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Iraqi National Pediatric Guideline for Tuberculosis management pediatric TB.pdf · a. To guide the TB Program managers in identifying and managing the TB suspects (pediatric) by effective

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Page 1: Iraqi National Pediatric Guideline for Tuberculosis management pediatric TB.pdf · a. To guide the TB Program managers in identifying and managing the TB suspects (pediatric) by effective

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Iraqi National Pediatric Guideline for Tuberculosis management

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Contents Preface .................................................................................................................................................... v

Acronyms ............................................................................................................................................... vi

Drugs.................................................................................................................................................. vi

1. Introduction ........................................................................................................................................ 1

1.1 What is Tuberculosis ..................................................................................................................... 1

1.1.1Standardized case definitions of TB: ....................................................................................... 3

2. Recommended approach to diagnosing TB in children ....................................................................... 4

2.1Risk factors for TB .......................................................................................................................... 5

3. Investigation & Management of children suspected to have Tuberculosis ......................................... 5

3.1 The criteria to suspect TB in a child ............................................................................................... 5

3.2. Criteria Suggestive of Tuberculosis disease .................................................................................. 5

Figure1.Diagnostic algorithm for pediatric pulmonary TB ...................................................................... 7

3.3. Scoring system and diagnosis of childhood TB: ............................................................................ 8

3.4. Investigations to Diagnose TB ...................................................................................................... 8

4. Treatment of childhood Tuberculosis in Iraq .................................................................................... 11

4.1. Objectives of anti-TB treatment ................................................................................................. 11

4.2. Recommended Pediatric TB treatment regimens ....................................................................... 12

4.3. Management of TB meningitis, miliary TB and disseminated TB ................................................ 14

4.4. Management of drug-resistant TB in children ............................................................................ 14

4.4.1DR-TB types ........................................................................................................................... 14

4.4.2 Management of Child contacts of infectious MDR-TB cases ................................................. 16

4.5.Management of congenital and neonatal TB .............................................................................. 16

4.5.1.Mode of Infection ................................................................................................................ 16

4.5.2. Beitzki and Cantwell Diagnostic Criteria of Congenital Tuberculosis ................................... 17

4.5.3. Clinical Manifestation.......................................................................................................... 17

4.5.4 Investigations ....................................................................................................................... 17

4.5.5. Treatment ........................................................................................................................... 18

4.5.6. Prevention of TB in a baby born to a woman diagnosed with infectious pulmonary TB...... 19

5. Contact screening and management ................................................................................................. 19

5.1Assessment and management ..................................................................................................... 19

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6. TB and HIV Infection ......................................................................................................................... 21

6.1Diagnosis of TB in HIV-­‐infected children .................................................................................... 21

6.1.1Antiretroviral therapy in children with TB/HIV co-infection.................................................. 21

7. Isoniazid Preventive therapy............................................................................................................. 21

8. Monitoring (Recording and Reporting) ............................................................................................. 23

8.1. Definitions of standard treatment outcomes ............................................................................. 24

9. BCG vaccination in children............................................................................................................... 24

10. Infection control in health-care settings ......................................................................................... 25

10.1. Risk of transmission of tuberculosis in health-care settings ..................................................... 25

10.2. Infection control strategies ...................................................................................................... 25

10.2.1. Workplace and administrative (managerial) control measures ......................................... 25

10.2.2. Environmental control measures ...................................................................................... 26

10.2.3. Personal protective equipment (respiratory protection) ................................................... 26

11. Research Priorities in pediatric TB .................................................................................................. 26

11.1. Childhood TB research areas .................................................................................................... 27

12. BCG Disease .................................................................................................................................... 29

Annex 1. ................................................................................................................................................ 30

Administering, reading and interpreting a tuberculin skin test ............................................................. 30

Annex 2. ................................................................................................................................................ 31

Management of a child contact of a newly diagnosed patient with tuberculosis ................................. 31

Annex3. Diagnostic Algorithm for Pediatric Pulmonary TB ................................................................... 32

Annex 4. TB treatment categories ........................................................................................................ 33

Annex5. Managing Patients with Interruptions in Treatment ............................................................... 34

Annex 6. Dose recommendations for INH preventive therapy.............................................................. 34

Annex 7.Lab register ............................................................................................................................. 35

Annex 8. Patient referral/Transfer card ................................................................................................ 36

Annex 9. Patient Identity Form ............................................................................................................. 38

Annex 10. Sputum Request form .......................................................................................................... 40

Annex 11. Patient Treatment Card........................................................................................................ 41

Annex 12.TB Register ............................................................................................................................ 43

References ............................................................................................................................................ 44

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Preface

The World Health Organization (WHO) first published guidance for National Tuberculosis control programs on managing tuberculosis in children. The Guidance follows the principles of a public health approach aimed at optimizing outcomes, including the quality of life and survival, of children with tuberculosis; it also serves as a reference tool for countries to adopt and adapt according to their national circumstances. During 2009 and 2010, WHO updated the Guidance through a series of coordinated efforts to review and synthesize evidence on the correct dosages of anti tuberculosis medicines for use in children and the regimens that should be used for different manifestations of the disease in children. This evidence was assembled following systematic reviews, pharmacokinetic simulations and the preparation of evidence summaries, using grade profiles and analysis where appropriate.

There have been major developments in advancing the use of new diagnostic tools, but these tools are not recommended for the diagnosis of latent tuberculosis infection or active tuberculosis disease in children.

The pediatric guidelines have been produced to help NTP staff, physicians and health workers to effectively treat and manage TB in children

The main objectives of these guidelines are:

a. To guide the TB Program managers in identifying and managing the TB suspects (pediatric) by effective implementation of DOTS

b. To guide health workers and community TB supporters to refer TB suspects. c. To guide all clinicians involved in TB management to effectively diagnose, treat and

monitor the condition.

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Acronyms

AFB ---- acid fast bacilli

ART --- anti-retroviral therapy

BCG --- Bacillus Calmette –Guerin

DOT --- directly observed treatment

EPTB --- extra pulmonary tuberculosis

FDC --- fixed dose combination

HIV --- human immunodeficiency virus

Kg --- kilogram

Mg --- milligram

NTP --- national tuberculosis program

PTB --- pulmonary tuberculosis

PPD --- purified protein derivative

TST --- tuberculin sensitivity test

WHO --- world health organization

Drugs

E --- Ethambutol

H --- Isoniazid

R --- Rifampicin

S --- Streptomycin

Z --- Pyrazinamide

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1. Introduction The World Health Organization (WHO) has estimated that around 10% of global tuberculosis (TB) caseload occurs in children (0-14 years). Children can present with TB at any age, but the most common age is between 1 and 4 years. Diagnosis of tuberculosis in children is difficult. The burden of pediatric disease in TB endemic settings is usually tilted towards the infants and young children (< 5 years of age) from whom it is difficult to obtain sputum, and the disease in this age group is usually paucibacillary and needs sputum culture to improve yield of diagnostic confirmation. Therefore, most children with a diagnosis of TB are categorized by National TB Programs (NTPs) as either ‘‘sputum smear-negative’’ PTB or extra-pulmonary TB (EPTB) cases

Great care should be taken to rapidly identify serious forms of tuberculosis such as disseminated tuberculosis, tuberculous meningitis, spinal tuberculosis and tuberculosis in immunosuppressed children. These can be life-threatening conditions and they require prompt diagnosis and treatment if death or disability is to be avoided. This is especially true in very small children (under 2 years of age) and particularly in children who have been in contact with smear-positive pulmonary tuberculosis patients. In the majority of instances, however, childhood tuberculosis is a mild disease. Nevertheless, children with tuberculosis should be treated to prevent complications and to ensure that they do not subsequently develop tuberculosis from reactivation of their infection.

1.1 What is Tuberculosis

Tuberculosis (TB) is an infectious disease that is caused by a bacterium called Mycobacterium tuberculosis (also called tubercle bacilli). Tubercle bacillus primarily affects lungs and is called Pulmonary Tuberculosis. It can also affect other organs like lymph nodes, bones, meninges, intestines etc. (Extra Pulmonary Tuberculosis). Pulmonary tuberculosis is most common of the two worldwide. Patients with pulmonary tuberculosis are infectious where as those with extra pulmonary are usually not infectious. Pulmonary TB patient when sneezes or coughs releases the bacilli into the air in tiny droplets and people who inhale the droplets get infected. Although the natural course of Tuberculosis in children follows a continuum, defining different stages of the disease is found useful in the management of Tuberculosis

Stage 1

Exposure has occurred, implying that the child has had recent contact with an adult who has contagious TB. The child has no physical signs or symptoms and has a negative tuberculin skin test (TST) result. Chest radiography does not reveal any changes at this stage. Not all patients who are exposed become infected, and the TST result may not be positive for 3 months. Unfortunately, children younger than 5

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years may develop disseminated TB in the form of miliary disease or TB meningitis before the TST result becomes positive. Thus, a very high index of suspicion is required when a young patient has a history of contact.

Stage 2

This second stage is heralded by a positive TST result. No signs and symptoms occur, although an incidental chest radiograph may reveal the primary complex.

Stage 3

TB disease occurs and is characterized by the appearance of signs and symptoms depending on the location of the disease. Radiographic abnormalities may also be seen.

Stage 4

Stage 4 is defined as TB with no current disease. This implies that the patient has a history of previous episodes of TB or abnormal, stable radiographic findings with a significant reaction to the TST and negative bacteriologic studies. No clinical findings suggesting current disease are present.

Stage 5

TB is suspected, and the diagnosis is pending.

Tuberculosis is classified as Pulmonary Tuberculosis and Extra-Pulmonary Tuberculosis.

Pulmonary TB: In the majority of cases, children with pulmonary TB have CXR changes suggestive of TB. The commonest picture is that of persistent opacification in the lung together with enlarged hilar or subcarinal lymph glands. A miliary pattern of opacification is highly suggestive of TB. Patients with persistent opacification that does not improve after a course of antibiotics should be investigated for TB. Adolescent patients with TB have CXR changes similar to adult patients, with large pleural effusions and apical infiltrates with cavity formation being the most common forms of presentation. Adolescents may also develop primary disease, with hilar adenopathy and collapse lesions visible on CXR.

Extra- Pulmonary TB: In most of these cases, TB will be suspected from the clinical picture and confirmed by histopathology or other special investigations.

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1.1.1Standardized case definitions of TB:

TB suspects

• Ill child with a history of contact with a suspect or confirmed case of pulmonary TB. • Does not return to normal health after measles or whooping cough. • Having weight loss, cough and fever who does not respond to antibiotic therapy (other than anti

tuberculous or fluroquinlone) for acute respiratory disease. • With abdominal swelling, hard painless mass and free fluid. • Presence of painless firm or soft swelling in a group of superficial lymph nodes. • With signs suggesting meningitis or disease in the central nervous system.

Sputum smears positive-Pulmonary Tuberculosis

• One or more initial sputum smear examinations positive for AFB, or • One sputum culture positive for M. tuberculosis.

Children with smear-positive disease are more likely to be adolescent patients or children of any age with severe Intra-thoracic disease

Sputum smears negative-Pulmonary Tuberculosis

A case of pulmonary TB that does not meet the above definition for smear-positive TB. In keeping with good clinical and public health practice, diagnostic criteria for pulmonary TB should include:

- At least two sputum specimens negative for AFB and Radiographic abnormalities consistent with active pulmonary TB, and no response to a course of broad spectrum antibiotics for 14 days (other than anti-tuberculosis). -Decision by a clinician to treat with a full course of tuberculosis chemotherapy.

Extra –Pulmonary Tuberculosis (TB of organs other than lungs) Children with only extra-pulmonary TB (i.e., TB of organs other than the lungs) should be classified under this case definition.

Children who have both pulmonary and extra-pulmonary TB should be classified under the case definition of pulmonary TB.

Drug resistant Tuberculosis (MDR-TB, XDR-TB) Drug resistant tuberculosis (MDR-TB) refers to resistance to any of the first line anti tuberculosis drugs.

Multidrug resistance is resistance to both isoniazid and rifampicin, with or without resistance to other first-line drugs. Extensively drug-resistant TB (XDR) has also emerged which, in addition to rifampicin and isoniazid, is resistant to Floroquinolones and injectable second line agents.

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Drug-resistant TB is a laboratory diagnosis. However, drug-resistant TB should be suspected if any of the following situations below are present:

1. Conditions in the source case suggestive of drug-resistant:

- Contact with a known case of drug resistance - A source case who remains smear-positive after 3 months of treatment - History of previously treated TB - History of treatment interruption.

2. Condition of a child suspected of having drug-resistant TB:

- Contact with known case of drug-resistant TB - Child not responding to the TB treatment regimen - Child with recurrence of TB after adherent treatment.

The diagnosis and treatment of drug-resistant TB in children is complex and should be done at referral centers.

2. Recommended approach to diagnosing TB in children

• Careful history including history of TB contact and symptoms consistent with TB. • Thorough clinical examination including growth assessment. • Tuberculin skin test(also called Manteaux) • Sputum smear microscopy and culture(if possible especially in children >8 years of age) • HIV testing-Provider initiated testing and counseling(PITC)

Points to remember

The presence of two or more of the following criteria should strongly suggest TB

Cough of any duration (productive or nonproductive) Unexplained weight loss not responding to treatment or food supplements Fever and/or night sweats Failure to thrive

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2.1Risk factors for TB • Household contact with a newly diagnosed smear-positive case. • Age of 5 years and below. • HIV infection and immune suppressed patients. • Severe malnutrition.

Any child with signs and symptoms suggestive of TB should be investigated.

3. Investigation & Management of children suspected to have Tuberculosis

3.1 The criteria to suspect TB in a child a. Child who is ill, with a history of contact with a suspect or confirmed case of pulmonary TB.

Contact (defined as a child especially those <5 years of age who has been in close contact with a case of smear positive TB) must be screened for TB.A close contact is defined as living in the same household or in frequent contact with a source case (e.g. care giver) with sputum smears positive TB. Source cases who are sputum smear negative but culture- positive are also infectious, but to a much lesser degree.

b. Child that does not return to normal health after measles or whooping cough, c. Child complaining of Weight loss, cough, fever that does not respond to therapy for acute

respiratory disease. d. Child With abdominal swelling, hard painless mass and or free fluid. e. Presence of painless firm or soft swelling in a group of superficial lymph nodes. f. Having signs suggesting meningitis or disease in the central nervous system or neurological

manifestations.

3.2. Criteria Suggestive of Tuberculosis disease While the above criteria aid in identifying a TB suspect the features that strongly suggest Tuberculosis disease in a child are as follows:

The presence of one or more of the following should strongly suggest the diagnosis of TB

a. Chronic symptoms suggestive of TB.

• Chronic cough: an unremitting cough that is not improving and has been present for 2 weeks or more.

• Prolonged fever for 14 days after common causes (ex. Pneumonia) have been excluded. Weight loss or failure to thrive, and growth assessment from the child’s growth chart.

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b. Physical signs (clinical examination) highly suggestive of TB

Chest examination with stony dull percussion in a child not acutely ill is specific symptom complex of TB pleural effusion

Physical signs suggestive of extra-pulmonary TB:

Recent onset of Gibbous (suspected vertebral TB) Enlarged cervical lymphadenopathy (usually non painful one) with or without fistula.

Physical signs requiring investigation to exclude extra-pulmonary TB:

Meningitis not responding to antibiotic treatment, with raised intracranial pressure. -Pleural effusion. -Pericardial effusion. Distended abdomen with ascites. Non-painful enlarged lymph nodes without fistula formation. Non-painful enlarged joint. Signs of tuberculin hypersensitivity: phlyctenular conjunctivitis, erythema nodosum.

(Note documented weight loss or failure to gain weight, especially after being treated in a nutritional rehabilitation program, is a good indicator of chronic disease in children, and TB may be the cause.)

c. Positive tuberculin skin test.

A positive TT occurs when a child is infected with M. tuberculosis. However, in children, TT (Manteaux test) can also be used as an adjunct in diagnosing TB disease, when it is used in conjunction with signs and symptoms of TB and other diagnostic tests.

d. Chest radiograph suggestive of TB.

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Figure1.Diagnostic algorithm for pediatric pulmonary TB

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3.3. Scoring system and diagnosis of childhood TB: The Iraqi NTP did decide to adopt and use a score chart for the diagnosis of TB in children, although these have rarely been evaluated and validated against a gold standard. They are considered as screening tools and not as a means of making a firm diagnosis.

Scoring Criteria for supporting Diagnosis of Childhood TB in Iraq

Table1

criterion Scoring less than 5 years Scoring more than 5Ys

History of contact 2 2

Skin test 2 1

Cough 2 2

Weight loss(failure to thrive) 3 3

Prolong Fever 1 2

Total More than 5 More than 5

3.4. Investigations to Diagnose TB 1. Mantoux test

Primary infection with M. tuberculosis is followed after four to six weeks by the development of cell-mediated delayed-type skin hypersensitivity, The Skin-test conversion may be due to infection with a variety of mycobacterial species other than M. tuberculosis, including BCG.The tuberculin skin test measures only the degree of hypersensitivity and not immunity to tuberculosis, the time of infection or the presence or extent of disease. Repeated tuberculin testing at the same site creates local memory and subsequent tests may be enhanced. Repeated testing even after as long as a year may lead to "boosting" of a response even if a fresh site is used. This phenomenon does not mean that a fresh infection has occurred. The reading of a Mantoux test is limited to a single aspect of the reaction, the transverse diameter of the induration. A significantly positive Monteux test in a young child provides considerable support for a diagnosis of tuberculosis in the presence of other non-specific features.

The TT used in Iraq is 2TU (tuberculin units) of tuberculin purified protein derivative (PPD) in infected children, previously (Rt20 tween80). A tuberculin test is classified as positive based on the diameter of the induration in concurrence with certain patient-specific risk factors.

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• In a healthy person whose immune system is normal, induration greater than or equal to 15 mm is considered a positive skin test. If blisters are present (vesiculation), the test is also considered positive.

• In high risk patients (high risk includes severely malnourished children, i.e., those with clinical evidence of severe malnutrition and immune compromised patients.) 5 mm of induration is considered a positive skin test result.

• Induration of less than 2 mm, without blistering, is considered a negative skin test. Table 2

Causes of False Negative TT

Causes of False Positive TT

TT of 10 mm and more indurations are regarded as positive (whether or not they have been BCG vaccinated).

Infection with non-tuberculous mycobacteria

Incorrect administration or interpretation of test

BCG Vaccination

Severe pulmonary Tuberculosis case Incorrect interpretation of test

Low protein states.

HIV infection. Improper storage of Tuberculin Viral infections (measles, Varicella) Vaccination with live viral vaccine (within 6 weeks).

Genitourinary infection.

Malnutrition

Bacterial infections (typhoid, leprosy, pertusis)

Immune suppressive medications.

Neonatal patient

Primary immunodeficiencies. Diseases of lymphoid tissue.

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2. Chest X ray

The most common radiological signs of TB in children are

• Enlarged hilar lymph nodes and /or a broad mediastinum due to enlarged lymph nodes (this is most common presentation in children.

• Lobar disease may also be seen following dissemination of military disease • Isolated pleural effusions(usually in children >5 years of age) • Compression of airways due to diseased lymph nodes

CXR is useful in HIV infected children but the presentation may overlap with other HIV related diseases.

Important: TB disease should not be diagnosed from CXR alone but whole clinical picture should be taken into account.

Sputum/early morning gastric washings/induced sputum for AFB

• Expectoration: Sputum for smear microscopy is a useful test and should always be obtained in adults and older children (10 years of age) who are pulmonary TB suspects. Among younger children, especially children. 5 years of age, sputum is difficult to obtain and most children are sputum smear negative. As with adult TB suspects, two sputum specimens should be obtained: spot specimen (at first evaluation) and early morning,

• Gastric aspirates: Early morning gastric aspiration using a nasogastric feeding tube can be performed in young children who are unable or unwilling to expectorate sputum. If performed, gastric aspirates should be sent for smear microscopy and mycobacterium culture.

• Sputum induction: Training and specialized equipment are required to perform this test properly.

Key points

TB in children is usually sputum smear negative for the following reasons:

• Lung cavities are rare • Paucibacillary • Difficulty in collecting adequate amount of

sputum from young children

However the sputum smear exam (and culture) is valuable tests to perform in any child who is able to produce sputum specimen. In children unable to expectorate spontaneously, gastric wash and sputum induction are other alternatives

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3. Other tests for sample collection for AFB microscopy and culture • Fine needle aspiration(FNA) : In children with large cervical lymph nodes, fine needle

aspiration of the node offers a convenient way to collect sample for AFB microscopy (and culture if facilities are available)

• Lumbar Puncture : Specially useful in TB meningitis

4. Other tests (not recommended for the routine diagnosis of childhood TB) • Serological and nucleic acid amplification (e.g., polymerase chain reaction [PCR]) tests

which is available at the national reference laboratory and it should be considered if facilities are available)

• Computerized chest tomography and bronchoscopy

HIV testing

HIV counseling and testing is recommended for all TB patients with symptoms and/or signs of HIV-related conditions, though prevalence is very low.

4. Treatment of childhood Tuberculosis in Iraq

4.1. Objectives of anti-TB treatment • Cure the patient of TB (eliminating most of the bacilli) • Prevent death from active TB or its late effects • Prevent relapse of TB (eliminating the dormant bacilli) • Prevent the development of drug resistance (using a combination of drugs) • Decrease TB transmission to others (though it’s rare).

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4.2. Recommended Pediatric TB treatment regimens

The new drug dosages for pediatric TB treatment are shown in the following table

Table3.

TB treatment is divided into 2 phases

1. Intensive phase: The purpose of the intensive phase is to rapidly eliminate the majority of organisms and to prevent the emergence of drug resistance. This phase uses a greater number of drugs than the continuation phase. 2. Continuation phase: The purpose of the continuation phase is to eradicate the dormant organisms. Fewer drugs are generally used in this phase because the risk of acquiring drug resistance is low, as most of the organisms have already been eliminated. Given the risk of drug-induced hepatotoxicity, WHO recommends the dosages of anti tuberculosis medicines for the treatment of tuberculosis in children as inTable3 Note: Streptomycin is no longer used in first line regimens.

Drug Daily Recommended Dose Minimum Maximum

Isoniazid(H) 10mg/kg (range10-15) 300mg/day

Rifampicin(R) 15mg/kg(range10-20) 600 mg/day

Pyrazinamide(Z) 35 mg/kg(range30-40) Ethambutol(E) 20 mg/kg(range15-

25mg/kg)

Streptomycin 15mg/kg(12-15)

Drug Thrice weekly dosage Isoniazid(H) 10mg/kg(8-12)

Rifampicin(R) 10mg/kg(8-12)

Pyrazinamide(Z) 35 mg/kg(range30-40)

Ethambutol(E) 30mg/kg(20-35)

Streptomycin 15mg/kg(12-18)

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It is very important to check the weight of the child at every visit and adjust the dosage accordingly.

The following table shows the classification of patient types and treatment outcomes

Table4.

Type of patient Bacteriology Outcome of Treatment New cases Positive or Negative Previously Treated Relapse

Failure Default

+

Cured

Treatment completed

+ +

Treatment failed Defaulted

Transfer in Positive or Negative Still on Treatment Other Positive or negative Patients previously treated with unknown

treatment outcome or who have returned to treatment with smear negative PTB or bacteriological negative EPTB

Recommended treatment regimens for defined situations (based on site of disease)

Table5.

SITE OF TB DISEASE

HRZE HR

TOTAL LENGTH OF TREATMENT

TB MENINGITIS MILIARY TB BONE TB (SPINE, JOINTS)

2 MONTHS

10 MONTHS

12 MONTHS

PULMONARY TB TB LYMPHADENITIS ALL OTHER FORMS OF TB

2 MONTHS

4 MONTHS

6

MONTHS

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4.3. Management of TB meningitis, miliary TB and disseminated TB

TB meningitis and miliary TB are more common in young children and are associated with high rates of death and disability, particularly if the diagnosis is delayed. Miliary or haematogenously disseminated TB has a high risk (60–70%) of meningeal involvement and should therefore be managed similarly to TB meningitis. The child should undergo a lumbar puncture to test for the presence of meningitis. Culture for this lumber test is available at the national reference laboratory.

Children with TB meningitis or miliary TB should be hospitalized, preferably for at least the first 2 months. Corticosteroids (usually prednisone) are recommended for all children with TB meningitis in a dosage of 2 mg/kg daily for 4 weeks. The dose should then be gradually reduced (tapered) over 1–2 weeks before stopping. The dosage of prednisone can be increased to 4 mg/kg daily (maximum 60 mg/day) in the case of seriously ill children because rifampicin will decrease corticosteroid concentrations, but higher doses carry a risk of greater immune suppression. Children with suspected or confirmed osteo-articular tuberculosis should be treated for a total of12 months with the standard 4 medicine regimen, consisting of a 2 month intensive phase with the standard 4 medicine regimen (INH + RMP + PZA + EMB) and a 10 month continuation phase consisting of 2 medicines (INH + RMP). 4.4. Management of drug-resistant TB in children 4.4.1DR-TB types

1. Multidrug-resistant (MDR) TB: defined as in vitro resistance to isoniazid (INH) and rifampicin (RMP).It is caused by inadequate chemotherapy due to medical malpractice (misuse of medications) or interrupted treatment due to any cause. Drug-resistant TB is as infectious (easily transmitted to children) as drug-susceptible TB.

2. Poly-drug resistance: resistance to 2 or more drugs, but not to both INH and R. 3. Extensively drug-resistant (XDR) TB: defined as MDR-TB also resistant to fluoroquinolones

and at least one of the second-line injectable drugs. 4. New DR (primary): No previous anti-TB Rx or less than 1 month. 5. Previously Rx DR (acquired): Previous anti-TB Rx >1 month.

4.4.1.1Features in the index case suggestive of MDR TB • Index case remaining smear-positive after 3 months of treatment • History of previous TB, treatment interruption or recurrence after completion of TB Treatment • Contact with a known case of MDR TB • Child not responding to adherent standard TB treatment

Some basic principles of treatment are as follows:

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a. Initial assessment before commencing treatment i. baseline renal and liver function

ii. baseline hearing test iii. CXR

b. Do not add a drug to a failing regimen. c. Treat the child according to the drug susceptibility pattern (and using the treatment history) of

the source cases M. tuberculosis strain if an isolate from the child is not available. d. Use at least four drugs to be certain that treatment is effective. e. Use daily treatment only; directly observed therapy is essential. f. Counsel the child’s caregiver at every visit, to provide support, advice about adverse events and

the importance of compliance and completion of treatment. g. Follow-up is essential: clinical, radiological and bacteriological (mycobacterial culture for any

child who had bacteriologically confirmed disease at diagnosis). -Treatment duration depends on the extent of the disease, but in most cases will be 18 months or more (or at least 12 months after the last positive culture).

h. With correct dosing, few long-term adverse events are seen with any of the more toxic second line drugs in children, including ethionamide and the fluoroquinolones.

i. Children with MDR-TB should be treated with the first-line drugs to which their M. tuberculosis strain (or that of their source case) is susceptible including streptomycin, ethambutol and pyrazinamide.

j. Ethambutol is bactericidal at higher doses, so daily doses up to 25 mg/kg should be used in children being treated for MDR-TB.

Table6. Second line anti-TB drugs for treatment of MDR-TB in children

Drug Mode of action

Common side effects

Recommended daily dose

Ethionamide Prothionamide

bactericidal vomiting Range(mg/kg BW) Maximum GIT upset

15-20 1000

Floroquinolones Ofloxacin Levofloxacin Moxifloxacin Gatifloxacin Ciprofloxacin

bactericidal arthropathy,arthritis 15-20 7.5-10

800 -

7.5-10 - 7.5-10 - 20-30 1500

Aminoglycosides Kanamycin Capreomycin

Ototoxicity Hepatotoxicity

15-30 1000 15-30 1000

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Amikacin 15-22 1500 Cycloserine Terizidone

bacteristatic Psychiatric neurological

10-20 1000

Key points Suspect MDR-TB in any child:

• who is a contact of an adult MDR-TB case and has symptoms and signs suggestive of TB

disease. • Who remains symptomatic after completion of first-line TB treatment (with

good medication adherence).

4.4.2 Management of Child contacts of infectious MDR-TB cases The only chemoprophylaxis regimens to have been studied are based on isoniazid and, to a lesser extent, on rifampicin. Since by definition MDR-TB is resistant to both of these drugs, it is unlikely that use of these drugs to treat latent infection caused by an MDR-M. Tuberculosis strain will prevent the development of active TB disease. Close contacts of MDR-TB patients should receive careful clinical follow-up for a period of at least 2 years. If active disease develops, prompt initiation of treatment with a regimen designed to treat MDR-TB is recommended. On the basis of the currently available evidence, WHO does not recommend second-line drugs for chemoprophylaxis in MDR-TB contacts. 4.5. Management of congenital and neonatal TB Congenital tuberculosis is a very rare condition. Even though, tuberculosis (TB) among pregnant women is not uncommon, documented cases of congenital TB are conspicuous by their rarity. It is because placenta forms a protective barrier against the invasion of the fetus by the tuberculous organisms. It is assumed that the infection has been acquired in utero, the possibility of infection increases based on:

• The age of the infant, • Absence of any known contact with an open case of TB, and • Generalized dissemination of the disease.

The risk of TB in pregnancy has increased owing to recent changes in the epidemiology of the disease, which has led to an increased risk of congenital TB, although a rare disease, congenital TB should be distinguished from the more frequent acquired neonatal TB, in which the infant is infected after birth by an adult suffering from the disease.

4.5.1. Mode of Infection • Hematogenous infection via the umbilical vein • Fetal aspiration of infected amniotic fluid and • Fetal ingestion of infected amniotic fluid.

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4.5.2. Beitzki and Cantwell Diagnostic Criteria of Congenital Tuberculosis Diagnostic criteria for the diagnosis of congenital tuberculosis were laid down by Beitzki in 1935 and revised later by Cantwell in 1994.

A. Beitzki criteria: • Isolation of M. tuberculosis from the infant • Demonstration of the primary complex in the liver • In the absence of primary complex in the liver:

- Evidence of tuberculosis within days after birth. - Absence of contact with a case of tuberculosis after birth.

B. Cantwell Revised Criteria: Proven tuberculosis lesions in the infant plus one of the following:

• Lesions occurring in the first week of life • A primary hepatic complex • Maternal genital tract or placental tuberculosis • Exclusion of postnatal transmission by thorough investigation of contacts.

4.5.3. Clinical Manifestation The affected infant is frequently born premature, but signs of disease usually do not appear for several days or weeks. Below is the table showing the clinical manifestations of congenital and neonatal TB.

Table7.

Common less common Rare Respiratory distress Lethargy Poor feeding Fever Irritability Failure to thrive Abdominal distension Hepatosplenomegaly Lymphadenopathy Ear discharge

Meningitis Jaundice Progressive liver dysfunction

Otitis media, with or without Mastoiditis. Obstructive jaundice (due to glands in the porta hepatics) Papular or Postular skin lesion.

4.5.4 Investigations Congenital TB is particularly difficult to diagnose. The mothers are often apparently healthy. In one review, 24 of 32 mothers were asymptomatic, because the signs and symptoms of tuberculosis in neonates are nonspecific; they are initially attributed to other causes like prematurity, congenital viral infections or sepsis, so the diagnostic testing for tuberculosis is necessary.

A. Mantoux test is frequently negative B. Chest radiography and computed tomography show the presence of scattered infiltrates,

bronchopneumonia, consolidation or periportal hypodensity.

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C. Positive smear and / or culture results can often be obtained from gastric washings, open liver biopsy, lymph node biopsy, spinal fluid, ear discharge, endotracheal aspirate or bone marrow.

D. Newer modalities like polymerase chain reaction (PCR) are highly beneficial in the diagnosis of congenital TB.

E. Recently phage typing has been used to establish the identity of mycobacterium isolated from mother and the infant.

4.5.5. Treatment Congenital TB is a rare entity, even in human immunodeficiency virus (HIV) endemic populations, and is uniformly fatal if untreated. Treatment of the infant should begin as soon as the diagnosis is suspected without waiting for laboratory confirmation, while appropriate specimens should be obtained fast for bacteriological and histological examination. Treatment regimens should contain at least 2 and preferably 3 drugs to which the organisms are likely to be susceptible. Complete recovery has been obtained by combination of isoniazid, rifampin and pyrazinamide for 18 months with intravenous Amikacin for initial 2 months. A 6 month course of isoniazid (H), rifampicin (R), pyrazinamide (Z) and streptomycin (S) for 2 months and biweekly (R and H) for 4 months has shown good results with a relapse of only 1%, and no deaths from the disease.

If a mother is diagnosed with TB before the third trimester of pregnancy, who is taking TB medications with good adherence and is clinically well:

• Examine her baby for signs of disease. If the baby is well, no action is required. • Refer all other household children <5years of age to the TB clinic for clinical assessment.

If the mother is diagnosed with TB in the third trimester of pregnancy or shortly after delivery:

• Examine her baby for signs of disease and consider investigations if available (CXR, gastric aspirates).

• Do not give BCG (as BCG is a live vaccine, INH will kill the vaccine and prevent an effective immune response from developing).

• If the baby is well commence isoniazid (INH) prophylaxis at 10mg/kg/day and continue for 6 months.

• If the baby is not well and has signs/symptoms suggestive of TB disease, collect gastric aspirates where possible and commence full TB treatment.

Infants should have clinical assessment at 1, 3, and 6 months and regular weight checkup after starting INH therapy. If INH is started within 12 weeks of BCG vaccination, repeat BCG at the end of treatment. Table8.

Weight Isoniazid Dosage Under 2.5 kg 25 mg (1/4 tablet) 24-hourly 2.5-5 kg 50 mg (1/2 tablet) 24-hourly 5-10 kg 100 mg (1 tablet) 24-hourly

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4.5.6. Prevention of TB in a baby born to a woman diagnosed with infectious pulmonary TB Once a pregnant woman has been on treatment for at least 2–3 weeks, she is generally no longer infectious. If a pregnant woman with TB has been on treatment for TB for several weeks before delivery, it is less likely that the baby will become infected. The risk is highest if a mother is diagnosed at the time of delivery or shortly thereafter. If a pregnant woman is found to have pulmonary TB shortly before delivery, then the baby, and if possible, the placenta, should be investigated for evidence of congenital TB infection and, if found, the baby treated. A breastfeeding infant has a high risk of infection from a mother with smear-positive pulmonary TB, and has a high risk of developing TB. The infant should receive 6 months of isoniazid preventive therapy, followed by BCG immunization. Breastfeeding can be safely continued during this period. An alternative policy is to give 3 months' isoniazid, then perform a TT. If the test is negative, isoniazid should be stopped and BCG vaccination given. If the test is positive, isoniazid should be continued for another 3 months, after which it should be stopped and BCG given.

5. Contact screening and management Numerous studies have found that contact investigations are a valuable means of identifying new TB cases, and they are recommended by WHO and the International Union against Tuberculosis and Lung Disease It is recommended that the NTP should screen household contacts for symptoms of disease and offer isoniazid preventive therapy (i.e. daily isoniazid for at least 6 months) to children aged less than 5 years. As these people are at risk of infection and disease, this strategy is desirable where it is feasible. Young children living in close contact with a source case of smear-positive pulmonary TB are at particular risk of TB infection and disease .The risk of infection is greatest if the contact is close and prolonged such as the contact an infant or toddler has with a mother or other caregivers in the household. The risk of developing disease after infection is much greater for infants and young children under 5 years than it is for children aged 5 years or older. If disease does develop, it usually does so within 2 years of infection, but in infants the time-lag can be as short as a few weeks. Isoniazid preventive therapy for young children with infection who have not yet developed disease will greatly reduce the likelihood of developing TB during childhood. The main purposes of child contact screening are to: § Identify symptomatic children (i.e. children of any age with undiagnosed TB disease); § Provide preventive therapy for susceptible individuals (i.e. asymptomatic children under 5 years

of age in close contact with a smear-positive pulmonary TB case).

5.1Assessment and management Clinical assessment alone is sufficient to decide whether the contact is well or symptomatic. Routine assessment of exposed contacts may not require CXR or TT. If the contact of a source case with smear-negative pulmonary TB is symptomatic, then the diagnosis of TB needs to be investigated whatever the

Definitions used in contact screening § Source case A case of pulmonary TB (usually sputum smear-positive) which results in

infection or disease among contacts § Contacts for screening All children aged under 5 years (whether sick or well) and

children 5 years or older if symptomatic, who are in close contact with a source case § Close contact living in the same household as a source case (e.g. the child’s caregiver)

or in frequent contact with a source case

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contacts age. If the contact is asymptomatic, further investigation and follow-up will depend on national policy and practice. Recommended treatment for a healthy contact aged less than 5 years is isoniazid 5 mg/kg daily for 6 months. Follow-up should be carried out at least every 2 months until treatment is complete. Referral to a district or tertiary hospital may be necessary when there are uncertainties of diagnosis. Contacts with TB disease should be registered and treated.

Key points to remember

§ Children age <14 years & adults: any person who coughs & who was in contact with smear positive index case should have three sputum examinations .

§ If the contact of a source case with smear-negative pulmonary TB is symptomatic, then the diagnosis of TB needs to be investigated as above whatever the contacts age.

§ Any contact aged less than 5 years who has a positive tuberculin that not previously vaccinated with B.C.G with signs or symptoms of TB should be treated as suffering from active TB.

§ Those without signs or symptoms of disease should be given preventive chemotherapy.

§ Children less than one year : with mothers are being treated for smear positive pulmonary TB should be given Isoniazid if the tuberculin test is negative at the end of three months the INH may be stopped & B.C.G may be given .

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6. TB and HIV Infection

6.1Diagnosis of TB in HIV-­‐infected children The current approach to clinical diagnosis of TB in HIV-infected children is similar to that recommended for HIV-uninfected children. It is currently recommended that HIV-infected children are treated with the same TB treatment regimens and for the same duration as HIV-uninfected children in the same treatment category. Children with TB/HIV must be followed up regularly and have dosages adjusted for weight gained. HIV-infected children being treated for TB must be started on cotrimoxazole preventive therapy (CPT) and should also be started on ART within 2 weeks of commencing TB treatment, or on the same day if stable.

6.1.1Antiretroviral therapy in children with TB/HIV co-infection ART is indicated for all HIV-infected children and infants with any form of TB. Children must be followed regularly and drug doses for ART and anti-TB treatment adjusted for changes in weight.

7. Isoniazid Preventive therapy Preventive therapy is medicine (isoniazid, INH) that is given to young and vulnerable children (<5 years old or HIV-infected) who do not have TB disease at this moment, but are at high risk to develop TB disease in the near future

These children had close contact with a TB index case and are highly likely to be infected with the TB organism (a positive TT may provide proof of TB infection, but this is not essential). Target group to receive IPT Due to limited resources, preventive therapy is only given to the most vulnerable children, those at highest risk to develop TB disease in the near future.

Following documented TB exposure and/or infection, two groups of children should receive preventive therapy:

i. Young children (<5 years of age)

Key facts TB is common in HIV-infected children and HIV infection is common in children with TB in regions endemic for TB/HIV HIV-infected children are more likely to be exposed and infected with M. Tuberculosis than HIV-uninfected children HIV-infected children are at increased risk of TB disease if infected with TB and this risk is related to the degree of immune suppression

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ii. HIV-infected children (irrespective of their age)

Note: If the child contact is HIV-infected and asymptomatic, then isoniazid preventive therapy should be considered for all ages, including those 5 years and older. As with other contacts, active disease should be ruled out before providing HIV-infected children with isoniazid preventive therapy. HIV infected children who have symptoms should be carefully evaluated for TB, and if found to have TB should be referred to the NTP for registration and initiation of treatment Preventive therapy comprises of isoniazid (INH) mono-therapy for 6 months (refer dose recommendations in annex6). This is usually not given as directly observed therapy (DOTS), but poor adherence is a serious concern and parents/caregivers must be adequately counseled to explain why the medicine is given and to encourage good adherence. Parents/caregivers should also be counseled to recognize the symptoms of TB disease, such as a persistent non-remitting cough or fever, unusual fatigue or lethargy and/or weight loss, which should prompt them to bring the children back to the clinic for further evaluation. Administering treatment and ensuring adherence Children, their parents and other family members, and other caregivers should be educated about TB and the importance of completing treatment. The support of the child's parents and immediate family is vital to ensure a satisfactory outcome of treatment. Children with severe forms of TB should be hospitalized for intensive management where possible. Conditions that merit hospitalization

• TB meningitis and miliary TB, preferably for at least the first 2 months • Respiratory distress • Spinal TB • Severe adverse events like clinical signs of hepatotoxicity.

If it is not possible to ensure good adherence and treatment outcome on an outpatient basis, hospitalization is needed. Some children may require hospitalization for social or logistic reasons.

Follow-up Ideally, each child should be assessed by the NTP (or those designated by the NTP to provide treatment) at least at the following intervals: 2 weeks after treatment initiation, at the end of the intensive phase and every 2 months until treatment completion. The assessment should include:

• Symptom assessment. • Assessment of treatment adherence. • Enquiry about any adverse events and weight measurement. • Medication dosages should be adjusted to account for any weight gain. Adherence should

be assessed by reviewing the treatment card. A follow up sputum sample for smear microscopy at 2 months after treatment initiation should be obtained for any child who was smear-positive at diagnosis.

Follow-up CXRs are not routinely required in children, particularly as many children will have a slow radiological response to treatment. A child who is not responding to anti-TB treatment should be

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referred for further assessment and management. These children may have drug-resistant TB, an unusual complication of pulmonary TB, other causes of lung disease or problems with treatment adherence. The NTP is responsible for organizing treatment in line with the Stop TB Strategy, and ensuring the recording and reporting of cases and their outcomes. Good communication is necessary between the NTP and clinicians treating children with TB. Adverse events noted by clinicians should be reported to the NTP. Adherence is a serious concern and parents/caregivers must be adequately counseled to explain why the medicine is given and to encourage good adherence. Parents/caregivers should also be counseled to recognize the symptoms of TB disease, such as a persistent non-remitting cough or fever, unusual fatigue or lethargy and/or weight loss, which should prompt them to bring the child back to the clinic for further evaluation. Administering treatment and ensuring adherence Children, their parents and other family members, and other caregivers should be educated about TB and the importance of completing treatment. The support of the child's parents and immediate family is vital to ensure a satisfactory outcome of treatment. Children with severe forms of TB should be hospitalized for intensive management where possible. Conditions that merit hospitalization include:

• TB meningitis and miliary TB, preferably for at least the first 2 months. • Respiratory distress. • Spinal TB, • Severe adverse events, such as clinical signs of hepatotoxicity (e.g. jaundice).

If it is not possible to ensure good adherence and treatment outcome on an outpatient basis, some children may require hospitalization for social or logistic reasons.

8. Monitoring (Recording and Reporting) Children with TB should always be included in the routine NTP recording and reporting system. It is crucial to notify the NTP of all identified TB cases in children, register them for treatment and record their treatment outcome. At the end of the treatment course for each child with TB, the district TB officer should record the outcome in the district TB register The NTP used to record and report two age groups for children (0–4 years and 5–14 years). This has considerable advantages:

• Important in ensuring the management of childhood TB as part of routine NTP activities. • Useful in ordering drugs, since child-friendly formulations are particularly important in children

aged 0–4 years. • Important in monitoring of trends in these two distinct age groups, since children aged 0–4

years are the most vulnerable, and infection at these early ages indicates recent transmission. • Provides valuable and continuous information on market needs concerning child-friendly

formulations of anti-TB drugs. • Consistent with age groupings used in the Integrated Management of Childhood Illness (IMCI).

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8.1. Definitions of standard treatment outcomes Cured Patient: who is sputum smear-negative in the last month of treatment And on at least one previous occasion Completed treatment Patient who has completed treatment but who does not meet the criteria to be classified as cured or treatment failure. Defaulted Patient: whose treatment was interrupted for 2 consecutive months or more Died Patient who dies for any reason during the course of treatment. Treatment failure: Patient who is sputum smear-positive at 5 months or later after starting treatment. Transferred out: Patient who has been transferred to another recording and reporting unit and for whom the treatment outcome is not known. Four of the above standard outcomes are applicable to children with smear-negative pulmonary or Extra-pulmonary TB: treatment completion, default, death and transfer out. The locality TB coordinator compiles and sends the locality quarterly reports of all cases registered and their treatment outcomes to the state TB coordinator. The state TB coordinator verifies that the district reports are correct, complete and consistent, and compiles and submits a state report to the central NTP. Recording and reporting two age groups for children (0–4 years and 5–14 years) in the TB registers is useful to order anti-TB drugs (in child-friendly formulations for young children) and to monitor trends of case-finding and treatment outcomes .

9. BCG vaccination in children BCG is a live attenuated vaccine derived from M. bovis. The WHO Expanded Program on Immunization recommends BCG vaccination as soon as possible after birth in countries with a high TB prevalence. High TB-prevalence countries are those not meeting the criteria for low TB prevalence.

In all countries, children with known primary (e.g. congenital) immunodeficiency should not receive BCG vaccination. Although BCG has been given to children since the 1920s, controversies about its effectiveness in preventing TB disease among adults remain. Efficacy ranges from 0% to 80% in published studies from several areas of the world. The reasons for this variability may be multiple, including different types of BCG used in different areas, differences in the strains of M. tuberculosis in different regions, different levels of exposure and immunity to environmental mycobacterium and differences in immunization practices. However, it is generally accepted that after effective BCG vaccination there is protection against the more severe types of TB such as miliary TB and TB meningitis, which are most common in young children. The HIV pandemic has implications for BCG vaccination. The immune response to BCG vaccination may be reduced in HIV-infected individuals, and the conversion to a positive TST after BCG is less frequent in HIV-infected individuals. Although there have been several reports of disseminated BCG disease in HIV- Infected individuals, BCG appears to be safe in the vast majority of cases. It is recommended that BCG vaccination policy should depend on the prevalence of TB in a country. There is no evidence that

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revaccination with BCG affords any additional protection and therefore revaccination is not recommended. A small number of children (1–2%) develop complications following BCG vaccination. These most common BCG complications include:

- Local abscesses, - Secondary bacterial infections, - Supportive adenitis, and - Local keloid formation.

Most of these reactions will resolve over a few months. However, children who develop disseminated BCG disease should be investigated for immunodeficiency and treated for TB using a first-line regimen (except pyrazinamide, to which M. bovis is uniformly resistant). Some children with persistent localized reactions may benefit from surgical excision. Management of adverse reactions in HIV-infected children or children with other immunodeficiency is more complicated and may require specialist referral.

10. Infection control in health-care settings Measures to improve infection control in health-care settings received relatively low priority, since the introduction of short course treatment. Given the rapid sterilizing effect of rifampicin, the isolation of infectious TB patients from other hospital patients and from the community was no longer considered important. As a result, TB isolation wards were discontinued, and measures such as cough hygiene and wearing of surgical masks by infectious patients were no longer encouraged. The increasing importance of drug-resistant TB, has led to a reappraisal of the importance of infection control in health-care and other congregate settings.

10.1. Risk of transmission of tuberculosis in health-care settings Health-care workers are at much higher risk of TB infection and disease compared with the general population. In health-care settings, other non-medical staff may also be at risk through contact with infectious sources. Waiting rooms (or corridors) where patients and accompanying people, including children, wait to receive medical care are often areas of particular risk. In hospitals, the risk of transmission is relatively high, especially in pulmonary disease wards.

10.2. Infection control strategies The three levels of TB infection control are workplace and administrative (managerial) control measures, environmental control measures and personal protective equipment (respiratory protection). Each level operates at a different point in the transmission process:

10.2.1. Workplace and administrative (managerial) control measures § Infection control plan § Administrative support for procedures contained in the plan, including quality assurance; § Training of health-care and other staff; § Education of patients and increasing community awareness § Coordination and communication with the TB control programme.

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10.2.2. Environmental control measures § Ventilation (natural and mechanical) § Filtration § Ultraviolet germicidal irradiation.

Ventilation Controlled natural ventilation considerably reduces the risk of spreading M. tuberculosis. When fresh air enters a room, it dilutes the concentration of particles in room air, such as droplet nuclei containing M. tuberculosis

Filtration In small rooms with a limited number of patients or in other small, enclosed areas, room air cleaners with high efficiency particulate air (HEPA) filters may be a useful alternative to mechanical ventilation requiring structural changes. Ultraviolet germicidal irradiation M. tuberculosis is killed if the organisms are exposed to sufficient ultraviolet germicidal irradiation (UVGI). However, effectiveness depends on close contact with the UV light source and may be limited if humidity is high (over 60%) and where dust levels are high.

10.2.3. Personal protective equipment (respiratory protection) Personal respiratory protection involves training in the selection and use of respirators. Respirators should not be relied upon to protect health care workers from inhaling tubercle bacilli

11. Research Priorities in pediatric TB “While new breakthrough diagnostic tests for TB are being developed, there is a paucity of diagnostic research and of reliable diagnostic tools for TB in children. Historically, children have received a lower priority than adults in TB control efforts because they are both considered less infectious and are more difficult to diagnose.

Because their symptoms are different to the classic chronic cough of TB in adults, children usually go to a children's health service or a general clinic rather than a TB diagnostic center. The result is that many cases go undiagnosed or are diagnosed incorrectly, so that children are more likely to rapidly progress to a severe state such as TB meningitis, which has harmful long term effects and high mortality.”

The 3 main challenges that hamper the efforts to control TB are

• Ability to identify and diagnose TB due to poor availability and quality of surveillance data. • Need to prevent and control emergence and spread of drug resistant strains by improving

individual case management.

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• Need for better tuberculosis vaccine to provide a complete and long lasting protection against TB.

11.1. Childhood TB research areas • Epidemiology • Immune mechanisms • Program monitoring and evaluation. • Diagnosis • Treatment • Contact-screening and -management • Roles and responsibilities of health staff and family • BCG vaccination.

Epidemiology

§ Evaluate data already existing in some NTPs to assess how best to use these data to improve the documentation of the burden of childhood TB.

§ Determine prospectively the incidence of childhood TB in different communities making use of the diagnostic criteria in the WHO policy document (WHO, 2006b).

§ Study the annual risk of tuberculosis infection (ARTI) in children across a spectrum of communities in rural and urban areas. Describe the local transmission dynamics and circulating strains, including resistant strains. Investigational studies of the effects of malnutrition on national burden of childhood TB.

Immune mechanisms: On the background of the developing immune system in children, a combination of host, bacterial, and environmental factors contribute to the immunological responses to MTB. Research efforts understand the factors and mechanisms of immunological responses in children, particularly those aged 0 - 2 years. Program monitoring and evaluation

§ Evaluate how NTPs can ensure that the reporting and recording of childhood TB is an integral part of the routine NTP recording and reporting system.

§ Evaluate trends in case detection of childhood TB making use of data already available within some NTPs.

§ Assess NTP performance with reference to childhood TB using the standard indicators for case detection and treatment outcomes.

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Childhood TB diagnosis

§ Evaluate the use of the criteria as suggested and defined in the WHO policy document (WHO, 2006b) to suspect and diagnose childhood TB, and evaluate available new methodologies for assisting or confirming the diagnosis of TB in children.

§ Evaluate new methodologies to aid the diagnosis of M. tuberculosis infection and TB disease in children.

Treatment of childhood TB

§ Review existing literature relating to the treatment of childhood TB to establish the response to treatment and recurrence rates, and to identify already existing information regarding the pharmacokinetics of antituberculosis drugs in children.

§ Evaluate the treatment of drug-resistant TB in children and determine the most effective regimens, to support a diagnosis of M. tuberculosis infection.

§ Contact-screening and management § Explore different methodologies to ensure adherence with recommendations for

chemoprophylaxis. § Study chemoprophylaxis for the childhood contacts of adults with sputum smear negative and

smear-positive drug-resistant TB. § Assess the value of standard isoniazid prophylaxis and compare it to shorter multidrug

chemoprophylaxis in children.

Roles and responsibilities of health staff and families

§ Evaluate the availability of qualified staff and different investigations at various levels of care under different circumstances and the accuracy of the diagnosis of TB in children.

§ Study the effectiveness of a family-oriented approach to contact-tracing, and of the mobilization of family members as treatment supporters (for directly observed treatment) regarding their own child’s adherence to treatment or chemoprophylaxis (in addition to the counseling and advice that all parents or other child-careers should receive).

§ Evaluate the role of family-centered clinics and services in managing children with TB, including those with HIV co-infection.

§ Document the pathway followed to diagnose childhood TB under different epidemiological and social circumstances, and the personnel responsible for this process.

§ Document the role of the private sector in all aspects of the management of childhood TB and the extent to which existing public/private partnerships are aware of childhood TB and its particular problems

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BCG vaccination

§ Carry out a prospective evaluation of the incidence of BCG disease and the drug sensitivities of the BCG organisms for the various anti-tuberculosis agents.

§ NTPs to collaborate in the establishment of vaccine trial sites for the evaluation of new vaccines. a. Determination of the beneficial efficacy and/or the harmful effects (i.e. risk of

disseminated disease) of the BCG vaccine in HIV-infected individuals b. Increased research efforts and clinical trials to develop a more effective TB vaccine c. Enhanced research into the ‘correlates of immune protection’ for TB

12. BCG Disease Presence of axillary or regional lymph nodes in a child or infant within two years of the vaccination requires further evaluation to rule out BCG disease.

• If child is HIV infected and recently started ART, it is likely to be BCG IRIS. - If child is well and no signs of disseminated disease-no drug treatment except for

repeated needle aspiration of the large fluctuant lymph node until it resolves. - If it fails to resolve or there is disseminated disease then do a surgical resection of the

node and/or TB treatment. • If HIV status unknown, HIV testing is done.

- If uninfected and thriving-no treatment is required except for frequent needle aspiration of the fluctuant lymph node until it resolves.

- HIV infected and otherwise well, refer the patient for ART. Needle aspiration of the large fluctuant lymph node is needed.

- HIV infected and unwell – hospitalize the patient and treat for disseminated disease. These children always require TB treatment as co-infection with M. Tuberculosis may occur.

- Bacilli Calmette –Guerin (BCG) is a live attenuated vaccine given to newly

born in the deltoid muscle, in the first week of life. - BCG vaccination may sometimes cause injection site abscesses, adenitis and

very rarely disseminated disease. - HIV infected and other immunocompromised children are at a greater risk of

BCG related complications

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Annex 1. Administering, reading and interpreting a tuberculin skin test

• Prepare syringe - Check expiration date on vial and ensure vial contains tuberculin PPD-S (5 TU per 0.1

ml). - Use a single-dose tuberculin syringe with a short (¼- to ½-inch) 27-gauge needle with a

short bevel. - Fill the syringe with 0.1 ml tuberculin.

• Inject tuberculin - Insert the needle slowly, bevel up, at an angle of 5–15 °. Needle bevel should be visible

just below skin surface. • Check injection site

- After injection, a flat intradermal wheal of 8–10 mm diameter should appear. If not, repeat the injection at a site at least 5 cm (2 inches) away from the original site.

• Record information - Record all the information required by your institution for documentation (e.g. date and

time of test administration, injection site location, lot number of tuberculin). • Reading

- The results should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will probably need to be rescheduled for another TT.

- Measure diameter of induration using a clear flexible ruler - Place “0” of ruler line on the inside-left edge of the induration.

Read ruler line on the inside-right edge of the induration (use lower measurement if between two gradations on mm scale).

• Interpretation

TT interpretation depends on two factors:

- Diameter of the induration. - Person’s risk of being infected with TB and risk of progression to disease if infected. - Diameter of induration of ≥5 mm is considered positive in: - HIV-infected children - Severely malnourished children (with clinical evidence of marasmus or kwashiorkor). - Diameter of induration of ≥10 mm is considered positive in: - All other children (whether or not they have received BCG vaccination).

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Annex 2. Management of a child contact of a newly diagnosed patient with tuberculosis

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Annex3. Diagnostic Algorithm for Pediatric Pulmonary TB

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Annex 4. TB treatment categories

TB treatment category TB patients

Regimen daily or 3 times weekly Intensive phase Continuation

phase

I

1. New smear +ve patients, 2. New smear -ve with extensive

pulmonary parenchyma involvement, severe form of EPTB(other than TB meningitis)

3. Severe concomitant HIV disease or severe forms of extra-pulmonary TB.

2HRZE 4HR

II

Previously treated sputum smear +ve pulmonary TB: 1. Relapse 2. Treatment after interruption, 3. Treatment failure

2HRZES/1HRZE 5HRE

III 1. New smear -ve pulmonary TB(other

than category I) 2. Less severe forms of extra pulmonary

TB

2HRZ 4HR

IV 1. Patients in whom treatment fails even in category II are declared as category-IV patients i.e. MDR-TB.

Individualized regimens

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Annex5. Managing Patients with Interruptions in Treatment

Duration of Therapy Duration of Interruption Decision Up to 4 weeks 4-8 weeks >8 weeks

<2 weeks >2 weeks <2 weeks 2-8 weeks >8 weeks <2 weeks >2 weeks

Resume original regime Reassess and start treatment again Resume original regime Extend intensive phase by 1 more month Category II if diagnosis is still TB Resume original regime Review activity

• Continue same treatment if no active disease

• Category II therapy for active diseases

Annex 6. Dose recommendations for INH preventive therapy

Body Weight (Kg)

Isoniazid(INH) 100mg tablets

Crush the appropriate fraction and dissolve in water or multivitamin syrup

2-3.9 ¼ tab 4-9.9 ½ tab

10-19.9 1 tab 20-29.9 2 tabs

>30 3 tabs

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Annex 8. Patient referral/Transfer card

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References

1. (WHO/HTM/TB/2010.13 ) Rapid Advice, Treatment of Tuberculosis in children

2. Marks SM, et al. “Outcomes of contact investigations of infectious tuberculosis patients.” American Journal of Respiratory and Critical Care Medicine. Dec; 162(6):2033-8. 2000.

3. Loffler AM. “Pediatric tuberculosis.” Seminar in Respiratory Infections. Dec; 18(4):272-91. 2003.

4. Zar HJ et al. Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa. Archives of Disease in Childhood, 2000, 82:305–308.

5. Treating opportunistic infections among HIV-exposed and infected children. Recommendations from

CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR.

Recommendations and reports: Morbidity and Mortality Weekly Report, 2004, 53(RR- 14):1–63.

6. Guidelines for cotrimoxazole prophylaxis for HIV-related infections in children, adolescents and adults in resource-limited settings. Recommendations for a public health approach, Geneva, World Health Organization, 2006.

7. (http://emedicine.medscape.com/article/96940)

8. NTP pediatric guidelines update-2011)’

9. Treatment of Tuberculosis –Guidelines for national programs.

10. Pediatric Respiratory Reviews; Treatment of pediatric TB-revised WHO guidelines