Tuberculosis – an overview

Presented by: Dave Jay S. Manriquez RN.

February 1, 2009

TB - Prevalence

• 1/3rd of humanity (2 billion people) infected

• One new infection every second

• 8.8 million new cases per year

• 1.6 million deaths/year

• Kills more humans per year than any other infectious disease

TB – worldwide distribution

 Estimated Tuberculosis Case Rates, 1997

• India 1,799,000• China: 1,402,000• Indonesia: 583,000• Bangladesh: 300,000• Pakistan: 261,000• Nigeria 253,000• Philippines 222,000• South Africa 170,000• Russian Federation 156,000• Ethiopia 156,000• Vietnam 145,000• Democratic Republic of Congo 129,000 

• Adapted from Dye C, Scheele S, Dolin P, et al. Consensus statement. Global burden of tuberculosis: Estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999;282:677–686.

TB global stats

• 1/3rd of all new incident cases in Asia

• ½ of all deaths from tb occur in Asia

• In Africa, grew rapidly over last two decades due to HIV

• Period of decline, altered by worldwide epidemic of HIV

Bach Christian Hospital TB stats (2002)

• 141 new cases of tuberculosis (over 11 new cases per month)

• 840 total TB patients under treatment

• 100 patients discharged having completed treatment

TB and HIV

Tuberculosis and HIV

- over 8 million coinfected

- reactivation rates 20 times higher than in non HIV-infected persons

- 50% with dual infection develop active tb

Tuberculosis - resistance

- ½ of all new cases have some resistance

- Worst in 6 Asian countries of Bangladesh, China, India, Indonesia, Pakistan and Philippines

- Every country has resistance to at least one single drug

MDR Tuberculosis

• Defined as resistance to at least INH and rifampicin

• 450,000 cases per year

• XDR – extensive drug resistance – Generally where there is also HIV

Tuberculosis MDR distribution

• Highest in former USSR and China

Mycobacterium others, generally opportunistic and assoc. with HIV

M. Avium Intracellulare

M. Asiaticum

M. Flavenscens

M. fortuitum complex

M. Heamophilum

M. Kanasasii

M. Malmoense

M. Marinum

M. Scrofulaceum

M. Simiae

M. Genavense

M. xenopi

Mycobacterium tuberculosis- the pathogen – AFB staining

Mycobacterium tuberculosis – immune response

• Principle response is formation of a granuloma – monocyte and t cells are with multi-nucleated giant cells on the edge of an area of caseation

• Caseous necrosis and calcium deposition

Tuberculosis - pathology

• Caseous necrosis in kidney

Tuberculosis – clinical presentation

• Primary tb in childhood– Inhalation of organisms– Formation of hilar LAD– Only 5% develop symptomatic disease– 30% develop established infection– 3-5% chance of reactivation– 1/3rd of adult presentations due to new

infection

Primary Tuberculosis-hilar adenopathy and infiltrate

Pulmonary Tuberculosis

• Most cases reactivation of disease acquired years earlier

• Predominant symptoms of cough (78%), weight loss (74%), fatigue (68%), fever (60%), night sweats (55%), hemoptysis (33%)

Pulmonary Tuberculosis – CXR findings

• Apical lesions – mod. and severe w/cavity

Chest X-Ray findings, atypical

• Pneumonic consolidation

Pulmonary Tuberculosis – pleural effusion

• Usually appear 3-6 months after primary disease

• With or without lung infection

• Usually unilateral

• Predominance of lymphs

• Exudative w/protein >3 gms/dl

• Often AFB neg, cx positive

Miliary tuberculosis

• In immune-suppressed

• Follows blood-borne dissemination

• May present as FUO• High mortality rate

Miliary Tuberculosis - choroidal

Extra-pulmonary TBScrofula (lymphadenitis)

• most frequent extrapulmonary manifestation

• 80% cervical• Nearly always PPD

positive• Granulomas on

biopsy• Persistent nodes after

tx common

Extrapulmonary tb - GI

• Anywhere from mouth to anus

• 70% w/advanced pulmonary get GI

• Small bowell- ileocecal valve

• Perforations common• Responds well to tx

tapeworms roundworms

Extrapulmonary TB - peritonitis

• Ascites, pain, +/- fever, wt. loss

• Ascitic fluid seldom AFB positive

• Culture positive in only 25%

• Need tissue biopsy

• Diagnosis often delayed

Extrapulmonary TB - meningitis

• In early childhood, post-primary

• May present with subtle symptoms

• 3/4ths with miliary pattern on CXR

• AFB positive in 37% initially, 90% after 4th spinal tap

Extrapulmonary TB – osteomyelitis

• Pott’s most common – 50% of all osteo

• Low thoracic most common

• Anterior destruction

Extrapulmonary TB - arthritis

• Chronic, progressive, monoarticular

• Usually hip or knee

• AFB positive in only 1/4th

• Ideally, synovial biopsy

Extrapulmonary TB – cold abscesses

Extrapulmonary TB - urogenital

• Often asymptomatic, but kidney most commonly affected

• May present with cystitis symptoms, sterile pyuria

• Cultures 90% sensitive

• Males – scrotal mass, oligospermia

• Female – infertility with hematogenous focus in endosalpinx

Tuberculosis – laboratory investigations

• AFB – inexpensive

• Cultures – expensive, sensitivities helpful in MDR

• PCR – out of reach in poorer countries

• ESR – inexpensive and helpful, decreases with treatment

• Anemia of chronic disease

Tuberculosis - PPD

• 10mm – 90% infected

• >15mm – virtually all

• 5-10mm – may be result of BCG

• Unless recent BCG administration, if >10mm, then not from BCG

BCG vaccine

• Routinely administered in much of the world

• Efficacy 60-80%, though not uniformly

Tuberculosis - treatment

• INH (isoniazid) – bactericidal– Most common side effect hepatotoxicity – Check LFTs (20% of patients)– If occurs, may reintroduce one med at a time– Other side effect – peripheral neuritis,

prevented by coadministration of piridoxine

Tuberculosis - treatment

• Rifampin– Bactericidal– Many interactions with other drugs– Hepatotoxicity

Tuberculosis - treatment

• Pyrizinimide– GI intolerance– Hepatotoxicity – from elevated transaminases

to liver failure

Tuberculosis - treatment

• Ethambutol

-bactericidal

-side effect – retrobulbar neuritis, presenting initially with blurred vision

Tuberculosis – treatment

• Streptomycin– First antituberculous med– Side effects of ototoxicity, nephrotoxicity– Given IM

Tuberculosis – treatmentSecond line drugs

• Ethionamide

• Ciprofloxacin

• Capreomycin

• Kanamycin

• Amikacin

• Cycloserine

• Thiacetazone

Tuberculosis – treatment

• Bacteria killed over 6-mo period, but patient clinically improves in a few weeks

• Can do a 1-3 month interval AFB or culture evaluation

• Can follow ESR/weights

Tuberculosis - treatment

• Variety of regimens• BCH regimen

- for first 2 months, four drugs (INH/rifampin, pyrizinamide, ethambutal- next four months, only INH/rifampin

- CNS – 12 months - depending on clinical scenario DOTS Use of steroids

Leprosy

• Organism – mycobacterium leprae

• Infection of skin and nerves

Leprosy

Prevalence - 10-15 million in 1950s - 600,000 in 2000 Countries affected (>1/10,000) 122 in 1985 15 in 200083% in India, Brazil, Myanmar, Madagascar,

Nepal, Mozambique

Leprosy - transmission

• Generally nasal secretions, particularly in lepromatous

• Importance of proximity, but most cases sporadic

Leprosy - presentation

• Subclinical more common than clinical, as incubation 4-10 years

• Clinical – tuberculoid vs. lepromatous

Leprosy – clinical presentation

• Tuberculoid – limited by vigorous cell-mediated response

• Lepromatous – proliferation of bacteria with extensive skin and nerve involvement

Leprosy - tuberculoid

Leprosy - lepromatous

Leprosy - lepromatous

Leprosy – borderline tuberculoid

Leprosy – mid borderline

Leprosy – clinical presentation

• Reversal reactions– Occur in all forms except polar tuberculoid– Sometimes after initiation of treatment– Inflammation of existing lesions or new skin

lesions, may present with acutely swollen nerves

– Respond to steroids

Leprosy – reversal reactions

Leprosy - treatment

• Combination therapy with dapsone, rifampin, clofazimine, quinolones, minocycline, azithromycin

• Multibacillary vs. paucibacillary

• High dose steroids for reversal reactions