Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Comparison of the Diagnostic Performance of a Rapid Antigen Test with Real-Time Polymerase Chain Reaction for Detection of SARS-CoV-2 Among Patients Diagnosed with COVID-19 at Selected Hospitals in Addis Ababa, Ethiopia.

Background: When faced with a public health problem such as the COVID-19 pandemic, devising a test with an accurate and rapid diagnostic capacity is critical to contain the disease. We compared the diagnostic performance of a rapid antigen test in comparison with a reference method, namely a real-time polymerase chain reaction (RT-PCR) assay. Methods: We enrolled patients with confirmed COVID-19 from two selected hospital in Addis Ababa, Ethiopia, between January and November 2021. We assessed the performance of the Standard Q COVID-19 Ag Kit (SD Biosensor, Republic of Korea) in 200 nasopharyngeal and nasal swab samples. Results: Out of the 200 samples utilized for the diagnostic performance evaluation, equal proportion of the samples were confirmed positive and negative for SARS-CoV-2 based on RT-PCR. Of the 100 confirmed positive cases, 95 showed positive results with the rapid antigen test, yielding a sensitivity of 95% (95% confidence interval [CI] 88.7-98.4%). Of the 100 confirmed negative cases, there were three false-positive results, yielding a specificity of 97% (95% CI 91.5-99.4%). The sensitivity of the rapid antigen test was higher for samples with an RT-PCR cycle threshold (Ct) value ≤25 compared with samples with a higher Ct value. Conclusion: The finding demonstrated that the detection capacity of the Standard Q COVID-19 Ag Test meets the requirements set by the Ministry of Health Ethiopia. The high sensitivity and specificity of the test device indicate the possibility of using it for diagnostic and clinical purposes in resource-constrained settings such as Ethiopia.

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.

Evaluation of COVID-19 related knowledge and preparedness in health professionals at selected health facilities in a resource-limited setting in Addis Ababa, Ethiopia.

BACKGROUND: The World Health Organization has declared that infection with SARS-CoV-2 is a pandemic. Experiences with SARS in 2003 and SARS-CoV-2 have shown that health professionals are at higher risk of contracting COVID-19. Hence, it has been recommended that aperiodic wide-scale assessment of the knowledge and preparedness of health professionals regarding the current COVID-19 pandemic is critical. OBJECTIVES: This study aimed to assess the knowledge and preparedness of health professionals regarding COVID-19 among selected hospitals in Addis Ababa, Ethiopia. METHODS: A facility-based cross-sectional study was conducted from the last week of March to early April, 2020. Government (n = 6) and private hospitals (n = 4) were included. The front-line participants with high exposure were proportionally recruited from their departments. The collected data from a self-administered questionnaire were entered using EpiData and analyzed in SPSS software. Both descriptive statistics and inferential statistics (chi-square tests) are presented. RESULTS: A total of 1334 health professionals participated in the study. The majority (675, 50.7%) of the participants were female. Of the total, 532 (39.9%) subjects were nurses/midwives, followed by doctors (397, 29.8%) and pharmacists (193, 14.5%). Of these, one-third had received formal training on COVID-19. The mean knowledge score of participants was 16.45 (±4.4). Regarding knowledge about COVID-19, 783 (58.7%), 354 (26.5%), and 196 (14.7%) participants had moderate, good, and poor knowledge, respectively. Lower scores were seen in younger age groups, females, and non-physicians. Two-thirds (63.2%) of the subjects responded that they had been updated by their hospital on COVID-19. Of the total, 1020 (76.5%) participants responded that television, radio, and newspapers were their primary sources of information. Established hospital preparedness measures were confirmed by 43-57% of participants. CONCLUSION: The current study revealed that health professionals in Addis Ababa, Ethiopia, already know important facts but had moderate overall knowledge about the COVID-19 pandemic. There were unmet needs in younger age groups, non-physicians, and females. Half of the respondents mentioning inadequate preparedness of their hospitals point to the need for more global solidarity, especially concerning the shortage of consumables and lack of equipment.

COVID-19 and the public response: Knowledge, attitude and practice of the public in mitigating the pandemic in Addis Ababa, Ethiopia.

BACKGROUND: The COVID-19 pandemic is impacting the global community in many ways. Combating the COVID-19 pandemic requires a coordinated effort through engaging public and service providers in preventive measures. The government of Ethiopia had already announced prevention guidelines for the public. However, there is a scarcity of evidence-based data on the public knowledge, attitude, and practice (KAP) and response of the service providers regarding COVID-19. OBJECTIVE: This study aimed to assess the public KAP and service providers' preparedness towards the pandemic in Addis Ababa, Ethiopia. METHODS: A community-based cross-sectional study was conducted in Addis Ababa, Ethiopia, from late March to the first week of April 2020. Participants were conveniently sampled from 10 different city sites. Data collection was performed using a self-administered questionnaire and observational assessment using a checklist. All statistical analysis was performed using SPSS version Descriptive statistics, correlation coefficient and chi-square tests were performed. RESULT: A total of 839 public participants and 420 service providers enrolled in the study. The mean age was 30.30 (range = 18-72) years. The majority of the respondents (58.6%) had moderate knowledge about COVID-19, whereas 37.2% had good knowledge. Moreover, 60.7% and 59.8% of the participants had a positive attitude towards preventive measures and good practice to mitigate the pandemic, respectively. There was a moderate positive correlation between knowledge and attitude, whereas the correlations between knowledge and practice and attitude and practice were weak. With regard to service providers' preparedness, 70% have made hand-washing facilities available. A large majority of the respondents (84.4%) were using government-owned media followed by social media (46.0%) as a main source of information. CONCLUSION: The public in Addis Ababa had moderate knowledge, an optimistic attitude and descent practice. The information flow from government and social media seemed successful seeing the majority of the respondents identifying preventive measures, signs and symptoms and transmission route of SARS-CoV-2. Knowledge and attitude was not associated with practice, thus, additional innovative strategies for practice changes are needed. Two thirds of the service provider made available hand washing facilities which seems a first positive step. However, periodic evaluation of the public KAP and assessment of service providers' preparedness is mandatory to combat the pandemic effectively.

Preliminary study on investigation of zoonotic visceral leishmaniasis in endemic foci of Ethiopia by detecting Leishmania infections in rodents.

OBJECTIVE: To investigate the zoonotic visceral leishmaniasis (ZVL) by identification of the most probable reservoir hosts using parasite isolation and analysis of a possible transmission dynamics of the disease in extra-domestic agricultural fields and rural villages. METHODS: Rodents were collected from selected study sites in kala-azar endemic areas based on information for localities of kala-azar cases for screening of Leishmania infections using parasitological, serological and polymerase chain reaction (PCR) from March, 2013 to January, 2014. Ketamine (Clorketam Veterinary) was used to anaesthesize the rodents according the prescribed dosage (average 2 mg/kg for intra-venous route). The blood obtained using sterile needle was dropped into sterile filter paper and allowed to air dry before sealing in plastic bags. The tissues from liver, spleen and skin were macerated in Locke's solution before transferring them into NNN medium. Blood and touch smears of liver, spleen, skin and bone marrow were prepared for fixing using methanol and staining by Giemsa stain for microscopy. These tissues were also used for DNA extractions and PCR amplification of Leishmania infection. RESULTS: A total of 335 rodents (13 species) were analyzed by sampling internal organs. The infection rate by PCR was 11.1% (6/54) for Arvicanthis nilothicus compared to 17.6% (3/17) and 12.5% (2/16) for Acomys cahirinus and Tarera (G) robustus respectively. Almost all the infections were found from bone marrow samples (8/48 or 16.7%) compared with 1/91 (1.1%) liver, 2/87 (2.2%) spleen and 0/87 (0%) skin. In all study sites with past human VL cases, rodents and proved vectors shared similar habitats. CONCLUSIONS: Leishmania donovani might circulate among different species of rodents in kala-azar endemic lowlands and valleys of Ethiopia by Phlebotomus orientalis and Phlebotomus martini. Detailed studies to substantiate the preliminary data on the possible role of these rodents are urgently needed.

Comparison of point-of-care tests for the rapid diagnosis of visceral leishmaniasis in East African patients.

The development of rK39-based rapid diagnostic tests (RDTs) has greatly aided the diagnosis of visceral leishmaniasis, especially in the Indian subcontinent and Brazil, by offering high sensitivity and specificity. However, these tests have been less sensitive and less specific in sub-Saharan Africa. To improve upon the performance of rK39 in Africa, we engineered the fusion molecule rK28, which retained some of the rK39 repeats and combined them with repeat sequences from two additional Leishmania genes. This polyprotein was used in the development of several prototype RDTs by different commercial manufacturers with the goal of assessing relative performance in inexpensive formats. Here, we report field studies showing that the rK28 antigen could be readily adapted to a variety of RDT formats to achieve high sensitivity, generally > 90%, and adequate specificity to aid in the diagnosis of human visceral leishmaniasis in East Africa, Asia, and South America.

Evaluation of PCR procedures for detecting and quantifying Leishmania donovani DNA in large numbers of dried human blood samples from a visceral leishmaniasis focus in Northern Ethiopia.

BACKGROUND: Visceral Leishmaniasis (VL) is a disseminated protozoan infection caused by Leishmania donovani parasites which affects almost half a million persons annually. Most of these are from the Indian sub-continent, East Africa and Brazil. Our study was designed to elucidate the role of symptomatic and asymptomatic Leishmania donovani infected persons in the epidemiology of VL in Northern Ethiopia. METHODS: The efficacy of quantitative real-time kinetoplast DNA/PCR (qRT-kDNA PCR) for detecting Leishmania donovani in dried-blood samples was assessed in volunteers living in an endemic focus. RESULTS: Of 4,757 samples, 680 (14.3%) were found positive for Leishmania k-DNA but most of those (69%) had less than 10 parasites/ml of blood. Samples were re-tested using identical protocols and only 59.3% of the samples with 10 parasite/ml or less were qRT-kDNA PCR positive the second time. Furthermore, 10.8% of the PCR negative samples were positive in the second test. Most samples with higher parasitemias remained positive upon re-examination (55/59 =93%). We also compared three different methods for DNA preparation. Phenol-chloroform was more efficient than sodium hydroxide or potassium acetate. DNA sequencing of ITS1 PCR products showed that 20/22 samples were Leishmania donovani while two had ITS1 sequences homologous to Leishmania major. CONCLUSIONS: Although qRT-kDNA PCR is a highly sensitive test, the dependability of low positives remains questionable. It is crucial to correlate between PCR parasitemia and infectivity to sand flies. While optimal sensitivity is achieved by targeting k-DNA, it is important to validate the causative species of VL by DNA sequencing.

Lymphatic filariasis in western Ethiopia with special emphasis on prevalence of Wuchereria bancrofti antigenaemia in and around onchocerciasis endemic areas.

Lymphatic filariasis is known to be endemic in Gambella Region, western Ethiopia, but the full extent of its endemicity in other regions is unknown. A national mapping program for Ethiopia was initiated in 2008. This report summarizes initial data on the prevalence of Wuchereria bancrofti antigenaemia based on surveys carried out in a sampled population of 11685 individuals living in 125 villages (112 districts) of western Ethiopia. The overall prevalence rate was 3.7%, but high geographical clustering and variation in prevalence (ranging from 0% to more than 50%) was found. The prevalence of hydrocele (in males) and lymphoedema of limbs was 0.8% and 3.6% respectively. Significantly higher (χ(2)=49.6; P<0.01) prevalence of antigenaemia was noted in known onchocerciasis endemic districts (4.7%) compared to non-onchocerciasis endemic districts (2.3%). Thirty-four of the 112 districts, with a population of 1547685 in 2007, were found to be endemic. Of these, the numbers of districts with prevalence rates of >20%, 10-20% and 5-9% were nine, 14 and 20 respectively. Twenty-nine of these 34 endemic districts were found in three regions: Gambella Region (seven districts), Beneshangul-Gumuz Region (13 districts), and Southern Nations, Nationalities and Peoples' Region (SNNPR) (nine districts). The other five were from Amhara (two districts) and Oromia (three districts) regions. A tentative distribution map has been drawn to facilitate the launching of the Ethiopia LF elimination program.