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Despite advancements in military medical treatment and evacuation, soldiers in austere environments remain vulnerable to disease and non-battle injury and may face prolonged evacuation before receiving definitive care. In particular, arranging care for a soldier presenting with a conditions that has a wide differential diagnosis, such as acute altered mental status (AMS), can be especially challenging. We highlight the case of an otherwise young, healthy U.S. Soldier serving in Indonesia, who presented with acute AMS concerning for undifferentiated infection. Subsequent workup at the receiving hospital following evacuation revealed Salmonella enterica infection, more commonly known as typhoid. However, even with clinical findings of typhoid encephalitis and initiation of empiric treatment, medical care proved challenging in the resource-limited local facilities, despite multiple escalations of care. Ultimately, the patient was evacuated to a tertiary facility in Singapore, where his condition improved, and 4 days after initial presentation the patient had no definitive findings of infections on lumbar puncture. This case not only highlights the threat of typhoid and other infectious diseases in modern operations but also the challenges of suboptimal medical care in both the prehospital and hospital settings when utilizing host nation facilities., Competing Interests: None, (2024.)

Background: Salmonella enterica serotype Typhi is one of the major pathogens causing typhoid fever and a public health burden worldwide. Recently, the increasing number of multidrug-resistant strains of Salmonella spp. has made this utmost necessary to consider bacteriophages as a potential alternative to antibiotics for S. Typhi infection treatment. Salmonella phage STWB21, isolated from environmental water, has earlier been reported to be effective as a safe biocontrol agent by our group. In this study, we evaluated the efficacy of phage STWB21 in reducing the burden of salmonellosis in a mammalian host by inhibiting Salmonella Typhi invasion into the liver and spleen tissue., Results: Phage treatment significantly improved the survival percentage of infected mice. This study also demonstrated that oral administration of phage treatment could be beneficial in both preventive and therapeutic treatment of salmonellosis caused by S. Typhi. Altogether the result showed that the phage treatment could control tissue inflammation in mice before and after Salmonella infection., Conclusions: To the best of our knowledge, this is the first report of phage therapy in a mouse model against a clinically isolated Salmonella Typhi strain that includes direct visualization of histopathology and ultrathin section microscopy images from the liver and spleen sections., (© 2023. The Author(s).)

Salmonella is a gram-negative, motile, nonsporulating, facultative anaerobic bacillus, belongs to the family Enterobacteriaceae. The bacteria were first identified in 1884. It is transmitted through direct contact with an infected person or indirect contact by the consumption of contaminated food and water. More than 2500 serotypes of Salmonella enterica have been identified but less than 100 serotypes are known to cause infections in humans. S. enterica serovar typhi (S. typhi) and S. enterica serovar paratyphi (S. paratyphi A B C) cause enteric fever, whereas nontyphoidal Salmonella serotypes (NTS) cause diarrhea. NTS commonly presents with gastroenteritis and is a self-limiting disease. Enteric fever is a potentially life-threatening acute febrile systemic infection and is diagnosed by isolating a pathogen on culture. With the emergence of the extensive drug-resistant (XDR) S. typhi clone, limited treatment options are available. Vaccination of persons at risk, improvement of sanitation, promotion of food hygiene, and detection and control of chronic carriers are essential preventive control measures of enteric fever., Competing Interests: Disclosure The authors have no conflict of interest, nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction. Enteric fever (caused by Salmonella enterica serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics. Gap Statement. Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns. Aim. By characterising factors associated with antimicrobial resistance in cases of S . Typhi and S . Paratyphi imported to England, we aim to guide effective empirical treatment. Methodology. All English isolates of S . Typhi and S . Paratyphi 2014-2019 underwent antimicrobial susceptibility testing; results were compared to a previous survey in London 2005-2012. Risk factors for antimicrobial resistance were analysed with logistic regression models to predict adjusted odds ratios (aOR) for resistance to individual antibiotics and multi-drug resistance. Results. We identified 1088 cases of S . Typhi, 729  S . Paratyphi A, 93  S . Paratyphi B, and one S . Paratyphi C. In total, 93 % were imported. Overall, 90 % of S . Typhi and 97 % of S . Paratyphi A isolates were resistant to ciprofloxacin; 26 % of S . Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of S . Typhi showed an extended drug resistance (XDR) phenotype of MDR+FQ plus resistance to third-generation cephalosporins, with cases of XDR rising sharply in recent years (none before 2017, one in 2017, six in 2018, 32 in 2019). For S . Typhi isolates, resistance to ciprofloxacin was associated with travel to Pakistan (aOR=32.0, 95 % CI: 15.4-66.4), India (aOR=21.8, 95 % CI: 11.6-41.2), and Bangladesh (aOR=6.2, 95 % CI: 2.8-13.6) compared to travel elsewhere, after adjusting for rising prevalence of resistance over time. MDR+FQ resistance in S . Typhi isolates was associated with travel to Pakistan (aOR=3.5, 95 % CI: 2.4-5.2) and less likely with travel to India (aOR=0.07, 95 % CI 0.04-0.15) compared to travel elsewhere. All XDR cases were imported from Pakistan. No isolate was resistant to azithromycin. Comparison with the 2005-2012 London survey indicates substantial increases in the prevalence of resistance of S . Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79-98 %) and Africa (from 12-60 %). Conclusion. Third-generation cephalosporins and azithromycin remain appropriate choices for empirical treatment of enteric fever in most returning travellers to the UK from endemic countries, except from Pakistan, where XDR represents a significant risk.

The incidence of extraintestinal infection caused by Salmonella spp has been increased during the past decade. Here we report a case of a parotid abscess caused by Salmonella enterica subspecies enterica serotype Typhi ( S Typhi) in an individual without any significant abnormality of the parotid gland. A 68-year-old man presented to the surgical department with high-grade intermittent fever associated with painful swelling over the right side of the face, extending into the neck. An ultrasound of the neck revealed an abscess of the right parotid gland. S Typhi was isolated from the pus drained from the parotid gland. The patient was treated with intravenous followed by oral cephalosporin for a period of 7 days. This case gives an insight into one of the rarer aetiological agents causing parotid abscess., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The burden of diarrheal diseases is very high, accounting for 1.7 to 5 billion cases per year worldwide. Typhoid fever (TF) and cholera are potentially life-threatening infectious diseases, and are mainly transmitted through the consumption of food, drink or water that have been contaminated by the feces or urine of subjects excreting the pathogen. TF is mainly caused by Salmonella typhi, whereas cholera is caused by intestinal infection by the toxin-producing bacterium Vibrio cholerae. These diseases typically affect low- and middle-income countries where housing is overcrowded and water and sanitation are poor, or where conflicts or natural disasters have led to the collapse of the water, sanitation and healthcare systems. Mortality is higher in children under 5 years of age. Regarding their geographical distribution, TF has a high incidence in sub-Saharan Africa, India and south-east Asia, while cholera has a high incidence in a few African countries, particularly in the Horn of Africa and the Arabian Peninsula. In the fight against these diseases, preventive measures are fundamental. With modern air travel, transmissible diseases can spread across continents and oceans in a few days, constituting a threat to global public health. Nowadays, people travel for many reasons, such as tourism and business. Several surveys have shown that a high proportion of travelers lack adequate information on safety issues, such as timely vaccination and prophylactic medications. The main objective of this overview is to provide information to help European travelers to stay healthy while abroad, and thus also to reduce the potential importation of these diseases and their consequent implications for public health and society. The preventive measures to be implemented in the case of travel to countries where these diseases are still endemic are well known: the adoption of safe practices and vaccinations. It is important to stress that an effective preventive strategy should be based both on vaccinations and on hygiene travel guidelines. Furthermore, the emergence of multidrug-resistant strains is becoming a serious problem in the clinical treatment of these diseases. For this reason, vaccination is the main solution., (©2019 Pacini Editore SRL, Pisa, Italy.)

Typhoidal Salmonella is a major global problem affecting more than 12 million people annually. Controlled human infection models (CHIMs) in high-resource settings have had an important role in accelerating the development of conjugate vaccines against Salmonella Typhi.The typhoidal Salmonella model has an established safety profile in over 2000 volunteers in high-income settings, and trial protocols, with modification, could be readily transferred to new study sites. To date, a typhoidal Salmonella CHIM has not been conducted in a low-resource setting, although it is being considered.Our article describes the challenges posed by a typhoidal Salmonella CHIM in the high-resource setting of Oxford and explores considerations for an endemic setting.Development of CHIMs in endemic settings is scientifically justifiable as it remains unclear whether findings from challenge studies performed in high-resource non-endemic settings can be extrapolated to endemic settings, where the burden of invasive Salmonella is highest. Volunteers are likely to differ across a range of important variables such as previous Salmonella exposure, diet, intestinal microbiota, and genetic profile. CHIMs in endemic settings arguably are ethically justifiable as affected communities are more likely to gain benefit from the study. Local training and research capacity may be bolstered.Safety was of primary importance in the Oxford model. Risk of harm to the individual was mitigated by careful inclusion and exclusion criteria; close monitoring with online diary and daily visits; 24/7 on-call staffing; and access to appropriate hospital facilities with capacity for in-patient admission. Risk of harm to the community was mitigated by exclusion of participants with contact with vulnerable persons; stringent hygiene and sanitation precautions; and demonstration of clearance of Salmonella infection from stool following antibiotic treatment.Safety measures should be more stringent in settings where health systems, transport networks, and sanitation are less robust.We compare the following issues between high- and low-resource settings: scientific justification, risk of harm to the individual and community, benefits to the individual and community, participant understanding, compensation, and regulatory requirements.We conclude that, with careful consideration of country-specific ethical and practical issues, a typhoidal Salmonella CHIM in an endemic setting is possible.

CME: Typhoid Fever - Clinical Manifestation, Diagnosis, Therapy and Prevention Abstract. Thypoid fever is rare in Western countries. It is, however, among the most common etiologies for febrile illness in the traveller returning from tropical areas (especially South(east) Asia and Sub-Saharan Africa). There are several signs that have been described as classical findings in typhoid fever: i) febrile temperatures with relative bradycardia, ii) eosinopenia, iii) slow defervescence, and iv) systemic manifestations (e.g. hepatitis). Diagnosis is confirmed by positive blood cultures. Pretravel vaccination and safe food and water practices can prevent typhoid fever.

Background: Despite their potential, there is limited uptake of formal qualitative methods in model development by modellers and health economists. The aim of this case study was to highlight in a real-world context how a qualitative approach has been applied to gain insight into current practice (delineating existing care pathways) for typhoid fever in Ghana, which can then assist in model structure conceptualisation in a model-based cost-effectiveness analysis., Methods: The perspectives of a range of healthcare professionals working in different settings and across different practices in the Eastern region of Ghana were captured with a self-administered survey using open-ended questions and analysed using the framework method., Results: A total of 51 completed questionnaires were retrieved representing a 73% response rate. It was found that two main care pathways for typhoid fever exist in Ghana and there was no consensus on how a new test might be applied to the existing pathways., Conclusion: The two settings in Ghana have different care pathways and any cost-effectiveness analysis should consider the alternative pathways separately. This study demonstrated that framework analysis is a qualitative methodology that is likely to be accessible and feasible across a wide range of health economic settings.

Typhoid fever is a systemic infection caused by Salmonella Typhi and occurs predominantly in association with poor sanitation and lack of clean drinking water. Despite recent progress in water and sanitation coverage, the disease remains a substantial public health problem in many developing countries. A mathematical model for the spread of typhoid has been formulated using non linear ordinary differential equations. The model includes a special treatment function to assess the effects of limited treatment resources on the spread of typhoid. It is shown that the model has multiple equilibria and using the center manifold theory, the model exhibits the phenomenon of backward bifurcation whose implications are discussed. The results suggest the need for comprehensive and accessible treatment facilities to curtail typhoid infection.

Extra-intestinal complications of Salmonella Typhi (S. Typhi) infections usually occur in endemic countries and in patients with underlying risk conditions. A 14-year-old immunocompetent girl was admitted with respiratory distress owing to S. Typhi pneumonia and pleural empyema. She was a native of Ivory Coast but had lived in France for 4 years and had not travelled abroad for several years. There were no gastro-intestinal symptoms and no S. Typhi carriage was detected in her family. She recovered completely with ceftriaxone and ciprofloxacin and pleural drainage was not required. An atypical presentation of S. Typhi should be considered even in settings where there are no risk factors.

Recently, a Salmonella Typhi isolate producing CTX-M-15 extended spectrum β-lactamase (ESBL) and with decreased ciprofloxacin susceptibility was isolated in the Democratic Republic of the Congo. We have selected bacteriophages that show strong lytic activity against this isolate and have potential for phage-based treatment of S . Typhi, and Salmonella in general., Competing Interests: The authors declare no conflict of interest.

Background: Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP., Methods: We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding., Results: Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (OR adj  = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (OR adj  = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (OR adj  = 9.0, 95%CI = 1.1-78)., Conclusion: Delay in seeking treatment increased the risk of TIPs. For future outbreaks, we recommended aggressive community case-finding, and informational campaigns in affected communities and among local healthcare providers to increase awareness of the need for early and appropriate treatment.

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S . Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S . Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S . Typhi strains would be key for effective therapeutic management and cancer prevention., Competing Interests: The authors declare no conflict of interest.

Enteric fever is an important public-health problem in India. The clinical presentation of typhoid fever is very variable, ranging from fever with little other morbidities to marked toxemia and associated multisystem complications. Fever is present in majority of patients (>90 %) irrespective of their age group. Mortality is higher in younger children. Blood culture remains gold standard for diagnosis. Widal test has low sensitivity and specificity but may be used in second week to support the diagnosis. Emerging resistance to several antibiotics should be kept in mind when selecting antibiotics or revising the treatment. The key preventive strategies are safe water, safe food, personal hygiene, and appropriate sanitation. Vaccination is an additional effective tool for prevention.

Typhoid toxin is a unique A 2 B 5 exotoxin and an important virulence factor for Salmonella Typhi, the cause of typhoid fever. In the decade since its initial discovery, great strides have been made in deciphering the unusual biological program of this toxin, which is fundamentally different from related toxins in many ways. Purified typhoid toxin administered to laboratory animals causes many of the symptoms of typhoid fever, suggesting that typhoid toxin is a central factor in this disease. Further advances in understanding the biology of this toxin will help guide the development of badly needed diagnostics and therapeutic interventions that target this toxin to detect, prevent or treat typhoid fever., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The burden of typhoid fever (TF) in sub-Saharan Africa is largely unknown but is increasingly thought to be high, given that water and sanitary conditions remain unimproved in many countries. To address this gap in information, the Typhoid Fever Surveillance in Africa Program (TSAP) founded a surveillance system for TF in 10 African countries. This study was a component of the TSAP surveillance project in Madagascar., Methods: The study entailed a qualitative assessment of patients' experiences and perceptions of services for febrile symptoms at the studies' rural and urban sentinel public health clinics. The study examined influences on the use of these facilities, alternative sources of care, and providers' descriptions of medical consultations and challenges in providing services. Data were collected through semistructured and open-ended individual interviews and a focus group with patients, caregivers, and medical personnel., Results: Thirty-three patients and 12 healthcare providers participated in the data collection across the 2 healthcare facilities. The quality of services, cost, and travel distance were key factors that enabled access to and use of these clinics. Divergent healthcare-seeking patterns were related to variability in the care utilized, socioeconomic status, and potential distance from the facilities : These factors influenced delivery of care, patient access, and the health facilities' capacity to identify cases of febrile illness such as TF., Conclusions: This approach provided an in-depth investigation and understanding of healthcare-seeking behavior at the study facilities, and factors that facilitated or acted as barriers to their use. Our findings demonstrate the relevance of these public health clinics as sites for the surveillance of TF in their role as central healthcare sources for families and communities within these rural and urban areas of Madagascar., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Assessing healthcare utilization is important to identify weaknesses of healthcare systems, to outline action points for preventive measures and interventions, and to more accurately estimate the disease burden in a population., Methods: A healthcare utilization survey was developed for the Typhoid Fever Surveillance in Africa Program (TSAP) to adjust incidences of salmonellosis determined through passive, healthcare facility-based surveillance. This cross-sectional survey was conducted at 11 sites in 9 sub-Saharan African countries. Demographic data and healthcare-seeking behavior were assessed at selected households. Overall and age-stratified percentages of each study population that sought healthcare at a TSAP healthcare facility and elsewhere were determined., Results: Overall, 88% (1007/1145) and 81% (1811/2238) of the population in Polesgo and Nioko 2, Burkina Faso, respectively, and 63% (1636/2590) in Butajira, Ethiopia, sought healthcare for fever at any TSAP healthcare facility. A far smaller proportion-namely, 20%-45% of the population in Bissau, Guinea-Bissau (1743/3885), Pikine, Senegal (1473/4659), Wad-Medani, Sudan (861/3169), and Pietermaritzburg, South Africa (667/2819); 18% (483/2622) and 9% (197/2293) in Imerintsiatosika and Isotry, Madagascar, respectively; and 4% (127/3089) in Moshi, Tanzania-sought healthcare at a TSAP healthcare facility. Patients with fever preferred to visit pharmacies in Imerintsiatosika and Isotry, and favored self-management of fever in Moshi. Age-dependent differences in healthcare utilization were also observed within and across sites., Conclusions: Healthcare utilization for fever varied greatly across sites, and revealed that not all studied populations were under optimal surveillance. This demonstrates the importance of assessing healthcare utilization. Survey data were pivotal for the adjustment of the program's estimates of salmonellosis and other conditions associated with fever., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Increasing development of antimicrobial resistance is driving a resurgence in interest in phage therapy: the use of bacteriophages to treat bacterial infections. As the lytic action of bacteriophages is unaffected by the antibiotic resistance status of their bacterial target, it is thought that phage therapy may have considerable potential in the treatment of a wide range of topical and localized infections. As yet this interest has not extended to intravenous (IV) use, which is surprising given that the historical record shows that phages are likely to be safe and effective when delivered by this route. Starting almost 100 years ago, phages were administered intravenously in treatment of systemic infections including typhoid, and Staphylococcal bacteremia. There was extensive IV use of phages in the 1940s to treat typhoid, reportedly with outstanding efficacy and safety. The safety of IV phage administration is also underpinned by the detailed work of Ochs and colleagues in Seattle who have over four decades' experience with IV injection into human subjects of large doses of highly purified coliphage PhiX174. Though these subjects included a large number of immune-deficient children, no serious side effects were observed over this extended time period. The large and continuing global health problems of typhoid and Staphylococcus aureus are exacerbated by the increasing antibiotic resistance of these pathogens. We contend that these infections are excellent candidates for use of IV phage therapy., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A 2-year-6-month old, appropriately immunised, well-thriving boy, symptomatic for the past 6 months, presented with recurrent fever, progressive pallor, lymphadenopathy and a raw area on the right cheek, with discharging sinus. The necrotising infection of the face developed after one and half months of febrile illness. This febrile illness with bicytopaenia was diagnosed as enteric fever and treated with antibiotics. Skin grafting was performed for the full-thickness defect of the face. The patient continued to have a non-healing oral ulcer with progressive pallor and was finally diagnosed as having acute lymphoblastic leukaemia. Immunodeficiency was ruled out by appropriate investigations. Noma is an indirect measure of extreme poverty, but malignancy is known to predispose to this debilitating condition. The worldwide incidence of Noma is reported to be 30,000-140,000, with a preponderance in sub-Saharan Africa. This case emphasises the need for a thorough search for the underlying illness predisposing to a rare opportunistic infection such as Noma in a well-thriving child., (2016 BMJ Publishing Group Ltd.)

For most of the time, biomedical researchers have been dealing with ordinal outcome variable in multilevel models where patients are nested in doctors. We can justifiably apply multilevel cumulative logit model, where the outcome variable represents the mild, severe, and extremely severe intensity of diseases like malaria and typhoid in the form of ordered categories. Based on our simulation conditions, Maximum Likelihood (ML) method is better than Penalized Quasilikelihood (PQL) method in three-category ordinal outcome variable. PQL method, however, performs equally well as ML method where five-category ordinal outcome variable is used. Further, to achieve power more than 0.80, at least 50 groups are required for both ML and PQL methods of estimation. It may be pointed out that, for five-category ordinal response variable model, the power of PQL method is slightly higher than the power of ML method., Competing Interests: The authors declare that there is no conflict of interests regarding publication of this paper.

Introduction: Salmonella is a rare cause of urinary tract infections. We report here a unique case of pyonephrosis due to Salmonella Typhi (S. Typhi) complication, a stone-related obstructive pyelonephritis., Case Report: A 47-year-old man, without any history of typhoid fever or gastrointestinal symptoms, presented with a pyonephrosis and life-threatening bacteremia following an acute obstructive right pyelonephritis caused by S. Typhi. The patient was treated by urinary drainage (ureteral stent), antibiotics, and delayed right nephrectomy. We postulated that urolithiasis could explain asymptomatic chronic urinary carriage of S. Typhi., Conclusion: S. Typhi is one possible cause of life-threatening urinary tract infection, especially in the context of urolithiasis., (© 2014 S. Karger AG, Basel.)

Salmonellosis-induced diarrhea, is one of the commonest cause of childhood mortality in developing countries. Using of probiotics is viewed as a promising means for reducing the pathogenic loads of bacterial infection. The current study aimed to evaluate the potential antimicrobial and immunomodulatory efficacy of isolated lactobacillus strains against the enteropathogenic effect of S. Typhi. Different Lactobacillus strains were isolated from 13 dairy products. Their antimicrobial activities were tested against different bacterial strains. Six groups of CD1 mice were treated for 8 days as follows: group (1) untreated control; group (2) was challenged with single inoculation S. typhi, and groups (3) and (4) were treated with Lactobacillus plantarum (LA5) or Lactobacillus paracsi (LA7) for 7 days, respectively. Groups (5) and (6) were challenged with S. typhi, and then treated with either LA5 or LA 7 for 7 days, respectively. Isolated Lactobacillus showed antimicrobial activity against wide range of bacterial strains. Salmonellosis showed high widal titer, induced significant disturbance of TNF and IL-1β, while sever changes of the histological patterns of the intestinal villi and hepatocytes have been illustrated. LA5 or LA7 succeeded to eradicate typhoid infection, restore the values of inflammatory cytokines to typical levels of control group, and improve histological pictures of intestinal and hepatic tissues. It can be concluded that lactobacilli are promising candidate in protection and eradication against bacterial infection induced by S. Typhi due to its antimicrobial, anti-inflammatory, and immunomodulatory activities., (© The Author(s) 2015.)

Objectives: Typhoid fever (TF) occurs rarely in industrialized countries because of advances in health care and improvement of drinking water. Conversely, non-typhoid salmonellosis (NTS) remains widespread, because of food contamination or asymptomatic carriage. Non-typhoid salmonellosis can be severe when becoming invasive non-typhoid salmonellosis (iNTS). Although established prognostic indicators of the two pathologies are different, direct comparisons between iNTS and TF in the literature remain scarce. The purpose of this study was to analyse and compare demographic, clinical features and outcome of hospitalized patients with TF and iNTS., Methods: Demographic, clinical features and outcome were retrospectively analysed in a series of patients hospitalized between 2007 and 2012., Results: A total of 33 patients were enrolled, including 13 with established TF and 20 with iNTS. No differences between TF and iNTS patients were observed in incidence of fever, abdominal cramps, diarrhoea, headache, nausea and vomiting and duration of antibiotic therapy (≤ 7 days in both groups). Although the clinical outcome of TF patients was identical to that of iNTS patients, including incidence of complications, length of hospitalization and mortality (1/13 (7.7%) vs 2/20 (10%), P = 0.43), comorbidities were less frequent in the TF group than in the iNTS group (2/13 vs 15/20, P = 0.003)., Conclusion: The clinical profile and outcome of TF patients are similar to those with iNTS. Although comorbidities are more often associated with iNTS, the results of our study suggest that clinical management of these two diseases should remain similar.

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries., (Copyright © 2015. Published by Elsevier Ltd.)

Salmonella infection, ranging from mild, self-limiting diarrhea to severe gastrointestinal, septicemic disease and enteric fever, is a global health problem both in humans and animals. Rapid development of microbial drug resistance has led to a need for efficacious and affordable vaccines against Salmonella. Microbial heat shock proteins (HSPs), including HSP60 and HSP70, are the dominant antigens that promote the host immune response. Co-administration of these antigens with cytokines, such as IL-22, which plays an important role in antimicrobial defense, can enhance the immune response and protection against pathogens. Therefore, the aim of the present study was to determine the immunogenicity of rGroEL (Hsp60) of S. Typhi, alone or administered in combination with murine rIL-22, and its protective efficacy against lethal infection with Salmonella, in mice. There was appreciable stimulation of the humoral and cell-mediated immune responses in mice immunized with rGroEL alone. However, co-administration of rGroEL with rIL-22 further boosted the antibody titers (IgG, IgG1 and IgG2a), T-cell proliferative responses and the secretion of both Th1 and Th2 cytokines. Additionally, rGroEL alone accorded 65%-70% protection against lethal challenge with S. Typhi and S. Typhimurium, which increased to 90% when co-administered with rIL-22.

Background: Typhoid fever remains a major health problem in the developing world. Intestinal perforation is a lethal complication and continues to occur in impoverished areas despite advances in preventive and therapeutic strategies., Objectives: To estimate the case fatality rate (CFR) and length of hospital stay among patients with typhoid intestinal perforation in developing countries., Data Sources: Peer-reviewed publications listed in PubMed and Google Scholar., Study Eligibility: The publications containing data on CFR or length of hospitalization for typhoid fever from low, lower middle and upper middle income countries based on World Bank classification. Limits are English language, human research and publication date from 1st January 1991 to 31st December 2011., Participants: Subjects with reported typhoid intestinal perforation., Interventions: None, standard practice as reported in the publication., Study Appraisal and Synthesis Methods: Systematic literature review followed by meta-analysis after regional classification on primary data. Descriptive methods were applied on secondary data., Results: From 42 published reports, a total of 4,626 hospitalized typhoid intestinal perforation cases and 706 deaths were recorded (CFR = 15·4%; 95% CI; 13·0%-17·8%) with a significant regional differences. The overall mean length of hospitalization for intestinal perforation from 23 studies was 18.4 days (N = 2,542; 95% CI; 15.6-21.1)., Limitations: Most typhoid intestinal perforation studies featured in this review were from a limited number of countries., Conclusions: The CFR estimated in this review is a substantial reduction from the 39.6% reported from a literature review for years 1960 to 1990. Aggressive resuscitation, appropriate antimicrobial coverage, and prompt surgical intervention may have contributed to decrease mortality., Implications: The quantification of intestinal perforation outcomes and its regional disparities as presented here is valuable in prioritizing and targeting typhoid-preventive interventions to the most affected areas.

Lower gastrointestinal haemorrhage due to enteric fever is uncommon and potentially fatal. The majority of patients recover with conservative treatment, with surgery reserved for life-threatening bleeding. Given the advances in radiologically guided procedures, there have been numerous reports of successful embolisation for gastrointestinal haemorrhage, although few of these involved enteric fever as the causative agent. We report an uncommon case of haemorrhagic enteric fever treated successfully with embolisation using polyvinyl alcohol particles and coils.

Background: Typhoid is a leading cause of fever in returning travelers. The prevalence is highest in migrants visiting friends and relatives (VFR travelers) in the Indian subcontinent, where reports of resistance have been of concern. This study is a retrospective analysis of patients with typhoid, seen over a 5-year period, in a tertiary center that serves a large immigrant population., Methods: Patients with blood cultures positive for Salmonella Typhi were identified between 2006 and 2010. Charts were reviewed for demographic data, travel history, symptoms and signs, basic laboratory results, susceptibility profiles, treatment, and clinical course. Resistance to nalidixic acid was used as a marker of decreased susceptibility to quinolones., Results: Seventeen patients were identified with S Typhi. The median age was 12 years (range: 2-47 y) and 94% (16 of 17) were hospitalized with a median stay of 7 days; two were admitted to the intensive care unit. Fourteen patients (82%) had a history of recent travel. Twelve were VFR travelers in Bangladesh and Pakistan and two had recently immigrated. In our study, typhoid patients had low eosinophil counts and elevated transaminases. Seventy-six percent (12 of 17) of all isolates were resistant to nalidixic acid, 23.5% (4 of 17) were resistant to ampicillin and co-trimoxazole, and one was resistant to ciprofloxacin. All isolates were susceptible to third-generation cephalosporins., Conclusions: Younger VFR travelers appear to be at greater risk of acquiring infection and developing complications. Absolute eosinopenia and increased liver function test values could be useful early diagnostic clues in a returning traveler with fever, once malaria has been excluded. There was a high rate of decreased susceptibility to fluoroquinolones, confirming that the use of third-generation cephalosporins or macrolides in patients from the Indian subcontinent is most appropriate. Prevention in VFR travelers to South Asia is critical and efforts should be targeted at better education and pre-travel immunization., (© 2012 International Society of Travel Medicine.)

In recent years, a significant number of physicians want to spend part of their medical training in health facilities in developing countries. In this setting, clinical skills are extremely important due to the limited available diagnostic resources. Bacterial diseases are common, but bacterial cultures are rarely accessible. In Africa, tuberculosis affects over 200 cases per 100,000 persons, and more than 22 million people live with HIV infection; both diseases are a serious public health problem. Malnutrition is endemic in many countries in Africa and is compounded by the continuous humanitarian and food crisis. In this paper, basic concepts of epidemiology, clinical features, diagnosis and treatment of major diseases that can be found in a rural health post in the tropics are discussed., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Salmonella species are a group of Gram-negative enterobacteria and known human pathogens in developing as well as industrialized countries. Despite significant advances in sanitation, provision of potable water, and highly controlled food chain surveillance, transmission of Salmonella spp. continues to affect communities, preferentially children, worldwide. This review summarizes updated concepts on typhoidal and non-typhoidal Salmonella infections, starting with a historical perspective that implicates typhoid Salmonella as a significant human pathogen since ancient times. We describe the epidemiology of this pathogen with emphasis on the most recent non-typhoidal Salmonella outbreaks in industrialized countries and continued outbreaks of typhoid Salmonella in underserved countries. An overview of clinical aspects of typhoid and non-typhoid infections in developing and industrialized countries, respectively, is provided, followed by a description on current treatment concepts and challenges treating multidrug-resistant Salmonella infections. We conclude with prevention recommendations, and recent research studies on vaccine prevention., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To generate community-based estimates of the public (paid by the government) and private (paid by households) costs of blood culture-confirmed typhoid fever in Hechi, China; North Jakarta, Indonesia; Kolkata, India; Karachi, Pakistan and Hue, Vietnam., Methods: To measure out-of-pocket costs of illness and lost earnings, families with culture-proven cases were surveyed 7, 14 and 90 days after onset of illness. Public costs of treatment were measured at local health facilities using a micro costing (bottom-up) method., Results: The costs of hospitalized cases ranged from USD 129 in Kolkata to USD 432 in North Jakarta (hospitalization rates varied from 2% in Kolkata to 40% in Hechi) and the costs of non-hospitalized cases ranged from USD 13 in Kolkata to USD 67 in Hechi. Where costs were highest (Hechi, North Jakarta and Karachi), the bulk of the costs of hospitalized cases was borne by families, comprising up to 15% of annual household income., Conclusion: Although these estimates may understate true costs due to the fact that higher quality treatment may have been provided earlier-than-usual, this multi-country community-based study contributes to evidence on the public and private costs of typhoid fever in developing countries. These cost estimates were used in a cost-effectiveness analysis of typhoid vaccines and will help policymakers respond to World Health Organization's updated typhoid fever immunization recommendations., (© 2011 Blackwell Publishing Ltd.)

Typhoid fever is endemic in the Mediterranean North African countries (Morocco, Algeria, Tunisia, Libya, and Egypt) with an estimated incidence of 10-100 cases per 100,000 persons. Outbreaks caused by Salmonella enterica serovar Typhi are common and mainly due to the consumption of untreated or sewage-contaminated water. Salmonella enterica Paratyphi B is more commonly involved in nosocomial cases of enteric fever in North Africa than expected and leads to high mortality rates among infants with congenital anomalies. Prevalence among travellers returning from this region is low, with an estimate of less than one per 100,000. Although multidrug resistant strains of Salmonella Typhi and Paratyphi are prevalent in this region, the re-emergence of chloramphenicol- and ampicillin-susceptible strains has been observed. In order to better understand the epidemiology of enteric fever in the Mediterranean North African region, population-based studies are needed. These will assist the health authorities in the region in preventing and controlling this important disease.

The purpose of this study was to estimate treatment cost for typhoid fever at two hospitals in Kolkata, India. This study was an incidence-based cost-of-illness analysis from the providers' perspective. Micro-costing approach was employed for calculating patient-specific data. Unit costs of medical services used in the calculation were directly measured from the study hospital by standard method. The study hospitals were selected based on accessibility to data and cooperation. Eighty-three Widal-positive and/or culture-confirmed patients with typhoid fever during November 2003-April 2006 were included in the study. Most (93%) patients were children. Eighty-one percent was treated at the outpatient department. The average duration of hospitalization for child and adult patients was 8.4 and 4.2 days respectively. The average cost of treating children, adults, and all patients was US$ 16.72, 72.71, and 20.77 respectively (in 2004 prices). Recalculation based on 80% occupancy rate in inpatient wards (following the recommendation of the World Health Organization) found that the cost of treating children, adults, and all patients was US$ 14.53, 36.44, and 16.11 respectively.

International travel is increasing. Most physicians and general practitioners will encounter returned travellers with fever and the majority of travel-related infection is associated with travel to the tropics. In those returning from the tropics malaria must always be excluded, and HIV considered, from all settings. Common causes of non-malarial fever include from Africa rickettsial diseases, amoebic liver abscess and Katayama syndrome; from South and South East Asia, enteric fever and arboviral infection; from the Middle East, brucellosis and from the Horn of Africa visceral leishmaniasis. Other rare but important diseases from particular geographical areas include leptospirosis, trypanosomiasis and viral haemorrhagic fever. North and South America, Europe and Australia also have infections which are geographically concentrated. Empirical treatment may have to be started based on epidemiological probability of infection whilst waiting for results to return. The evidence base for much of the management of tropical infections is limited. These recommendations provide a pragmatic approach to the initial diagnosis and management of fever in returned travellers, based on evidence where it is available and on consensus of expert opinion where it is not. With early diagnosis and treatment the majority of patients with a potentially fatal infection related to travel will make a rapid and full recovery.

Enteric fever (typhoid and paratyphoid fever) is a major human bacterial infection. Although the disease is not common in industrialised countries, it remains an important and persistent health problem in developing nations. Hospital-based studies and outbreak reports from India indicate that enteric fever is a major public health problem in this country, with Salmonella enterica serovar Typhi (S. Typhi) the most common aetiologic agent but with an apparently increasing number of cases due to S. Paratyphi A (SPA). Because risk factors such as poor sanitation, lack of a safe drinking water supply and low socio economic conditions in resource-poor countries are amplified by the evolution of multidrug resistant salmonellae with reduced susceptibility to fluoroquinolone, treatment failure cases have been reported in India, which is associated with increased mortality and morbidity. Vaccination, which requires strict planning and proper targeting of the vulnerable age groups, is considered to be an effective tool in controlling this disease in endemic areas, given there is development of a conjugate vaccine against both serovars (S. Typhi and S. Para A).

Background: Ileostomy is usually performed for patients of typhoid intestinal perforation with poor general condition, but it is associated with significant morbidity. We have used the T-tube in such patients as an alternative to ileostomy., Methods: This is a prospective evaluation of a cohort of children with proven typhoid intestinal perforation. Patients with multiple perforations and poor general condition were managed with a T-tube inserted into the bowel lumen after closing all distal perforations (group 3). They were compared with patients who had primary closure of perforation (group 1) or bowel resection (group 2) to determine the efficacy of the use of T-tube., Results: The total number of patients for groups 1, 2, and 3 was 51, 4, and 12 (n = 67). The mean number of perforations for the three groups was 1, 3.5 +/- 0.58, and 4.25 +/- 0.97. The operation time for the three groups was 37.29 +/- 3.24, 59.25 +/- 3.09, and 59.17 +/- 4.17 minutes, respectively. The T-tube was removed after 13.17 days. The mean duration of fistula at T-tube site to heal was 8.58 +/- 2.11 days. The overall follow-up period was 10.94 +/- 1.15 months and none of the patients with T-tube placement had features of intestinal obstruction., Conclusions: In children with multiple typhoid intestinal perforations and poor general condition, the use of T-tube may be an effective management option.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a disease transmitted by the faecal-oral route. It continues to be a public health problem in many developing countries in sub-Saharan Africa. School-age children, especially those from resource-poor settings with inadequate water and sanitation systems, are disproportionately affected. It is estimated that a total of 400,000 cases occur annually in Africa, an incidence of 50 per 100,000 persons per year. Lack of effective diagnosis often leads to inappropriate treatment and management of these infections. Additionally, the emergence and spread of S. Typhi strains having multiple resistance to nearly all commonly available drugs in most developing countries has been a major challenge to health care systems, reducing the effective treatment options for the disease, increasing treatment costs and increasing the risk of complications and death. Although not much data from sub-Saharan Africa has been published, it seems clear that typhoid is common in Nigeria, Mali, Ethiopia and Kenya. Given the importance of information on disease incidence for targeting control measures, including improved sanitation and water supply, vaccination and assessing impact, priority should be given to strengthening surveillance systems for typhoid fever.

Background: Salmonella species are responsible for two distinct syndromes. Nontyphoidal Salmonella are common causes of food borne gastroenteritis. Typhoidal Salmonella cause enteric fever; an important differential diagnosis in any traveller returning from a tropical country with fever., Objective: This article describes the spectrum of disease that occurs with Salmonellosis infections and particular subgroups of patients who are more susceptible to severe disease. An appreciation of this will allow the clinician to manage these infections appropriately., Discussion: Nontyphoidal Salmonellosis infections causing gastroenteritis are common in our community. Infection is caused by ingesting contaminated food or water, or occasionally by contact with an infected person. Most cases are self limiting and the focus of management is effective rehydration. Antibiotic therapy is seldom warranted but important exceptions exist including neonates, the immunocompromised, and in particular circumstances, the elderly. Enteric fever always warrants antibiotic treatment. Notification to the appropriate health authority assists with investigating possible outbreaks.