Melioidosis

Transcript

1 Melioidosis S Melioidosis is also known as Pseudoglanders or Whitmore Disease. l i d Melioidosis e Pseudoglanders Whitmore Disease 1 In today’s presentation we will cover information regarding the organism S Overview that causes Melioidosis and its epidemiology. We will also talk about the l history of the disease, how it is transmitted, and the clinical signs in • Organism i • History humans and animals. Finally, we will address prevention and control d Epidemiology • measures for Melioidosis. e Transmission • • Disease in Humans Disease in Animals • 2 Control Prevention and • Center for Food Security and Public Health, Iowa State University, 2011 S l i d The Organism e 3 like S “Melioidosis” is derived from the Greek word meaning glanders - Organism illness or distemper of the asses. It is caused by the bacterium l Burkholderia pseudomallei (previously called Pseudomonas • Burkholderia pseudomallei i – Aerobic, gram - negative - pseudomallei ). It is an aerobic, gram negative motile bacillus found in d motile bacillus water and moist soil and is endemic in tropical and subtropical countries. – Found in water and e soil moist It is an opportunistic pathogen that produces exotoxins. Because it can Opportunistic pathogen – survive in phagocytic cells, latent infections ar e a common disease – Produces exotoxins 4 – cells phagocytic Can survive in manifestation. Latent infections common • Center for Food Security and Public Health, Iowa State University, 2011 [Image from: CDC/ Courtesy of Larry Stauffer, Oregon State Public Health Laboratory.] 1 Center for Food Security and Public Health, Iowa State University, 2011

2 Melioidosis S l i d History e 5 S In 1912, Captain Alfred Whitmore (a pathologist) a nd his assistant C. S. History Krishnaswami noted a disease similar to glanders in emaciated morphine l addicts in Rangoon, Burma. However, the patients had no history of • 1912, Burma i Alfred Whitmore • equine exposure and the colony morphology of the organism differed d Organism isolated • Burkh olderia mallei ). This led to the discovery of a from that of glanders ( in humans e and melioidosis, Burkholderia pseudomallei new organism and disease, disease like Glanders – - • Colony growth differed respectively. Melioidosis is also called “Whitmore” disease, in his honor. exposure – No equine 1941 - Alfred Whitmore 1876 6 Whitmore further documented the pathology of the disease from “Whitmore” disease – su bsequent cases, most of whom were morphine addicts. He determined Center for Food Security and Public Health, Iowa State University, 2011 that the disease was a consequence of the general debility and wasting found in these patients, rather than from the direct inoculation of the organism. tropical diseases, the Wellcome Trust. [Image from: illustrated history of Edited by FEG Cox.] In 1913, in Malaysia, a fatal ‘distemper - S like’ outbreak occurred in History animals at the Institute for Medical Research. Although the bacterium l Ambrose Thomas B. was isolated, it was not until 1917 that it was identified as • 1913, Malaysia Stanton i • Stanton and Fletcher pseudomallei Bacillus (then called or Wh pseudomallei itmore’s bacillus). d • “ Distemper - like” This was discovered by Ambrose Thomas Stanton, a bacteriologist, and outbreak in animals e William Fletcher, a pathologist. Over the next decade, they documented Isolated – B. pseudomallei 39 human cases and several cases in wild and domesticated animals. They Pioneered serological • 7 William ogical tests used for diagnosing the disease. also pioneered the serol Fletcher tests for diagnosis During this time the disease was also found in Vietnam, Sri Lanka and Center for Food Security and Public Health, Iowa State University, 2011 Indonesia. Stanton and Fletcher originally associated rodent excreta to the zoonotic transmission. This has since been disproved. rom: illustrated history of tropical diseases, the Wellcome Trust. [Image f Edited by FEG Cox.] Melioidosis has been recognized in soldiers stationed in endemic areas. S History At least 100 cases among French forces in Indochina wer e reported from l 1948 through 1954 during the war of Vietnamese independence from - 1954, Indo - China • 1948 i – Over 100 French soldiers French colonial rule. As American troops replaced the French, they were d • 1973, Vietnam also affected. By 1973, over 300 cases of melioidosis had been diagnosed – Over 300 American soldiers e ned in Vietnam. Most cases were acquired among American soldiers statio “Vietnamese time bomb” – Infections reoccurred after latent period • by direct contact of wounds with mud and water. However, an unusual Military dogs in Vietnam also affected – 8 number of cases among helicopter crews suggested that inhalation of the myalgia Fever, • , dermal abscesses organism could also cause infection. Military dogs stationed in Vietnam Center for Food Security and Public Health, Iowa State University, 2011 wer e also affected and developed fever, myalgia and dermal abscesses from the organism. The latent nature of melioidosis was discovered as many soldiers had reoccurrence, often fatal, of infection after returning to Center for Food Security and Public Health, Iowa State University, 2011 2

3 Melioidosis s been called the “Vietnamese the States. For this reason, melioidosis ha time bomb”. The current record for the latent period is 26 years, and cases are still occurring in Vietnam veterans today. An estimated 225,000 Americans were potentially exposed while in Vietnam. Unfortunately, a good test to determine latent infection is not currently available. [Image from: http://commons.wikimedia.org] S Since its discovery, Burkholderia been found pseudomallei has History worldwide. It is most prevalent in tropical and sub tropical regions. l It was first However - 1970’s an outbreak occurred in France . in the mid • 1970s , France i – Numerous horses and zoo discovered during a necropsy of a horse. Samples from the liver and d animals affected spleen grew the organism. Later the soil was found to be contaminated Melioidosis – in temperate climates e ive disinfection and animal slaughter with the organism. An intens 1989 • Effective antibiotic – treatment identified program was initiated. This outbreak shows that melioidosis can be 9 established and transmitted within temperate regions. Acute melioidosis was highly fatal prior to antibiotic therapy. In 1989, the use of Center for Food Security and Public Health, Iowa State University, 2011 for treatment of melioidosis was found to decrease ceftazidimine mortality in these cases by 50%. S l i d Transmission e 1 0 Transmission of S Burkholderia pseudomallei can occur in several ways. Transmission The most common way is through contact of skin wounds with l contaminated soil or water. Additional routes of infection include • Wound infection i – Contact with contaminated soil or water aspiration or ingestion of contaminated water and inhalation of dust from d • Ingestion soil. Transmission between infected animals and/or infected people is – Contaminated water e Inhalation • to - - ry rare. Person ve person transmission has been described rarely, Dust from contaminated soil – generally to family members in close contact (e.g. family members who Rarely • 1 - person – Person - to nursed patients). Sexual transmission has also been suggested in some person to - Animal – - cases. Vertical transmission has rarely been prove n, although a few cases 1 Center for Food Security and Public Health, Iowa State University, 2011 were described in newborns. One infant may have contracted the bacteria by nursing culture positive breast milk. - 3 Center for Food Security and Public Health, Iowa State University, 2011

4 Melioidosis S l i d Epidemiology e 1 2 occurs in several areas in the tropics and subtropics. Most S Meliodosis o o Epidemiology S. Melioidosis N and 20 endemic regions are between the latitudes of 20 l is endemic in Southeast Asia, China, the Indian subcontinent and parts of • Endemic in tropics and subtropics i – Southeast Asia, China, India, Australia. It has also been reported from the C aribbean, the Middle East, d parts of Australia South America, Singapore and Taiwan. The situation in Africa is Also reported in: • e uncertain. Although isolated cases were reported from some African Caribbean, Middle East, South America, – Singapore, Taiwan countries in the past, melioidosis is not a commonly reported disease in – May be present in Africa 1 ated cases have also been reported in Hawaii and Africa. In the U.S., isol • U.S. cases linked with travel abroad Georgia, however, most were associated with travel abroad. 3 Center for Food Security and Public Health, Iowa State University, 2011 S On the map, the orange areas indicate endemic areas while the light blue Distribution of Melioidosis areas indicate intermittent cases. l i [Image from: illustrated history of tropical diseases, the Wellcome Trust. d Edited by FEG Cox.] e 1 4 Center for Food Security and Public Health, Iowa State University, 2011 al disease is relatively uncommon. In certain endemic areas, 5 to Clinic S Epidemiology 20% of agricultural workers have antibodies to B. pseudomallei; l however, they have not shown overt disease. Outbreaks and cases Clinical disease uncommon • i In endemic areas – y rainfall in typically occur during the wet season or after periods of heav d Antibodies in • of 5 to 20 % areas with high humidity or temperature. agricultural workers e • No history of clinical disease Wet season • [Bottom image from: illustrated history of tropical diseases, the – Heavy rainfall High humidity – 1 Wellcome Trust. Edited by FEG Cox.] or temperature 5 Center for Food Security and Public Health, Iowa State University, 2011 S l i d Disease in Humans e 1 6 Center for Food Security and Public Health, Iowa State University, 2011 4

5 Melioidosis Melioidosis in humans has a variable incubation period from less than 1 S Human Disease day (after very high exposure) to several months to many years. Due to l the ability of B. pseudomallei to survive in phagocytic cells, many cases • Incubation period: < 1 day to years i – Latent infection of melioidosis occur after a latent period. Immunosuppressive events or d Most infections asymptomatic • chronic diseases, such as diabetes mellitus or renal disease, have been • Clinical forms e Acute pulmonary infection – reported to be a risk factor for disease reoccurrence. Based on serologic Most common • ical disease studies, most infections are asymptomatic. When clin Focal infection – Septicemia – 1 develops, many manifestations can occur. The most common form is Neurological (rare) – acute pulmonary infection. Additionally, melioidosis can be limited to a 7 Center for Food Security and Public Health, Iowa State University, 2011 focal infection. Localized lesions may occur in the skin (as a result of infected wounds) or various inte rnal organs (as a result of septicemic spread). Many times focal infections become chronic conditions. The disease can also occur in a severe septicemic form. This can either be nondisseminated (only involving one organ) or disseminated. Finally, on rare o ccasions, melioidosis can produce neurological disease. S As previously mentioned, most infections of melioidosis are usually Acute Pulmonary Infection asymptomatic. However of clinical infections, pulmonary infection is the l most common form seen. Infection may occur either through inhalation or • Most common form i • High fever, headache by septicemic spread of the organism to the lungs. It is demonstrated by a d Dull aching chest pain • high fever, headache and pneumonia with caseous lesions. A dull aching e Cough, tachypnea, rales • . Chest x chest pain, cough, tachypnea, and rales can also occur rays may - • Chest X - rays show upper lobe consolidation, nodular lesions or pleural effusion. – Upper lobe consolidation Nodular lesions – 1 Pleural effusion – 8 Center for Food Security and Public Health, Iowa State University, 2011 Focal melioidosis involves abscess formation in various tissues or organs. S Focal Infection The lesions can be either acute (abscess) or chron ic (granulomatous). l Infection typically occurs from a contaminated wound or trauma. Skin, • Abscess or granuloma i formation bone, muscle and joints may be affected this way. Hematogenous spread d Skin – from wounds may then further infect internal organs such as the liver, – Bone and/or muscle e spleen, heart, and genito urinary tract. Infrequently infection of the – Joints – Internal organs nervous system may occur, resulting in meningitis, encephalitis and – Genitourinary 1 motor paralysis. – Nervous system (infrequent) 9 Center for Food Security and Public Health, Iowa State University, 2011 [Image from: illustrated history of tropical diseases, the Wellcome Trust. Edited by FEG Cox.] Septicemic melioidosis is acute in onset and fatal without treatment. S Melioidosis Septicemic Clinical signs for this form of melioidosis include high fever, tachypnea l and dyspnea, myalgia, hepatosplenomegaly, and septic shock. Acute onset • i – High fever, tachypnea, dyspnea, Additionally, disorie ntation, severe headache, pharyngitis, diarrhea and d myalgia, hepatosplenomegaly, pustular skin lesions may be noted. This form of melioidosis is rapidly septic shock e • Concurrent disease progressive with a mortality of 90% without treatment and 50% with • Mortality treatment. It has been reported that the onset of septicemic or c hronic – 90% without treatment 2 melioidosis is much more common in persons suffering from a – 50% with treatment debilitating illness, such as diabetes mellitus. In one study conducted in 0 Center for Food Security and Public Health, Iowa State University, 2011 Thailand, 17 of 29 patients with disseminated melioidosis were found to itus. be suffering from concurrent diabetes mell 5 Center for Food Security and Public Health, Iowa State University, 2011

6 Melioidosis Diagnosis of melioidosis is difficult. It has been called the great imitator S Diagnosis and Treatment because there are no pathognomonic lesions. Isolation of the organism l from blood, sputum, tissues or wound exudates can help to di agnose the Diagnosis • i Isolation of organism – disease. Serological tests for titers may also be used for diagnosis. Various serological tests – d Serological tests available include agglutination tests, indirect • Treatment e – Systemic antibiotics hemagglutination, complement fixation, immunofluorescence and Trimethoprim sulfa • Ceftazidime • enzyme assays. Improved methods for rapid diagn osis are being – Surgical drainage of skin wounds 2 Burkholderia reactions may occur in serologic tests with - evaluated. Cross • No vaccine available (causative agent for glanders). mallei B. pseudomallei is variably 1 Center for Food Security and Public Health, Iowa State University, 2011 susceptible to antibiotics. Long - term treatment and multiple drugs will be necessary for chronic an d severe cases. Relapses, as soon as 6 months after treatment, are common. Surgical drainage of skin wounds can be effective for localized infection. Currently there is no vaccine available, however, experimental vaccines used in dolphins and other cetacea ns reduced mortality. S l i d Animals and Melioidosis e 2 2 Many animal species are affected by melioidosis ; infection generally S Species Affected results from grazing on contaminated soil or drinking contaminated l water. Infected animals can excrete the organism in saliva, pus, urine, and Severe • disease in sheep, goats i • Pigs (chronic form) feces, leading to contamination of the environment. Severe disease occurs d • Occasional infection in sheep, goats; pigs tend to develop chronic disease. Cases have occurred – Cattle, horses, dogs, cats, buffalo e in cattle, dogs, cats, horses, buffalo, rodents, camels, alpacas, various – camels, alpacas Monkeys, rodents, – Birds, tropical fish nonhuman primates, some species of birds, and tropical fish, just to name Incubation period • 2 a few. The incubation period for animals is variab le ranging from a few Variable, days to years – days to many years. Some abscesses are carried asymptomatically. 3 Center for Food Security and Public Health, Iowa State University, 2011 Pulmonary melioidosis is common in sheep; typical symptoms are fever, S Goats, Sheep, and Pigs severe coughing, respiratory distress and profuse mucopurulent yellow l • Sheep nasal and ocular discharge. Some sheep become arthritic and lame. In i – Severe respiratory disease others, the only symptoms may be fever and generalized weakness. Arthritis, lameness – d Neurological signs including circling, incoordination, blindness, – Neurological disease e • Goats hyperesthesia, nystagmus and spasms have also been reported. Orchitis – Moderate respiratory disease with testicular nodules can occur in rams. In goats, respiratory disease is – Lameness, mastitis, abortion 2 less severe than in sheep, and coughing is not a prominent sign. • Pigs – Chronic – splenic abscesses Progressive emaciation, lameness or hindleg paresis, and abortions have 4 Center for Food Security and Public Health, Iowa State University, 2011 also been reported in goats. Mastitis and aortic aneurysms may be particularly common in this species. Pigs may be relatively resistant to melioidosis when husbandry and nutrition are good. Adult pigs tend to develop chronic infections with few symptoms; however, e nlarged lymph nodes (particularly the submandibular nodes) may be palpable. Progressive emaciation, neurological signs, incoordination, multiple skin ulcers and diarrhea have also been reported. Young pigs can develop Center for Food Security and Public Health, Iowa State University, 2011 6

7 Melioidosis acute septicemia with fever, anorexi a, coughing and nasal and ocular discharge. Occasional abortions or stillbirths have been seen in sows, and orchitis can occur in boars. In endemic regions, asymptomatic splenic abscesses are often found in pigs at slaughter. Melioidosis in other species is sporadic and occurs as isolated cases. S Species Other Clinical signs for horses include fever, anorexia, dyspnea, mild cough and l occasionally, purulent nasal discharge. Cattle are rarely affected but may Horses and cattle • i Neurologic signs – show similar signs as h orses. Canine melioidosis is rarely seen, however, d – Respiratory disease seven cases in U.S. military dogs in Vietnam were reported. Clinical • Dogs (rare) e signs may include fever, dermal abscesses, epididymitis, lameness and – Dermal abscesses, epididymitis, lameness, le leg swelling. Postmortem lesions in these dogs consisted of multip leg swelling 2 abscesses of the skin, lungs, liver and epididymitis. Rodents are very Rodents • Very susceptible – susceptible to melioidosis. Guinea pigs and hamsters develop fatal 5 Center for Food Security and Public Health, Iowa State University, 2011 disease when as few as 10 organisms are injected intraperitoneally. These animals are frequently used in melioidosi s research and for testing soil for contamination by the organism. S l i d Prevention and Control e 2 6 S Melioidosis is usually acquired from the environment, particularly after Control and Prevention contact with soil or water. To minimize contact with dirt, animals can be l raised on wooden slats, concrete or paved floors. Providing safe drinking Avoid contact with soil and water • i in endemic areas mallei water is important in endemic areas. B. pseudo is particularly d Husbandry practices – common in muddy water, and it is less likely to be found in fresh or clear D rinking water – e Use fresh sources • water. Although small numbers of bacteria may survive treatment, Chlorination effective • chlorination of the water supply decreases the risk of infection. Care • Use care during necropsies 2 should also be taken d uring animal necropsies. This is especially wounds Thorough cleaning of • • No vaccine available important for immunocompromised persons or anyone with a chronic 7 Center for Food Security and Public Health, Iowa State University, 2011 medical condition such as diabetes mellitus or renal disease. If wounds do become contaminated with soil or water, thorough cleaning of the wound ith disinfectant soap and water will help to prevent infection. There is w no licensed vaccine for melioidosis available. 7 Center for Food Security and Public Health, Iowa State University, 2011

8 Melioidosis Melioidosis is listed by the CDC as a Category B potential bioterrorism S Melioidosis as a Bioweapon agent. This indicate s agents which are moderately easy to disseminate. l Additionally, moderate morbidity and low mortality is noted with these CDC Category B Agent • i – Moderately easy to disseminate agents. Specific diagnostics will be required in the event of an attack. As d Moderate morbidity – Burkholderia pseudomallei an agent, the can be very stable in Low mortality – e environment, persisting for months. However, it can be killed very easily Specific diagnostics required – • Very stable in the environment by heat. Killed very easily by heat • 2 8 Center for Food Security and Public Health, Iowa State University, 2011 S Additional Resources l CDC • i – National Center for Zoonotic, Vector - d Borne, and Enteric Diseases http://www.cdc.gov/nczved/divisions/df – e bmd/diseases/melioidosis / 2 9 Center for Food Security and Public Health, Iowa State University, 2011 S Additional Resources l World Organization for Animal Health • i (OIE) – www.oie.int d • U.S. Department of Agriculture (USDA) – www.aphis.usda.gov e • Center for Food Security and Public Health – www.cfsph.iastate.edu • USAHA Foreign Animal Diseases (“The Gray Book”) 3 – www.usaha.org/pubs/fad.pdf 0 Center for Food Security and Public Health, Iowa State University, 2011 S Acknowledgments l Development of this presentation i was funded by grants from the Centers for Disease Control and Prevention, d the Iowa Homeland Security and Emergency Management Division, and the Iowa Department e of Agriculture and Land Stewardship to the Center for Food Security and Public Health at Iowa State University. Authors: Glenda Dvorak, DVM, MS, MPH, DACVPM; Radford Davis, DVM, MPH, DACVPM 3 Voge , MS; Kerry Leedom Gayle Brown, DVM, PhD, Bindy Sornsin, BA; Jared Reviewers: Larson, DVM, MPH, PhD 1 Center for Food Security and Public Health, Iowa State University, 2011 8 Center for Food Security and Public Health, Iowa State University, 2011

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