Typhoid and Cholera

Question 1

Two organisms prevalent in disasters

Answer 1

• Both begin as intestinal disease
• One causes fever, other bloodless massive water loss
• one invasion-based. other toxin

Question 2

Typhoid or Enteric Fever

Answer 2

• Caused by specific serotype of a subspecies of Salmonella enterica.
• There are many types of subspecies and serotypes
• Salmonella enterica subspecies enterica serotype typhi causes typhoid fever.
• Salmonella enterica serotype enteritidis causes gastro enteritis.
• Salmonella enterica serotypes paratyphi A, B and C cause paratyphoid fever ( weaker version of fever).

Question 3

Typhoid Fever

Answer 3

• Rare in developed countries that are now termed as High Income Countries
• More prevalent in low/ middle income countries

Question 4

Salmonella species

Answer 4

• Gram-negative bacilli (rod shaped)
• oxidase negative
• highly motile by peritrichous flagella ( flagella that cover the whole cell)
• Differentiate by serotyping

Question 5

Typhoid fever: Identification

Answer 5

Blood culture, stool (xylose lysine deoxycholate, XLD media). Serology using antibodies to detect for antigens in patient blood: Widal test-50% effective: Serotype typhi Kaufmann-White agglutination. O or somatic antigen- IgM appears early. Vi antigen - surface polysaccharide and important Virulence factor. H or flagella antigen - IgG appear later. A,B,C Para typhi have O and H antigens. ELISA: uses antigens specific to each serotype to detect antibodies for differentiation.

Question 6

Typhoid Disease transmission

Answer 6

• Through ingestion of food or drink contaminated by faeces/ urine of infected people
• Healthy carriers excluded from handling food to avoid continued contamination as symptoms usually develop 1-3 weeks after exposure and can be mild or severe with a healthy carrier state following acute illness.

Question 7

Typhoid Disease symptoms

Answer 7

• Develop 1-3 weeks after exposure, may be mild or severe.
• High fever, malaise, headache, constipation or diarrhoea, rose-coloured spots on the chest, enlarged spleen and liver.

Question 8

Typhoid disease treatment

Answer 8

• Antibiotics
• widespread resistance to common antimicrobials

Question 9

Typhoid Route of transmission

Answer 9

• Typhi and paratyphi
  strains are primarily pathogens of humans.
• Rarely if ever isolated from other animals
• Ingestion of organisms from an individual or contaminated source (human faeces)
• Healthy carriers excluded from handling food to avoid continued contamination as symptoms usually develop 1-3 weeks after exposure and can be mild or severe with a healthy carrier state following acute illness.
  Infective dose though to be about 10^6 and 10^9 (some <103 for typhi). Variation in virulence- low acidity of host stomach, immunosuppression

Question 10

Typhoid Colonisation, spread and clinical disease

Answer 10

Enter via M cells (non typhoid). Bind to host via fimbriae to CFTM ( Cystic fibrosis transmembrane conductance receptor). Type III secretion system induces bacterial mediated endocytosis (BME). Up-regulate CFTM, so more entry. First bacteraemia/stage: causes initial symptoms. Replicate inside macrophages released to mesenteric lymph nodes and then to cells of phagocyte system (liver, gall bladder, spleen, kidney and bone marrow). 7-10 days incubation period. Second: after further multiplication organism pass into the blood- spread to other organs.

Question 11

Typhoid Clinical Disease

Answer 11

• Coincides with symptoms; fever
  Further invasion of intestine from gall bladder can lead to perforation due to intense immune response. Incubation period can be 5 to 50 days although its usually 2 weeks

Question 12

Typhoid Symptoms

Answer 12

Often vague – dry cough, nose bleeds with anorexia, dull continuous headache, abdominal tenderness and discomfort. Diarrhoea uncommon – many may complain of constipation. Anaemia, leukopenia and if untreated temperature will rise step wise for 1st week, Remain high for 7-10 days ,Fall during 3rd and 4th week. Brachycardia, Hepatomegaly and splenatomegaly. Jaundice if reaches liver. Rash of rose spots. Intestinal haemorrhage and perforation are serious complications. Relapse in 5-10% cases – less severe. Mild, asymptomatic or 20% mortality if untreated

Question 13

Cases and Vaccines - Typhoid

Answer 13

-WHO: 21 million typhoid cases and 216,000-600,000 typhoid-related deaths annually worldwide. Typhoid vaccines available internationally, both considered safe and effective: Injectable polysaccharide vaccine based on the purified Vi antigen (aka Vi-PS vaccine) for children < two years of age. Live attenuated oral Ty21a vaccine available in capsules for > five years of age.

Question 14

Vi and other virulence factors

Answer 14

Vi Antigen : Immunosuppressive, so prevents diarrheal disease. Anti phagocytic, allows survival in macrophages. Reduces complement killing. Resistance to oxidative burst

Question 15

Antibiotics

Answer 15

Fever, so systemic, so you do use them

Resistance to Chloramphenicol , co-trimoxazole, ampicillin, ciprofloxacin (also in non-typhoid strains due to farm use of antibiotics). If bacteria is sensitive use ciprofloxacin. If resistant: ceftriaxone ( cephalosporin) and azithromycin (long half-life macrolide): risk of utli-drug resistance.

Question 16

Vaccinations WHO Recommendations

Answer 16

WHO recommends use of the Vi-PS and Ty21a vaccines to control endemic disease and for outbreak control and typhoid fever vaccination programmes implemented to control the disease including: health education, water quality and sanitation improvements, and training of health professionals in diagnosis and treatment.

Question 17

Cholera bacteriae: Vibrio cholerae

Answer 17

Vibrio cholerae. Gram negative bacilli “comma shaped”. Oxidase positive. Motile – single polar flagellum. Tolerant to alkali – growth range pH 6.8 to 10.2. More than 130 serotypes. Vibrio cholerae O1 is the main cause of epidemic cholera.

Question 18

Cholera- Serogroups

Answer 18

• Two serogroups of V.cholera - O1 and O139
• New variant strains detected in several parts of Asia and Africa. Non-O1 and non-0138: cause mild diarrhoea but not epidemics: dont have the cholera toxin.

Question 19

Cholera reservoirs

Answer 19

• Main reservoirs of V. cholerae are people and aquatic sources such as brackish water and estuaries, often associated with algal blooms.
• Recent studies indicate global warming creates favourable environment for bacteria

Question 20

Cholera - Pathology

Answer 20

• Cholera: acute intestinal infection caused by ingestion of food or water contaminated with bacterium V. Cholerae
• Short incubation period, produces an enterotoxin that causes a copious painless watery diarrhoea. Vomiting also occurs in most patients.
• Most persons infected with V. cholerae dont become ill, although bacterium is present in their faeces for 7-14 days.
• 80-90% of illness= mild or moderate severity and are difficult to distinguish clinically from other types of acute diarrhoea.
• Less than 20% of ill persons develop typical cholera with signs of moderates or severe dehydration.

Question 21

Cholera- Incomplete data

Answer 21

• Global threat and remains a challenge in countries without safe drinking water and adequate sanitiation
• Disease no longer poses a threat to countries with minimum standards of hygiene
• Limitations in surveillance systems and fear of trade and travel sanctions mean cases are unaccounted for. True burden of disease is estimated to be 4 million cases and 140,000 deaths annually.

Question 22

Cholera - biotypes

Answer 22

• Serotype: Antibody will bind
• Biotype: more on the phenotype and what it will do
• Two biotypes of V.Cholera O1 serotypes
• Classical and El Tor
• Both biotypes produce major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT)
• El Tor produces haemolysin and is resistant to Polymixin B
• Vibrio cholerae serogroup O139 emerged in 1992 in Madras

Question 23

Cholera transmission

Answer 23

Waterborne
Water contaminated with human faeces
Organism commonly found as resident of aquatic environment in non-endemic areas

Question 24

Cholera - Clinical Disease

Answer 24

Vibrio cholerae ingested – small dose. Multiplies in alkaline small intestine. Organisms migrate and adhere to epithelial cells (toxin co-regulated pilus). Adherent bacteria produce cholera toxin – powerful enterotoxin. Toxin activates the adenylate cyclase enzyme. Leads to overproduction of cAMP – cyclic adenosine monophosphate. Inhibits Na and Cl uptake and consequently water. Serious loss of water and electrolytes

Question 25

Cholera - Symptoms

Answer 25

Sudden onset of effortless vomiting. Profuse watery diarrhoea. Rapid dehydration and shock – fatal 12-24 hours. Profuse, watery, colourless stools with flecks of mucus and fishy odour. “Rice water stools”. Anuria, Muscle cramps. Weak and lethargic, loss of skin tone. Low blood pressure, absent or weak pulse. Milder cases. Symptomless cases common

Question 26

Cholera - Treatment

Answer 26

• Rehydration
  Oral rehydration standard
  Severe cases intravenous rehydration
  But only works with non-contaminated water

Question 27

Cholera Treatment - Antibiotics

Answer 27

• Antibiotics? - Treatment to reduce volume of water loss
• Children under 12 years of age should be given a 3-day course of erythromycin
• Children under 5 years of age should also be given zinc for 10 days (10 mg per day under 6 months, 20 mg per day above 6 months).
• For older children and adults, a 3-day course of tetracycline (12.5 mg/kg – 4 times a day) or a single dose of doxycycline (300 mg) is recommended.

Question 28

Cholera Detection - When should a case be suspected?

Answer 28

• in an area where the disease is not known to be present, a patient aged 5 years or more develops severe dehydration or dies from acute watery diarrhoea;
• in an area where there is a cholera epidemic, a patient aged 5 years or more develops acute watery diarrhoea, with or without vomiting.
• A case of cholera is confirmed when Vibrio cholerae O1 or O139 is isolated from any patient with diarrhoea.
• TCBS (Thiosulfate citrate bile salts) sucrose agar
• Alkaline peptone water selects for the organism
• Toxin, serotyping, genetic typing

Question 29

Cholera Vaccine - oral vaccines

Answer 29

Two types of oral cholera vaccine (OCVs):
- a monovalent vaccine based on formalin and heat-killed whole cells of V. cholerae O1 plus recombinant cholera toxin B subunit
- provides short-term protection in all age groups evaluated at 4-6 months following vaccination.

• bivalent killed vaccine based on V. cholerae serogroups O1 and O139
• evidence of efficacy persisting over 5 years in children under five years of age at vaccination has been reported (2017). No B subunit

used in conjunction with other prevention and control strategies