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

Abstract

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.

Figure 1. Assembly of Cases

* Eligibility criteria: three or more bowel movements per 24 h or at least one loose stool with blood, and consent from patient or parent/guardian.

Figure 2. Overall Shigellosis Incidence by Age Group at Study Sites in Six Asian Countries

Note: Shigellosis incidence in the age group 0–4 y is 13.2/1,000/y.

Figure 3. Clinical Presentation of Shigellosis Episodes

A history of more than one clinical sign and symptom during a single episode is possible.

Figure 4. The Relative Distribution of S. flexneri and S. sonnei at Study Sites in Six Asian Countries

S. flexneri (left bar graph) was more frequently isolated from diarrhea patients 5 y and older (p < 0.0001). In contrast, S. sonnei (right bar graph) was more frequently isolated from children under 5 y of age (p < 0.0001).

Figure 5. Relation of Proportion of ipaH-Positive Faecal Specimens and PCR Cycle Number to Age

The percentage of Shigella culture-negative stool specimens from diarrhea patients in which ipaH was detected and the mean PCR cycle number required to detect ipaH by patient age suggests that children between ages 2 and 4 y and adults over age 40 y with diarrhoea are most likely to have ipaH in their stool specimens and the bacterial load is likely to be highest in these two age groups.