Factors associated with stunting in under-five children with environmental enteropathy in slum areas of Jimma town, Ethiopia.

Introduction: Stunting is a major public health issue with a significant influence on the health and development of children in low-income countries, where it affects up to 32% of children. Nutritional intake is impacted by alterations in intestinal permeability and underlying chronic inflammation, which hinder children's normal linear growth. Environmental enteropathy is a poorly understood condition with chronic intestinal inflammation. The purpose of this study was to identify the magnitude of stunting, change in growth, and factors associated with stunting and change in height for the age Z-score of children with an elevated lactulose-to-mannitol ratio. Methods: An observational follow-up study was conducted to follow children with an elevated lactulose-to-mannitol ratio for changes in their linear growth. A lactulose-mannitol test was performed to identify children with elevated lactulose-to-mannitol ratios, indicative of environmental enteropathy. After a 1-year follow-up, anthropometry was repeated to assess their linear growth. A multivariable logistic regression analysis was performed to identify the independent predictors for stunting in children with elevated lactulose-to-mannitol ratios. All tests were two-sided, and a p-value of <0.05 was considered significant. Results: The prevalence of stunting in children with an elevated L:M at baseline and end line was found to be 72.4% (95% CI: 60.3, 84.5) and 78.4% (95% CI: 66.7, 90.2), respectively. In a multivariate analysis, a low dietary diversity score (<4 food groups), presence of flies and insects in the toilet area, poor handwashing practices during a critical time, and MUAC z < -2 were significantly associated with stunting. Flies and insects in the toilet area and unsafe disposal of feces were significantly associated with changes in HAZ in children with elevated lactulose-to-mannitol ratios, an indicator of environmental enteropathy. Conclusion: Most of the children with an elevated lactulose-to-mannitol ratio in the study population were stunted, and no significant change in their linear growth was observed after 1-year follow-up. Therefore, further investigation and urgent intervention are needed to prevent environmental enteropathy and stunting among under-five children in this community who are exposed to very poor sanitary conditions and other risk factors for malnutrition.

Environmental enteropathy and its association with water sanitation and hygiene in slum areas of Jimma Town Ethiopia.

BACKGROUND: Environmental Enteropathy is an inflammatory condition of the gut that leads to intestinal barrier dysfunction. It is a common problem in resource-limited countries and results from exposure to larger quantities of fecal bacteria to poor personal hygiene and environmental sanitation. Due to poor intestinal permeability, there is a problem with absorption of nutrients, which in turn leads to growth faltering, poor cognitive development, and oral-vaccine failure. The aim of this study was to identify the children with an elevated lactulose to mannitol ratio (indicative of possible environmental enteropathy) and its association with water sanitation and hygiene in slum areas of Jimma Town so as to mitigate the problem of malnutrition in under-five children. METHODS: A community-based cross-sectional study was carried out from January to April 2021. A Lactulose mannitol test was performed to determine the prevalence of elevated lactulose to mannitol ratio (possibly environmental enteropathy) in children aged 12 to 59 months. A pretested questionnaire was used to collect data on water sanitation and hygiene (WASH) indicators and sociodemographic characteristics. A multivariable logistic regression analysis was used to isolate independent predictors for possible environmental enteropathy. All tests were two-sided and statistical significance was declared at P<0.05. RESULTS: The results of this study showed that 19.3% (95%CI: 14.8-23.7) of children had an increased lactulose to mannitol ratio (>0.15). On multivariable logistic regression analysis, the variables drinking water from unimproved water sources (AOR 3.741; 95%CI: 0.914-15.310,p = 0.048), unsafe coverage of water storage (AOR 0.363; 95%CI: 0.169-0.777, P = 0.009), public latrine utilization (AOR 0.139 95%CI: 0.024-0.816, P = 0.029),and hand washing less than 3 critical time of hand washing practices (AOR 4.369;95%CI: 1.411-13.524,P = 0.011) were significantly associated with an increased in lactulose mannitol ratio (possible indicative of intestinal permeability/environmental enteropathy). CONCLUSION: This study showed that one fifth of under-five children in Jimma Town had an elevated lactulose to mannitol ratio (possibly environmental enteropathy). The WASH sectors and other governmental organizations should give emphasis to areas with poor water sanitation and hygiene to mitigate the problem of environmental enteropathy and related consequences like growth faltering, poor cognitive development, and oral-vaccine failure in the study area.

Environmental Enteropathy and Anaemia Status Among Under-Five Children, in Slum Areas of Jimma Town, Ethiopia.

Background: The most important anemia next to iron deficiency is anemia of inflammation. Micronutrient deficits, such as those in zinc and iron, can be caused by intestinal permeability and gut inflammation brought on by environmental enteric dysfunction. This study was aimed to evaluate the prevalence and association of anemia with Environmental Enteropathy. Methods: Data on water sanitation and hygiene indicators and sociodemographic characteristics were collected using structured questionnaire. The lactulose to mannitol ratio (L:M) was calculated from the concentration of both sugars in the urine. Level of Hemoglobin was detected by using Hemocue-301 digital photometer. Blood and urine sample was collected from three hundred children aged 12-59 months to determine the status of Anaemia and Environmental Enteropathy respectively. Results: Data were analyzed by using Descriptive statistics, cross-tabulation, and logistic regression model to indicate prevalence and association of anemia with environmental Enteropathy in children less than five years old. The prevalence of anemia in children with environmental enteropathy was 63.8% (95% CI: 57.6, 71.7), and there was a significant association (p = 0.0001, AOR 3.502, 95% CI: 1.929-6.371) between anemia and environmental enteropathy. In a multivariate analysis, children aged 1-3 years with caretakers who had no or only primary education and with monthly income of less than 3000 ETB were more likely to develop anemia. Conclusion: The result of this study indicated that two-thirds of children less than five with environmental enteropathy had developed anemia, and there is a significant association between environmental enteropathy and anemia. Even though there are other causes of anemia, based on the findings of this study, more research is needed to identify factors associated with environmental enteropathy to mitigate anemia due to intestinal permeability or malabsorption and its impact in children under the age of five.

Quality-by-Design Principles Applied to the Establishment of a Pharmaceutical Quality Control Laboratory in a Resource-Limited Setting: The Lab Water.

Quality-by-design (QbD) is defined as a systematic approach to design and develop a product/service based on sound science and quality risk management. It is already frequently applied in the pharmaceutical industry mainly in the development of pharmaceutical products and analytical methods but is not well established in the setup of facilities like quality control (QC) laboratory (lab). Therefore, lab QbD (lQbD) concept is introduced considering lab water purification system as an example. The water purification system comprising distillation unit coupled with Nanopure Analytical Ultrapure Water System combined with a 0.2-micron filter was established in Jimma University Laboratory of Drug Quality (JuLaDQ). The consistent capability of the established water purification system was evaluated through routine monitoring of the critical quality parameters (i.e., physicochemical, HPLC-DAD chromatogram total peak area, and resistivity) of freshly prepared lab water for a period of one year. In addition, quality of different grade water (tap water, distilled water (before and/or after cleaning distillation unit), and fresh ultrapure water (18.2 MΩ × cm at 25°C)) used in JuLaDQ was evaluated. The results of routine analysis of water quality revealed that HPLC global peak area at 210 and 254 nm could serve as one of the discriminatory control strategies to evaluate the capability of water purification system to produce the desired quality of lab water; and thus, we proposed a specification limit of 5,000 mAU∗s and 5,500 mAU∗s for global peak area at 254 and 210 nm, respectively, as system suitability parameter.

Dissolution Profile Evaluation of Eight Brands of Metformin Hydrochloride Tablets Available in Jimma, Southwest Ethiopia.

BACKGROUND: Dissolution is the critical quality control parameter and used to predict an in vivo oral bioavailability, and it is used to support bio-waiver. AIM: To evaluate and compare the dissolution profile of eight brands of metformin HCL 500 mg tablets available in Jimma town, Southwest Ethiopia. METHODS: The study was conducted in Jimma town, Ethiopia. Eight (seven brands and one comparator) metformin HCL 500 mg tablets were included. The dissolution study was conducted as per United States Pharmacopeia, and the dissolution profile was compared by one-way ANOVA, model-dependent and model-independent approaches. RESULTS: All of the included tablet brands complied with single-point dissolution study specification. Statistical comparisons of the dissolution profile by one-way ANOVA revealed that all brands had similar dissolution profiles (p=0.89). All of the brands had a similarity factor (f2) >50% and the difference factor (f1) <15. The entire brands followed the Weibull curve approach (the highest coefficient of determination and lowest Akaike Information Criteria) for the release of an active pharmaceutical ingredient. CONCLUSION: All of the brands complied with single point dissolution study and all of them could be used interchangeably with the innovator drug. All brands followed the Weibull method for the release of the drug substance.

Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets.

BACKGROUND: Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets. METHODS: The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products. RESULTS: A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r2 = 0.999) over the concentration range of 6.25-100 µg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality. CONCLUSIONS: The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets.

Quality of fixed dose artemether/lumefantrine products in Jimma Zone, Ethiopia.

BACKGROUND: Malaria caused by Plasmodium vivax and Plasmodium falciparum is among the major public health problems in most endemic areas of the world. Artemisinin-based combination therapy (ACT) has been recommended as a first-line treatment for uncomplicated Plasmodium falciparum malaria almost in all endemic regions. Since ineffectively regulated medicines in resource limited settings could favour infiltration of poor quality anti-malarial medicines into pharmaceutical supply chain and jeopardize a positive treatment outcome, regular monitoring of the quality of anti-malarial medicines is critical. Thus, the aim of this study was to assess the quality of fixed dose combination (FDC) artemether (ART)/lumefantrine (LUM) tablets available in Jimma zone, Ethiopia. METHODS: This study was conducted in Jimma zone, Ethiopia. A total of 74 samples of FDC ART/LUM (20 mg ART/120 mg LUM) tablets were collected from 27 public facilities. All samples were subjected to visual inspection and the relevant information was recorded. The samples were transported to Jimma University Laboratory of Drug Quality (JuLaDQ) and stored at ambient temperature (20 °C to 25 °C) until analysis. The Pharmacopoeial conform/non-conform methods and the risk-based Derringer's desirability function approach were employed to assess the pharmaceutical quality of the investigated products. RESULTS: The visual inspection results revealed that there were no signs of falsified in the investigated products. Identification test results of samples indicated that all samples contained the stated active pharmaceutical ingredients (APIs). The results of uniformity of mass indicated that all samples complied with International Pharmacopoeial specification limits. The assay results, expressed as percent label claim (%lc) of ART (89.8 to 108.8%, mean ± SD = 99.1 ± 3.9%) and LUM (90.0 to 111.9%, mean ± SD = 98.2 ± 3.8%) revealed that, all samples complied with International Pharmacopoeia acceptance specification limits (i.e. 90-110%lc), except one generic product (IPCA Laboratories Ltd., India) which contains excessive LUM (111.9 ± 1.7%lc). The risk priority number (RPN) results revealed that assay (RPN = 392) is relatively the most critical quality attribute followed by identity (RPN = 280) and mass uniformity (40). Quality evaluation based on psycho-physical Harrington's scale revealed that more than 96% of samples were within the acceptable ranges (D ≥ 0.7-1.0). CONCLUSIONS: Both Pharmacopoeial and risk-based desirability function approaches to quality evaluation applied to the investigated products revealed that above 96% FDC ART/LUM tablets circulating in public settings of Jimma zone are of good quality.