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.

Utilization of integrated community case management service of childhood illness (ICCM) and associated factors among under-five children in Shashogo district, Hadiya zone, south Ethiopia.

Background: Integrated community case management (ICCM) service is provision of concurrent clinical and preventive care by trained community health workers for common childhood illnesses in the community. In Ethiopia, integrated community case management (ICCM) service utilization is low and its magnitude is unknown as well as no adequate evidence on its associated factors. This study aimed to investigate use of integrated community case management service of childhood illness and factors associated with it. Methods: A community-based cross-sectional study was conducted in Shashogo district. A total of 422 mothers who have under-five children were selected using simple random sampling method. Structured interviewer administered pre-tested in 5% of the sample; questionnaire was used to collect data. Descriptive statistics, binary and multivariable logistic regression analyses were used. Results: The proportion of integrated community case management (ICCM) service utilization among sick under-five children in past six months at Shashogo district was found was 199(47.2%, with 95%CI:(43.2, 51.2)). Receiving training on health extension packages as model family AOR = 2.07(1.05, 4.08), experiencing frequent childhood illness AOR = 1.92(1.11, 3.33), having information about ICCM service AOR = 3.73(1.42, 9.76), and having a postnatal care visit in recent child AOR = 13(7.37, 23.06) were associated with utilization of integrated community case management service. Conclusion: ICCM service was not used as planned though there is offer of free of charge service nearby. ICCM service is affected by maternal and child health utilization. Hence, collaborative activities of information, education, and communication activities are needed.

Prevalence of human papillomavirus and Helicobacter pylori in esophageal and gastroesophageal junction cancer biopsies from a case-control study in Ethiopia.

BACKGROUND: Ethiopia lies in the high-risk corridor of esophageal squamous cell carcinoma in East Africa, where individuals with this malignancy often do not report established risk factors, suggesting unidentified etiologies. Here, we report the prevalence of mucosal human papillomavirus (HPV) and of Helicobacter pylori (H. pylori) detection in endoscopy-obtained esophageal and gastroesophageal junction biopsies and in oral cell specimens taken at the time of esophageal cancer diagnosis in a case-control study in Addis Ababa, Ethiopia. METHODS: DNA extraction was performed from fresh frozen tissue and oral cell pellets obtained with saline solution gargling subsequently fixed with ethanol. Mucosal HPV and H. pylori DNA was detected using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. The proportions of specimens testing positive were expressed as percentages, with binomial 95% confidence intervals. Agreement of results between tissue biopsy and oral cell specimens was estimated using the kappa statistic. Comparison of study participants' characteristics by test results was done using the Pearson chi-square test. RESULTS: HPV DNA was detected in 1 of 62 tumor specimens (2, 95% confidence interval (CI): 0-9%), corresponding to HPV16 type. HPV DNA was detected in the oral cavity of 7 cases (11, 95% CI: 5-22%) and 4 of 56 matched healthy controls (7, 95% CI: 2-17%), with multiple HPV types detected. Detection of H. pylori DNA was 55% (95% CI: 42-68%), and 20 of 34 H. pylori-positive specimens (59, 95% CI: 41-75%) were positive for the cagA gene. Agreement of detection rates between tissue and oral cells in cases was poor for HPV and for H. pylori. CONCLUSIONS: The prevalence of mucosal-type HPV was very low, whereas H. pylori was more commonly detected, with a high proportion testing positive for the pro-inflammatory gene cagA. These novel findings remain to be replicated in larger studies and with the addition of serological determinations to better understand their biological significance in the context of esophageal and gastroesophageal junction cancers.

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.

Qat use and esophageal cancer in Ethiopia: A pilot case-control study.

BACKGROUND: Qat (Catha edulis) chewing is reported to induce lesions in the buccal mucosa, irritation of the esophagus, and esophageal reflux. Case series suggest a possible etiological role in oral and esophageal cancers. This pilot study aimed to generate preliminary estimates of the magnitude and direction of the association between qat use and esophageal cancer (EC) risk and to inform the logistics required to conduct a multi-center case-control study. METHODS: Between May 2012 and May 2013, 73 EC cases (including 12 gastro-esophageal junction cases) and 133 controls matched individually on sex, age, and residence were enrolled at two endoscopy clinics and a cancer treatment hospital in Addis Ababa. A face-to-face structured questionnaire was administered. Qat use was defined as ever having chewed qat once a week or more frequently for at least one year. Odds ratios were calculated using conditional logistic regression. RESULTS: Only 8% of cases resided in Addis Ababa. Qat use was more frequent in cases (36%) than in controls (26%). A 2-fold elevation in EC risk was observed in ever qat chewers compared with never users in unadjusted conditional logistic regression (OR = 2.12; 95% CI = 0.94, 4.74), an association that disappeared after adjusting for differences in tobacco use, consumption of alcohol and green vegetables, education level, and religion (OR = 0.95; 0.22, 4.22). Among never tobacco users, however, a non-significant increase in EC risk was suggested in ever qat users also after adjustment. Increases in EC risk were observed with ever tobacco use, alcohol consumption, low consumption of green vegetables, a salty diet, illiteracy, and among Muslims; the four latter associations were significant. CONCLUSIONS: This pilot study generated EC risk estimates in association with a habit practiced by millions of people and never before studied in a case-control design. Results must be interpreted cautiously in light of possible selection bias, with some demographics such as education level and religion differing between cases and controls. A large case-control study with enrolment of EC cases and carefully matched controls at health facilities from high-risk areas in the countryside, where the majority of cases occur, is needed to further investigate the association between qat use and EC.

COMMON GENOTYPES AND TREATMENT OUTCOMES OF HCV INFECTION AMONG ETHIOPIAN PATIENTS: A PROSPECTIVE STUDY.

BACKGROUND: The treatment response of HCV infection is dependent on genotype and stage of the disease. However, genotype pattern and treatment outcomes of HCV infection among Ethiopian patients has not been studied so far. OBJECTIVES: To evaluate the common HCV genotypes and treatment outcomes among Ethiopian adult patients. METHOD: Adult patients aged 18 and above with HCV infection referred from various regions of the country were included in the study after written informed consent. As there was no free or insurance coverage for treatment of HCV infection in the country, those who could afford to pay for treatment with PEG Interferon and Ribavirin were recruited during January 1, 2008 through December 31,2013 at United Vision, Adera. Old Airport, and Mexico referral higher clinics in Addis Ababa. Patients with decompensated cirrhosis and pregnant ladies were excluded from the study. The patients were counseled on treatment options, cost, treatment outcomes, adverse drug effects, and possible complications. Data were collected on demographic features, clinical characteristics, viral genotypes, and treatment outcomes during follow up visits until six months after completion of recommended standard treatment. Data were analyzed using SPSS software. RESULTS: A total of 200 adults with chronic HCV infection were treated with PEG-Interferon and Ribavirin (for 24 or 48 weeks according to the genotypes) during the study period. Of the 200 patients enrolled in the study, 120 (60%) were male, 90% were from Addis Ababa, and the median age was 48 years. Sixty per cent of the patients were infected with genotype 4,17% with genotype 1, 13.5% with genotype 2 and 9.5% with genotype 3. Eighty percent of the patients had end of treatment response; of these, 74.4% had undetectable HCV RNA at 6th month after end of treatment. The end of treatment response was noted to be close to 90% for patients with HCV genotypes 2 and.3 infections. CONCLUSION: This study indicates that genotype 4 is the prevalent HCV genotype followed by 1, 2, and 3 among Ethiopian patients. Treatment with interferon and ribavirin was well tolerated and provided a very good response.

A case report of celiac disease; a report done at Tikur Anbessa Specialized Hospital, Addis Ababa.

A 23 year old male patient who was diagnosed to have malabsorption syndrome secondary to celiac disease after he presented with 08 months' duration of chronic diarrhea, significant weight loss and marked body weakness with easy fatigability. Celiac disease is one of the rare causes of malabsorption in African countries. The diagnosis requires appropriate clinical history, high index of suspicion, exclusion of common causes of chronic diarrhea and confirmation by histology after the characteristic endoscopy appearance is identified. Supportive care and gluten restriction was advised and the patient has shown marked improvement in symptoms and general wellbeing. Celiac disease needs to be considered in patients who present with chronic diarrhea that doesn't respond to conventional management.

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.

Piloleiomyoma in a 45 year old patient.

A middle aged man from rural Ethiopia with disseminated type of multiple piloleiomyoma is reported. He showed multiple painful nodules on the chest, shoulders, abdomen and the left lower extremity. He had right renal mass lesion which had rendered his kidney non-functional. Multiple piloleiomyoma is rare in general and to date, there was no report from Ethiopia. The case is presented and discussed with review of literature.

Surgical management of bleeding esopageal varices: the Tikur Anbessa hospital experience.

Surgery is one of the modalities of treatment of portal hypertension with bleeding esophageal varices. Between 1992 and 2003, a total of 33 patients with esophageal varices secondary to hepatic or pre-hepatic causes of portal hypertension underwent proto-azygeal disconnection surgery at Tikur Anbessa Hospital, Addis Ababa University. Twenty-five, (69. 7%) were men and 8 (24.3%) were women. Their age ranged between 13 and 54 years with a mean age of 24.3 years. Eighty two percent of the patients had hematemesis and melena. Thirty-two, (97%) patients had splenomegaly and of these; 27 (84%) had splenomegaqly with hyperslenism. Twenty-one, (63.6%) and 12 (36.6%) patients had child's A and B functional class, respectively. None of the patients was in class C. The condition of the liver as assessed macroscopically at surgery showed portal fibrosis in 22 (66.7%), cirrhosis in 3 (9.1%) and normal liver in 8 (24.2%) patients. There was no significant correlation between variceal bleeding episode and type of liver pathology. Four patients (12%) died after surgery and re-bleeding occurred in one (3%) patients. Porto-azygeal disconnection surgery can be done safely in patients with esophageal varices and good liver function in order to prevent further bleeding episode.

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).

Antimicrobial susceptibility pattern of Helicobacter pylori strains isolated from adult dyspeptic patients in Tikur Anbassa University Hospital, Addis Ababa, Ethiopia.

Presently, there is no published information on the antimicrobial susceptibility pattern of H. pylori strains in Ethiopia to guide the choice of drug for therapy. Therefore, it is becoming clinically relevant to test the in vitro susceptibility of H. pylori clinical isolates prior to treating patients. Susceptibility testing was performed on 50 clinical H. pylori isolates obtained from adult dyspeptic patients referred to the gastrointestinal (GI) Clinic of Tikur Anbassa University Hospital. Five antibiotics were evaluated, by using the Episolmeter test (E-test). The antibiogram of 50 H. pylori clinical isolates showed that all strains were sensitive to clarithromycin, erythromycin and tetracycline, while 38/50 (76%) and 3/50 (6%) of the strains were resistant to metronidazole and amoxicillin, respectively. Infection by metronidazole or amoxicillin resistant H. pylori is an important factor leading to treatment failure. Testing of all H. pylori clinical isolates to metronidazole and amoxicillin is recommended. If it is not possible to perform susceptibility tests on each clinical isolate, a program to survey the prevalence of resistance should be implemented in a given area or population. When treatment of H. pylori infection is indicated in dyspeptic patients, the potential availability, simplicity of use, safety and low cost of the antimicrobial agents have to be taken into account.

Upper gastrointestinal endoscopy: a review of 10,000 cases.

A total of 10,000 patients underwent upper gastrointestinal endosopy examination between August 1979 and October 1994 at Tikur Anbessa Hospital, Addis Ababa. The major indications were dyspepsia (59.4%), upper gastrointestinal bleeding (18%) and liver disease (10.8%). The other indications include dysphagia (2.2%), gastric outlet obstruction (2.1%), postoperative dyspeptic symptoms (1.9%), weight loss and/or anemia (1.4%), epigastric mass (0.6%) and odynophagia 0.2%. The mean age of the patients and their sex ratio was 36 years and 2:1, respectively. Twenty eight percent of the patients had normal findings. The commonest abnormal findings include duodenal ulcer (41%), esophageal varices (9%), acute gastritis (6%), duodenitis (3.4%), and reflux esophagitis (2.3%). Benign gastric ulcer was rare. The ratio of duodenal ulcer to gastric ulcer was 19.1%. Duodenal ulcer (45.6%), esophageal varices (15.6) and acute gastritis (5.7%) were found to be the commonest causes of upper gastrointestinal bleeding. The endoscopy or histology diagnosis of cancer in both the esophagus and stomach was 2.8% and 1.3%, respectively. The agreement between endoscopy and histology in the diagnosis of esophageal and gastric cancer was 80%. There was no major complication related to endoscopy or premeditation. Endoscopy is a fairly accurate and safe procedure and therefore should be available and applied widely for the diagnosis of upper gastrointestinal diseases in Ethiopia.