Simon Flexner:Discoverer of Shigella dysenteriae (1899)

Compiled by: Else Marais, Marlene Kassel, Naseema Aithma, Angela PotgieterRob Stewart, Branca Fernandes, and Janet Loakes

Gastro-intestinal infectionsGastro-intestinal infections

Acute inflammatory enteritis:

• Campylobacter• Salmonella• Shigella• Certain parasites

Acute dysenteryAcute 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 speciesOverview 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 speciesOverview of Shigella species

• Sensitive to heat, kill in 55 c in 1 hr• S.sonnei survive in soil & room temprature for 9-

12 days• Survive on fingers for sometime & transmit

through hand contact• If suitable,survive in milk & other food(15 days in

sea water)

• Sensitive to heat, kill in 55 c in 1 hr• S.sonnei survive in soil & room temprature for 9-

12 days• Survive on fingers for sometime & transmit

through hand contact• If suitable,survive in milk & other food(15 days in

sea water)

• 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 inepidemics of S. dysenteriae all age group equal

Overview

Overview 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

• 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

هزار نفر 100 در 11/8: 1383بروز در سال (63سيستان و بلوچستان)

هزار نفر 100 در 11/8: 1383بروز در سال (63سيستان و بلوچستان)

IranIran

• 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%)

• 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 epidemiologyDescriptive 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

• 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 factorsPredisposing 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

• 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 & resistanceSensitivity & 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…)

• 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…)

TransmissionTransmission

• 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

• 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

TransmissionTransmission

• 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

• 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 featuresClinical 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 historyClinical 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%

• 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•

تعريف اپيدميولوژيك ندارد.•گزارش غير فوري•در صورت بروز همه گيري گزارش فوري•

VirulenceVirulence

• 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

VirulenceVirulence

• 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

• 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 detectionMolecular methods of detection

• Isolation difficult• Genetic probe to the virulence-plasmid developed and being tested• PCR not routinely done for detection

OutbreaksOutbreaks• 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 outbreaksPatterns of outbreaks

• Cyclic patterns of 20-30 years• From 1900-1925 S.dysenteriae predominated while from 1926-1938, S.flexneri was common• Currently S.sonnei predominates in Europe and USA

• S.flexneri is predominant in developing countries( with boydii & dysenteriae)

Controlprimary prevention

Controlprimary 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 preventionprimary 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

• 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 PreventionSecondary Prevention

• Early treatment shorten acute phase of disease & mo. shedding

• Early treatment shorten acute phase of disease & mo. shedding

TreatmentTreatment

• 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