Presented by: Arif Fakhrudin February 22 nd 2011

 AFB

BCG
BMI BW

IBW
TB TST

WHO

: Acid Fast Bacilli : Bacill Calmete Guerin : Body Mass Index : Body Weight : Ideal Body Weight : Tuberculosis : Tuberculin Skin Test : World Health Organization

Introduction

Miliary TB

a form of progressive tuberculosis resulting from massive lymphohematogenous dissemination of Mycobacterium tuberculosis from a pulmonary or extrapulmonary focus to various organs.
Chest radiography: Millet like (range 1-5 mm) seeding of TB Bacilli
Baker SK, Glassroth J. Milliary tuberculosis. In: Rom WN, Garay SM, editors. Tuberculosis. 2 ed. Philadelphia: Lippincott William&Wilkins, 2003:427-44.

Miliary TB must be considered in the differential diagnosis when antibiotic therapy for common organisms fails to treat pneumonia.

About 50-90% of patients present the miliary pattern with disseminated tuberculosis

Fernandes SR, Homa MN, Igarashi A, Salles AL, Jaloretto AP, Freitas MS, et al. Miliary tuberculosis with positive acid-fast bacilli in a pediatric patient. Sao Paulo Med J 2003;121(3):125-7.

Predisposing factors of miliary TB: immunodeficiency, malnutrition, corticosteroids and immunosuppressive therapy
The risk of TB infection ~ duration and proximity of exposure to an infectious case

Initial primary exposure plays significant role in the development of a latent TB infection
Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam Physician 2005;72(9):1761-8. Sablan B. An update on primary care management for tuberculosis in children. Curr Opin Pediatr 2009;21(6):801-4.

A first episode of TB may be primary or post primary (reactivation of the dormant tubercle)

The characteristic feature of post primary TB: - Extensive lung destruction with cavitation, - Positif sputum smear, - Upper lobe involvement - Usually no intrathoracic lymphadenopathy.
Maher D. The natural history of Mycobacterium tuberculosis infection in adults. In: Schaaf HS, Zumla A, editors. Tuberculosis a comprehensive clinical reference. London: Saunders Elsevier, 2009.129-32

OBJECTIVE

Present a case of miliary tuberculosis after pneumonia infection in a chlid.

Case Report

Case Report
A, 3 years old girl

Main complaint:
Shortness of breath since 3 days before admission. Preceded by a productive cough 10 days prior admission. High grade fever 3 days prior admission. No other people around her has same sign and symptom.
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Previous and family history No history of chronic cough and dyspneu. No complaint of vomiting, lost of appetite or weight lost. Her weight one month before was 20 kg.

TB contact: Her mother had been treated with anti tuberculosis drug when she was 1 years old. Her uncle wich is her neighbour has been treating antituberculosis drug since 3 months ago.
Immunization: complete
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Physical examination An alert, irritable girl BP: 90/60 mmHg, Pulse: 126 x/min, RR: 60 x/min t : 38,9 C. Dyspneu (+), nasal flare (+) Chest symetric, retraction intercostal spaces, epigastric and clavicula region The breath sound: vesiculer/vesiculer, coarse rales +/+, wheezing -/ Heart : normal Abdominal : normal Extremities : normal Enlargement of lymph nodes
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Nutritional status

BW=19 kg BH=95cm BMI 21kg/m2 > 3SD

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Laboratory examination
Hb WBC Platelet Hct pH pCO2 pO2 HCO3 BE SaO2 :11.1 g/dl : 21.5 K/uL : 465 K/uL : 30.9% : 7.47 : 27 : 48 : 19.7 : -4.0 : 86% Potassium Sodium Chloride Calsium AST ALT CRP : 4.6meq/l : 144 meq/l : 106 mmol/l : 7.9 meq/l : 42 U/I : 34 U/I : 87,5

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Chest X-ray

The heart was normal in shape and size. The diffuse spread of infiltrat was found in both of the lung field. There were no lung cavity, pneumatocele and pleural efusion

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History Clinical manifestations Laboratory findings Radiology findings

Initial treatments: - Oxygenation - Ampicilin sulbactam - Amikacin - Antipyretic - Adequate fluid and nutrition
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Severe Pneumonia with Obesity

On the 7th day of admission

-Weak condition, no fever, dyspnue, chest retraction -Tuberculin skin test + (induration 15 mm) -Acid Fast Bacilli +

Dx: severe pneumonia, miliary tuberculosis and obesity. Antibiotic was continued, antiTB drug was administered

Chest x-ray: Miliary spot in both of the lung fields without pleural effusion, cavity and pneumatocele
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On the 13th day of admission, six days of antitubercolosis treatment

No any complaint. There were no fever, dyspneu, chest retraction and rales. The blood culture was no bacterial overgrowt.

The patient was discharged with a good condition and was planned to routinely going to Pediatric Pulmonary Outpatient Clinic of DR Soetomo General Hospital.

The chest radiograph still revealed miliary spot in the both of lung field.
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Discussion

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The progression of chest x-ray

On admission 7th days of admission 13th days of admission

The diffuse spread of infiltrat

Miliary spot in both of the lung

still revealed miliary spot

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On the admission Dx: severe pneumonia although there was TB contact

- Cough - Dyspnea - Fever - Moist rales -Infiltrat in xray

Pneumonia

The WHO has defined pneumonia solely on the basis of clinical findings obtained by visual inspection and timing of the respiratory rate. Pneumonia is respiratory disease which shown evidence of cough, dyspnoe, fever, moist rales and infiltrate in radiographic features of the chest
McIntosh K. Community-acquired pneumonia in children.N Engl J Med 2002;346(6):42937.

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-3 years old, -dyspnea, - high fever, -leucocytosis, -diffuse infiltrate on chest x-ray

Bacterial infection

Tx: B lactame and aminoglicoside

Bacterial infections such as Streptoccocus Pneumoniae < 5years. Bacterial pneumonia usually presence suddenly, The patient seen toxic, high fever with trembling and dyspneu getting worse in short time.
McIntosh K. Community-acquired pneumonia in children. Engl J Med 2002;346(6):42937. Ostachuck M, Robert DM, Haddy R. Community-aquired pneumonia in infant and children. Am Fam Physician

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After 7 days of treatment: The sign and symptom were improved. - Tuberculin skin test + - Acid Fast Bacilli + - Chest x-ray: suggesting TB (miliary spot)

TB score:6

Dx: Miliary TB
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In this patient we found high fever, cough and no weight loss The onset of miliary TB is insidious: weight loss, fever, cough. Usually chest sign are not present at the onset but later fine crackles may be heard over the whole of the chest. The fever runs a irregular course with spikes up to 400C. Wasting may be extreme.

Robinson MJ, Lee EL. Tuberculosis in childhood. In: Robinson MJ, Lee EL, editors. Paediatric problem in tropical countrie. 2 ed. Singapura: PG Publishin, 1991:193-8.

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On this patient, had BCG immunization, and TST result + (15 mm of induration) A positive or reactive TST indicates TB infection. Defined as > 10 mm diameter of induration when read 48-72 hours after administration in any child irrespective of BCG immunization. False positive reaction can be caused by cross sensitization to antigens of nontuberculous mycobacteria (<10-12 mm of induration)
Graham SM, Marais BJ, Gie RP. clinical features and index of suspicion of tuberculosis in children. In: Schaaf HS, Zumla A, editors. Tuberculosis a comprehensive clinical reference. London: Saunder Elsevier, 2009:154-63. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 1994;271(9):698-702.

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The mother got antiTB drugs for 3 years ago, and now already improved. Unfortunately she still have a tuberculosis contact from her uncle.

The mother and uncle had obviously infected this patient

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This patient The chest x-ray showed wide spread miliary TB but in the first time of chest x-ray revealed difuse infiltrate.

The chest X-ray shows a miliary pattern at presentation in more than half of the patients. It is important to note that even if not present initially, miliary patterns often become apparent days to weeks later.

Baker SK, Glassroth J. Milliary tuberculosis. In: Rom WN, Garay SM, editors. Tuberculosis. 2 ed. Philadelphia: Lippincott William&Wilkins, 2003:427-44.

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On this patient: had positive AFB from gastric aspirates

AFB was gold standar for TB diagnosis in adult but no for children.

AFB (+) indicated the infection of the endobroncial due to post primary TB.

Fernandes SR, Homa MN, Igarashi A, Salles AL, Jaloretto AP, Freitas MS, et al. Miliary tuberculosis with positive acid-fast bacilli in a pediatric patient. Sao Paulo Med J 2003;121(3):125-7.

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Miliary tuberculosis is due to spread through the blood stream of large number of TB which the patients defences are to week to kill off.

Reactivation of an old tuberculous lession (primary or post primary) with erosions of a blood vessel. Reactivation may occur if the patients defences are lowered

The immunosupresion was caused by severe pneumonia and also caused by obesity
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Many cases of primary TB infection in children are asymptomatic, self-healing and remain completely unnoticed or accidentally discovered at a later stage.

Factors :host genetics, microbial virulence and underlying conditions that impair immune competence determine the outcome of infection.

a reflection on the immaturity of the immune response.

Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis 2008;8(8):498-510.

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This child was a three years old Age is an important aspect of the epidemiology of childhood tuberculosis. About 60% of tuberculosis cases in children in the United States occur in infants and children <5 years of age.

Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Nelson LJ, et al. The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis 2004;8(3):278-85.

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Table 1 Risk of pulmonary and extra-pulmonary disease in children following infection with MTB
Risk of disease following primary infection (%) Age at infection (years) <1 1-2 10-20 2-5 30-40 10-20 50 75-80 High rates of morbidity and mortality 2-5 5-10 0.5 <0.5 5 2 95 98 Safe school years Disseminated TB Pulmonary TB No disease Comments

>10 <0.5 10-20 80-90 Effusions or adultHowever age and immunodeficiency are important type pulmonary disease factors to influence TB infection

From: Lancet Infect Dis. 2008 August; 8(8): 498510.

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This patient has obese of nutrition status

Nutritional status is significantly lower in patients with active pulmonary TBcompared with healthy controls in different studies in Indonesia, England, India, and Japan.

In Indian study, tuberculosis patients were respectively 11 and 7 times more likely to have a BMI < 18.5
Gupta KB, Gupta R, Atreja A, Verma M, Vishvkarma S. Tuberculosis and nutrition. Lung India 2009;26(1):9-16. Lamas O, Marti A, Martinez JA. Obesity and immunocompetence. Eur J Clin Nutr 2002;56 Suppl 3:S42-5.

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M. TB spread promptly from the primary site of infection via lymphatics and the bloodstream to hilar lymph nodes, apices of both lungs, and sites throughout the body, where they can remain dormant but viable, capable of reactivating disease at any time.

Positing that cytokines from adipocytes cannot be important in this arena because they are restricted to areas near their secretion site and do not reach the site of the infection, the lung
Lamas O, Marti A, Martinez JA. Obesity and immunocompetence. Eur J Clin Nutr 2002;56 Suppl 3:S42-5.

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Summary

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A case of miliary tuberculosis after pneumonia infection has been presented. Post primary TB occured after a latent period of 3 years after primary infection, with tuberculosis contact, tuberculin skin test, acid fast bacilli from gastric aspirates and chest x-ray was supported

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Thankyou

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Parameter system for diagnosis tb in children 0 1 Table Scoring

2 Cavity +,AFB not clear

Tbcontact
Tuberculin test

Not clear neg

Family report, AFB or not clear

AFB +
Positive ( 10 mm or 5mm inimmunocompromised condition)

Bodyweight or nutritional status

BW/H< 90 % or BW/age < 80 %, BW not >> in2 mo

Severe malnutrition or BW/ H <70% or BW/age <60

Fever unclear source

Cough

2 weeks
3 weeks 1 cm, count 1, painless

Cervical lymphnode, axillar, inguinal enlargement

Swelling at bone/pelvic,knee ,phalang joint Chest radiography

swelling
Infiltrates,lymphnoN or de enlargement,segunclear mental or lobar consolidation,atelectasis Calcification+in filtrates,lymphnode enlargement + infiltr-

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Source: Nastiti NR, Darfioes B, Makmuri, Cissy K. Pedoman Nasional Tuberkulosis Anak. UKK Pulmonologi PP IDAI 2005

In our case

History of contact with adult active tuberculosis patient

Chest Ro : miliary TB

BMI > 3SD

PULMONARY TUBERCULOSIS

Fever Cough

Environment: Poor ventilation room

Tuberculin test positive 15 mm AFB positive

Anti TB Drugs

Mechanism of Action
Isoniazid Bactericidal & bacteriostatic Inhibition of biosintesis mycolic acid especially organism that actively developed penetrates rapidly into all tissues & lesions, its activity is not influenced by the pH of the environment

Side Effect
Hepatotoksic Neuritis

Rifampisin

Strong bactericidal & bacteriostatic DNA-dependent RNA polymerase (rantai sintesis RNA) inhibition Bacteriostatic (inhibition of biosintesis of arabinogalactan, main polisacarid Mycobacterium membrane) Effective for INH/RIF resisten

Hepatotoksic

Ethambutol

Neuritis Retrobulbar Uric acid

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Mechanism of Action
Pyrazinamid

Side Effect

Bacterisidal, sterilizing effect inside Hepatotoksic macrophages where organisms grow slowly because of the acid pH of the environment

Streptomisin

Bacterisidal & bacteriostatic (supression, not eradication) Disturb protein synthesis (ribosom subunit 30S) Can get into cavity, but cant penetrates into intracelluler fluid

Ototoksic Nefrotoksic

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Improvement of M.tb infection

Th

Th1

+ Th2

IL12

IFN

IL-2

IL-4

IgE

This patient suffer from TB so does her mother and uncle Genetic as well as acquired defects in host immune response pathways greatly increase the risk of progressive disease. TB disease susceptibility is highly likely to be polygenic, with contributions from many minor loci. A large number of TB susceptibility markers have been identified from candidate gene studies as disease-causing genes including TIRAP, HLA DQB1, VDR, IL-12, IL12R1, IFN-, SLC11A1 and MCP-1.
Levin M, Newport M. Understanding the genetic basis of susceptibility to mycobacterial infection. Proc Assoc Am Physicians 1999;111(4):308-12.

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Nutritional status

BW=19 kg BH=95cm IBW 14.5 kg

130% IBW
Mild obese.

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Nutritional status

BW=19 kg BH=95cm BMI =21 kg/m2

> P 95

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