Predictors of survival among adult Ethiopian patients in the national ART program at Seven University Teaching Hospitals: A prospective cohort study

Background: In Ethiopia, the publicly funded antiretroviral treatment (ART) program was started in 2005. Two hundred seventy-five thousand patients were enrolled in the national ART program by 2012. However, there is limited data on mortality and predictors of death among adult patients in the ART program. The study aimed to estimate mortality and risk factors for death among adult, ART-naïve patients,  started in the national ART program from January 2009 to July 2013.Methods: Multi-site, prospective, observational cohort study of adult, age > 18 years, ART-naïve patients, started in the national ART program at seven university-affiliated hospitals from January 2009 - July 2013. Kaplan-Meier and Cox  regression analyses were used to estimate survival and determine risk factors for death.Results: A total of 976 patients, 594 females (60.9 %), were enrolled into the study. Median age of the cohort was 33years. The median CD4 count at start of ART was 144 cells/μl (interquartile range (IQR) 78-205), and 34.2% (330/965) had CD4 < 100. Sixty-three percent (536/851) had viral load greater than 5 log copies/ml (IQR 4.7-5.7) at base line. One hundred and one deaths were recorded during  follow-up period, all-cause mortality rate 10.3%; 5.4 deaths/100 person years of observation, 95% confidence interval 4.4-6.5. Seventy percent of the deaths occurred within six months of starting ART. Cox regression analyses showed that the following measures independently predicted mortality: age >51 years, (Adjusted Hazard Ratio (AHR) 4.01, P=0.003), WHO stages III&IV, (AHR 1.76, p = 0.025), CD4 count, <100, (AHR 2.36, p =0.006), and viral load >5 log copies /ml (CHR 1.71, p = 0.037).Conclusion: There is high early on- ART mortality in patients presenting with advanced immunodeficiency. Detecting cases and initiating ART before onset of advanced immunodeficiency might improve survival.Key Words: Ethiopia, HIV clinical cohort, Antiretroviral therapy, Surviva

Magnitude of Antiretroviral Drug toxicity in adult HIV patients in Ethiopia: A cohort study at seven teaching hospitals

Background: The introduction of antiretroviral therapy (ART) has resulted in significant mortality reduction and improvement in the quality of life. However, this has come at a cost of increased drug toxicity. The objective of this study was to assess the patterns and predictors of ART toxicity in adult HIV patients in Ethiopia.Methods: This is a prospective cohort study conducted at seven teaching hospitals between September 2009 and December 2013 involving 3921 HIV patients on ART. Adverse drug reactions (ADR) due to ART were identified based on clinical assessment and/or laboratory parameters. Multivariable random effects Poisson regression analysis was used to identify factors independently associated with toxicity.Result: ADR due to ART drugs was reported in 867 (22.1 %) of the participants; 374 (9.5%) had severe forms. About 87% of reported toxicities were limited to three organ systems – the skin, nervous system and blood. The overall incidence of ADR was 9 per 100 person years. About a third of toxicities occurred during the first six months after ART initiation with the incidence rate of 22.4 per 100 person years. Concomitant anti-tuberculosis treatment was the strongest independent predictor of toxicity.Conclusion: ADR was found to be highly prevalent in HIV patients on ART at tertiary hospitals in Ethiopia. Most of these conditions occurred early after ART initiation and in those with concomitant anti-tuberculosis treatment. Thus, routine monitoring of patients on ART should be strengthened with particular emphasis in the first 6 months. Strategies should also be devised to replace older and more toxic agents with newer and safer drugs available.Key words: HIV, ART, adverse drug reaction, incidence rate, ACM, Ethiopi

Establishing a multicenter longitudinal clinical cohort Study in Ethiopia: Advanced Clinical Monitoring of Antiretroviral Treatment Project

Background: The purpose of this paper is to describe the establishment of the  Advanced Clinical Monitoring of ART Project in Ethiopia for monitoring and  evaluation of the longitudinal effectiveness of the ART program and to show the opportunities it presents. This cohort was established in response to the 2005 call by WHO for establishing additional mechanisms for stronger monitoring of ART and the need for creating the platform to generate evidence to guide the care given for the ever increasing number of patients on ART in Ethiopia.Method: A participatory and multi-stage process which started from a consensus building workshop and steered by a mother protocol as well as guiding documents which dictated the degree of engagement and expectations was followed. The primary and secondary aims of the study were agreed upon. A multi-site longitudinal observational clinical cohort was established by a consortium of stakeholders including seven Ethiopian medical schools and their affiliated referral hospitals, John Hopkins University, Ethiopian Public Health Institute, Ministry of Science and Technology, US Centers for Disease Prevention and Control - CDC-Ethiopia, and the Federal Ministry of Health. Adult and adolescent cohorts covering the age range of 14+ years) and pediatric cohorts covering those below age 14 years were the two main cohorts. During the initial recruitment of these cohorts information was extracted from existing documents for a total of 2,100 adult participants. In parallel, a prospective cohort of 1,400 adult and adolescent patients were enrolled for ART initiation and follow-up. Using similar recruitment procedures, a total of 120 children were enrolled in each of retrospective and prospective cohorts. Replacement of participants were made in subsequent years based on lost follow up and death rates to maintain adequacy of the sample to be followed-up.Achievements: Between January 2005 and August 2013 a total of 4,339 patients were followed for a median of 41.6 months and data on demographic characteristics, baseline and ongoing clinical features, hospitalization history, medication and laboratory information were collected. 39,762 aliquots and 25,515 specimens of plasma and dry-blood-spots respectively were obtained and stored longitudinally from October 2009 to August 2013. The project created a research platform for researchers, policy and decision makers. Moreover, it encouraged local and international investigators to identify and answer clinically and programmatically relevant research questions using the available data and specimens. Calls for concept notes paired with multiple trainings to stimulate investigators to conduct analyses further boosted the potential for doing research.Conclusions: A comprehensive and resourceful mechanism for scientific inquiry was established to support the national HIV/ART program. With meaningful involvement and defined roles, establishment of a study, which involved multiple institutions and investigators, was possible. Since ACM is the largest multi-site clinical cohort of patients on antiretroviral treatment in Ethiopia---which can be used for research and for improving clinical management---considering options to sustain the project is crucial. Key Words: Ethiopia, HIV clinical cohort, Antiretroviral therapy, Establishing Longitudinal Cohort Study, ART Monitoring and Evaluatio

Monitoring and risk assessment of pesticides in irrigation systems in Debra Zeit, Ethiopia.

Since Ethiopia is going through a rapid transformation of its agricultural sector, we assessed the human health and environmental risks due to the past use of organochlorine pesticides (OCPs) as well as the risks of the current pesticide use by farmers. A monitoring programme and risk assessment was carried out for the Wedecha-Belbela irrigation system in the Debra Zeit area. The Wedecha and Belbela rivers and adjacent temporary ponds were sampled and examined for the presence of OCPs between August and October 2014, while data on the current pesticide use by small- and large-scale farmers was collected by interviews. The usage patterns were evaluated for risks of using the river or temporary ponds as source of drinking water and for risks for the aquatic ecosystems in the river and ponds with the aid of the PRIMET_Registration_Ethiopa_1.1 model. The samples were collected in five sampling periods, and results indicate that most of the 18 target OCPs were not detected above the detection limit, while g-chlordane may pose chronic risks when surface water is used as drinking water. Endosulfan and heptachlor pose risks to aquatic organisms at second-tier level, while for heptachlor-epoxide B, g-chlordane and b-BHC only risks could be determined at the first tier due to a lack of data. For all nine pesticides used by small-scale farmers the calculated acute risks to humans were low. Second tier risk assessment for the aquatic ecosystem indicated that lambda-cyhalothrin, endosulfan, profenofos, and diazinon may pose high risks

Sensitivity of Ethiopian aquatic macroinvertebrates to the pesticides endosulfan and diazinon, compared to literature data

The aims of the present study were to present a methodology for toxicity tests that can be used when analytical resources to verify the test concentrations are limited, and to evaluate whether the sensitivity of a limited number of Ethiopian species to pesticides differs from literature values for, mainly, temperate species. Acute toxicity tests were performed using three Ethiopian aquatic invertebrate species, one crustacean (Diaphanosoma brachyurum) and two insects (Anopheles pharoensis and Culex pipiens) and using the pesticides endosulfan and diazinon. All species–pesticide combinations were tested in duplicate to estimate the consistency, i.e. the intra-laboratory variation, in test results. Daphnia magna was tested as well to allow the test results to be compared directly with values from the literature. Results indicate that the differences between the EC50s obtained for D. magna in this study and those reported in the literature were less than a factor of 2. This indicates that the methodology used is able to provide credible toxicity values. The results of the duplicated tests showed intra-laboratory variation in EC50 values of up to a factor of 3, with one test showing a difference of a factor of 6 at 48 h. Comparison with available literature results for arthropod species using species sensitivity distributions indicated that the test results obtained in this study fit well in the log-normal distribution of the literature values. We conclude that the methodology of performing multiple tests to check for consistency of test results and performing tests with D. magna for comparison with literature values to check for accuracy is able to provide reliable effect threshold levels and that the tested Ethiopian species did not differ in sensitivity from the arthropod species reported on in the literature

The use of a simple model for the regulatory environmental risk assessment of pesticides in Ethiopia

Pesticide registration in developing countries like Ethiopia is often not supported by substantiated risk assessment procedures. In this study, we evaluated the PRIMET (Pesticide Risks in the Tropics for Man, Environment and Trade) Registration_Ethiopia_1.1 model which is a tool developed to assess the risks to non-target protection goals. All the 103 registered active ingredients (a.i.) in Ethiopia, except those used for flower and storage pest control purposes, were evaluated on their environmental risks. Data on physico-chemical characteristics, toxicity and pesticide use patterns were mined from either the information given in the dossier or public databases. Together with scenarios specifically developed for Ethiopia, these data were used to perform a risk assessment for the aquatic and terrestrial environment as well as for vertebrates including humans via contaminated drinking water exposure. Results indicated that 11 and 16% of the a.i.s are indicated to pose high acute risk and 7.3 and 11% high chronic risks for fish and aquatic invertebrates, respectively. Similarly, 5.5 and 8.7% high acute risks and 6.8 and 3.9% high chronic risks were observed for the soil ecosystem and birds, respectively. 23% of the evaluated active ingredients were indicated to be highly risky to bees when beehives are present inside the sprayed crop while 7.8% of them are highly risky when beehives are present outside the field of the sprayed crop. The fungicide metalaxyl, the herbicides acetochlor, alachlor, mecoprop and tembotrion, and the insecticides carbaryl, chlorpyrifos, diazinon and methidathion were predicted to pose high acute or chronic risks to humans or other vertebrates if surface water is used as a source of drinking water. Future studies should give emphasis on how the risk assessment results of this study can be implemented to aid the registration process

Monitoring and risk assessment of pesticides in irrigation systems in Debra Zeit, Ethiopia.

<p>Since Ethiopia is going through a rapid transformation of its agricultural sector, we assessed the human health and environmental risks due to the past use of organochlorine pesticides (OCPs) as well as the risks of the current pesticide use by farmers. A monitoring programme and risk assessment was carried out for the Wedecha-Belbela irrigation system in the Debra Zeit area. The Wedecha and Belbela rivers and adjacent temporary ponds were sampled and examined for the presence of OCPs between August and October 2014, while data on the current pesticide use by small- and large-scale farmers was collected by interviews. The usage patterns were evaluated for risks of using the river or temporary ponds as source of drinking water and for risks for the aquatic ecosystems in the river and ponds with the aid of the PRIMET_Registration_Ethiopa_1.1 model. The samples were collected in five sampling periods, and results indicate that most of the 18 target OCPs were not detected above the detection limit, while g-chlordane may pose chronic risks when surface water is used as drinking water. Endosulfan and heptachlor pose risks to aquatic organisms at second-tier level, while for heptachlor-epoxide B, g-chlordane and b-BHC only risks could be determined at the first tier due to a lack of data. For all nine pesticides used by small-scale farmers the calculated acute risks to humans were low. Second tier risk assessment for the aquatic ecosystem indicated that lambda-cyhalothrin, endosulfan, profenofos, and diazinon may pose high risks.</p

Impacts of nutrients and pesticides from small- and large-scale agriculture on the water quality of Lake Ziway, Ethiopia

The area around Lake Ziway in Ethiopia is going through a major agricultural transformation with both small-scale farmers and large horticultural companies using pesticides and fertilisers at an increased rate. To be able to understand how this influences the water quality of Lake Ziway, water quality data was gathered to study the dynamics of pesticide concentrations and physicochemical parameters for the years from 2009 to 2015. Results indicate that for some physicochemical parameters, including pH, potassium and iron, over 50 % of the values were above the maximum permissible limit of the Ethiopian standard for drinking water. The insecticide spiroxamine poses a high chronic risk when the water is used for drinking water, while the estimated intake of diazinon was approximately 50 % of the acceptable daily intake. Higher-tier risk assessment indicated that the fungicide spiroxamine poses a high acute risk to aquatic organisms, while possible acute risks were indicated for the insecticides deltamethrin and endosulfan. Longer-term monitoring needs to be established to show the water quality changes across time and space, and the current study can be used as a baseline measurement for further research in the area as well as an example for other surface water systems in Ethiopia and Africa