Focusing on prevention of shigellosis seen to produce an immediate benefit

Shigellosis, or bacterial dysentery, seems to be more widespread among poor populations in Asia than previously thought, and antibiotic resistant strains of different species have emerged, a large multi-country disease burden study coordinated by the IVI has found.

In the population-based study led by Dr. Lorenz von Seidlein of the IVI, over 600,000 people of all ages living in low-income study sites in six Asian countries were monitored through passive surveillance, using standardized epidemiological and laboratory methods. 

Collaborating organizations included ICDDR,B: Center for Health and Population Research, Bangladesh; Fudan University, China; Aga Khan University, Pakistan; the National Institute of Health Research and Development and the Ministry of Health, Indonesia; the National Institute of Hygiene and Epidemology, Vietnam; and Thammasat University Rangsit Center, Thailand.

The Shigella pathogen was isolated from 2,927 (5%) of 56,958 diarrhoea episodes detected at these sites between 2000 and 2004. The overall incidence of treated shigellosis was 2.1 episodes per 1,000 people per year in all ages, and was more than six times that in children under five years of age (13.2 per 1,000).

By far the greatest incidence was found in Dhaka, Bangladesh site, where 46/1,000 children 0-4 years old and nearly 8/1,000 persons of all ages had confirmed shigellosis per year (figure). Incidence in children under five was also high in Hebei province in China, Karachi and rural villages in Pakistan, and in North Jakarta, Indonesia. 

Figure 1. Incidence rates per 1,000 population per year of culture-proven shigellosis in six Asian countries (2001-2004)

 
The overall shigellosis incidence in the study sites is about 100 times that of industrialized countries. In the United States in 1999 and the Netherlands 1996–2000, the estimated shigellosis incidence in all ages was 0.037 and 0.032, respectively, per 1,000 per year.

Although this diarrheal disease has been thought to cause considerable morbidity and mortality with up to one million deaths worldwide per year, little recent data are available to guide intervention strategies in Asia and elsewhere in the developing world, where the great majority of cases occur. Despite high incidence, there is no licensed vaccine against Shigella.

“This is the largest epidemiological study on shigellosis ever done,” said Dr. John Clemens, Director- General of the IVI. “The result has profound implications in designing strategies to counter this important disease.”

The study, which appeared in the open access journal, PLoS Medicine in September 2006 (Read the journal article), is part of IVI’s Disease of the Most Impoverished (DOMI), a program of research to accelerate the development and introduction of new vaccines against shigellosis, typhoid fever and cholera. The program is supported by the Bill and Melinda Gates Foundation and the Swedish International Development Cooperation Agency, as well as the governments of Korea and Kuwait.

Another important finding from the study is the fact that, while children under 10 years of age and especially those 0-4 years old are at highest risk of getting the disease, shigellosis incidence increases steadily after the age of 40 – with persons 70 and over having the second highest rate in the overall study population after 0-4 year olds. The elderly in China and Vietnam were especially vulnerable to the disease. These findings have important implications for the control of shigellosis, including future vaccination, once an effective vaccine is developed.

Figure 2. Annual shigellosis incidence by age group in all six DOMI study sites combined

The study showed that S. flexneri was the most frequently isolated Shigella species (68% of confirmed cases) in all sites but Thailand, where S. sonnei was most common (85%). This is consistent with previous reports in which S. flexneri has been found to be the main species in less developed countries, while S. sonnei predominates in industrialized countries. The specific sub-types of S. flexneri were found to vary substantially from site to site, and even from year to year.

Also of concern is the finding that most S. flexneri isolates in each site were resistant to the first-line antibiotics, amoxicillin and cotrimoxazole, rendering these inexpensive and commonly used drugs ineffective. And resistance to ciprofloxacin, which is increasingly replacing the first-line antibiotics as the drug of choice, is also beginning to appear. Ciprofloxacin resistance was found in 6% of  S. flexneri isolates in China, 3.3% of those in Pakistan, and 1.8% of those in Vietnam.

Figure 3. Rates of antibiotic resistant Shigella isolates (all species) by study site

IVI scientists and their collaborators conclude that focusing on prevention of shigellosis could produce an immediate benefit by drastically reducing the overall diarrhoeal disease burden in the region and by curbing the spread of pan-resistant Shigella strains.

The differences of Shigella species and serotype distribution suggest that it will be necessary to develop vaccines consisting of a broad “cocktail” of different Shigella organisms or ones that protect across species in order to have an important impact on reducing the incidence of this disease in Asia.