The Topic of This Month Vol. 30, No. 3 (No. 350)

Typhoid fever and paratyphoid fever in Japan, 2005-2008
(IASR 30: 91-92, April 2009)

Typhoid fever and paratyphoid fever are caused respectively by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi) and Salmonella enterica subsp. enterica serovar Paratyphi A (S. Paratyphi A). They are characterized by ulceration of Peyer's patches in the ileum and multiplication of the bacteria in the reticuloendotherial system followed by bacteremia. The clinical picture is distinct from nontyphoidal Salmonella infections. S. Sendai, S. Paratyphi B, and S. Paratyphi C cause symptoms similar to typhoid fever but they are treated as nontyphoidal Salmonella infections in Japan.

Typhoid fever and paratyphoid fever were categorized as category II infectious diseases in the Infectious Diseases Control Law enacted in April 1999 (IASR 22: 55-56, 2001 & 26: 87-88, 2005), but are now categorized as category III infectious diseases after enactment of the revised version of the law in April 2007. Physicians are under obligation of notifying the prefectural governor through the nearest health center when they have made confirmed diagnosis of patients or asymptomatic carriers or when they encountered confirmed or suspected deceased cases ( Prefectural health departments are under obligation of sending isolates from the patients or carriers to National Institute of Infectious Diseases (NIID). The Department of Bacteriology, NIID performs phage typing and drug-sensitivity testing and provides results back to the prefectures, which also appear on the IASR web site (

National Epidemiological Surveillance of Infectious Diseases (NESID): Reported cases (including patients and carriers, hereafter) of typhoid fever was 50 in 2005, 72 in 2006, 47 in 2007, and 58 in 2008 (Table 1). The number of paratyphoid fever reported in 2005-2008 remained in the range of 20-27 per year. Many of the typhoid and paratyphoid cases were imported ones, occupying 81% of typhoid fever cases and 93% of paratyphoid cases. Cases occurred more frequently in April-May and September-October seasons (Fig. 1). Males are affected more frequently than females, and 20-39 year-old individuals occupy 67% of all the patients (Fig. 2). The clustering of the age of the cases to 20-39 years is probably because young students or office workers traveled abroad during spring and summer vacations to South-East Asia, Indian subcontinent and other endemic area of this disease. The time lag of about two months between infection (travel in these countries during vacation seasons) and diagnosis (the peak seasons of the report of this disease) is probably caused by the time elapsed from infection to the final diagnosis.

Among countries where the typhoid and paratyphoid cases were presumed to have acquired infection in 2005-2008 (Fig. 3), 78% were Asian countries for typhoid cases, such as India (79 cases), Indonesia (30 cases), Nepal (14 cases), Philippines (8 cases), Bangladesh (6 cases), Pakistan (5 cases), Thailand (3 cases), Myanmar (2 cases), and Sri Lanka, Viet Nam, Malaysia, and Laos (1 case each). Twenty-seven cases had journeyed in Indian subcontinent passing through more than two countries. Countries visited by the cases other than Asian countries were Central South America (2 cases), Africa, and Oceania (1 case each). For paratyphoid cases, Asia occupied 86%, such as, India (35 cases), Bangladesh (8 cases), Nepal (7 cases), Indonesia (7 cases), China (6 cases), Myanmar (5 cases), Cambodia (2 cases), Thailand, Singapore, Philippines, and Maldives (1 case each). Eight cases visited two or more Asian countries, and two visited African countries.

Phage types: The most frequent phage type for S. Typhi in 2005-2008 was E1 (Table 2). Among isolates from cases infected in India, most frequent was also phage type E1, but E9 that increased in 2004 was also isolated in 2006-2008. Phage type M1 was isolated in low numbers, 2-5, in every year. For S. Paratyphi A (Table 3), though predominant were phage types 2, 4 and 6 in 2005, phage type 1 became predominant in 2006 and persisted later together with phage types 2, 4 and 6.

Drug-resistance and therapy: Typhoid and paratyphoid fever are treated with oral administration of fluoroquinolones. In recent years, however, S. Typhi and S. Paratyphi A lowly sensitive to fluoroquinolones have been isolated at high frequencies (Fig. 4). S. Typhi strains resistant to fluoroquinolones were isolated from three patients (2 in 2006 and 1 in 2007) who traveled in India (see p. 93 of this issue). As fluoroquinolones are ineffective to such patients, high body temperature persists and recovery needs long treatment. For such cases, the third generation cephem antibiotics and macrolides are used in combination (see p. 93 of this issue).

Summary: In endemic areas, infection primarily occurs via consumption of contaminated water or foods. Consumption of unboiled water, raw fruits and uncooked food materials should be avoided while traveling in such areas. Those who plan a trip to Indian subcontinent where fluoroquinolone low sensitive or resistant strains were isolated may have to consider vaccination as one of preventive measures (see p. 95 & 96 of this issue).

As it is becoming increasingly important to monitor drug resistant strains that may compromise the therapy, it is requested that increasing efforts are made for isolating bacteria from typhoid and paratyphoid fever patients and sending them to NIID (Notice from the Ministry of Health, Labour and Welfare, IASR 29: 314-315, 2008).

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