HIV Infection Disrupts the Sympatric HostPathogen Relationship in Human Tuberculosis

Fenner, et al. PLoS Genetics,

March 2013. 9:3.
Presenter: Hina Khatri

About Mycobacterium tuberculosis

Obligate human pathogen
6 main phylogenetic lineages
Sympatric are locally adapted strains
Euro-American lineage in European patient

Allopatric strains are from elsewhere

East-Asian lineage in European patient

What was already known?

Studies of several invertebrate systems have
shown that sympatric pathogens usually
outperform allopatric pathogens
HIV and TB co-infection
Effect on immune system

Goal and strategy

Find evidence of a link between HIV infection
and its effects on the sympatric host-pathogen
relationship of human TB
Used a population-based molecularepidemiological study of HIV positive and HIV
negative TB patients in Switzerland between
2000 and 2008

Demographics of study
518 TB patients
112 HIV positive
233 European
117 Swiss*

Sympatric: Lineage 4 (Euro-American)

Allopatric: Lineages 1, 2, 3, 5 and 6

Distribution of main M. tuberculosis

lineages in surveyed patients

Figure 1

What was hypothesized?

The presence of HIV will alter the sympatric
relationship of TB and the host
Allopatric TB infections will occur in a higher
proportion for HIV patients
Immune suppression in HIV patients will cause
this interference

Regarding M. tuberculosis transmission

Transmission was more likely for sympatric
strains than allopatric strains

Impact of HIV infection on TB

HIV infection was strongly associated with
allopatric M. tuberculosis lineages among
European patients
9 patients: HIV positive and allopatric TB lineage
Lineages 1, 2 or 3

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Characteristics of 233 European TB patients

Table 1

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Level of immunosuppression caused by HIV

as a factor
Tested if degree of immunodeficiency had an
effect on the pathogen lineage present in host
Measured nadir CD4 T cell count

Association between HIV infection and allopatry

increased when a decreased nadir CD4 T cell
count was measured

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Replication on second panel of M.

tuberculosis strains
Ongoing population-based TB study in Canton of
Bern, Switzerland between 1991-2011
Proportion of HIV infection was 4.5 times higher
in patients with allopatric strains than sympatric
strains

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HIV status in TB patients in second panel of

M. tuberculosis strains

Table 2

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What do these results mean?

Allopatric host-pathogen relationships were
associated with HIV co-infection in European
born TB patients
This association became stronger when the patient
was more immunosuppressed

M. tuberculosis adapts to different human

populations

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Strengths of the study

Replicated panel was used
Clear distinctions between allopatric lineages
and sympatric lineages in European born
patients

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Limitations of the study

Small sample size that only included the
European-born TB patients
Exclusion of African and Asian patients with indepth study

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Top 20 TB-burden countries in the world

(2012)
Source:
www.stopTB.org

Figure 2

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Further research possibilities

Additional studies in areas of Asia and Africa
Investigating the impact of HIV on genetic
population structure of M. tuberculosis
What effect does HIV have on M. tuberculosis
ability to be transmitted and cause disease?

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Questions?