Cholera

Question 1

How has cholera infiltrated Zambia

Answer 1

• Socio-cultural factors
• War

Question 2

Geographical distribution of reported cholera cases: September to November 2024

Answer 2

• not a disease of the past
• poor sanitation
• Africa, Afghanistan, Somalia (war); Gaza, Haiti
• water supply

Question 3

SMDWS

Answer 3

• Safely managed drinking water services
• sanitary analysis
• 4bn: no access
• one in three people used
  SMDWS in LMICs in 2020
• faecal contamination:
  primary limiting factor
  affecting almost half of the
  population of LMICs
• cholera (water-borne) risk

Question 4

Cholera gravis

Answer 4

• incubation period: ~0.5-5 days
• abrupt onset: watery diarrhoea & vomiting; generally clear and odourless
• severe dehydration
• absent or low-volume pulse
• undetectable blood pressure
• poor skin turgor
• sunken eyes
• wrinkled hands and feet
• initially restless and thirsty; patients later become apathetic and may lose consciousness as shock progresses
• respiratory distress
• metabolic acidosis
• most deaths occur in the first day; can be within a few hours

Question 5

emergence of modern cholera

Answer 5

• severe diarrhoea and vomiting known throughout recorded history (e.g. Chaucer)
• initially known as ‘Asiatic Cholera’
• contemporary: Vibrio cholerae
• frequently epidemic and pandemic
• the ‘First Pandemic’: India, 1817
• in the absence of microbiological/ancient DNA data, older cases are uncertain

Question 6

Chaucer

Answer 6

‘Comth of the grete superfluitee Of youre rede Colera’

Question 7

Pandemic cholera in the 19th Century - the basics

Answer 7

• First: 1817-1824
• Second: 1827-1837
• Third: 1839-1855
• Fourth: 1863-1874

Question 8

Pandemic cholera in the 19th Century - the specifics

Answer 8

• spread out of India with British troop movements and trade shipping routes; globalisation
• successive waves
• introduction of disease congresses of control

Question 9

The 19C context

Answer 9

• great increase in Eurasian trade through Suez Canal

Question 10

The 19C British perspective

Answer 10

British wanted to keep free trade, not stopping pandemic

Question 11

Cholera science in the 19th Century

Answer 11

• Pacini 1854: ‘comma shaped’ bacteria in stools
• Snow 1854: water-borne
• Koch 1883: V. cholera isolation
• gradual introduction of improved
  sanitation in Europe & North
  America

Question 12

John Snow and cholera

Answer 12

• pioneering: the birth of epidemiology; “father of field epidemiology.”
• did not accept the ‘miasma’ hypothesis
• espoused the contagion hypothesis
• Broad Street Pump (1854)
• ‘On the mode of communication of Cholera’ (1855)
• no germ theory

Question 13

John Snow’s Cholera Map

Answer 13

• coldspots workhouse, brewery
• took the handle off the pump and stopped the outbreak
• single point contaminant outbreak

Question 14

John Snow’s Map Revisited: LACKINGS

Answer 14

• estimates of the population at risk;
• assessment of progression over time

Question 15

John’s Snow’s Map Revisited: Modern analysis

Answer 15

• GIS approaches confirmed Snow’s findings
• consistent with his conclusion that the outbreak was waterborne

Question 16

20th Century

Answer 16

– intravenous/oral rehydration therapy;
– discovery of cholera toxin;
– vaccines and drug therapy;
– molecular characterisation of V. cholerae (WGS)

Question 17

21st Century

Answer 17

– continued epidemics (Haiti outbreak)
– genomic epidemiology

Question 18

Molecular characterisation of V. cholerae

Answer 18

2 chromosomes; v unusual

Question 19

Vibrio cholerae

Answer 19

• Gram -ve bacterium
• commonly found in brackish estuarine water
• serological differentiation: LPS O antigen
• O1/139 serogroups Tox+
• all pathogenic V. cholerae express Ctx and Tcp

Question 20

O1/139 serogroups

Answer 20

• cholera toxin-producing strains
• cause the great majority of
  disease

Question 21

Ctx

Answer 21

• cholera toxin
• ctxA/B genes on a filamentous phage

Question 22

Tcp

Answer 22

• toxin co-regulated pilus
• tcp gene: on pathogenicity island

Question 23

Relationships of Vibrio cholerae variants

Answer 23

• O1-200 of Vibrio cholerae exist
• O1/139 capable of causing cholera when ingested
• selected for in the host
• Tox- are selected against

Question 24

O1-200

Answer 24

> 200 serogroups exist