A multi-centered cross-sectional study was carried out to examine tuberculin (Mantoux) response among household contacts of pulmonary TB (PTB) patients registered in Kota Bharu Hospital, Kelantan; Alor Setar Hospital Kedah and Institute of Respiratory Medicine, Kuala Lumpur from year 2000 through 2004

Abu Bakar, Mohd Hilmi

Ahmad, Norita

Iyawo, Kuppusamy

Joseph, Michael Stephen

Mohammad, Zahiruddin

Naing, Nyi Nyi

Salleh, Rosemi

Shaban, Hamidah

Simon, George Kutty

English

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IIIIIIIIIIA MULTI - CENTERED STUDY OF THE INFLUENCE OF HIVINFECTION ON THE TRANSMISSION OF TUBERCULOSIS TOHOUSEHOLD CONTACTS THREE STATES OF MALAYSIANyi Nyi Naing1, Zahiruddin Mohammad2, Mohd Hilmi Abu Bakar1, RosemiSaUeh3 , Norita Ahmad3, Kuppusamy Iyawo4 , Hamidah Shaban4 , GeorgeKutty SimonS, Michael Stephen Joseph 5 lUnit of Biostatistics and ResearchMethodology, School of Medical Sciences, Universiti Sains Malaysia, KubangKerian, Kelantan, Malaysia, 2Disease Control Division (AIDS/SID Section),Department of Public Health, Ministry of Health Malaysia, 3Hospital Kota Bharu,Kelantan, 4 Institute of Respiratory Medicine, Kuala Lumpur and SHospital AlorSetar, Kedah, MalaysiaAbstractA multi-centered cross-sectional study was carried out to examinetuberculin (Mantoux) response among household contacts of pulmonary TB(PTB) patients registered in Kota Bharu Hospital, Kelantan; Alor Setar HospitalKedah and Institute of Respiratory Medicine, Kuala Lumpur from year 2000through 2004. H IV status 0 f patients based on ELISA results. Information 0 nhousehold contacts was recorded during house visit. Three hundred and twentyhousehold contacts of 165 HIV-negative patients and 84 household contacts of50cases ofHIV-positive PTB patients were included. Thirty-three percent (28/84) ofhousehold contacts of HIV-positive PTB had positive tuberculin responsecompared with 52% (166/320) to HIV-negative patients. The difference,however, was not significant after performing multiple logistic regressionanalysis to adjust for variables associated with infectiousness of TB (OR=0.62,95% CI 0.35-1.10, P = 0.103). Adult contacts aged 25 - 44, having longerduration of stay with index cases and presence of positive sputum smear in theindex cases were significantly associated with tuberculin positive amonghousehold contacts. It is suggested that HIV-infected PTB patients are not moreinfectious to their household contacts than HIV-negative patients.Keywords: multi centered, pulmonary tuberculosis, HIV, household contacts,secondary transmissionAddress for correspondence: Assoc. Prof. Dr. Nyi Nyi Naing, Unit ofBiostatistics & Research Methodology, School of Medical Sciences, UniversitiSains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia; phone 609-7664899,fax 609-7653370, email drsyedhatim@yahoo.com&"3 -r1IIIIIIIIIIINTRODUCTIONAccording to the World Health Organization (WHO), one third of theworld's population is already infected with M tuberculosis which causing about3 million deaths each year (Kochi et al., 1995). The Human ImmunodeficiencyVirus (HIV) pandemic is also increasing rapidly in many communitiesworldwide; m ore than 40 million people are currently infected with 3 millionreported AIDS by year 2003 (UNAIDS, 2003). Nearly 14 million people are.expected to be infected with HIV and TB by the year 2000 (WHO, 1998). In year2000, the revised estimates of global HIVrrB burden indicated that nine percentout of total 8.3 million new TB cases in adults (15 - 49 years) and 12 percent ofthe 1.8 million deaths were attributable to HIV infection (Corbett et aI, 2003).TB is an important cause of mortality amongst the infectious diseases inMalaysia. Data from the Ministry ofHealth showed that the incidence ofTB werein the range of 60 to 65 per 100, 000 population annually for the last five years(Ministry of Health Malaysia, 2003). There were about 50,000 reported HIVinfected cases in the country until year 2003, and the trend is increasing year byyear. All TB patients have been routinely screened for HIV status in Malaysiasince 1990, and the trend ofHIV/TB continuously increased (Ministry of HealthMalaysia, 2003).Few reports have specifically investigated the rate of TB in the contactsof HIV infected tuberculous index cases. It is interesting to note that theinformation on the potential for HIV-associated TB cases to transmit Mtuberculosis and to produce a secondary increase in TB morbidity in thecommunity is relatively unknown in this region. If alterations in the TB mediatedby HIV infection result in more efficient transmission or behavioral factors resultin the exposure of more contacts, there would be a potential for an acceleratedepidemic. It is of considerable importance of public health concern to establishwhether patients with HIV-associated TB are more or less infectious than thosewithout HIV infection. The purpose of this study was to identify the influence ofHIV on the epidemiological transmission of TB to the household contacts, and todetermine whether necessary changes are required in the management of TB aswell as their contacts in light of the HIV epidemic.2IIIIIIIIIIMATERIALS AND METHODSThis cross-sectional study was conducted to compare the prevalence oftuberculosis infection between household contacts of HIV-positive and HIV-negative PTB index cases, based on a survey of the tuberculin reactivity in thehousehold contacts. The study population was represented by the TB patients andtheir household contacts attended Kota Bharu Hospital in Ke1antan (easternregion of Malaysia), Alor Star Bospital in Kedah (northern region) and Instituteof Respiratory Medicine, a tertiary TB center in Kuala Lumpur between years2000 and 2004.Required sample size determined for index cases was 50 for HIV positiveTB patients and 100 for HIV negative TB patients. For household contacts, 100for HIY positive TB patients and 200 for HIY negative TB patient. The samplesize managed to achieve was 50 HIV positive TB patients and 165 HIV negativeTB patients. For household contacts, 84 HIV positive TB patients and 320 HIYnegative TB patients were obtained. All cases of HIY positive TB cases wereincluded in the study as there were very limited cases. For HIV negative TBcases, systematic sampling was applied.After obtaining informed consent, index cases of pulmonary TB patients(PTB) with known HIY status and their respective adult household contacts aged12 years and above were selected for the study. The contacts of newly diagnosedPTB index cases were interviewed during home visits using structuredquestionnaires and records of their tuberculin (Mantoux) testing done under theTB contact managements at the clinics were traced. Those who have notundergone the test were subjected for the intradermal injection of 10 T.U in 0.1ml tuberculin solution (Tuberculin PPD RT 23 SSI, Denmark®) and the resultswere read after 72 hours to determine the size of indurations in millimeters bytwo experienced nurses at the participating chest clinics.Information on demographic data, clinical and radiological fmdings of newlydiagnosed PTB index cases were obtained from the medical records. HIV statuswas determined from the enzyme-linked irnmunosorbent assays (ELISA) test(Abbot Diagnostics, USA®) and by Particle Agglutination (PA) of Serodia ofJapan®.3IIIIIIIIIIStatistical analysisSPSS® Version 10.0 was used for data entry and analysis. Descriptive statistics and cross-tabulations were used to explore all data. Univariate analyses including Student's t test were usedto compare means of continuous variables while the chi-square test was used to detect thesignificance of association between categorical variables. For dichotomous variables with smallcell sizes, Fisher's exact test was used. The level of significance (p value) was taken at 0.05.Because M tuberculosis infection tends to aggregate within households, analyses of treat. each household contacts as an independent observation would give precise results. Therelationship between positive tuberculin responses ofhousehold contacts (with induration of;:: 10mm) and the HIV status of the index cases, and also other variables related to the index patientsincluding household setting were examined by using backword stepwise multiple logisticbinomial regressions. Simple logistic regression was applied in univariate analysis to determinepotential predictors. Variables found to be statistically significant in univariate analysis (p < 0.25)and also proven significant in other studies were included in multivariate modeling. The statisticalsignificance based on likelihood Ratio test statistics, biological plausibility, clinical importanceand variables found significant by previous studies were considered in the final model. Resultswere tabulated with crude and adjusted OR, 95% confidence intervals and p values.4IIIIIIIIIIRESULTSA total of215 index cases ofPTB cases and 404 household contacts fromthe 3 centers were recruited (Table I). There were 50 index cases ofHIV-positivePTB and 165 index cases of HIY-negative PTB together with their 84 and 320household contacts respectively who were included for the analysis.Characteristics of index PTB casesMajority of HIV-positive PTB patients were from the younger age group(78% aged 25 - 44 years) compared to HIY-negative PTB index cases (Table 2).Only one of HIY-positive PTB index cases was female while majority of themwere Malays and single. Analysis on the clinical features showed that there weresome significant differences in the TB sites and chest X-rays results betweenHIY-positive and HIY-negative index PTB cases. Higher proportion of HIV-positive PTB cases were found to be either extra-pulmonary or both types, whilechest X-rays results showed more of minimal lesions with less cavitation andnormal x-ray fmdings when compared to fmdings in HIV-negative PTB cases.Meanwhile, there was no significant differences in cough duration and sputumsmear positivity between HIV-positive and negative PTB cases. With regards tobehavioural risk of HIV infection, majority of HIV-positive PTB index casesseemed to be infected through injecting drug use.5

A Multi - Centered Study Of The Influence Of Hiv Infection On The Transmission Of Tuberculosis To Household Contacts Three States Of Malaysia.

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A Multi - Centered Study Of The Influence Of Hiv Infection On The Transmission Of Tuberculosis To Household Contacts Three States Of Malaysia.

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