One health research ethics

Emerging and re-emerging infectious diseases (EIDs) present major threats to public health, global security, and economic development. Coronavirus disease 2019 (COVID-19) is the latest EID to demonstrate the devastation, suffering, and scale of death that an EID can cause. Pandemics involving emerging and re-emerging infectious agents and associated infectious diseases, climate change, urbanization, biodiversity loss and financial instability have been identified as the most critical global issues today (1). Close to three-quarters of today’s EIDs are known to be of zoonotic origin (where infectious agents spread to humans from domestic or wild animals), and their frequency and economic impact are on the ris

Study on knowledge, attitude and dog ownership patterns related to rabies prevention and control in Addis Ababa, Ethiopia

The study was conducted from May 2003 to August 2003 in Addis Ababa with the objective of understanding the distribution of stray and owned dogs, dog ownership patterns and attitudes of people towards rabies and its prevention and control methods. A total of 2390 households were selected from 6 Sub Cities of Addis Ababa using stratified random sampling and were interviewed using structured questionnaires. From the total households interviewed, 969 (40.5%) of them were known to own one or more dogs, and the total number of owned dogs was estimated to be 225,078. Male dogs make up 1042 (78.4%) of the total owned dogs. Almost half of all the dogs 463 (47.8%) were tied only for some time during the day whereas 320 (33.1%) of the dogs were not tied at all and freely move from place to place and contribute to high dog bites in human beings and for the widespread occurrence of canine rabies in Addis Ababa. Six hundred fifty five (67.6%) of the interviewed households who owned dogs had a well fenced house. Most of the owned dogs 856 (88.4%) get their food from their owners and only 321 (33.3%) of the owners reported that they let their dogs to be vaccinated while the majority of the owners 644 (66.5%) do not let their dogs vaccinated regularly. A significant proportion of the interviewed households 2,323 (97.2%), (P < 0.05) indicated that they have the knowledge that dogs, cats and other animals can transmit rabies to humans and 1,752 (73.4%) of the households replied that rabies can be transmitted through bite, scratch and lick to open wounds. Analysis of the list of 2400 post exposure human antirabies treatments recorded at the EHNRI Zoonoses Laboratory from February 2002 to October 2003 showed that the most common animals involved in biting people were dogs. A total of 2198 (91.6%) people were bitten by dogs during the same period and most of them, 2053 (85.5%) were bitten on their hands and legs. All the above data indicated the need for a strong and coordinated rabies control activities to be conducted in the city

Overview of Rabies in and around Addis Ababa, in Animals Examined in EHNRI Zoonoses Laboratory Between, 2003 and 2009

A retrospective data on the number of confirmed animal rabies cases and applied rabies control measures over the period 2003-2009 were collected and analyzed to elucidate the situation of animal rabies in and around Addis Ababa. Over the last seven years, 2517 animals brain tissue samples from Dogs, Cats, Cattle, Horses, Donkeys, Shoats, Hyenas and Monkeys were examined for rabies using Fluorescent Antibody Test. Out of all samples examined, 76.9% (n=1936) were positive for rabies antigen. A statistically significant difference (χ2 = 34.08(1),

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Early or deferred initiation of efavirenz during rifampicin‐based TB therapy has no significant effect on CYP3A induction in TB‐HIV infected patients

Background and Purpose: In TB‐HIV co‐infection, prompt initiation of TB therapy is recommended but anti‐retroviral treatment (ART) is often delayed due to potential drug–drug interactions between rifampicin and efavirenz. In a longitudinal cohort study, we evaluated the effects of efavirenz/rifampicin co‐treatment and time of ART initiation on CYP3A induction. / Experimental Approach: Treatment‐naïve TB‐HIV co‐infected patients (n = 102) were randomized to efavirenz‐based‐ART after 4 (n = 69) or 8 weeks (n = 33) of commencing rifampicin‐based anti‐TB therapy. HIV patients without TB (n = 94) receiving efavirenz‐based‐ART only were enrolled as control. Plasma 4β‐hydroxycholesterol/cholesterol (4β‐OHC/Chol) ratio, an endogenous biomarker for CYP3A activity, was determined at baseline, at 4 and 16 weeks of ART. / Key Results: In patients treated with efavirenz only, median 4β‐OHC/Chol ratios increased from baseline by 269% and 275% after 4 and 16 weeks of ART, respectively. In TB‐HIV patients, rifampicin only therapy for 4 and 8 weeks increased median 4β‐OHC/Chol ratios from baseline by 378% and 576% respectively. After efavirenz/rifampicin co‐treatment, 4β‐OHC/Chol ratios increased by 560% of baseline (4 weeks) and 456% of baseline (16 weeks). Neither time of ART initiation, sex, genotype nor efavirenz plasma concentration were significant predictors of 4β‐OHC/Chol ratios after 4 weeks of efavirenz/rifampicin co‐treatment. / Conclusion and Implications: Rifampicin induced CYP3A more potently than efavirenz, with maximum induction occurring within the first 4 weeks of rifampicin therapy. We provide pharmacological evidence that early (4 weeks) or deferred (8 weeks) ART initiation during anti‐TB therapy has no significant effect on CYP3A induction

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

Large-plot based performance evaluation of pigeon pea (Cajanus cajan L. Millsp.) Varieties for grain yield and agronomic traits under irrigation condition in Mandura District, North-West, Ethiopia

The experiment was conducted during the offseason at Mandura district, North-West, Ethiopia under irrigation condition with the objective, to test and evaluate the adaptability and performance of seven introduced ESA pigeonpea varieties for grain yield and other agronomic traits with standard check during 2017/2018 cropping season. The agronomic traits evaluated and tested were stand count at initial, days to flowering, days to maturity, plant height, and stand count at harvest, seeds per pod, seeds per plant, wilt score, hundred seed weight and usable grain yield per hectare. The evaluated materials showed three maturity class i.e. early, medium, and long durations. Among the tested materials, ICEAP-00557 scored the highest grain yield (2349kg/ha), followed by ICEAP-00576-1 (1737kg/ha), however, the standard check ICEAP-87091 score was comparatively inferior (1390kg/ha). At times there was great variability in the biomass of the varieties which deserves serious attention for the producers. Thus, it was suggested the existence of sufficient variability for key economic yield that gives an option for promoting for high socio-economic performance through adaptation and commercialization

Remote sampling of biomarkers of inflammation with linked patient generated health data in patients with rheumatic diseases:an Ecological Momentary Assessment feasibility study

BACKGROUND: People with rheumatic diseases experience troublesome fluctuations in fatigue. Debated causes include pain, mood and inflammation. To determine the relationships between these potential causes, serial assessments are required but are methodologically challenging. This mobile health (mHealth) study explored the viability of using a smartphone app to collect patient-reported symptoms with contemporaneous Dried Blood Spot Sampling (DBSS) for inflammation. METHODS: Over 30 days, thirty-eight participants (12 RA, 13 OA, and 13 FM) used uMotif, a smartphone app, to report fatigue, pain and mood, on 5-point ordinal scales, twice daily. Daily DBSS, from which C-reactive Protein (CRP) values were extracted, were completed on days 1–7, 14 and 30. Participant engagement was determined based on frequency of data entry and ability to calculate within- and between-day symptom changes. DBSS feasibility and engagement was determined based on the proportion of samples returned and usable for extraction, and the number of days between which between-day changes in CRP which could be calculated (days 1–7). RESULTS: Fatigue was reported at least once on 1085/1140 days (95.2%). Approximately 65% of within- and between-day fatigue changes could be calculated. Rates were similar for pain and mood. A total of 287/342 (83.9%) DBSS, were returned, and all samples were viable for CRP extraction. Fatigue, pain and mood varied considerably, but clinically meaningful (≥ 5 mg/L) CRP changes were uncommon. CONCLUSIONS: Embedding DBSS in mHealth studies will enable researchers to obtain serial symptom assessments with matched biological samples. This provides exciting opportunities to address hitherto unanswerable questions, such as elucidating the mechanisms of fatigue fluctuations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05723-w

Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options

There are four solid tumors with common screening options in the average-risk population aged 21 to 75 years (breast, cervical, colorectal, and, based on personalized risk assessment, prostate), but many cancers lack recommended population screening and are often detected at advanced stages when mortality is high. Blood-based multi-cancer early detection tests have the potential to improve cancer mortality through additional population screening. Reported here is a post-hoc analysis from the third Circulating Cell-free Genome Atlas substudy to examine multi-cancer early detection test performance in solid tumors with and without population screening recommendations and in hematologic malignancies. Participants with cancer in the third Circulating Cell-free Genome Atlas substudy analysis were split into three subgroups: solid screened tumors (breast, cervical, colorectal, prostate), solid unscreened tumors, and hematologic malignancies. In this post hoc analysis, sensitivity is reported for each subgroup across all ages and those aged ⩾50 years overall, by cancer, and by clinical cancer stage. Aggregate sensitivity in the solid screened, solid unscreened, and hematologic malignancy subgroups was 34%, 66%, and 55% across all cancer stages, respectively; restricting to participants aged ⩾50 years showed similar aggregate sensitivity. Aggregate sensitivity was 27%, 53%, and 60% across stages I to III, respectively. Within the solid unscreened subgroup, aggregate sensitivity was >75% in 8/18 cancers (44%) and >50% in 13/18 (72%). This multi-cancer early detection test detected cancer signals at high (>75%) sensitivity for multiple cancers without existing population screening recommendations, suggesting its potential to complement recommended screening programs. Clinical trial identifier: NCT02889978

Health care seeking among pulmonary tuberculosis suspects and patients in rural Ethiopia: a community-based study

<p>Abstract</p> <p>Background</p> <p>Health care seeking is a dynamic process that is influenced by socio-demographic, cultural and other factors. In Ethiopia, there are limited studies regarding the health seeking behaviour of tuberculosis (TB) suspects and TB patients. However, a thorough understanding of patients' motivation and actions is crucial to understanding TB and the treatment of disease. Such insights would conceivably help to reduce delay in diagnosis, improve treatment adherence and thereby reduce transmission of TB in the community. The objective of this study was to describe and analyze health care seeking among TB suspects and pulmonary TB (PTB) cases in a rural district of the Amhara Region in Ethiopia.</p> <p>Methods</p> <p>Study <it>kebeles </it>were randomly selected in a cross-sectional study design. House-to-house visits were conducted in which individuals aged 15 years and above in all households of the <it>kebeles </it>were included. Subjects with symptoms suggestive of TB were interviewed about their health seeking behaviour, socio-demographic and clinical factors using a semi-structured questionnaire. Logistics regression analysis was employed to assess associations between the independent and outcome variables.</p> <p>Results</p> <p>The majority, 787 (78%), TB suspects and 33 (82.5%) PTB cases had taken health care actions for symptoms from sources outside their homes. The median delay before the first action was 30 days. In logistics regression, women (AOR 0.8, 95% CI 0.6, 0.9) were found to be less likely to visit a medical health provider than men. Those with a long duration of cough (AOR 1.5, 95% CI 1.03, 2.1) and those with a previous history of TB (AOR 1.5, 95% CI 1.03, 2.3) were more likely to visit a medical health provider compared to those with a shorter duration of cough and with no history of TB.</p> <p>Conclusion</p> <p>The majority of TB suspects and PTB cases had already taken health care actions for their symptoms at the time of the survey. The availability of a simple and rapid diagnostic TB test for use at the lowest level of health care and the involvement of all health providers in case finding activities are imperative for early TB case detection.</p