The Spectrum of Hepatic Injury in Enteric Fever

Thirty six patients with culture-proven enteric fever and 15 patients of fever with etiology other than enteric fever as a control group were studied, with special reference to hepatic dysfunction and its relation to clinical features of the disease. Hepatomegaly was observed in 55% of enteric fever patients, and was slightly more common than splenomegaly (50%). Its incidence in typhoid fever (67%) was three times higher than in paratyphoid fever (22%). Hepatic dysfunction occurred in 55% of cases. Jaundice was noted in only 8% of the cases, whereas hyperbilirubinemia (serum bilirubin greater than 1.8 mg %) was present in 17%. Although hepatic manifestations of enteric fever were mild, a small but important group had sufficient hepatic involvement to mimick the clinical picture seen in viral hepatitis, amebic liver disease, and malaria with jaundice. It may be considered of clinical significance, since enteric hepatitis responds very well to specific therapy.     

Clinical and Microbiological Profile of a Retrospective Cohort of Enteric Fever in 2 Spanish Tertiary Hospitals

Enteric fever in high-income countries is diagnosed mainly in patients returning from endemic countries. We assess the clinical, microbiological, and prognosis aspects of enteric fever in 2 Spanish tertiary hospitals.A retrospective observational study was conducted at Vall d’Hebron University Hospital and Ramón y Cajal University Hospital in Spain. We reviewed medical records of all patients who were diagnosed with enteric fever from January 2000 to January 2014 at these hospitals.We identified 47 patients with enteric fever episodes. According to their travel history, 35 (74.5%) patients had travelled to highly endemic countries. Imported enteric fever was acquired mainly in Asia (70.3%). Imported infections were implicated in travelers (48.6%), visiting friends and relatives (40%) and immigrants (11.4%). We found that 12 patients were diagnosed with enteric fever without a travel history (autochthonous infection). The resistance profile of the isolates showed decreased ciprofloxacin susceptibility in 66.7% of the imported group and 8.3% of the autochthonous group (P = 0.001). Salmonella strains from patients returning from Asia had an increased risk of having decreased ciprofloxacin susceptibility (odds ratio, 52.25; 95% confidence interval: 8.6–317.7).Patients with imported enteric fever are at higher risk for having a Salmonella strain with decreased ciprofloxacin susceptibility, especially in patients returning from Asia. Initial treatment with third-generation cephalosporin or azithromycin is strongly recommended until a drug-susceptibility test is available. Prevention strategies such as pretravel counseling and immunization before travel may be beneficial.     

Imported Enteric Fever: Case Series from the Hospital for Tropical Diseases,London, United Kingdom

Our current knowledge of the clinical characteristics of enteric fever is drawn mainly from population-based studies in disease-endemic countries, and there are limited data published on cases in returning travelers. We report the clinical characteristics of enteric fever in 92 travelers returning to London, United Kingdom. Salmonella typhi and S. paratyphi resulted in an almost indistinguishable clinical picture. Rose spots and relative bradycardia were found only in a few patients. A total of 91% of the patients had a normal leukocyte count, which was associated with a markedly increased level of alanine aminotransferase in 82%. A total of 57% of the S. typhi isolates had decreased susceptibility to ciprofloxacin and resistance to nalidixic acid; these isolates were from southern Asia. Thirty percent were multidrug resistant; all were from southern Asia and Nigeria. None of the paratyphoid isolates were multidrug resistant but rates of decreased susceptibility to fluoroquinolones were higher than in S. typhi (74%).     

Enteric adenoviruses

Human adenoviruses are classified into 47 serotypes and six subgenera (A-F) with different tropisms. In recent years adenovirus type 40 (Ad40) and 41 (Ad41) of subgenus F have been shown to be causative agents in enteric infections, which is second in importance only to rotaviruses as a cause of infantile gastroenteritis. Infection with EAds occurs worldwide and has been associated with 4-17% of cases of diarrhoea in children. AD40 and Ad41 primarily affect young children less than 2 years of age and occur throughout the year. The clinical characteristics include watery diarrhoea accompanied by vomiting, low grade fever and mild dehydration. A distinct feature of EAds infection is the protracted diarrhoea (mean 8.6 and 12.2 days for Ad40 and Ad41, respectively). Respiratory symptoms are infrequent. Serotypes Ad40 and Ad41 differ from all other (established) adenoviruses by being unable to replicate in conventional cell cultures. These fastidious viruses only grow in selected cell lines, 293 cells being the most commonly used. In spite of the difficulty of isolating Ad40 and Ad41, they can be directly identified and typed by ELISA and solid-phase immune electron microscopy. The amount of viral DNA in stool specimens is sufficient for identification by DNA restriction and dot-blot assays. The recent development of highly sensitive and specific monoclonal antibody-based ELISAs enable accurate diagnosis of adenovirus gastroenteritis in routine work and make possible the evaluation of the role of the enteric adenoviruses in diarrhoeal disease in the developing countries.     

Enteric neuroimmunophysiology and pathophysiology

Minute-to-minute behavior of the bowel, whether it is normal or disordered, is determined by integrative functions of the enteric nervous system (ENS). Information input processed by the ENS is derived from local sensory receptors, the central nervous system, and immune/inflammatory cells including mast cells. Enteric mast cells use the power of the immune system for detection of antigenic threats and for long-term memory of the identity of the specific antigens. Specific antibodies attach to the mast cells and enable the mast cell to detect sensitizing antigens when they reappear in the gut lumen. Should the sensitizing antigen reappear, mast cells detect it and signal its presence to the ENS. The ENS interprets the mast cell signal as a threat and calls up from its program library secretory and propulsive motor behavior that is organized to eliminate the threat rapidly and effectively. Operation of the alarm program protects the individual, but at the expense of symptoms that include cramping abdominal pain, fecal urgency, and diarrhea. Enteric mast cells use immunologic memory functions to detect foreign antigens as they appear and reappear throughout the life of the individual. Mast cells use paracrine signaling for the transfer of chemical information to the neural networks of the ENS. Integrative circuits in the ENS receive and interpret the chemical signals from the mast cells. Signals from the mast cells are interpreted by the ENS as a labeled code for the presence of a threat in the intestinal lumen.     

Clostridium difficile-associated Enteric Disease

Clostridium difficile was identified as the putative agent of antibiotic-associated pseudomembranous colitis in 1978 and is now recognized as the major identifiable cause of antibioticassociated diarrhea. This microbe causes a spectrum of enteric disease ranging from nuisance diarrhea to life-threatening colitis. Risk factors include increasing age, exposure to antibiotics, colonization or acquisition of toxin-producing strains of C. difficile, and lack of circulating antibody to C. difficile toxin A. Detection is relatively simple by stool assay for C. difficile toxin—usually an enzyme immunoassay that will detect toxin A and B. Most nonsevere cases will respond with discontinuation of the implicated antibiotic. More severe cases require metronidazole and supportive care. The major complications include ileus, toxic megacolon, relapsing disease after antibiotic treatment, and nosocomial epidemics.     

Enteric neuromuscular pathology update

The recent development of consensus guidelines for the preparation and staining of tissues, the publication of the London Classification, and reviews of what is normal in the enteric neuromusculature have been significant steps forward in this field. Increased accessibility to full-thickness biopsies of the bowel wall facilitated by advances in laparoscopic surgery have also played a part in making the decision to ask for a tissue diagnosis easier. Better antibodies for immunohistochemistry and a better understanding of disease processes at work, such as those seen in filamin mutations, all help inform the range of information that can be gleaned from what is usually a very limited sample. Clinical phenotyping remains difficult in many patients, but the availability of specialist pathologic review and the standardization of staining between laboratories are leading to better defined histologic phenotypes, that inform, in turn, possible biological processes at work in these patients. In many instances, a diagnosis may come to light only after some time, and the retention of pathologic samples in paraffin wax, as is standard practice in most laboratories, is of great value in reassessing samples, often after many years, in the light of new advances. The highest quality information, and the best answer for the patient, is, as ever, achieved by close working relationships and excellent communication between clinicians and pathologists.