Tuberculosis caused 20% of all human deaths in the Western world between the 17th and 19th centuries, and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. Here we used 259 whole-genome sequences to reconstruct the evolutionary history of the Mycobacterium tuberculosis complex (MTBC). Coalescent analyses indicate that MTBC emerged about 70 thousand years ago, accompanied migrations of anatomically modern humans out of Africa, and expanded as a consequence of increases in human population density during the Neolithic. This long co-evolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low- and high host densities.

SUMMARY To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.

SummaryBackgroundAvailable incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents.MethodsWe established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment.FindingsBetween March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0–0) in Sudan to 383 (274–535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178–316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau.InterpretationTyphoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study.FundingBill & Melinda Gates Foundation.

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.

A comparative study on the prevalence and pathology of bovine tuberculosis (TB) was conducted on 5,424 cattle (2,578 zebus, 1,921 crosses, and 925 Holsteins), which were kept on pasture in the central highlands of Ethiopia, using a comparative intradermal tuberculin test, postmortem examination, and bacteriology. The overall prevalence of bovine TB was 13.5%; prevalence was higher in Holsteins than either zebus (22.2% versus 11.6%, 2 ‫؍‬ 61.8; P < 0.001) or crosses (22.2% versus 11.9%, 2 ‫؍‬ 50.7; P < 0.001). Moreover, the severity of pathology in Holsteins (mean ؎ standard error of the mean [SEM], 6.84 ؎ 0.79) was significantly higher (P ‫؍‬ 0.018) than the severity of pathology in zebus (5.21 ؎ 0.30). In addition, the risk of TB in Holsteins was more than twice (odds ratio [OR] ‫؍‬ 2.32; 95% confidence interval [CI] ‫؍‬ 1.89, 2.85) that in zebus. Animals between 5 and 9 years of age were at higher (OR ‫؍‬ 2.37; 95% CI ‫؍‬ 1.80, 3.12) risk of bovine TB than those 2 years of age or below. A significant difference ( 2 ‫؍‬ 351; P < 0.001) in the occurrence of TB lesions in lymph nodes was recorded; the mesenteric lymph node (mean pathology score ؎ SEM, 1.95 ؎ 0.08) was most severely affected, followed by the retropharyngeal (0.80 ؎ 0.05) and caudal mediastinal (0.8 ؎ 0.06) lymph nodes. Fifty-six percent (n ‫؍‬ 145) of the animals with gross TB lesions were culture positive; the lowest culture positivity was recorded in the skin lesions (27.3%) and the lesions of the mesenteric lymph node (31.5%). Both the skin test response and the postmortem findings suggested a higher susceptibility to bovine TB in Holsteins than zebus under identical field husbandry conditions (on pasture). In the light of increased numbers of Holstein cattle introduced into this area to raise milk production to satisfy the needs of Addis Ababa's growing population, these findings highlight the need for a control program in these herds.Bovine tuberculosis (TB) is caused by intracellular infection with the acid-fast bacterium Mycobacterium bovis. In cattle, exposure to this organism can result in a chronic disease that jeopardizes animal welfare and productivity and in some countries leads to significant economic losses (36). Moreover, human TB of animal origin caused by M. bovis is becoming increasingly important in developing countries. In sub-Saharan Africa, humans and animals share the same microenvironment and water holes, especially during droughts and the dry season, thereby potentially promoting the transmission of M. bovis from animals to humans. In industrialized countries, bovine TB is controlled by testing and slaughter of animals and pasteurization of milk, and therefore the risk of human infection is minimized. In Africa, however, bovine TB represents potential health hazards for both animals and humans. Nonetheless, in most African countries, M. bovis infection remains an uninvestigated problem (13). In general, the epidemiology and public health significance of bovine TB in Africa remain largely unknown. Many of the factors which...

BackgroundPerceived stigma and lack of awareness could contribute to the late presentation and low detection rate of tuberculosis (TB). We conducted a study in rural southwest Ethiopia among TB suspects to assess knowledge about and stigma towards TB and their health seeking behavior.MethodsA community based cross sectional survey was conducted from February to March 2009 in the Gilgel Gibe field research area. Any person 15 years and above with cough for at least 2 weeks was considered a TB suspect and included in the study. Data were collected by trained personnel using a pretested structured questionnaire. Logistic regression analysis was done using SPSS 15.0 statistical software.ResultsOf the 476 pulmonary TB suspects, 395 (83.0%) had ever heard of TB; “evil eye” (50.4%) was the commonly mentioned cause of TB. Individuals who could read and write were more likely to be aware about TB [(crude OR = 2.98, (95%CI: 1.25, 7.08)] and more likely to know that TB is caused by a microorganism [(adjusted OR = 3.16, (95%CI: 1.77, 5.65)] than non-educated individuals. Males were more likely to know the cause of TB [(adjusted OR = 1.92, (95%CI: 1.22, 3.03)] than females. 51.3% of TB suspects perceived that other people would consider them inferior if they had TB. High stigma towards TB was reported by 199(51.2%). 220 (46.2%) did not seek help for their illness. Individuals who had previous anti-TB treatment were more likely to have appropriate health seeking behavior [(adjusted OR = 3.65, (95%CI: 1.89, 7.06)] than those who had not.ConclusionThere was little knowledge about TB in the Gilgel Gibe field research area. We observed inappropriate health seeking behavior and stigma towards TB. TB control programs in Ethiopia should educate rural communities, particularly females and non-educated individuals, about the cause and the importance of early diagnosis and treatment of TB.

BackgroundMonitoring the outcome of tuberculosis treatment and understanding the specific reasons for unsuccessful treatment outcome are important in evaluating the effectiveness of tuberculosis control program. This study investigated tuberculosis treatment outcomes and predictors for unsuccessful treatment outcome in the Tigray region of Ethiopia.MethodsMedical records of smear-positive pulmonary tuberculosis (PTB) patients registered from September 2009 to June 2011 in 15 districts of Tigray region, Northern Ethiopia, were reviewed. Additional data were collected using a structured questionnaire administered through house-to-house visits by trained nurses. Tuberculosis treatment outcomes were assessed according to WHO guidelines. The association of unsuccessful treatment outcome with socio-demographic and clinical factors was analyzed using logistic regression model.ResultsOut of the 407 PTB patients (221 males and 186 females) aged 15 years and above, 89.2% had successful and 10.8% had unsuccessful treatment outcome. In the final multivariate logistic model, the odds of unsuccessful treatment outcome was higher among patients older than 40 years of age (adj. OR = 2.50, 95% CI: 1.12-5.59), family size greater than 5 persons (adj. OR = 3.26, 95% CI: 1.43-7.44), unemployed (adj. OR = 3.10, 95% CI: 1.33-7.24) and among retreatment cases (adj. OR = 2.00, 95% CI: 1.37-2.92) as compared to their respective comparison groups.ConclusionsTreatment outcome among smear-positive PTB patients was satisfactory in the Tigray region of Ethiopia. Nonetheless, those patients at high risk of an unfavorable treatment outcome should be identified early and given additional follow-up and social support.

BackgroundBovine 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 FindingsHere 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/SignificanceOur analysis has revealed that bTB is widely spread throughout Ethiopia, albeit at a low prevalence, and provides underpinning evidence for public health policy formulation.