The Wellcome Trust Bovine TB Project in Ethiopia: The Bovine TB Project Team

AbstractThe importance of bovine tuberculosis to the economy and public health is being assessed in Ethiopia to generate the evidence base for better control options. A cross sectional prevalence survey in cattle and human populations will be conducted. The influence of cattle genetic background on susceptibility to bovine TB will be studied. Prevalence and type of M. bovis in exotic and local breeds will be compared and the immunology, pathology and genetics of cattle susceptibility studied. The efficacy of neonatal BCG vaccination will be tested in a natural transmission setting and a protocol developed for such trials. The cost of bovine TB to the society will be estimated and a cost-benefit model of intervention developed. The project will strengthen local capacity to undertake mycobacterial typing and epidemiological modelling studies. [Ethiop.J.Health Dev. 2008;22(Special Issue):128-131

Approach to assess the economic impact of bovine tuberculosis in Ethiopia

AbstractBovine TB is prevalent in Ethiopian cattle and represents a serious zoonotic risk. However, extensive epidemiological data in the human and livestock sector are lacking. Create a dynamic transmission model of disease between animal and human, as a prerequisite for economic analysis of the most profitable intervention to control BTB in Ethiopia. Study on-going (2005-2010), epidemiological (prevalence, risk factors) and cost (human and livestock) data are collected in eight sites over a period of four years and fed into a compartmental trans-sectoral framework that simulates disease transmission. Different intervention scenarios will then be simulated in the model. The most profitable intervention to control BTB in Ethiopia has to be assessed as well as the cost sharing scheme between the public health and agricultural sectors. It has been postulated that a test and slaughter policy would have a negative economic impact in Ethiopia. Alternatives need to be assessed. [Ethiop.J.Health Dev. 2008;22(Special Issue):135-13

Pneumococcal carriage, serotype distribution and risk factors in children with community-acquired pneumonia, 5 years after introduction of the 10-valent pneumococcal conjugate vaccine in Ethiopia

Background: There is a scarcity of data on pneumococcal serotypes carried by children in Ethiopia. We studied pneumococcal nasopharyngeal carriage rate, serotypes, and risk factors among children with community acquired pneumonia (CAP). Methods: A prospective observational cohort study was performed in children with CAP, aged 0-15 years, in 2 pediatric emergency departments in Addis Ababa, Ethiopia. Nasopharyngeal swabs were cultured, and serotypes of Streptococcus pneumoniae were determined by sequencing the cpsB gene and by the Quellung reaction. Risk factors were analyzed by using binary logistic regression. Results: Nasopharyngeal swabs were collected from 362 children with CAP. Pneumococcal carriage rate was 21.5% (78 of 362). The most common serotypes were 19A (27%), 16F (8.5%), and 6A (4.9%). In addition, 8.5% of the pneumococcal isolates were nontypeable. In bivariate analysis, children with a parent that smokes were more likely to carry pneumococci (crude odds ratio, 3.9; 95% confidence interval [CI], 1.2-12.3; P =.023) than those with parents that do not smoke. In multivariable analysis, living in a house with >= 2 rooms (adjusted odds ratio [AOR], 0.48; 95% CI, 0.28-0.82; P =.007) and vaccination with = 2 doses of 10-valent pneumococcal conjugate vaccine (PCV10) (AOR, 0.37; 95% CI, 0.15-0.92; P =.033) were protective of pneumococcal carriage. Conclusions: Five years after introduction of PCV10 in Ethiopia, the vaccine-related serotype 19A was predominant in the nasopharynx of children with CAP. Continued evaluation of the direct and indirect impact of PCV10 on pneumococcal serotype distribution in Ethiopia is warranted

Bovine tuberculosis and brucellosis prevalence in cattle from selected milk cooperatives in Arsi zone, Oromia region, Ethiopia

Bovine tuberculosis (BTB) and bovine brucellosis are two important milk-borne zoonoses that have been shown to be prevalent to various degrees in Ethiopian cattle. The study was carried out in four Woredas (districts) around Asella town, Arsi Zone between October 2011 and March 2012 and included 318 small-holders in 13 dairy cooperatives that marketed the delivered milk. The aims of the study were i) to assess the prevalence of the two diseases in cattle in a cross-sectional study, ii) to assess potential risk factors of BTB and brucellosis to humans as well as the knowledge-attitude-practice (KAP) among these farmers towards these diseases.; BTB testing using the comparative intradermal skin test (CIDT) was done on 584 milking cows, out of which 417 were serologically tested for brucellosis using the Rose Bengal Plate Test and reactors confirmed with an indirect ELISA test (PrioCHECK®). The individual animal prevalence was 0.3% (95% CI 0.1% to 1.3%) for BTB, 1.7% (95% CI 0.8% to 3.5%) for brucellosis and 8.9% (95% CI 6.8% to 11.5%) for MAC (Mycobacterium avium complex). Of the 13 milk cooperatives, two had at least one positive BTB reactor and five had animals positive for brucellosis. Cross-breeds accounted for 100% and 71.4% of the BTB and brucellosis reactors respectively. For both diseases, there were prevalence variations depending on Woreda. No animal was concomitant reactor for BTB and brucellosis. Raw milk was consumed by 55.4% of the respondents. 79.2% of the respondents reported touching the afterbirth with bare hands. The latter was fed to dogs in 83% of the households. One cow among the herds of the 130 interviewees had aborted in the last 12 months. Among the interviewees, 77% stated knowing tuberculosis in general but 42 out of the 130 respondents (32.3%) did not know that BTB was transmitted by livestock. Less than half (47.7%) of the respondents knew about brucellosis.; Low prevalence of both diseases reflected the potential for the area to compete with the growing milk demand. The authors discussed the possible control strategies for the area

Prediction of HLA class II alleles using SNPs in an African population

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 countrie

A comparative study on the epidemiology and immuno-pathology of bovine tuberculosis in Bos indicus and Bos taurus cattle in Ethiopia

AbstractBovine tuberculosis is a disease of dual effect, having public health and economic implications. The present study was conducted on its epidemiology and immuno-pathology in Holstein and Zebu breeds of cattle. Skin test, post mortem examination and pathology scoring, bacteriology, whole blood gamma interferon assay, ELISPOT assay, and lateral flow assay were used. An overall prevalence of 13.5% (n=5,424) was recorded; both prevalence (2 =61.8; P<0.001) and severity of pathology (mean pathology scores + SEM: 6.84±0.79 vs. 5.21±0.30; P=0.018, Mann-Whitney test) were significantly higher in Holstein than in Zebu. Similarly, IFN- responses to avian PPD (0.490.10 vs. 0.390.07), bovine PPD (0.630.11 vs. 0.430.07), or the ESAT6-CFP10 protein cocktail (0.430.01 vs. 0.300.05) were significantly higher (for all antigens: p<0.02) in Holstein than in Zebu cattle. However, both Holstein and Zebu exhibited similar T cell and antibody responses to different mycobacterial antigens i.e. no repertoire difference was observed between the two breeds. Thus, the present study showed increased susceptibility of Holsteins to bovine TB as compared to Zebu, similarity between Holsteins and Zebus in their antigen responses, and a positive correlation between IFN- responses and severity of pathology of bovine TB. [Ethiop.J.Health Dev. 2008;22(Special Issue):132-134

Polyclonal spread of blaCTX-M-15 through high-risk clones of Escherichia coli at a tertiary hospital in Ethiopia

Objectives: The burden of antimicrobial resistance and spread of epidemic clones are rarely reported from low-income countries. We aimed to investigate the genome-based epidemiology of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) at a tertiary hospital in Jimma, Ethiopia. Methods: Bacteria were isolated from clinical specimens at Jimma Medical Center and subjected to species identification (MALDI-TOF), antimicrobial susceptibility testing (disk diffusion) and whole-genome sequencing (Illumina, HiSeq2500). Genomic data analysis was performed using EnteroBase and Center for Genomic Epidemiology bioinformatics pipelines. A maximum likelihood tree was generated using FastTree/2.1.8 based on single nucleotide polymorphisms (SNPs) in shared genomic regions to identify transmission clusters. Results: Escherichia coli isolates (n = 261) were collected from 1087 single non-duplicate clinical specimens over a 5-month period in 2016. The prevalence of ESBL-EC was 54.8% (143/261), 96% of which were resistant to multiple antibiotic classes. The blaCTX-M-15 ESBL gene was present in 88.4.% of isolates (122/138). Genes conferring resistance to aminoglycosides and ciprofloxacin [aac(6′)-Ib-cr, 62.3% (86/138)], phenicols [catB3, 56.5% (78/138)], sulfonamides [sul1, 68.1% (94/138), trimethoprim [dfrA17, 58.0% (80/138)] and macrolides [mph(A), 67.4% (93/138) were detected. The most prevalent sequence types were ST410 (23%), ST648 (17%), ST131 (10%) and ST167 (7%). Isolates of the same sequence type collected from different units of the hospital were highly similar in the SNP analysis. Conclusion: A high prevalence of ESBLs and dissemination of blaCTX-M-15 through multiple high-risk E. coli clones was detected. Nosocomial spread of multidrug-resistant ESBL-EC within the hospital puts vulnerable patients at risk of difficult-to-treat infections

Anti-mycobacterial recall responses differentiate female patients with genital tuberculosis from patients with other gynecological problems

Background: Female Genital Tuberculosis (FGTB) is one form of extra pulmonary tuberculosis affecting the female reproductive organs, most commonly the fallopian tubes and the endometrium. It affects young women aged between 20 and 40 years of age and is an important cause of infertility. It often occurs as a secondary complication following pulmonary tuberculosis. Diagnosis depends mainly on clinical suspicion in countries where facilities for mycobacterial culture and histopathology are unavailable. Even in places where these facilities exist, diagnosis still remains difficult because of the lower sensitivity and specificity of the methods as well as the invasive procedure of acquiring biopsy specimens. Objective: To explore the immunological profiles of female genital tuberculosis (FGTB) patients in response to mycobacterial antigens. Methods: Twenty-five clinically suspected cases of FGTB and 12 control subjects who came to the Black Lion hospital for unrelated gynecological problems were included in the study. Peripheral blood samples were collected from each subject. Plasma was separated by centrifugation and PBMC were isolated over ficoll-hypaque and stimulated in vitro with mycobacterial antigens to examine their proliferative response as incorporation of tritiated thymidine using a β-counter. HIV status and total IgG-, IgA- and IgM- antibody levels were determined by ELISA tests.Results: In vitro recall responses to M. tuberculosis antigens (PPD and BCG sonicate) as well as plasma levels of IgGIgA- and IgM-antibodies to MPT59 showed statistically significant differences between the patients and the controls (

Ex vivo cytokine mRNA levels correlate with changing clinical status of ethiopian TB patients and their contacts over time.

There is an increasing body of evidence which suggests that IL-4 plays a role in the pathogenesis of TB, but a general consensus on its role remains elusive. We have previously published data from a cohort of Ethiopian TB patients, their contacts, and community controls suggesting that enhanced IL-4 production is associated with infection with M. tuberculosis, rather than overt disease and that long-term protection in infected community controls is associated with co-production of the IL-4 antagonist IL-4d2, alongside elevated IL-4. Here, for the first time, we compare data on expression of IFN-gamma, IL-4 and IL-4delta2 over time in TB patients and their household contacts. During the follow-up period, the TB patients completed therapy and ceased to display TB-like symptoms. This correlated with a decrease in the relative amount of IL-4 expressed. Over the same period, the clinical status of some of their contacts also changed, with a number developing TB-like symptoms or clinically apparent TB. IL-4 expression was disproportionately increased in this group. The findings support the hypothesis that elevated IL-4 production is generally associated with infection, but that TB disease is associated with a relatively increased expression of IL-4 compared to IFN-gamma and IL-4delta2. However, the data also suggest that there are no clear-cut differences between groups: the immune response over time appears to include changes in the expression of IFN-gamma, IL-4 and IL-4delta2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status

Bacteremic community-acquired pneumonia in Ethiopian children : etiology, antibiotic resistance, risk factors, and clinical outcome

Background: Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality. We sought to determine the magnitude, etiology, and risk factors of CAP in children 5 years after introduction of pneumococcal conjugate vaccine (PCV) 10 in Ethiopia. Methods: We conducted a prospective observational study on the bacterial etiology and risk factors of CAP among children aged 0–15 years in 2 pediatric emergency departments in Addis Ababa, Ethiopia. Blood culture, antibiotic susceptibility testing, and amplification of pneumococcal lytA and cpsB genes were performed. Serotypes of Streptococcus pneumoniae were determined by Quellung reaction and sequencing the cpsB gene. Results: Out of 643 eligible children, 549 were enrolled. The prevalence of bacteremic pneumonia was 5.6%. Staphylococcus aureus (26.5%) was the predominant pathogenic species, followed by Enterococcus faecium (11.8%), Escherichia coli (11.8%), and Klebsiella pneumoniae (11.8%). In univariate analysis, parental smoking and nonvaccination with PCV10 were associated with bacteremic CAP. In multivariable analysis, female sex (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1–4.9), weight-for-age z-score (WAZ) <–2 SDs (aOR, 2.2; 95% CI, 1.1–4.8), and lower chest indrawing (aOR, 0.44; 95% CI, 0.2–0.95) were independently associated with bacteremic CAP. The overall in-hospital case fatality rate was 2.37% (13/549), and WAZ <–3 SDs (OR, 13.5; 95% CI, 3.95–46.12) was associated with mortality. Conclusions: Five years after the introduction of PCV10 in Ethiopia, S. aureus was the main cause of bacteremic CAP in children, the contribution of S. pneumoniae was low, and there was a high level of antibiotic resistance among isolates