Shigella

  • Shigella is Gram-negative, non-motile bacteria, closely related to Escherichia coli (E. coli).
  • There are four different Serogroups of Shigella (S. sonnei, S. flexneri, S. boydii, and S. dysenteriae) and ~50 Serotypes that can cause diarrhoeal disease.
    -Flexneri (16 Serotypes)
    -Sonnei (1 Serotype)
    -Bodyii (19 Serotypes)
    -Dysenteriae (15 Serotypes)
  • Shigella is transmitted via the faeco-oral route, through direct person-to-person or sexual contact, or indirectly through contaminated food, water, or fomites.
  • Shigella induced Diarrhoea is prevalent in the developing countries and low and middle income countries (LMIC). Its prevalence is highest in the African countries.

Fig. 1 Shigella pathogen

Fig 2: Global prevalence of Shigella

Ref:
1. Vaccines to tackle drug resistant infections - An evaluation of R&D opportunities.
2. PATH

Mortality:
  • Bacterial dysentery due to Shigella species is a major cause of morbidity and mortality.
  • 188 million cases of Shigella diarrhoea or dysentery occur annually worldwide, with 164,000 associated deaths.
  • Shigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212,438 deaths (95% UI 136,979–326,913) and 63,713 deaths (41,191–93,611) among children younger than 5 years.
  • 23% of the overall deaths, caused by Shigella, occur in children below 5 years of age.
  • Among children under the age of five years in low and middle income countries, Shigella species are the most common cause of dysentery and the second most common cause of diarrhoea overall.
Fig 3: Geographical prevalence of Shigella

Ref:
1) Khalil, I.A., Troeger, C., Blacker, B.F., Rao, P.C., Brown, A., Atherly, D.E., Brewer, T.G., Engmann, C.M., Houpt, E.R., Kang, G. and Kotloff, K.L., 2018. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016. The Lancet Infectious Diseases, 18(11), pp.1229-1240.
2. Kotloff KL, Riddle MS, Platts-Mills JA, et al. Shigellosis. Lancet 2018; 391:801.
3. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet. 2016;388(10051):1291.

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Fig 4: Prevalence of EDD pathogens
Shigella and Enteric Diarrhoeal Diseases (EDD):
  • Prevalence of Shigella is highest among other major EDD infections specifically in children between the age group of 12 – 30 months, causing ~28% of total EDD cases.
  • This data specifically represents the developing countries and LMIC, where the incidence of EDD is much higher than the developed world.
  • Such high prevalence indicates the need to focus on developing effective techniques to downregulate this trend, and vaccines can be an appropriate option.

Ref: https://path.azureedge.net/media/documents/VAC-etec-investment-rpt.pdf

Current treatment

Current treatment options:
  • Shigellosis can be mild and typically resolves within 4–7 days without treatment.
  • Although antimicrobial treatment, when given early in the course of illness, can slightly shorten the duration of symptoms and of carriage.
  • First line treatment varies depending on regional resistance patterns but is typically a course of treatment with fluoroquinolone. Although treatment duration varies; a three-day course is typical.
  • Rates of multidrug resistance among Shigella spp., including resistance to fluoroquinolones, azithromycin, and third- and fourth-generation cephalosporins, are high outside the United States, particularly in South and East Asia.
  • Currently no licensed vaccine is available for Shigella, which gives the developers an opportunity to fill the void.
AMR threat:
  • Shigella is listed as ‘medium’ in the WHO priority list of R&D for new antibiotics and as a ‘serious’ threat in the CDC’s list of biggest threats from AMR.
  • In Asia and Africa, 65-85% of Shigella infections are resistant to nalidixic acid and trimethoprim-sulfamethoxazole, and 20-30% are resistant to fluoroquinolones.
  • A strain in Vietnam has displayed resistance to third generation cephalosporins and fluoroquinolones, and strains in Bangladesh, requiring treatment with the last-line antibiotic meropenem, have been reported.

Ref:
Centers for Disease Control and Prevention