in 2018. Most of the cases of XDR S. typhi infection treated with antibiotics improve without any complications. Failure to respond to appropriate antibiotics should raise the suspicion of visceral abscesses. Splenic abscess is a rare complication of S. typhi infection. A patient with splenic abscess due to XDR S. typhi has been reported who responded to prolonged antibiotic treatment. We report the case of a young boy from Peshawar with multiple splenic abscesses due to XDR S. typhi which did not respond to percutaneous aspiration and culture-guided antibiotics for two weeks. Eventually, he had to undergo splenectomy. He has remained afebrile since then.

Utilization Of The Complete Blood Count In Diagnosing Endemic Diseases In Pakistan.

Numerous infectious diseases, including enteric fever, malaria, dengue fever, and, most recently, coronavirus disease-2019, are prevalent in Pakistan. All these diseases have overlapping clinical symptoms and can present a diagnostic challenge for the general practitioner. Since definitive testing for these disorders is time-consuming and expensive, basic clinical testing, such as a complete blood count, should be utilised to supplement clinical diagnosis, when possible. The current narrative review was planned to present specific alterations in haematological parameters for each of these disorders. The review was intended as a guide for practising physicians in their decision-making.

Neutralization of Typhoid Toxin by Alpaca-Derived, Single-Domain Antibodies Targeting the PltB and CdtB Subunits.

Typhoid toxin is secreted by the typhoid fever-causing bacterial pathogen Salmonella enterica serovar Typhi and has tropism for immune cells and brain endothelial cells. Here, we generated a camelid single-domain antibody (VHH) library from typhoid toxoid-immunized alpacas and identified 41 VHHs selected on the glycan receptor-binding PltB and nuclease CdtB. VHHs exhibiting potent in vitro neutralizing activities from each sequence-based family were epitope binned via competition enzyme-linked immunosorbent assays (ELISAs), leading to 6 distinct VHHs, 2 anti-PltBs (T2E7 and T2G9), and 4 anti-CdtB VHHs (T4C4, T4C12, T4E5, and T4E8), whose in vivo neutralizing activities and associated toxin-neutralizing mechanisms were investigated. We found that T2E7, T2G9, and T4E5 effectively neutralized typhoid toxin in vivo, as demonstrated by 100% survival of mice administered a lethal dose of typhoid toxin and with little to no typhoid toxin-mediated upper motor function defect. Cumulatively, these results highlight the potential of the compact antibodies to neutralize typhoid toxin by targeting the glycan-binding and/or nuclease subunits.