Melioidosis- An overview, covers the Aetiology, Epidemiology, World as well as Indian Scenario of Meliodosis, Its public health impact, control strategy and Indian Research prospects of the disease. All credit goes to Dr. Gazanfar Abass, MVSc Scholar at Division of Veterinary Public Health, Indian Veterinary Research Institute, izatnagar UP, India

1. Credit Seminar
On
Presenter:
Dr.Gazanfar Abass
Masters Scholar
VPH, IVRI-ICAR
Melioidosis : An Overview

2. OVERVIEW
Introduction Etiology Epidemiology Transmission
Symptoms Diagnosis Treatment
Control
measures
Conclusion

4. “ A condition similar to glanders, in asses”
synonyms :
Whitmore's disease
Pseudoglanders
Nightcliff gardener's disease
Paddy-field disease
Morphia infector’s Septicemia
Vietnamese Time-Bomb Disease
‘Great mimicker’

6. • Aetiology Burkholderia peudomallei
• Motile, gram Negative
• Rod shaped bacilli, Ubiquitous
• Bipolar staining ( I/C beta-hydroxy butyric acid)
• Named after W.H.Burkholder
• Saprophyte isolated from various soil types & surface water of varying depth
• B. pseudomallei category B bioterrorism agent
• IP---- 10-15 days to years (62 yrs documented) (Ngauy et al., 2005)
http://www.cdc.gov/meli

7. epidemiology

8. Determinants Associated with Agent, Host, Environment
Determinants Associated
Agent •Virulence factor- Produces extracellular capsular polysaccharide (2-O- acetyl-6-
deoxy-beta-D-heptopyranose).
(Atkins et al., 2004)
•The deposition of complement factor C3b on bacterial cell is lower in presence of
capsular polysaccharide
(Reckseidler et al., 2007)
•Delivery of bacterial effector molecules into the host-cell cytoplasm- encoded by 3
TTSS gene clusters.
(Wiersinga et al., 2006)

9. Determinants……………Continued …
Determinants Associated
Encodes 6 type VI secretion systems, implicated in bacterial virulence, intracellular
survival, and competition within bacterial communities.
(Burtnick et al., 2011)
Burkholderia lethal factor 1: similar to E. coli cytotoxic necrotizing factor 1;
- interferes with the initiation of translation, alters actin cytoskeleton leading to
cell death.
Cruz-Migoni et al., 2011)
B. pseudomallei- intrinsically resistant to many antibiotics— class A beta-lactamase
gene and class D beta-lactamase gene.
(Chen et al., 2004)
Morphotype switching: Alteration of surface determinents for in vivo phenotypic
changes.
(Chantratita et al., 2007)

10. Determinants………………
Determinants Associated
Host •People suffering from immunocompromising diseases are more susceptible to
contract the severe form of disease
•High risk group include patients with Diabetes mellitus, chronic Kidney
disease ,chronic pulmonary disease, prolonged glucocorticoid therapy,
cancer, cystic fibrosis and excessive alcohol intake..
` (Currie et al., 2010)
Environment • Outbreaks- associated with the heavy rainfall, flooding, high humidity or
temperature.

11. Determinants………
Determinants Associated
• All soil types especially anthrosol and acrisol soil types are strongly associated
with the presence of B. pseudomallei
(Direk et al., 2016)
High salinity and high proportion of gravel are associated with the presence of
B. pseudomelli.
(Direk et al., 2016)
Impaired neutrophil function, such as mobilization, delivery, adherence and
ingestion, in the people suffering from Diabetes, excessive alcohol intake,
kidney failure, chronic lung infection, malignancy or immunosuppressive
disease like HIV, etc are susceptible to Melioidosis.
(Jones et al., 1996)

12. transmission

13. Transmission
• Bacterial Inoculation
• Ingestion
• Inhalation
• Direct contact with contaminated
soil or water
(Navaneethan et al., 2006)
• Vector-borne transmission via
mosquito (Aedes agypti) and rat
flea (Xenopsylla cheopsis) has
been described
(Nguyen et al., 1972)
• Human-to-human transmission is
very rare.
Melioidosis has been transmitted to infants through breast milk from infected mothers
(Cheng et al ., 2005)

14. pathogenesis

15. T3SS3
Effector
molecule BopE
Suppress iNOS BimA protein
Joost et al., 2006/ Nature Vol. 4
Pathogenesis
Actin based membrane
protrusions

16. WORLD SCENARIO

17. World Scenario
Country Year Comments References
Myanmar 1911 •FIRST human case reported
•The total of 38 cases were reported in 10
months.
Whitmore et al., 1912
Malaysia 1924 •Scattered human cases were reported. Stanton et al., 1924
South
Vietnam
1925 •Multiple human cases were reported
•8 patients succumbed to death
Pons et al., 1927
Sri Lanka 1927 •Reported human case followed by cases in
cows.
Denny et al., 1927
Indonesia 1929 •229 confirmed human cases with 35% mortality
rate
Ertug et al., 1961
Thailand 1955 •The first human case of melioidosis reported.
•By 1966, organism was isolated from
countrywide.
•595 cases were reported between 1955 and
1985
Jittivej et al., 1956
Leelarasamee et al., 1989
Patamasucon et al., 1990

18. World Scenario…..Continued..
Country Year Comments References
Western
Europe
1975 •Outbreak of melioidosis at the Paris Zoo was
doubtless the most unusual spread of bacteria to
non-endemic region.
(http://www.cfsph.iastate.e
du/Factsheets/pdfs/melioid
osis.pdf)
Spain 1982 •Bacteria isolated from horses Galimand et al., 1983
Queensland 1981
-83
•Intermittent Porcine outbreaks were reported
•Total of 943 porcine cases with 31% mortality rate.
Ketterer et al., 1986
Northern
Australia
1998
-
2010
•Most common cause of community-acquired
bacteremic pneumonia.
•The animal species affected were goats (31), pigs
(8), cattle (4), deer (1), horse (1), and wild animals
in captivity (camel, crocodile, monkey, and zebra [1
each])
Currie et al., 2000
Direk et al., 2011

19. World Scenario…..Continued…
Country Year Comments References
Brazil 2003 Reported sporadic human cases Dionne et al., 2005
Southern
Thailand
2004 •Reported outbreak following tsunami in Indian
ocean
Kongsaengdao et al., 2005
Thailand 2007 •1,865 culture confirmed melioidosis cases
were recorded.
•Third most frequent cause of death from
Melioidosis after HIV/AIDS & TB.
Limmathurotsakul et al., 2010

20. World Scenario…..Continued…
Country Year Comments References
Malaysia 2007 only 1 of 440 wild birds admitted to a research
center over 9 years was found to have
melioidosis
Ouadah et al., 2011
Thailand 2008 •2,557 culture confirmed melioidosis case with
a Case fatality of 42.6% were recorded.
Wongratanacheewin et al 2011
USA 2008-
13
•37 confirmed cases of melioidosis (34 human
cases and three animal cases) by CDC’s
Bacterial Special Pathogens Branch (BSPB) of
human infections
CDC/MMWR/Surveillence
Sumaries/Vol.64/No.5

21. Endemicity of Melioidosis

22. Seasonal variation of Melioidosis Incidence from 1992-97 in Darwin among sheep, goat and pigs
Jodie et al., 2000

23. INDIAN SCENARIO

25. Seasonal Distribution of Melioidosis and Rainfall
(India)
Kavitha et al., 2010

26. Kavitha et al., 2010
Annual Distribution of Melioidosis in Humans

27. Demographic data of 32 patients with melioidosis
Gopalakrishnan
et al., 2013
In animal - “hugely underdiagnosed or misdiagnosed in India

28. PREDICTED FUTURE TREND

29. Dr Direk (Presented at 2nd GRF One Health Summit 2013, Davos )

30. Dr Direk (Presented at 2nd GRF One Health Summit 2013, Davos )

31. Countries with greatest predicted
incidence in near future
The southern Pacific
Sri Lanka
Mexico
Peru
Brazil
Parts of Africa and Middle East
India
Panama
http://www.cdc.gov/melioidosis/exposure/index.htm

33. Clinical
presentation

34. Clinical Signs……Humans
Localized Infection:
 Localized pain or
swelling
 Fever
 Ulceration
 Abscess
Bloodstream Infection:
 Fever
 Headache
 Respiratory distress
 Abdominal
discomfort
 Joint pain
 Disorientation
Pulmonary Form:
 Cough
 Chest pain
 High fever
 Headache
 Anorexia
Disseminated Infection:
 Fever
 Weight loss
 Stomach or chest pain
 Muscle or joint pain
 Headache
 Seizures
http://www.cdc.gov/melioidosis/signs-symptoms.html

35. Clinical Signs ……..Animals
• NO specific clinical presentation
• Widely vary within a species, depending on the site of infection, and range from
acute to chronic
• Subclinical infection is common
• Single or multiple suppurative or caseous nodules/abscesses
• Organs most commonly affected include the lungs, spleen, liver, and associated
lymph nodes.
• Goats often develop mastitis
• The respiratory system is involved preferentially in sheep
www.merckvetmanual.com/mvm/generalized_conditions/melioidosis/overview_of_melioidosis.html

36. • Fatalities occur when vital organs are involved.
• CNS involvement with overt signs seen in all the affected species.
• In dogs, disease may be acute, subacute, or chronic
 Acute form--septicemia with fever, severe diarrhea, and fulminant
pneumonia are common.
 Subacute form--may present as a skin lesion with lymphangitis and
lymphadenitis
 Chronic form-- can occur in any organ with clinical signs that include
anorexia, myalgia, edema of the limbs, abscesses, etc.
www.merckvetmanual.com/mvm/generalized_conditions/melioidosis/overview_of_melioidosis.html
……..Animals

37. diagnosis

38. Diagnosis
• Clinical signs ( need expertise)
• Isolation and Identification-----------Gold standard
• Culture of B. pseudomallei from blood, sputum, pus, urine, synovial fluid, peritoneal
fluid, or pericardial fluid.
(Leelarasamee et al., 1989)
• Swabs(ulcer, throat, rectal, etc) : placed into Ashdown’s selective medium & B.
pseudomallei Selective Agar(BPSA) (Ashdown et al., 1979)
• Serological evidence of infection can be obtained by IHA (Yap et al., 1991)
• IHA ----titre >1:160 in the absence of a positive culture is therefore regarded as
supportive rather than definitive evidence of melioidosis. (leelarasamee et al., 1989)
• Biochemical Tests:
 Gram staining ---------------------- (gram +ive)

39. …..………Cont.
 Bipolar staining, Motility test
• A commercial ELISA kit for melioidosis appears to perform well .
(Direk et al., 2011)
• No ELISA test has yet been clinically validated as diagnostic tool.
(Peacock et al., 2011)
• PCR ---- No. of genes amplified
 E.g. A0179 protein 1 and type III secretion system (TTSS-1) gene
(Novak et al., 2006)

40. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 2, February 2015

41. treatment

42. Treatment
• Antibiotics: Ceftazidime +/plus co-trimoxazole
Ceftazidime resistant B.peudomallei reported from Andhra Pradesh (India) treated
successfully with imipenem.
(Bijayini et al., 2012)
 Carbepenams and cephalosporins are effective
• Regular monitoring of urea and electrolytes, creatinine, LFTs, body vitals
• For neurological melioidosis, osteomyelitis, septic arthritis, genitourinary
infection- trimethoprim+sulfamethoxazole
No Vaccine is available to date for the public use

45. • Deadly tropical infections that kill within 48 hours don’t usually go unnoticed.But
one killer has been largely ignored for decades. Now, thanks to worries about
bioterror, it is being taken more seriously.
E.g. of some initiative taken
 Menzies School of Health Research in Darwin running a self-funded project.
 US NIAID is now encouraging microbiologists to begin working on the bacterium
 B.mallei evolved directly from B.pseudomallei, losing parts of its genome
(Godoy et al.,2003)
 Publication of the complete genome sequence of B. pseudomallei
(Holden et al., 2004)
NATURE|VOL 434|7 APRIL 2005|www.nature.com/nature

46. control
measures

47. • Personal Protective Measures: like wearing protective equipment such as gloves
and suitable clothing High risk group-Agricultural worker, etc.
• Community Measures: Disinfection (chlorination or chloramination )of the
drinking water supply (Howard et al., 2005)
• Awareness raiser among veterinary and human health authorities
(Ketterer et al., 1986)
• Obtaining data by repeated environmental investigations .
(Inglis et al., 2001)
• Mechanization of agricultural activities in disease endemic areas
• Laboratory Workers: Handled under BSL-3 (CDC., 2009)

48. Protective and Mitigating responses
• Governmental preparedness
• Cross Sector planning and collaboration
• Cross Boundary planning and collaboration
• Expansion of Surveillance, Case tracking and Epidemiology
• Laboratory Diagnostic Enhancement
• Improved information systems

49. Indian research
prospects

50. KMC, Manipal,
Karnataka
CMC, Vellore, Tamil Nadu AIMS, Kochi, Karela
Trivandrum Medical College,
Thiruvananthapuram, Kerala
JIPMER, Gorimedu, Puducherry AIIMS, Delhi
Indian Institutions diagnosing the disease

51. Indian melioidosis research overview

52. conclusion

53. Conclusion
• 165000 human cases are estimated per year worldwide with a case fatality of 55%.
(Direk et al., 2016)
• No international standard for diagnosis of melioidosis exists which is the drawback
in reliable proceedings.
• No evaluated test kit neither based on the detection of specific antibodies, specific
antigens, nor on the amplification of species specific DNA sequences is
commercially available.
Efforts have to be made for closing this gap in future
• The large numbers of estimated cases and fatalities emphasize that the disease
warrants renewed attention from public health officials and policy makers.

54. • Physicians should consider melioidosis in the differential diagnosis of
patients with acute febrile illnesses, risk factors for melioidosis, and
compatible travel or exposure history
• Personnel at risk for occupational exposure (e.g. laboratory workers or
researchers) follow proper safety practices, which includes using appropriate
PPE when working with unknown pathogens
• High time for the scientific society, policy makers, government
& health experts of the country like India, where the disease is
endemic, and predicted to be fatal in the near future , to work
together with the objective of preventing any irrecoverable
catastrophe in any form of life.
……Con.

55. ??