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Open Access Highly Accessed Research article

Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania

Ruth Stavrum1*, George PrayGod2, Nyagosya Range3, Daniel Faurholt-Jepsen4, Kidola Jeremiah2, Maria Faurholt-Jepsen4, Henrik Krarup5, Martine G Aabye6, John Changalucha2, Henrik Friis4, Aase B Andersen7 and Harleen MS Grewal18

Author Affiliations

1 Department of Clinical Science, Infection, Faculty of Medicine and Dentristry, University of Bergen, Bergen, Norway

2 Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

3 Muhimbili Research Centre, National Institute for Medical Research, Dar Es Salaam, Tanzania

4 Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark

5 Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

6 Clinical Research Centre, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark

7 Department of Infectious Diseases, Odense University Hospital, Odense, Denmark

8 Department of Microbiology, Haukeland University Hospital, Bergen, Norway

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BMC Infectious Diseases 2014, 14:309  doi:10.1186/1471-2334-14-309

Published: 5 June 2014

Abstract

Background

There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages.

Methods

Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients’ level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M. tuberculosis lineage of the infectious agent for each patient.

Results

The most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST’s out of 248 isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the ‘modern’ (TbD1-) Euro-American lineage induced higher levels of α1-acid glycoprotein (β = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (β = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (β = -1.0, P = 0.04; 95% CI[-1.89 – (-0.03)]). LAM11_ZWE (‘modern’) isolates induced higher levels of CRP (β = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (β = 0.9, P = 0.03; 95% CI[0.09-1.70]).

Conclusion

The low diversity of genotypes may be explained by an evolutionary advantage of the most common lineages over other lineages combined with optimal conditions for transmission, such as overcrowding and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by ‘modern’ lineage isolates compared to ‘ancient’ lineages may suggest increased virulence among ‘modern’ lineage isolates.