1. 30 July – 01 August, Chonburi, Thailand
Global Situation for Plague, Anthrax, West Nile Virus, Leptospirosis and Dengue
Workshop on Laboratory Diagnosis for Zoonotic Pathogens
30 July – 01 August, Chonburi, Thailand
Dr Richard Brown, WHO Thailand

2. Plague Causative Agent When infections occur Distribution Reservoir
Yersinia Pestis
When infections occur
Through the bite of an infected rat flea
Distribution
Americas, Central / southern Africa, Central Asia, China, India, Mongolia (Myanmar, Laos PDR)
Reservoir
Wild rodents (rats) are important as hosts for the flea vectors
Transmission to humans
Humans encounter infection ‘in the wild’ (hunting, trapping, trekking, farming)
Humans encounter infection in domestic settings / households (poverty, low levels hygiene)
Deliberate release…?

3. Plague ecology

4. Distribution of plague cases by country, 2013
Global plague cases:
2013: 859 cases (136 deaths)
Distribution of plague cases by country, 2013

5. Distribution of plague cases reported to WHO, 2000-2009

6. Plague in South-East Asia
India: Pneumonic plague outbreak in Himanchal Pradesh in Feb 2002 and bubonic plague in Uttarkashi in Oct 2004
Indonesia: Pasuruan district of East Java in Feb 2007
Myanmar: 1994
Nepal: 1968
Plague is a notifiable disease in Bhutan, India, Indonesia, Maldives, Myanmar and Sri Lanka

7. Plague Incubation period Period of communicability Susceptibility
1-7 days
Period of communicability
Fleas may remain infective for months
Bubonic plague not normally transmitted human-to-human unless there is direct contact with pus
Pneumonic plague may be highly communicable if there is overcrowding and cool temperatures
Susceptibility
Humans are normally susceptible
Immunity after infection may not protect against a new infection

8. Plague Clinical presentation and course of illness Treatment Diagnosis
Initial signs and symptoms may be non-specific with fever, chills, malaise, myalgia nausea, sore throat and headache
Lymphadenitis often develops at the site of inoculation (bubonic plague), e.g. a bite on the leg may lead to development of buboes in the inguinal area (groin)
Septicaemic plague may follow infection and may be associated with DIC.
Involvement of the lungs results in pneumonia and this may lead to secondary pneumonic plague
With secondary pneumonic plague, transmission can occur human-to-human leading to localized outbreaks or devastating epidemics
If untreated, for bubonic plague the case fatality rate is 50-60%
Untreated septicaemic or pneumonic plague are normally fatal
Treatment
Antibiotics (streptomycin, gentamicin, tetracyclines, chloramphenicol)
Diagnosis
Clinical: signs , symptoms and an exposure history (hunting for marmots in Central Asia)
Laboratory …..

9. World Health Organization
12 April 2017
Bubonic plague
Buboes usually in groin as most ppl get bitten on the leg. When on neck prob bitten during sleep.
Bubo very painful.

10. Plague Preventive / control measures
Rodent control
Wear gloves when handling wild animals (i.e. when hunting)
Vaccine..?
Should not be only the protection
Adverse reactions and unproven efficacy…
Isolate individuals with pneumonic plague and implement infection control measures
Consider chemoprophylaxis for people sharing a house with a case, or contacts of pneumonic plague
Quarantine is not generally effective - and may induce panic
Why is laboratory diagnosis / confirmation important?
Although clinical presentation may be typical, any rare event needs confirmation
May be part of an outbreak
Confirmation will lead to specific treatment and control measures
Confirm antibiotic sensitivity

11. Early detection and confirmation in remote areas
Pneumonic plague outbreak
Zobia, DRC, 2005
alert
International team on the field
Collection kits and Rapid tests, but with training !

12. Anthrax Causative Agent When infections occur Distribution Reservoir
Bacillus anthracis
When infections occur
Primarily a disease of herbivores, humans are incidental hosts
Infrequent and sporadic
Occupational hazard of workers who process hides, wool, hair (especially goats)
Deliberate release..?
Distribution
Sub-Saharan Africa, Asia, South / Central America, South / Eastern Europe
Reservoir
Normally herbivores (domestic and wild)
Dried or processed skins may harbour spores for years (important is spread of disease)

13. Anthrax Transmission Incubation period Period of communicability
Animals shed bacilli in blood through haemorrhaging at the time of death
Cutaneous infection normally requires a pre-existing break in the skin
Intestinal anthrax acquired through eating poorly cooked meat
Inhalational anthrax through inhalation of spores through ‘risky industrial processes’
Incubation period
Typically 1-7 days, although it can be much longer
Period of communicability
Human-to-human transmission is very rare (never reported for inhalational or intestinal disease)
Susceptibility
Immunity may be partial (second attacks can occur)

14. Anthrax Clinical presentation and course of illness Cutaneous
More than 95% human infections are cutaneous – present with itching, followed by a lesion that becomes papular, then vesicular and then develops over 2-6 days into a depressed black ‘eschar’ with surrounding oedema
Pain is unusual
Typically on exposed areas of the body: involvement of the face / neck may lead to airway obstruction
Intestinal
Intestinal anthrax is rare and difficult to recognize – associated with outbreaks
Abdominal distress accompanied by pain, nausea and vomiting, fever, septicaemia and death
Inhalational
Initially mild, then Fever, malaise, mild cough, chest pain, acute respiratory distress, and eventually death

15. Cutaneous anthrax

16. Anthrax Treatment Diagnosis Preventive / control measures
Ciprofloxacin, alternatives are doxycycline and amoxycillin
Diagnosis
Clinical: signs , symptoms and an exposure / occupational history
Laboratory …..
Preventive / control measures
Prevent in animals (vaccination of livestock in endemic regions)
Education of people with occupational risk , control dust in ‘at-risk’ industrial settings
Vaccination available for laboratory workers at high risk
Isolation not needed for human cases (standard precautions)
Why is laboratory diagnosis / confirmation important?
Rare disease, specific treatment available – implications for animal health
May be part of an outbreak

17. West Nile Virus Causative Agent When infections occur Distribution
Through the bite of an infected mosquito (that has also bitten an infected bird in an endemic area)
Risk of human infection probably depends on levels of native immunity in wild birds
Distribution
Africa, Southern Europe, Central & East Asia, (including India)
Introduced recently into the Americas (through New York)
Reservoir
Susceptible wild birds

18. WNV transmission cycle

19. West Nile Virus Transmission Incubation period
Rare cases of human infection through trans-placental transmission, organ transplantation and blood transfusion
Incubation period
5-15 days
Period of communicability
Humans not normally infectious to other humans (virus not detectable in blood after onset of disease)
Susceptibility
Disease most common in infancy and old age – severity increase with age
Infection thought to result in immunity

20. West Nile Virus Clinical presentation and course of illness Treatment
Most infections asymptomatic
Mild case have fever with headache, or occasionally aseptic meningitis
Severe infections present with acute onset of severe headache, high fever, meningeal signs, altered mental state, and occasional acute flaccid paralysis
Case fatality rate up to 25% for encephalitis
Treatment
Supportive
Diagnosis
Clinical: (encephalitis with acute flaccid paralysis is quite rare)
Laboratory…

21. West Nile Virus Preventive / control measures
Control of mosquitoes
Prevention of mosquito bites
Spraying aircraft arriving from endemic areas?
Why is laboratory diagnosis / confirmation important?
Important to differentiate from other infectious / non-infectious causes of acute neurological disease (some of which may have specific treatment
May be part of an outbreak
Allows institution of control measures

22. Leptospirosis Causative Agent When infections occur? Distribution
Pathogenic Leptospires are spirochetes that belong to seven main species, with many subtypes…
When infections occur?
Mostly exposure to water contaminated by rat urine
Occupational hazard for farmers, veterinarians, sewer workers, military (and others)
Outbreaks associated with flooding
Distribution
Worldwide, except in polar regions
Endemic in rural farming areas and urban settings ( especially with unplanned development)
Reservoir
Maintained in genital tract and renal tubules of wild and domestic animals
Serovars are adapted to one or more animal species (dogs, swine and cattle as well as rats)

23. Geographical distribution of leptospirosis
Fort Brag Fever
Rice Field
Leptospirosis
Cane cutter’s disease
Mud Fever
Swine herd’s disease
Seven day fever
Has been found wherever it has been looked for

25. Leptospirosis Transmission Incubation period Period of communicability
Contact of skin (especially if broken) or mucosal membranes with contaminated water or vegetation
Occasionally through ingestion or inhalation of droplet aerosols
Incubation period
5-14 days, (range of 2-30 days)
Period of communicability
Direct human-to-human transmission is very rare
Susceptibility
Humans are generally susceptible, infection provide serovar-specific immunity

26. Leptospirosis Clinical presentation and course of illness Treatment
Two phases – 1.] leptospiraemic and 2.] convalescent (may be separated by 3-4 days, or be absent)
1.] Early phase illness abrupt onset of high fever, myalgia, headache, nausea, vomiting, abdominal pain, diarrhoea, rash. Conjunctival suffusion seen in 30%
2.] Late phase illness occurs 4-9 days after onset includes prolonged fever and systemic complications including jaundice, renal failure, bleeding, hypotension, pulmonary haemorrhage, myocarditis, meningitis
Case fatality rates approximately 10% for acute renal failure and 50% for pulmonary
Treatment
Antibiotics
Supportive
Diagnosis
Clinical can be difficult, but conjunctival suffusion is said to be pathognomic
Laboratory….

27. Leptospirosis Preventive / control measures
Rodent control…
Education – especially for those at occupational risk, or during floods
No need to isolate patients
Why is laboratory diagnosis / confirmation important?
Early clinical diagnosis may be difficult, but specific treatment available
Early detection of complications
May be part of an outbreak
Serological classification may provide useful epidemiological information
WHO perspective
Development of Regional Strategic Framework for Prevention and Control of Leptospirosis in the South East Asia Region
Support establishment of National Leptospirosis Reference Laboratory and laboratory networking
Strengthen capacity building for clinical case management in Member States

28. Dengue Causative Agent When infections occur Distribution Reservoir
Flavivirus - types 1-5
When infections occur
Bite of infected mosquitoes (during the day)
Distribution
Endemic in most tropical countries
Prevalence / incidence may be increasing
Distribution may be changing as a result of climate change
Reservoir
Human / mosquito cycle in tropical urban areas
Monkey / mosquito cycle may serve as a reservoir in some areas

29. Average annual number of dengue and severe dengue cases reported to WHO in 1955–2007, and no. of cases reported, 2008–2010

32. 32 32

33. Dengue Transmission Incubation period Period of communicability
Bite of infected mosquitoes – mainly Aedes aegypti, but also albopictus
Incubation period
3-14 days, commonly 4-7 days
Period of communicability
No direct human-to-human transmission
Humans are infective for mosquitoes during high viraemia
Susceptibility
Susceptibility universal in humans, but illness may be milder in children
Recovery provides serotype-specific immunity, but may make disease worse if infection occurs with another serotype

34. Vectors for transmission
Aedes aegypti Aedes albopictus

35. Percent of dengue cases by age group, Thailand (2002 – 2011)

36. Dengue Clinical presentation and course of illness Treatment Diagnosis
Supportive, including oral rehydration
Aspirin should not be used
Careful fluid resuscitation is very important
Treatment
Supportive, but management of i.v. fluids is very important
Diagnosis
Clinical: early clinical diagnosis is important, but may be difficult. The tourniquet test is helpful, but is a relatively late sign
Laboratory…

37. Dengue Preventive / control measures
Mosquito control
Preventive education
No need to isolate patients
Why is laboratory diagnosis / confirmation important?
Differentiates from other infections that have specific treatment
Facilitates supportive treatment of dengue May indicate an outbreak / upsurge of cases
Allows institution of control measures
WHO perspective
The Asia- Pacific Dengue Partnership (APDP) was set up in March 2006 to support and facilitate effective implementation of prevention and control.
In 2007, the South-East Asia and the Western Pacific Regions jointly formulated the Bi-Regional Dengue Strategic Plan, endorsed by the RC in 2008.

38. Raising Awareness: ASEAN Dengue Day
Observed every 15th of June
Simultaneous activities in key cities of the ASEAN countries

39. Thank you!