Case Study Pathogenic Bacteriology 2009

1. Case StudyPathogenic Bacteriology2009 Case #8

2. Case Summary The patient was a 55-year-old male with a 2-month history of fevers, night sweats, increased cough with sputum production, and a 25-lb weight loss. Personal History: • Denied intravenous drug use or homosexual activity • had multiple sexual encounters • “sipped” a pint of gin a day • was in jail for 2 years • Had gunshot and stab wounds in the past. Physical Examination • Temperature above normal (39.4 degree Celsius) • Lymph nodes adenopathy (neck, armpit) • Positive HIV serology • Low absolute CD4+ lymphocyte count • Acid-fast positive for stain of sputum • Organism was detected in bronchoalveolar lavage fluid from right middle lobe

3. Bronchoalveolar Lavage Fluid • Bronchoalveolar Lavage Fluid (BALF): Body fluid obtained by washout of the alveolar compartment of the lung. • BAL is a medical procedure in which a bronchoscope is passed through the mouth and nose into the lungs. Fluid is then squirted into a small part of the lung and recollected for examination.

4. Key Information Pointing to Diagnosis • Fevers • Cough with sputum production • Weight loss • Heavy drinker • Enlarged lymph nodes • HIV + • Low CD4+ lymphocyte counts • Acid fast + • Presence of BALF in right middle lobe

5. Organism of Infection • Organisms that can be positive for acid-fast are: • Mycobacterium • Nocardia • Corynebacterium • Based on the medical history of the patient, the most likely organism to be causing the infection is Mycobacterium tuberculosis.

6. Mycobacterium tuberculosis Classifications: • Family Mycobacteriaceae • Obligate aerobe • Acid-fast bacilli • Slow growing • Weakly G+ rods • Nonmotile • nonsporing

7. Mycobacterium tuberculosis • Colonies are rough, dry, granular, non-pigmented to buff colored colonies

8. Disease and Pathogenesis of M. tuberculosis • Causative agent of tuberculosis • Latent tuberculosis: no symptoms and not contagious. Latent infection can become active. • Active tuberculosis: developed various symptoms and are contagious. • Mode of transmission • Spread through droplets: when someone coughs, sneezes, or talks, tiny droplets of saliva or mucus are expelled into the air, which can be inhaled by another person. • Once infectious particles reach the alveoli, macrophage engulfs the TB bacteria, transmitting it to the lymphatic system and bloodstream, where it gets spread to other organs. • The bacteria further multiply in organs that have high oxygen pressures (i.e upper lobes of lungs, the kidneys, bone marrow, and meninges) • Virulence factors: • cord factor – glycolipid, trehalose 6,6’ dimycolate; toxic to leukocytes; resistant to chemical damage; interferes with mitochondrial function in mice; develops granulomatous lesions. • Intracellular growth - sulfolipids prevent phagosome-lysosome fusion so that the organisms are not exposed to lysosomal enzymes. • Iron capturing ability – required for survival inside phagocytes.

9. Diagnosis/Identification of M. Tuberculosis Diagnostic methods: • Acid fast staining • Tuberculin skin test (Mantoux skin test or PPD) - determines if someone has developed an immune response to the bacterium that causes TB, indicated by a hard, raised margins at the injection site. • Lumbar puncture • Chest X-ray • Sputum or biopsy or body fluid culture • Lowenstein-Jensen medium (slow growth: 18-24 days) • Middlebrook medium (faster growth: 12-14 days) • Polymerase Chain Reaction (PCR) Identification: • Rate of growth • Pigmentation and photoreactivity (nonphotochromogens-may produce pigment ranging from white to yellow, but pigment does not intensify upon exposure to light.) • Biochemical tests: • Niacin + • Nitrate reduction + and Catalase – at 68 degree Celsius

10. Before treatment After treatment Chest X-ray

11. 1950-medication was not available Placed paraffin sheet on top of cavity-like lesion Chest X-ray

12. Therapy and Prevention of Patient Infected with M. tuberculosis Some effective drugs: • Isoniazid (INH) • Rifampin • Streptomycin • Pyrazinamide • Ethambutol Prevention: • BCG vaccine (could give TB skin test a false-positive) • Those identified with latent tuberculosis are given INH every 6-12 months to prevent M. tb from becoming active. • Those identified with active tuberculosis are hospitalized and kept in a room with controlled ventilation and airflow until they can no longer spread the tb germs. Hospitals and clinics can take precautions to prevent the spread of tb by using ultraviolet light to sterilize the air, special filters, and special respirators and masks.

13. Tuberculosis Risk Factors in Adultsin King County, Washington • Buskin SE, Gale JL, Weiss NS, Nolan CM. Tuberculosis risk factors in adults in King County, Washington, 1988 through 1990. Am J Public Health 1994;84:1750–1756. • Purpose: to examine risk factors contributing to tuberculosis in adults (over a course of 3 years) • Risk factors include age, gender, race, place of birth, alcohol and smoking status, and medical history. • Methods: In King County, Washington State (1988-1990), the characteristics of patients with tuberculosis were compared with census data, and a case-control study was conducted. Self-administered questionnaires were completed by 151 patients with active tb and 545 control subjects without active tb.

14. Results

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17. Results (cont.)

18. Results: Infection with the human immunodeficiency virus, non-White race/ethnicity, and foreign birthplace were each associated with a sixfold or greater increase in risk. Each of the following was associated with at least a doubled risk: history of medical conditions, low weight for height, low socioeconomic status, and age 70 years and older. Men had 1.9 times the risk of women, smokers of 20 years or more duration had 2.6 times the risk of nonsmokers, and heavy alcohol consumers has 2 times the risk of nondrinkers. • Conclusion: Targeting the identified groups may be an effective way to reducing the incidence of tuberculosis.

19. Take Home Message • Mycobacterium Tuberculosis • Tuberculosis involves association between person to person. • Typical symptoms • Fever • night sweats • progressive coughs • chest pain • weight loss • Diagnostics procedures • acid-fast stain • Tuberculin skin test • Lumber puncture • Sputum or biopsy or body fluid • Therapy is based on zzz (tuberculin skin test?) • Prognosis: Active tb can almost always be cured with combinations of antibotics over a course of 6-8 months of daily treatments. • Prevention: • BCG vaccine • Preventive therapy of household members • Minimize exposure to patients with active tuberculosis • Reduce risk factors by not smoking, drinking, or undertake activities that contribute to poor health. • Transmission is through air droplets, by means of coughs, sneezes, talks. • Threat : consuming large amount of alcohol, smoking heavily, drug-abuse, harmful/unprotected activities, ect.

20. References • Buskin SE, Gale JL, Weiss NS, Nolan CM. Tuberculosis risk factors in adults in King County, Washington, 1988 through 1990. Am J Public Health 1994;84:1750–1756. • Singh, V. Tuberculosis in developing countries: diagnosis and treatment. Paediatric Respiratory Reviews 7 2006. 132-135. • DeRiemer K et al. Quantitative impact of human immunodeficiency virus infection on tuberculosis dynamics. Am J Respir Crit Care Med 2007 Nov 1; 176:936. • Centers for Disease Control. The use of preventive therapy for tuberculosis infection in the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMAR. 1990; • Rieder HL, Cauthen GM, Kelly GD. Tuberculosis in the United States. JAMA. 1989;262:385-389. • 39(RR-8):9-12.McQueen, Nancy. Winter 2009. Mycobacteriaceae.

21. Point Spread