Global Situation for Plague, Anthrax, West Nile Virus, Leptospirosis and Dengue

1. 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 • 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. Global plague cases: 1969-2013 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 • 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 • 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. Bubonic plague

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

12. Anthrax • Causative Agent • 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 • 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 • 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 • West Nile Virus • When infections occur • 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 • 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 • 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 • 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. Swine herd’s disease Mud Fever Fort Brag Fever Seven day fever Rice Field Leptospirosis Cane cutter’s disease Geographical distribution of leptospirosis Has been found wherever it has been looked for

25. Leptospirosis • Transmission • 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 • 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 • 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

33. Dengue • Transmission • 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 • 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 2008-2015 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!