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author:("hail, Elena")
1.  Transmission of Mycobacterium tuberculosis between Farmers and Cattle in Central Ethiopia 
PLoS ONE  2013;8(10):e76891.
Background
Transmission of Mycobacterium tuberculosis (M. tuberculosis) complex could be possible between farmers and their cattle in Ethiopia.
Methodology/Principal Findings
A study was conducted in mixed type multi-purposes cattle raising region of Ethiopia on 287 households (146 households with case of pulmonary tuberculosis (TB) and 141 free of TB) and 287 herds consisting of 2,033 cattle belonging to these households to evaluate transmission of TB between cattle and farmers. Interview, bacteriological examinations and molecular typing were used for human subjects while comparative intradermal tuberculin (CIDT) test, post mortem and bacteriological examinations, and molecular typing were used for animal studies. Herd prevalence of CIDT reactors was 9.4% and was higher (p<0.01) in herds owned by households with TB than in herds owned by TB free households. Animal prevalence was 1.8% and also higher (p<0.01) in cattle owned by households with TB case than in those owned by TB free households. All mycobacteria (141) isolated from farmers were M. tuberculosis, while only five of the 16 isolates from cattle were members of the M. tuberculosis complex (MTC) while the remaining 11 were members of non-tuberculosis mycobacteria (NTM). Further speciation of the five MTC isolates showed that three of the isolates were M. bovis (strain SB1176), while the remaining two were M. tuberculosis strains (SIT149 and SIT53). Pathology scoring method described by “Vordermeier et al. (2002)” was applied and the average severity of pathology in two cattle infected with M. bovis, in 11 infected with NTM and two infected with M. tuberculosis were 5.5, 2.1 and 0.5, respectively.
Conclusions/Significance
The results showed that transmission of TB from farmers to cattle by the airborne route sensitizes the cows but rarely leads to TB. Similarly, low transmission of M. bovis between farmers and their cattle was found, suggesting requirement of ingestion of contaminated milk from cows with tuberculous mastitis.
doi:10.1371/journal.pone.0076891
PMCID: PMC3794923  PMID: 24130804
2.  Population-based prevalence survey of tuberculosis in the Tigray region of Ethiopia 
BMC Infectious Diseases  2013;13:448.
Background
Population based prevalence survey is an important epidemiological index to measure the burden of tuberculosis (TB) disease and monitor progress towards TB control in high burden countries like Ethiopia. This study was aimed to estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) in the Tigray region of Ethiopia.
Methods
Sixteen rural and urban villages were randomly selected in a stratified multistage cluster sampling. Individuals aged 15 years and older were screened by symptom inquiry for PTB. Those individuals who were symptomatic of PTB provided two sputum samples for smear microscopy, culture and molecular typing.
Results
The study covering 4,765 households screened a total of 12,175 individuals aged 15 years and above. The overall weighted prevalence of bacteriologically confirmed PTB in the Tigray region of Ethiopia was found to be 216/100,000 (95% CI: 202.08, 230.76) while the weighted prevalence of smear-positive PTB was 169/100,000 (95% CI: 155.53, 181.60). The prevalence of bacteriologically confirmed TB was higher amongst males (352/100 000; 95% CI: 339.05, 364.52) than females (162/100 000; 95% CI: 153.60, 171.17) and among rural (222/100,000; 95% CI: 212.77-231.53) as compared to urban residents (193/100,000; 95% CI: 183.39-203.59).
Conclusions
This study found a relatively higher prevalence smear-positive PTB in the region than in a same period nationwide survey and identified a significant number of undetected PTB cases. The urgency for improved TB case detection and intensified community awareness is emphasized.
doi:10.1186/1471-2334-13-448
PMCID: PMC3849763  PMID: 24073793
Bacteriologically confirmed; Cross-sectional; Pulmonary tuberculosis; Tigray region; Ethiopia
3.  Mycobacterial Lineages Causing Pulmonary and Extrapulmonary Tuberculosis, Ethiopia 
Emerging Infectious Diseases  2013;19(3):460-463.
Molecular typing of 964 specimens from patients in Ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of Mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for M. bovis. We report a novel phylogenetic lineage of M. tuberculosis strongly associated with the Horn of Africa.
doi:10.3201/eid1903.120256
PMCID: PMC3647644  PMID: 23622814
Tuberculosis and other mycobacteria; tuberculosis; Mycobacterium tuberculosis; Mycobacterium bovis; bacteria; bovine; pulmonary tuberculosis; extrapulmonary tuberculosis; TB lymphadenitis; cervical lymph nodes; lymph nodes; lineage; zoonoses; zoonotic transmission; Ethiopia
4.  High Prevalence of Bovine Tuberculosis in Dairy Cattle in Central Ethiopia: Implications for the Dairy Industry and Public Health 
PLoS ONE  2012;7(12):e52851.
Background
Ethiopia has the largest cattle population in Africa. The vast majority of the national herd is of indigenous zebu cattle maintained in rural areas under extensive husbandry systems. However, in response to the increasing demand for milk products and the Ethiopian government's efforts to improve productivity in the livestock sector, recent years have seen increased intensive husbandry settings holding exotic and cross breeds. This drive for increased productivity is however threatened by animal diseases that thrive under intensive settings, such as bovine tuberculosis (BTB), a disease that is already endemic in Ethiopia.
Methodology/Principal Findings
An extensive study was conducted to: estimate the prevalence of BTB in intensive dairy farms in central Ethiopia; identify associated risk factors; and characterize circulating strains of the causative agent, Mycobacterium bovis. The comparative intradermal tuberculin test (CIDT), questionnaire survey, post-mortem examination, bacteriology, and molecular typing were used to get a better understanding of the BTB prevalence among dairy farms in the study area. Based on the CIDT, our findings showed that around 30% of 2956 tested dairy cattle from 88 herds were positive for BTB while the herd prevalence was over 50%. Post-mortem examination revealed gross tuberculous lesions in 34/36 CIDT positive cattle and acid-fast bacilli were recovered from 31 animals. Molecular typing identified all isolates as M. bovis and further characterization by spoligotyping and MIRU-VNTR typing indicated low strain diversity within the study area.
Conclusions/Significance
This study showed an overall BTB herd prevalence of 50% in intensive dairy farms in Addis Ababa and surroundings, signalling an urgent need for intervention to control the disease and prevent zoonotic transmission of M. bovis to human populations consuming dairy products coming from these farms. It is suggested that government and policy makers should work together with stakeholders to design methods for the control of BTB in intensive farms in Ethiopia.
doi:10.1371/journal.pone.0052851
PMCID: PMC3532161  PMID: 23285202
5.  HLA Class II Locus and Susceptibility to Podoconiosis 
The New England Journal of Medicine  2012;366(13):1200-1208.
BACKGROUND
Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%).
METHODS
We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls.
RESULTS
We found a genomewide significant association of podoconiosis with the single-nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P = 1.42×10−9; and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P = 3.44×10−8), and suggestive associations (P<1.0×10−5) with seven other SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds ratio, 1.79) and the HLA-DRB1*0701–DQB1*0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis.
CONCLUSIONS
Association between variants in HLA class II loci with podoconiosis (a noncommuni-cable disease) suggests that the condition may be a T-cell–mediated inflammatory disease and is a model for gene–environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.)
doi:10.1056/NEJMoa1108448
PMCID: PMC3350841  PMID: 22455414
7.  Correction: Prediction of HLA Class II Alleles Using SNPs in an African Population 
PLoS ONE  2012;7(7):10.1371/annotation/3529a6a2-4ba2-47dc-929e-399d441b0afa.
doi:10.1371/annotation/3529a6a2-4ba2-47dc-929e-399d441b0afa
PMCID: PMC3393640
8.  Prediction of HLA Class II Alleles Using SNPs in an African Population 
PLoS ONE  2012;7(6):e40206.
Background
Despite the importance of the human leukocyte antigen (HLA) gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs). However, the utility of these methods in African populations has not been systematically evaluated.
Methodology/Principal Findings
In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1) alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit) resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.
Conclusions/Significance
We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit) resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.
doi:10.1371/journal.pone.0040206
PMCID: PMC3386230  PMID: 22761960
9.  Zoonotic Transmission of Tuberculosis Between Pastoralists and Their Livestock in South-East Ethiopia 
Ecohealth  2012;9(2):139-149.
Despite huge global efforts in tuberculosis (TB) control, pastoral areas remain under-investigated. During two years sputum and fine needle aspirate (FNA) specimens were collected from 260 Ethiopian pastoralists of Oromia and Somali Regional States with suspected pulmonary TB and from 32 cases with suspected TB lymphadenitis. In parallel, 207 suspected tuberculous lesions were collected from cattle, camels and goats at abattoirs. All specimens were processed and cultured for mycobacteria; samples with acid-fast stained bacilli (AFB) were further characterized by molecular methods including genus and deletion typing as well as spoligotyping. Non-tuberculous mycobacteria (NTM) were sequenced at the 16S rDNA locus. Culturing of AFB from human sputum and FNA samples gave a yield of 174 (67%) and 9 (28%) isolates, respectively. Molecular typing was performed on 173 of these isolates and 160 were confirmed as Mycobacterium tuberculosis, three as M. bovis, and the remaining 10 were typed as NTMs. Similarly, 48 AFB isolates (23%) yielded from tuberculous lesions of livestock, of which 39 were molecular typed, including 24 M. bovis and 4 NTMs from cattle, 1 M. tuberculosis and 1 NTM from camels and 9 NTMs from goats. Isolation of M. bovis from humans and M. tuberculosis from livestock suggests transmission between livestock and humans in the pastoral areas of South-East Ethiopia
doi:10.1007/s10393-012-0754-x
PMCID: PMC3415617  PMID: 22526748
mycobacteria; Mycobacterium tuberculosis; Mycobacterium bovis; humans; cattle; camels
10.  Bovine tuberculosis at a cattle-small ruminant-human interface in Meskan, Gurage region, Central Ethiopia 
BMC Infectious Diseases  2011;11:318.
Background
Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. The aim of this study was to assess BTB prevalence at an intensive contact interface in Meskan Woreda (district) in cattle, small ruminants and suspected TB-lymphadenitis (TBLN) human patients.
Methods
The comparative intradermal test (CIDT) was carried out for all animals involved in the cross-sectional study and results interpreted using a > 4 mm and a > 2 mm cut-off. One PPD positive goat was slaughtered and lymph nodes subjected to culture and molecular typing. In the same villages, people with lymphadenitis were subjected to clinical examination. Fine needle aspirates (FNA) were taken from suspected TBLN and analyzed by smear microscopy and molecular typing.
Results
A total of 1214 cattle and 406 small ruminants were tested for BTB. In cattle, overall individual prevalence (> 2 mm cut-off) was 6.8% (CI: 5.4-8.5%) with 100% herd prevalence. Only three small ruminants (2 sheep and 1 goat) were reactors. The overall individual prevalence in small ruminants (> 2 mm cut-off) was 0.4% (CI: 0.03-5.1%) with 25% herd prevalence. Cattle from owners with PPD positive small ruminants were all PPD negative. 83% of the owners kept their sheep and goats inside their house at night and 5% drank regularly goat milk.
FNAs were taken from 33 TBLN suspected cases out of a total of 127 screened individuals with lymph node swellings. Based on cytology results, 12 were confirmed TBLN cases. Nine out of 33 cultures were AFB positive. Culture positive samples were subjected to molecular typing and they all yielded M. tuberculosis. M. tuberculosis was also isolated from the goat that was slaughtered.
Conclusions
This study highlighted a low BTB prevalence in sheep and goats despite intensive contact with cattle reactors. TBLN in humans was caused entirely by M. tuberculosis, the human pathogen. M. tuberculosis seems to circulate also in livestock but their role at the interface is unknown.
doi:10.1186/1471-2334-11-318
PMCID: PMC3235076  PMID: 22085784
11.  African 2, a Clonal Complex of Mycobacterium bovis Epidemiologically Important in East Africa▿ †  
Journal of Bacteriology  2010;193(3):670-678.
We have identified a clonal complex of Mycobacterium bovis isolated at high frequency from cattle in Uganda, Burundi, Tanzania, and Ethiopia. We have named this related group of M. bovis strains the African 2 (Af2) clonal complex of M. bovis. Af2 strains are defined by a specific chromosomal deletion (RDAf2) and can be identified by the absence of spacers 3 to 7 in their spoligotype patterns. Deletion analysis of M. bovis isolates from Algeria, Mali, Chad, Nigeria, Cameroon, South Africa, and Mozambique did not identify any strains of the Af2 clonal complex, suggesting that this clonal complex of M. bovis is localized in East Africa. The specific spoligotype pattern of the Af2 clonal complex was rarely identified among isolates from outside Africa, and the few isolates that were found and tested were intact at the RDAf2 locus. We conclude that the Af2 clonal complex is localized to cattle in East Africa. We found that strains of the Af2 clonal complex of M. bovis have, in general, four or more copies of the insertion sequence IS6110, in contrast to the majority of M. bovis strains isolated from cattle, which are thought to carry only one or a few copies.
doi:10.1128/JB.00750-10
PMCID: PMC3021238  PMID: 21097608
12.  Bovine Tuberculosis at the Wildlife-Livestock-Human Interface in Hamer Woreda, South Omo, Southern Ethiopia 
PLoS ONE  2010;5(8):e12205.
Bovine tuberculosis (BTB) is endemic in cattle in the Ethiopian Highlands but no studies have been done so far in pastoralists in South Omo. This study assessed the prevalence of bovine tuberculosis (BTB) at an intensive interface of livestock, wildlife and pastoralists in Hamer Woreda (South Omo), Ethiopia. A cross-sectional survey including a comparative intradermal skin testing (CIDT) was conducted in 499 zebu cattle and 186 goats in 12 settlements. Sputum samples from 26 symptomatic livestock owners were cultured for TB. Fifty-one wildlife samples from 13 different species were also collected in the same area and tested with serological (lateral flow assay) and bacteriological (culture of lymph nodes) techniques. Individual BTB prevalence in cattle was 0.8% (CI: 0.3%–2%) with the >4 mm cut-off and 3.4% (CI: 2.1%–5.4%) with the >2 mm cut-off. Herd prevalence was 33.3% and 83% when using the >4 and the >2 mm cut-off respectively. There was no correlation between age, sex, body condition and positive reactors upon univariate analysis. None of the goats were reactors for BTB. Acid fast bacilli (AFB) were detected in 50% of the wildlife cultures, 79.2% of which were identified as Mycobacterium terrae complex. No M. bovis was detected. Twenty-seven percent of tested wildlife were sero-positive. Four sputum cultures (15.4%) yielded AFB positive colonies among which one was M. tuberculosis and 3 non-tuberculous mycobacteria (NTM). The prevalence of M. avium-complex (MAC) was 4.2% in wildlife, 2.5% in cattle and 0.5% in goats. In conclusion, individual BTB prevalence was low, but herd prevalence high in cattle and BTB was not detected in goats, wildlife and humans despite an intensive contact interface. On the contrary, NTMs were highly prevalent and some Mycobacterium spp were more prevalent in specific species. The role of NTMs in livestock and co-infection with BTB need further research.
doi:10.1371/journal.pone.0012205
PMCID: PMC2923162  PMID: 20808913

Results 1-12 (12)