Simon Flexner: Discoverer of Shigella dysenteriae (1899) Compiled by: Else Marais, Marlene Kassel, Naseema Aithma, Angela Potgieter Rob Stewart, Branca Fernandes, and Janet Loakes Gastro-intestinal infections Acute inflammatory enteritis: • Campylobacter • Salmonella • Shigella • Certain parasites Acute dysentery • Frequent small bowel movements • Blood and mucous • Tenesmus • Pain on defecation • Inflammatory invasion of intestinal mucosa • Bacterial, cytotoxic or parasitic destruction Overview of Shigella species • Small, Gram-negative rods • Non-motile, non-encapsulated • Family: Enterobacteriaceae; Tribe: Escherichieae; Genus Shigella •40 serotypes, 4 groups: A - Shigella dysenteriae B - Shigella flexneri C - Shigella boydii D - Shigella sonnei Overview of Shigella species • Sensitive to heat, kill in 55 c in 1 hr • S.sonnei survive in soil & room temprature for 912 days • Survive on fingers for sometime & transmit through hand contact • If suitable,survive in milk & other food(15 days in sea water) Overview • Shigella species • 140-200 million people infected annually • 650,000 deaths per year, worldwide(esp. developing countries) •intracellular pathogens •Incubation: 6 hrs to 9 days(1-7 days) •AB resistance (multiple) •2/3 of all cases and most of deaths in < 10 y/o •Developing countries: 1-4 y/o but in epidemics of S. dysenteriae all age group equal Overview • In 5-15 % of diarrhea & 30-50 % of dysentry • S.flexeneri : the most important in endemic shigellosis • Africa: 15 country with outbreak (30% attack rate in general population & 50% in < 5 y/o • Developed countries: children, daycare centers, immigrant workers, travelers to developing • 2/3 of cases in < 10 y/o بروز در سال 11/8 :1383در 100هزار نفر سيستان و بلوچستان()63 Iran • Tehran: 52% S.flexeneri, 37 % S.sonnei – Resistance to ampi, co-trimoxazole, tetra, amoxi, chloramphenicole, cephalotin(more in S.flexeneri) – The most effective AB is ciprofloxacin & then ceftizoxime • Shiraz: 60% S.flexeneri, 28% S.sonnei, 12% S.boydii, 34% in preschool age – Resistance to ampi, co-trimoxazole – Sensitive to nalidixic acid, ceftriaxone, ceftazidime, ciprofloxacin(100%) Descriptive epidemiology • Time trend – – – – More common in warm seasons Equal in both sexes In temperate climate: warm season In tropics: rainy season • Preschool & early school age • 1-4 y/o (adult get disease from children) • Infants(1- 6 mo) are resistant due to nursing Predisposing factors • HIV +( chronic & relapsing and causing bateremia in spite of AB) • Septicemia in Malnutrition, early infancy & S.dysenteriae type 1 • EL-Nino phenomenon • a dry not rainy winter & rainy spring increase in dysentery in summer Sensitivity & resistance • 10-100 micro-organism ingestion in volunteers: diarrhea in 10-40 % • More virulent in children, malnutrition, debilitated old-mostly sub-clinical in adults • Oral vaccine: some success (short- term) • Attenuated oral vaccine prevent clinical dx • 2nd attack rate in household contact: 40 % • Epidemics in crowding, bad public health( day care center, long term care center…) Transmission • Fecal-Oral(direct or indirect) from patient or carrier – No handwashing after bowel movement( direct contact) – Contaminated food( not usual but can cause major epidemics) – Carriers:without treatment microorganism shedding for 1-4 wks( but the number is low, so communicability is lower than pts) – Nosocomial infection: from pts to healthworkers & to other pts. • Shigella can survive on lab equipments for some time – Homosexual: oral-anal, penile-oral Transmission • Contaminated water & milk – 4-6 wks survive in water( shorter in sun-exposed water) – Pasteurization eliminate the mo. • Insects – Fly: mechanical, biological • Communicable for 4 wks • Humans and primates: only reservoirs • Crowded living conditions • Poor quality water supplies • Inadequate sewage disposal • Increase risk of infection Clinical features • From asymptomatic to severe (Mortality rates vary from 5-10 %) • Bacilli ingested by epithelial cells of the intestinal villi • Organisms multiply and spread laterally into lamina propria • Inflammatory reaction develops with capillary thrombosis • Necrotic epithelium sloughed leading to ulceration • Severe cases may become life threatening Clinical features & natural history • 7-12 bowel movement/day • Watery, green or yellow, containing mucous blood or undigested food • Convulsion, Acute bloody dysentery • Fever, malaise, headache, abdominal pain • Usually self limited and recovery after 4-7 days, sometimes persistent diarrhea • HUS • Mortality in hospital: 20% • تعريف اپيدميولوژيك ندارد. • گزارش غير فوري • در صورت بروز همه گيري گزارش فوري Virulence • S.dysenteriae forms potent exotoxin • Fluid transuding action as well as • Lipo-polysaccharide endotoxin • Described as a neurotoxin • Toxin levels of S.dysenteriae, highest • S.sonnei causes mild illness(short symptomatic period & and very low mortality) • S. flexneri and S.boydii range in severity • S.flexneri bacteremia, predisposed by ulcers Virulence • Commonly a self-limited disease(mild or mod) • 4-7 days(several days to weeks) • S.dysenteriae cause more severe disease(20% mortality in admitted patients) • If untreated: + stool culture for 30 days or more Molecular methods of detection • Isolation difficult • Genetic probe to the virulence-plasmid developed and being tested • PCR not routinely done for detection Outbreaks • From contaminated water or food • contaminated potato salad • inadequate toilet facilities • Origin of infection- food handler • Secondary transmission may occur • Flies aid transmission • Infants resistant to shigellosis •More in formula fed) Patterns of outbreaks • Cyclic patterns of 20-30 years • From 1900-1925 S.dysenteriae predominated while from 19261938, S.flexneri was common • Currently S.sonnei predominates in Europe and USA • S.flexneri is predominant in developing countries( with boydii & dysenteriae) Control primary prevention • Chlorinated water, waterborne sewage • Rigorous hand washing • Institutional outbreaks: Isolation of the infected • Infected food handlers - 2 negative cultures •Insecticides •After P/E of the patient: hand washing, disinfection of exam. Equipments •Vaccination: under trial primary prevention • Enteric precaution, disinfection of contaminated equipment & stool( if there is not modern sewage) • Infected person withhold from children, other pts and food handling: 2 consecutive stool culture in 24 hr interval 48 hr after D/C of AB • AB treatment of carriers( without any sign or symptoms) : not recommended • Common writing equipment(pen,…) • nursing Secondary Prevention • Early treatment shorten acute phase of disease & mo. shedding Treatment • Fluid replacement • Antimicrobial therapy- reduces duration of symptoms • Reduces secretion of organisms • Adults- oral ciprofloxacin or ofloxacin • Children- cotrimoxazole, ampicillin,nalidixic acid, ceftriaxone, azithromycin • Agents decreasing intestinal motility should not be used • Untreated lasts 1 day - 1 month (average 7days) • Complications - dehydration, seizures, septicaemia, pneumonia, keratoconjunctivitis and arthritis • Travellers: Eat well cooked food Bottled water Peel all fruit and vegetables Perhaps use prophylactic flouroquinolones