Application of Biotechnology in Diagnosis and Treatment of Human Genetic Disorders

Biotechnology is the application of biological molecules to make useful products that can be used to solve problems in different sectors. Medical biotechnology in particular aims to know the root causes of genetic disorders and develop therapeutic strategies. Although human diseases are caused by different factors, those caused by genetic disorders are increasing in prevalent worldwide. Early detection and treatment of these condition is paramount important. Chemical treatments that cure only the symptom of genetic disorders were practiced so far to manage the effect. However, as a result of advances in understanding of biological molecules, treatment of the cause of the disease called gene therapy has been developed more popularity nowadays. Moreover, most research centers abandoned the classical techniques that are prone to error, and began to use high throughput technologies to correct genetic disorders. Among these, CRISPR Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats Associated Cas9) is the most easy to use and allows precise gene editing in higher organisms to repair disease-causing genes by homologous directed repair. The recent development of modified versions CAs9 Nickase that  reduce off target effects and  the “base editor” that preform without double strand DNA break and  without the need to template indicated its application for therapeutic genome editing in man in the future. Keywords: Biotechnology, CRISPR Cas9, gene therapy, Nickase DOI: 10.7176/ALST/76-02 Publication date:September 30th 201

A survey on occurrence of internal and external fish parasites and causes of fish population reduction in Lake Hashenge, Tigray, Ethiopia

A cross-sectional study was conducted from November 2015 to June 2016 to determine the occurrence of internal and external parasites in wild fish population of Lake Hashenge and identify the causes of the trends in reduction of fish population. A total of 125 randomly selected fish samples comprising 122 (97.6%) Nile tilapia (Oreochromis niloticus) and 3(2.4%) T. zilli were examined for internal helminthes and external parasites. Overall, 37.6% (47/125) of fish were infested by internal parasites (adults or eggs/larva) while none of them were infested with external parasites. The internal parasites recovered were Clinostomum, Acanthocephalues and Capillaria accounting for 15.2%, 11.2%, and 7.2% of the total infection respectively, while 4% had mixed infection. Moreover, the distribution of parasitic genera were found to be significantly different (p<0.05) with respect to sex, weight, and lengths of the sampled fish, in that females (n=48, 24.8%), fish with body weight 500-1000g (n=89, 30.4%), and length 20-40cm (n=68, 22.4%) were found to be more infected. Most of the respondents (92%) indicated a great reduction in the water and the fish population of the lack from its previous state. All of the respondents have stated that residents of the area wash their clothes in the Lake using synthetic and/or natural detergents and 86% of the respondents believed that Lake Hashenge receives flooding water from nearby uphills and the people use the water from the Lake for small scale irrigation purposes. These findings demand a future focus and stretch of intervention programs for alleviation of the problems facing the Lake before its exhaustion.Keywords: Fish; Lake Hashenge; Parasites; Prevalence; Population reductio

Zoonotic tuberculosis in a high bovine tuberculosis burden area of Ethiopia

BackgroundTuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide, caused by species of the Mycobacterium tuberculosis complex (MTBC), with Mycobacterium tuberculosis being the dominant pathogen in humans and Mycobacterium bovis in cattle. Zoonotic transmission of TB (zTB) to humans is frequent particularly where TB prevalence is high in cattle. In this study, we explored the prevalence of zTB in central Ethiopia, an area highly affected by bovine TB (bTB) in cattle.MethodA convenient sample of 385 patients with pulmonary tuberculosis (PTB, N = 287) and tuberculous lymphadenitis (TBLN, N = 98) were included in this cross-sectional study in central Ethiopia. Sputum and fine needle aspirate (FNA) samples were obtained from patients with PTB and TBLN, respectively, and cultures were performed using BACTEC™ MGIT™ 960. All culture positive samples were subjected to quantitative PCR (qPCR) assays, targeting IS1081, RD9 and RD4 genomic regions for detection of MTBC, M. tuberculosis and M. bovis, respectively.ResultsTwo hundred and fifty-five out of 385 sampled patients were culture positive and all were isolates identified as MTBC by being positive for the IS1081 assay. Among them, 249 (97.6%) samples had also a positive RD9 result (intact RD9 locus) and were consequently classified as M. tuberculosis. The remaining six (2.4%) isolates were RD4 deficient and thereby classified as M. bovis. Five out of these six M. bovis strains originated from PTB patients whereas one was isolated from a TBLN patient. Occupational risk and the widespread consumption of raw animal products were identified as potential sources of M. bovis infection in humans, and the isolation of M. bovis from PTB patients suggests the possibility of human-to-human transmission, particularly in patients with no known contact history with animals.ConclusionThe detected proportion of culture positive cases of 2.4% being M. bovis from this region was higher zTB rate than previously reported for the general population of Ethiopia. Patients with M. bovis infection are more likely to get less efficient TB treatment because M. bovis is inherently resistant to pyrazinamide. MTBC species identification should be performed where M. bovis is common in cattle, especially in patients who have a history of recurrence or treatment failure

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Sanitary Survey in Gondar Town

Background: The health and well being of population is directly affected by extremely low coverage of water supply and sanitation. Objectives: This study aims to assess the environmental sanitation status of Gondar town. Methods: A cross-sectional study was conducted on the basis of the administrative structure of the town. The town was stratified into high density and low-density areas from which households were selected randomly from each stratum. A structured questionnaire was used for the household survey. Results: There is a relatively high risk of exposure to poor environmental conditions in high population than low population density area. The association between educational status and income with availability of latrine was statistically significant, the literates and the economically better-off have a better sanitary facility. Excreta disposal facilities are generally inadequate and poorly maintained. The per capita water consumption was 12 liters/day, which is very low when compared to 30-40 liters per day for urban residents, as per the WHO standard. Conclusion and recommendation: This study found that the sanitary status of the town to be poor. Thus, the municipality should give priority attention to improve the sanitary conditions in the town. Ethiop.J.Health Dev. 2003;(3):215-21

Sanitary Survey in Gondar Town

Background: The health and well being of population is directly affected by extremely low coverage of water supply and sanitation. Objectives: This study aims to assess the environmental sanitation status of Gondar town. Methods: A cross-sectional study was conducted on the basis of the administrative structure of the town. The town was stratified into high density and low-density areas from which households were selected randomly from each stratum. A structured questionnaire was used for the household survey. Results: There is a relatively high risk of exposure to poor environmental conditions in high population than low population density area. The association between educational status and income with availability of latrine was statistically significant, the literates and the economically better-off have a better sanitary facility. Excreta disposal facilities are generally inadequate and poorly maintained. The per capita water consumption was 12 liters/day, which is very low when compared to 30-40 liters per day for urban residents, as per the WHO standard. Conclusion and recommendation: This study found that the sanitary status of the town to be poor. Thus, the municipality should give priority attention to improve the sanitary conditions in the town. [Ethiop.J.Health Dev. 2004;18(1):39-42

Risk factors for surgical site infections in obstetrics: a retrospective study in an Ethiopian referral hospital

Abstract Background Pregnant women are at risk of infection during labor and delivery. Infection in obstetrics accounts for the second most common cause of maternal mortality next to post partum hemorrhage. Knowing the prevalence and associated risk factors would help to undertake optimal precautions and standard surgical techniques to reduce surgical site infection which poses increased hospital cost and total hospital stay of the patients. Method Facility based retrospective observational study design was carried out purposively to assess the prevalence of surgical site infections and associated risk factors among mothers who had delivery related surgery at obstetric ward of Assela teaching referral hospital from April, 23, 2015 to September 5, 2015. A total of 384 women who had surgery for delivery were included in the study. The risk associated with SSIs was assessed by multivariate regression logistic analysis. Results The age of the women ranged from 17 to 40 years with the mean age of 26 (±5) years. The rate of surgical site infection was 9.4%(36/384). The risk factors for surgical site infection were age less than 19 (OR = 3.5, 95%CI 1.17–10.01), preterm gestation age (OR = 4.225 95%CI 1.254–14.238), duration of labor ≥24 h (OR = 2.219 95%CI1.054–4.670), duration of rupture of membrane ≥12 h (OR = 5.99, 95% CI2.75–13.02),chorioamnionitis (OR = 9.743, 95%CI 3.077–30.848), vertical skin incision(OR = 4,95%CI 1.709–13.322), pre operation Hematocrit (OR = 6.4,95%CI1.021–40.137),perioperative blood transfusion(OR = 6.75,95%CI 2.47,18.49), abdominal hysterectomy(OR = 7.9,95%CI1.698–36.960), and diabetic mellitus (OR = 3.7,95%CI 1.112–12.519). Conclusions Obstetric ward of Assela teaching referral hospital are encouraged to use properly WHO surgical safety checklist and examine how to sensibly integrate these essential safety steps into their normal operative workflow. Prophylactic antibiotic administration should be provided within one hour before the surgical incision or within two hours if the patient is receiving vancomycin or floroquinolones

Evaluation of the effect of therapeutic durations on small ruminant bacterial pneumonia

Abstract Background Sheep and goat production in Ethiopia is hindered by numerous substandard production systems and various diseases. Respiratory disease complexes (RDC) pose a significant threat to the productivity of these animals. Pneumonia is a common manifestation of respiratory disease complexes and often necessitates a prolonged course of antibiotic treatment. This study aimed to optimize and propose the ideal duration of therapy for pneumonia in sheep and goats. Methods The study was conducted from February to June 2021 at the Veterinary Teaching Hospital of the College of Veterinary Medicine and Agriculture, Addis Ababa University. The study recruited 54 sheep and goats presented to the hospital for treatment with a confirmed RDC as determined based on clinical signs and bacteriological methods. The animals were randomly allocated to 5 groups each group receiving 10% oxytetracycline (Phenxyl, Phenix, Belgum) intramuscularly for a duration of 3, 4, 5, 6 and 7 consecutive days. The treatment outcomes were assessed by recording vital signs (body temperature, respiratory rate, heart rate, coughing, and nasal discharges), performing lung ultrasonography (L-USG) as well as collection of nasal swabs for bacterial isolation and molecular identification before and after completion of the treatment. An ordered logistic regression model with random effects was employed to determine the optimal therapeutic duration, taking into account the cumulative scores of the outcome variables across the different groups. Results Among the 54 sheep and goats treated with 10% oxytetracycline, a total of 74.07% (95% CI, 60.35–85.04) achieved complete recovery, as confirmed through clinical, ultrasound, and bacteriological methods. In Group 1 (G1), out of 12 sheep and goats, 8 (83.0%) recovered completely; in Group 2 (G2), out of 11 animals, 9 (82.0%) recovered completely; in Group 3 (G3), out of 11 animals, 10 (93.0%) recovered completely; in Group 4 (G4), out of 9 animals, 9 (100.0%) recovered completely; and in Group 5 (G5), out of 11 animals, 10 (91.0%) recovered completely. Bacteriological examination of nasal swabs indicated involvement of M. hemolytica in 27 (50.00%) and P. multocida in 13 (24.07%) of pneumonic animals. Detection of specific marker genes confirmed only five of the presumptive M. hemolytica isolates, whilst no isolates tested positive for P. multocida. Post-treatment samples collected from recovered animals did not yield any M. hemolytica nor P. multocida. Based on results from clinical signs, L-USG, and bacterial infection variables, the group of sheep and goats treated for seven consecutive days (G5) showed the highest recovery score compared to the other groups, and there was a statistically significant difference (coefficient (β) = − 2.296, p = 0.021) in variable score between G5 and G1. These findings suggest that the administration of 10% oxytetracycline for a full course of seven consecutive days resulted in symptomatic and clinical recovery rates from respiratory disease in sheep and goats

Additional file 1 of Evaluation of the effect of therapeutic durations on small ruminant bacterial pneumonia

Supplementary material 1