Pharmacogenetics in type 2 diabetes:Influence on response to oral hypoglycemic agents

Adem Yesuf Dawed, Kaixin Zhou, Ewan Robert Pearson  Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, Scotland, UK Abstract: Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs) are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs results in unnecessary treatment failure. In addition to nongenetic factors, genetic factors are thought to contribute to much of such variability, highlighting the importance of the potential of pharmacogenetics to improve therapeutic outcome. Despite the presence of conflicting results, significant progress has been made in an effort to identify the genetic markers associated with pharmacokinetics, pharmacodynamics, and ultimately therapeutic response and/or adverse outcomes to OHAs. As such, this article presents a comprehensive review of current knowledge on pharmacogenetics of OHAs and provides insights into knowledge gaps and future directions. Keywords: pharmacogenetics, type 2 diabetes, oral hypoglycemic agents, pharmacokinetics, pharmacodynamics, respons

Tuberculosis Lymphadenitis and Human Immunodeficiency Virus Co-infections among Lymphadenitis Patients in Northwest Ethiopia

BACKGROUND: Tuberculosis and human immunodeficiency virus (HIV) are among the major health problems in Ethiopia. This study assessed the proportion of tuberculosis lymphadenitis (TBLN), HIV infection and their co-infection among TBLN presumptive individuals at the selected hospitals in NorthwestEthiopia.METHODS: Institution based cross sectional study was carried out. Data on demographic and clinical variables were collected with standardized questionnaire. Microbiological culture was done on specimen obtained by fine needle aspirates. The HIV status was determined by rapid anti-HIV antibody test. Data was entered and scrutinized using SPSS version 20 statistical packages. A stepwise logistic regression model was used. The result was considered as statistically significant at P<0. 05.RESULTS: A total of 381 lymphadenitis patients were included in the study. The overall prevalence of TBLN and HIV were at 250(65.6%) and 9(2.4%), respectively and their co-infection was at 6(2.4%). Based on the cytological examination, 301(79.0%) of them were diagnosed as TBLN. The age group, (P=0.01) and residency, (P=0.01) were found significantly associated with TBLN. Similarly, unsafe sex was also statistically significant for HIV infection (P=0.007).CONCLUSION: Tuberculosis lymphadenitis is the leading cause of TB and lymphadenitis in the region. However, TBLN-HIV coinfection was promisingly low. High rate of discrepancy was noticed between cytological and culture results. Hence, the TBLN diagnostic criteria shall pursue revision

Drug resistance patterns of bacterial isolates from infected wounds at Bahir Dar Regional Health Research Laboratory Center, Northwest Ethiopia

Background: An increased antibiotic resistance of bacterial isolates from wound infections is a major therapeutic challenge. The aim of this study was to identify bacterial isolates associated with wound infection and to determine their current antimicrobial susceptibility profile.Methods: This is a retrospective cross-sectional study in which we analyzed the records of 380 wound swab culture results that have been processed at Bahir Dar Regional Health Research Laboratory Center in the period of 1 January 2013 to 30 December 2015. Swabs from different wound types were collected aseptically and analyzed using standard bacteriological procedures. Antimicrobial susceptibility testing was performed using disc diffusion technique as per the standard protocol. Demographic and bacteriological data were collected using a data extraction sheet. The data were cleaned, entered and analyzed using SPSS version 22.Results: The overall bacterial isolation rate was at 61.6% (234/380). More than half 123 (52.6%) of the isolates were gram positive and 111 (47.4%) were gram negatives. The predominant isolates were S. aureus at 100 (42.7%) followed by E. coli, 33 (14.1%), P. aeruginosa, 26 (11.1%) and S. pyogenes, at 23 (9.8%). The proportion of multidrug resistant (MDR) bacterial pathogens was at 54.3%. Out of these, 35 (15.1%) of the isolates were resistant to more than five drugs. The highest resistance rate at (85.9%) was documented for ampicillin by gram-negative isolates. Whereas the highest resistance rate among gram positive isolates was against erythromycin (31.1%). The resistance rate of S. aureus for penicillin was at 69.7%.Conclusions: High frequency of mono and multi-drug resistant bacterial pathogens were documented. Thus, an alternative method to the causative agent and antimicrobial susceptibility testing surveillance in areas where there is no culture facility is needed to assist health professionals for the selection of appropriate antibiotics. [Ethiop. J. Health Dev. 2016;30(3):112-117]Keywords: Wound infection, bacterial isolates, and antimicrobial susceptibility profil

Health impacts of bedbug infestation: A case of five towns in Amhara Region, Ethiopia

Background: Bedbug is a wingless human blood-sucking bug that generally infests houses and beds. Bedbug infestation is prevalent across the country. Despite its prevalence, however, there is scarce information on the epidemiological, psychological, social and public health impacts of the infestation. This lack may arise from the absence of sufficient research in the area. The impetus for this study arose from this recognition. This study therefore assessed the extent of bedbug infestation in five towns in Amhara Regional State, Ethiopia, and its impact on public health in the areas considered in this study.Methods: A community-based cross sectional study was conducted in five towns of Amhara Regional State from 1 March 2015 to 30 June 2016. Bedbug inspection was done following the Michigan manual for prevention and control of bedbug recommendation. The presence of a living or dead bedbugs, their eggs, their skin discarded in shedding, and their fecal stains or droppings were taken as an infestation. In addition, data from households were collected using pretested, structured and interviewer-administered questionnaire. The data were analyzed using SPSS version 20. Both bivariate and multivariate logistic regressions were computed to identify associated factors.Results: From the 203 residential institutions surveyed, evidence of prevalence of bedbugs was located in 75.9% (154) houses. From among the infested residents, 87%, 83.1%, and 71.4% had faced one or more psychological, social and health impacts, respectively. Residential institutions in Bahir Dar town administration were 3.4 times more likely to be infested by bedbug than those in Amanuel town (AOR: 3.4; 95% CI: 1-11). The chances that residents of Kobo town administration had to be infested by bedbug were 41 times more than that of the residents in Amanuel town (AOR: 41; 95%CI: 8-206). However, no statistically significant difference was observed between the rates of bedbug infestation and the type of residential institutions.Conclusions: Bedbug infestation was found to be a major public health problem in Bahir Dar, Woreta and Kobo towns. A significant psychological, social and health impact was observed in the communities. Thus, aggressive public health promotion campaigns against bedbug are recommended to empower the communities and equip them with preventive strategies. Moreover, an effective pest management strategy also needs to be made a priority health agenda, in the particular areas of study. A larger study is recommended to assess more in-depth impacts of bedbug infestation on public health [Ethiop. J. Health Dev. 2017;31(4):251-258]Keywords: Bedbug infestation, Ethiopi

Knowledge and practice on magnitude, diagnosis, treatment and prevention strategies of Hepatocellular Carcinoma in Ethiopia: A Systematic Review

Introduction: In Ethiopia, hepatocellular carcinoma (HCC) is the most common cancer with 100% fatality rate. HCC cases in low income countries die within few months following diagnosis. There is lack of information on the burden, risk factors, diagnosis modalities, surveillance strategies and treatment approaches to HCC in Ethiopia.Objective: To analyze the existing evidence related to burden, risk factors, diagnosis modalities, surveillance strategies, and treatment and prevention strategies of HCC in Ethiopia.Methods: All studies done on HCC in Ethiopian irrespective of year of publication and study types were included. Literatures were retrieved from electronic database of PubMedand Cochrane library during September/2016 to January 2/2017. Key words and mesh terms such as ‘hepatocellular carcinoma’, ‘hcc’, ‘hepatoma’, ‘malignant hepatoma’, ‘hepatocarcinoma’ were used to search for documents. Besides, we searched for articles, guidelines and reviews from world health organizations, lancet and Google scholar sites. Each of the retrieved studies was assessed by two authors for inclusion based on the eligibility criteria, and for quality using the critical appraisal checklist. Qualitative data were synthesized for analyzing the theories of studies. Medley reference manager was used to manage citations.Results: A total of 1448 literatures were retrieved. Eight studies fulfill the eligibility criteria, however, only three were full-fledged articles. HCC is clinically characterized by exhaustion, loss of appetite, rapid loss of weight, epigastric pain, right upper abdominal quadrant pain with a rapidly growing mass, jaundice, and ascites with or without hepatomegaly and splenomegaly. Data on HCC proportion among liver disease patients lies between 16.1%-19.2%. Cirrhosis followed by hepatotoxic indigenous drugs and viral hepatitis were found to be as major risk factor for HCC. In Ethiopia, there is no surveillance activity and no standard staging systems. Furthermore, there was no policy frame -work for management of HCC.Conclusion: As compared to other countries, Ethiopia is far behind in addressing HCC. There is no national policy framework and guideline for the management of HCC. Moreover, HCC is a neglected cancer that is considered as a death penalty by the community. Health professionals working in health facilities and health offices should share the data they have to the scientific community and policy makers, for further searching solutions and informed decision, respectively. An intensified public health strategy on health education and early case detection is of critical importance. In addition concerted effort should be made to develop HCC prevention and treatment modality.Key words: Hepatocellular Carcinoma, Ethiopi

Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis and its Rifampicin resistance at Felege Hiwot and Debre Tabor Hospitals, Northwest Ethiopia: A preliminary implementation research

Background: The World Health Organization endorsed GeneXpert MTB/RIF (Xpert) assay for the diagnosis of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB) in 2010. However, the practice of using this novel diagnostic method is still limited in a high TB and human immunodeficiency virus (HIV) burden settings, including Ethiopia. Therefore, we conducted this study aimed at describing the first implementation status of Xpert assay in the diagnosis of TB and MDR-TB at Felege Hiwot Referral Hospital (FHRH) and Debre Tabor General Hospital (DTGH), Northwest Ethiopia.Methods: We analyzed the records of 1922 (FHRH=544 and DTGH=1378) presumptive TB patients diagnosed using Xpert test from 1 November 2015 to 30 April 2016 at FHRH and DTGH, Northwest Ethiopia. All patients who had registered data on their sex, age, HIV status, presumptive MDR-TB status and Xpert results were included for analysis. Data were retrieved directly from GeneXpert result registration log book using data extraction sheet. Data were entered, cleaned, and analyzed using SPSS statistical software package; p < 0.05 was considered to be significant.Results: Overall Xpert assay properly diagnosed 14.6% of the cases (258/1922). Among these, rifampicin (RIF) resistance was detected at 9.3% (24/258). In the studied settings, clinical data showed that 81.0% (1556/1922) of the cases were MDR- TB. Among the study subjects, 888 (46.2 %) of them were HIV positive. However, TB-HIV co-infection rate was at 41.9% (108/258). Of the total patients registered, 1005 (52.3%) of whom were males. The mean age of patients was 31.1 years with SD of 17.5. Significant predictors of the Xpert test were: age (p=0.000), sex (p=0.009), HIV status (p=0.003) and presumptive MDR-TB (p=0.000).Conclusions: In the studied areas, large proportion of clinically TB suspected patients were wrongly diagnosed with MDR-TB. Therefore, the use of Xpert assay in health settings with no culture facility will decrease the unnecessary use of anti-TB drugs and improve rapid TB, and MDR-TB detection and proper management of the cases. [Ethiop. J. Health Dev. 2016;30(2):60-65]Keywords: TB, GeneXpert, MTB/RIF assay, Northwest Ethiopi

BURDEN AND DETERMINANT FACTORS OF ANEMIA AMONG ELEMENTARY SCHOOL CHILDREN IN NORTHWEST ETHIOPIA: A COMPARATIVE CROSS SECTIONAL STUDY

Background: Anemia is an indicator of both poor nutrition and health. In low-income countries like Ethiopia, the prevalence of anemia remains high due to several determinant factors. There is a lack of regular surveillance system to determine the magnitude of anemia among school age children. The aim of this study was to determine the burden and determinant factors of anemia among school children. Materials and Methods: A comparative cross-sectional study was conducted from March 2014 to May 2014 among elementary school children in Northwest Ethiopia. Multi stage and simple random sampling techniques were used to select the schools and the study subjects. Standard questionnaire was employed to assess the socioeconomic status of study participants. Intestinal parasitosis infections and hemoglobin level were determined by formula ether concentration technique and automated hematology analyzer, respectively. Descriptive statistics were used to determine the burden of anemia. Stepwise logistic regression was used to identify the determinants of anemia. Results: Among 2,372 elementary school children, the prevalence of anemia was 7.6% (95 % CI: 7% - 9%). The mean hemoglobin level was 11.6 g/dl ranging from 10 g/dl to 13g/dl. The magnitude of hookworm infection was 530 (22.3%). In multivariate analysis anemia was found associated with residence, source of water, availability of latrine, maternal education, family size and hookworm infection. Conclusion: Anemia still remains as a major public health problem among the school children in the study area. Residence, source of water, availability of latrine, maternal education, family size and hookworm infection are also the major determinant factors for the high prevalence of anemia. Therefore, health education, iron supplement and deworming should be given to school age children

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Prevalence of Cryptococcal Antigenemia and Associated Factors among HIV/AIDS Patients at Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia

Background. Cryptococcosis is the most common opportunistic fungal infection. High morbidity and mortality are frequently observed among hospitalized HIV/AIDS patients, particularly having CD4 count ≤100 cells/μl. Therefore, this study aimed to determine the prevalence of cryptococcal antigenemia and associated factors among HIV/AIDS patients. Methods. A hospital-based cross-sectional study was conducted among 140 HIV/AIDS patients. A cryptococcal antigen test was performed for all patients along with medical chart and laboratory registration book review. Cryptococcal antigen was detected from serum by using Remel Cryptococcal Antigen Test Kit. Data related to possible associated factors were extracted from patients’ charts and laboratory registration book. Data were coded, entered, and analyzed using SPSS version 20. Logistic regression analysis was done to see the association between dependent and independent variables. A P value <0.05 was considered statistically significant. Finally, data were presented in the form of texts, figures, and tables. Result. Among 140 serum cryptococcal antigenemia-tested study subjects, 16 (11.43%) were positive for serum cryptococcal antigen. Of them, 43.8% (7/16) were pulmonary tuberculosis coinfected, 31.2% (5/16) were extrapulmonary tuberculosis positive, and 25% (4/16) had bacterial bloodstream infections. In addition, 68.7% (11/16) had CD4 count less than 100 cells/μl, 18.7% (3/16) had CD4 count 100–150 cells/μl, 50% (8/16) were antiretroviral therapy defaulters, and 31.3% (5/16) were naïve. In this study, the majority, 75% (12/16), of the serum cryptococcal antigen-positive subjects were clinical stage IV. Of the assessed associated factors, tuberculosis coinfection (AOR: 0.04; 95% CI [0.005–0.25]) and antiretroviral therapy status (AOR: 0.02; 95% CI [0.001–0.5]) were significantly associated factors enhancing serum cryptococcal antigenemia. Conclusion. In this study, the high rate of cryptococcal antigenemia was observed among hospitalized HIV/AIDS patients, and it is alarming and highlights the need for improving CD4 status, expanding serum cryptococcal antigen screening, and strengthening regular cryptococcal antigenemia surveillance systems