A STUDY OF MAGNITUDE OF HIV INFECTION IN TUBERCULAR

CHILDREN AND THEIR CLINICAL PROFILE

Presented byDr. Virendra Gupta

Guided byDr. Jagdish Singh

SPMCHI, SMS Medical College, Jaipur

INTRODUCTION

• Tuberculosis (TB) is a leading killer among people living with human immunodeficiency virus (HIV).

• More than 33 million people now live with HIV/AIDS, out of them 2.5 million are under the age of 15yr(UNICEF report 2010)

• At least one in four deaths among people living with HIV can be attributed to TB.

• Addressing the TB and HIV epidemics are key priorities for WHO.

HIV Prevalence in Incident TB Cases 2010

• Global 23.0%

• India 5.0%

• Rajasthan 2.0%

• Sources: WHO, Global Tuberculosis Control 2011, available at http://www.who.int/tb/publications/global_report/en/index.html .

For country data, see also WHO, TB database, available at http://www.who.int/tb/country/data/download/en/index.html .

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AIMS AND OBJECTIVES

• To know the magnitude of HIV infection in

patients diagnosed with tuberculosis.

• To know the differences in clinical profile of

tuberculosis between HIV+ve and HIV-ve patients

in pediatric age group

MATERIAL AND METHODS

Study design and setting : Hospital based, observational, descriptive study.

Subjects :Patients with diagnosis of tuberculosis(as per RNTCP guidelines) attending the pediatric DOTS Center / OPD and IPD Patients of SPMCHI .

Sample size :Included 315 eligible patients from Sept. 2011 to Sept. 2012.

INCLUSION CRITERIA

• Age - 6 weeks to 15 years.

• Fulfilling the criteria for diagnosis of tuberculosis. (As per RNTCP guidelines )

• Willing to give written informed consent.

METHODS

•Detailed clinical history

•Complete general, physical and systemic examination

•Relevant investigations

•Fulfilled the criteria for diagnosis of tuberculosis were screened for HIV infection

( As Per NACO Guidelines )

NACO Guidelines to diagnose HIV

• < 18 Month-DNA PCR

• > 18 Month –

3 Different antibody test

A1- Combaid Test Kit (ELISA)

A2- SD Bioline (Immunochromatographic)

A3- Tridot Test Kit (Immunofiltration)

A1

A1 +Ve A1 -Ve(Report Negative)

A2

A1 + A2+ A1+ A2-( Report positive )

A3

A1+ A2- A3 + A1+ A2- A3 -(Indeterminate ) ( Report Negative)

3 Test kits required

STATISTICAL ANALYSIS

• Qualitative Data summarized in percentage & Quantitative data in form of mean +/- SD

• Quantitative data analyzed with parametric tests (unpaired t-test) while Qualitative data analyzed with non- parametric tests (χ2 test and z-test for difference of proportions).

RESULTS

6.98%

92.02%

Out of 315 patients, 22 were HIV positive(6.98%)

HIV +veHIV-Ve

Age and sex distribution of total TB patients

Age group MaleNo.(%)

FemaleNo.(%)

TotalNo.(%)

06wk -1 year(Infancy)

16 (05.07) 11 (03.49) 27 (08.57)

1y-5y(Pre school )

58 (18.41) 46 (14.60) 104 (33.01)

5y-10y(School going)

54 (17.14) 43 (13.65) 97 (30.79)

>10y(Adolescent)

48 (15.24) 39 (12.38) 87 (27.62)

Total 176 (55.87) 139 (44.12) 315

Age and Sex Distribution of Total TB Patient

06wk -1 year 1y-5y 5y-10y >10y0

10

20

30

40

50

60

Male To Female Ratio - 1.21:1

Male Female

No.

of

pati

en

ts

Male Female Total

Mean age 7.18 ± 4.39 Yr 7.30 ± 4.36 Yr 7.23 ± 4.35 Yr

OPD/IPD Distribution of Total TB Patient

HIV+ve Hiv-ve Total0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

16(72.73%)

78(26.62%)

94(29.84%)

6(27.27%)

215(73.38%)

221(70.16%)

IPD

OPD

Socio-Demogrphic Distribution

HIV+ve Hiv-ve Total

14(63.64%)

167(57.00%)

181(57.46%)

8(36.36%) 126

(43.00%)134

(42.54%)

Rural Urban

Distribution of tuberculosis patients according to type of

tuberculosis and HIV serostatus

Chi- square = 86.070 p-value = <0.0001

Pulmonary Disseminated/Miliary

Extra-Pulmonary

HIV+Ve 12.77 10 1.83

HIV-Ve 87.23 90 98.17

5%

25%

45%

65%

85%

18(12.77%)

1(10%) 3

(1.83%)

123(87.23%)

9(90%)

161(98.17%)

Nutritional Status of Tubercular children according to HIV

serostatus

HIV+ve HIV-ve Total54.00%56.00%58.00%60.00%62.00%64.00%66.00%68.00%70.00%72.00%

60.37%

70.69% 69.95%

Wt/Age %

Mean Wt/Age

Chi- square = 48.039 p-value = 0.038

Comparison of Symptoms profile in HIV +ve And HIV –ve Tubercular

Children

Weight loss

Pyrexia >14 Days

cough >14 Days

Loose Motion

0

10

20

30

40

50

60

70

80

90 81.81%

59.09% 59.09%

45.45%

63.48%71.33%

45.05%

10.23%

HIV +ve HIV-ve

symptom HIV +veNo.(%)

HIV-ve No.(%)

TotalNo.(%)

p-value

Weight loss

18(81.81)

186( 63.48)

206(65.39)

0.13

Pyrexia >14 Day

13(59.09)

209(71.33)

222(70.47)

0.33

cough >14 Day

13(59.09)

132(45.05 )

145(46.03)

0.29

Loose Motion

10(45.45)

30(10.23 )

40(12.70)

<0.001

Comparison of Signs in HIV +ve And HIV –ve Tubercular

Children Sign HIV +ve

NO(%)

HIV-ve

NO(%)

Total

NO(%)

p-value

Pallor 15(68.18)

182(62.12)

197(62.54)

NS

HSM 07(41.81)

45(15.35)

52(60.50)

0.04

LNP 05(27.77)

41( 13.99)

46(14.60)

0.12Pallor HSM LNP

0

10

20

30

40

50

60

7068.18%

41.81%

27.77%

62.12%

15.35% 13.99%

HIV +ve HIV-ve

HSM=Hepatospleenomegaly ,LNP= Lymphadenopathy

Comparison of Investigations in HIV+ve And HIV–ve Tubercular

Children

Radiological Le-sion

Mantoux Test BCG Scar Sputum /GA AFB

HIV+ve 68.18 40.9 7.27 0

HIV-ve 53.92 49.48 35.49 4.43

Total 54.92 48.49 38.1 4.43

5152535455565

68.18

40.9

7.270

53.9249.48

35.49

4.43

54.9248.49

38.1

4.43

%

CONCLUSION

• Magnitude of HIV sero-positivity is 6.98% in Tubercular

children.

• Co-existence of HIV is more with Pulmonary,

Disseminated & Miliary tuberculosis than Extra-

pulmonary tuberculosis.

• HIV positive children suffer more often with severe

symptoms.

RECOMMENDATIONS

• Health personnel need to recognize such

dual infection and take proper steps to

manage the epidemic.

• HIV screening should be carried out in all

tubercular children.

THANKSTHANK you

DR. VIRENDRA GUPTA

FLOW CHART

334 CASE EXCLUDED•Not Given Consent•Unwilling To Blood Sampling•Drop Out

315 CASES INCLUDED IN STUDY

649 CASE DIAGNOSED TB(As Per RNTCP Guidelines )

HIV TEST DONE(As Per NACO Guidelines)

22 case HIV +Ve 293 CASE HIV -Ve

Results are shown after statistical data applied

RESULTS

• Out of 315 patients, 22 were HIV positive(6.98%).• 57.46% were rural, Most patients were in the

school going age (43.80%).• M:F ratio was 1.21:1, Mean weight for age was

69.94%.• History of contact with tuberculosis in 47.94%.• 52.06% of cases had one or more extra-pulmonary

tubercular sites.• And 3.17% disseminated or military tuberculosis

RESULTS

• Out of 315 tubercular children, 22 were HIV positive(6.98%).

• 57.46% were rural patients

• Most patients were in the school going age (5-12yr)group (43.80%).

• Male to female ratio was 1.21:1.

• Mean weight for age was 69.94%.

• History of contact with tuberculosis in 47.94%.

• 52.06% of cases had one or more extra-pulmonary tubercular sites.

• And 3.17% disseminated or military tuberculosis

Distribution of tuberculosis patients according to type of tuberculosis.. and HIV serostatus

Type of disease HIV +Ve HIV –Ve Total

Pulmonary 18 (81.81) 123 (41.97) 141 (44.76 )

Diss.TB / Mill.TB 1 (04.55) 9 (03.07) 10 (03.17)

Extra-pulmonary

3 (13.64) 161 (54.95) 164 (52.06)

TOTAL 22 (06.98) 293 (93.02) 315(100)

P- Value < .0001

82%

4.5%

4.5%

4.5% 4.5%

HIV +Ve

Pulmonary TBMPleural effusion Lymphadenopathy(LN)Abd. Tb(ABD) other Diss.tb/Mill.

Distribution of tuberculosis patients according to type of tuberculosis and HIV serostatus

42%

28%

10%

10%6%1%3%

HIV -Ve

Signs and symptoms

HIV +ve HIV-ve Total p-value

Pyrexia >14 Day

13(59.09) 209(71.33) 222(70.47) 0.14

cough >14 Day

13(59.09) 132(45.05 ) 145(46.03) 0.07

Weight loss 18(81.81) 186( 63.48) 206(65.39) 0.04

Mean Wt/Age

60.37% 70.69% 69.95% 0.03

Lymphadenopathy

05(27.77) 41( 13.99) 46(14.60) 0.12

Hepatospleenomegaly

07(41.81) 45(15.35) 52(60.50) 0.04

Loos Motion 10(45.45) 30(10.23 ) 40(12.70) <0.0007

Comparison of clinical profile in HIV +ve And HIV –ve Tubercular Children

Wt loss Fever > 14 D

cough >14 D

H S M Loos Mo-tion

BCG Scar L. N .

HIV +ve 81.81 59.09 59.09 41.81 45.45 27.27 18.18

HIV-ve 63.48 71.33 45.05 15.35 10.23 35.49 20.13

5

15

25

35

45

55

65

75

85

%Comparison of clinical profile in HIV +ve And HIV –ve Tubercular

Children

Study the Magnitude of HIV Infection in Tubercular Children and Their Clinical ProfileABSTRACTIntroduction: Tuberculosis was noted to be the most frequent cause of death amongst people living with HIV not only in India but all over the world.Aims and objectives: To know the magnitude and differences in clinical profile of HIV infection in tubercular children.Study design and setting: Hospital based cross-sectional & descriptive study.Material & method: Study group included patients attending hospital during period Sept. 2011 to Sept. 2012, diagnosed with tuberculosis as per NACO guidelines and screened for HIV infection.Results: Out of 315 tubercular children, 22 were HIV positive giving a magnitude of 6.98%, Most patients were in the school going age (5-12yr)group (43.80%). The male to female ratio was1.21:1. Mean weight for age was 69.94%. History of contact with tuberculosis was present in 47.94%. Out of HIV positive cases Fever(81.81%),weight loss(81.81%) and weakness(81.81%) were most frequent complaints followed by cough(68.18%). Examination showed hepatosplenomegaly(41.81%) and lymphadenopathy(18.18%). Chest X-ray revealed miliary findings in 10.8%.Out of total number, 57.46% were rural patients. 52.06% of cases had one or more extra-pulmonary tubercular sites, and 03.17% disseminated or military tuberculosis. BCG vaccination was seen in only 34.92% cases. Overall Mantoux test positivity was 8.49%.Conclusion: Increasing magnitude of HIV seropositivity with positive patients more likely to suffer from pulmonary tuberculosis while HIV negative with extra pulmonary involvement. HIV-positive children suffer from prolonged symptoms. Health personnel need to recognize such dual infection and take proper steps to manage the epidemic. HIV screening should be carried out in patients with prolonged illness resistant to usual mode of treatment.Keywords: HIV, Paediatric tuberculosis, Magnitude, seropositivity

IAP GUIDELINES

RNTCP

FINAL DIAGNOSIS

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Prevalence of Human Immunodeficiency Virus Infection inChildren with Tuberculosis

T. Shahab, M.S. Zoha, M. Ashraf Malik, Abida Malik* and K. AfzalFrom the Departments of Pediatrics and Microbiology*, Jawaharlal Nehru Medical College,

AMU, Aligarh, UP 202 002, India.Correspondence to: Dr. Kamran Afzal, Department of Pediatrics, JN Medical College, Aligarh

Mulsim University, Aligarh, UP 202 002, India. E-mail: drkafzal@hotmail.comManuscript received: July 1, 2003, Initial review completed: August 14, 2003;

Revision accepted: November 28, 2003.

ABSTRECTThis prospective study was carried out in the pediatric ward and outpatient department of a tertiary care centre to estimate the prevalence of HIV seropositivity in children with tuberculosis. Two hundred and fifty consecutive children below 12 years of age with (pulmonary and Extrapulmonary) tuberculosis diagnosed between March 1999 and July 2000 were screened for HIV infection. A patient was labeled as HIV positive if two consecutive ELISA tests were found positive using different antigen/principle. Supplemental western blot test was also done. Parents ofseropositive children were also screened for HIV infection and tuberculosis. Total 5 cases were HIV positive giving a seroprevalence of 2%. All the five patients had disseminated tuberculosis. We suggest regular screening of children with disseminated/miliary tuberculosis for HIV co-infection.

SEED ARTICLE

THANKSTHANKSDR. VIRENDRA GUPTA

• “PREVALENCE OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN CHILDREN WITH TUBERCULOSIS” conducted by Shahab et al. from the AMU, UP, India,

CONCLUSION: prevalence of HIV seropositivity in children up to age of 12 year with tuberculosis are 2%(INDIAN PEDIATRICS,VOLUME 41__JUNE 17, 2004)

1-An study conducted by Hussain et al.“Seroprevalence of HIV infection among pediatric tuberculosis patients in Agra, India”: from 2003 to 2004, CONCLUSION:•Seroprevalence of HIV infection among paediatric TB patients in Agra is 8.51% (23/270).• Among the HIV-positive children with TB, 86.75% were of pulmonary and 13.04% were of extra-pulmonary type.

2-Recently published sentinel surveillance report by National AIDS Control Organization (NACO) shows an alarming HIV seroprevalence of 9.0 per cent amongst TB patients form four districts, each one in high prevalence State (12).

REVIEW OF LITERATURESeed article

Other article

                           

General InformationThe SD BIOLINE HIV-1/2 test is an immunochromatographic test for the qualitative detection of antibodies of all isotyoes (IgG, IgM, IgA) specific to HIV-1 including subtype O and HIV-2 simultaneously, in human serum, plasma or whole blood.•3rd Generation Method (Direct Sandwich Method, Ag-Ab-Ag) •Serum, Plasma, Whole Blood •Detects all antibodies including Subtype "O" •Highly sensitive, even to IgM during early infection stage •Differentiation of HIV-1 and HIV-2 by clear 3-line formation. •Sensitivity: 100%, Specificity : 99.8% •Capture Ag: HIV-1 (p24, gp41),HIV-2 (gp36)Ag •Evaluated by WHO (Sensitivity 100%, Specificty 99.3%) •Procured by WHO,UNICEF, etc. •Long shelf life: 24 months at Room Temperature

S D RAPID KIT TEST

PRINCIPLE OF THE TESTHIV antigens are immobilized on a porous immunofiltration membrane. Sample and reagents pass through the membrane and are absorbed into the underlying absorbent. As the patient's sample passes through the membrane, HIV antibodies, if present, bind to the Immobilized antigens. Conjugate binds to the Fc portion of the HIV antibodies to give distinct pinkish purple DOT against a white background. (Fig.-3)

LIMITATIONS OF THE TEST1. The kit works best when used with fresh samples. Samples which have been frozen and thawed several times contain particulates which can block the membrane, hence resulting in improper flow of reagents and high background colour which may make the interpretation of results difficult.2. Optimum test performance depends on strict adherence to the test procedure as described in this manual. Any deviation from test procedure may lead to erratic results.3. HIV-1 and HIV-2 viruses share many morphological and biological characteristics. It is likely that due to this, their antibodies have a cross reactivity of 30-70%. Appearance of test for HIV-1& /or HIV-2 antibodies on the test device does not necessarily imply co-infection from HIV-1 & HIV-2.4. Some samples show cross reactivity for HIV antibodies. Following factors are found to cause false positive HIV antibody test results: Naturally occurring antibodies, Passive immunization, Leprosy, Tuberculosis, Myco-bacterium avium, Herpes simplex, Hypergamma-globulinemia, Malignant neoplasms, Rheumatoid arthritis, Tetanus vaccination, Autoimmune diseases, Blood Transfusion, Multiple myeloma, Haemophelia, Heat treated specimens, Lipemic serum, Anti-nuclear antibodies, T-cell leukocyte antigen antibodies, Epstein Barr virus, HLA antibodies and other retroviruses.5. This is only a screening test. All samples detected reactive must be confirmed by using HIV Western Blot. Therefore for a definitive diagnosis, the patient’s clinical history, symptomatology as well as serological data, should be considered. The results should be reported only after complying with above procedure.

BI-DOT RAPID KIT TEST

NACO Guidelines to detect HIV infection in Asymptomatic individuals 3 test kit RequiredSlide 7