BackgroundThe 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 FindingsOver 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%]).ConclusionsShigella 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.

Objective We aimed to determine the burden of bacillary dysentery in China, its cross-regional variations, trends in morbidity and mortality, the causative bacterial species and antimicrobial resistance patterns. Methods We extracted and integrated governmental statistics and relevant medical literature published from 1991 to 2000. Data were also collected from one general hospital each for the six provinces and Jin-an district, Shanghai, representative of six geographical regions and a modern city. Findings In 2000, 0.8-1.7 million episodes of bacillary dysentery occurred of which 0.5 to 0.7 million were treated at health-care facilities and 0.15-0.20 million patients were hospitalized. The highest morbidity and mortality rates were among the youngest and oldest age groups. Bacillary dysentery peaked during the summer months. The major causative species was Shigella flexneri (86%) and the predominant S. flexneri serotype was 2a (80%). About 74-80% of Shigella isolates remained susceptible to fluorinated quinolones. Conclusion We conclude that while morbidity and mortality due to bacillary dysentery has decreased considerably in China in the past decade due to increasing access to affordable health care and antibiotics, a considerable burden exists among the youngest and oldest age groups and in regions with low economic development. We suggest that while a vaccine would be effective for short-and medium-term control of bacillary dysentery, improved water supply, sanitation, and hygiene are likely to be required for long-term control.Bulletin of the World Health Organization 2006;84:561-568.Voir page 567 le résumé en français. En la página 567 figura un resumen en español. IntroductionGlobally, morbidity and mortality due to diarrhoea has decreased from 4.6 million deaths in 1982 to 3.3 million in 1992 to 2.5 million in 2003.1-3 A review published in 1999 reported that bacillary dysentery caused by Shigella species (S. flexneri, S. sonnei, S. boydii, and S. dyse e enteriae) remains a major source of diarr r rhoea, especially in developing countries. It also reported that of the 164.7 million episodes of shigellosis (Shigellarrelated diarrhoea) occurring worldwide each year, 163.2 million were in developing countries; however, the review included sparse data from China. 5 Even so diarrhoeal diseases remain an important public health problem. A crossrsectional survey conducted in 1988 estimated that of the 84 million diarrhoeal episodes that ocr r curred in China annually, 25% affected children less than five years of age. The survey also found that Shigella is one of the principle etiologic organisms for diarrhoea.6 A live oral Shigella vaccine which was developed and produced in China in 1997 reportedly provides 60-70% protection against S. flexneri 2a and S. sonnei infections. 7A continuing analysis of the disease burden of bacillary dysentery would be required for effective treatment and prevention policies, health prioritization debates, and cost-benefit assessments to enable rational decisions on research, ...

Shigella spp. are exquisitely fastidious gram-negative organisms which frequently escape detection by traditional culture methods. To get a more complete understanding of the disease burden caused by Shigella in Nha Trang, Vietnam, real-time PCR was used to detect Shigella DNA. Randomly selected rectal swab specimens from 60 Shigella culture-positive patients and 500 Shigella culture-negative patients detected by populationbased surveillance of patients seeking care for diarrhea were processed by real-time PCR. The target of the primer pair is the invasion plasmid antigen H gene sequence (ipaH), carried by all four Shigella species and enteroinvasive Escherichia coli. Shigella spp. could be isolated from the rectal swabs of 547 of 19,206 (3%) patients with diarrhea. IpaH was detected in 55 of 60 (93%) Shigella culture-positive specimens, whereas it was detected in 87 of 245 (36%) culture-negative patients free of dysentery (P < 0.001). The number of PCR cycles required to detect a PCR product was highest for culture-negative, nonbloody diarrheal specimens (mean number of cycles to detection, 36.6) and was lowest for children with culture-positive, bloody diarrheal specimens (mean number of cycles, 25.3) (P < 0.001). The data from real-time PCR amplification indicate that the culture-proven prevalence of Shigella among patients with diarrhea may underestimate the prevalence of Shigella infections. The clinical presentation of shigellosis may be directly related to the bacterial load.

In Vietnam, shigellosis, typhoid fever, and cholera are important enteric diseases. To determine their magnitude and geographical distribution, and explore associated risk factors, we examined national surveillance data from 1991 to 2001 and potential ecological determinants. Average annual incidence rates were calculated and mapped for each province. Bivariate and multiple regression analyses were used to explore associations with selected environmental and human risk factors. Overall, shigellosis rates per 100,000 population (median, 41; mean, 70) were higher and more widespread than rates for typhoid fever (median, 7; mean, 23) and cholera (median, 0.3; mean, 2.7). Shigellosis was highest in the Central Highlands and was significantly associated with rainfall and urban poverty; typhoid fever prevailed in the Mekong River Delta and was most associated with vapor pressure and river/stream drinking water; and cholera predominated along the Central Coastal regions and correlated positively with rainfall and public well drinking water. The distinct geographical patterns of each disease appear to be driven by a combination of different ecological factors.

Background: In preparation of vaccines trials to estimate protection against shigellosis and cholera we conducted a two-year community-based surveillance study in an impoverished area of North Jakarta which provided updated information on the disease burden in the area.

ObjectiveIn Vietnam, shigellosis/dysentery, typhoid fever, and cholera are important enteric diseases. To better understand their epidemiology, we determined temporal trends, seasonal patterns, and climatic factors associated with high risk periods in eight regions across Vietnam.MethodsWe quantified monthly cases and incidence rates (IR) for each region from national surveillance data (1991–2001). High- and low-disease periods were defined from the highest and lowest IRs (1 SD above and below the mean) and from outbreaks from positive outliers (4 SDs higher in 1 month or 2 SDs higher in ≥ 2 consecutive months). We used general linear models to compare precipitation, temperature, and humidity between high- and low-risk periods.ResultsShigellosis/dysentery was widespread and increased 2.5 times during the study period, with the highest average IRs found between June and August (2.1/100,000–26.2/100,000). Typhoid fever was endemic in the Mekong River Delta and emerged in the Northwest in the mid-1990s, with peaks between April and August (0.38–8.6). Cholera was mostly epidemic along the central coast between May and November (0.07–2.7), and then decreased dramatically nationwide from 1997 onward. Significant climate differences were found only between high- and low-disease periods. We were able to define 4 shigellosis/dysentery, 14 typhoid fever, and 8 cholera outbreaks, with minimal geotemporal overlap and no significant climatic associations.ConclusionsIn Vietnam, bacterial enteric diseases have distinct temporal trends and seasonal patterns. Climate plays a role in defining high- and low-disease periods, but it does not appear to be an important factor influencing outbreaks.

f Mycobacterium tuberculosis is the major causative agent of tuberculosis (TB). The gamma interferon (IFN-␥) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied to the commercial IFN-␥ release assay, QuantiFERON-TB Gold In-Tube, and plasma samples were analyzed for interleukin-2 (IL-2), IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNF-␣), IFN-␥, monokine induced by IFN-␥ (MIG), interferon gamma inducible protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant (I-TAC), and monocyte chemoattractant protein 1 (MCP-1) by using a commercial cytometric bead array. The Mycobacterium tuberculosis antigen-specific production of most of the assayed cytokines and chemokines was higher in the active TB than in the LTBI group. The mitogen-induced responses were lower in the active TB than in the LTBI group. When the ratio of TB-specific to mitogen-induced responses was calculated, IL-2, IL-6, IL-10, IL-13, TNF-␣, IFN-␥, MIG, and IP-10 were more useful in discriminating active TB from LTBI. In particular, most patients showed higher IP-10 production to Mycobacterium tuberculosis antigens than to mitogen at the individual level, and the ratio for IP-10 was the strongest indicator of active infection versus LTBI with 93.9% sensitivity and 90% specificity. In conclusion, the ratio of the TB-specific to the mitogen-induced IP-10 responses showed the most promising accuracy for discriminating active TB versus LTBI and should be further studied to determine whether it can serve as a biomarker that might help clinicians administer appropriate treatments. M ycobacterium tuberculosis, the major causative agent for tuberculosis (TB), is among the most successful human pathogens, infecting approximately 8.6 million people and leading to 1.3 million deaths each year (1). It is estimated that 2 billion people live with latent TB infection (LTBI) and are therefore a potential source of active TB (2, 3). Identifying LTBI is necessary in order to reduce the risk of development of the disease, while diagnosis of active TB can enable rapid treatment and disease control. To this end, diagnostic biomarkers that can accurately indicate disease status are needed (4, 5).There is presently no diagnostic gold standard for LTBI. Until recently, the tuberculin skin test (TST) involving the intracutaneous injection of purified protein derivative (PPD) into the forearm was the only available method for diagnosing LTBI. However, PPD cross-reacts with nontuberculous mycobacteria as well as with Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine and has poor sensitivity in immunocompromised patients (6). The interferon gamma (IFN-␥) release assay (IGRA) has been widely used in clinical practice a...

Sang-Nae cho 3,4 , Young Ae Kang 2,3* & Sang-Guk Lee 1* Although tuberculosis (TB) is a severe health problem worldwide, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used in the study of infectious diseases. We performed metabolome profiling to identify potential biomarkers in patients with active TB. Serum samples from 21 patients with active pulmonary TB, 20 subjects with latent TB infection (LTBI), and 28 healthy controls were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by multivariate and univariate analyses. Metabolic profiles indicated higher serum levels of glutamate, sulfoxy methionine, and aspartate and lower serum levels of glutamine, methionine, and asparagine in active TB patients than in LTBI subjects or healthy controls. The ratios between metabolically related partners (glutamate/glutamine, sulfoxy methionine/methionine, and aspartate/asparagine) were also elevated in the active TB group. There was no significant difference in the serum concentration of these metabolites according to the disease extent or risk of relapse in active TB patients. Novel serum biomarkers such as glutamate, sulfoxy methionine, aspartate, glutamine, methionine, and asparagine are potentially useful for adjunctive, rapid, and noninvasive pulmonary TB diagnosis. According to the World Health Organization report, Tuberculosis (TB) caused approximately 10.0 million patients and 1.6 million deaths globally in 2017 1. Timely diagnosis and treatment are critical in controlling TB successfully. Currently, TB exposure is evaluated with two methods: a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA). However, existing diagnostic techniques cannot distinguish latent tuberculosis infection (LTBI) from active TB because they indirectly identify TB infection through detection of the immunologic reaction to the Mycobacterium tuberculosis (Mtb) antigen 2. Therefore, the identification of blood markers representing the actual TB bacterial presence/burden in the human body is needed to tailor treatment options for patients with positive TST or IGRA results. Recently, metabolomics has emerged as a potential tool making remarkable progress in novel biomarker research. It can execute multiplexed profiling and compare multiple metabolites in a biological sample 3. It aims the comprehensive measurement of the metabolites; therefore, highly specialized analytical techniques in combination with sophisticated statistical, mathematical, and bioinformatics analyses are required 4. Accordingly, metabolomics technologies have been widely utilized in various diseases to screen novel biomarkers, understand the biologic processes and metabolic pathways, and comprehend the response of the host, which enables researchers to develop improved diagnostic tools and treatment strategies 5,6. Several metabolomics studies used sputum 7,8 , blood 9-14 , breath 15,16 , and urine 17 to identify new markers of TB infection or treatment response. However, the number...