Lawrence Yamuah

The Burden of Mycobacterial Disease in Ethiopian Cattle: Implications for Public Health

Background Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a debilitating disease of cattle. Ethiopia has one of the largest cattle populations in the world, with an economy highly dependent on its livestock. Furthermore, Ethiopia has one of the highest incidence rates of human extrapulmonary TB in the world, a clinical presentation that is often associated with transmission of M. bovis from cattle to humans. Methodology/Principal Findings Here we present a comprehensive investigation of the prevalence of bTB in Ethiopia based on cases identified at slaughterhouses. Out of approximately 32,800 inspected cattle, ∼4.7% showed suspect tuberculous lesions. Culture of suspect lesions yielded acid-fast bacilli in ∼11% of cases, with M. bovis accounting for 58 of 171 acid-fast cultures, while 53 isolates were non-tuberculous mycobacteria. Strikingly, M. tuberculosis was isolated from eight cattle, an unusual finding that suggests human to animal transmission. Conclusions/Significance Our analysis has revealed that bTB is widely spread throughout Ethiopia, albeit at a low prevalence, and provides underpinning evidence for public health policy formulation.

Mycobacterial Lineages Causing Pulmonary and Extrapulmonary Tuberculosis, Ethiopia

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.

Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit, Ethiopia.

BackgroundPlasmodium vivax accounts for about 40% of all malaria infection in Ethiopia. Chloroquine (CQ) is the first line treatment for confirmed P. vivax malaria in the country. The first report of CQ treatment failure in P. vivax was from Debre Zeit, which suggested the presence of chloroquine resistance.MethodsAn in vivo drug efficacy study was conducted in Debre Zeit from June to August 2006. Eighty-seven patients with microscopically confirmed P. vivax malaria, aged between 8 months and 52 years, were recruited and treated under supervision with CQ (25 mg/kg over three days). Clinical and parasitological parameters were assessed during the 28 day follow-up period. CQ and desethylchloroquine (DCQ) blood and serum concentrations were determined with high performance liquid chromatography (HPLC) in patients who showed recurrent parasitaemia.ResultsOf the 87 patients recruited in the study, one was lost to follow-up and three were excluded due to P. falciparum infection during follow-up. A total of 83 (95%) of the study participants completed the follow-up. On enrolment, 39.8% had documented fever and 60.2% had a history of fever. The geometric mean parasite density of the patients was 7045 parasites/μl. Among these, four patients had recurrent parasitaemia on Day 28. The blood CQ plus DCQ concentrations of these four patients were all above the minimal effective concentration (> 100 ng/ml).ConclusionChloroquine-resistant P. vivax parasites are emerging in Debre Zeit, Ethiopia. A multi-centre national survey is needed to better understand the extent of P. vivax resistance to CQ in Ethiopia.

Anti-tuberculosis therapy-induced hepatotoxicity among Ethiopian HIV-positive and negative patients.

Background To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia. Methodology/Principal Findings In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1%) developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg. Conclusions/Significance Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002), concomitant drug intake (p = 0.008), and decrease in CD4 count (p = 0.001). Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.

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-γ, IL-4 and IL-4δ2 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-γ and IL-4δ2. 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-γ, IL-4 and IL-4δ2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status.

High Prevalence of Bovine Tuberculosis in Dairy Cattle in Central Ethiopia: Implications for the Dairy Industry and Public Health

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 governments 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.

High Diversity of Group A Streptococcal emm Types among Healthy Schoolchildren in Ethiopia

BACKGROUND Although the prevalence of rheumatic heart disease in Ethiopia is one of the highest in the world, the epidemiology of group A streptococci (GAS) in this country is little known. GAS typing is a hallmark of both the epidemiology and understanding of diseases caused by these organisms. We have therefore conducted this study to investigate the emm (M-protein gene) type distribution of GAS carriers among Ethiopian schoolchildren. METHODS In the present study, we performed emm typing of 82 GAS isolates collected from the throats of healthy schoolchildren (6-14 years of age) residing in 3 different urban sites in Ethiopia: Addis Ababa, Gondar, and Dire Dawa. RESULTS We report high diversity of GAS isolates recovered from healthy schoolchildren. Eighty-two isolates represented 43 different sequence types. Thirteen newly described subtypes were detected in this study. Of the emm types prevalent in the study communities, 46% were not included in the 26-valent GAS vaccine. CONCLUSIONS The high diversity of emm types encountered within 3 months of collection suggest that production of a vaccine candidate based on the M-protein amino termini appears to be impractical for this population. We suggest that investigations of other vaccine candidates, including the C5a peptidase, GAS carbohydrate, and fibronectin-binding proteins, as well as conserved M-protein region vaccines, should be intensified to address the needs of this population.

The Diversity of Meningococcal Carriage Across the African Meningitis Belt and the Impact of Vaccination With a Group A Meningococcal Conjugate Vaccine

Background. Study of meningococcal carriage is essential to understanding the epidemiology of Neisseria meningitidis infection. Methods. Twenty cross-sectional carriage surveys were conducted in 7 countries in the African meningitis belt; 5 surveys were conducted after introduction of a new serogroup A meningococcal conjugate vaccine (MenAfriVac). Pharyngeal swab specimens were collected, and Neisseria species were identified by microbiological and molecular techniques. Results. A total of 1687 of 48 490 participants (3.4%; 95% confidence interval [CI], 3.2%–3.6%) carried meningococci. Carriage was more frequent in individuals aged 5–14 years, relative to those aged 15–29 years (adjusted odds ratio [OR], 1.41; 95% CI, 1.25–1.60); in males, relative to females (adjusted OR, 1.17; 95% CI, 1.10–1.24); in individuals in rural areas, relative to those in urban areas (adjusted OR, 1.44; 95% CI, 1.28–1.63); and in the dry season, relative to the rainy season (adjusted OR, 1.54; 95% CI, 1.37–1.75). Forty-eight percent of isolates had genes encoding disease-associated polysaccharide capsules; genogroup W predominated, and genogroup A was rare. Strain diversity was lower in countries in the center of the meningitis belt than in Senegal or Ethiopia. The prevalence of genogroup A fell from 0.7% to 0.02% in Chad following mass vaccination with MenAfriVac. Conclusions. The prevalence of meningococcal carriage in the African meningitis belt is lower than in industrialized countries and is very diverse and dynamic, even in the absence of vaccination.

Prevalence of bovine tuberculosis in pastoral cattle herds in the Oromia region, southern Ethiopia

A cross-sectional study of bovine tuberculosis (BTB) was conducted in pastoral cattle herds in southern Ethiopia, from February to August 2008 using the comparative intradermal tuberculin test. The prevalence of BTB and the risk factors for having positive reactor herds were assessed in four pastoral associations in two districts of southern Ethiopia, namely Goro-Dola with 242 cattle in 16 herds and Liben with 231 cattle in 15 herds. A herd was considered positive if there was at least one reactor animal in a herd. The test results were interpreted based on the Office Internationale des Epizooties recommended 4-mm and a recently suggested 2-mm cut-off. The apparent individual animal prevalence of tuberculin reactors was 5.5% (95% confidence interval (CI), 4.0–8.0%) and 7.0% (95% CI, 5.0–10.0%), whereas the true prevalence estimate was 4.4% (95% CI, 0.8–8.0%) and 6.1% (95% CI, 2.6–9.5%), when using the 4-mm and the 2-mm cut-offs, respectively. The overall herd apparent prevalence of tuberculin reactor animals was 41.9% (95% CI, 24.9–60.9%) and 48.4% (95% CI, 30.2–66.9%) with the 4-mm and 2-mm cut-offs, respectively. A positive tuberculin test was associated with the age of animals and the main drinking water sources during dry seasons. In order to investigate the public health risks and the epidemiological importance of BTB in the area, we recommend to include other livestock species (camels and goats) as well as humans in future studies.

Is tuberculous lymphadenitis over-diagnosed in Ethiopia? Comparative performance of diagnostic tests for mycobacterial lymphadenitis in a high-burden country.

Ethiopia reports the third highest number of extrapulmonary TB cases globally, most of which are lymph node TB (TBLN). We investigated the performance of the available diagnostic tests for TBLN. Fine needle aspirate (FNA) and excision biopsy samples from affected lymph nodes were collected from 150 consenting patients with suspected TBLN visiting regional hospitals in Ethiopia. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of histopathology against culture as reference was 92%, 88%, 97% and 77% and of FNA cytology (FNAC) 76%, 88%, 100% and 55%, respectively. Naked eye examination of FNA had 67% sensitivity and 64% specificity. HIV coinfection did not diminish the performance of macroscopic examination, Ziehl-Neelsen stain, histology or cytology examinations. When any positive result in ZN, histopathology or culture was considered confirmatory, clinical diagnosis could be confirmed in 85% of the patients, suggesting that TBLN is over-diagnosed in up to 15% of cases. With combined criteria as reference standard, the sensitivity, specificity, PPV and NPV of FNAC was 72%, 100%, 100% and 55%, respectively. FNAC is a practical tool that can improve the diagnosis of TBLN in high-burden settings. Over-diagnosis alone cannot explain the high burden of LNTB in Ethiopia.