Heat stress impairs egg production in commercial laying hens infected by fowl typhoid.

Salmonella Gallinarum (SG) is an avian-restricted pathogen that causes fowl typhoid in poultry. Although it has been reported frequently over many decades in poultry flocks worldwide, the microorganism is more commonly associated with poultry in developing countries, particularly those with high ambient temperatures, where the acute form of the disease results in considerable economic losses. A more detailed investigation of environmental factors that affect the course of disease may assist in identifying effective prevention and control measures. Heat stress is known to impair the immunological response to a variety of pathogens and clearly may be an important contributory factor in the prevalence of disease in countries with warm or hot climates. Thus, the objective of the present study was to evaluate the effects of heat stress on chickens infected with SG. For this, light and semi-heavy commercial laying hens were distributed randomly within four groups as follows: infected and non-infected groups in rooms held at ambient temperature, and infected and non-infected groups under heat stress. Clinical signs, egg production, and mortality were recorded daily. Bacteriological counts in liver and spleen samples were estimated at 2, 5, 7, and 14 days post-infection. The results showed that both SG infection and heat stress had similar effects on egg production and a synergistic effect of the two stressors was observed. The data show an interaction between disease and heat stress which could point towards environmental and biosecurity approaches to resolving the possible 30% fall in production observed in such countries.

Epithelial invasion by Salmonella Typhi using STIV-Met interaction.

Typhoid is a life-threatening febrile illness that affects ~24.2 million people worldwide and is caused by the intracellular bacteria Salmonella Typhi (S. Typhi). Intestinal epithelial invasion by S. Typhi is essential for the establishment of successful infection and is traditionally believed to depend on Salmonella pathogenicity island 1-encoded type 3 secretion system 1 (T3SS-1). We had previously reported that bacterial outer membrane protein T2942/STIV functions as a standalone invasin and contributes to the pathogenesis of S. Typhi by promoting epithelial invasion independent of T3SS-1 (Cell Microbiol, 2015). Here, we show that STIV, by using its 20-amino-acid extracellular loop, interacts with receptor tyrosine kinase, Met, of host intestinal epithelial cells. This interaction leads to Met phosphorylation and activation of a downstream signalling cascade, involving Src, phosphatidylinositol 3-kinase/Akt, and Rac1, which culminates into localized actin polymerisation and bacterial engulfment by the cell. Inhibition of Met tyrosine kinase activity severely limited intestinal invasion and systemic infection by S. Typhi in vivo, highlighting the importance of this invasion pathway in disease progression. This is the first report elucidating the mechanism of T3SS-1-independent epithelial invasion of S. Typhi, and this crucial host-pathogen interaction may be targeted therapeutically to restrict pathogenesis.

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi (S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

Typhoidal Salmonella: Distinctive virulence factors and pathogenesis.

Although nontyphoidal Salmonella (NTS; including Salmonella Typhimurium) mainly cause gastroenteritis, typhoidal serovars (Salmonella Typhi and Salmonella Paratyphi A) cause typhoid fever, the treatment of which is threatened by increasing drug resistance. Our understanding of S. Typhi infection in human remains poorly understood, likely due to the host restriction of typhoidal strains and the subsequent popularity of the S. Typhimurium mouse typhoid model. However, translating findings with S. Typhimurium across to S. Typhi has some limitations. Notably, S. Typhi has specific virulence factors, including typhoid toxin and Vi antigen, involved in symptom development and immune evasion, respectively. In addition to unique virulence factors, both typhoidal and NTS rely on two pathogenicity-island encoded type III secretion systems (T3SS), the SPI-1 and SPI-2 T3SS, for invasion and intracellular replication. Marked differences have been observed in terms of T3SS regulation in response to bile, oxygen, and fever-like temperatures. Moreover, approximately half of effectors found in S. Typhimurium are either absent or pseudogenes in S. Typhi, with most of the remaining exhibiting sequence variation. Typhoidal-specific T3SS effectors have also been described. This review discusses what is known about the pathogenesis of typhoidal Salmonella with emphasis on unique behaviours and key differences when compared with S. Typhimurium.

Evaluation of hematological indices of childhood illnesses in Tamale Metropolis of Ghana.

BACKGROUND: Although hematological indices cannot in entirety be used to diagnose diseases or defects, the appropriate interpretation of these indices could complement diagnostics such as microscopy and serology for numerous illnesses in children. This study sought to evaluate distinct hematological indices characterizing different childhood illnesses. METHODS: Full blood counts from 150 children (age range from 1 to 15 year) presenting different disease conditions at the Tamale Central Hospital were assessed. The hematological indices were compared between disease categories, and relationships between disease indicators were determined. RESULTS: The prevalence of the diagnosed childhood illness were: 50.7% malaria, 20.0% diarrhea, 13.3% typhoid fever, 10.0% Sickle Cell Disease (SCD), and 6.0% malaria-typhoid co-infection. Fever was diagnosed in a majority (66.0%) of the children, but was independent of each disease group, (χ2 = 9.18, P = .057). Of the 24 hematological indices analyzed, eight; red blood cell (RBC) (P < .001), hemoglobin (Hb) (P < .001), mean cell volume (MCV) (P = .002), mean cell hemoglobin (MCH) (P < .001; lowest and below normal range for SCD), red cell distribution width (RDW_CV) (P < .001), eosinophil percentage [EOS (%)] (P = .001), eosinophil number [EOS#] (P = .002), and platelets (PLT) (P = .001; lowest for malaria) differed significantly across the different disease groups. Levels of Hb and/or MCV were below the normal reference ranges for most of the diagnosed diseases. In addition, low PLT and MCH were respectively distinct for children with malaria and SCD. CONCLUSION: Hematological indices including Hb, MCV and PLT, or MCH may be useful indices that could incite further diagnostic tests for malaria or SCD among children in Ghana.

What Have We Learned From the Typhoid Fever Surveillance in Africa Program?

The Typhoid Fever Surveillance in Africa Program (TSAP) was established in 2009 to fill the data void concerning invasive Salmonella disease in sub-Saharan Africa, and to specifically estimate the burden of bloodstream infections caused by the key pathogen, Salmonella enterica serovar Typhi. TSAP has achieved this ambitious target, finding high incidences of typhoid fever in both rural and urban populations in several countries in sub-Saharan Africa. The results of TSAP will undoubtedly dictate the direction of future typhoid fever research in Africa, and at last provides a key piece of the disease burden jigsaw puzzle. With the dawn of new Vi conjugate vaccines against Salmonella Typhi, the next priority for the typhoid community must be providing the required data on these vaccines so they can be licensed and provided to those in high-risk groups and locations across sub-Saharan Africa.

Challenges and Opportunities for Typhoid Fever Control: A Call for Coordinated Action.

The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines.

Epidemiological investigation of an outbreak of typhoid fever in Jorhat town of Assam, India.

BACKGROUND & OBJECTIVES: Typhoid fever is a global health problem and is also endemic in India. An outbreak of fever occurred in January 2014 in Jorhat Town in Assam, India. Here we report the results of an investigation done to find out the aetiology and source of the outbreak. METHODS: The affected areas were visited on January 23, 2014 by a team of Jorhat district Integrated Disease Surveillance Project personnel. A total of 13 blood samples from patients with fever as first symptom and six water samples were collected from the affected areas. The blood samples were cultured and isolates were identified using standard biochemical tests. Isolates were also tested for antimicrobial sensitivity. Widal test was performed on 10 of the 13 blood samples collected. Sanitary survey was carried out to find any leakage in the water supply and also the sewage system of the Jorhat town. RESULTS: Blood culture yielded Salmonella enterica serovar Typhi in six (46.15%) patients whereas Widal test was positive in 10 (76.9%) of 13 patients. Water culture showed presumptive coliform count of >180/100 ml in two out of the six samples tested. Salmonella Typhi was also isolated from water culture of these two samples. Sanitary survey carried out in the affected places showed that the water supply pipes of urban water supply were in close proximity to the sewage drainage system and there were few leakages. INTERPRETATION & CONCLUSIONS: The outbreak occurred due to S. Typhi contaminating the water supply. Sanitation and immunization are the two most important components to be stressed to prevent such outbreaks.

Comparison of clinical characteristics and laboratory findings of malaria, dengue, and enteric fever in returning travelers: 8-year experience at a referral center in Tokyo, Japan.

BACKGROUND: Without specific symptoms, diagnosis of febrile illness in returning travelers is challenging. Dengue, malaria, and enteric fever are common causes of fever in returning travelers and timely and appropriate treatment is important. However, differentiation is difficult without specific diagnostic tests. METHODS: A retrospective study was conducted at the National Centre for Global Health and Medicine (NCGM) from April 2005 to March 2013. Febrile travelers returning from overseas who were diagnosed with dengue, malaria, or enteric fever were included in this study. Clinical characteristics and laboratory findings were compared for each diagnosis. RESULTS: During the study period, 86 malaria, 85 dengue, and 31 enteric fever cases were identified. The mean age of the study cohort was 33.1 ± 12 years and 134 (66.3%) study participants were male. Asia was the most common area visited by returning travelers with fevers (89% of dengue, 18.6% of malaria, and 100% of enteric fever cases), followed by Africa (1.2% of dengue and 70.9% of malaria cases). Clinical characteristics and laboratory findings were significantly different among each group with each diagnosis. Decision tree models revealed that returning from Africa and CRP levels <10 mg/L were factors specific for diagnosis of malaria and dengue fever, respectively. CONCLUSION: Clinical manifestations, simple laboratory test results, and regions of travel are helpful to distinguish between dengue, malaria, and enteric fever in febrile returning travelers with non-specific symptoms.

Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

Validation of the proposed clinical diagnostic criteria of enteric fever.

BACKGROUND: Enteric fever is very common infectious disease in developing countries like Nepal. Due to lack of resources diagnosis has to be clinical most of the time. Hence a proposal of clinical diagnostic criteria and validation of the same would be very useful. OBJECTIVE: To validate the proposed clinical diagnostic criterion including features characterized as major and minor criteria. METHODS: This study was done in the department of medicine of Kathmandu Medical College Teaching hospital, from June 2009 to January 2012. A total of 114 patients presenting with fever were included in the study. After proposal of clinical diagnostic criteria for enteric fever, by a prior published study, all the fever patients were grouped according to criteria positive or negative. The most significant criteria were validated by calculating sensitivity and specificity along with positive and negative likelihood ratios with blood culture taken as gold standard. RESULTS: A total of 114 patients were enrolled. Total patients diagnosed as enteric was 47.3 %. Clinical diagnostic criterion B which included three major (headache, fever and relative bradycardia) and three minor criteria (abdominal pain, vomiting, diarrhea, splenomegaly and chills) was highly significant (p=<.0001) in diagnosing enteric fever and had a sensitivity of 72.2% ( 95% CI 58.1- 83.1) and specificity of 98.3% ( 95% CI 89.8-99-9). The positive likelihood ratio was 43.33 (95 % CI 6.16-304.77) and negative likelihood ratio as 0.28 (95% CI 0.18-0.43). CONCLUSION: Clinical diagnostic criteria can be a very useful tool for diagnosis of enteric fever when culture facility is not available.

Use of Typhoid Vi-Polysaccharide Vaccine as a Vaccine Probe to Delineate Clinical Criteria for Typhoid Fever.

Blood cultures (BCs) detect an estimated 50% of typhoid fever cases. There is need for validated clinical criteria to define cases that are BC negative, both to help direct empiric antibiotic treatment and to better evaluate the magnitude of protection conferred by typhoid vaccines. To derive and validate a clinical rule for defining BC-negative typhoid fever, we assessed, in a cluster-randomized effectiveness trial of Vi-polysaccharide (ViPS) typhoid vaccine in Kolkata, India, 14,797 episodes of fever lasting at least 3 days during 4 years of comprehensive, BC-based surveillance of 70,865 persons. A recursive partitioning algorithm was used to develop a decision rule to predict BC-proven typhoid cases with a diagnostic specificity of 97-98%. To validate this rule as a definition for BC-negative typhoid fever, we assessed whether the rule defined culture-negative syndromes prevented by ViPS vaccine. In a training subset of individuals, we identified the following two rules: rule 1: patients aged < 15 years with prolonged fever accompanied by a measured body temperature ≥ 100°F, headache, and nausea; rule 2: patients aged ≥ 15 years with prolonged fever accompanied by nausea and palpable liver but without constipation. The adjusted protective efficacy of ViPS against clinical typhoid defined by these rules in persons aged ≥ 2 years in a separate validation subset was 33% (95% CI: 4-53%). We have defined and validated a clinical rule for predicting BC-negative typhoid fever using a novel vaccine probe approach. If validated in other settings, this rule may be useful to guide clinical care and to enhance typhoid vaccine evaluations.

Increasing rates and clinical consequences of nalidixic acid-resistant isolates causing enteric fever in returned travellers: an 18-year experience.

The purpose of this study was to examine the rate and clinical consequences of nalidixic acid-resistant (NAR) isolates in travellers with enteric fever presenting to a hospital in a developed country. We retrospectively examined microbiologically confirmed cases of enteric fever in adult returned travellers over an 18-year period presenting to two tertiary referral hospitals in Melbourne, Australia. There were 59 cases of Salmonella typhi infection, 43 cases of S. paratyphi A infection and two cases of S. paratyphi B infection. Most patients reported recent travel to India (36%) or Indonesia (29%). NAR isolates were commonly encountered (41% of all isolates), particularly from India (75%), Pakistan (80%) and Bangladesh (60%). The number of NAR isolates increased progressively after 2003. Patients with NAR isolates had prolonged mean fever clearance time (5.6 vs. 3.3 days, P = 0.03) and prolonged hospital stay (7.9 vs. 5.7 days, P = 0.02) compared to non-resistant isolates. This represents the largest report of NAR enteric fever in returned travellers. NAR isolates predominate in cases of enteric fever from South Asia and result in prolonged fever clearance time and hospital stay. Empiric therapy with alternative antibiotics such as ceftriaxone or azithromycin should be considered in patients with suspected enteric fever from this region.

Treatment failure in case of typhoid fever imported from India to Czech Republic, December 2008--January 2009.

In this report we describe a case of typhoid fever in a Czech patient with history of travel to India and discuss antibiotic treatment failure which led to the relapse of fever.

Predictive value of clinical and laboratory findings in the diagnosis of the enteric fever.

Although the definitive diagnosis of enteric fever requires the isolation of Salmonella enterica serotype typhi or paratyphi, the diagnosis is usually made according to clinical and laboratory findings. There is usually a diagnostic dilemma. The aim of this study was to determine the minimum required parameters that could be valuable in the diagnosis of enteric fever. A retrospective study was performed to compare the clinical and laboratory findings in 60 patients who proved to have enteric fever by cultures and 58 patients with non-enteric fever. Features independently predictive of enteric fever were assessed by multivariate logistic regression. Sensitivity, specificity and positive predictive and negative predictive values were estimated. Significant clinical features of enteric fever were hepatomegaly, splenomegaly, relative bradycardia, rose spots, leucopenia, trombocytopenia, eosinopenia and elevated AST level. Five of these features were found to be predictive for the diagnosis of enteric fever; splenomegaly, relative bradycardia, rose spots and trombocytopenia and elevated AST level. In conclusion, clinical and laboratory findings can help the clinician to diagnose enteric fever in the absence of microbiological confirmation.

Unusual presentations of Salmonella Typhi infections in children.

We report on three children with Salmonella typhi presenting with fever and urticaria, thrombocytopenic purpura and meningitis. We suggest that clinicians should consider S. typhi infection as a diagnosis even when the presenting features are more typical of other illnesses.

Intracranial haemorrhage in typhoid fever.

Intracranial haemorrhage in typhoid fever is very rare. We report another case of non-traumatic intracranial hemorrhage in a 6-year-old boy suffering from typhoid fever, unconsciousness, seizure and non-coherent speech. Investigations revealed severe thrombocytopenia and prolonged prothrombin time. CT scan of brain showed intraparenchymal haemorrhage in frontal regions bilaterally with perilesional oedema, subarachnoid bleed and extension into the lateral ventricles. No aneurysm or arterio-venous malformation was seen on MR angiography. The patient recovered without any neurological deficit.