Transmission of Mycobacterium tuberculosis (M. tuberculosis) complex could be possible between farmers and their cattle in Ethiopia.
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.
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.
Paediatric tuberculosis (TB) is poorly addressed in Ethiopia and information about its magnitude and the genotype distribution of the causative Mycobacterium tuberculosis strains responsible for its spread are scanty.
Gastric lavage or sputum samples were collected from consecutively enrolled TB suspect children visiting Jimma University Hospital in 2011 and cultured on Middlebrook 7H11 and Löwenstein-Jensen media. Acid fast bacterial (AFB) isolates were subjected to molecular typing targeting regions of difference (RDs), 16S rDNA gene and the direct repeat (DR) region using multiplex polymerase chain reaction (mPCR), gene sequencing and spoligotyping, respectively. Molecular drug susceptibility testing of M. tuberculosis isolates was performed by Genotype®MTBDRplus line probe assay (LPA) (Hain Life Sciences, Germany).
Gastric lavage (n = 43) or sputum (n = 58) samples were collected from 101 children and 31.7% (32/101) of the samples were positive for AFB by microscopy, culture and/or PCR. Out of 25 AFB isolates, 60% (15/25) were identified as M. tuberculosis by PCR, and 40% isolates (10/25) were confirmed to be non-tuberculous mycobacteria (NTM) by genus typing and 16S rDNA gene sequencing. Lineage classification assigned the M. tuberculosis strains into Euro-American (EUA, 66.7%; 10/15), East-African-Indian (EAI; 2/15), East-Asian (EA; 1/15) and Indio-Oceanic (IO; 1/15) lineages. Seven M. tuberculosis strains were new to the SpolDB4 database. All of the M. tuberculosis isolates were susceptible to isoniazid (INH) and rifampicin (RIF), except for one strain (of spoligotype SIT-149 or T3_ETH family) which had a mutation at the inhA locus which often confers resistance to INH (low level) and ethionamide.
Analysis of the genetic population structure of paediatric M. tuberculosis strains suggested similarity with that of adults, indicating an on-going and active transmission of M. tuberculosis from adults to children in Ethiopia. There were no multidrug-resistant TB (MDR-TB) strains among the isolates.
Paediatric TB; Mycobacterium; Paediatric spoligotype; Gastric lavage
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.
Bovine brucellosis; Bovine tuberculosis; Cattle; Milk cooperatives; Disease prevalence; Ethiopia
Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine.
We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR.
PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1.
This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected.
M. tuberculosis remains one of the world’s deadliest pathogens in part because of its ability to establish persistent, latent infections, which can later reactivate to cause disease. In regions of the globe where disease is endemic, as much as 50% of the population is thought to be latently infected, complicating diagnosis and tuberculosis control. The tools most commonly used for diagnosis of latent M. tuberculosis infection are the tuberculin skin test and the newer interferon-gamma release assays, both of which rely on an antigen-specific memory response as an indicator of infection. It is clear that the two tests, do not always give concordant results, but the factors leading to this are only partially understood.
In this study we examined 245 healthy school children aged from 12 to 20 years from Addis Ababa, a tuberculosis-endemic region, characterised them with regard to response in the tuberculin skin test and QuantIFERON™ test and assessed factors that might contribute to discordant responses.
Although concordance between the tests was generally fair (90% concordance), there was a subset of children who had a positive QuantIFERON™ result but a negative tuberculin skin test. After analysis of multiple parameters the data suggest that discordance was most strongly associated with the presence of parasites in the stool.
Parasitic gut infections are frequent in most regions where M. tuberculosis is endemic. This study, while preliminary, suggests that the tuberculin skin test should be interpreted with caution where this may be the case.
Latent tuberculosis; QuantiFERON; TST; Adolescents; Children; Parasites
In Libo Kemkem (a district of Amhara region, Ethiopia), no cases of kala-azar had ever been reported until 2005 when an outbreak occurred. Over one-third of those cases were children under 15 years of age. The aim of the present study was to determine the prevalence of Leishmania infection in children aged 4–15 years. A cross-sectional survey was conducted in 2009. Children participating in the survey were selected using a three-stage cluster sampling method. A total of 386 children were included in the study. The overall prevalence of Leishmania infection (direct agglutination test- and/or rK39 immunochromatographic test- and/or leishmanin skin test-positive subjects) in this population was 1.02% (95% confidence interval = 0–4.54), and prevalence was higher in boys and children older than 12 years. Only one case of active disease was encountered. The results suggest that the conditions responsible for the outbreak no longer reign. However, active surveillance remains necessary.
Despite major public health initiatives and the existence of efficacious treatment regimes, tuberculosis (TB) remains a threat, particularly in resource-limited settings. A significant part of the problem is the difficulty of rapidly identifying infected individuals, and as a result, there has been renewed interest in developing better diagnostics for infection or disease caused by Mycobacterium tuberculosis. Many of the existing tools, however, have limitations such as poor sensitivity or specificity, or the need for well-equipped laboratories to function effectively. Serodiagnostic approaches in particular have long drawn attention, due to their potential utility in large field studies, particularly in resource-poor settings. Unfortunately none of the serodiagnostic approaches have so far proven useful under field conditions.
We screened a large panel of antigens with serodiagnostic potential by ELISA and selected a subpanel that was strongly and broadly recognised by TB patients, but not by controls. These antigens were then formulated into a simple immuno-chromatographic lateral flow assay format, suitable for field use, and tested against panels of plasma and blood samples from individuals with different clinical status (confirmed TB patients, household contacts, and apparently healthy community controls), recruited from Ethiopia (a highly TB-endemic country) and Turkey (a TB meso-endemic country). While specificity was good (97-100% in non TB-endemic controls), the sensitivity was not as high as expected (46-54% in pulmonary TB, 25-29% in extra-pulmonary TB).
Though below the level of sensitivity the consortium had set for commercial development, the assay specifically identified M. tuberculosis-infected individuals, and provides a valuable proof of concept.
IgG; Antibody; TB; Antigen; Serology; Diagnosis; ELISA
Leprosy is not eradicable with currently available diagnostics or interventions as evidenced by its stable incidence. Early diagnosis of Mycobacterium leprae infection should therefore be emphasized in leprosy-research. It remains challenging to develop tests based on immunological biomarkers that distinguish individuals controlling bacterial replication from those developing disease.
To identify biomarkers for field-applicable diagnostics, we determined cytokines/chemokines induced by M. leprae proteins in blood of leprosy patients and controls (EC) from high leprosy-prevalence areas (Bangladesh, Brazil, Ethiopia) and from South Korea where leprosy is not endemic anymore.
M. leprae- sonicate induced IFN-γ was similar for all groups, excluding M. leprae/IFN-γ as a diagnostic read-out. By contrast, ML2478 and ML0840 induced high IFN-γ concentrations in Bangladeshi EC, which were completely absent for South Korean controls. Importantly, ML2478/IFN-γ could indicate distinct degrees of M. leprae exposure, and thereby the risk of infection and transmission, in different parts of Brazilian and Ethiopian cities.
Notwithstanding these discriminatory responses, M. leprae proteins did not distinguish patients from EC in one leprosy endemic area based on IFN-γ. Analyses of additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concentrations of MCP-1, MIP-1β and IL-1β in patients compared to EC, whereas IP-10, like IFN-γ, differed between EC from areas with dissimilar leprosy prevalence.
This study identifies M. leprae-unique antigens, particularly ML2478, as biomarker tools to measure M. leprae exposure using IFN-γ or IP-10, and also shows that MCP-1, MIP-1β and IL-1β can potentially distinguish pathogenic immune responses from those induced during asymptomatic exposure to M. leprae.
Mycobacterium leprae (M. leprae); biomarkers; leprosy; multiplex analysis
In areas where visceral leishmaniasis is anthroponotic, asymptomatically infected patients may play a role in transmission. Additionally, the number of asymptomatic patients in a disease-endemic area will also provide information on transmission dynamics. Libo Kemkem and Fogera districts (Amhara State, Ethiopia) are now considered newly established areas to which visceral leishmaniasis is endemic. In selected villages in these districts, we conducted a study to assess the usefulness of different approaches to estimate the asymptomatic infection rate. Of 605 participants, the rK39 immunochromatographic test was able to detect asymptomatic infection in 1.5% (9 of 605), direct agglutination test in 5.3% (32 of 605), and leishmanin skin test in 5.6% (33 of 589); the combined use of serologic methods and leishmanin skin test enabled detecting asymptomatic infection in 10.1% (61 of 605). We conclude that the best option to detect asymptomatic infection in this new visceral leishmaniasis–endemic focus is the combined use of the direct agglutination test and the leishmanin skin test.
Cryptococcal disease is estimated to be responsible for significant mortality in Sub-Saharan Africa; however, only scarce epidemiology data exists. We sought to evaluate the prevalence of and risk factors for cryptococcal antigenemia in Ethiopia.
Consecutive adult HIV-infected patients from two public HIV clinics in Addis Ababa, Ethiopia were enrolled into the study. A CD4 count ≤200 cells/μl was required for study participation. Patients receiving anti-retroviral therapy (ART) were not excluded. A cryptococcal antigen test was performed for all patients along with an interview, physical exam, and medical chart abstraction. Logistic regression analysis was used to assess risk factors for cryptococcal antigenemia.
369 HIV-infected patients were enrolled; mean CD4 123 cells/μl and 74% receiving ART. The overall prevalence of cryptococcal antigenemia was 8.4%; 11% in patients with a CD4 count <100 cells/μl, 8.9% with CD4 100 to 150 cells/μl and 5.7% with CD4150-200 cell/μl. 84% of patients with cryptococcal antigenemia were receiving ART. In multivariable analysis, increasing age, self reported fever, CD4 count <100 cells/μl, and site of screening were associated with an increased risk of cryptococcal antigenemia. No individual or combination of clinical symptoms had optimal sensitivity or specificity for cryptococcal antigenemia.
Cryptococcal antigenemia is high in Ethiopia and rapid scale up of screening programs is needed. Screening should be implemented for HIV-infected patients with low CD4 counts regardless of symptoms or receipt of ART. Further study into the effect of location and environment on cryptococcal disease is warranted.
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.
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
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.
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.
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.
Understanding the genetic diversity of Mycobacterium tuberculosis is needed for a better understanding of the epidemiology of TB and could have implications for the development of new diagnostics, drugs, and vaccines. M. tuberculosis isolates were characterized using spoligotyping and were compared with the SpoIDB4 database of the Pasteur Institute of Guadeloupe. A total of 53 different patterns were identified among 192 isolates examined. 169 of the isolates were classified into one of the 33 shared SITs, whereas the remaining 23 corresponded to 20 orphan patterns. 54% of the isolates were ascribed to the T family, a family which has not been well defined to date. Other prominent families were CAS, Haarlem, LAM, Beijing, and Unknown comprising 26%, 13%, 2.6%, 0.5%, and 2.1%, respectively. Among HIV-positive patients, 10 patterns were observed among 25 isolates. The T (38.5%), H (26.9%), and CAS (23.1%) families were the most common among HIV-positive individuals. The diversity of the M. tuberculosis strains found in this study is very high, and there was no difference in the distribution of families in HIV-positive and HIV-negative TB patients except the H family. Tuberculosis transmission in Addis Ababa is due to only the modern M. tuberculosis families (CAS, LAM, T, Beijing, Haarlem, and U).
Neglected tropical diseases (NTDs) are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward.
This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA), the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway.
Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of NTDs, integrated mapping, rapid scale up of interventions and operational research into co implementation of intervention packages will be crucial.
Names of WHO listed neglected tropical disease; Integration; Elimination; Ethiopia
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%).
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.
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.
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.)
In northern Ethiopia the prevalence of visceral leishmaniasis is steadily rising posing an increasing public health concern. In order to develop effective control strategies on the transmission of the disease it is important to generate knowledge on the epidemiological determinants of the infection.
We conducted a cross-sectional survey on children 4–15 years of age using a multi staged stratified cluster sampling on high incidence sub-districts of Amhara regional state, Ethiopia. The survey included a socio-demographic, health and dietary questionnaire, and anthropometric measurements. We performed rK39-ICT and DAT serological tests in order to detect anti-Leishmania antibodies and carried out Leishmanin Skin Test (LST) using L.major antigen. Logistic regression models were used. Of the 565 children surveyed 56 children were positive to infection (9.9%). The individual variables that showed a positive association with infection were increasing age, being male and sleeping outside [adjusted odds ratios (95% CI): 1.15 (1.03, 1.29), 2.56 (1.19, 5.48) and 2.21 (1.03, 4.71) respectively] and in relation to the household: past history of VL in the family, living in a straw roofed house and if the family owned sheep [adjusted OR (95% CI): 2.92 (1.25, 6.81), 2.71 (1.21, 6.07) and 4.16 (1.41, 12.31) respectively].
A behavioural pattern like sleeping outside is determinant in the transmission of the infection in this area. Protective measures should be implemented against this identified risk activity. Results also suggest a geographical clustering and a household focalization of the infection. The behaviour of the vector in the area needs to be clarified in order to establish the role of domestic animals and house materials in the transmission of the infection.
Visceral leishmaniasis is a vector borne disease that can be fatal if left untreated. Its prevalence is steadily rising in northern Ethiopia posing a public health challenge in the region. We conducted a study on the factors associated to asymptomatic infection in Libo Kemkem and Fogera, Amhara regional state, where little is known about Leishmania transmission. Sleeping outside was identified as a risk activity so measures towards it are recommended. Our results also showed a geographical clustering and a household focalization of the infection although the reasons behind it are not clearly understood. More entomological studies are needed in order to clarify the vecto's behaviour in the area. Individuals living in houses that owned sheep were more likely to be infected but no association was found with other domestic animals like cattle chicken or dogs. These results add up to the debate found in the literature regarding the role of domestic animals in the transmission of Leishmania in different regions of the world. No specific recommendation should be given until the exact role of the domestic animal in the transmission cycle is clearly understood.
Epidemiological evidence from tuberculosis outbreaks revealed that some genotypes of M. tuberculosis are more transmissible and capable of causing disease than others. We analysed the plasma cytokine levels of pulmonary tuberculosis patients infected with different strains of M. tuberculosis to test the hypothesis that immune responses would be linked to the bacterial genotype. Spoligotyping was carried out for genotyping, and we used Luminex technology to measure 17 cytokines (EGF, fractalkine, GM-CSF, IFN-γ, IL-1, IL-10, IL-12, IL-17, IL-4, IL-7, IL-9, IP-10, MCP-1, MCP-3, MIP-1β, TNF, and VEGF) from plasma samples of tuberculosis patients. The levels of IL-12 (p40), IL-4, IL-7, and MIP-1beta were higher in patients infected with lineage 3, however, it was only IL-4 which showed statistically significant difference (P < 0.05) between lineage 3 and lineage 4. We further grouped the lineages into families (CAS, H and T families), and we found that the plasma level of IL-4 was significantly higher in patients infected with the CAS family (P < 0.05) in comparison with T and H families. However, there was no difference between T and H families. Therefore, the higher level of IL-4 in lineage 3 families might indicate that possible differences in the response elicited from host depend on strain lineages in the studied population.
Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls.
Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment.
Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well.
One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group.
One third of the world’s population is thought to have latent tuberculosis infection (LTBI) with the potential for subsequent reactivation of disease. To better characterize this important population, studies comparing Tuberculin Skin Test (TST) and the new interferon-γ release assays including QuantiFERON®-TB Gold In-Tube (QFT-GIT) have been conducted in different parts of the world, but most of these have been in countries with a low incidence of tuberculosis (TB). The aim of this study was therefore to evaluate the use of QFT-GIT assay as compared with TST in the diagnosis of LTBI in Ethiopia, a country with a high burden of TB and routine BCG vaccination at birth.
Healthy medical and paramedical male students at the Faculty of Medicine, Addis Ababa University, Ethiopia were enrolled into the study from December 2008 to February 2009. The TST and QFTG-IT assay were performed using standard methods.
The mean age of the study participants was 20.9 years. From a total of 107 study participants, 46.7% (95%CI: 37.0% to 56.6%) had a positive TST result (TST≥10 mm), 43.9% (95%CI: 34.3% to 53.9%) had a positive QFT-GIT assay result and 44.9% (95%CI: 35.2% to 54.8%) had BCG scar. There was strong agreement between TST (TST ≥10mm) and QFT-GIT assay (Kappa = 0.83, p value = 0.000).
The TST and QFT-GIT assay show similar efficacy for the diagnosis of LTBI in healthy young adults residing in Ethiopia, a country with high TB incidence.
Tuberculosis; Latent; BCG; Tuberculin skin test; Interferon-γ release assay; Ethiopia
Monitoring 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.
Medical 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.
Out 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.
Treatment 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.
Smear-positive; Treatment outcome; Pulmonary tuberculosis; Tigray; Ethiopia
In Ethiopia where there is no strong surveillance system and diagnostic facilities are limited, the real burden of tuberculosis (TB) lymphadenitis is not well known. Therefore, we conducted a study to estimate the prevalence of TB lymphadenitis in Southwest Ethiopia.
A community based cross-sectional study was conducted from February to March 2009 in the Gilgel Gibe field research area. A total of 30,040 individuals 15 years or older in 10,882 households were screened for TB lymphadenitis. Any individual 15 years or older with lumps in the neck, armpits or groin up on interview were considered TB lymphadenitis suspect. The diagnosis of TB lymphadenitis was established when acid fast bacilli (AFB) smear microscopy of fine needle aspiration (FNA) sample, culture or cytology suggested TB. HIV counseling and testing was offered to all TB lymphadenitis suspects. Descriptive and bivariate analysis was done using SPSS version 15.
Complete data were available for 27,597 individuals. A total of 87 TB lymphadenitis suspects were identified. Most of the TB lymphadenitis suspects were females (72.4%). Sixteen cases of TB lymphadenitis were confirmed. The prevalence of TB lymphadenitis was thus 58.0 per 100,000 people (16/27,597) (95% CI 35.7-94.2). Individuals who had a contact history with chronic coughers (OR 5.58, 95% CI 1.23-25.43) were more likely to have TB lymphadenitis. Lymph nodes with caseous FNA were more likely to be positive for TB lymphadenitis (OR 5.46, 95% CI 1.69-17.61).
The prevalence of TB lymphadenitis in Gilgel Gibe is similar with the WHO estimates for Ethiopia. Screening of TB lymphadenitis particularly for family members who have contact with chronic coughers is recommended. Health extension workers could be trained to screen and refer TB lymphadenitis suspects using simple methods.
TB lymphadenitis; Prevalence; Jimma; Ethiopia
Background and Objective
The relative contribution of nitric oxide (NO) to the killing of Mycobacterium tuberculosis in human tuberculosis (TB) is controversial, although this has been firmly established in rodents. Studies have demonstrated that clinical strains of M. tuberculosis differ in susceptibility to NO, but how this correlates to drug susceptibility and clinical outcome is not known.
In this study, 50 sputum smear- and culture-positive patients with pulmonary TB in Gondar, Ethiopia were included. Clinical parameters were recorded and drug susceptibility profile and spoligotyping patterns were investigated. NO susceptibility was studied by exposing the strains to the NO donor DETA/NO.
Clinical isolates of M. tuberculosis showed a dose- and time-dependent response when exposed to NO. The most frequent spoligotypes found were CAS1-Delhi and T3_ETH in a total of nine known spoligotypes and four orphan patterns. There was a significant association between reduced susceptibility to NO (>10% survival after exposure to 1 mM DETA/NO) and resistance against first-line anti-TB drugs, in particular isoniazid (INH). Patients infected with strains of M. tuberculosis with reduced susceptibility to NO showed no difference in cure rate or other clinical parameters but a tendency towards lower rate of weight gain after two months of treatment, independent of antibiotic resistance.
There is a correlation between resistance to first-line anti-TB drugs and reduced NO susceptibility in clinical strains of M. tuberculosis. Further studies including the mechanisms of reduced NO susceptibility are warranted and could identify targets for new therapeutic interventions.
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.
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.
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.