Coinfection of enteric fever and hepatitis A
- 1 General Medicine, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India
- 2 General Medicine, Amrita Vishwa Vidyapeetham-Kochi Campus, Kochi, Kerala, India
- Correspondence to Dr Bhagya Lakxmi C; bhagyalakxmic@gmail.com
Abstract
Poor sanitation and contaminated food and water are major risk factors for several infectious diseases like enteric fever and hepatitis A, but their coinfection is uncommon. Although the liver is frequently affected in typhoid fever, substantial hepatic dysfunction in an appropriately treated patient is uncommon. Our patient had high-grade fever with mild transaminitis and blood culture that grew Salmonella typhi. Despite being treated with culture-sensitive antibiotic at adequate dosage, he developed jaundice and had worsening transaminitis (>1000 IU/L) which was suggestive of hepatotropic virus infection. Hepatitis A IgM was positive. He was treated appropriately with which clinical and laboratory parameters resolved.
Background
Developing countries are endemic to several infectious diseases like enteric fever and hepatitis A. Poor sanitation and contaminated food and water aid the feco-oral spread of these diseases given that humans are the only reservoir for both. In few cases, enteric fever and hepatitis A coexist and cause diagnostic ambiguity, thereby leading to delayed diagnosis and treatment.1 This case report is about a 35-year-old man, who had concurrent infection with Salmonella typhi and hepatitis A.
Case presentation
A 35-year-old man having no known comorbidities presented with diarrhoea for 7 days and intermittent fever of high grade which was associated with rigours and chills for 5 days. There were no other associated symptoms. His medical, personal and family history were unremarkable. On admission, general examination revealed signs of dehydration and there was no pallor, icterus or lymphadenopathy. His vital signs showed the following: pulse rate, 98 beats/min; blood pressure, 120/78 mm Hg; temperature, 100°F; respiratory rate, 20/min with a saturation of 98% in room air. Abdominal examination revealed no tenderness, guarding, rigidity or organomegaly, and the rest of the physical examination was normal.
Investigations
Initial laboratory investigations showed the following: elevated C reactive protein (167 mg/L) with total blood count (5.94 K/μL), neutrophil (79.6%), lymphocyte (15.7%), haemoglobin (13.0 g/dL), platelets (162 x 109/L), hyponatraemia (116.4 mmol/L), hypokalaemia (2.9 mmol/L), mild transaminitis (alanine aminotransferase (ALT), 112.9 IU/L and aspartate aminotransferase (AST), 174.6 IU/L). Other liver parameters were normal including total bilirubin (0.73 mg/dL), direct bilirubin (0.27 mg/dL) and International Normalized Ratio (1.19). Hepatitis B antigen screen, anti-Hepatitis C virus screen and HIV screen were negative. Ultrasonogram of the abdomen and pelvis showed hepatomegaly and Salmonella IgM antibody was positive.
Treatment
He was started on intravenous fluids for dehydration and dyselectrolytaemia correction was done. Intravenous ceftriaxone and other supportive medications were instituted. Subsequently, blood culture grew pan-sensitive S. typhi. Despite the patient being on culture-sensitive antibiotic, he had on and off fever, developed jaundice (total bilirubin, 3.81 mg/dL; direct bilirubin, 2.51 mg/dL, as shown in figure 1) and had worsening transaminitis (ALT, 5965 IU/L and AST, 3420 IU/L, as shown in figure 2) with elevated INR (2.2). The clinical and laboratory profiles in the background of consumption of contaminated food suggested the possibility of hepatotropic virus infection especially when incubation period is considered. Hepatitis A virus (HAV) IgM and hepatitis E virus were sent. Hepatitis A IgM was positive (1.99 IU/L) (normal value: <0.4 IU/L). Hepatitis E IgM was negative. Other causes of viral hepatitis like hepatitis B, hepatitis C, cytomegalovirus and herpes simplex virus were ruled out. HAV PCR test was not done as it is available only in specialised laboratories. However, HAV IgM is the gold standard test for diagnosing acute HAV. He was continued on antibiotic and with supportive management for viral hepatitis. Health education on hygienic practices was given.
The trend of liver enzymes during his course of illness. ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Bilirubin profile of the patient during admission. D. Bili, direct bilirubin; T. Bili, total bilirubin.
Outcome and follow-up
The patient improved symptomatically; his fever reduced and laboratory parameters improved, thus he was discharged. On review after 2 weeks, the patient was asymptomatic, with no fever spikes, icterus resolved and liver parameters normalised (ALT, 40 IU/L; AST, 25 IU/L; total bilirubin, 1.06 mg/dL; direct bilirubin, 0.6 mg/dL). He was advised to follow safe hygiene practices. He returned to work and then was followed up through telemedicine.
Discussion
S. typhi is a Gram-negative bacterium that affects the reticulo-endothelial system and causes systemic disease after 10–14 days of incubation.2 The disease is spread through feco-oral route by consumption of contaminated water or food. The majority of patients who develop uncomplicated typhoid fever experience symptoms, such as a gradual onset of persistent fever, malaise, anorexia, and occasionally constipation or diarrhoea.3 Typhoid hepatitis is caused by typhoid endotoxemia, cytotoxins or direct bacterial invasion, according to some theories.4 About 0.5%–1% of patients have either intestinal perforation or haemorrhage as complications that occur, particularly in untreated cases or individuals who have received inappropriate therapy. Our patient had consumed food outside.
Hepatitis A is an RNA virus from the Picornaviridae family which is non-enveloped.5 HAV can persist in the environment, be transmitted via feco-oral route and humans are the sole natural host. The incubation period of HAV ranges from 15 to 50 days and an average of 28 days.6 The viral particles enter the portal circulation and then the hepatocytes. Virions then proliferate, assemble and are released in the biliary canaliculus, where they enter the small intestine via the bile duct. This enterohepatic cycle continues until it is interrupted by neutralising antibodies or other immune mechanisms.7 HAV is serologically diagnosed by IgM anti-HAV detection in the early stages. This forms 3 weeks following inoculation via oral route, peaks at early convalescent stages of the infection, and after 3– 6 months it fades away. IgG anti-HAV peaks during convalescence and can last for years; the existence of which suggests past infection with life-long immunity, therefore it can be used for a seroepidemiological population study. HAV infection has myriad of clinical patterns. It can range from asymptomatic infection to fulminant hepatitis.
Fever with jaundice is a clinical feature of both typhoid hepatitis and viral hepatitis A. Our patient was initially treated for enteric fever because of culture-growing Salmonella. We suspected coexisting viral hepatitis because of elevation of liver enzymes (>1000 IU/L) with ALT>AST and elevated prothrombin time despite more than 1 week of culture-sensitive antibiotic with appropriate dosage in the background of consumption of contaminated food. Cholangitis, cholecystitis and Salmonella liver abscess are other causes of worsening jaundice in typhoid fever.8 The symptoms of acute viral hepatitis A are analogous to those of typhoid hepatitis which our patient had.
However, in patients with acute viral hepatitis A, fever generally subsides when jaundice appears, and the time between the fever onset and the emergence of jaundice is often 1–7 days.9–11 Whereas in enteric fever, jaundice normally appears at the peak of the illness and the fever lingers beyond the onset of jaundice. Fever spikes should usually subside by day 4–5 of illness in patients with enteric fever with an early onset of treatment.12 However, in patients with coexisting infections, as in our patient, it may take longer. Jagadish et al 8 conducted a study on hepatic manifestations in typhoid. They observed that, while liver enzymes were high in more than 60% of cases, only 9.7% of those had prolonged prothrombin time. The synergistic action of typhoid and viral hepatitis is unknown but it results in more significant liver damage than the individual diseases itself.11
As per our paediatric immunisation guidelines, typhoid and hepatitis A vaccines are routinely recommended in children. According to our guidelines, typhoid and hepatitis A vaccinations are not routinely recommended in adults. Hepatitis A vaccination is indicated in circumstances, such as in persons with chronic liver disease not already immune to HAV, persons infected with other hepatitis virus infections, and all candidates for liver or kidney transplants with chronic hepatitis B or C infection. It is also recommended in illicit drug users, men who have sex with men and people who receive clotting factor concentrates.13–15 On the other hand, typhoid vaccination is advised only during outbreaks in adults.16 It does not provide protection for paratyphoid fever. A combined hepatitis A and typhoid fever vaccine is available in Europe and Canada; however, it is not available in India.17 Hence, focus should be made on public health measures like proper hand hygiene, consumption of safe food and water, and adequate sanitation services as they are important to prevent both hepatitis A and enteric fever.18
Learning points
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In a patient with enteric fever, when one encounters transaminitis (>1000 IU/L), clinicians should strongly suspect coinfection with viral hepatitis A or E as both are caused by consumption of contaminated food and water.
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The incubation period of infectious disease provides insight regarding the symptom onset and diagnosis.
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The public should be educated on proper sanitation and hygiene practices in developing countries.
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Vaccination for hepatitis A and typhoid should be administered appropriately to decrease its incidence.
Ethics statements
Patient consent for publication
Acknowledgments
I thank my family, my colleagues, and faculties at the Department of General Medicine, AIMS, Amrita Vishwa Vidyapeetham for helping me do this.
Footnotes
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Contributors BL prepared the manuscript. ATO and MGP edited and approved the final draft of the manuscript. BL and ATO were involved in the management of the patient.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
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