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Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 57-61

Spectrum of enteric fever complications: As wide as in yesteryears

1 Department of Medicine, Jaipur Golden Hospital, New Delhi, India
2 Department of Family Medicine, Jaipur Golden Hospital, New Delhi, India

Date of Submission09-Aug-2021
Date of Decision22-Sep-2021
Date of Acceptance22-Sep-2021
Date of Web Publication24-Jan-2022

Correspondence Address:
Dr. Vinay Kumar Rastogi
Jaipur Golden Hospital, Sector 3, Rohini, New Delhi - 110 085
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/INJMS.INJMS_92_21

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Enteric fever can have wide clinical presentation in humans. We report few rare complications of enteric fever such as secondary hemophagocytic lymphohistiocytosis, liver abscess, encephalopathy, and myopericarditis. Interestingly none of these cases are easy to recognize in early days in far flung remote areas where facilities are lacking. In our observance, first case was of 59-year-old male, who presented with acute febrile illness, thrombocytopenia, and hepatosplenomegaly. The patient had progressive pancytopenia with clinical deterioration. A diagnosis of secondary hemophagocytic lymphohistiocytosis was made and managed. The second case presented as fever with acute abdomen, which was due to pyogenic liver abscess caused by Salmonella typhi (S. typhi). Third case was 65-year-old female who presented with fever associated with neuropschychiatric and cerebeller signs. She was diagnosed as enteric encephalitis and managed with antibiotics along with corticosteroids. Fourth case was of 22-year-old female with blood culture positive for S. typhi and positive serum Widal test who after 3 days of treatment developed sudden cardiogenic shock and echocardiography confirmed presence of myopericarditis with mild pericardial effusion.

Keywords: Encephalopathy, enteric fever, hemophagocytic lymphohistiocytosis syndrome, liver abcess, myopericarditis, salmonella, typhoid, WIDAL

How to cite this article:
Rastogi VK, Passi P, Bembey RA, Chatterjee D, Bhattacharya S. Spectrum of enteric fever complications: As wide as in yesteryears. Indian J Med Spec 2022;13:57-61

How to cite this URL:
Rastogi VK, Passi P, Bembey RA, Chatterjee D, Bhattacharya S. Spectrum of enteric fever complications: As wide as in yesteryears. Indian J Med Spec [serial online] 2022 [cited 2022 Nov 26];13:57-61. Available from: http://www.ijms.in/text.asp?2022/13/1/57/336430

  Introduction Top

Enteric fever is an endemic disease recognized as systemic disease characterized by fever and abdominal pain and caused by dissemination of  Salmonella More Details typhi (S. typhi) or Salmonella paratyphi (S. paratyphi). Risk factors include contaminated water and food. Salmonella is motile Gram negative bacilli that may infect or colonize a wide range of mammalian hosts. Most common presenting features such as gastroenteritis, enteric fever, bacteremia but after entering the blood stream, all tissues and organs are susceptible and may manifest in a variety of clinical entities depending upon the site of localization.

  Case Reports Top

Case report 1

A patient, 59-year-old male, presented with complaint of high-grade fever, severe pain abdomen, recurrent stools, generalized weakness for 10 days before admission. On examination, conscious oriented, PR: 130/min, Spo2: 97% on room air, blood pressure (BP): 100/80 mm Hg, respiratory rate (RR): 28/min, temperature: 102°F, signs of dehydration, pallor, no icterus or lymphadenopathy, normal jugular venous pressure. On systemic examination, mild hepatosplenomegaly, was present, rest of systemic examination was unremarkable. Considering the differentials for an acute onset fever with thrombocytopenia with hepatosplenomegaly, dengue, malaria, leptospirosis, scrub typhus were considered as the differential diagnosis which were negative. He was started empirically on injection ceftriaxone 2 g intravenous (IV) BID along with supportive measures including hydration and antipyretics. Blood reports revealed progressive cytopenia and elevation of liver enzymes. In view of the presentation with fever, splenomegaly and progressive cytopenia with rapid clinical deterioration, a workup for iron deficiency, Vitamin B12 deficiency, folic acid deficiency and secondary hemophagocytic lymphohistiocytosis (HLH) was considered [Table 1] and [Figure 1]. Iron study, Vitamin B12, and folate levels were within normal range. A computed tomography (CT) scan of the abdomen done in view of persisting abdominal symptoms, showed ileocecal thickening with hepatosplenomegaly. Widal test results were showing O titer of >1:320. Blood culture showed S. typhi growth. The antibiotics were continued and on the 7th day of admission, the patient became afebrile. The patient needed 2-unit packed red blood cells (RBCs) transfusion and 4-unit Random donor platelets (RDP) as cytopenia persisted. Thereafter, the patient was started with injection dexamethasone at day 5 after consideration with hematologist in view of HLH and patient's blood counts improved subsequently.
Figure 1: Approach to hemophagocytic lymphohistiocytosis secondary to Salmonella infection. IVIG = intravenous immunoglobulin; *value suggested by authors; in the original diagnostic criteria, ferritin is >500 ng/ml; ** dexamethasone 10 mg/m/d for days followed by 6 mg/m2/d until complete response

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Table 1: Blood test reports of consecutive days of patient with hemophagocytic lymphohistiocytosis syndrome

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Case report 2

A patient, 59-year-old male, was admitted with complaints of high-grade fever with chills and rigors, severe abdominal pain in the epigastric region, recurrent vomiting, severe nausea for 1 week before admission, diarrhea and pain abdomen for 1 month. On examination, conscious, oriented, temperature: 102°F, PR: 160/min. BP: 100/60 mmHg, icterus was present. Per abdomen examination elicited the tenderness in the right hypochondrium and epigastric region, and liver was palpable about 6 cm below the costal margin. Rest of the systemic examination was within normal limits.

Serology for HIV, hepatitis B surface antigen, and anti-Hepatitis C virus were nonreactive. Widal test, immunoglobulin M (IgM) leptospira were negative and other test details are shown in [Table 2]. Ultrasonography of the abdomen showed enlargement of the liver with features suggestive of abscess measuring 4 cm × 4 cm × 4.6 cm and volume 180 cc involving segments VI and VII along with mild ascites. The patient was empirically started on IV ceftriaxone and metronidazole for liver abscess, but patient's condition deteriorated further with persistent high-grade fever and abdominal pain. Contrast-enhanced CT scan abdomen revealed a large liver abscess in the right lobe of size 5 cm × 4.9 cm × 4.6 cm. Ultrasound-guided liver aspiration was done. About 30 ml of pus was aspirated and sent for microbiological investigations. Pus culture revealed growth of S. typhi subspecies and IV antibiotics changed accordingly and IV metronidazole stopped. Blood and urine cultures were sterile. No pathogenic organism was grown in stool culture. Amoebic serology was negative. The patient improved gradually, responding well to the antibiotics as subsequent ultrasounds showed decreasing size of liver abscess. The patient was discharged on day 14 on oral antibiotics and other supportive treatment.
Table 2: Consecutive blood reports of patient with salmonella liver abscess

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Case report 3

A patient, 65-year-old female, presented with complaints of onset of high-grade continuous fever with severe headache, unsteadiness of gait simultaneously which became more unsteady over past 3 days before admission. Three to four episodes of tonic–clonic seizures followed by altered mentation. Multiple episodes of nonprojectile nonbilious vomiting and decreased oral intake were present. The patient primarily received antibiotics from local practitioner but did not improve and thus got admitted for further management. On examination, conscious, confused, agitated, toxic, temperature: 102°F, BP: 120/70 mmHg, PR: 99/min. Neurological examination revealed horizontal nystagmus, ataxia, hyporeflexia in all the four limbs, Babinski's sign was bilaterally positive, neck stiffness was negative and Kernig's sign was negative. Cerebrospinal fluid (CSF) report was within normal limits and showed colorless transparent fluid, total leukocyte count: 7/hpf (all lymphocytes), CSFprotein: 131 mg/dl, CSFsugar: 65 mg/dl. No organisms were seen in CSF on culture or Ziehl–Neelsen stain.

Brain magnetic resonance imaging (MRI) was done which showed a small infarct on the left side of cerebellum, rest within normal limits. Widal test: S. typhi, O: 1:640, S. typhi H: 1:320, S. paratyphi A and B negative. Blood culture grew S. typhi. She was treated with I.V ceftriaxone 2 g IV BID for 14 days along with IV levetiracetam 500 mg BID for convulsions and supportive care. Normal MRI excluded acute demyelinating encephalomyelitis and CSF culture excluded bacterial meningoencephalitis. Considering the hypothesis of a toxic reaction, treatment started with corticosteroids (Prednisone 1 mg/kg/day). She became afebrile within 2 days of starting the treatment and gradually, her neurological disorders also started reducing in intensity. After 14 days of treatment with ceftriaxone, she improved gradually became afebrile, conscious, oriented and was discharged later on in a hemodynamically stable condition.

Case report 4

A 22-year-old female presented to emergency room, with chief complaint of high-grade fever associated with chills from last 8 to 9 days. She also had complaints of mild breathlessness on exertion, nausea, recurrent vomiting episodes with pain abdomen and 4 episodes of loose stools watery to semi solid in consistency from the past 3 days, associated with poor appetite.

Her reports showed hemoglobin (Hb): 9.8, packed cell volume (PCV): 29.6, RBC: 3.60 million/cumm, Total leukocyte count (TLC): 5800, N75, L20, E5, B0, M2, erythrocyte sedimentation rate: 45, platelet count 1.40 lakh/cumm, MCV 82.2 fl, mean corpuscular hemoglobin (MCH): 27.2 pcg, MCH concentration (MCHC): 32 g/dl, WIDAL O and H titer 1:160.

She also had past episode of enteric fever in year 2019. After brief evaluation, her vitals were noted and general examination done: sick, dehydrated, toxic look, conscious, oriented, temperature: 100.4°E, BP: 100/60 mmHg, PR: 100/min, RR: 18/min, systemic examination: was normal except, mild tenderness at epigastrium and right hypochondrium. After assessment, relevant investigation was sent and treatment started with IV fluids at 80 ml/h, injection ceftriaxone – 2 g IV bd, tablet azithromycin – 500 mg bd, injection esomeprazole – 40 mg IV bd, injection ondansetron – 4 mg IV tds, tablet paracetamol – 650 mg stat, and SOS.

Report showed ABG: PH 7.46, pCO2: 32, pO2: 73, HCO3: 22.8, cardiac biomarkers were positive (troponin- 1.05 and brain natriuretic peptide- 253), Hb: 9.4 gm/dl, PCV: 29.3, RBC: 3.63, MCV: 80.6, MCH: 25.8, MCHC: 32, TLC: 7400, N89, L8, E1, B0, M2, platelet 1.50 lakh/cumm, USG whole abdomen revealed: bilateral pleural effusion, with passive lung collapse, GB wall edema, grade 1 hepatosplenomegaly (spleen size –13.5 cm) with mild ascites. Reports showed total bilirubin – 1.74, direct – 1.15, serum glutamic-oxaloacetic transaminase (SGOT) – 86, serum glutamic pyruvic transaminase – 47, alkaline phosphate – 251, gamma-glutamyltransferase – 96, C-reactive protein – 12.4 mg/dl, blood urea nitrogen – 6, Creatinine – 0.50, calcium – 7.8, sodium – 134, potassium – 3.6, chloride – 102, D-Dimer – 5040 ng/ml, COVID reverse transcription polymerase chain reaction and Dengue NS 1 antigen were negative, PS for MP was not seen, electrocardiography showed low voltage sinus borderline tachycardia, chest X-ray showed bilateral obtundation of costodiaphragmatic angles. Urgent cardiologist opinion was taken in view of positive Trop I and raised BNP [Figure 2]. Two-dimensional echocardiography was done at bed side which reveals heart rates – 97 bpm, mild global hypokinesia, ejection fraction – 51%, left ventricular internal dimension – 4.6 cm, Lad – 3.2 cm, inferior vena cava – 18 cm with >50% respiratory variation, normal right ventricle, no clot, minimal pericardial effusion seen [Figure 3]. Further advised for CPK – 107, CPKMB – 11.8 ng/ml, procalcitonin – 0.84 ng/ml and also her blood culture grew S. typhi with sensitivity toward ampicillin, azithromycin, ceftriaxone, chloramphenicol, co-trimoxazole, and resistant to fluoroquinolones.
Figure 2: Electrocardiography typically showing slight diffuse ST elevation and PR depression, progressing to normalization of segments with subsequent T-wave inversion in V1. Cardiac triage showing positive troponin I and BNP

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Figure 3: Echocardiography suggestive of myopericarditis with mild pericardial effusion

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Other test done shows contrast-enhanced CT chest: dense air space opacities in the central and periphery area of the peribronchovascular region in right upper, middle lobe, apico-posterior segment of left upper lobe, lingular segment and left lower lobe suggestive of acute respiratory distress syndrome with infective etiology. Right-sided mild-to-moderate pleural effusion with left-sided mild pleural effusion, hepatitis A virus and HEV IgM negative, HIV I, II negative, PT – 13.3, international normalized – 1.13, activated partial thromboplastin time – 31.51, Vitamin B12 – 951 pg/ml, Vitamin D3 <8 ng/ml.

She was managed with above medication along with injection multivitamin, injection enoxaparin – 40 mg subcutaneous OD, and tablet ursodeoxycholic acid – 300 mg bd as advised by cardiologist and gastroenterologist. She recovered gradually and became afebrile. Gradually, after stabilization, she was discharged with injection ceftriaxone for 2 weeks and advised to vaccinate against S. Typhi for future prevention of disease.

  Discussion Top

Enteric fever is a nonspecific febrile illness caused by typhoidal salmonella (S. typhi and S. paratyphi A, B, and C), characterized by inflammation of Peyer's patches, intestinal ulceration, and mesenteric lymphadenitis. The diagnosis should be considered in any patient with otherwise unexplained prolonged fever. Other clinical features include headache, chills, cough, myalgia, arthralgia, anorexia, abdominal pain, diarrhea, constipation, coated tongue, hepatosplenomegaly, and rarely a rash. The sinister presentation in our first case made us workup the case in lines of secondary HLH in enteric fever. Such presentation has been reported in a few cases earlier[1],[2] where the patient had rhabdomyolysis, sepsis and secondary HLH in a setting of enteric fever. Our patient had severe anemia which required blood transfusions, high lactate dehydrogenase, high triglycerides, high ferritin, high aspartate transaminase, and alanine transaminase levels which all pointed out to the possibility of HLH.

Hepatic abscess, classified by etiology, could be pyogenic, amoebic, fungal. The most common pathogens of the pyogenic hepatic abscesses are  Escherichia More Details coli, Klebsiella pneumoniae, Bacteroides, Enterococci, Streptococci, Staphylococci. Pyogenic liver abscess due to Salmonella species is not that common, and low incidence of hepatic manifestations may be explained by the phagocytic activity of its well-established reticuloendothelial system. Salmonella liver abscess have been reported with some preexisting hepatobiliary diseases such as cholelithiasis, amoebic abscess, echinococcal cysts, intrahepatic hematoma, and hepatocellular carcinoma. Salmonella liver abscess is mostly seen in the immunocompromised state, while our case was an immunocompetent adult male with no preexisting hepatobiliary disease. The blood culture was sterile in this case and likely source of the liver abscess in our patient could be secondary to the seeding of infection from the transient portal bacteremia or infection localized in the gall bladder could have travelled to the liver parenchyma.

Neurological manifestations of typhoid fever are very uncommon and hard to identify in regular practice. We have to think of possibilities of encephalopathy in these types of cases, considering the symptoms and history of fever associated with headache, nonprojectile vomiting, seizures with altered mentation, with supporting diagnostic result favoring systemic typhoidal infection with negative CSF and neuroimaging modalities in old persons with postantibiotic toxemia. Stupor, delirium, and coma are associated with a poor prognosis and a mortality rate above 40% in the tropics. Neuroimaging findings of typhoid-associated encephalopathy are sparse, with diffuse edema, symmetrical hypodensity, multifocal cerebellar hyperdensity, and generalized cerebral atrophy. In the present case, neurological complications within 1 week of starting antibiotic treatment raised the possible role of typhoid endotoxemia. In addition, the neurological status of the patient only improved after corticosteroid treatment had been instituted. Such reactions are considered as a result of adverse reaction to toxins released by Salmonella (whichever serotype is Typhi or Paratyphi) during bacterial lysis with typhoid toxins having an important affinity for the central nervous system. It has been suggested that endotoxins released by S. typhi could stimulate macrophages to produce cytokines, arachidonic acid and its metabolites that could be responsible for the toxic effects, particularly those seen in enteric fever's encephalopathy.[3],[4]

Pericarditis and pericardial effusion are the most common pathologic processes involving the pericardium. Acute pericarditis is very often a life-threatening condition. Common infectious causes of pericarditis are Streptococcus pneumoniae, other Streptococcus species, and Staphylococcus aureus, etc., but in our case, the cause of acute myopericarditis along with mild pericardial effusion was S. Typhi isolated in blood culture causing sudden cardiogenic shock in our patient.

Pericarditis is a rare complication of Salmonella infections, only about 30 cases have been reported so far. The mortality has been very high in these cases but our patient responded well to the treatment and became hemodynamically stable. In such cases, transient salmonella bacteremia from the gastrointestinal tract has also been previously noted just as in this case report.

Nontyphoidal Salmonella pericarditis has been reported as early as 1936 in a 36-year-old woman.[5] Another case report was from a 42-year-male who had pericarditis following bacteremia after an episode of gastroenteritis.[6]  Salmonella typhimurium Scientific Name Search is the most common organism isolated in nontyphoidal suppurative pericarditis, accounting for 50% of the reported cases. Most other cases are due to  Salmonella enteritidis Scientific Name Search species. Salmonella pericarditis has also been reported in systemic lupus erythematosus patients on dialysis due to defect in host defense against salmonella.

Although enteric fever is a common clinical entity in the tropics, it will be worthwhile to state that its clinical manifestations can be varied. When encountering uncommon clinical manifestations, the treating doctor needs to remember that the etiology is likely to be a common disease with an uncommon manifestation, rather than an uncommon disease with a common manifestation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

George N, Sethi P, Nischal N, Kumar A, Siripurapu G, Wig N, et al. A catastrophic presentation of enteric fever with secondary hemophagocytic lymphohistiocytosis. J Assoc Physicians India 2018;66:11-2.  Back to cited text no. 1
Non LR, Patel R, Esmaeeli A, Despotovic V. Typhoid fever complicated by hemophagocytic lymphohistiocytosis and rhabdomyolysis. Am J Trop Med Hyg 2015;93:1068-9.  Back to cited text no. 2
Azmel AA, Azmel A, Shunmugarajoo A. Typhoid associated encephalopathy–A case report and review of literature. Asian J Med Biomed 2018;2018:1.  Back to cited text no. 3
Sejvar J, Lutterloh E, Naiene J, Likaka A, Manda R, Nygren B, et al. Neurologic manifestations associated with an outbreak of typhoid fever, Malawi–Mozambique, 2009: An epidemiologic investigation. PLoS One 2012;7:e46099.  Back to cited text no. 4
Cohen L, Fink H, Gray I. Salmonella suipestifer bacteraemia: With pericarditis, pneumonitis, and pleural effusion. JAMA 1936;107:331-3.  Back to cited text no. 5
Can F, Demirbilek M, Erdem B, Ciftci U, Tunaoglu M, Laleli Y. A purulent pericarditis caused by Salmonella typhimurium. J Med Microbiol 2004;53:1051-2.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


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