Paratyphoid Fever: Rising Infection Rates and Resistance to Fluoroquinolones
Abstract & Commentary
By Mary-Louise Scully, MD
Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, CA.
Dr. Scully reports no financial relationship relevant to this field of study.
Synopsis: The incidence of paratyphoid fever is increasing globally. In Asia, Salmonella enterica serotype Paratyphi A strains are often resistant to commonly used fluoroquinolones such as ciprofloxacin.
Source: Gupta SK, et al. Laboratory-Based Surveillance of Paratyphoid Fever in the United States: Travel and Antimicrobial Resistance. Clin Infect Dis. 2008;46:1656-1663.
The Division of Foodborne, Bacterial, and Mycotic Diseases of the CDC, in conjunction with state and local health departments, conducted a study to better understand the epidemiologic and laboratory characteristics of paratyphoid fever in the United States. All 50 U.S. state health departments, along with the Houston, Los Angeles, and New York City metropolitan health departments, participated in the study. A case was defined as an acute illness compatible with paratyphoid fever with a confirmed laboratory isolate of either Salmonella enterica serotype Paratyphi A, Paratyphi B, or Paratyphi C during April 1, 2005 through March 31, 2006. An attempt was made to interview all patients, and susceptibility testing was performed on all of the isolates.
One hundred forty-nine patients were confirmed as having Salmonella enterica, serotype Paratyphi A (S. Paratyphi A) infection; 12 had Salmonella enterica serotype Paratyphi B (S. Paratyphi B), and 1 had Salmonella enterica serotype Paratyphi C (S. Paratyphi C). During this same time period, 378 patients were found to have Salmonella enterica serotype Typhi (S. Typhi). Therefore, of all the reported cases of enteric fever during the year of study, 30% were secondary to paratyphoid fever.
Epidemiological information could be obtained on 60% of the patients infected with S. Paratyphi A. The median age was 26 years, and 49% were male. Ninety-six percent of cases had traveled outside the United States in the 30 days before becoming ill. Of the 79 patients who reported travel to a single nonindustrialized country, 72% traveled to India, 16% to Bangladesh, 5% to Pakistan, 3% to Cambodia, and 3% to Indonesia. Infections secondary to S. Paratyphi A occurred most frequently during early spring and late summer. Ninety-one percent of cases were United States residents, but 71% were actually born outside the United States, implying that many individuals likely were traveling to visit friends and relatives. Of the isolates tested (n=146), 87% were nalidixic acid-resistant. All nalidixic acid-resistant isolates showed decreased susceptibility to ciprofloxacin with an MIC of ≥ 0.12 mcg/mL.
Of the six patients with S. Paratyphi B who were interviewed, five patients (83%) had traveled internationally within 30 days of onset of illness. Of these, two had traveled to Bolivia, one to Peru, one to Bolivia and Peru, and one to Ethiopia. Only one S.Paratyphi B isolate was resistant to nalidixic acid. The one case of S. Paratyphi C was a urinary infection in a male who had traveled to Mauritania and Senegal; that strain was susceptible to all antibiotics tested.
This is the first study to examine the epidemiology of paratyphoid fever and infections in the United States. Infection with S.Paratyphi A was associated with travel to both south and southeast Asia, whereas S. Paratyphi B seemed to be associated with travel to the Andean region of South America. Importantly, travel to both south Asia and southeast Asia was associated with acquisition of nalidixic acid-resistant strains of S. Paratyphi A.
Commentary
Paratyphoid fever is a systemic illness caused by S. Paratyphi A, Paratyphi B, or Paratyphi C. Infection is acquired by ingestion of contaminated food or water. Although rare in the United States, an estimated 5,400,000 cases of paratyphoid fever occurred throughout the world in the year 2000.1 Previously, paratyphoid fever was thought to cause a milder disease than typhoid fever, but a recent study in Nepal found that the clinical presentation and complication rates were indistinguishable between enteric fever caused by S. Typhi versus S. Paratyphi A.2 Similarly, a study in Israel also found that S. Paratyphi A was associated with more severe clinical outcomes and higher rates of complications. In contrast, in this same study, S. Paratyphi B was associated with milder illness, was typically found in children, and was associated with a more self-limited gastroenteritis-like illness.3
Incidence rates for S. Paratyphi A are rising globally. In Asia, a surveillance study showed a significant proportion of enteric fever was secondary to S. Paratyphi A (64% in China, 24% in India, 15% in Pakistan, and 14% in Indonesia).4 In addition, increasing antibiotic resistance of S. Paratyphi A is of particular concern in Asia. Nalidixic acid resistance is a marker for reduced susceptibility to fluoroquinolones and potentially poorer clinical outcomes. The emergence of antibiotic resistance is likely related to the widespread use and easy availability of fluoroquinolones without a prescription in many countries. Physicians need to be aware of these resistance patterns in choosing antibiotic treatment regimens in returning ill travelers from this area of the world and in choosing empiric antibiotics for travelers to carry with them. For now, azithromycin remains effective against S. Paratyphi A strains in both south and southeast Asia. A third generation cephalosporin, such as ceftriaxone, is appropriate when clinical illness is severe and parenteral treatment is needed.
The two commercially available typhoid vaccines worldwide (Vi polysaccharide vaccine and the oral Ty21a vaccine) provide 50-80% protection against typhoid fever, but neither seems to provide protection against paratyphoid fever.5 Certainly, the Vi vaccine would be unlikely to protect against S. Paratyphi A since the Vi antigen is absent in S. Paratyphi A and S. Paratyphi B strains. There have been conflicting data on whether the oral Ty21a vaccine might give some cross-protection against paratyphoid fever. A recent re-analysis of some of the original early trials of oral Ty21a vaccine in South America showed a trend toward protection against S. Paratyphi B but not S. Paratyphi A strains.6 Clearly, a vaccine for S. Paratyphi strains or a bivalent vaccine for both S. Typhi and S. Paratyphi strains that could be used in endemic countries as well as in travelers is urgently needed.
References
- Crump JA et al. The global burden of typhoid fever. Bull WHO. 2004; 82:346-353.
- Maskey AP, et al. Salmonella enterica serovar Paratyphi A and Salmonella enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal. Clin Infect Dis. 2006;42:1247-1253.
- Meltzer E, et al. Epidemiology and clinical aspects of enteric fever in Israel. Am J Trop Med Hyg. 2006; 74(4):540-545.
- Ochiai RL, et al. Salmonella Paratyphi A rates, Asia. Emerg Infect Dis. 2005;11:1764-1766.
- Basnyat B, et al. Enteric (Typhoid) Fever in Travelers. Clin Infect Dis. 2005;41:1467-1472.
- Levine MM, et al. Ty21a live oral typhoid vaccine and prevention of paratyphoid fever caused by Salmonella enterica serovar Paratyphi B. Clin Infect Dis. 2007:45(Suppl 1):S24-28.
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