Abstract

Typhoid fever, endemic in the developing world, is associated with international travel in developed nations. We present a case of Salmonella enterica infection in a patient without a history of international travel acquired from his traveling ex‐wife. History of overseas travel in family members should be investigated when evaluating suspected cases.

Typhoid fever, or infection with Salmonella enterica serotype typhi, is endemic in much of the developing world, but in North America, the disease is increasingly associated with international travel. Of 400 1 cases reported annually in the United States and 75 cases in Canada, 2 only 25% 2,3 are domestically acquired. We present a case of typhoid fever in a patient without history of international travel.

Case Presentation

A 57‐year‐old African American male with no significant past medical history presented with 1 week of fevers to 39.4°C, myalgias, abdominal pain, constipation, and decreased oral intake. Review of symptoms was also significant for night sweats, weight loss, nonproductive cough, and headache. The patient denied recent travel, sick contacts, having contact with recent immigrants, or exposure to high‐risk foods. Initial evaluation in the emergency room 2 days prior to admission resulted in diagnosis of viral syndrome and symptomatic treatment.

Physical examination revealed an ill appearing and diaphoretic male with a temperature of 39.4°C, a heart rate of 90, and a blood pressure of 130/54 mm Hg with notable emotional lability on mental status exam. Cardiovascular, lung, and abdominal exams were normal. Skin exam revealed no lesions and no lymphadenopathy was noted.

Laboratory values revealed a pancytopenia and transaminitis but were otherwise unremarkable. Lumbar puncture showed no white blood cells with normal glucose and protein. Abdominal computed tomography scan showed terminal ileum bowel wall thickening, regional lymphadenopathy, splenomegaly, and a right iliacus fluid collection.

Two days after admission, following repeated febrile episodes with relative bradycardia, multiple blood cultures grew S enterica serotype typhi. Following intravenous ciprofloxacin infusion, clinical improvement occurred in 48 hours with near resolution of symptoms at 4 days. Multiple stool cultures were negative. Epidemiological investigation with directed questioning revealed that his ex‐wife was foreign born and had frequent travels to the Philippines; she was later found to be a carrier of S enterica and was treated by the public health department. No information was available on her treatment course or predisposing factors for colonization.

Discussion

Our case is an unusual example of domestically acquired typhoid. While domestically acquired cases do occur, they are much less common as over the past 50 years, it has become largely a disease associated with travel to endemic areas, particularly the Indian subcontinent. Among reported typhoid cases in the United States between 1984 and 1994, travel to the Indian subcontinent 4 was associated with an 18‐fold increase in cases over travel to other regions. 5

Incidence of travel‐related typhoid is reported as 0.26 to 0.93 per 100,000 (16.7 per 100,000 in travelers to India), 4–6 with the majority (80%) of cases visiting friends and relatives (VFR) 3 (as our patient’s ex‐wife was). A second study revealed 66% of cases were foreign‐born US residents or immigrants, 6 suggesting a possible high‐yield population for an intervention strategy.

Our patient relayed no known exposures to common sources of S enterica such as recent immigrants, imported foods, or international travel. His ex‐wife with whom he had infrequent contact and who had immigrated several years ago was an atypical source and missed during the history. Whereas typhoid related to international travel is well characterized, the origin of domestically acquired cases is less clear as a majority of cases are sporadic, with cases rarely being traced to a carrier, making source finding difficult. 3–6 Ingestion of contaminated food, 7 a sexually transmitted disease in men who have sex with men, 8 and laboratory exposure have been identified as sources of domestic cases. 9 Outbreaks do sometimes lead to better understanding of exposure risks in domestic cases. US outbreaks comprise 7% to 19% of overall typhoid cases; 4–6 a major review of these outbreaks from 1960 to 1999 found that 72% of cases were food borne and 17% related to water or ice. 7

Recently, domestic cases of S enterica with wide geographic distribution were linked to consumption of frozen fruit shakes. 10 Contaminated fruit imported from Guatemala and Honduras affected a food product prepared in the United States. As increasingly produce is imported from the developing world to developed nations, this likely will not represent the last of such cases. Given the success of universal hepatitis A vaccination in reducing domestic U.S. food‐borne cases of hepatitis A, 11 this raises the question of targeted or universal typhoid vaccination to affect a similar response. The cost–benefit in western countries of universal vaccine is not currently feasible given the low number of overall typhoid cases but targeted vaccination may be feasible in source countries 12 who export produce with both countries benefiting.

Also illustrated by our case, the symptoms of typhoid fever are nonspecific and can be misdiagnosed as more common illnesses. In a study of French travelers with typhoid fever, the most common symptoms were fever (100%), headache (82%), diarrhea (50%), and chills (50%). 13 A majority of patients had normal leukocyte counts, with leukopenia noted in 27% and transaminitis in 72%. The authors emphasize the unreliability of signs, symptoms, and laboratory in diagnosis.

While our patient’s isolate was sensitive to all commonly used antibiotics for S enterica, this is becoming less common. Of S enterica isolated in the United States, 22% to 25% are resistant to at least one antibiotic and 17% are resistant to five or more, 6 rendering first‐line agents like ampicillin, chloramphenicol, and trimethoprim–sulfamethoxazole ineffective empiric treatment choices. Fluoroquinolones and third‐generation cephalosporins are now preferred. Multidrug‐resistant (MDR)S enterica is classically defined as resistance to ampicillin, chloramphenicol, and trimethoprim–sulfamethoxazole. 14 Travel to India and Vietnam has been associated with disproportionately higher rates of MDR S enterica and decreasing fluoroquinolone susceptibility. Further complicating the issue is the possibility of mixed Salmonella infection, which has been reported and could result in organisms with different susceptibility patterns. 15

With antibiotic resistance rates rising, preventive strategies are increasingly important and might additionally reduce cases of S enterica infection. Had our patient’s ex‐wife been vaccinated or received food and water hygiene education prior to her travel, this case could have been prevented. Though the reported rate of typhoid fever in previously vaccinated travelers is roughly 4%, 2,6 the two commercially available typhoid vaccines orally administered attenuated (Ty21a) and intramuscularly injected Vi capsular polysaccharide (ViCPS) have protective efficacies of 51% and 55%, respectively, in a recent meta‐analysis. 16 A conjugated typhoid vaccination with more promising results and efficacy in children is also under development. 17 Vaccines fail to protect against Salmonella paratyphi A, however, which is an emerging cause of enteric fever 18 among travelers and mimics typhoid fever.

In the developed world, typhoid is largely a disease related to travel. Domestically acquired cases do occur usually among noncitizen immigrants or imported foodstuffs. Typhoid is rare, often presents with nonspecific symptoms, and is transmitted from asymptomatic carriers. As illustrated by our case, a thorough travel history including that of family members is very important when no obvious source of typhoid fever has been elicited. Also, like many other reported typhoid cases, our patient’s source (ex‐wife) did not receive the typhoid vaccination prior to her trip, demonstrating the importance of pretravel counseling and immunization, particularly among VFRs to decrease the rates of travel‐related illness.

Disclaimer

The opinions and assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the US Department of Defense or the Department of the Navy.

Declaration of interests

The authors state that they have no conflicts of interest.

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