Near‐Fatal Myocarditis Complicating Typhoid Fever in a Traveler Returning From Nepal

Michal Palombo MD, Reuma Margalit‐Yehuda MD, Eyal Leshem MD, Yechezkel Sidi MD, Eli Schwartz MD
DOI: 329-332 First published online: 1 September 2013


We report a 27‐year‐old traveler who returned from Nepal suffering from typhoid fever. His disease was complicated by life‐threatening myocarditis and ventricular fibrillation, a rare manifestation in travelers.

Enteric fever used to be a fatal disease with 10% to 20% mortality in the pre‐antibiotic era. With antibiotic treatment, fatality dropped to about 1% in the endemic countries. Fatal or complicated cases are rare in travelers, probably because of early antibiotic treatment even before specific diagnosis is made. With the emergence of antibiotic‐resistant Salmonella typhi, including multidrug resistant (MDR) strains, travel medicine practitioners may encounter complicated or life‐threatening cases.

Case Report

A 27‐year‐old Israeli traveler presented to a hospital in Israel with a 1‐week history of fever, rigors, abdominal pain, watery diarrhea, nausea, and anorexia. He had returned 11 days previously from a 6‐week trip including 4 weeks in Nepal, followed by 2 weeks in Thailand, where he had strictly adhered to kosher food. His pre‐travel vaccines included S typhi (Vi vaccine), which he had received 6 months prior to the trip.

The traveler was admitted to the hospital where initial blood cultures grew S typhi, and antibiotic treatment with ciprofloxacin was initiated according to antibiogram. The nalidixic acid susceptibility test was not performed. On day 5 of ciprofloxacin treatment, the patient was still febrile and symptoms were worsening; therefore, he was transferred to Sheba Medical Center.

On admission, the patient appeared ill and jaundiced but was alert, oriented, and hemodynamically stable with heart rate of 80 per minute. His temperature was 38.5°C (101.3 F). His heart sounds were not muffled. Initial blood tests were notable for hyperbilirubinemia (up to 9.23 mg/dL), elevated transaminases [alanine transaminase (ALT) 303 U/L and aspartate transaminase (AST) 548 U/L], prolonged international normalized ratio, thrombocytopenia (72 × 109/L), and hypokalemia (3.6 mmol/L). His antibiotic treatment was switched to ceftriaxone 2 g/day and azithromycin 500 mg/day (which is our treatment policy) and his condition improved. Repeated blood cultures from his admission to Sheba Medical Center indeed grew nalidixic acid‐resistant S typhi susceptible to ceftriaxone and azithromycin.

On the third day of the combined therapy of ceftriaxone and azithromycin (the beginning of the third week of the patient's illness), his temperature was near normal, but he had a bout of bloody diarrhea. Three hours later, a witnessed cardiac arrest due to ventricular fibrillation (VF) occurred and cardio‐pulmonary resuscitation (CPR) was performed according to the American Heart Association VF protocol. After resuscitation, he regained consciousness. Electrocardiography (ECG) revealed sinus rhythm with prolonged QT (QTc–541 millisecond) and incomplete right bundle branch block (ICRBBB) which was not noticed on previous ECG.

Blood tests showed K‐3.1 mmol/L and borderline troponin level of 0.088 mcg/L (normal value <0.07).

Echocardiography revealed profound left ventricle hypokinesis with an ejection fraction of 30%. On repeated ECG, prolonged QTc had reached 700 milliseconds. Cardiac magnetic resonance imaging showed reduced function of both ventricles and no radiological evidence of cardiomyopathy.

On specific questioning of the family regarding cardiac history of the patient, they had recalled that 3 years earlier he was diagnosed with myocarditis, which was related to viral infection with cytomegalovirus. He had been treated conservatively, recovered with normal cardiac function, and had remained asymptomatic during the 3 years preceding the current event. He had resumed full activities including regular sports training and performed significant physical effort during his trip to Nepal, including trekking up to an altitude of 5400 m. There was no history of sudden cardiac death in the family.

Three weeks after the cardiac arrest, the patient had no symptoms of enteric fever, and the QTc returned to normal with no ICRBBB. The patient was discharged with a wearable cardioverter defibrillator, which he used for 7 weeks. He returned to his daily activities; however, the last echocardiography, performed 7 months after the event, still revealed mild left ventricle (LV) dilation and mild global dysfunction with left ventricle ejection fraction (LVEF) of 44%.


We present a case of severe enteric fever due to S typhi infection. Considering an average incubation period of 14 to 21 days and beginning of symptoms 4 days before his return to Israel, the infection was most likely acquired in Nepal. Treating typhoid fever in the era of MDR strains becomes a challenge. These strains are found mainly in the Indian subcontinent where travelers acquire most cases of typhoid fever.1 It is important to note that on antibiogram, strains may appear susceptible to quinolones but resistant to nalidixic acid. These isolates should not be considered quinolone‐sensitive. Indeed, in this case, the S typhi strain was nalidixic acid‐resistant and did not respond to quinolone treatment. According to our own experience, in these cases, the use of a combination therapy with azithromycin and ceftriaxone appears to be highly effective, with a shorter defervescence time and without relapses.2

Untreated typhoid fever carried a high mortality rate that was drastically reduced in the antibiotic era to less than 1%. Life‐threatening typhoid fever complications are classically described during the third week of infection primarily due to gastrointestinal complications;3 however, extraintestinal manifestations may coincide. These include central nervous system involvement (3%–35%), pulmonary involvement (1%–86%), bone and joints (≤1%), hepatobiliary system (1%–26%), and genitourinary system (<1%). Cardiovascular complications occurred in 1% to 5%, and included myocarditis and endocarditis as the main complications, and pericarditis and arteritis, which are less common.4

Previous reports described myocarditis in approximately 4% to 7% of the patients with enteric fever.5–7 Prabha and colleagues found myocarditis in 7% of patients with enteric fever demonstrated by blood culture or serologically proved enteric fever.7 They also found that 46% of patients had ECG changes, where the commonest ECG abnormality was QTc prolongation (29%) followed by ST‐T changes (20%), bundle branch block (BBB, 7%), first degree A‐V block (%), and arrhythmia (2%). All the ECG changes were transient except BBB which persisted in three cases. However, all of the aforementioned case series were reported from endemic countries.

An exceptional report was described by Bobin and colleagues,8 who reported a series of autopsy findings of Soviet soldiers who suffered from typhoid fever during the Afghanistan war in the 1980s. The most frequent findings on autopsy among 65 fatal typhoid fever cases were: myocarditis (84.6%), pneumonia (75.4%), hemorrhagic syndrome (50.8%), and intestinal perforation (49.2%).

Literature search revealed very few reports about travelers with typhoid myocarditis. A recently published review of 17 cases of typhoid in travelers, mostly VFRs (visits to friends and relatives), from a New York hospital makes no mention of myocarditis in any of their cases.9 We found only two case reports of cardiac complications due to S typhi in residents of non‐endemic countries. Türoff and colleagues10 described a German woman who presented to the hospital with 10 days of high fever after returning from a visit to Pakistan. She was not vaccinated prior to her travel. ECG at admission was normal. The patient was treated with oral ciprofloxacin. Four days after admission, although clinical improvement was noticed, she suffered a cardiac arrest with subsequent successful resuscitation (Table 1). Of note is the fact that the patient developed a typhoid relapse 14 days following completion of quinolone treatment. The antibiotic treatment was switched to ceftriaxone for 14 days with a complete remission.

View this table:
Table 1

Typhoid myocarditis in travelers

Pathogen (blood cultures)Interval from disease onset to cardiac event (days)Cardiac manifestationBlood testECGEchoOutcome
M/27*S typhi17VFCK‐70 (N < 190), troponin I‐0.088 (N < 0.07)Prolonged QT ICRBBBLVEF 30%LVEF 44% with mild dilation and mild global dysfunction of the left ventricle and normal ECG at 7 months
F/4210S typhi14Pulmonary edema, cardiac arrestCK‐902 (N < 140), troponin T‐normalProlonged QTDecreased global cardiac functionNormal echo and function after 1 month
M/3411S typhi3Pulmonary edemaCK‐ 6341, troponin I‐7.86 (N < 0.08)Tachycardia and nonspecific ST, T changesLVEF 23%LVEF 42% with mild global hypokinesia at 5 months
  • ECG = electrocardiogram; Echo = echocardiography; M = male; F = female; VF = ventricular fibrillation; CK = creatinine kinase; ICRBBB = incomplete right bundle branch block; LVEF = left ventricle ejection fraction.

  • * Present case.

  • The case presentation notes that history data were limited upon presentation.

  • Normal values were not mentioned in the text.

Al‐aqeedi and colleagues11 described a 34‐year‐old Indian man who traveled to Qatar and presented to the emergency room after 3 days of febrile illness with severe typhoid fever and multiorgan failure. His cardiac complications included myocarditis with pulmonary edema (Table 1).

The common features to these three cases were the growth of S typhi in blood cultures. In all three cases, there was cardiac damage demonstrated by echocardiography, and the LVEF recovery was incomplete in two of three cases. We also noted that in Türoff's case as well as in our case, proper antibiotic treatment was delayed and therefore the patients reached the third week of illness, when complications are much more common.

The lack of more case reports implies that although myocarditis might be more common in endemic areas, it is much less common in travelers. A possible explanation is that most travelers have better access to appropriate medical care.

The reason for the VF in our patient is likely multifactorial. It might be induced by hypokalemia in a patient with a diseased heart and a prolonged QT interval. The myocardial dysfunction might be the direct effect of the typhoid infection as well as the prolonged QT, which is described in typhoid fever.7 Toxic reaction at the beginning of antibiotic treatment has been described and is thought to be due to the release of endotoxin after bacteria lysis. The endotoxin can cause neurologic symptoms, cardiovascular collapse, and temperature deregulation. These reactions were described after using chloramphenicol, amoxicillin, fluoroquinolones, and third‐generation cephalosporins.12 Our patient was treated with third‐generation cephalosporin and azithromycin. A recent study showed increased cardiac death and all‐cause mortality among patients who received azithromycin.13


In case of travelers returning from an endemic area with typhoid fever, myocarditis might develop especially when early proper antibiotic treatment is not given. This complication can be life‐threatening. The risk of MDR strains should be considered when choosing antibiotics. ECG and electrolyte levels should be carefully and consistently monitored throughout the course of treatment.

Figure 1

This is a typical food cart along the lake shore in Pokhara in Nepal, the country where typhoid fever was acquired by the patient reported by Michal Palombo et al. (see pages 329‐332). Traveling to the Indian subcontinent is associated with a higher risk of enteric fever. Photo Credit: Eric Caumes

Declaration of Interests

The authors state that they have no conflicts of interest to declare.


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