JOURNAL CLUBJOURNAL CLUB

Moderator-Dr NATESH Moderator-Dr NATESH

Management of Pediatric Management of Pediatric Tuberculosis under the Tuberculosis under the Revised National Revised National Tuberculosis Control Tuberculosis Control Program (RNTCP)Program (RNTCP)

"A joint statement of the Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare, and experts from Indian Academy of Pediatrics"

INTRODUCTIONINTRODUCTION

• 10% of total TB caseload is found 10% of total TB caseload is found amongst children.amongst children.

• The actual Global estimates of 1.5 million The actual Global estimates of 1.5 million new cases and 130,000 deaths due to TB new cases and 130,000 deaths due to TB per year amongst children is reported.per year amongst children is reported.

Childhood TB prevalence Childhood TB prevalence indicates:indicates:

• • community prevalence of sputum smear-community prevalence of sputum smear-positive pulmonary tuberculosis (PTB) positive pulmonary tuberculosis (PTB)

• age-related prevalence of sputum smear-age-related prevalence of sputum smear-positive PTB positive PTB

• prevalence of childhood risk factors for prevalence of childhood risk factors for diseasedisease

• childhood TB is accorded low priority by childhood TB is accorded low priority by National TB Control programs. Probable National TB Control programs. Probable reasons include:reasons include:

• Diagnostic difficultiesDiagnostic difficulties• Rarely infectiousRarely infectious• Limited resources Limited resources • Misplaced faith in BCGMisplaced faith in BCG• Lack of data on treatmentLack of data on treatment

• Children can present with TB at any age, but the Children can present with TB at any age, but the majority of cases present between 1 and 4 majority of cases present between 1 and 4 years.years.

• Disease usually develops within one year of Disease usually develops within one year of infection - the younger, the earlier and the more infection - the younger, the earlier and the more disseminated.disseminated.

• PTB is usually smear-negative.PTB is usually smear-negative.• PTB to extra-pulmonary TB (EPTB) ratio is PTB to extra-pulmonary TB (EPTB) ratio is

usually around 1:3 usually around 1:3

• The PTB prevalence is normally low The PTB prevalence is normally low between the ages of 5 and 12 years, and between the ages of 5 and 12 years, and then increases in adolescence when PTB then increases in adolescence when PTB manifests like adult PTB (post primary manifests like adult PTB (post primary tuberculosis).tuberculosis).

Revised National TB Control Revised National TB Control Program Program • India has had a National Tuberculosis Program India has had a National Tuberculosis Program

(NTP) in operation since 1962.(NTP) in operation since 1962.

• In 1992, a joint Government of India/World In 1992, a joint Government of India/World Health Organisation review found that despite Health Organisation review found that despite the existence of the NTP, TB patients were not the existence of the NTP, TB patients were not being accurately diagnosed and that the majority being accurately diagnosed and that the majority of diagnosed patients did not complete of diagnosed patients did not complete treatment.treatment.

•

• Based on the recommendations of the Based on the recommendations of the review, the Revised National review, the Revised National Tuberculosis Control Program Tuberculosis Control Program (RNTCP), incorporating the (RNTCP), incorporating the internationally recommended DOTS internationally recommended DOTS strategy, was developed. strategy, was developed.

• In 2002, of the 2,45,051 new smear positive PTB In 2002, of the 2,45,051 new smear positive PTB cases initiated on treatment under RNTCP, cases initiated on treatment under RNTCP, 4,159 (1.7%) were aged 0-14 years. 4,159 (1.7%) were aged 0-14 years.

• From a survey of RNTCP implementing districts, From a survey of RNTCP implementing districts, Pediatric cases were seen to make up 3% of the Pediatric cases were seen to make up 3% of the total load of new cases registered under total load of new cases registered under RNTCP. RNTCP.

• Lymph node (LN) TB cases predominated Lymph node (LN) TB cases predominated (>75%) amongst the paediatric EPTB cases (>75%) amongst the paediatric EPTB cases registered under RNTCP. registered under RNTCP.

• An almost equivalent number of Pediatric TB An almost equivalent number of Pediatric TB cases were being diagnosed in the same cases were being diagnosed in the same health facilities, but were not being registered health facilities, but were not being registered under RNTCP. under RNTCP.

• Of those Pediatric cases treated under Of those Pediatric cases treated under RNTCP, cure and completion rates were both RNTCP, cure and completion rates were both above 90%. above 90%.

• Comparative figures for those cases not Comparative figures for those cases not treated under RNTCP were 80% and 70%, treated under RNTCP were 80% and 70%, with default rates between 27-33%. (Central with default rates between 27-33%. (Central TB Division.). TB Division.).

• Hence for RNTCP, there are the issues of Hence for RNTCP, there are the issues of under diagnosis and under registration of under diagnosis and under registration of Pediatric TB cases in the program.Pediatric TB cases in the program.

• To seek consensus on improved case To seek consensus on improved case detection and improved treatment outcomes detection and improved treatment outcomes for all diagnosed pediatric TB cases, a for all diagnosed pediatric TB cases, a workshop on the "Formulation of guidelines workshop on the "Formulation of guidelines for diagnosis and treatment of Pediatric TB for diagnosis and treatment of Pediatric TB cases under RNTCP" was held in New Delhi cases under RNTCP" was held in New Delhi on 6th and 7th August 2003.on 6th and 7th August 2003.

• In attendance were National and In attendance were National and International Pediatricians, TB experts and International Pediatricians, TB experts and TB Control Program Managers.TB Control Program Managers.

Symptoms Descriptor Exclusions Specific points

Fever

Recent onset of persistent fever >3 weeks Fever can be of any type in a child with TB

Recurrent fever 

Fever should be documented as far as possible.

CoughRecent onset of cough withfever is significant

Recurrent / episodiccough without fever

Recurrent cough / fever with interveningnormal periodis often due to diseases other than TB

Unexplainedrecent loss ofweight / appetite

Recent onset of symptomsare relevant

More relevant in infancyNonspecific symptoms due to many organic or functional disorders

Contact history 

Any adult taking anti-TB treatment currentlyor in the past 2 years

Younger the child more important is household contact survey

Risk factors     

Age <1 year / failure to thrive / recent measles orwhooping cough / immunocompormized state /steroid therapy 

In suspicious clinical settings, presence of risk factors increase the probability of disease.Enlarged superficial lymphonodes must be looked for.Therapeutic trial of anti-TB drugs is not recommended.

• Diagnosis to be based on a combination of Diagnosis to be based on a combination of clinical presentation, sputum examination clinical presentation, sputum examination wherever possible, Chest X-ray (PA view), wherever possible, Chest X-ray (PA view), Mantoux test (1 TU PPD RT23 with Tween Mantoux test (1 TU PPD RT23 with Tween 80, positive if induration >10mm after 48-80, positive if induration >10mm after 48-72 hours) and history of contact.72 hours) and history of contact.

• Diagnosis of TB in children should be Diagnosis of TB in children should be made by a Medical Officer. made by a Medical Officer.

• Where diagnostic difficulties are faced, Where diagnostic difficulties are faced, referral of the child should be made to a referral of the child should be made to a Pediatrician for further management. The Pediatrician for further management. The existing RNTCP case definitions will be existing RNTCP case definitions will be used for all cases diagnosedused for all cases diagnosed

Test Technique Interpretation Specific points

Mantoux test     

1 TU PPD RT 23 with Tween 80intradermally Read after 48-72 hours (may be up-to 7 days if +ve) 

Induration of 10 mm or more in largest diameter is highly suggestiveof natural infection irrespective ofBCG vaccine status.

Induration of 6 mms or more thanprevious test results is suggestiveof natural infection.

A MT positive in a child less than 2 years of age is highly suggestive of recent infection and must betreated. Beyond 2 years of age, a positive MT alongwith history of contact, symptoms and signs and presence of risk factors increase the risk of thedisease. In case of doubtful or inconclusive testresults, repeat test is required.

Repeat MTPreferably on other forearm

   

BCG Test – – BCG test is of no value & not recommended

Radiology      

X-ray Chest

Ideal X-ray Chest is taken in uprightposition PA view Well centered good exposed mid-inspiratory film is ideal. Lateral viewis useful in case of suspicion    

The following radiological patternsstrongly suggest a lesion diagnosticof TB:1. Miliary lesion2. Unilateral Pleural effusion3. Fibrocaseous cavitatory lesions4. Pneumonia with enlarged media- stinal lymph nodes.5. Persistent pneumonia in a symptomatic child inspite of antibiotic therapy.

Radiological lesions do not indicate etiology.         

Repeat X-ray Chest    

Deterioration or absence of clinicalImprovement ORIn presence of good clinicalimprovementIn every child.

After 2-3 weeks of treatment  At the end of intensive phase- 2 monthsof treatmentat the end of successful treatment.

CT Scan ChestHigh resolution CT Scan is preferred

Caseating & matted Lymph nodes onCT Scan

Routine CT Scan Chest is not recommended

Bacteriology  

Sputum or gastric lavage is examinedMultiple samples should be examinedBactec method

Positive yeild in 30-40% of the patientsIncreases yeildNewer methods offer results in 7-10 days. No increase in the yeild

GOLD standard & must be attempted in all patients Costly and not available easily

PCR   

Some studies suggest use of two probesPCR in Pulmonary TB & in gastricaspiratePCR in CSF & Pleural fluid

Result depends on the type of gene-ration of probe used.Low sensitivity - as low as 20% High sensitivity & specificity

Routine use of PCR not recommended   May be useful in Neurotuberculosis

Serology 

Commercially available tests at presentare not ideal

Variable factors in host, mycobacterium & environment makes interpretationof these tests difficult

Serology is not recommended in childhood TB 

CBC/ESR –These are nonspecific indicators ofinflammation

They have no value in diagnosis or follow up of childhood TB

  

• Mantoux test:Mantoux test:

Test may be repeated few Test may be repeated few weeks or months after the first test. weeks or months after the first test. Induration of 6mm or more than Induration of 6mm or more than previous test results may be previous test results may be suggestive of natural infection. suggestive of natural infection.

• SSmear positive TB-mear positive TB-At least two At least two initial sputum smears initial sputum smears positive for positive for AFB OR AFB positive smear &one AFB OR AFB positive smear &one positive culture.positive culture.

• Smear negative TB-Smear negative TB- At least three At least three negative smears, but TB suggestive negative smears, but TB suggestive symptoms & x-ray abnormalities symptoms & x-ray abnormalities OR positive culture.OR positive culture.

Definitions

DefinitionsDefinitions

• New caseNew case. A patient with sputum positive . A patient with sputum positive PTB who has never had treatment for TB PTB who has never had treatment for TB or who has taken antituberculosis drugs or who has taken antituberculosis drugs for less than 1 month.for less than 1 month.

• RelapseRelapse. A patient previously treated for . A patient previously treated for TB who has been declared cured or TB who has been declared cured or treatment completed, and is diagnosed treatment completed, and is diagnosed with bacteriologically positive (smear or with bacteriologically positive (smear or culture) tuberculosis.culture) tuberculosis.

DefinitionsDefinitions

• Treatment failure. Treatment failure. A patient who was A patient who was initially smear positive ,who began initially smear positive ,who began treatment & who remained Or became treatment & who remained Or became smear positive again at five months or smear positive again at five months or later during course of treatment. later during course of treatment.

• Treatment after default. Treatment after default. A patient who A patient who returns to treatment, positive returns to treatment, positive bacteriologically, following interruption of bacteriologically, following interruption of treatment for 2 months or moretreatment for 2 months or more

• Cure Cure Patient who is sputum smear-Patient who is sputum smear-negative in thenegative in the

last month of treatment and on at last month of treatment and on at least one previous occasion.least one previous occasion.

• Treatment completedTreatment completed Patient who Patient who has completed treatment but who has completed treatment but who does not meet the criteria to be does not meet the criteria to be classified as a cure or a failure.classified as a cure or a failure.

• CONTACT –defined as any child who CONTACT –defined as any child who lives in a house hold with an adult lives in a house hold with an adult taking anti-TB therapy or has taken taking anti-TB therapy or has taken such a therapy in the past 2yrs.such a therapy in the past 2yrs.

   TB treatment regimens

Category oftreatment

Type of patientsIntensive phase

Continuation phase

Category I 

• New sputum smear-positive PTB• Seriously ill* sputum smear-negative PTB• Seriously ill extra-pulmonary TB

2 H3R3Z3E3***

 

4 H3R3

 

Category II 

• Sputum smear-positive relapse• Sputum smear-positive treatment failure.•Sputum smear-positive treatment after default.

2 S3H3R3Z3E3

/1H3R3Z3E3

5 H3R3E3

 

Category III

• Sputum smear-negative and Extra-pulmonary TB, not seriously ill**

2 H3R3Z3 4 H3R3

• *Seriously ill sputum smear-negative PTB *Seriously ill sputum smear-negative PTB includes all forms of PTB other than primary includes all forms of PTB other than primary complex; complex;

• seriously ill EPTB includes TB meningitis (TBM), seriously ill EPTB includes TB meningitis (TBM), disseminated/miliary TB, TB pericarditis, TB disseminated/miliary TB, TB pericarditis, TB peritonitis and intestinal TB, bilateral or peritonitis and intestinal TB, bilateral or extensive pleurisy, spinal TB with or without extensive pleurisy, spinal TB with or without neurological complications, genito-urinary tract neurological complications, genito-urinary tract TB, bone and joint TB. **TB, bone and joint TB. **

• Not-seriously ill EPTB includes lymph Not-seriously ill EPTB includes lymph

node TB and unilateral pleural effusion. node TB and unilateral pleural effusion.

***Prefix indicates month and subscript ***Prefix indicates month and subscript

indicates thrice weekly.indicates thrice weekly.

• In patients with TBM on Category I treatment, In patients with TBM on Category I treatment, the four drugs used during the intensive phase the four drugs used during the intensive phase should be HRZS or HRZE.should be HRZS or HRZE.

• Continuation phase of treatment in TBM and Continuation phase of treatment in TBM and spinal TB with neurological complications should spinal TB with neurological complications should be given for 6-7 months, extending the total be given for 6-7 months, extending the total duration of treatment to 8-9 monthsduration of treatment to 8-9 months

• Steroids should be used initially in Steroids should be used initially in hospitalised cases of TBM and TB hospitalised cases of TBM and TB pericarditis and reduced gradually over 6-8 pericarditis and reduced gradually over 6-8 weeks. weeks.

• In all instances before starting a child on In all instances before starting a child on Category II treatment, s/he should be Category II treatment, s/he should be examined by a Pediatrician or TB expert, examined by a Pediatrician or TB expert, wherever available. wherever available.

• To assist in calculating required dosages To assist in calculating required dosages and administration of anti-TB drugs for and administration of anti-TB drugs for children, the medication should be made children, the medication should be made available in the form of combipacks in available in the form of combipacks in patient wise-boxes, linked to the child’s patient wise-boxes, linked to the child’s weightweight

Chemo prophylaxis Chemo prophylaxis

• Asymptomatic children under 6 years of Asymptomatic children under 6 years of age, exposed to an adult with infectious age, exposed to an adult with infectious (smear-positive) tuberculosis, from the (smear-positive) tuberculosis, from the same household, will be given 6 months of same household, will be given 6 months of isoniazid (5 mg per kg daily) isoniazid (5 mg per kg daily) chemoprophylaxis. chemoprophylaxis.

4. Monitoring and evaluation4. Monitoring and evaluation

• Pediatric-focused monitoring may preferably be an Pediatric-focused monitoring may preferably be an integral part of the program.integral part of the program.

• Wherever possible, follow-up sputum examination is Wherever possible, follow-up sputum examination is to be performed with the same frequency as in to be performed with the same frequency as in adults. adults.

• Clinical or symptomatic improvement is to be Clinical or symptomatic improvement is to be assessed at the end of the intensive phase of assessed at the end of the intensive phase of treatment and at the end of treatmenttreatment and at the end of treatment

• Improvement should be judged by absence of fever Improvement should be judged by absence of fever or cough, a decrease in the size of lymph node(s), or cough, a decrease in the size of lymph node(s), weight gain. weight gain.

• A review of the RNTCP existing treatment card A review of the RNTCP existing treatment card will be undertaken as the collecting of additional will be undertaken as the collecting of additional information in relation to Pediatric TB patients, information in relation to Pediatric TB patients, such as the basis for starting treatment along such as the basis for starting treatment along with categorization, documentation of clinical with categorization, documentation of clinical and radiological monitoring is required. and radiological monitoring is required.

• Until this review is completed, the remarks Until this review is completed, the remarks section in the current card should be used to section in the current card should be used to document diagnostic and clinical data as document diagnostic and clinical data as needed. needed.

• Also there will be an evaluation of the Also there will be an evaluation of the need for modification in other RNTCP need for modification in other RNTCP formats and registers to facilitate drug formats and registers to facilitate drug ordering of pediatric formulations and ordering of pediatric formulations and potential analyses of data by age groups.potential analyses of data by age groups.

General issuesGeneral issues

• A revision of the RNTCP training modules will be A revision of the RNTCP training modules will be undertaken to include Pediatric TB issues.undertaken to include Pediatric TB issues.

• District TB Control Societies should include District TB Control Societies should include representatives from the local bodies of representatives from the local bodies of Pediatricians. Pediatricians.

• In coordination with the Indian Academy of In coordination with the Indian Academy of Pediatrics (IAP), RNTCP should organize Pediatrics (IAP), RNTCP should organize sensitization of Pediatricians regarding the sensitization of Pediatricians regarding the programprogram

Operational research issuesOperational research issues

• Identified operational research should be Identified operational research should be prioritised and conducted. prioritised and conducted.

• Topics include: development of, and Topics include: development of, and implementation of a multicentric field evaluation of implementation of a multicentric field evaluation of a Pediatric TB diagnostic scoring system; a Pediatric TB diagnostic scoring system;

• feasibility of using mothers as DOT providers for feasibility of using mothers as DOT providers for children with TB; children with TB;

• examination of the Pediatric TB case yield if the examination of the Pediatric TB case yield if the children who have a history of contact with smear children who have a history of contact with smear negative patients are additionally screened. negative patients are additionally screened.

• THANK YOUTHANK YOU

• In 1993, RNTCP was started in pilot areas In 1993, RNTCP was started in pilot areas covering a population of 18 million. Large-covering a population of 18 million. Large-scale implementation of the RNTCP began scale implementation of the RNTCP began in 1998, with a World Bank credit of Rs in 1998, with a World Bank credit of Rs 604 crore. 604 crore.

• Since 1998, the RNTCP has been rapidly Since 1998, the RNTCP has been rapidly expanding and to date covers over 740 million expanding and to date covers over 740 million of the population.of the population.

• RNTCP is the fastest expanding TB control RNTCP is the fastest expanding TB control program in the history of DOTS, and nation-program in the history of DOTS, and nation-wide coverage is planned by 2005. wide coverage is planned by 2005.

• In 2002, over 6.2 lakh patients were initiated In 2002, over 6.2 lakh patients were initiated on treatment under RNTCP. Of these, almost on treatment under RNTCP. Of these, almost 2.5 lakh were infectious new sputum smear 2.5 lakh were infectious new sputum smear positive pulmonary TB.positive pulmonary TB.

• Over 70,000 patients are now being placed Over 70,000 patients are now being placed on treatment each month. on treatment each month.