Regional and temporal variations in COVID-19 cases and deaths in Ethiopia: Lessons learned from the COVID-19 enhanced surveillance and response.

BACKGROUND: The COVID-19 pandemic is one of the most devastating public health emergencies of international concern to have occurred in the past century. To ensure a safe, scalable, and sustainable response, it is imperative to understand the burden of disease, epidemiological trends, and responses to activities that have already been implemented. We aimed to analyze how COVID-19 tests, cases, and deaths varied by time and region in the general population and healthcare workers (HCWs) in Ethiopia. METHODS: COVID-19 data were captured between October 01, 2021, and September 30, 2022, in 64 systematically selected health facilities throughout Ethiopia. The number of health facilities included in the study was proportionally allocated to the regional states of Ethiopia. Data were captured by standardized tools and formats. Analysis of COVID-19 testing performed, cases detected, and deaths registered by region and time was carried out. RESULTS: We analyzed 215,024 individuals' data that were captured through COVID-19 surveillance in Ethiopia. Of the 215,024 total tests, 18,964 COVID-19 cases (8.8%, 95% CI: 8.7%- 9.0%) were identified and 534 (2.8%, 95% CI: 2.6%- 3.1%) were deceased. The positivity rate ranged from 1% in the Afar region to 15% in the Sidama region. Eight (1.2%, 95% CI: 0.4%- 2.0%) HCWs died out of 664 infected HCWs, of which 81.5% were from Addis Ababa. Three waves of outbreaks were detected during the analysis period, with the highest positivity rate of 35% during the Omicron period and the highest rate of ICU beds and mechanical ventilators (38%) occupied by COVID-19 patients during the Delta period. CONCLUSIONS: The temporal and regional variations in COVID-19 cases and deaths in Ethiopia underscore the need for concerted efforts to address the disparities in the COVID-19 surveillance and response system. These lessons should be critically considered during the integration of the COVID-19 surveillance system into the routine surveillance system.

SARS-CoV-2 co-detection with influenza and human respiratory syncytial virus in Ethiopia: Findings from the severe acute respiratory illness (SARI) and influenza-like illness (ILI) sentinel surveillance, January 01, 2021, to June 30, 2022.

SARS-CoV-2 co-infection with the influenza virus or human respiratory syncytial virus (RSV) may complicate its progress and clinical outcomes. However, data on the co-detection of SARS-CoV-2 with other respiratory viruses are limited in Ethiopia and other parts of Africa to inform evidence-based response and decision-making. We analyzed 4,989 patients' data captured from the national severe acute respiratory illness (SARI) and influenza-like illness (ILI) sentinel surveillance sites over 18 months period from January 01, 2021, to June 30, 2022. Laboratory specimens were collected from the patients and tested for viral respiratory pathogens by real-time, reverse transcription polymerase chain reaction (RT-PCR) at the national influenza center. The median age of the patients was 14 years (IQR: 1-35 years), with a slight preponderance of them being at the age of 15 to less than 50 years. SARS-CoV-2 was detected among 459 (9.2%, 95% CI: 8.4-10.0) patients, and 64 (1.3%, 95% CI: 1.0-1.6) of SARS-CoV-2 were co-detected either with Influenza virus (54.7%) or RSV (32.8%) and 12.5% were detected with both of the viruses. A substantial proportion (54.7%) of SARS-CoV-2 co-detection with other respiratory viruses was identified among patients in the age group from 15 to less than 50 years. The multivariable analysis found that the odds of SARS-CoV-2 co-detection was higher among individuals with the age category of 20 to 39 years as compared to those less than 20 years old (AOR: 1.98, 95%CI:1.15-3.42) while the odds of SARS-CoV-2 co-detection was lower among cases from other regions of the country as compared to those from Addis Ababa (AOR:0.16 95%CI:0.07-0.34). Although the SARS-CoV-2 co-detection with other respiratory viral pathogens was minimal, the findings of this study underscore that it is critical to continuously monitor the co-infections to reduce transmission and improve patient outcomes, particularly among the youth and patients with ILI.

Prevalence of respiratory syncytial virus infection and associated factors in children aged under five years with severe acute respiratory illness and influenza-like illness in Ethiopia.

Objectives: Acute respiratory infections because of respiratory syncytial viruses (RSVs) are among the major leading causes of morbidity and mortality in children worldwide. RSV prevalence and its contributing factors among children aged under 5 years in Ethiopia are not well studied. To assess the prevalence and associated factors of RSV infection in children aged under 5 years using influenza sentinel surveillance sites in Ethiopia. Methods: A cross-sectional study design was used utilizing influenza-like illness/sever acute respiratory illness surveillance data from January 2021 to December 2022 at the Ethiopian Public Health Institute. Results: In total, 2234 cases were included, with an overall RSV positivity rate of 16.2%. The RSV positivity rate was high in children aged under 1 year (22.8%) and during fall season (24.8%). The RSV positivity rate was significantly associated with ages under 1 year (adjusted odds ratio [AOR] 2.8, 95% confidence interval [CI]: 1.89-4.15) and 1-2 years (AOR 1.9, 95% CI: 1.26-2.73) and the fall season (AOR 1.67, 95% CI: 1.17-2.38). Conclusion: The study revealed that a considerably high RSV positivity rate was detected in children aged under 5 years. The age of children and season have a significant association with RSV positivity rate. Further studies of RSV viral genotype, clinical characteristics, and disease outcome need to be conducted for a better understanding of the virus and disease outcome.

Exploring Community Perceptions of COVID-19 and Vaccine Hesitancy in Selected Cities of Ethiopia: A Qualitative Study.

Even though the COVID-19 vaccine has been available and free of charge to the targeted population in Ethiopia, the vaccination rate was lower than needed to achieve herd immunity at community level. This study aimed to explore community perceptions of COVID-19 and vaccine hesitancy in selected cities of Ethiopia involving 70 in-depth interviews and 28 focused group discussions. The audio-taped data were transcribed verbatim, translated into English, and analyzed using a qualitative content analysis approach using the ATLAS.ti software version 8. The findings revealed that COVID-19 was perceived as evil and caused fear and frustration upon its emergence. The community initially used traditional remedies for its prevention but later transitioned to employing non-pharmaceutical interventions. The primary reasons for vaccine hesitancy were misinformation and misconceptions, such as connecting the vaccine with the mark of the beast, a lack of trust due to the multiple vaccine types, a shorter production timeline resulting in distrust of its effectiveness, and a fear of pain and side effects. Based on our findings, we recommend monitoring the use of social media and countering misinformation with the correct information and continuous public health campaigns. Further studies should be conducted to assess the types and magnitude of impacts from the myths and misconceptions on vaccination uptake.

The Burden of Epstein-Barr Virus (EBV) and Its Determinants among Adult HIV-Positive Individuals in Ethiopia.

Epstein-Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin's lymphoma (HL), and Non-Hodgkin's lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia. Hence, this study aimed to determine the burden of EBV infection among adult HIV-positive individuals in Ethiopia and assess the determinants of EBV DNA positivity. We conducted a cross-sectional study at the Tikur Anbessa Specialised Hospital from March 2020 to March 2021. Two hundred and sixty individuals were enrolled in this study, including 179 HIV-positive and 81 HIV-negative individuals. A structured questionnaire was used to capture demographic and individual attributes. In addition, the clinical data of patients were also retrieved from clinical records. EBV viral capsid antigen (VCA) IgG antibody was measured by multiplex flow immunoassay, and EBV DNA levels were tested by quantitative real-time polymerase chain reaction (q-PCR) assays targeting the EBNA-1 open reading frame (ORF). Descriptive statistics were conducted to assess each study variable. A multivariable logistic regression model was applied to evaluate the determinants of EBV infection. Statistical significance was determined at a p-value < 0.05. Two hundred and fifty-three (97.7%) study participants were seropositive for the EBV VCA IgG antibody. Disaggregated by HIV status, 99.4% of HIV-positive and 93.8% of HIV-negative participants were EBV seropositive. In this study, 49.7% of HIV-positive and 24.7% of HIV-negative individuals were EBV DNA positive. PWH had a higher risk of EBV DNA positivity at 3.05 times (AOR: 3.05, 95% CI: 1.40-6.67). Moreover, among PWH, those with an HIV viral load greater than 1000 RNA copies/mL (AOR = 5.81, 95% CI = 1.40, 24.13) had a higher likelihood of EBV DNA positivity. The prevalence of EBV among PWH was significantly higher than among HIV-negative individuals. Higher HIV viral loads in PWH were associated with an increased risk of EBV DNA positivity. Since the increases in the viral load of EBV DNA among PWH could be related to the risk of developing EBV-associated cancers, it is necessary for more research on the role of EBV in EBV-associated cancer in this population group to be carried out.

Causes of stillbirth and death among children younger than 5 years in eastern Hararghe, Ethiopia: a population-based post-mortem study.

BACKGROUND: Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia. METHODS: In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children-or their mothers, in the case of stillbirths and deaths in children younger than 6 months-had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0-27 days), and child deaths (aged 28 days to <5 years). FINDINGS: Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae. INTERPRETATION: Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake. FUNDING: Bill & Melinda Gates Foundation.

Helminth species-specific effects on IFN-γ producing T cells during active and latent tuberculosis.

BACKGROUND: Interferon-γ (IFN-γ) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-γ production by T cells, although its connection with disease severity and immune recovery during treatment is unexplored. We investigated the species-specific effect of helminths on the IFN-γ production by T cells in relation to disease severity during active and latent TB infection (LTBI). METHODS: In this study, 69 active pulmonary TB patients (PTB), 28 with LTBI and 66 healthy controls were included. Active TB was diagnosed using GenXpert MTB/RIF while QuantiFERON test (QFT) was used for the screening of healthy community controls (CCs) and for the diagnosis of LTBI. Helminth infection was identified by routine diagnosis whereas clinical disease severity was evaluated by the TB score. Intracellular IFN-γ production of T cells in stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry using TB antigens (PPD), the polyclonal T cell activator staphylococcal enterotoxin B (SEB), or medium as unstimulated control. RESULTS: Helminth infected CCs and LTBI subjects showed a significant reduction of IFN-γ+ CD4+ T cells by PPD-stimulation compared to non-helminth infected control groups. The significant reduction in the frequency of IFN-γ+ T cells in both latent and active PTB patients following SEB stimulation was mostly attributed to Schistosoma mansoni infection, whereas Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection contributed equally in CCs. Following anti-helminthic and anti-TB treatment for 2 months, the frequency of IFN-γ+ CD4 T cells in helminth coinfected PTB was restored to levels of helminth negative PTB before treatment. Helminth coinfected PTB patients with an intermediate and severe clinical course had reduced capacity for production of IFN-γ+ T cells compared to the corresponding non-helminth infected PTB. CONCLUSION: We found a reduction in IFN-γ producing T cells by helminth coinfection which was restored following anti-helminthic treatment. This reduction was helminth species-dependent in an exploratory sub-analysis and correlated to increased disease severity.

An investigation of a hundred COVID-19 cases and close contacts in Ethiopia, May to June, 2020: A prospective case-ascertained study.

BACKGROUND: Corona Virus Disease 2019 is a novel respiratory disease commonly transmitted through respiratory droplets. The disease has currently expanded all over the world with differing epidemiologic trajectories. This investigation was conducted to determine the basic clinical and epidemiological characteristics of the disease in Ethiopia. METHODS: A prospective case-ascertained study of laboratory-confirmed COVID-19 cases and their close contacts were conducted. The study included 100 COVID-19 laboratory-confirmed cases reported from May 15, 2020 to June 15, 2020 and 300 close contacts. Epidemiological and clinical information were collected using the WHO standard data collection tool developed first-few cases and contacts investigation. Nasopharyngeal and Oropharyngeal samples were collected by using polystyrene tipped swab and transported to the laboratory by viral transport media maintaining an optimal temperature. Clinical and epidemiological parameters were calculated in terms of ratios, proportions, and rates with 95% CI. RESULT: A total of 400 participants were investigated, 100 confirmed COVID-19 cases and 300 close contacts of the cases. The symptomatic proportion of cases was 23% (23) (95% CI: 15.2%-32.5%), the proportion of cases required hospitalization were 8% (8) (95%CI: 3.5%-15.2%) and 2% (95%CI: 0.24% - 7.04%) required mechanical ventilation. The secondary infection rate, secondary clinical attack rate, median incubation period and median serial interval were 42% (126) (95% CI: 36.4%-47.8%), 11.7% (35) (95% CI: 8.3%-15.9%), 7 days (IQR: 4-13.8) and 11 days (IQR: 8-11.8) respectively. The basic reproduction number (RO) was 1.26 (95% CI: 1.0-1.5). CONCLUSION: The proportion of asymptomatic infection, as well as secondary infection rate among close contacts, are higher compared to other studies. The long serial interval and low basic reproduction number might contribute to the observed slow progression of the pandemic, which gives a wide window of opportunities and time to control the spread. Testing, prevention, and control measures should be intensified.

Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls.

Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and QuantiFERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.

Spatial distribution and determinants of HIV prevalence among adults in urban Ethiopia: Findings from the Ethiopia Population-based HIV Impact Assessment Survey (2017-2018).

The design and evaluation of national HIV programs often rely on aggregated national data, which may obscure localized HIV epidemics. In Ethiopia, even though the national adult HIV prevalence has decreased, little information is available about local areas and subpopulations. To inform HIV prevention efforts for specific populations, we identified geographic locations and drivers of HIV transmission. We used data from adults aged 15-64 years who participated in the Ethiopian Population-based HIV Impact Assessment survey (October 2017-April 2018). Location-related information for the survey clusters was obtained from the 2007 Ethiopia population census. Spatial autocorrelation of HIV prevalence data were analyzed via a Global Moran's I test. Geographically weighted regression analysis was used to show the relationship of covariates. The finding indicated that uncircumcised men in certain hotspot towns and divorced or widowed individuals in hotspot woredas/towns might have contributed to the average increase in HIV prevalence in the hotspot areas. Hotspot analysis findings indicated that, localized, context-specific intervention efforts tailored to at-risk populations, such as divorced or widowed women or uncircumcised men, could decrease HIV transmission and prevalence in urban Ethiopia.

Reference Intervals for Absolute and Percentage CD4+ T Lymphocytes among an Apparently Healthy Population in Addis Ababa, Ethiopia.

Background: Reference intervals for clinical laboratory parameters differ based on several factors, including age, sex, genetic variation, and geographic location. This variation influences clinical decisions and treatment monitoring. Currently, Ethiopia has used adopted reference intervals from manufacturer values derived from non-Africans. Therefore, the aim this study was to determine reference intervals for absolute and percentage CD4+ T cells for an apparently healthy population in Addis Ababa, Ethiopia. Methods: A community-based cross-sectional study was conducted on 361 apparently healthy people in four subcities in Addis Ababa from January to June 2019. Sociodemographic and clinical data were collected using a structured questionnaire after informed consent had been obtained. Blood samples were collected and CD4+ T-lymphocyte enumeration performed using a BD FACSPresto near-patient CD4 counter. Data were entered and analyzed using SPSS 20. Reference intervals were determined by a nonparametric test estimating percentiles 2.5 (lower limit) and 97.5 (upper limit) with 95% CIs. P<0.05 was considered statistically significant. Results: A total of 337 (183 female and 154 male) healthy participants of median age 28 (IQR 17-35) years were included in the final analysis. Medians of absolute and percentage CD4+ T-cell counts (932.0 and 42.9, respectively) of female participants were significantly higher than male participants (802.5 and 38.7, respectively; P<0.05). Reference intervals for absolute CD4+ T-cell count and percentages in males were 483.8-1,310 cells/µL and 18.1-57.3 and in females 447.8-1,479.8 cells/µL and 25.6-58.9, respectively. Conclusion: The CD4+ T-count reference intervals established in this study showed some inconsistency from the manufacturer's provided values and other studies and also revealed sex differences, necessitating sex-specific locally established reference intervals.

Comparing the accuracy of two diagnostic methods for detection of light Schistosoma haematobium infection in an elimination setting in Wolaita Zone, South Western Ethiopia.

Reagent urinalysis dipstick and filtration have been recommended diagnostic methods for the detection of urogenital schistosomiasis. However, the accurate diagnosis of light infections using these methods presents a major challenge. This study evaluates the diagnosis accuracy of light infection with Schistosoma haematobium in study participants living in Wolaita Zone, an area targeted for sustainable control of Schistosomiasis, and ultimately interrupt transmission. Urine samples were collected from children and adults in surveys carried out during baseline and longitudinal sentinel site surveys conducted from 2018 to 2020. All urine samples were tested using a reagent urinalysis dipstick test (Haemastix) to detect microhaematuria with reference urine filtration technique as a proxy for S. haematobium infection. Sensitivity and specificity were determined in diagnosing urogenital schistosomiasis. Cohen's Kappa statistics was done for the agreement of these diagnostic methods. A total of 12,102 participants were enrolled in the current baseline study. Among them, 285 (2.35%) samples tested positive for microhaematuria and 21 (0.20%) positive for S. haematobium eggs. A total of 4,357 samples were examined in year 1 and year 2 using urine dipsticks, and urine filtration 172 (3.95%) and 2 (0.05%) were positive for microhaematuria and S. haematobium eggs. The reagent urinalysis dipsticks showed the highest sensitivity and specificity for diagnosing light intensity of infection,100% (95% CI:85.18-100.00) and 97.4% (95% CI: 97.10-97.60), respectively. There is a slight agreement between the two methods (Kappa = 0.09, 95% CI: 0.01-0.18). The present study revealed very low prevalence and light intensity of S. haematobium infections. The study also highlights that the dipstick test is considered a useful adjunct diagnostic tool for population-based control of urogenital schistosomiasis.

First PCR Confirmed anthrax outbreaks in Ethiopia-Amhara region, 2018-2019.

BACKGROUND: Anthrax is a disease that affects humans and animals. In Ethiopia, anthrax is a reportable disease and assumed to be endemic, although laboratory confirmation has not been routinely performed until recently. We describe the findings from the investigation of two outbreaks in Amhara region. METHODS: Following reports of suspected outbreaks in Wag Hamra zone (Outbreak 1) and South Gondar zone (Outbreak 2), multi-sectoral teams involving both animal and public health officials were deployed to investigate and establish control programs. A suspect case was defined as: sudden death with rapid bloating or bleeding from orifice(s) with unclotted blood (animals); and signs compatible with cutaneous, ingestion, or inhalation anthrax ≤7 days after exposure to a suspect animal (humans). Suspect human cases were interviewed using a standard questionnaire. Samples were collected from humans with suspected anthrax (Outbreak 1 and Outbreak 2) as well as dried meat of suspect animal cases (Outbreak 2). A case was confirmed if a positive test was returned using real-time polymerase chain reaction (qPCR). RESULTS: In Outbreak 1, a total of 49 cows died due to suspected anthrax and 22 humans developed symptoms consistent with cutaneous anthrax (40% attack rate), two of whom died due to suspected ingestion anthrax. Three people were confirmed to have anthrax by qPCR. In Outbreak 2, anthrax was suspected to have caused the deaths of two livestock animals and one human. Subsequent investigation revealed 18 suspected cases of cutaneous anthrax in humans (27% attack rate). None of the 12 human samples collected tested positive, however, a swab taken from the dried meat of one animal case (goat) was positive by qPCR. CONCLUSION: We report the first qPCR-confirmed outbreaks of anthrax in Ethiopia. Both outbreaks were controlled through active case finding, carcass management, ring vaccination of livestock, training of health professionals and outreach with livestock owners. Human and animal health authorities should work together using a One Health approach to improve case reporting and vaccine coverage.

Baseline malaria prevalence at the targeted pre-elimination districts in Ethiopia.

BACKGROUND: Encouraged by the previous success in malaria control and prevention strategies, the Ethiopian ministry of health launched malaria elimination with a stepwise approach by primarily targeting the low-transmission Districts and their adjacent areas/zones in order to shrink the country's malaria map progressively. Hence, this community survey was conducted to establish baseline malaria information at the preliminary phase of elimination at targeted settings. METHODS: A community-based cross-sectional survey was conducted at 20 malaria-elimination targeted Districts selected from five Regional states and one city administration in Ethiopia. The GPS-enabled smartphones programmed with Open Data Kit were used to enumerate 9326 study households and collect data from 29,993 residents. CareStart™ Malaria PAN (pLDH) Rapid Diagnostic Tests (RDTs) were used for blood testing at the field level. Armpit digital thermometers were used to measure axillary temperature. RESULT: Overall malaria prevalence by RDTs was 1.17% (339/28973). The prevalence at District levels ranged from 0.0 to 4.7%. The proportion of symptomatic cases (axillary temperature > 37.5oc) in the survey was 9.2% (2760/29993). Among the 2510 symptomatic individuals tested with RDTs, only 3.35% (84/2510) were malaria positive. The 75.2% (255/339) of all malaria positives were asymptomatic. Of the total asymptomatic malaria cases, 10.2% (26/255) were under-five children and 89.8% (229/255) were above 5 years of age. CONCLUSION: The study shows a decrease in malaria prevalence compared to the reports of previous malaria indicator surveys in the country. The finding can be used as a baseline for measuring the achievement of ongoing malaria elimination efforts. Particularly, the high prevalence of asymptomatic individuals (0.88%) in these transmission settings indicates there may be sustaining hidden transmission. Therefore, active case detection with more sensitive diagnostic techniques is suggested to know more real magnitude of residual malaria in the elimination-targeted areas.

Differential effects of asymptomatic Ascaris lumbricoides, Schistosoma mansoni or hook worm infection on the frequency and TGF-beta-producing capacity of regulatory T cells during active tuberculosis.

Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-ß producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients (PTB) and 69 community controls (CCs) from Gondar, Ethiopia, were included. Clinical disease severity was graded by TB score, and flow cytometry used to characterize Treg frequency and functionality measured as their TGF-ß-producing capacity. In helminth positive PTB patients (Helminth+PTB+) compared to helminth negative PTB or CCs, TGF-ß+ Tregs were significantly increased mainly in hookworm coinfection whereas S. mansoni increased TGF-ß+ Tregs in CCs. Treatment of TB and helminths decreased TGF-ß+ Tregs in Helminth+PTB+ at 2 months follow-up. There were no overall differences in the frequency of Tregs in CCs or PTB unless stratification on TB disease severity was performed. At inclusion Helminth+PTB+ had increased frequency of Tregs already at low disease severity, and TGF-ß+ Tregs correlated to intermediate-to-high disease severity. In conclusion, helminth specific increase of TGF-ß+ Tregs in PTB patients was correlated to TB disease severity and was restored following anti-helminth treatment.

Prognostic factors and outcomes of COVID-19 cases in Ethiopia: multi-center cohort study protocol.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) and became pandemic after emerging in Wuhan, China, in December 2019. Several studies have been conducted to understand the key features of COVID-19 and its public health impact. However, the prognostic factors of COVID-19 are not well studied in the African setting. In this study, we aim to determine the epidemiological and clinical features of COVID-19 cases, immunological and virological courses, interaction with nutritional status, and response to treatment for COVID-19 patients in Ethiopia. METHODS: A multi-center cohort study design will be performed. Patients with confirmed COVID-19 infection admitted to selected treatment centers will be enrolled irrespective of their symptoms and followed-up for 12 months. Baseline epidemiological, clinical, laboratory and imaging data will be collected from treatment records, interviews, physical measurements, and biological samples. Follow-up data collection involves treatment and prognostic outcomes to be measured using different biomarkers and clinical parameters. Data collection will be done electronically using the Open Data Kit (ODK) software package and then exported to STATA/SPSS for analysis. Both descriptive and multivariable analyses will be performed to assess the independent determinants of the treatment outcome and prognosis to generate relevant information for informed prevention and case management. The primary outcomes of this study are death/survival and viral shedding. Secondary outcomes include epidemiological characteristics, clinical features, genetic frequency shifts (genotypic variations), and nutritional status. DISCUSSION: This is the first large prospective cohort study of patients in hospitals with COVID-19 in Ethiopia. The results will enable us to better understand the epidemiology of SARS-CoV-2 in Africa. This study will also provide useful information for effective public health measures and future pandemic preparedness and in response to outbreaks. It will also support policymakers in managing the epidemic based on scientific evidence. TRIAL REGISTRATION: The Protocol prospectively registered in ClinicalTrials.gov (NCT04584424) on 30 October, 2020.

Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia.

In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.

African National Public Health Institutes Responses to COVID-19: Innovations, Systems Changes, and Challenges.

National public health institutes (NPHIs)-science-based governmental agencies typically part of, or closely aligned with, ministries of health-have played a critical part in many countries' responses to the COVID-19 pandemic. Through listening sessions with NPHI leadership, we captured the experiences of NPHIs in Africa. Our research was further supplemented by a review of the literature. To address issues related to COVID-19, NPHIs in Africa developed a variety of innovative approaches, such as working with the private sector to procure and manage vital supplies and address key information needs. Creative uses of technology, including virtual training and messaging from drones, contributed to sharing information and battling misinformation. Positive impacts of the pandemic response include increased laboratory capacity in many countries, modernized surveillance systems, and strengthened public-private partnerships; much of this enhanced capacity is expected to persist beyond the pandemic. However, several challenges remain, including the lack of staff trained in areas like bioinformatics (essential for genomic analysis) and the need for sustained relationships and data sharing between NPHIs and agencies not traditionally considered public health (eg, those related to border crossings), as well as the impact of the pandemic on prevention and control of non-COVID-19 conditions-both infectious and noncommunicable. Participants in the listening sessions also highlighted concerns about inequities in access to, and quality of, the public health services and clinical care with resultant disproportionate impact of the pandemic on certain populations. COVID-19 responses and challenges highlight the need for continued investment to strengthen NPHIs and public health infrastructure to address longstanding deficiencies and ensure preparedness for the next public health crisis.

Seroprevalence and risk factors for SARS-CoV-2 Infection in selected urban areas in Ethiopia: a cross-sectional evaluation during July 2020.

BACKGROUND: Ethiopia reported the first case of COVID-19 on 13th March, 2020 with community transmission ensuing by mid-May. A national, population-based serosurvey against anti-SARS-CoV-2 IgG was conducted to measure the prevalence of prior COVID-19 infections and better approximate the burden across major towns in Ethiopia. METHODS: We conducted a cross-sectional, population-based serosurvey from June 24 to July 8, 2020 in 14 major urban areas. Two-stage cluster sampling was used to randomly select enumeration areas and households. All persons aged ≥15 years were enrolled. Serum samples were tested by Abbott™ ARCHITECT™ assay for SARS-CoV-2 IgG antibodies. National COVID-19 surveillance data on the median date of the serosurvey is analyzed for comparison. FINDINGS: Adjusted seroprevalence was 3.5% (95% CI: 3.2%-3.8%) after controlling for age, sex and test kit performance. Males (3.7%) and females (3.3%) were nearly equally infected, while middle-aged adults '40-65 years' had the highest (4.0%) prevalence. Gambella (7.5%), Dire Dawa (6.2%) and Jigjiga (6.1%) were the most affected towns. About 6.7% and 8.0% of seropositives had symptoms and chronic underlying illness, respectively. A surveillance system had identified 4,416 RT-PCR confirmed cases in Addis Ababa. INTERPRETATION: This serosurvey shows that a majority of urban Ethiopians remain uninfected with SARS-CoV-2. Most anti-SARS-CoV-2 IgG positive cases were asymptomatic with no underlying illness, keeping case detection to a minimum.

Effect of co-infection with intestinal parasites on COVID-19 severity: A prospective observational cohort study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a spectrum of clinical presentations. Evidence from Africa indicates that significantly less COVID-19 patients suffer from serious symptoms than in the industrialized world. We and others previously postulated a partial explanation for this phenomenon, being a different, more activated immune system due to parasite infections. Here, we aimed to test this hypothesis by investigating a potential correlation of co-infection with parasites with COVID-19 severity in an endemic area in Africa. Methods: Ethiopian COVID-19 patients were enrolled and screened for intestinal parasites, between July 2020 and March 2021. The primary outcome was the proportion of patients with severe COVID-19. Ordinal logistic regression models were used to estimate the association between parasite infection, and COVID-19 severity. Models were adjusted for sex, age, residence, education level, occupation, body mass index, and comorbidities. Findings: 751 SARS-CoV-2 infected patients were enrolled, of whom 284 (37.8%) had intestinal parasitic infection. Only 27/255 (10.6%) severe COVID-19 patients were co-infected with intestinal parasites, while 257/496 (51.8%) non-severe COVID-19 patients were parasite positive (p<0.0001). Patients co-infected with parasites had lower odds of developing severe COVID-19, with an adjusted odds ratio (aOR) of 0.23 (95% CI 0.17-0.30; p<0.0001) for all parasites, aOR 0.37 ([95% CI 0.26-0.51]; p<0.0001) for protozoa, and aOR 0.26 ([95% CI 0.19-0.35]; p<0.0001) for helminths. When stratified by species, co-infection with Entamoeba spp., Hymenolepis nana, Schistosoma mansoni, and Trichuris trichiura implied lower probability of developing severe COVID-19. There were 11 deaths (1.5%), and all were among patients without parasites (p = 0.009). Interpretation: Parasite co-infection is associated with a reduced risk of severe COVID-19 in African patients. Parasite-driven immunomodulatory responses may mute hyper-inflammation associated with severe COVID-19. Funding: European and Developing Countries Clinical Trials Partnership (EDCTP) - European Union, and Joep Lange Institute (JLI), The Netherlands. Trial registration: Clinicaltrials.gov: NCT04473365.