CHEMO-IMMUNOTHERAPY FOR GLANDERS
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CHEMO-IMMUNOTHERAPY FOR GLANDERS
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CHEMO-IMMUNOTHERAPY FOR GLANDERS
- 1. Presenter: Naveen Verma SEMINAR ON CHEMOIMMUNOTHERAP Y A PROMISE TO GLANDERS PRESENTOR: Dr. NAVEEN VERMA
- 2. History and organism Epidemiology Transmission and disease Therapy and prevention Outline
- 3. Glanders • It is an acute to chronic disease of mainly solipeds characterized by pustular skin lesions , multiple abscess ,necrosis in respiratory tract pneumonia and sepsis . • It is called “glanders” when the principal lesions are seen in the nostrils, submaxillary glands and lungs. • & • It is called “farcy” when lesions are on the surface of limbs or body.
- 4. HISTORY
- 5. History • World War I • Suspected use as biological agent to infect Russian horses and mules. • Large number of human cases in Russia during and after WWI.
- 6. History • World War II • Japanese handling infected horses, civilians, and POWs • U.S. and Russia investigated use as biological weapon. Center for Food Security and Public Health, Iowa State University, 2011
- 8. The Organism • Burkholderia mallei • Gram negative bacillus • Exists primarily in infected host • Prolonged survival in favorable environments • Inactivated by heat and sunlight • Related to Burkholderia pseudomallei • Cause of meliodosis
- 9. Epidemiology • Endemic • Africa, Asia, the Middle East and Central and South America, Northern Australia specially during rainy season. • Sporadic cases • Central America • Once widespread, has been eradicated from many countries
- 11. Transmission: Animals • Ingestion • Contaminated food and water • Skin exudates, respiratory secretions • Inhalation • Direct contact • Fomites • Grooming tools • Harnesses
- 12. Host Range • Affects solipeds • Donkeys • Acute form • Horses • Chronic form • Carnivores, humans, and goats susceptible • Swine and cattle resistant
- 13. • Veterinarians • Grooms • Horsemen • Butchers • Lab workers Who Is At Risk?
- 14. Forms of disease not clearly distinct • May occur simultaneously • Incubation period: 2 to 6 weeks is typical GLANDERS
- 16. GLANDERS
- 17. • Ulcers, nodules, stellate scars in upper respiratory • Pneumonia • Firm rounded miliary nodules • Swollen lymph nodes and vessels NECROPSY FINDINGS
- 19. Diagnosis: Animals • Isolation of Burkholderia mallei • Blood, sputum, urine or skin lesions • Mallein test • Intrapalpebral or conjunctival injection • Swelling 1 to 2 days later • Serology • Compliment fixation and ELISA • Most reliable in horses
- 20. DIAGNOSIS MALLEIN TEST • •Ocular swelling, lacrimation, suppurative inflammation, fever within1-2 days
- 21. COMPLEMENT FIXATION TEST ISOLATION From fresh lesions or lymph nodes •Gram staining •Motility test •No selective agar available
- 22. Strauss reaction in guinea pigs after infection with material from glanderous lesions PURULENT ORCHITIS
- 23. MULTIPLE NODULES IN THE LIVER LARGE WHITE NODULE IN THE LUNG WITH DRY ,WHITE TO YELLOW CUT SURFACE CONTAINING ONION –SKIN LAYERED GREY MATERIAL
- 24. Differential Diagnosis • Melioidosis • Strangles • Lymphangitis • Other forms of pneumonia • Gutteral pouch empyema • Dermatophilosis • Dermatomycoses
- 25. Treatment • Limited information on treatment • Long term antibiotic treatment necessary (1 to 12 months) • Multiple drug therapy • Drain abscesses
- 27. Ringer's-lactate-dextrose 500 ml + dimetyl-sulfoxide 60-80 ml intravenously and Inj. Norfloxacin 5% 35-50 ml intramuscularly (1st round of treatment). (Ghulam mohammmed ,2001)
- 28. (Philippe Bossi et.al )
- 33. Prevention & Control No vaccine is available for animal as well as human use. Identification and elimination of foci of infection Surveillance and monitoring of equine herds especially in endemic areas Positive animals should be slaughtered immediately & carcass should be disposed off by incineration or deep burial In-contact & exposed animals should be segregated , Re- tested to detect and destroy the positives according to The Glander & Farcy Act XIII, 1899
Editor's Notes
- Animated pointer and light-up text (Advanced) To reproduce the background effects on this slide, do the following: On the Home tab, in the Slides group, click Layout, and then click Blank. Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Solid fill in the right pane, and select White, Background 1 (first row, first option from the left). To reproduce the rectangle on this slide, do the following: On the Home tab, in the Drawing group, click Shapes, and then under Rectangles click Rounded Rectangle (second option from the left). On the slide, drag to draw a rounded rectangle. Select the rectangle. Drag the yellow diamond adjustment handle to the left to decrease the amount of rounding on the corners. With the rounded rectangle still selected, under Drawing Tools, on the Format tab, in the Size group, do the following: In the Shape Height box, enter 3.5”. 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In the Shape Width box, enter 7.5”. With the arc still selected, on the Home tab, in the Drawing group, click the arrow next to Shape Outline and then do the following: Under Theme Colors, click White, Background 1, Darker 15% (third row, first option from the left). Point to Dashes, and then click Dash (fourth option from the top). On the slide, drag the yellow diamond adjustment handle on the right side of the arc to the bottom of the arc to create a half circle. Drag the arc until the yellow diamond adjustment handles are on the left edge of the slide. With the arc still selected, on the Home tab, in the Drawing group, click the arrow under Arrange, point to Align, and then do the following: Click Align to Slide. Click Align Middle. To reproduce the half circle on this slide, do the following: On the slide, select the arc. On the Home tab, in the Clipboard group, click the arrow to the right of Copy, and then click Duplicate. Select the duplicate arc. 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In the Distance box, enter 4 pt. On the slide, drag the second arc until the yellow diamond adjustment handles are on the left edge of the slide. On the Home tab, in the Drawing group, click Arrange, and then do the following: Point to Align, and then click Align to Slide. Point to Align, and then click Align Middle. Click Send to Back. To reproduce the button shapes on this slide, do the following: On the Home tab, in the Drawing group, click Shapes, and then under Basic Shapes click Oval (first row, second option from the left). On the slide, drag to draw an oval. Select the oval. Under Drawing Tools, on the Format tab, in the Size group, do the following: In the Shape Height box, enter 0.34”. In the Shape Width box, enter 0.34”. Under Drawing Tools, on the Format tab, in the Shape Styles group, click More, and then click Light 1 Outline, Colored Fill – Olive Green, Accent 3 (third row, first option from the left). 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Also in the Format Shape dialog box, click 3-D Format in the left pane, and then do the following in the 3-D Format pane: Under Bevel, click the button next to Top, and then under Bevel click Art Deco (third row, fourth option from the left). Next to Top, in the Width box, enter 5 pt, and in the Height box, enter 5 pt. Under Contour, click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left). In the Size box, enter 3.5 pt. Under Surface, click the button next to Material, and then under Standard click Matte (first row, first option from the left). Click the button next to Lighting, and then under Neutral click Soft (first row, third option from the left). On the slide, select the oval. Under Drawing Tools, on the Format tab, in the bottom right corner of the Size group, click the Size and Position dialog box launcher. 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In the Format Shape dialog box, click Position in the left pane, and in the Position pane, do the following to position the third and fourth ovals: Select the third oval on the slide, and then enter 3.52” in the Horizontal box and 4.27” in the Vertical box. Select the fourth oval on the slide, and then enter 2.99” in the Horizontal box and 5.66” in the Vertical box. To reproduce the text on this slide, do the following: On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box. Enter text in the text box and select the text. On the Home tab, in the Font group, do the following: In the Font list, select Corbel. In the Font Size list, select 22. Click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left). On the Home tab, in the Paragraph group, click Align Text Left to align the text left in the text box. On the slide, drag the text box to the right of the first oval. Select the text box. On the Home tab, in the Clipboard group, click the arrow to the right of Copy, and then click Duplicate. Click in the text box and edit the text. Drag the second text box to the right of the second oval. Repeat steps 5-7 to create the third and fourth text boxes, dragging them to the right of the third and fourth ovals. To reproduce the animation effects on this slide, do the following: On the Home tab, in the Editing group, click Select, and then click Selection Pane. In the Selection and Visibility task pane, select the rectangle group. On the Animations tab, in the Advanced Animation group, click Add Animation, and then under Emphasis click Spin. Also on the Animations tab, in the Animation group, click the Effect Options dialog box launcher. In the Spin dialog box, do the following: On the Effects tab, in the Amount list, in the Custom box, enter 123°, and then press ENTER. Also in the Amount list, click Counterclockwise. On the Timing tab, in the Duration box, select 1.00. On the Timing tab, in the Start list, select With Previous. On the slide, select the first oval. On the Animations tab, in the Advanced Animation group, click Add Animation, and then click More Emphasis Effects. In the Add Emphasis Effect dialog box, under Basic, click Fill Color. On the Animations tab, in the Animation group, click the Effect Options dialog box launcher. In Fill Color dialog box, the do the following: On the Effects tab, in the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red:130, Green:153, Blue: 117. On the Timing tab, in the Duration box, , enter 0.50. On the Timing tab, in the Start list, select After Previous. On the slide, select the first text box. On the Animations tab, in the Advanced Animation group, click Add Animation, and then under Entrance click Fade. Also on the Animations tab, in the Timing group, do the following: In the Start list, select With Previous. In the Duration box, enter 0.50. In the Selection and Visibility task pane, select the rectangle group. On the Animations tab, in the Advanced Animation group, click Add Animation, and then under Emphasis click Spin. Also on the Animations tab, in the Animation group, click the Effect Options dialog box launcher. In the Spin dialog box, do the following: On the Effects tab, in the Amount list, in the Custom box, enter 22°, and then press ENTER. Also in the Amount list, click Clockwise. On the Timing tab, in the Start list, select On Click. On the Timing tab, in the Duration box, enter 0.50. On the slide, select the second oval. On the Animations tab, in the Advanced Animation group, click Add Animation, and then click More Emphasis Effects. In the Add Emphasis Effect dialog box, under Basic, click Fill Color. On the Animations tab, in the Animation group, click the Effect Options dialog box launcher. In the Fill Color dialog box, do the following: On the Effects tab, in the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red:130, Green:153, Blue: 117. On the Timing tab, in the Start list, select After Previous. On the Timing tab, in the Duration box, enter 0.50. On the slide, select the second text box. On the Animations tab, in the Advanced Animation group, click Add Animation, and then under Entrance click Fade. Also on the Animations tab, in the Timing group, do the following: In the Start list, select With Previous. In the Duration box, enter 0.50. On the slide, select the third oval. On the Animations tab, in the Advanced Animation group, click Add Animation, and then click More Emphasis Effects. In the Add Emphasis Effect dialog box, under Basic, click Fill Color. On the Animations tab, in the Animation group, click the Effect Options dialog box launcher. In the Fill Color dialog box, do the following: On the Effects tab, in the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red:130, Green:153, Blue: 117. On the Timing tab, in the Start list, select After Previous. On the Timing tab, in the Speed list, select Very Fast. On the slide, select the third text box. On the Animations tab, in the Advanced Animation group, click Add Animation, and then under Entrance click Fade. Also on the Animations tab, in the Timing group, do the following: In the Start list, select With Previous. In the Duration box, enter 0.50. On the slide, select the fourth oval. On the Animations tab, in the Advanced Animation group, click Add Animation, and then click More Emphasis Effects. In the Add Emphasis Effect dialog box, under Basic, click Fill Color. On the Animations tab, in the Animation group, click the Effect Options dialog box launcher. In the Fill Color dialog box, do the following: On the Effects tab, in the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red:130, Green:153, Blue: 117. On the Timing tab, in the Start list, select After Previous. On the Timing tab, in the Duration box, enter 0.50. On the slide, select the fourth text box. On the Animations tab, in the Advanced Animation group, click Add Animation, and then under Entrance click Fade. On the Animations tab, in the Timing group, do the following: In the Start list, select With Previous. In the Duration box, enter 0:50.
- The first recorded description of glanders was in the third century by Aristotle. In 1664, glanders was recognized as a contagious organism, and in 1830 its zoonotic potential was suspected. In the late 1800s, the Mallein test was developed for the diagnosis of glanders. At the turn of the century, the U.S., Canada, and Great Britain all implemented glanders-control programs.
- During World War I, glanders was believed to have been spread deliberately to infect large numbers of Russian horses and mules on the Eastern Front. This affected the troops and supply convoys, as well as artillery movement because of their dependence on horses and mules. Human cases of glanders also increased in Russia during and after WWI. [Photo: Allied cavalries, such as this Belgian convoy, may have been the target of glanders attacks in World War I. Source: Nova Online, Iowa Public Television.]
- It is widely held that the Japanese deliberately infected horses, civilians, and prisoners of war with glanders during World War II. The United States studied glanders as a possible biological weapon in 1943-44 but did not weaponize it. The former Soviet Union is also believed to have been interested in B. mallei as a potential biological weapon agent after World War II. (Photos: Soldiers with their horses. Source: (Bottom right) www.civilwarhome.com/images/cavalry.jpg; www.continet.com/ppsh/cavalry.jpg; www.firstworldwar.com/diaries/ graphics/horsesdrinking.jpg)
- Glanders is caused by the bacteria Burkholderia mallei. This organism has gone through several name changes, including Pseudomonas mallei, Malleomyces mallei, and Actinomyces mallei. It is a Gram negative bacillus and predominantly exists in infected hosts, but may remain viable for several months in warm moist environments. Although this organism is inactivated by heat and sunlight, its survival is prolonged in wet or humid environments. B. mallei remains viable in room temperature water for up to a month, and may be viable for more than a year in favorable environments. The organism is closely related to Burkholderia pseudomallei, the causative agent of melioidosis; the two are serologically indistinguishable in some cases. The genetic homology between the two organisms is great, and because of this, many consider them to be biotypes or isotypes of the same organism. [Photo: Scanning electron micrograph of the bacillus shape of Burkholderia. Source: CDC Public Health Image Library]
- Glanders is endemic in parts of Asia, Africa, the Middle East, South America and possibly the Balkan states, former Soviet republics, and Mexico. Sporadic cases occur in Central America. Between 1998 and 2007, cases were reported from Brazil, Turkey, the former U.S.S.R., Eritrea, Ethiopia, Iran, Iraq, United Arab Emirates, and Mongolia. This disease may also exist in Pakistan. The geographic distribution of B. mallei is difficult to determine precisely as cross reactions with serological tests for melioidosis (Burkholderia pseudomallei) most likely confound the true estimates of worldwide distribution. Although glanders was once widespread throughout the world, it has been eradicated from many countries by test and slaughter programs. In countries that have eradicated glanders, cases may occur in researchers who work with this agent.
- Glanders is introduced into horse populations by diseased or latently infected animals. Ingestion of the organism is the major route of infection. Experimental evidence suggests that inhalation of the organism is less likely to result in typical cases of the disease. Acquiring the disease through skin or mucous membranes is possible but regarded as of minor importance in the natural spread of the disease. Close contact between animals alone does not usually result in transmission, but transmission is facilitated if animals share feeding or watering facilities. B. mallei is readily spread on fomites, including harnesses, grooming tools, and food and water troughs. Carnivores usually become infected when they eat contaminated meat. [Photo: two horses sharing water. Source: Katie Lawless/nationalgeographic.com] [
- Glanders is primarily a disease of solipeds – particularly horses, donkeys, and mules. Donkeys have been regarded as most likely to experience the acute form of the disease, while a more chronic form of the disease is common in horses. Sources disagree whether mules are more likely to develop acute or chronic disease. Carnivores are susceptible if they consume infected meat; felids appear to be more susceptible than canids. Several laboratory animals are susceptible to infection, including hamsters and guinea pigs. Humans also are susceptible to infection. Swine and cattle are resistant, but goats and sheep can be infected. Most domesticated animals other than cattle, pigs, and rats can be infected experimentally. Wildlife species, including bears, wolves, field mice, rabbits, and voles, have also been infected. Hamsters and guinea pigs are the most susceptible rodents. Mice are resistant to disease unless the dose of organisms is high. [Photo: (Top) Horses. Source: U.S. Department of Agriculture. (Bottom): Donkey. Source: Wikimedia Commons]
- Humans that have occupational exposure are at the highest risk for infection. This includes: workers in laboratory settings, veterinarians, grooms, horsemen, butchers, and any other people who work closely with horses. [Photo: (Top) Veterinarian floating a horses teeth. Source: horsebackmagazine.com; (Middle) Grooming horse. Source: Michigan State University Extension; (Bottom) Laboratorian swabbing a petri dish. Source: www.labtestsonline.com]
- At necropsy there may be ulcers, nodules, and stellate scars in the nasal cavity, trachea, pharynx, larynx, skin, and subcutaneous tissues. Catarrhal bronchopneumonia with enlarged bronchial lymph nodes may be present. The lungs, liver, spleen and kidneys may contain firm, rounded, encapsulated miliary gray nodules similar to tubercles. The lymphatic vessels may be swollen, the lymph nodes are typically enlarged and fibrotic and contain focal abscesses. In addition, necrosis may be noted in the internal organs and testes. The upper photo shows a granulomatous lesion in the lip of a donkey. Lower photo is an extensive pyogenic granulomatous pneumonia in a donkey. (Photos: (Top) A granulomatous lesion in the lip of a donkey. (Bottom) Extensive pyogenic granulomatous pneumonia in a donkey. Source: USAHA Foreign Animal Diseases (The Gray Book) at http://www.aphis.usda.gov/emergency_response/downloads/nahems/fad.pdf]
- Glanders can be diagnosed by bacteriologic isolation of B. mallei from skin lesions or blood samples. Inoculation into guinea pigs, the mallein test, and serology can also be used. With the mallein test, a positive reaction is indicated by eyelid swelling 1 to 2 days after intrapalpebral injection of a protein fraction of B. mallei, or by conjunctivitis after administration in eyedrops. This is similar to tuberculin testing. A variety of serologic tests are available, including complement fixation, ELISA, indirect hemagglutination, counter-immunoelectrophoresis and immunofluorescence. The most accurate and reliable tests in horses are complement fixation and ELISA. Agglutination and precipitin tests are unreliable for horses with chronic glanders and animals in poor condition. Serological tests cannot distinguish reactions to B. mallei from reactions to B. pseudomallei.
- Signs of glanders must be distinguished from melioidosis, strangles, lymphangitis, ulcerative lymphangitis, and other forms of pneumonia. Purulent sinusitis, gutteral pouch empyema, and other causes of nasal catarrh should also be considered. Skin lesions may be similar to those of dermatophilosis or dermatomycoses, such as sporotrichosis.
- Limited information exists regarding antibiotic treatment of glanders since the disease had largely disappeared by the time antibiotics became available. Long term treatment and multiple drugs may be necessary, up to 12 months for extrapulmonary suppurative disease. Few studies have been published on the antibiotic susceptibility of B. mallei, but some treatment recommendations are available. This organism is usually resistant to some classes of antibiotics. Abscesses may need to be drained.
- In countries where glanders is endemic in animals, prevention of the disease in humans involves identification and elimination of the infection in animal populations. Within the health care setting, transmission can be prevented by using common blood and body fluid precautions. Biosafety level 3 containment practices are required for laboratory staff when working with glanders. Field veterinarians and veterinary pathologists must take strict precautions to prevent human infections by the cutaneous or respiratory route during clinical or post-mortem exams of suspected cases. Adequate protective clothing, including gloves and face masks, should be worn.