A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology.

BACKGROUND: The burden of shigellosis is greatest in resource-poor countries. Although this diarrheal disease has been thought to cause considerable morbidity and mortality in excess of 1,000,000 deaths globally per year, little recent data are available to guide intervention strategies in Asia. We conducted a prospective, population-based study in six Asian countries to gain a better understanding of the current disease burden, clinical manifestations, and microbiology of shigellosis in Asia. METHODS AND FINDINGS: Over 600,000 persons of all ages residing in Bangladesh, China, Pakistan, Indonesia, Vietnam, and Thailand were included in the surveillance. Shigella was isolated from 2,927 (5%) of 56,958 diarrhoea episodes detected between 2000 and 2004. The overall incidence of treated shigellosis was 2.1 episodes per 1,000 residents per year in all ages and 13.2/1,000/y in children under 60 months old. Shigellosis incidence increased after age 40 years. S. flexneri was the most frequently isolated Shigella species (1,976/2,927 [68%]) in all sites except in Thailand, where S. sonnei was most frequently detected (124/146 [85%]). S. flexneri serotypes were highly heterogeneous in their distribution from site to site, and even from year to year. PCR detected ipaH, the gene encoding invasion plasmid antigen H in 33% of a sample of culture-negative stool specimens. The majority of S. flexneri isolates in each site were resistant to amoxicillin and cotrimoxazole. Ciprofloxacin-resistant S. flexneri isolates were identified in China (18/305 [6%]), Pakistan (8/242 [3%]), and Vietnam (5/282 [2%]). CONCLUSIONS: Shigella appears to be more ubiquitous in Asian impoverished populations than previously thought, and antibiotic-resistant strains of different species and serotypes have emerged. Focusing on prevention of shigellosis could exert an immediate benefit first by substantially reducing the overall diarrhoea burden in the region and second by preventing the spread of panresistant Shigella strains. The heterogeneous distribution of Shigella species and serotypes suggest that multivalent or cross-protective Shigella vaccines will be needed to prevent shigellosis in Asia.

Surveillance of shigellosis by real-time PCR suggests underestimation of shigellosis prevalence by culture-based methods in a population of rural China.

INTRODUCTION: Shigellosis is a leading public health issue in China, especially in Children under 5 years of age. The disease burden of shigellosis is usually underestimated by conventional culture. In this study, real-time PCR was applied to detect Shigella infection in parallel with routine culture, to investigate the true burden of disease caused by Shigella spp. METHODS: Rectal swab specimens of 39 Shigella culture positive and 298 Shigella culture negative patients from a population-based surveillance study were selected randomly. Real-time PCR targeting the invasion plasmid antigen H gene sequence (ipaH) was used to detect DNA sequences characteristic for Shigella spp. RESULTS: ipaH were detected in 174 of 298 (58%) randomly selected Shigella culture negative specimens and in 38 of 39 (97%) Shigella culture positive specimens (p < 0.001). Among 10 variables, culture results was the strongest predictive factor (OR = 15.5; 95% CI: 2.0-119.0), followed by a clinical presentation of diarrhea with fever (OR = 2.8; 95% CI: 1.2-6.2), epidemic season (OR = 2.4; 95% CI: 1.4-4.3), and female gender (OR = 1.8; 95% CI: 1.1-3.0). CONCLUSION: The high detection rate of ipaH in culture negative specimens through use of real-time PCR suggests that earlier estimates of shigellosis burden measured by conventional culture may have underestimated the true disease burden.