Trends in HIV-1 pretreatment drug resistance and HIV-1 variant dynamics among antiretroviral therapy-naive Ethiopians from 2003 to 2018: a pooled sequence analysis.

BACKGROUND: Ethiopia is among the highly HIV-affected countries, with reported 12,000 and 12,000 AIDS-related deaths and incidents as per reports from 2021. Although the country has made a promising progress in antiretroviral therapy, recent studies have indicated that pretreatment drug resistance (PDR) is alarmingly increasing, which has become a challenge for the effectiveness of HIV treatment. Epidemiologic data on PDR is necessary to help establish ART regimens with good efficacy. Thus, this systematic review aimed to determine the trend analysis of PDR among ART-naïve individuals along with HIV variant dynamics in Ethiopia. METHOD: HIV-1 pol sequences from studies conducted between 2003 and 2018 among ART-naïve Ethiopian individuals were retrieved from GenBank and analyzed for the presence of PDR mutations (PDRM) along with the analysis of HIV-1 variant dynamics. The Calibrated Population Resistance (CPR) tool Version 8.1 and the REGA HIV-1 Subtyping Tool Version 3 were used to determine the PDRM and HIV-1 genetic diversity, respectively. RESULT: We identified nine studies and analyzed 1070 retrieved HIV-1 pol sequences in this systematic review. The pooled prevalence of PDR was 4.8% (51/1070), including 1.4% (15/1070), 2.8% (30/1070), and 0.8% (9/1070) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI), and protease inhibitor (PI) resistance, respectively. NRTI and NNRTI concurrent PDRM were observed among 0.2% (2/799) of the analyzed sequences. The overall PDR prevalence has been increasing over the years. Though the prevalence of the NNRTI, NRTI, and PI PDR also increased over the years, the NNRTI increment was more pronounced than the others, reaching 7.84% in 2018 from 2.19% in 2003. The majority (97%; 1038/1070) of the genetic diversity was HIV-1 subtype C virus, followed by subtype C' (2%; 20/1038) and other subtypes (1%; 10/1038). CONCLUSIONS: According to this systematic review, the overall pooled prevalence of PDR is low. Despite the low prevalence, there has been an increasing trend of PDR over the years, which implies the need for routine surveillance of PDRMs along with preventive measures. Hence, this supports the recently endorsed transition of ART regimens from NNRTI to integrase strand transfer inhibitor-based regimens recommended by the WHO. In addition, this finding underscores the need for routine baseline genotypic drug resistance testing for all newly diagnosed HIV-infected patients before initiating treatment to halt the upward trend of PDR.

Immune reconstitution inflammatory syndrome, a controversial burden in the East African context: a systematic review and meta-analysis.

Introduction: It is well established that starting antiretroviral therapy (ART) increases a patient's life expectancy among HIV-positive individuals. Considering the HIV pandemic, the major concern is initiation of ARTs to the large segment of HIV infected population, not adverse events from immune restoration. The prevalence of HIV-associated immune reconstitution inflammatory syndrome (IRIS) is poorly estimated due to Africa's underdeveloped infrastructure, particularly in Eastern Africa. Therefore, this study compiled data regarding the magnitude and associated factors of IRIS in the context of Eastern Africa. Methods: The electronic databases such as Google Scholar, PubMed, Web of Science, and free Google access were searched till 5 June 2021, and the search was lastly updated on 30 June 2022 for studies of interest. The pooled prevalence, and associated factors with a 95% confidence interval were estimated using the random effects model. The I2 and Egger's tests were used for heterogeneity and publication bias assessment, respectively. Results: The development of HIV-associated IRIS in Eastern Africa was estimated to be 18.18% (95% CI 13.30-23.06) in the current review. The two most common predictors of IRIS associated with Eastern Africa were the lower pre-ART CD4 T-cell count of 50 cells/µl and the low baseline body mass index level. Therefore, attention should be focused on the early detection and care of HIV-associated IRIS to reduce the morbidity and death caused by IRIS.

Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians.

With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limited in Ethiopia. Thus, this study aimed to assess INSTI RMs and polymorphisms at the gene locus coding for Integrase (IN) among viral isolates from ART-naive HIV-1 infected Ethiopian population. This was a cross-sectional study involving isolation of HIV-1 from plasma of 49 newly diagnosed drug-naive HIV-1 infected individuals in Addis-Ababa during the period between June to December 2018. The IN region covering the first 263 codons of blood samples was amplified and sequenced using an in-house assay. INSTIs RMs were examined using calibrated population resistance tool version 8.0 from Stanford HIV drug resistance database while both REGA version 3 online HIV-1 subtyping tool and the jumping profile Hidden Markov Model from GOBICS were used to examine HIV-1 genetic diversity. Among the 49 study participants, 1 (1/49; 2%) harbored a major INSTIs RM (R263K). In addition, blood specimens from 14 (14/49; 28.5%) patients had accessory mutations. Among these, the M50I accessory mutation was observed in a highest frequency (13/49; 28.3%) followed by L74I (1/49; 2%), S119R (1/49; 2%), and S230N (1/49; 2%). Concerning HIV-1 subtype distribution, all the entire study subjects were detected to harbor HIV-1C strain as per the IN gene analysis. This study showed that the level of primary HIV-1 drug resistance to INSTIs is still low in Ethiopia reflecting the cumulative natural occurrence of these mutations in the absence of selective drug pressure and supports the use of INSTIs in the country. However, continues monitoring of drug resistance should be enhanced since the virus potentially develop resistance to this drug classes as time goes by.

Diabetes mellitus among adults on highly active anti-retroviral therapy and its associated factors in Ethiopia: Systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus occurs as a comorbid illness among people living with HIV and, in particular those on Highly Active Anti-retroviral therapies (HAART). Previous studies have documented the prevalence of diabetes mellitus among adults on HAART; however, there is lack of comprehensive estimation. Hence, this study was aimed to estimate the pooled prevalence and associated factors of diabetes mellitus among adults on HAART in Ethiopia. METHODS: Primary studies were exhaustively searched using Cochrane, PubMed, Google Scholar, Scopus and Web of science databases until February 2021. Eligible studies were selected and critically appraised for quality using the Joanna Briggs Institute (JBI) quality appraisal checklist. The required data were extracted and exported to Stata version 16 for meta-analysis. The overall prevalence of diabetes mellitus among adults on HAART was estimated using a weighted inverse random effect model. Sensitivity and sub-group analysis were conducted for evidence of heterogeneity. Trim and fill analysis was performed after Egger's test and funnel plot were indicating the presence of publication bias. RESULTS: A total of 17 studies with 6,052 subjects on HAART were included. The pooled prevalence of diabetes mellitus among patients on HAART was 16.04% [95% Confidence Interval (CI); 11.6, 20.92]. Abnormal High Density Lipoprotein Cholesterol (HDL-C) [Adjusted Odd Ratio (AOR) = 4.68, 95% CI; 2.54, 6.82], Body Mass Index (BMI) ≥ 25 kg/m2 [AOR = 7.41, 95% CI; 2.75, 12.08], ≥6 years ART [AOR = 8.14, 95% CI; 5.85, 30.43], hypertension [AOR = 3.29, 95% CI; 2.13, 4.45], age 35-44 years [AOR = 6.28; 95% CI; 4.20, 8.37, BMI ≥ 30 kg/m2 [AOR = 7.81, 95% CI; 4.97, 10.64], educational status above diploma [AOR = 6.42, 95% CI; 1.28, 11.57] and age 45-55 years [AOR = 4.46, 95% CI; 2.81, 6.10] were positively associated with diabetes mellitus comorbidity among adults on HAART. CONCLUSION: The higher prevalence of diabetes mellitus was observed for adults on HAART. HDL-C, duration of ART, hypertension, overweight, obesity, age and educational status of participants increases the prevalence of diabetes mellitus. The study highlights the importance of timely screening of HDL-C level, blood pressure and BMI for adults on HAART.

Macrosomia and its predictors in pregnant women with diabetes in Ethiopia.

BACKGROUND: To estimate the prevalence of macrosomia and contributing factors among pregnant women with diabetes in Ethiopia. METHODS: The Cochrane, PubMed, Google Scholar, SCOPUS, Web of Science electronic databases and grey literature found in online university repositories were searched for primary studies reporting the prevalence of macrosomia (birth weight ≥4 kg, irrespective of gestational age) and/or at least one determinant factor using WHO diabetes diagnosis criteria were involved. Variations across the studies were checked using the I2  statistic; funnel plot and Egger's test were used to assess publication bias. A weighted inverse random effect model was used to estimate the overall prevalence of macrosomia. RESULTS: The overall prevalence of macrosomic newborns among pregnant women with diabetes [15.1% (95% CI: 9.0%, 21.2%)] was higher than the prevalence among non-diabetic mothers (3.9%). Maternal blood glucose level >100 mg/dl [AOR = 10.5: 95% CI: 5.9, 15.1] and >120 mg/dl [AOR = 8.8: 95% CI: 4.5, 13.0], lack of Antenatal Care (ANC) visit [AOR = 10.8: 95% CI: 6.0, 15.0], previous adverse birth outcomes and advanced maternal age [AOR = 3.5: 95% CI: 1.0, 5.9] were significantly associated with the prevalence of macrosomia at 95% CI. CONCLUSION: The pooled prevalence of macrosomia among pregnant women with diabetes was higher than the prevalence among non-diabetic pregnant women (3.9%). Advanced maternal age, previous adverse birth outcomes, lack of ANC and uncontrolled maternal plasma glucose level were independent predictors of macrosomia.

Coagulopathy in SARS-CoV-2 Infected Patients: Implication for the Management of COVID-19.

COVID-19 disease has led to an extraordinary inclusive health crisis globally. Elevation of D-dimer is the major remarkable abnormal coagulation test in seriously ill COVID-19 patients. In nearly 50% of COVID-19 patients, the value of D-dimer was significantly enhancing. Recent literature indicated that COVID-19 patients were at higher risk of developing disseminated intravascular coagulation. Pro-inflammatory cytokines and chemokines are some of the factors leading to these conditions. The majority of COVID-19 patients showed a higher profile of pro-inflammatory cytokines and chemokines in severe clinical conditions. Tumor necrosis factor-α (TNF-α) and interleukins (ILs) elevated in COVID-19 infected patients. TNF-α, IL-6, and IL-1 are major cytokines vital for the inhibition of intrinsic anticoagulant pathways. COVID-19 becomes a higher complication with a significant effect on blood cell production and hemostasis cascades. Deep vein thrombosis and arterial thrombosis are common complications. Changes in hematological parameters are also frequently observed in COVID-19 patients. Especially, thrombocytopenia is an indicator for poor prognosis of the disease and is highly expected and aggravates the likelihood of death of SARS-CoV-2 infected individuals. Thrombopoiesis reduction in COVID-19 patients might be due to viral abuse of the bone marrow/the viral load may affect thrombopoietin production and function. In other ways, immune-inflammation-mediated destruction and increased consumption of platelets are also the possible proposed mechanisms for thrombocytopenia. Therefore, the counting of platelet cells is an easily accessible biomarker for disease monitoring. All SARS-CoV-2 infected patients should be admitted and identifying potential higher-risk patients. It is also obligatory to provide appropriate treatments with intensive care and strict follow-up. In addition, considerations of chronic diseases are essential for better prognosis and recovery. The current review discusses coagulopathy among SARS-CoV-2 infected individuals and its complication for the management of the disease.

Prevalence and Determinants of Pre-Cancerous Cervical Lesion and Human Papillomavirus Among HIV-Infected and HIV-Uninfected Women in North-West Ethiopia: A Comparative Retrospective Cross-Sectional Study.

BACKGROUND: The poor socio-economic status, underdeveloped health care system, and the high HIV/AIDS burden have potentially increased the incidence of cervical cancer in sub-Saharan Africa (SSA) including Ethiopia. Studies on the magnitude of pre-cancerous cervical lesion and human papillomavirus (HPV) among HIV-infected women are still limited, particularly in the current study setting. Thus, we determined the prevalence of pre-cancerous cervical lesion and HPV among HIV-infected women in comparison with HIV-uninfected women at Debre Tabor Comprehensive Specialized Hospital (DTCSH), North-West Ethiopia. METHODS: Hospital-based comparative retrospective cross-sectional study was conducted among 546 women from July 2018 to January 2020 at DTCSH. All records during the study period were collected using a structured checklist. Epi data version 4.02 and SPSS version 25.0 were used for data entry and analysis, respectively. RESULTS: The overall prevalence of pre-cancerous cervical lesion among 546 women was 8.8%. The prevalence of pre-cancerous cervical lesion was comparable between HIV-infected (9.3%) and HIV-uninfected women (8.6%) (p = 0.859). Age >45 years old, widowed marital status, multiparous (women ≥ 5 childbirths), and educational status were independent contributing factors of a pre-cancerous cervical lesion. Regarding HPV prevalence, among 109 screened women, 7 (6.4%) were positive for both HPV 16 and 18 strains. CONCLUSION: HIV infection was not statistically correlated with the magnitude of pre-cancerous cervical lesion (p = 0.859). Women in the study setting developed pre-cancerous cervical lesions irrespective of their HIV status. Hence, we recommend routine screening of women for pre-cancerous cervical lesion and HPV infection regardless of their HIV status for early management and prevention of associated morbidity and/or mortality.

Viral Etiologies of Meningitis in Patients with Presumed Pyogenic Meningitis at University Hospitals in Ethiopia.

INTRODUCTION: Viral meningitis is common in most resource-limited settings, posing a challenge for the management and prognosis of suspected patients. No study has been done on the detection of either viral or viral-bacterial co-infection among presumed pyogenic meningitis cases in Ethiopia. We, therefore, aimed to determine the distribution of cytomegalovirus (CMV) and human enteroviruses (HEVs) among patients with presumptive pyogenic meningitis at University hospitals in Ethiopia. METHODS: Viral nucleic acid was extracted from 86 repository CSF samples, which were collected from patients presumptively diagnosed with pyogenic meningitis between 2012 and 2013. PCR was done consecutively to investigate the possible viral etiologic agents of meningitis. RESULTS: HEVs were detected in 11 (12.8%) of the analyzed samples while none of the 86 samples were tested positive for CMV. Viral-bacterial co-infections were found among 4/11 (36.4%) confirmed cases. The majority of the patients (10/11) with HEVs were younger aged ≤ 19 years old. CONCLUSIONS: In this study, the magnitude of HEVs was shown to have a significant role in presumed pyogenic meningitis cases. Therefore, we recommend presumed pyogenic meningitis cases to be inspected for viral etiologies and improve meningeal symptoms interpretations.

Human cytomegalovirus infection among treatment-naive HIV-1 infected patients in Ethiopia.

Subclinical human cytomegalovirus (HCMV) replication is associated with immune dysfunction in immuno-suppressed antiretroviral therapy (ART) naive HIV infected individuals. No data is documented in Ethiopia so far concerning HCMV co-infection among HIV infected individuals. Hence, this study was aimed at generating data regarding the prevalence of active HCMV infection among treatment-naive HIV-infected individuals from Ethiopia. For this purpose, we enrolled 97 treatment-naive HIV infected study subjects in Addis Ababa from June to December 2018. ELISA and conventional PCR were performed consecutively to detect HCMV specific IgM antibody and HCMV DNA respectively. Of the 97 study subjects, 12 (12.4%) were positive for anti-CMV IgM antibodies but were not confirmed by PCR. With regard to the PCR positivity, 4/97 (4.1%) samples were positive for HCMV DNA. No statically significant associations were found between the dependent and independent variables. The presence of HCMV DNA in the current study highlights the need for a routine laboratory diagnosis for preventing HCMV disease among HIV-infected individuals early. Besides, the use of anti-CMV therapy for these CMV viremic individuals is also recommended as this can reduce the burden of CMV complications and consecutively prolonging the life of HIV infected individuals.

Neopterin: A Promising Candidate Biomarker for Severe COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has rapidly spread across the world since its first emergence in China in late 2019. It is a major public health concern with no effective treatct 3ments. The immunopathology of SARS-CoV-2 is associated with an excessive inflammatory response. Macrophage activation syndrome (MAS) is also associated with the severity of the disease in SARS-CoV-2-infected patients. Neopterin is a macrophage activation marker produced by monocytes and macrophages upon activation by interferon-gamma (IFN-γ). Neopterin is a well-established marker in a variety of diseases, and recent evidence indicates that it could be helpful in early prediction of the severity of COVID-19 disease and serve as a prognostic marker. Here, we outline the role of macrophage activation syndrome in the pathogenesis of SARS-CoV-2 and suggest that neopterin could be used as a biomarker for progression of COVID-19.

Enhanced identification of Group B streptococcus in infants with suspected meningitis in Ethiopia.

Meningitis is one of the top ten causes of death among Ethiopian infants. Group B streptococcus (GBS) has emerged as a leading cause of meningitis in neonates and young infants, resulting in high mortality. Despite this, there is no report on GBS associated meningitis in Ethiopia where infant meningitis is common. Hence, the aim of this study was to determine the proportion of GBS associated meningitis among Ethiopian infants. PCR was prospectively used to detect GBS in culture-negative cerebrospinal fluid (CSF) samples, which were collected from infants suspected for meningitis, at Tikur Anbessa specialized hospital, Ethiopia, over a one-year period. GBS was detected by PCR in 63.9% of culture-negative CSF samples. Out of the 46 GBS positive infants, 10.9% (n = 5) of them died. The late onset of GBS (LOGBS) disease was noted to have a poor outcome with 3 LOGBS out of 5 GBS positive samples collected from patients with the final outcome of death. PCR was advantageous in the identification of GBS in culture-negative CSF samples. GBS was detected in 64% of the CSF samples from infants with meningitis compared with zero-detection rate by culture.

COVID-19 pandemic: current knowledge about the role of pets and other animals in disease transmission.

On 11 March 2020, the World Health Organization (WHO) announced Corona Virus Disease (COVID-19), a disease caused by a pathogen called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pandemic. This ongoing pandemic has now been reported in 215 countries with more than 23 million confirmed cases and more than 803 thousand deaths worldwide as of August 22, 2020. Although efforts are undergoing, there is no approved vaccine or any specific antiretroviral drug to treat COVID-19 so far. It is now known that SARS-CoV-2 can affect not only humans but also pets and other domestic and wild animals, making it a one health global problem. Several published scientific evidence has shown that bats are the initial reservoir hosts of SARS-CoV-2, and pangolins are suggested as an intermediate hosts. So far, little is known concerning the role of pets and other animals in the transmission of COVID-19. Therefore, updated knowledge about the potential role of pets in the current outbreak will be of paramount importance for effective prevention and control of the disease. This review summarized the current evidence about the role of pets and other animals in the transmission of COVID-19.

Immunoglobulin G2 Antibody as a Potential Target for COVID-19 Vaccine.

The global threat of COVID-19 is continued with no commercially available vaccine or drug yet. While the application of convalescent therapy is usually beneficial, for critically ill patients, the detrimental effect associated with some antibodies is also reported. The immunoglobulin G (IgG) antibody in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is described, albeit the lack of defining whether the difference in subclasses has a beneficial or detrimental role. IgG2 has limited ability to activate innate immune cells and complement-mediated inflammation, which have been inversely described in SARS-CoV-2 pathogenesis. The expansion of IgG2 is promoted by interferon γ (IFN-γ); however, there is a low level of IFN-γ in COVID-19 patients. Therefore, this review describes the importance of targeting IgG2, with IFN-γ in minimizing the SARS-CoV-2 associated inflammation, and may provide insight into the design of vaccine or antibody-based therapies to COVID-19 disease.

Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia.

BACKGROUND: The development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR mutations among ART-naive recently diagnosed HIV-1 infected individuals in Addis Ababa, Ethiopia. METHODS: Institutional based cross-sectional study was conducted from June to December 2018 in Addis Ababa among ART-naive recently diagnosed individuals. Partial HIV-1 pol region covering the entire protease (PR) and partial reverse transcriptase (RT) regions of 51 samples were amplified and sequenced using an in-house assay. Drug resistance mutations were examined using calibrated population resistance (CPR) tool version 6.0 from the Stanford HIV drug resistance database and the International Antiviral Society-USA (IAS-USA) 2019 mutation list. RESULTS: According to both algorithms used, 9.8% (5/51) of analyzed samples had at least one PDR Mutation. PDR mutations to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) were the most frequently detected (7.8% and 9.8%, according to the CPR tool and IAS-USA algorithm, respectively). The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only. Y115F and M184V (mutations that confer resistance to NRTIs) dual mutations were detected according to both criteria in a single study participant (2%). PDR mutation to protease inhibitors was found to be low (only G73S; 2% according to the CPR tool). Phylogenetic analysis showed that 98% (50/51) of the study participants were infected with HIV-1C virus while one individual (2%) was infected with HIV-1A1 virus. CONCLUSIONS: This study showed an increased level of PDR and persistence HIV-1C clade homogeneity after 15 years of the rollout of ART and 3 decades of HIV-1C circulation in Ethiopia, respectively. Therefore, we recommend routine baseline genotypic drug resistance testing for all newly diagnosed HIV infected patients before initiating treatment. This will aid the selection of appropriate therapy in achieving the 90% of patients having an undetectable viral load in consonance with the UN target.

Schistosoma mansoni infection among patients visiting a health centre near Gilgel Gibe Dam, Jimma, south Western Ethiopia.

OBJECTIVE: Schistosomiasis is a global parasitic disease and ranks second to malaria in terms of socio-economic and public health importance in tropical and subtropical areas. It is a disease which remains a major health problem due to the lack of vaccines, the failure to eradicate the mollusc vector and the recent development of parasite resistance to antischistosome drugs. METHODS: A cross- sectional study was conducted to determine the prevalence of Schistosoma mansoni infection among patients visiting Assendabo health center, nearby Gilgel Gibe hydroelectric dam, South-Western Ethiopia. RESULTS: From the total of 198 patients with stool sample 21(10.61%) were positive for Schistosoma mansoni infection. Of the infected subjects, 11.6% had contact with water for one or more reasons. CONCLUSION: The severity of infection and subsequent impact on the socio-cultural condition needs appropriate control measures especially where the water body which can act as habitat for the intermediate host is available.

Schistosoma mansoni infection among patients visiting a health centre near Gilgel Gibe Dam, Jimma, south western Ethiopia.

OBJECTIVE: Schistosomiasis is a global parasitic disease and ranks second to malaria in terms of socioeconomic and public health importance in tropical and subtropical areas. It is a disease which remains a major health problem due to the lack of vaccines, the failure to eradicate the mollusc vector and the recent development of parasite resistance to antischistosome drugs. A cross-sectional study was conducted to determine the prevalence of Schistosoma mansoni infection among patients visiting Assendabo health center, nearby Gilgel Gibe hydroelectric dam, South-Western Ethiopia. RESULTS: From the total of 198 patients with stool sample 21 (10.61%) were positive for Schistosoma mansoni infection. Of the infected subjects, 11.6% had contact with water for one or more reasons. CONCLUSION: The severity of infection and subsequent impact on the socio-cultural condition needs appropriate control measures especially where the water body which can act as habitat for the intermediate host is available.