Rotavirus A Infection Prevalence and Spatio-Temporal Genotype Shift among Under-Five Children in Amhara National Regional State, Ethiopia: A Multi-Center Cross-Sectional Study.

Background: Globally, rotavirus (RV) A (RVA) is the most common cause of severe and sometimes fatal diarrhea in young children. It is also the major cause of acute gastroenteritis among children in Ethiopia. Currently, the WHO has prequalified four RVA vaccines for universal childhood immunization. Ethiopia introduced the monovalent Rotarix vaccine into its national immunization program in 2013. Since then, only a few studies on the burden and genotype distribution of RVA infection post-vaccine introduction have been conducted (mostly at sentinel surveillance sites). Therefore, this study aimed to assess RVA prevalence and genotype distribution among children under five years in Ethiopia (February 2021-December 2022). Methods: This multi-center hospital-based cross-sectional study involved 537 diarrheic children under-five years old. Rotavirus A detection was conducted using a one-step reverse-transcriptase polymerase chain reaction (RT-PCR). Genotyping was conducted by Sanger sequencing of the VP7 (complete) and VP4 (partial) genes. Descriptive analysis and Pearson's chi-squared test were carried out using SPSS version 29. Phylogenetic analysis with 1000 bootstrap replicates was performed using MEGA version 11 software. Statistical significance was set at p < 0.05 for all analyses. Results: The prevalence of RVA infection among diarrheic children was 17.5%. The most prevalent G-types identified were G3 (37%), the previously uncommon G12 (28%), and G1 (20%). The predominant P-types were P[8] (51%), P[6] (29%), and P[4] (14%). The three major G/P combinations observed were G3P[8] (32.8%), G12P[6] (28.4%), and G1P[8] (19.4%). Phylogenetic analysis revealed clustering of Ethiopian strains with the globally reported strains. Many strains exhibited amino acid differences in the VP4 (VP8* domain) and VP7 proteins compared to vaccine strains, potentially affecting virus neutralization. Conclusions: Despite the high RVA vaccination rate, the prevalence of RVA infection remains significant among diarrheic children in Ethiopia. There is an observable shift in circulating RVA genotypes from G1 to G3, alongside the emergence of unusual G/P genotype combinations such as G9P[4]. Many of these circulating RVA strains have shown amino acid substitutions that may allow for neutralization escape. Therefore, further studies are warranted to comprehend the emergence of these unusual RVA strains and the diverse factors influencing the vaccine's diminished effectiveness in developing countries.

Dolutegravir based therapy showed CD4+ T cell count recovery and viral load suppression among ART naïve people living with HIV AIDS: a pilot evaluation.

Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. However, its effectiveness in CD4+ T-cells count recovery and viral load suppression has not been studied yet in Ethiopia, where HIV is endemic. Therefore, we aimed to conduct a pilot assessment on the effect of DTG-based therapy on CD4+ T-cell count and viral load count among people living with HIV (PLWH) in Ethiopia. A longitudinal prospective cohort study was conducted from July 2020 to February 2021. 109 PLWH who are ART naive but plan to initiate DTG-based therapy were recruited. HIV viral ribonucleic acid (RNA) copies were determined using polymerase chain reaction. To compute the difference in viral load and CD4+ T-cell counts between the baseline, 3rd, and 6th months, a Friedman test was used. The study included 109 PLWH who had never received antiretroviral medication. Participants taking DTG-based treatment showed significantly decreasing median (IQR) values of viral load count (copies/mL) from 446,812 (237649.5-732994.5) at baseline to 34 (23.5-46) at 3 months and 0.0 (0-19) at 6 months of treatment follow-up. Although the treatment increases the proportion of participants with HIV-1 RNA 50 copies/mL from 0 (0% at baseline) to 87 (79.8%) and 100 (91.7%) at the 3rd and 6th months of treatment, respectively, On the other hand, the CD4+ T-cell count increased significantly during treatment: median (IQR): 209 (81.5-417.5) versus 291 (132-522) versus 378 (181-632.5) cells/L at baseline, the 3rd and 6th months of the treatment follow-up period, respectively. We found dolutegravir-based therapy was a promising option with high virological suppression rates and CD4+ T-cell count recovery, demonstrating a restoration of cellular immunity. Moreover, Viral load suppression rates were high after the initiation of the treatment. We recommend further research should be conducted with a larger number of participants to acquire greater awareness of the treatment outcomes.

Evaluation of the diagnostic performance of EpiTuub® Fecal Rotavirus Antigen Rapid Test Kit in Amhara National Regional State, Ethiopia: A multi-center cross-sectional study.

Rotavirus is the leading cause of morbidity and mortality due to acute gastroenteritis among children under five years globally. Early diagnosis of rotavirus infection minimizes its spread and helps to determine the appropriate management of diarrhea. The aim of this study was to evaluate the performance of EpiTuub® Fecal Rotavirus Antigen Rapid Test Kit for the diagnosis of rotavirus infection among diarrheic children under five years in Ethiopian healthcare settings. A total of 537 children with diarrhea were enrolled from three referral hospitals in Amhara National Regional State, Ethiopia. The samples were tested using one-step RT-PCR and EpiTuub® Fecal Rotavirus Antigen Rapid Test Kit (KTR-917, Epitope Diagnostics, San Diego USA) in parallel. Diagnostic performance of the rapid test kit was evaluated using the one-step RT-PCR as a gold standard. The sensitivity, specificity, and predictive values of the rapid test kit were determined. Moreover, the agreement of the rapid test kit with one step RT-PCR was determined by kappa statistics and receiver operators' curve (ROC) analysis was done to assess the overall diagnostic accuracy of the rapid test kit. Fecal Rotavirus Antigen Rapid Test Kit has shown a sensitivity of 75.5% and specificity of 98.2%. The kit was also found to have 89.9% and 95.0% positive and negative predictive values, respectively. The Fecal Rotavirus Antigen Rapid Test Kit has shown a substantial agreement (78.7%, p = 0.0001) with one-step RT-PCR. The overall accuracy of the Fecal Rotavirus Antigen Rapid Test Kit was excellent with the area under the ROC curve of 86.9% (95% CI = 81.6, 92.1%) (p = .0001). Thus, Fecal Rotavirus Antigen Rapid Test is a sensitive, specific, user-friendly, rapid, and equipment-free option to be used at points of care in Ethiopian health care settings where resource is limited precluding the use of one step RT-PCR. Furthermore, the kit could be used in the evaluation and monitoring of rotavirus vaccine effectiveness in the aforementioned settings.

Prevalence of Intestinal Helminths among Cancer Patients Who Are under Chemotherapy at the University of Gondar Comprehensive Specialized Hospital Oncology Clinic, Northwest Ethiopia.

Background: In developing countries, environmental and personal hygiene is playing a great role in the increasing of intestinal helminth infection. In countries with limited resources and poor hygiene practices, there is a substantial overlap of intestinal helminthic and chronic infections like HIV, TB, and cancer. Intestinal helminths like Ascaris lumbricoides, Trichuris trichiura, and hookworm cause malnutrition and induce a type-2 immune response that could worsen the severity and clinical outcomes of patients with cancer. Our aim was to determine the prevalence of intestinal helminths among cancer patients who are under chemotherapy. Methodology. A prospective cross-sectional study was conducted in volunteer cancer patients. Clinical information were collected from study participants using a structured questioner. Stool sample was collected for parasitological examination. Formol-ether concentration technique was done, and then, two microscopic slides were prepared. Examination was done by two laboratory technicians for the detection of helminths. SPSS version 22 was used for data analysis, and simple descriptive statistical analysis was done for data presentation. Result: The total study participants were 41, of these 31 (75.6%) were females and 10 (24.4%) were male. Breast cancer and colonic cancer were the highest proportion with the others, 43.9% and 17.1%, respectively. The prevalence of intestinal parasites were 7/41 (17%). Hookworm 3/41(7.3%), Ascaris lumbricoides 3/41(7.3%), and Hymenolepis nana 1/41(2.4%) are the isolated parasite. Conclusions and Recommendations. The prevalence of intestinal helminths in cancer is lower than HIV and DM in the study area. However, the prevalence in these cancer patients is still high and needs deworming and health education for the better management of these cancer patients.

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation.

Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.

The burden of hepatitis B virus (HBV) infection, genotypes and drug resistance mutations in human immunodeficiency virus-positive patients in Northwest Ethiopia.

BACKGROUND: In sub-Saharan Africa, the hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are endemic. Although there has been great progress in HIV care, universal HBV vaccination and care is lacking. In this study, we aimed to determine the prevalence of HBV, HBV genotypes, and drug resistance mutations in dual infected cases in a cohort of HIV patients in Northwest Ethiopia. METHODS: A total of 308 HIV-1 positive patients were enrolled into the study and tested for HBsAg in plasma. In HBsAg positive samples, HBV DNA was analyzed for HBV genotype using in-house nested PCR with HBV-specific pre-core / core or surface primers, and for HBV drug resistance mutations (DRMs) in polymerase region. Odds ratio at 95% confidence interval was calculated. RESULTS: Of the 308 HIV-positive subjects, 62.7% were female, median age 38 years (range 18-68, IQR: 27-49), and the median CD4 count 405 cells/µl (IQR: 75-734). Overall, 94.2% were on antiretroviral therapy (ART) frequently with combinations of Zidovudine (AZT)- Lamivudine (3TC)-Nevirapine (NVP). HBsAg was detected in 5.5% (95%CI 2.95-8.08%) of the study participants, of which the majority were infected with HBV genotype A (7A, 2E, 2D, 1C, 1 G). All HIV/HBV positive cases were on ART with anti-HBV activity (i.e., 3TC) and 3TC associated HBV DRMs (i.e., rtV173L, rtL180M, and rtM204V) were detected in 7/13 (53.8%) subjects. CONCLUSION: In this cross-sectional study of HIV-infected individuals, we found 5.5% HBV/HIV co-infected cases. Most were receiving the first generation anti-HBV therapy with a low genetic barrier to resistance, and several carried mutations associated with anti-HBV (3TC) drug resistance. These data underscore the importance of integrating HBV screening to the HIV treatment guidelines for better management and prevention of HBV-related liver disease.

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Dembia District, northwest Ethiopia.

BACKGROUND: Artemether-lumefantrine (AL) has been used as a first-line treatment for uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. Antimalarial drug resistance is one of the major obstacles for malaria control and curtails the lifespan of several drugs. Thus, continued monitoring of the efficacy of AL is of great public health importance in malaria endemic areas. OBJECTIVE: This study aimed to investigate the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum malaria in the Dembia district, northwest Ethiopia. METHODS: A prospective study was conducted from April 2015 to February 2016 at Kola Diba Health Center (KHC) in the Dembia district to determine the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum monoinfection. Patients were treated with the six-dose regimen of AL over 3 days and followed up for 28 days as per the World Health Organization protocol. RESULTS: Of the total 80 patients enrolled in the AL efficacy study, 75 patients completed the 28 days follow-up. None of the participants reported major adverse events. No early treatment failure or late clinical failure were observed during the study, but there were 6 (8.0%) late parasitological failures. The uncorrected per protocol cure rate of AL was 92.0 (95% CI: 85.7-98.3). Treatment with AL cleared parasitemia and fever in >95% of the patients by day 3. CONCLUSION: This study showed that AL is well tolerated and remains efficacious for treatment of uncomplicated P. falciparum malaria in northwest Ethiopia. However, the observed late parasitological failures in this study are of a concern and warrant continued monitoring of drug efficacy as per the World Health Organization recommendations.