The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

World Health Organization Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy

Background. In the last decades, medicines have had an unprecedented positive effect on health, leading to reduced mortality and disease burden and consequently to an improved quality of life. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. In the absence of the development of new generations of antibiotic drugs, appropriate use of existing antibiotics is needed to ensure the long-term availability of effective treatment for bacterial infections. Irrational use of antibiotics is an ongoing global public health problem that deserves more attention. This review is conducted to evaluate the prevalence of inappropriate antibiotic utilization and resistance to antibiotics in Ethiopia. Methods. Electronic search in PubMed/MEDLINE and Google was used to find published literature with reference lists of relevant articles searched manually. Titles and abstracts were initially screened for eligibility. The full texts of articles judged to be eligible were reviewed if they meet the inclusion criteria. Data were extracted on important variables like the sample size, region of the study, the inappropriate antibiotic use, bacterial detection rate, multidrug resistance pattern, and more other variables. Microsoft Excel was used for data extraction. Quantitative analysis was performed using STATA version 11. Results. The electronic searches identified 193 articles of which 33 were found eligible. The random-effects model was used to provide point estimates (with 95% confidence interval (CI)) of bacterial detection rate, inappropriate antibiotic use, and multidrug resistance rate to account for heterogeneity. The pooled bacteria detection rate was 29.1 with 95% CI (16.6–41.7). The pooled prevalence of multidrug resistant strains identified was 59.7% (95% CI: 43.5–75.9). The pooled estimate of inappropriate antibiotic use was 49.2% (95% CI: 32.2–66.2). The pooled proportion of self-antibiotic prescription was 43.3% (95% CI: 15.7–70.9). Other reasons for inappropriate antibiotic use included a wrong indication, wrong duration, improper route of administration, use of leftover antibiotics from a family member, and immature discontinuation of antibiotics. Conclusion and Recommendations. Inappropriate antibiotic use is a huge problem in Ethiopia, and many bacteria were resistant to commonly used antibiotics and similarly, multidrug-resistant bacterial strains are numerous. Appropriate antibiotic use should be ensured by prohibiting over-the-counter sale of antibiotics and strengthening antimicrobial stewardship.

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Antibiotic Use and Resistance Pattern in Ethiopia: Systematic Review and Meta-Analysis

The burden of methicillin resistant Staphylococcus aureus is a major public health concern worldwide; however the overall epidemiology of multidrug resistant strains is neither coordinated nor harmonized, particularly in developing countries including Ethiopia. Therefore, the aim of this meta-analysis was to assess the burden of methicillin resistant Staphylococcos aureus and its antibiotic resistance pattern in Ethiopia at large. PubMed, Google Scholar, and lancet databases were searched and a total of 20 studies have been selected for meta-analysis. Six authors have independently extracts data on the prevalence of methicillin resistant Staphylococcus aureus among clinical isolates of Staphylococcus aureus. Statistical analysis was achieved by using Open meta-analyst (version 3.13) and Comprehensive meta-analysis (version 3.3) softwares. The overall prevalence of methicillin resistant Staphylococcus aureus and its antibiotic resistance pattern were pooled by using the forest plot, table and figure with 95% CI. The pooled prevalence of methicillin resistant Staphylococcus aureus was 32.5% (95% CI, 24.1 to 40.9%). Moreover, methicillin resistant Staphylococcus aureus strains were found to be highly resistant to penicillin, ampicillin, erythromycin, and amoxicillin, with a pooled resistance ratio of 99.1, 98.1, 97.2 and 97.1%, respectively. On the other hand, comparably low levels of resistance ratio were noted to vancomycin, 5.3%. The overall burden of methicillin resistant Staphylococcus aureus is considerably high, besides these strains showed extreme resistance to penicillin, ampicillin, erythromycin and amoxicillin. In principle, appropriate use of antibiotics, applying safety precautions are the key to reduce the spread of multidrug resistant strains, methicillin resistant Staphylococcus aureus in particular.

https://link.springer.com/content/pdf/10.1186%2Fs12879-016-2014-0.pdf

Methicillin resistant Staphylococcus aureus in Ethiopia: a meta-analysis

Staphylococcus aureus is a contagious, opportunistic pathogen that causes clinical or subclinical mastitis in dairy cattle. The genetic background and antimicrobial resistance of isolates from Ethiopian dairy farms has not been studied. Therefore, the aim of this study was to characterize S. aureus from Ethiopian hand milked dairy cows, by spa, MLST and virulence factor typing, and by assessment of antimicrobial susceptibility. A total of 79 S. aureus isolates from intramammary infections was studied. A PCR was used to detect lukM-lukF’ and pvl genes encoding the bovine and human associated bi-component leukocidins, and the toxic shock syndrome toxin gene-1 (tst). Antimicrobial susceptibility was determined using the broth microdilution method. Twenty different spa types were identified, most isolates were t042 (58%), and the closely related t15786 (11%). The proportion of isolates positive for lukM-lukF’, tst and pvl was low at 0.04, 0.10 and 0.09 respectively, with lukM-lukF’ often co-occurring with tst, but not with pvl. Methicillin-resistance was not found, but resistance to penicillin/ampicillin (86%) and tetracycline (54%) was very common. We found a high degree of relatedness among bovine S. aureus isolates in North-Western Ethiopia, suggesting contagious within and between farm transmission of strains that are often resistant to commonly used antimicrobials. This highlights the need for effective preventive measures that aim at limiting transmission of bacteria rather than using antimicrobials to control S. aureus mastitis in Ethiopia.

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Characterization of Staphylococcus aureus isolated from milk samples of dairy cows in small holder farms of North-Western Ethiopia

In Ethiopia, there is lack of data on the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immune deficiency virus (HIV) infections in adult population at community level. This study aimed at determining the HBV, HCV and HIV seroprevalence in adult population at community level in East and West Gojjam zones in Amhara region, Ethiopia. A cross-sectional study was conducted between October 01 and November 30, 2015. The Hepatitis B surface antigen (HBsAg) and anti-HCV were detected using the standard serological tests. The antibody to HIV infection was tested using the national HIV rapid tests algorithms. A total of 481 adults comprised of 51% females with median age of 25 years took part in the study. Overall, 7.5% (95% CI: 5.5–10.2%) of adult population were infected either with HBV, HCV and HIV. The prevalence of HBV was 15 (3.1%) and for HIV was 16 (3.3%). The seroprevalence of HCV was five (1.0%). HIV-HCV co-infection was found to be two (0.4%). HIV prevalence was higher in non-educated population than their counter parts (P = 0.001). HIV prevalence was high in housewives (6.0%) and merchants (4.7%). This study revealed an intermediate HBV prevalence and low prevalence of HCV in adult population at community level. HIV prevalence is still a major public health problem in the area. To have the national data, we recommend further study on genotypes of HBV and HCV including local risk factors for transmissions. Moreover, health education on HBV, HCV and HIV transmission should be an intervention measure in the community.

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Community seroprevalence of hepatitis B, C and human immunodeficiency virus in adult population in gojjam zones, northwest Ethiopia.

Background 
MRSA infections are becoming more prevalent throughout the HIV community. MRSA infections are a challenge to both physicians and patients due to limited choice of therapeutic options and increased cost of care.


Objectives 
This study was aimed to determine the prevalence of colonization and co-resistance patterns of MRSA species among HIV positive pediatric patients in the Amhara National Regional State, Northwest Ethiopia.


Methods 
Culture swabs were collected from the anterior nares, the skin and the perineum of 400 participants. In vitro antimicrobial susceptibility testing was done on Muller Hinton Agar by the Kirby-Bauer disk diffusion method, using 30 μg cefoxitin (OXOID, ENGLAND) according to the recommendations of the Clinical and Laboratory Standards Institute. Methicillin sensitivity/resistance was tested using cefoxitin. Data was analyzed by descriptive statistics and logistic regression model using Epi Info 7.


Results 
S. aureus was detected in 206 participants (51.5%). The prevalence of MRSA colonization in this study was 16.8%. Colonization by S. aureus was associated with male gender (OR = 0.5869; 95% CI: 0.3812–0.9036; p-value = 0.0155), history of antibiotic use over the previous 3 months (OR = 2.3126; 95% CI: 1.0707–4.9948; p-value = 0.0329) and having CD4 T-cell counts of more than 350 x 106 cells / L (OR = 0.5739; 95% CI = 0.3343–0.9851; p-value = 0.0440). Colonization by MRSA was not associated with any one of the variables. Concomitant resistance of the MRSA to clindamycin, chloramphenicol, co-trimoxazole, ceftriaxone, erythromycin and tetracycline was 7.6%, 6%, 5.25%, 20.9%, 23.9% and 72.1%, respectively.


Conclusion 
High rates of colonization by pathogenic MRSA strains is observed among HIV positive pediatric patients in the Amhara National Regional state.

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Methicillin Resistant Staphylococcus aureus among HIV Infected Pediatric Patients in Northwest Ethiopia: Carriage Rates and Antibiotic Co-Resistance Profiles

Background 
Reference interval is crucial for disease screening, diagnosis, monitoring, progression and treatment efficacy. Due to lack of locally derived reference values for the parameters, clinicians use reference intervals derived from western population. But, studies conducted in different African countries have indicated differences between locally and western derived reference values. Different studies also indicated considerable variation in clinical chemistry reference intervals by several variables such as age, sex, geographical location, environment, lifestyle and genetic variation.


Objective 
This study aimed to determine the reference intervals of common clinical chemistry parameters of the community of Gojjam Zones, Northwest Ethiopia.


Method 
Population based cross-sectional study was conducted from November 2015 to December 2016 in healthy adult populations of Gojjam zone. Data such as, medical history, physical examination and socio-demographic data were collected. In addition, laboratory investigations were undertaken to screen the population. Clinical chemistry parameters were measured using Mindray BS 200 clinical chemistry autoanalyzer as per the manufacturer’s instructions. Descriptive statistics was used to calculate mean, median and 95th percentiles. Independent sample T-test and one way ANOVA were used to see association between variables.


Results 
After careful screening of a total of 799 apparently healthy adults who were consented for this study, complete data from 446 (224 females and 222 males) were included for the analysis. The mean age of both the study participants was 28.8 years. Males had high (P 0.05). Mean, median, 95% percentile values of AST, ALP, amylase, LDH, creatinine, total protein, total bilirubin, and direct bilirubin across all age groups of participants were similar (P>0.05). But, there was a significant difference in the value of ALT (P 1500 ETB compared to those with low monthly income. Significant (P<0.05) higher values of the ALT, ALP and total protein were observed in people living in high land compared to low land residences.


Conclusion 
The study showed that some of the common clinical chemistry parameters reference intervals of healthy adults in Gojjam zones were higher than the reference intervals generated from developed countries. Therefore, strict adherence to the reference values generated in developed countries could lead to inappropriate diagnosis and treatment of patients. There was also variation of reference interval values based on climate, gender, age, monthly income and geographical locations. Therefore, further study is required to establish reference intervals for Ethiopian population.

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Clinical chemistry reference intervals of healthy adult populations in Gojjam Zones of Amhara National Regional State, Northwest Ethiopia.

Introduction Establishing national population haematological and immunological reference ranges are essential for clinical management of patients. However, there is scarcity of information on community based haematological reference ranges established from Ethiopian population. Therefore, this study aimed at determining haematological and CD4+ T cells reference ranges in healthy adults from East and West Gojjam zones, Ethiopia. Methods Community based cross-sectional study was conducted from May 2015 to December 2015 in healthy adult residents of Gojjam zone. A total of 481(246 females and 235 males) healthy adults enrolled in the study. Healthy adults were defined by medical history, physical examination and laboratory screening for HIV, HBV, HCV and intestinal parasitosis. Haematological parameters were measured using haematology analyzer MindrayBC320 (Mindray Biomedical electronic Corporation, China). CD4+Tcells were enumerated using FACS count (Becton Dickinson). Results The median age of the participants was 25 years. The overall median and 95th percentile of CD4+ T cells count were 869 cells/mm3 and396–1598 cells/mm3, respectively. Females had a significantly higher CD4+ T cell counts compared to males (P = 0.002). The 95th percentile range for red blood cells (RBCs) was 3.93–6.1 x 106cells/mm3and for hematocrit (Hct) was 40–58% while for hemoglobin (Hb) was 15.69–17.84g/dl. Males had significantly higher values of RBC and Hct than females (P < 0.001). Females (120–379 x 106 cells/mm3) had significantly higher platelet counts than males (106–352 x106 cells/mm3) (P < 0.001). The overall median of WBC was6.78 x103/mm3and its95thpercentile range was3.5–11.5 x103/mm3. The overall 95th percentile range of MCV, MCH and MCHC were 89.5–107.5 fl, 28–34 pg and 30–33.2g/dl, respectively. The higher mean absolute count of RBCs was found in the youngest age groups (P = 0.03). The mean count of RBCs and Hct were significantly higher in highschool completed and above than other participants (P < 0.001). The lower and upper limit of platelet counts was significantly higher in highland (118 -383x106 cells/mm3) compared to lowland residents (107–352 x106 cells/mm3) (P < 0.001). Moreover, it was significantly higher in residents with better monthly income (124–383 x106 cells/mm3) compared to the counters (115–368 x106 cells/mm3) (P = 0.02). Conclusions Some of the haematological and CD4+ T cells reference ranges of the healthy adults in this study showed variations with the reference ranges used and reported so far in Ethiopia, Africa and Western countries. We recommend further study considering gender, altitude, and residency in other parts of Ethiopia to establish national reference ranges for Ethiopian population.

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Haematological and CD4+ T cells reference ranges in healthy adult populations in Gojjam zones in Amhara region, Ethiopia

HAART had significantly improved the quality of life of HIV patients. However, it results different adverse effects such as: hepatotoxicity, nephrotoxicity, lipodystrophy, anemia, diarrhea, psychiatric disorder and others. Therefore, this comparative cross sectional study was designed to investigate liver enzyme elevation in patients taking HAART compared with treatment naive controls at Debre Berhan Referral Hospital. A total of 152 individuals (76 cases and 76 controls) were included in this study. The mean ages of treatment and control groups were 37.37 and 36.38 respectively. The mean values of liver enzymes (ALT, AST and ALP), total bilirubin and direct bilirubin were significantly higher (p < 0.05) while, total protein and creatinine were significantly lower in patients taking HAART compared with treatment naive controls. In this study, about 19 (25%) of clients in HAART treated groups and 7 (9.2%) of treatment naive controls had showed liver enzyme changes. Moreover, 23.7% and 1.3% of the HAART treated groups developed mild and moderate liver enzyme elevation or hepatotoxicity, respectively. In this study, significant difference was observed in liver enzyme elevation between ART and pre-ART patients. As a result, regular clinical and laboratory monitoring of liver function will be necessary to prevent severe form of liver injury.

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Liver enzyme elevation in patients taking HAART compared with treatment naïve controls at Debre Berhan Referral Hospital: a comparative cross-sectional study, Northeast Ethiopia.

Zewdie Mekonnen

Papers

Community seroprevalence of hepatitis B, C and human immunodeficiency virus in adult population in gojjam zones, northwest Ethiopia.

Methicillin Resistant Staphylococcus aureus among HIV Infected Pediatric Patients in Northwest Ethiopia: Carriage Rates and Antibiotic Co-Resistance Profiles

Clinical chemistry reference intervals of healthy adult populations in Gojjam Zones of Amhara National Regional State, Northwest Ethiopia.

Haematological and CD4+ T cells reference ranges in healthy adult populations in Gojjam zones in Amhara region, Ethiopia

Liver enzyme elevation in patients taking HAART compared with treatment naïve controls at Debre Berhan Referral Hospital: a comparative cross-sectional study, Northeast Ethiopia.