Endogenously contracted typhoid fever has decreased dramatically in the .... such as malaria, rick- ettsioses, brucellosis, tularemia, infectious mononucleosis,.
Travel Trouble: Typhoid Fever-A Case Presentation and Review Edward I. Lifshitz, MD ...... -"'Jo._
Abstract. Endogenously contracted typhoid fever has decreased dramatically in the industrialized world. A practicing physician may not see a case in a lifetime, but health professionals should not allow typhoid to recede from their consciousness. Typhoid is still endemic in much of the developing world, and as travel increases, illnesses can and do skip around the world in a day. College students are at particular risk because they often travel on a low budget for extended periods, mix freel y with local populations in endemic regions, and are not aware of the risks of such travel. College health professionals need to be able to recognize typhoid fever, should it present, and give advice to patients on primary prevention. The author includes a case presentation that is not completely classical for typhoid fever, as well as a state-of-the-art review, including description, epidemiology, signs and symptoms, diagnosis, treatment, and prevention. Special attention is given to the question of who should be immunized and which vaccines are effective. Key Words: enteric fever, immunization, salmonella, students, travel, treatment, typhoid fever
Case Report
T
c is a 25-year-old male college student, originally
from Bangladesh, who presented on February 1, complaining of elevated temperatures (39.4°-40°C) for 15 to 16 days. His fever occurred almost entirely at night and was usually accompanied by rigors (chills). The patient also complained of vague lower back pain, as well as some slight nausea without vomiting, headaches, and general malaise. Over the past several days, he had developed a nonproductive cough. He denied having diarrhea, abdominal pain, dyspnea, or rash. He had a past medical history significant for a positive Mantoux test with a negative chest rad iograph 2 years before he appeared for treatment. Edward I. Lifshitz is a staff physician with the Rutgers Uni1·ersity Student Health Services in New Brunswick, New Jersey. VOL 45 1 NOV 1996
TC had been livi ng in the United States for approx imately 7 years and had begun to feel ill during a return trip to Bangladesh. He was initially seen by a physician there who told him he did not have malaria because his pulse was "too slow." He was placed on an unknown antibiotic with significant (but not complete) resolution of symptoms. The patient suffered a relapse of symptoms while on the plane returning co the United States, and he came to the health service for treatment. On presentation, TC had a temperature of 39.5°C (I 03. l °F), a pulse of 118, and a respiratory rate of 18. Blood pressure was 118170, and he was in no acute distress. I saw no rash, his lu ngs were clear, his heart regular without murmurs, and the abdominal exam was benign. His chest radi ograph showed no infiltrates. The patient's urine analysis was completely within normal limits, and his blood differentials revealed a white count of 9400/µL without significant bandemia or lymphocytosis. Chemistries were significant only for mild elevations in liver enzymes: SGOT!AST of 50 µIL (8-37), SGPT/ALT 98 µIL (30.....65), gam ma GT 93 µIL (5-85), total bilirubi n 0.6 mg/dL (0. 1- 1.1), and alkaline phosphatase 127 mg/dL (32-1 17). Thick and thin smears for plasmodium were negative. Blood cultures the following day revealed Salmonella typhi. Description Enteric fever may be caused by any bacteria in the Salmonella genus. S typhi is the exclusive causative agent of the most severe of the enteric fevers, typhoid fever. S typhi is a motile, gram-negative bacillus that, unlike many of the other Salmonella, has no zoonotic reservoir. Thus, except in very unusual circumstances, there is no person-to-person or animal-to-person transmission. 1 This almost-total reliance on the fecal-oral route of transmission makes typhoid fever largely a disease of developing countries, unlike Salmonel99
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tors have found students to be at greatest risk. Of those in
la gastroenteritis, which tends to be a disease of developed countries. 2 S typhi is not a particularly hardy bacterium. It survives in stool or sewage for only 3 to 5 days and in water for less than 2 weeks, although it can survive in ice. It does better in milk, within which it can thrive and multiply without changing the milk's appearance. It can also survive for several months in soil but probably does not multiply. 3 Most large outbreaks of typhoid fever can be traced to contaminated milk or water, although for water to be the source of an epidemic, it must be regularly recontaminated. Other documented sources include shellfish, tinned meat, and any uncooked food contaminated by a carrier (eg, Typhoid Mary). Rarely, direct contagion may come from infected clothes, and flies may also carry the bacillus from latrines to food. 3- 5
travel-related typhoid fever cases in the United States from 1975 to 1984 occurred in students.7 There is no clear-cut explanation for this trend, although it has been postulated that this may be because students travel more, and for longer periods of time, and are more frequently on a lower budget and therefore tend to travel through less sanitary areas than the general tourist population. In addition, many students originally from endemic areas return home frequently-often with the mistaken impression that they are immune to local maladies. Travel-related typhoid fever has a bimodal seasonal distribution, with a sharp peak in January and a higher, broader peak during the summer months.7 This distribution is probably at least partially due to travel patterns.
Epidemiology
Signs and Symptoms
As would be expected, the United States has not recently had a large number of typhoid cases, with only 441 cases of typhoid fever reported in the United States in 1994. Of these, 121 were in New York, New Jersey, and Pennsylvania. This represents 0.17 cases per 100,000 population, a rate that has been relatively stable since around 1960. In 1955, the rate was 1.05 cases per 100,000 population,6 and in the early part of this century, the rate was 50 per 100,000 (in 1920, the total was 35,994 cases). 7 Over time, the point of infection for cases diagnosed on American soil has gradually shifted. From 1967 to 1972, approximately 67% of the typhoid cases were domestically acquired, whereas from 1975 to 1984, only 38% were acquired in the United States. By 1990, this had further decreased to 29%. Only part of this swing could be attributed to Americans' increasing foreign travel. The rest of the decline is probably the result of increasingly good sanitation and infection controJ. 7- 10 Although travel to Mexico represents a plurality of foreign-acquired cases of typhoid fever (approximately 39%), Mexico is not near the top of the list of countries when adjusted for the number of travelers. Risks to Americans during foreign travel range from around 200 cases per 100,000 visits to Mexico to about 580 to 1,740 cases per 100,000 visits to Peru, India, Pakistan, and Chile. As a geographic region as a whole, Southeast Asia, including the Indian subcontinent, carries the highest risk of typhoid infection.7•9 Attempts to identify groups at high risk for acq uiring typhoid fever domestically have not demonstrated unusually large clusters. Although sewer workers were previously postulated as being at high risk, studies showed that they were not, but domestic workers and household contacts of known typhoid fever patients were fou nd to be at risk. Hospital workers, in general, and microbiology laboratory technicians, in particular, were found to have a small increase in risk.7- 9 Domestic outbreaks have occasionally been traced to immigrant carriers from endemic areas. 11 Among travel -related cases of typho id fever, investiga-
S typhi is absorbed in the gastrointestinal tract, whose mucosa then evolves through four stages. First hyperplasia develops, then necrosis and sloughing, which continues to ulceration, and finally healing. 12 Healing of ulcerations occurs without significant scarring, and strictures do not develop. 1 In addition to the gut, almost any other organ may be involved. Liver, spleen, kidney, heart, and lung are not infrequently affected. Deep venous thrombosis, "Zenker's degeneration" of skeletal muscle, and metastatic infection of bone may all occur. 12 The incubation period is directly related to the size of the inoculum. Illness typically develops in I to 2 weeks, but may take as few as 3 days or as many as 60 days. Most patients are totally asymptomatic during the incubation period, but they may develop diarrhea if the inoculum is large. Stool cultures during this time may be transiently positive, but they usually tum negative until the disease becomes active. 13•14 Typhoid fever is an insidious disease in which most patients are unable to pinpoint an exact begi nning to their illness. Symptoms usually develop once the organisms have penetrated the intestinal mucosa, are multiplying in lymphoid tissue, and have begun to gain access to the circulation. In most patients, the first sign is fever, which gradually increases over several days. This is soon followed by malaise, anorexia, muscular- skeletal discomfort, headache, cough, and pharyngitis (in decreasing frequency from around 90% to 20% to 40% of the cases). 1•13•14 Complete blood counts are nonspecific, but often reveal a leukopenia with relative lymphocytosis. A "pulse temperature deficit" is associated with typhoid fever. It is rare for the pulse to exceed 105 in adults during the 1st week, and the pulse is usually 85 to 95, even when the patient has a high fever. As the disease progresses, the pulse most commonly increases to from 110 to 130, although it may remain slow throughout the course of the infection. 3 It is interesting that our patient was told that his
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pulse was "too slow" for him to have malaria, although by the time he presented to us it had increased to 118. By the 2nd week of symptoms (usually the 3rd week after infection), the temperature becomes sustained at around 39.4°C to 40°C (103°F to 104°F). It is unusual for rigors to develop. Other commonly affected systems include the gastrointestinal tract, where constipation is more typical than diarrhea; the respiratory tract, most often a nonproductive cough without radiographic evidence of pneumonia; and the liver and spleen, which may become enlarged. A "feculent body odor" has been described, and "rose spots" on the skin are frequently found. Rose spots are slightly raised, discrete, irregular pink lesions 2 to 4 mm in diameter. They blanch with pressure and are most commonly found on the anterior trunk between the nipples and umbilicus. 1•3
Diagnosis
In patients who have all the classic signs and symptoms of typhoid fever-relative bradycardia, headache, rose spots, splenomegaly, leukopenia with relative lymphocytosis, prolonged fever-the diagnosis is strongly suggested. However, most patients do not have all these "classic" findings. Typhoid fever should therefore be suspected in any patient with a fever lasting more that 1 week without manifestation of other diseases, particularly if the individual has been traveling in an endemic region. 3 The differential diagnosis for typhoid fever is broad and includes any etiology that causes prolonged fever. This includes both infectious processes, such as malaria, rickettsioses, brucellosis, tularemia, infectious mononucleosis, hepatitis, miliary tuberculosis, typhus, endocarditis, cytomegalovirus, paratyphoid fever, and noninfectious conditions, including lymphoma and collagen vascular disease. To make the definitive diagnosis of typhoid fever, the clinician must isolate the S typhi organism, particularly from a nongastrointestinal site. S typhi is most reliably cultured from blood and bone marrow, both of which are positive in 80% to 90% of cases (culture of peripheral blood usually turns positive first, often during the 1st week of symptoms). When rose spots are present, S typhi may be cultured from them 60% of the time, and urine cultures will be positive in approximately 25% of the cases (Table I). 1-3, 1s
Serologic tests are less useful. Although an agglutination reaction (the Wida) test) is frequently seen to the H, 0 , and Vi agglutinin, it is typically not present until the 3rd or 4th week. In addition, because the test is complicated and costly to perform, it is not a practical option in most areas of the world where typhoid is endemic2 ; in nonendemic regions (eg, the United States) it is a poor test because of the greater likelihood of a false positive, either from other organisms with cross-reacting antigens or other conditions that produce globulins that react with the H and 0 agglutinin (eg, li ver disease). H agglutinin also increases after vaccination. Yi agglutinin and Yi antibody by radioimmunoassay do, however, both have value in identifying the typhoid-carrier statc.3· 11 VOL 45, NOV 1996
TABLE 1 Laboratory Findings in Untreated Typhoid Fever
Positive finding
Percentage
Blood culture Stool culture
80-90 Transiently positive 80 50 25 10 80-90 60 20 50 80
Urine culture Bone marrow culture Rose spot culture Wida) test
Weeks after infection 1.5- 3 0-1 2-4 4-5 2-4 4-5 2-4 2-4 1-2 2-3.5 3.5-carrier state
So11rce. Adapted from Rubin R, Weinste in L. Salmonel/osis. New
York: Stratton Intercontinental Medical Book Corporation ; 1977: 48-49.
Clinical Course lf left untreated, patients with typhoid fever typically experience gradual defervescence between the 3rd and 4th week of illness. Serious complications are not common, but they tend to occur in the more severe clinical presentations. For example, the more extreme the early symptoms are, the more likely that neuropsychiatric complications, most commonly delirium, will develop. Hematologic disorders, such as mild hemolytic anemia, leukopenia, and eosinophilia, are also frequently seen. The renal system is occasionally involved, and a toxic myocarditis may develop. Intestinal perforation occurs in 2% to 3% of illnesses, and hemorrhage may arise in anywhere from 3% to 21 % of cases. 1•3 All told, only seven deaths occurred in the United States between 1980 and 1990, a 1.5% case-fatality ratio. This is significantly lower than the mortality rates in most other countries.9 As is to be expected, most of the fatalities were among individuals who were already medically fragile. Metastatic infection secondary to sustained bacteremia may occur at any time-from acute infection to years later. Any area of the body may be invoived, but metastasis most often involves bone. Other common sites are the spleen, muscle, breasts, thyroid, cervical lymph nodes, salivary glands, and the abdominal cavity. 1 A concern in dealing with patients with typhoid fever is the development of a carrier state. About 3% to 13% of untreated patients will relapse (this number actually rises to 15% to 20% for those treated with chloramphenicol, suggesting an interference with the formation of protective antibodies).1.1 6 Approximately 3.3% of those infected become chronic carriers who are excreting S typhi in their stools for more than I year. 17 It is these patients who pose the greatest public health risk. 101
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Treatment
In the United States, three antibiotic treatments have traditionalJy been used for acute typhoid fever: chloramphenicol , trime thoprim-sulfamethoxazole (TMP-SMZ), and ampicillin/amoxicillin (co-trimoxazole is still commonly used outside of the United States). Worldwide, chloramphenicol has had the widest use and is the standard with which others are compared. Some common treatment regimens for representative agents from most of the commonl y used classes of antibiotics for typhoid fever are summarized in Table 2. C hloramphenicol has the advantage of being inexpensive, and it is available in both an intravenous and oral formulation. C linical effect is seen as rapidly with chloramphenicol as with any antibiotic (with the possible exception of ofloxacin). 18 Disadvantages include chloramphenicol's not being bactericidal at usual concentrations in blood or cerebrospinal fluid. In addition, bone marrow suppression is a real concern, particularly in those already at risk for increased incidence of severe typhoidal disease (eg, patients with AIDS, malignancy, sickle cell disease, and malaria). 19 In most areas of the world, resistance has remained low, although in some regions significant resistance has begun to develop. Key among these regions is the Far East.7·2 (}...22 Resistance is plasmid mediated and increases with increased use (and misuse) of chloramphenicol. 23 TMP-SMZ is also inexpensive and is available for both intravenous and oral administration. Along with amoxicillin, TMP-SMZ has been effective in at least some outbreaks of chloramphenicol-resistant typhoid fever. 20·24 H owever, there is still resistance (approximately 7% in the United States). 7 TMP-SMZ is not bactericidal, and significant hematologic, hepatic, and dermal toxicities-particularly in AIDS patients- may develop. Ampicillin and amoxicillin are inexpensive, bactericidal, available for use both intravenously and orally, and these
antibiotics reach high levels in the gallbladder but possibly not in the gallbladder wall. 25 Ampicillin and amoxfcillin are also subject to increasing resistance, as well as to frequent allergic reactions. 7•19- 21 Two relatively new classes of antibiotics have been found to be useful in treating typhoid fever. "Third-generation" cephalosporins (eg, cefotaxime, ceftriaxone, and cefoperazone) have very high activity against Salmonella. Althoug h these agents are very expensive and must be administered intravenously, they have certain distinct advantages. Resistance, to date, is very low, they are bactericidal, and they cross the blood-brain barrier well. Cefotaxime, in particular, is the drug of choice for Salmonella meningitis.26 Several studies have documented the efficacy of the flouroquinalones. Ofloxacin, norfloxacin, and ciprofloxacin have alJ been studied and shown to have cure rates approaching I 00%, even in S typhi resistant to chloramphenicol, TMP-SMX, and ampicillin.22·27•28 Ciprofloxacin is also available for both oral and intravenous adm inistration. The growing consensus is that, despite their expense, the flouroquinalones are the drugs of choice (except for children) for typhoid fever contracted in regions where resistance is common. 22•29 In patients for whom the risk of resistance is rel atively low, o ne of the three older, less-expensive antibiotics is appropriate. Relapse is a frequent complication of typhoid fever. In those not treated with anti biotics, relapse rates range from 3% to I 3% (and, as previously noted, the rate may even go as high as 20% in patients who are treated with chloramphenicol).1·16 Relapsing disease may be more severe than the initial presentation and may occur ei ther after convalescence develops or while signs and symptoms of the d isease are still present but have decreased in intensity. The source of relapse appears to be a protected intracellular population of S typhi in the liver, gall bladder, spleen, mesenteric lymph nodes, or Peyer's patches. The flouroquinalones are
TABLE 2 Selected Treatment Regimens for Acute Typhoid Fever in Adults
Agent Amoxicillin Chloramphenicol TMP-SMZ Cefotaxime Ci profl oxaci n Ofloxaxin
Dose each administration l.5g 500--700 mg 500--1,000 mg 800 mg (TMP)/ 160 mg (SMZ) 2-3g 500 mg 200mg 200-300 mg
Route
Number of daily administrations
PO PO IV PO
4 4 4 2
IV PO IV PO
3-6 2 2 2
Note. Duration of all regimens is usually 2 weeks. PO = orally administered ; IV = intravenously. Data from Rubin and Weinstein, 1 Gilman, Terminel, Levine et al, 24 Rodriguez-Noriega, Andrade-Villanueva, 27 25 26 ancl Amaya-Tapia, ~rand Overturf, Wang, Xian-jin, Mei-fang, and Tze-ying, and Stanley, Flegg, Manda !. nnd Geddes.
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active intracellularly, and there is some suggestion that the use of these agents may decrease the frequency of relapse. 30 As a general rule, no matter which regimen is chosen, typhoid fever should be treated for 2 weeks. 15 As previously mentioned, approximately 3.3% of patients with typhoid fever progress to the chronic carrier state. These are patients who are asymptomatic but who shed S typhi intermittently in their stools. They may not recollect having had an acute illness, but they may relapse at any time and are a public health risk-particularly if their employment involves handling food. Treatment of the carrier state has always been somewhat problematic. Sequestration of the bacterium, especially in the gallbladder, makes eradication difficult. Traditional treatment has combined long-term antibiotic use (either chloramphenicol or ampicillin) with cholecystectomy. Intravenous ampicillin for 15 days has shown promise in the past,3 1 but with increasing resistance, it is not now routinely used. Several of the third-generation cephalosporins (eg, ceftriaxone and cefoperazone) have been found to penetrate the gallbladder well and are quite effective. 32•33 But these agents are expensive, and only the intravenous cephalosporins have been studied for this indication. As in acute typhoid fever, the flouroquinalones are good agents with which to treat the carrier state. They have little effect on normal gastrointestinal flora, very little resistance, and they concentrate well in bile and the gallbladder wall. 25•27 ·34·35 Despite their expense, they are probably the drugs of choice in all patients except children. Prevention
As is true of any other infectious disease, typhoid fever's incidence may be decreased either by reducing exposure to
S typhi or by increasing human resistance. Exposure may be limited by having individuals avoid endemic areas and by paying fastidious attention to their personal, water, and food hygiene. This is especially important because development of typhoid fever is directly related to the degree of exposure; any of the existing vaccines may be overwhelmed by a large inoculum. Epidemiologic studies have shown that, in developing nations where typhoid is endemic, the highest incidence of typhoid fever is in children. Reinfection occasionally occurs, but the illness is often milder. 13·36 This has Jed to the assumption that exposure increases resistance and has helped spur the development of vaccines. Four vaccines are currently in use in the United States. One of these, an acetone-inactivated parenteral vaccine, has not been approved by the Food and Drug Administration (FDA), is available only to the armed services, and is beyond the scope of this article. See Table 3 for details about dosage and administration for the three commercially available vaccines. The oldest of the vaccines currently in use is parenteral heat-phenol-inactivated vaccine (Typhoid Vaccine) given in two doses separated by at least 4 weeks, or in an accelerated program of one dose every week for 3 weeks. Of all the currently available vaccines, this one has the highest incidence of adverse reactions, with fever noted in 6.7% to 29% of those inoculated, headache in 9% to 10%, and moderateto-severe local pain or swelling in up to 60%. As many as 24% of patients missed school or work secondary to an adverse reaction. Rare serious reactions, including anaphyJaxis, chest pain, liver damage, neurological problems, and reactive arthropathy, may also occur. All of these reactions are less common with booster injections, which are recommended every 3 years. 8·37
TABLE 3 Typhoid Fever Immunizations: Dosage and Administration
Vaccine Ty2 I a Primary Booster ViCPS Primary Booster Parenteral Inactivated Primary Primary Booster Booster Booster
Age
Dose
Route
Number of doses
Interval between doses
Boos ter
4 4
2 days 2 d ays
Every 5 y
NIA NIA
Every 2 y
2':6y 2':6y
I caps 1 caps
PO PO
2': 2 y 2': 2 y
0.50 mL 0.50 mL
IM IM
6 mo-JO y 2': 10 y 6 mo-JO y 2': 10 y 2':6 mo
0.25 mL 0.50 mL 0.25 mL 0.50 mL O.JO mLt
SC SC SC SC
ID
2
2 1
1
2: 4 wk 2: 4 wk
NIA NIA NIA
Every 3 y Every 3 y Every 3 y
Nore. NIA = not applicable; PO = oral administration; IM = intramuscular injection; SC o subcutaneous injection; ID = intradermal injection. t The parenteral inactivated vaccine booster has fewer adverse reactions when given intradermally.
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A newer option is an oral attenuated vaccine (Vivotif) derived from the Ty2la strain of S typhi. Immunization consists of administering one capsule with a cool liquid I hour before meals every other day for 7 days (a total of four capsules). Patients need to be reminded not to chew or bite the capsules. Adverse reactions are very rare. Occasionally nausea and vomiting may occur. Even more rarely rash, fever, abdominal cramps, diarrhea, and exacerbation of acne may develop.8 The Ty2la vaccine is not affected by administration of immunoglobulin, and short-term exposure to ambient temperature does not appear to compromise efficacy. No good data exist concerning administration within 30 days of live viral vaccines, but if the vaccine is warranted, it should be given. Simultaneous administration with live vaccines is effective. 37 ·38 Mefloquine (but not chloroquine) has been shown to decrease replication of Ty2la in vitro, and vaccination should not be administered within 24 hours of mefloquine ingestion. Similarly, it is prudent not to immunize within I day of other antimicrobial use. Children aged I to 5 years may have more common (but still rare) adverse reactions, but there are no data for efficacy in this group. Similarly, no data exist on safety in pregnant women; and as is true for other live vaccines, Ty2la should not be used in the immunocompromised (a parenteral vaccine is better for this group). A booster series is recommended every 5 years.37•38 The newest entry into this field is a polysaccharide vaccine derived from purified Vi antigen for parenteral use (Typhim Vi). This ViCPS (Vi capsular polysaccharide) has an excellent safety profile. Fever rarely occurs (< J %); headache (l.5% to 3%) and erythema or induration (7%) are also unusual. A booster is recommended every 2 years.8,37 As a group, all available vaccines have been shown to be effective. Only 5% of travel-related cases of typhoid fever were in patients who had been immunized within 2 years.7 Efficacy for the parenteral inactivated vaccine is estimated at 51 % to 77%. When taken as directed, Ty2 l a appears to be effective in more than 67% of the inoculees. ViCPS has been shown to raise antibody levels significantly in 93% of patients, and the level of protection from S typhi ranges from 50% to 74%.a Who should be immunized? As a general rule, there are three broad indications. The first and largest group are travelers to endemic regions who are expected to have significant exposure. The incidence of typhoid fever on shortterm package trips is extremely low.2 Strict attention to personal, food, and water hygiene can decrease this risk even further. Thus, only visitors who are on low-budget, backpack types of trip, those with significant exposure to the local population, or persons on extended excursions need to be vaccinated.8 Of course, this group frequently includes college students. As I mentioned earlier, many persons who return to the area where they were born do not appreciate that they may be at risk from typhoid fever (or other endemic di seases). 104
Clinical microbiology lab workers are the second group of patients for whom vaccination is indicated. They have constant contact with contaminated laboratory specimens. Twenty cases of typhoid fever were reported in this group between 1975 and J 984. 7- 9 Household contacts of known typhoid carriers are the last group for whom immunization should be considered. Although the exact magnitude of the risk is not known, it makes intuitive sense to vaccinate close contacts. 8 Which vaccine to use depends on several factors. All things being equal, the Ty21a vaccine is recommended for most patients. It is given orally, there are almost no adverse reactions, it is effective, and it offers the longest period of protection. It is not recommended, however, for children under the age of 6 years or immunocompromised patients. In these or other patients in whom the certainty of a single intramuscular injection is desired, the ViCPS vaccine is the better choice. Last, the parenteral, inactivated vaccine is the only one approved for children from age 6 months to 2 years. Expense sometimes intrudes on the decision-making process. If this is the case, the parenteral inactivated vaccine is the least expensive (Wyeth-Ayerst quotes the price for a five-immunization vial at $9.41 , approximately $ 1.88 per patient). The cost to the provider of both the Ty2 la (Berna) and ViCPS (Pasteur Merieux) vaccines is listed at $25.95 per immunization. Obviously, the price the patient must pay in a pharmacy will be higher. Whichever vaccine is used initially, a different one may be chosen when it is time for a booster. Summary
Although domestically acquired typhoid fever has decreased dramatically over the past several decades, there is still a significant risk to the traveler. College healthcare providers need to be aware of the common nonspecific presentation of typhoid fever and to have a high index of suspicion in any patient who has had a sustained fever for a period of more than 1 week. Particular concern should be given to those who have traveled abroad to endemic regions. Because prevention is the best treatment, we who provide healthcare need to be able to counsel our patients on how to lower their risk of infection. Thus, we need to be familiar with the S typhi endemic regions, including the poor, rural areas of tropical developing nations and areas such as Mexico, Peru, Chile, Southeast Asia, and the Indian subcontinent. We must also be able to counsel our patients on how to avoid high-risk activities, such as eating undercooked meats or drinking beverages that have not been purified by boiling or using chlorine or iodine tablets in an endemic area. Finally, for those whose travel plans place them at an unavoidably increased risk of exposure, we need to minimize the odds of contracting typhoid fever by using the correct immunization protocol. JACH
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