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Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection.

Berg S, Schelling E, Hailu E, Firdessa R, Gumi B, Erenso G, Gadisa E, Mengistu A, Habtamu M, Hussein J, Kiros T, Bekele S, Mekonnen W, Derese Y, Zinsstag J, Ameni G, Gagneux S, Robertson BD, Tschopp R, Hewinson G, Yamuah L, Gordon SV, Aseffa A - BMC Infect. Dis. (2015)

Bottom Line: However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN.High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024).The study suggests a complex role for multiple interacting factors in the epidemiology of extrapulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.

View Article: PubMed Central - PubMed

Affiliation: Animal and Plant Health Agency, TB Research Group, New Haw, Addlestone, Surrey, KT15 3NB, UK. stefan.berg@apha.gsi.gov.uk.

ABSTRACT

Background: Ethiopia, a high tuberculosis (TB) burden country, reports one of the highest incidence rates of extra-pulmonary TB dominated by cervical lymphadenitis (TBLN). Infection with Mycobacterium bovis has previously been excluded as the main reason for the high rate of extrapulmonary TB in Ethiopia.

Methods: Here we examined demographic and clinical characteristics of 953 pulmonary (PTB) and 1198 TBLN patients visiting 11 health facilities in distinct geographic areas of Ethiopia. Clinical characteristics were also correlated with genotypes of the causative agent, Mycobacterium tuberculosis.

Results: No major patient or bacterial strain factor could be identified as being responsible for the high rate of TBLN, and there was no association with HIV infection. However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN. Among PTB patients, those infected with Lineage 4 reported "contact with other TB patient" more often than patients infected with Lineage 3 did (OR = 1.6, CI 95% 1.0-2.7; p = 0.064). High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). On the other hand, TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3.

Conclusions: The study suggests a complex role for multiple interacting factors in the epidemiology of extrapulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.

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Representative lineages (in percentage) ofM. tuberculosis complexstrains collected from TB lymphadenitis and pulmonary TB patients in Ethiopia (data taken from Firdessaet al. [10]). Mb,M. bovis)PTB = pulmonary TB, TBLN = tuberculous lymphadenitis.
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Fig2: Representative lineages (in percentage) ofM. tuberculosis complexstrains collected from TB lymphadenitis and pulmonary TB patients in Ethiopia (data taken from Firdessaet al. [10]). Mb,M. bovis)PTB = pulmonary TB, TBLN = tuberculous lymphadenitis.

Mentions: The M. tuberculosis complex strains that caused TB in the 954 patients have been previously reported by Firdessa et al. [12]. A summary of the lineage distribution of these strains is shown in Figure 2, stratified by TBLN and pulmonary TB cases, respectively. Here we have made use of this information to seek correlations between demographic/clinical features and lineages of M. tuberculosis. Demographic and clinical data from the 328 patients with TBLN and the 626 cases with pulmonary TB were therefore stratified by M. tuberculosis lineage. Due to low statistical power for lineages with limited isolates, only Lineage 3 and Lineage 4 were compared individually to all other lineages (Additional file 2: Table S2A and Additional file 3: Table S3A). Analysis of demographic factors among pulmonary TB patients showed a borderline statistical difference between TB contact and M. tuberculosis lineage causing the disease; patients infected with Lineage 4 reported “contact with other TB patient” more often than patients infected with Lineage 3 did (OR = 1.6, CI 95% 1.0-2.7; p = 0.064). The analogous comparison in TBLN patients showed no significant difference. Moreover, pulmonary TB patients infected with Lineage 4 strains – in contrast to Lineage 3 – tended to have a more severe manifestation (OR > 1) for a majority of the constitutional symptoms (Additional file 2: Table S2A and Additional file 3: Table S3A). Fever was the most distinct symptom in this regard and it was further enhanced when data on type of fever was included (data not shown); high fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). Corresponding data collected from the TBLN patients generated a similar but reverse result: TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3.Figure 2


Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection.

Berg S, Schelling E, Hailu E, Firdessa R, Gumi B, Erenso G, Gadisa E, Mengistu A, Habtamu M, Hussein J, Kiros T, Bekele S, Mekonnen W, Derese Y, Zinsstag J, Ameni G, Gagneux S, Robertson BD, Tschopp R, Hewinson G, Yamuah L, Gordon SV, Aseffa A - BMC Infect. Dis. (2015)

Representative lineages (in percentage) ofM. tuberculosis complexstrains collected from TB lymphadenitis and pulmonary TB patients in Ethiopia (data taken from Firdessaet al. [10]). Mb,M. bovis)PTB = pulmonary TB, TBLN = tuberculous lymphadenitis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359574&req=5

Fig2: Representative lineages (in percentage) ofM. tuberculosis complexstrains collected from TB lymphadenitis and pulmonary TB patients in Ethiopia (data taken from Firdessaet al. [10]). Mb,M. bovis)PTB = pulmonary TB, TBLN = tuberculous lymphadenitis.
Mentions: The M. tuberculosis complex strains that caused TB in the 954 patients have been previously reported by Firdessa et al. [12]. A summary of the lineage distribution of these strains is shown in Figure 2, stratified by TBLN and pulmonary TB cases, respectively. Here we have made use of this information to seek correlations between demographic/clinical features and lineages of M. tuberculosis. Demographic and clinical data from the 328 patients with TBLN and the 626 cases with pulmonary TB were therefore stratified by M. tuberculosis lineage. Due to low statistical power for lineages with limited isolates, only Lineage 3 and Lineage 4 were compared individually to all other lineages (Additional file 2: Table S2A and Additional file 3: Table S3A). Analysis of demographic factors among pulmonary TB patients showed a borderline statistical difference between TB contact and M. tuberculosis lineage causing the disease; patients infected with Lineage 4 reported “contact with other TB patient” more often than patients infected with Lineage 3 did (OR = 1.6, CI 95% 1.0-2.7; p = 0.064). The analogous comparison in TBLN patients showed no significant difference. Moreover, pulmonary TB patients infected with Lineage 4 strains – in contrast to Lineage 3 – tended to have a more severe manifestation (OR > 1) for a majority of the constitutional symptoms (Additional file 2: Table S2A and Additional file 3: Table S3A). Fever was the most distinct symptom in this regard and it was further enhanced when data on type of fever was included (data not shown); high fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). Corresponding data collected from the TBLN patients generated a similar but reverse result: TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3.Figure 2

Bottom Line: However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN.High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024).The study suggests a complex role for multiple interacting factors in the epidemiology of extrapulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.

View Article: PubMed Central - PubMed

Affiliation: Animal and Plant Health Agency, TB Research Group, New Haw, Addlestone, Surrey, KT15 3NB, UK. stefan.berg@apha.gsi.gov.uk.

ABSTRACT

Background: Ethiopia, a high tuberculosis (TB) burden country, reports one of the highest incidence rates of extra-pulmonary TB dominated by cervical lymphadenitis (TBLN). Infection with Mycobacterium bovis has previously been excluded as the main reason for the high rate of extrapulmonary TB in Ethiopia.

Methods: Here we examined demographic and clinical characteristics of 953 pulmonary (PTB) and 1198 TBLN patients visiting 11 health facilities in distinct geographic areas of Ethiopia. Clinical characteristics were also correlated with genotypes of the causative agent, Mycobacterium tuberculosis.

Results: No major patient or bacterial strain factor could be identified as being responsible for the high rate of TBLN, and there was no association with HIV infection. However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN. Among PTB patients, those infected with Lineage 4 reported "contact with other TB patient" more often than patients infected with Lineage 3 did (OR = 1.6, CI 95% 1.0-2.7; p = 0.064). High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). On the other hand, TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3.

Conclusions: The study suggests a complex role for multiple interacting factors in the epidemiology of extrapulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.

Show MeSH
Related in: MedlinePlus