Immunohistochemistry-derived subtypes of breast cancer distribution in four regions of Ethiopia.

Purpose: Different biological characteristics, therapeutic responses, and disease-specific outcomes are associated with different molecular subtypes of breast cancer (BC). Although there have been different studies on BC in the Ethiopian capital city of Addis Ababa, there have been few studies in other parts of the nation, and none have evaluated biological characteristics in other locations in the context of the extensive ethnic and genetic diversity found in Ethiopia. This study was carried out to evaluate the distribution of immunohistochemistry (IHC) subtypes of BCs throughout four Ethiopian regions. Methods: A total of 227 formalin-fixed paraffin-embedded (FFPE) tissue blocks were collected from tertiary hospitals in four Ethiopian regions between 2015 and 2021. The IHC staining was performed for subtyping, ER, PR, HER2, and Ki-67 proliferation markers. Results: The mean age at diagnosis was 43.9 years. The percentage of ER and PR-negative tumors were 48.3% and 53.2%, respectively. The IHC subtypes showed the following distribution: 33.1% triple-negative breast cancer (TNBC), 27.6% luminal B, 25.2% luminal A, and 14.1% HER2 enriched. In multiple logistic regression analysis, grade III and HER2 positivity were associated with larger tumor size, and also originating from Jimma compared to Mekele. Conclusion: Patients with ER-negative, PR-negative, and TNBC were found in 48.3%, 53.2%, and 33.1% of cases, respectively, showing that half the patients could potentially benefit from endocrine treatment. A considerably high prevalence of TNBC was reported in our study, demanding additional research that includes genetic predisposition factors. Additionally, aggressive tumors were found in a high percentage of younger age groups, which must be considered when planning personalized treatment strategies.

Inflammatory immune profiles associated with disease severity in pulmonary tuberculosis patients with moderate to severe clinical TB or anemia.

Background: Immune control of Mycobacterium tuberculosis (Mtb) infection is largely influenced by the extensive disease heterogeneity that is typical for tuberculosis (TB). In this study, the peripheral inflammatory immune profile of different sub-groups of pulmonary TB patients was explored based on clinical disease severity, anemia of chronic disease, or the radiological extent of lung disease. Methods: Plasma samples were obtained from n=107 patients with active pulmonary TB at the time of diagnosis and after start of standard chemotherapy. A composite clinical TB symptoms score, blood hemoglobin status and chest X-ray imaging were used to sub-group TB patients into 1.) mild and moderate-severe clinical TB, 2.) anemic and non-anemic TB, or 3.) limited and extensive lung involvement. Plasma levels of biomarkers associated with inflammation pathways were assessed using a Bio-Plex Magpix 37-multiplex assay. In parallel, Th1/Th2 cytokines were quantified with a 27-multiplex in matched plasma and cell culture supernatants from whole blood stimulated with M. tuberculosis-antigens using the QuantiFERON-TB Gold assay. Results: Clinical TB disease severity correlated with low blood hemoglobin levels and anemia but not with radiological findings in this study cohort. Multiplex protein analyses revealed that distinct clusters of inflammation markers and cytokines separated the different TB disease sub-groups with variable efficacy. Several top-ranked markers overlapped, while other markers were unique with regards to their importance to differentiate the TB disease severity groups. A distinct immune response profile defined by elevated levels of BAFF, LIGHT, sTNF-R1 and 2, IP-10, osteopontin, chitinase-3-like protein 1, and IFNα2 and IL-8, were most effective in separating TB patients with different clinical disease severity and were also promising candidates for treatment monitoring. TB patients with mild disease displayed immune polarization towards mixed Th1/Th2 responses, while pro-inflammatory and B cell stimulating cytokines as well as immunomodulatory mediators predominated in moderate-severe TB disease and anemia of TB. Conclusions: Our data demonstrated that clinical disease severity in TB is associated with anemia and distinct inflammatory immune profiles. These results contribute to the understanding of immunopathology in pulmonary TB and define top-ranked inflammatory mediators as biomarkers of disease severity and treatment prognosis.

Anemia Is a Strong Predictor of Wasting, Disease Severity, and Progression, in Clinical Tuberculosis (TB).

A typical trait of chronic tuberculosis (TB) is substantial weight loss that concurs with a drop in blood hemoglobin (Hb) levels, causing anemia. In this observational study, we explored Hb levels in 345 pulmonary TB patients. They were divided into anemic or non-anemic groups which related to clinical symptoms, anthropometric measurements, and immune status. Data was obtained in a randomized controlled trial that we previously conducted using nutritional supplementation of TB patients in Ethiopia. A post hoc analysis demonstrated that anemic patients have a higher composite clinical TB score at baseline than non-anemic patients. Consequently, Hb values were significantly lower in underweight patients with moderate to severe disease and/or cavitary TB compared to normal weight patients with mild disease or non-cavitary TB. Anemia was associated with a low body mass index (BMI), low mid-upper arm circumference (MUAC), lower peripheral CD4 and CD8 T cells counts and IFN-γ levels, and a higher erythrocyte sedimentation rate (ESR). Chronic inflammation and TB disease progression appeared to be driven by elevated systemic levels of pro-inflammatory IL-6 in anemic patients. Multivariable modeling confirmed that a low Hb and a low BMI were key variables related to an unfavorable TB disease status. Although Hb levels increased with successful chemotherapy, anemic TB patients maintained a slower clinical recovery compared to non-anemic patients during the intensive phase treatment (two months). In conclusion, anemia is a strong predictor of wasting, disease severity, inflammation, and slower recovery in patients with pulmonary TB.

Immunosuppressive Features of the Microenvironment in Lymph Nodes Granulomas from Tuberculosis and HIV-Co-Infected Patients.

Tuberculosis (TB) and HIV co-infection claims many lives every year. This study assessed immune responses in Mycobacterium tuberculosis-infected lymph node tissues from HIV-negative and HIV-positive patients compared with the peripheral circulation with a focus on myeloid cells and the cell-signaling enzymes, inducible nitric oxide synthase, and arginase (Arg)-1. Methods included immunohistochemistry or confocal microscopy and computerized image analyses, quantitative real-time PCR, multiplex Luminex, and flow cytometry. These findings indicate enhanced chronic inflammation and immune activation in TB/HIV co-infection but also enhanced immunosuppressive responses. Poorly formed necrotic TB granulomas with a high expression of M. tuberculosis antigens were elevated in TB/HIV-co-infected lymph nodes, and inducible nitric oxide synthase and Arg-1 expression was significantly higher in TB/HIV-co-infected compared with HIV-negative TB or control tissues. High Arg-1 expression was found in myeloid cells with a phenotype characteristic of myeloid-derived suppressor cells (MDCS) that were particularly abundant in TB/HIV-co-infected tissues. Accordingly, Lin-/HLA-DRlow/int/CD33+/CD11b+/CD15+ granulocytic myeloid-derived suppressor cells were significantly elevated in blood samples from TB/HIV-co-infected patients. CD15+ myeloid-derived suppressor cells correlated with plasma HIV viral load and M. tuberculosis antigen load in tissue but were inversely associated with peripheral CD4 T-cells counts. Enhanced chronic inflammation driven by M. tuberculosis and HIV co-infection may promote Arg-1-expressing MDSCs at the site of infection thereby advancing TB disease progression.

Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field.

Tuberculosis (TB) remains one of the deadliest infectious diseases in the world and every 20 seconds a person dies from TB. An important attribute of human TB is induction of a granulomatous inflammation that creates a dynamic range of local microenvironments in infected organs, where the immune responses may be considerably different compared to the systemic circulation. New and improved technologies for in situ quantification and multimodal imaging of mRNA transcripts and protein expression at the single-cell level have enabled significantly improved insights into the local TB granuloma microenvironment. Here, we review the most recent data on regulation of immunity in the TB granuloma with an enhanced focus on selected in situ studies that enable spatial mapping of immune cell phenotypes and functions. We take advantage of the conceptual framework of the cancer-immunity cycle to speculate how local T cell responses may be enhanced in the granuloma microenvironment at the site of Mycobacterium tuberculosis infection. This includes an exploratory definition of "hot", immune-inflamed, and "cold", immune-excluded TB granulomas that does not refer to the level of bacterial replication or metabolic activity, but to the relative infiltration of T cells into the infected lesions. Finally, we reflect on the current knowledge and controversy related to reactivation of active TB in cancer patients treated with immune checkpoint inhibitors such as PD-1/PD-L1 and CTLA-4. An understanding of the underlying mechanisms involved in the induction and maintenance or disruption of immunoregulation in the TB granuloma microenvironment may provide new avenues for host-directed therapies that can support standard antibiotic treatment of persistent TB disease.

Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1.

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.

Daily Nutritional Supplementation with Vitamin D3 and Phenylbutyrate to Treatment-Naïve HIV Patients Tested in a Randomized Placebo-Controlled Trial.

Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD3) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD3 (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, n = 197) and per-protocol (n = 173) analyses. Secondary endpoints: longitudinal HIV viral load, T cell counts, body mass index (BMI), middle-upper-arm circumference (MUAC), and 25(OH)D3 levels in plasma. Baseline characteristics were detectable viral loads (median 7897 copies/mL), low CD4⁺ (median 410 cells/µL), and elevated CD8⁺ (median 930 cells/µL) T cell counts. Most subjects were vitD3 deficient at enrolment, but a gradual and significant improvement of vitD3 status was demonstrated in the vitD3 + PBA group compared with placebo (p < 0.0001) from week 0 to 16 (median 37.5 versus 115.5 nmol/L). No significant changes in HIV viral load, CD4⁺ or CD8⁺ T cell counts, BMI or MUAC could be detected. Clinical adverse events were similar in both groups. Daily vitD3 + PBA for 16 weeks was well-tolerated and effectively improved vitD3 status but did not reduce viral load, restore peripheral T cell counts or improve BMI or MUAC in HIV patients with slow progressive disease. Clinicaltrials.gov NCT01702974.

Vitamin D3 Status and the Association with Human Cathelicidin Expression in Patients with Different Clinical Forms of Active Tuberculosis.

Low vitamin D (vitD3) is one of the most common nutritional deficiencies in the world known to be associated with numerous medical conditions including infections such as tuberculosis (TB). In this study, vitD3 status and its association with the antimicrobial peptide, human cathelicidin (LL-37), was investigated in Ethiopian patients with different clinical forms of TB. Patients with active TB (n = 77) and non-TB controls (n = 78) were enrolled in Ethiopia, while another group of non-TB controls (n = 62) was from Sweden. Active TB included pulmonary TB (n = 32), pleural TB (n = 20), and lymph node TB (n = 25). Concentrations of 25-hydroxyvitamin D3 (25(OH)D3) were assessed in plasma, while LL-37 mRNA was measured in peripheral blood and in samples obtained from the site of infection. Median 25(OH)D3 plasma levels in active TB patients were similar to Ethiopian non-TB controls (38.5 versus 35.0 nmol/L) and vitD3 deficiency (.

LATENT TUBERCULOSIS AMONG ADULT ETHIOPIAN PATIENTS AT CHEST CLINIC, TIKURANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHIOPIA.

Background: One-third of the world population is infected with Mycobacterium tuberculosis. Most people exposed to M. tuberculosis showed no evidence of active disease. About 5-10% of people with latent tuberculosis infection (LTBI) without HIV will progress to develop active tuberculosis (TB) in their lifetimes. This study was conducted to determine the magnitude of latent TB among the adult population at a teaching and referral Hospital in Ethiopia. Methods: This study was conducted at the Chest clinic of Tikur Anbessa Specialized Hospital during 2010-2013. The study was a cross-sectional study conducted among healthy adults after informed consent was obtained from each individual. Tuberculin skin test (TST) and Interferon Gamma whole blood assay (Quantiferon-Tuberculosis- Gold) was performed using enzyme linked immuno-sorbent assay. Average CD4, CD8, CD3 and CD4:CD8 ratio was determined for all study participants. Results: From a total of 70 healthy adults tested for LTBI using Quantiferon Gold, 45(64%) tested positive and 25 (36%) were negative for latent tuberculosis infection. From the 66 healthy individuals who were tested using TST for LTBI, 42 (62%) individuals were TST positive and 25 (38%) individuals were TST negative. Average CD4, CD8, CD3 and CD4:CD8 ratio was 748, 598, 1401 and 1.4, respectively. Conclusions: The magnitude of latent tuberculosis infection was high in this study, which reflects existing high prevalence of TB. TST and Quantiferon-Tuberculosis-Gold assay show similar efficacy for the diagnosis of LTBI in healthy Ethiopian adults. The absolute CD4 T-cell counts of healthy HIV- negative Ethiopians are considerably lower than CD4 T cell counts in other countries.

Latent tuberculosis among adult Ethiopian patients at chest clinic, Tikuranbessa specialized hospital, Addis Ababa, Ethiopia

Background: One-third of the world population is infected with mycobacterium tuberculosis. Most people exposed to mycobacterium tuberculosis showed no evidence of active disease. About 5-10% of latent tuberculosis infection without HIV will progress to developed active tuberculosis in their lifetimes. This study was conducted to determine the magnitude of Latent TB among the adult population at a teaching and referral Hospital in Ethiopia.Methods: This study was conducted at the Chest clinic of Tikur Anbessa Specialized Hospital during 2010-2013.The study was a cross-sectional study conducted among healthy adults after informed consent was obtained from each individual. Tuberculin skin test and Interferon Gamma whole blood assay (Quantiferon-Tuberculosis-Gold) was performed using Enzyme linked Immuno-sorbent Assay. Average CD4, CD8, CD3 and CD4:CD8 ratio was determined for all study participants. Results:From a total of 70 healthy adults tested for latent tuberculosis infection using Quantiferon Gold,45(64%) tested positive and 25 (36%) were negative for latent tuberculosis infection. From the sixty six healthy individuals who were tested using tuberculin skin test for latent tuberculosis infection, 42 (62%) individuals were Tuberculin skin test positive and 25 (38%) individuals were Tuberculin skin test negative. Average CD4, CD8, CD3 and CD4:CD8 ratio was 748, 598, 1401 and 1.4, respectively. Conclusions: The magnitude of latent tuberculosis infection was high in this study, which reflects existing high prevalence of tuberculosis.Tuberculin skin test and Quantiferon-Tuberculosis-Goldassay show similar efficacy for the diagnosis of latent tuberculosis infection in healthy Ethiopian adults. The absolute CD4 T-cell counts of healthy HIV-negative Ethiopian's are considerably lower than other countries

Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3.

In this study, we explored the local cytokine/chemokine profiles in patients with active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of bronchoalveolar lavage and pleural fluid samples. Despite increased pro-inflammation compared to the uninfected controls; there was no up-regulation of IFN-γ or the T cell chemoattractant CCL5 in the lung of patients with pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4, CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN-γ, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2 immune response signature found in patients with progressive pulmonary TB could result from inappropriate cytokine/chemokine responses and excessive SOCS3 expression that may represent potential targets for clinical TB management.

Genotyping of human papillomavirus in paraffin embedded cervical tissue samples from women in Ethiopia and the Sudan.

Cervical cancer is the most frequent female malignancy in most developing countries. Previous studies have demonstrated a strong association of human papillomavirus (HPV) infection with dysplasia and carcinoma of the uterine cervix. The objective of this study was to identify the prevailing HPV genotypes responsible for the development of cervical cancer among women in Ethiopia and the Sudan. A molecular characterization of HPV was done on 245 paraffin embedded cervical biopsy samples collected from the two countries. Amplification of HPV and subsequent genotyping was done using SPF10 primers and Line probe assay. Of samples collected from Ethiopian patients, 93% (149/160) and 13% (21/160) had high risk and low risk HPV genotypes, respectively. Among samples collected from the Sudan, 94% (80/85) harbored high risk and 11.7% (10/85) low risk HPV genotypes. Human papillomavirus 16 was the most frequent genotype identified in samples from Ethiopia (91%, 136/149) and the Sudan (82.5%, 66/80). HPV 52, 58, and 18 were the second, third and fourth common genotypes identified in Ethiopia, whereas HPV 18, 45, and 52 were the second, third, and fourth genotypes identified in samples collected from the Sudan. Thus, individuals living in different geographical localities should receive vaccines based on the specific genotypes circulating in the area and a vaccine targeting HPV 16, 18, 45, 52, and 58 may be optimal for the control of cervical cancer in the two countries.

BCG-specific IgG-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in HIV negative and HIV positive patients.

BACKGROUND: Diagnosis of active tuberculosis (TB) among sputum-negative cases, patients with HIV infection and extra-pulmonary TB is difficult. In this study, assessment of BCG-specific IgG-secreting peripheral plasmablasts, was used to identify active TB in these high-risk groups. METHODS: Peripheral blood mononuclear cells were isolated from patients with TB and controls and cultured in vitro using an assay called Antibodies in Lymphocyte Supernatant, which measures spontaneous IgG antibody release from migratory plasmablasts. A BCG-specific ELISA and flow cytometry were used to quantify in vivo activated plasmablasts in blood samples from Ethiopian subjects who were HIV negative or HIV positive. Patients diagnosed with different clinical forms of sputum-negative active TB or other diseases (n=96) were compared with asymptomatic individuals including latent TB and non-TB controls (n=85). Immunodiagnosis of TB also included the tuberculin skin test and the interferon (IFN)-γ release assay, QuantiFERON. RESULTS: This study demonstrated that circulating IgG+ plasmablasts and spontaneous secretion of BCG-specific IgG antibodies were significantly higher in patients with active TB compared with latent TB cases and non-TB controls. BCG-specific IgG titres were particularly high among patients coinfected with TB and HIV with CD4 T-cell counts <200 cells/ml who produced low levels of Mycobacterium tuberculosis-specific IFNγ in vitro. CONCLUSIONS: These results suggest that BCG-specific IgG-secreting peripheral plasmablasts could be successfully used as a host-specific biomarker to improve diagnosis of active TB, particularly in people who are HIV positive, and facilitate administration of effective treatment to patients. Elevated IgG responses were associated with impaired peripheral T-cell responses, including reduced T-cell numbers and low M tuberculosis-specific IFNγ production.

Pattern of upper gastrointestinal tumors at Tikur Anbessa Teaching Hospital in Addis Ababa, Ethiopia: a ten-year review.

BACKGROUND: Due to lack of public awareness and cancer surveillance, patients in developing countries usually present with advanced and terminal malignancies. The absence of early diagnostic facilities and standard chemotherapeutic and radiotherapy services in low-income countries further confound the problem in the care of such patients. Moreover, the prevalence of cancers (including upper GI malignancies) is unknown in Ethiopia due to lack of national cancer registry. OBJECTIVE: To assess the type and the pattern of upper GI tumors among the patients whose upper GI tract biopsies were seen at the Tikur Anbessa Hospital (TAH) during September 1, 1992 through August 31, 2002. METHODOLOGY: A ten-year retrospective analysis of upper gastrointestinal tract (UGIT) biopsy reports of adult patients was made at the Tikur Anbessa teaching Hospital. RESULTS: There were 608 UGIT biopsy specimens submitted to the pathology department of Addis Ababa University Medical Faculty, from different hospitals and clinics in the country for histological studies. There were 369 males (67.7%) and 239 (39.3%) females with a male to female ratio of 1.5:1. The mean age for males was 50 years while 48 years for females. Although most of biopsies were submitted from Addis Ababa and Shewa, esophageal squamous cell carcinoma and adenocarcinoma were apparently predominant among the patients from Arsi and Bale areas as compared to Addis Ababa and other regions. The mean duration of major presenting symptoms was 4-6 months both for esophageal and gastric cancers. In this study, upper GI endoscopy had a 90% correlation with the histological diagnosis. CONCLUSION: Esophageal cancers were observed to be relatively common among the patients from Arsi and Bale zones while gastric cancers were apparently predominant among patients referred from Addis Ababa. Upper GI endoscopic diagnosis was also noted to correlate well with the histological diagnosis.

Identification and genotyping of the etiological agent of tuberculous lymphadenitis in Ethiopia.

BACKGROUND: In Ethiopia, little has been done to assess how Mycobacterium bovis has contributed to human tuberculosis, though the population routinely consumes unpasteurized milk and raw meat. The aim of this study was to determine the proportion of M. tuberculosis and M. bovis as etiological agents of tuberculous lymphadenitis (TBLN). METHODS: Patients with lymphadenopathy (n = 171) were included in a cross-sectional study at Butajira Hospital, Southern Ethiopia. Lymph node biopsies were cultured. Patients' HIV status was identified. DNA from positive cultures was tested by PCR to identify M. bovis and M. tuberculosis. Isolates were genotyped by multiplex ligation-dependent probe amplification (MLPA) assay. RESULTS: Among 171 patients, 156 had culture results. Of these, 107 (69%) were positive for M. tuberculosis complex (MTC). Six of the 10 HIV-positive patients were culture positive. M. tuberculosis specific sequences were identified in the DNA of each of 100 samples as assessed by RD10 targeted PCR, and each of the 95 isolates exhibited the M. tuberculosis specific TbD1 deletion by MLPA analysis. No M. bovis was identified. These results indicate that all the isolates were modern M. tuberculosis strains. Furthermore, MLPA studies confirmed that 42% of the isolates showed the Haarlem genotype and 12% displayed sequences compatible with INH resistance. No mutations conferring resistance to ethambutol or rifampicin were detected. CONCLUSIONS: Our data showed that M. tuberculosis strains had common characteristics with strains causing pulmonary TB, which appears to be the main etiological agent of TBLN.

Compartmentalization of immune responses in human tuberculosis: few CD8+ effector T cells but elevated levels of FoxP3+ regulatory t cells in the granulomatous lesions.

Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-beta and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-beta and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control.

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.

Most common causes of natural and injury-related deaths in Addis Ababa, Ethiopia.

In Ethiopia, like many developing countries, autopsy is rare unless conducted in the medico-legal arena, making vital statistics that include pathological diagnoses sparse. To determine the most common factors contributing to death among individuals who died from natural or injury-related events in Ethiopia 200 consecutive autopsies were conducted in 2006 at the Forensic Medico-legal Pathology Department, Menelik II Hospital, Addis Ababa, Ethiopia. The results describe significant pathological observations, putative cause of death, age distribution, and gender ratios. Eighty-one percent of the cases were male, and the mean age was 38.9 (+/-15.5 years). Fifty-two percent of the individuals died from natural causes, including infections, and 48% died from injury-related events. In the natural deaths group, as determined by gross examination at autopsy pulmonary complications were the most commonly reported cause of death, with suspected tuberculosis accounting for 12%. Tuberculosis (21, 8%) and liver disease (14, 5%) were the most common histopathological findings in the natural and injury-related causes groups, respectively. In the injury-related group, automobile accident was the most common cause of accidental death (80%), and homicide by beating was the most common cause of death in the intentional injury group (31%). These data provide valuable unbiased analyses of causes of death among individuals in Addis Ababa, Ethiopia.

Meningiomas: clinical correlates, skull x-ray, CT and pathological evaluations.

OBJECTIVE: To assess the frequency and the diagnostic performance of plain skull x-ray and and CT of meningiomas. METHODS: All pathologically diagnosed intracranial meningiomas in patients seen at Tikur Anbessa Hospitals were reviewed. RESULTS: Between December 1999 and July 2004 there were 25 histologically diagnosed cases of meningioma at the Tikur Anbessa Hospital (TAH). The duration of symptoms was ranging from 0.5-10 yrs. (mean 2.4 +/- 2.1 yrs) and age ranging from 21-57 yrs (mean age of 49.3 +/- 10 yrs.) with M:F ratio of 1.2:1. Blurring of vision was the commonest clinical presentation. Clinical correlates, skull x-rays, computerized tomographic results and pathology are evaluated. Plain skull x-ray findings were normal in 12/23 (52%); 10/23(43%) of the cases had non-specific sellar changes of raised intra-cranial pressure. Twenty-three of the 25 meningiomas had CT scanning done, and CT diagnosed 17/23 (74%) meningiomas correctly. Two meningiomas were unusual in location: one was intranasal and the other was intra-ventricular. Parasellar tumors were frequent sites of misdiagnosis. The commonest locations were parasellar and cerebral convexity, each accounting for 6/25 (24%) of the cases. The commonest CT observation was intense and homogeneous enhancement 15/23 (65%). Meningothelial meningioma was the commonest cellular type accounting for 11/25 (46%) of the pathologies followed by the transitional 4/25 (16%) and the atypical and psammomatous types, each with equalfrequency, 3/25 (12%). CONCLUSION: CT scan had a diagnostic accuracy of 83%, sensitivity of 74%, specificity of 95%, positive predictive value (PPV) of 95%, and negative predictive value (NPV) of 75%. Statistical analysis verifies the pre-operative reliability for diagnosing meningiomas by CT scanning.

Prevalence of Helicobacter pylori vacA and cagA genotypes in Ethiopian dyspeptic patients.

A total of 300 gastric biopsy samples and 50 Helicobacter pylori isolates were collected from Ethiopian adult dyspeptic patients. The vacA and cagA genes were detected in 90 and 79% of biopsy specimens, respectively, and in 100 and 87% of clinical isolates, respectively. Both genes were detected in 84% of the gastric biopsy samples and in 87% of the clinical isolates. Among vacA genotypes, the s1/m1 genotype was the most common in gastric biopsy samples (48%). The vacA and cagA positive H. pylori strains were detected to a higher degree in patients with chronic active gastritis (71%) than patients with other histopathological findings (29%) (P < 0.05).