Transmission Of Tuberculosis Among Household Contacts Of Multi-Drug Resistance Tuberculosis Patients In Peninsular Malaysia And Single Nucleotide Polymorphisms (Snp) Analysis For Three Candidate Genes

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dc.contributor.authorOmar Salad, Elmi
dc.date.accessioned2017-09-07T01:19:04Z
dc.date.available2017-09-07T01:19:04Z
dc.date.issued2015-02
dc.description.abstractBackground: Tuberculosis (TB) and Multi-drug Resistance Tuberculosis (MDR-TB) are a great public health threat to Malaysian national TB control program. Factors such as: socio-demographics, risk behaviour, co-morbidities and host genetic factors have been associated with development of MDR-TB and increased the incidence of TB transmission in Malaysia. Data on these phenomena is highly limited in this country. Objectives: The study was aimed to assess the burden, risk factors associated with MDR-TB and the treatment outcomes between MDR-TB and non-MDR-TB cases. This study also determined the prevalence of LTBI, effects of HIV on secondary transmission among household contacts of MDR-TB and agreement between QFT-G and TST test. It also explored the presence of SNP, allele frequency, and haplotype analysis of MCP-1, CCR2 and CD209 genes among household contacts of MDR-TB cases. Methods: Phase I, part one was a retrospective study conducted among all registered MDR-TB patients at five referral TB hospitals in Peninsular Malaysia. Phase I part two was a cross-sectional study conducted among household contacts of MDR-TB cases to detect the LTBI prevalence. In Phase II, cross-sectional study was conducted among household contacts of MDR-TB cases. Genomic DNA was extracted from household contacts for identifying genetic variations using PCR and RFLP for (PVUII) and FokI. Results: The main risk factors associated with MDR-TB were; previous TB treatment (AOR, 3.27; 95% CI: 1.80,5.94; P= 0.001), HIV Infection status (AOR, 0.22; 95% CI: 0.08, 0.61; P= 0.004), Immigrants status (AOR, 5.97: 95% CI: 2.73, 13. 08; P=0.001) and high load of positive for AFB smear (AOR, 7.04; 95% CI: 3.16, 15. 70; P= 0.001). A significant difference (P>0.001) were observed in the treatment success rate between MDR-TB and non-MDR TB patients. The overall prevalence of LTBI by QFT-G test 45% (95%CI % 51.9% and 75.3%). The agreement between two tests were relatively poor k = 0.236 95% CI (20.8%, 43.6%, P= 0.044). The MCP-1 and CCR2 genes were significantly associated with risk of TB (OR 3.16: CI 95% (1.22-8.15): (P= 0.015)) and (OR: 3.42: CI95%: (1.29-9.03) (P=0.011) respectively)). The study found significant difference in haplotype analysis and two SNP in the LD block strongly associated (r2 > 0.8). Conclusions: The findings revealed that patients who had previous TB treatment, HIV infection status, immigrants’ status and high load of positive for AFB smear were more likely to have MDR-TB. Poor treatment outcome was observed in MDRTB cases compared to non-MDR-TB. This study observed high prevalence of LTBI among household contacts of MDR-TB.The test agreement between QFT-G and TST were relatively poor. The findings of this study revealed that presence of the G allele may be associated with risk of developing active TB among LTBI individuals on MCP-1 -2518 A/G and CCR2 A/G genes. This study found significant association between haplotype analysis.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/4503
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectTransmission of Tuberculosisen_US
dc.subjecthousehold contacts MDR-TB, SNP analysis.en_US
dc.titleTransmission Of Tuberculosis Among Household Contacts Of Multi-Drug Resistance Tuberculosis Patients In Peninsular Malaysia And Single Nucleotide Polymorphisms (Snp) Analysis For Three Candidate Genesen_US
dc.typeThesisen_US
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