Typhoid Fever: Vaccination Failures

Abstract & Commentary

Synopsis: Three commercial typhoid fever vaccines are available, yet data on efficacy in travelers have been lacking. The occurrence of typhoid fever in a group of travelers to Indonesia who had been vaccinated against typhoid fever suggests incomplete efficacy.

Source: Cobelens FG, et al. Typhoid fever in group travelers: Opportunity for studying vaccine efficacy. J Travel Med 2000; 7:19-24.

In 1994, 91 cases of typhoid fever were reported to the Inspectorate of Healthcare of the Netherlands Ministry of Health. Eight patients had recently traveled to Indonesia, linked to package tours conducted by the same tour operator. One hundred ten travelers participated in a questionnaire-based study designed to describe demographics, history of typhoid fever vaccine use, pretravel medical conditions, medications, diagnosed or suspected typhoid fever, and details of their journey, including meals taken.

Six patients were defined as typhoid fever cases in which Salmonella typhi was isolated from one or more blood cultures. Fifteen others reported an illness compatible with typhoid fever but did not have positive blood cultures. Many were diagnosed with diarrheal illness or received empiric treatment with ciprofloxacin. Vaccination status was ascertained by asking the respondents to indicate the most recent entry for typhoid fever in their International Certificate for Yellow Fever vaccination or Military Passport of the Netherlands Armed Forces. Vaccination status was considered "documented" if either written proof was available or if the provider had confirmed the vaccination from records. Seven respondents were excluded because of reduced gastric acidity or use of an antibiotic. Of the remaining 103 respondents, 96 (93.2%) claimed to have been vaccinated against typhoid fever within the years preceding the journey. Immunization status was well documented for 85 (82.5%); however, 11 respondents who claimed to have received the oral typhoid vaccine did not have written documentation.

There were no differences in age, sex, or travel group. All cases of typhoid fever occurred in documented recipients of the oral Ty 21a vaccine with an attack rate of 8.6% (95% CI 3.2-17.7%) or 10.2% (95% CI 3.8- 20.8%) if restricted to respondents with documented vaccination status.

Comment by molly stenzel, md, and Maria D. Mileno, MD

This important publication clearly indicates that the risk of typhoid fever can be considerable, even for an immunized population of travelers. Other additional cases may well have been masked by antibiotic prophylaxis or by antibiotic treatment of diarrhea. The following case history illustrates the degree of morbidity that may accompany typhoid fever.

A 20-year-old, previously healthy, male college student from Rhode Island returned from a one-month stay in West Africa. He had traveled to Argentina 10 months prior to admission, to Senegal and the Ivory Coast five years ago, and had lived in Africa for several years as a young child. While recently abroad in Mauritania and Senegal he developed watery diarrhea without noting any blood in his stool, fevers, chills, or abdominal pain. He took several doses of loperamide, but he did not self-administer either ciprofloxacin or other antibiotics, and his diarrhea resolved within three days, and just prior to his return to the United States.

Four days prior to admission, he experienced headache, malaise, and generalized fatigue. The following evening he noted fever and rigors every 4-6 hours. Diarrhea symptoms returned, consisting of one or two watery, nonbloody stools per day with mild abdominal cramping. He denied photophobia, neck stiffness, or change in mentation, but stated that he felt "kind of slow," particularly when febrile. On the day of admission he experienced nausea and vomited once.

During his trip to West Africa, he first stayed in the coastal city of Nouakchott, then traveled along the southwest border of Mauritania. He resided in river villages and spent several days in the desert of Senegal. When traveling in rural areas, he stayed with families in tent homes or grass huts. He sustained mosquito bites, despite sleeping under mosquito netting. He was not aware of being bitten by flies or ticks. He drank primarily bottled or filtered water or hot tea, but did occasionally drink fruit juice or milk diluted with water obtained from uncertain sources. He ate well-cooked fish or meat, often from a communal bowl using his hands, without utensils as dictated by local custom. He sampled a drink consisting of sweetened camel’s milk. He had no sexual contact during his trip and received no blood transfusions.

The patient had received all of his routine childhood immunizations and yellow fever vaccines in 1995. He had been immunized with BCG vaccine as a small child. His most recent PPD test, during August 1999, was negative. He received a meningococcal vaccine just prior to his trip, but did not receive typhoid fever vaccine. However, he did obtain and use mefloquine prophylaxis before and during his stay in Africa.

Physical examination revealed a thin, flushed young man with a temperature of 39.4°C, a pulse of 96/min, and a respiratory rate of 16. There were no skin lesions. Aside from mild epigastric tenderness, his physical findings were otherwise normal.

Results of admission laboratory studies showed a white blood cell count of 5.9; 47% segmented neutrophils; 32% band forms; 13% lymphocytes; 8% monocytes; hemoglobin 14.6 g/dL with normal red cell morphology; platelets 148,000, creatinine 0.9 mg/dL; AST 64 IU/L (normal range 10-42): ALT, alkaline phosphatase, and total bilirubin were within normal limits. Urinalysis was normal except for mild proteinuria. Cerebrospinal fluid analysis revealed no abnormalities and the chest radiograph was normal.

Blood smears revealed no malaria parasites. Two sets of blood cultures drawn on admission, and another set drawn on the first hospital day, grew Salmonella typhi. The blood isolate was sensitive to all antibiotics tested, including trimethoprim/sulfamethoxazole, ampicillin, ceftriaxone, and ciprofloxacin. Stool examination revealed many cysts and trophozoites of Giardia lamblia.

Treatment with ciprofloxacin and metronidazole was initiated. Over the subsequent hospital days, the diarrhea resolved and he finally defervesced by day 8. A transient rise in hepatic transaminases (peak AST 488 IU/L) occurred on hospital day 6. Two weeks later he continued to have abdominal tenderness on palpation of the right upper quadrant, but was otherwise doing well. Follow-up stool cultures and examination were negative. This young man was relatively fortunate in that he did not experience an episode of severe gastrointestinal bleeding, intestinal perforation, bacterial peritonitis, or pneumonia. A review of the recent literature revealed no cases of typhoid fever reported from Mauritania. Surveillance of group travelers may reveal typhoid activity in regions where reporting is not adequate. (Dr. Mileno is Director, Travel Medicine, The Miriam Hospital, Assistant Professor of Medicine, Brown University, Providence, RI. Dr. Stenzel is an Infectious Disease Fellow at Brown University, Providence, RI.)

Which of the following is true about typhoid fever vaccination?

a. The oral formulation is as effective as the injectable.

b. It can free the traveler of strict food and water scrutiny.

c. It was shown to ameliorate but not eliminate typhoid.

d. Travelers have acquired typhoid fever despite vaccination.

e. a and d