Case StudyCase StudyPathogenic BacteriologyPathogenic Bacteriology

20092009

Case #8Case #8

Case SummaryCase SummaryThe patient was a 55-year-old male with a 2-month history of fevers, night sweats, 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.increased cough with sputum production, and a 25-lb weight loss.

Personal History:Personal History: Denied intravenous drug use or homosexual activityDenied intravenous drug use or homosexual activity had multiple sexual encountershad multiple sexual encounters ““sipped” a pint of gin a daysipped” a pint of gin a day was in jail for 2 years was in jail for 2 years Had gunshot and stab wounds in the past. Had gunshot and stab wounds in the past.

Physical ExaminationPhysical Examination Temperature above normal (39.4 degree Celsius)Temperature above normal (39.4 degree Celsius) Lymph nodes adenopathy (neck, armpit)Lymph nodes adenopathy (neck, armpit) Positive HIV serologyPositive HIV serology Low absolute CD4+ lymphocyte countLow absolute CD4+ lymphocyte count

Acid-fast positive for stain of sputumAcid-fast positive for stain of sputum Organism was detected in bronchoalveolar lavage fluid from right middle lobe Organism was detected in bronchoalveolar lavage fluid from right middle lobe

Bronchoalveolar Lavage FluidBronchoalveolar Lavage Fluid

Bronchoalveolar Lavage Fluid (BALF): Bronchoalveolar Lavage Fluid (BALF): Body fluid obtained by washout of the Body fluid obtained by washout of the alveolar compartment of the lung. alveolar compartment of the lung.

BAL is a medical procedure in which a BAL is a medical procedure in which a bronchoscope is passed through the bronchoscope is passed through the mouth and nose into the lungs. Fluid is mouth and nose into the lungs. Fluid is then squirted into a small part of the lung then squirted into a small part of the lung and recollected for examination.and recollected for examination.

Key Information Pointing to Key Information Pointing to DiagnosisDiagnosis

FeversFevers Cough with sputum productionCough with sputum production Weight lossWeight loss Heavy drinkerHeavy drinker Enlarged lymph nodesEnlarged lymph nodes HIV +HIV + Low CD4+ lymphocyte countsLow CD4+ lymphocyte counts Acid fast +Acid fast + Presence of BALF in right middle lobePresence of BALF in right middle lobe

Organism of Infection Organism of Infection

Organisms that can be positive for acid-Organisms that can be positive for acid-fast are:fast are:MycobacteriumMycobacteriumNocardiaNocardiaCorynebacteriumCorynebacterium

Based on the medical history of the Based on the medical history of the patient, the most likely organism to be patient, the most likely organism to be causing the infection is causing the infection is Mycobacterium Mycobacterium tuberculosis.tuberculosis.

Mycobacterium tuberculosisMycobacterium tuberculosis

Classifications:Classifications: Family MycobacteriaceaeFamily Mycobacteriaceae Obligate aerobeObligate aerobe Acid-fast bacilliAcid-fast bacilli Slow growingSlow growing Weakly G+ rodsWeakly G+ rods NonmotileNonmotile nonsporingnonsporing

Mycobacterium tuberculosisMycobacterium tuberculosis

Colonies are Colonies are rough, dry, rough, dry, granular, non-granular, non-pigmented to buff pigmented to buff colored coloniescolored colonies

Disease and Pathogenesis of Disease and Pathogenesis of M. tuberculosisM. tuberculosis

Causative agent of tuberculosisCausative agent of tuberculosis Latent tuberculosis: no symptoms and not contagious. Latent infection can become Latent tuberculosis: no symptoms and not contagious. Latent infection can become

active. active. Active tuberculosis: developed various symptoms and are contagious.Active tuberculosis: developed various symptoms and are contagious.

Mode of transmissionMode of transmission Spread through droplets: when someone coughs, sneezes, or talks, tiny droplets of 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.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, 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 transmitting it to the lymphatic system and bloodstream, where it gets spread to other organs.organs.

The bacteria further multiply in organs that have high oxygen pressures (i.e upper The bacteria further multiply in organs that have high oxygen pressures (i.e upper lobes of lungs, the kidneys, bone marrow, and meninges) lobes of lungs, the kidneys, bone marrow, and meninges)

Virulence factors:Virulence factors: cord factor – glycolipid, trehalose 6,6’ dimycolate; toxic to leukocytes; resistant to cord factor – glycolipid, trehalose 6,6’ dimycolate; toxic to leukocytes; resistant to

chemical damage; interferes with mitochondrial function in mice; develops chemical damage; interferes with mitochondrial function in mice; develops granulomatous lesions.granulomatous lesions.

Intracellular growth - sulfolipids prevent phagosome-lysosome fusion so that the Intracellular growth - sulfolipids prevent phagosome-lysosome fusion so that the organisms are not exposed to lysosomal enzymes.organisms are not exposed to lysosomal enzymes.

Iron capturing ability – required for survival inside phagocytes.Iron capturing ability – required for survival inside phagocytes.

Diagnosis/Identification of Diagnosis/Identification of M. M. TuberculosisTuberculosis

Diagnostic methods:Diagnostic methods: Acid fast stainingAcid fast staining Tuberculin skin test (Tuberculin skin test (Mantoux skin test or Mantoux skin test or PPD) - PPD) - determines if someone has determines if someone has

developed an immune response to the bacterium that causes TB, indicated by developed an immune response to the bacterium that causes TB, indicated by a hard, raised margins at the injection site.a hard, raised margins at the injection site.

Lumbar punctureLumbar puncture Chest X-rayChest X-ray Sputum or biopsy or body fluid culture Sputum or biopsy or body fluid culture

Lowenstein-Jensen medium (slow growth: 18-24 days) Lowenstein-Jensen medium (slow growth: 18-24 days) Middlebrook medium (faster growth: 12-14 days)Middlebrook medium (faster growth: 12-14 days)

Polymerase Chain Reaction (PCR)Polymerase Chain Reaction (PCR)

Identification:Identification: Rate of growthRate of growth Pigmentation and photoreactivity (nonphotochromogens-may produce pigment ranging Pigmentation and photoreactivity (nonphotochromogens-may produce pigment ranging

from white to yellow, but pigment does not intensify upon exposure to light.)from white to yellow, but pigment does not intensify upon exposure to light.) Biochemical tests:Biochemical tests:

Niacin +Niacin + Nitrate reduction + and Catalase – at 68 degree CelsiusNitrate reduction + and Catalase – at 68 degree Celsius

Chest X-rayChest X-ray

Before treatmentBefore treatment After treatmentAfter treatment

Chest X-rayChest X-ray

1950-1950-medication medication was not was not availableavailable

Placed Placed paraffin sheet paraffin sheet on top of on top of cavity-like cavity-like lesionlesion

Therapy and Prevention of Patient Therapy and Prevention of Patient Infected with Infected with M. tuberculosisM. tuberculosis

Some effective drugs:Some effective drugs: Isoniazid (INH)Isoniazid (INH) RifampinRifampin StreptomycinStreptomycin PyrazinamidePyrazinamide EthambutolEthambutol

Prevention:Prevention: BCG vaccine (could give TB skin test a false-positive)BCG vaccine (could give TB skin test a false-positive) Those identified with latent tuberculosis are given INH every 6-12 months to Those identified with latent tuberculosis are given INH every 6-12 months to

prevent M. tb from becoming active.prevent M. tb from becoming active. Those identified with active tuberculosis are hospitalized and kept in a room 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 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 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 tb by using ultraviolet light to sterilize the air, special filters, and special respirators and masks. respirators and masks.

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:Purpose: to examine risk factors contributing to tuberculosis in to examine risk factors contributing to tuberculosis in adults (over a course of 3 years)adults (over a course of 3 years) Risk factors include age, gender, race, place of birth, alcohol and Risk factors include age, gender, race, place of birth, alcohol and

smoking status, and medical history. smoking status, and medical history.

Methods:Methods: In King County, Washington State (1988-1990), the In King County, Washington State (1988-1990), the characteristics of patients with tuberculosis were compared with characteristics of patients with tuberculosis were compared with census data, and a case-control study was conducted. Self-census data, and a case-control study was conducted. Self-administered questionnaires were completed by 151 patients with administered questionnaires were completed by 151 patients with active tb and 545 control subjects without active tb.active tb and 545 control subjects without active tb.

ResultsResults

Results (cont.)Results (cont.)

Results (cont.)Results (cont.)

Results (cont.)Results (cont.)

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

Conclusion:Conclusion: Targeting the identified groups Targeting the identified groups may be an effective way to reducing the may be an effective way to reducing the incidence of tuberculosis. incidence of tuberculosis.

Take Home MessageTake Home Message Mycobacterium TuberculosisMycobacterium Tuberculosis Tuberculosis involves association between person to person.Tuberculosis involves association between person to person. Typical symptomsTypical symptoms

FeverFever night sweatsnight sweats progressive coughsprogressive coughs chest painchest pain weight lossweight loss

Diagnostics proceduresDiagnostics procedures acid-fast stainacid-fast stain Tuberculin skin testTuberculin skin test Lumber punctureLumber puncture Sputum or biopsy or body fluid Sputum or biopsy or body fluid

Therapy is based on zzz (tuberculin skin test?)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 Prognosis: Active tb can almost always be cured with combinations of antibotics over a course of 6-8 months of

daily treatments. daily treatments. Prevention:Prevention:

BCG vaccineBCG vaccine Preventive therapy of household members Preventive therapy of household members Minimize exposure to patients with active tuberculosisMinimize exposure to patients with active tuberculosis Reduce risk factors by not smoking, drinking, or undertake activities that contribute to poor health.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.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.Threat : consuming large amount of alcohol, smoking heavily, drug-abuse, harmful/unprotected activities, ect.

ReferencesReferences

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.

Point SpreadPoint SpreadCase summaryCase summary 55

Key Information pointing to DiagnosisKey Information pointing to Diagnosis 1010

DiagnosisDiagnosis 55

Microbiology of Pathogen Microbiology of Pathogen 1010

Pathogenesis of the diseasePathogenesis of the disease 1010

Diagnostic testsDiagnostic tests 55

Therapy and PrognosisTherapy and Prognosis 55

PreventionPrevention 55

Epidemiology and threatsEpidemiology and threats 55

Primary research article (last 5 years)Primary research article (last 5 years) 2020

Take home messageTake home message 55

Are all questions addressed?Are all questions addressed? 55

AppearanceAppearance 55

Presentation skills (individual)Presentation skills (individual) 55

Total Total 100100