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HIV Infection Disrupts the Sympatric Host-Pathogen Relationship in Human TuberculosisFenner, et al. PLoS Genetics, March 2013. 9:3.

Presenter: Hina Khatri

About Mycobacterium tuberculosisObligate human pathogen6 main phylogenetic lineagesSympatric are locally adapted strainsEuro-American lineage in European patientAllopatric strains are from elsewhereEast-Asian lineage in European patient2What was already known?Studies of several invertebrate systems have shown that sympatric pathogens usually outperform allopatric pathogensHIV and TB co-infectionEffect on immune system

3Goal and strategyFind evidence of a link between HIV infection and its effects on the sympatric host-pathogen relationship of human TBUsed a population-based molecular-epidemiological study of HIV positive and HIV negative TB patients in Switzerland between 2000 and 2008

4Demographics of study518 TB patients112 HIV positive233 European117 Swiss*Sympatric: Lineage 4 (Euro-American)Allopatric: Lineages 1, 2, 3, 5 and 655Distribution of main M. tuberculosis lineages in surveyed patients

Figure 16What was hypothesized?The presence of HIV will alter the sympatric relationship of TB and the hostAllopatric TB infections will occur in a higher proportion for HIV patientsImmune suppression in HIV patients will cause this interference7Regarding M. tuberculosis transmissionTransmission was more likely for sympatric strains than allopatric strains8Impact of HIV infection on TBHIV infection was strongly associated with allopatric M. tuberculosis lineages among European patients9 patients: HIV positive and allopatric TB lineageLineages 1, 2 or 3

9Characteristics of 233 European TB patients

Table 110Level of immunosuppression caused by HIV as a factorTested if degree of immunodeficiency had an effect on the pathogen lineage present in hostMeasured nadir CD4 T cell countAssociation between HIV infection and allopatry increased when a decreased nadir CD4 T cell count was measured

11Replication on second panel of M. tuberculosis strainsOngoing population-based TB study in Canton of Bern, Switzerland between 1991-2011Proportion of HIV infection was 4.5 times higher in patients with allopatric strains than sympatric strains

12HIV status in TB patients in second panel of M. tuberculosis strains

Table 213What do these results mean?Allopatric host-pathogen relationships were associated with HIV co-infection in European born TB patientsThis association became stronger when the patient was more immunosuppressedM. tuberculosis adapts to different human populations

14Strengths of the studyReplicated panel was usedClear distinctions between allopatric lineages and sympatric lineages in European born patients15Limitations of the studySmall sample size that only included the European-born TB patientsExclusion of African and Asian patients with in-depth study

16Top 20 TB-burden countries in the world

(2012)Source: www.stopTB.org

Figure 217Further research possibilitiesAdditional studies in areas of Asia and AfricaInvestigating the impact of HIV on genetic population structure of M. tuberculosisWhat effect does HIV have on M. tuberculosis ability to be transmitted and cause disease?18Questions?19