Genomic characterization of Dengue virus circulation in Ethiopia.

In Ethiopia, dengue virus (DENV) infections have been reported in several regions, however, little is known about the circulating genetic diversity. Here, we conducted clinical surveillance for DENV during the 2023 nationwide outbreak and sequenced DENV whole genomes for the first time in Ethiopia. We enrolled patients at three sentinel hospital sites. Using RT-PCR, we screened serum samples for three arboviruses followed by serotyping and sequencing for DENV-positive samples (10.4% of samples). We detected two DENV serotypes (DENV1 and DENV3). Phylogenetic analysis identified one transmission cluster of DENV1 (genotype III major lineage A), and two clusters of DENV3 (genotype III major lineage B). The first showed close evolutionary relationship to the 2023 Italian outbreak and the second cluster to Indian isolates. Co-circulation of DENV1 and DENV3 in some regions of Ethiopia highlights the potential for severe dengue. Intensified surveillance and coordinated public health response are needed to address the threat of severe dengue outbreaks.

Efficacy and safety of chloroquine plus primaquine for the treatment of Plasmodium vivax malaria in Hamusit site, Northwestern Ethiopia.

BACKGROUND: Plasmodium vivax malaria is still an important public health problem in Ethiopia. Unlike Plasmodium falciparum, P. vivax has a dormant liver stage (hypnozoite) that can be a risk of recurrent vivax malaria unless treated by radical cure with primaquine. Drug resistance to chloroquine is threatening malaria control and elimination efforts. This study assessed the therapeutic efficacy and safety of chloroquine plus 14 days of primaquine on P. vivax infection based on parasitological, clinical, and haematological parameters. METHODS: A single-arm in vivo prospective therapeutic efficacy study was conducted to assess the clinical and parasitological response to the first-line treatment of P. vivax in Ethiopia, chloroquine plus 14 days low dose of (0.25 mg/kg/day) primaquine between December 2022 and March 2023 at Hamusit Health Centre using the standard World Health Organization (WHO) protocol. A total of 100 study participants with P. vivax mono-infection who were over 6 months old were enrolled and monitored for adequate clinical and parasitological responses for 42 days. The WHO double-entry Excel sheet and SPSS v.25 software were used for Kaplan-Meier survival analysis, and a paired t-test was used for analysis of haemoglobin improvements between follow up days. RESULTS: A total of 100 patients were enrolled among those, 96% cases were rural residents, 93% had previous malaria exposure, and predominant age group was 5-15 years (61%). 92.6% (95% CI 85.1-96.4%) of enrolled patients were adequate clinical and parasitological response, and 7.4% (95% CI 3.6-14.9%) recurrences were observed among treated patients. The fever and parasite clearance rate on day 3 were 98% and 94%, respectively. The baseline haemoglobin levels improved significantly compared to those days 14 and 42 (p < 0.001). No serious adverse event was observed during the study period. CONCLUSIONS: In this study, co-administration of chloroquine with primaquine was efficacious and well-tolerated with fast resolution of fever and high parasites clearance rate. However, the 7.4% failure is reported is alarming that warrant further monitoring of the therapeutic efficacy study of P. vivax.

Chloroquine has shown high therapeutic efficacy against uncomplicated Plasmodium vivax malaria in southern Ethiopia: seven decades after its introduction.

BACKGROUND: Plasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia. METHODS: In 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28. RESULTS: A total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h. CONCLUSION: Despite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.

Therapeutic efficacy and safety of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria treatment in Metehara, Central-east Ethiopia.

BACKGROUND: Malaria remains a major global health problem although there was a remarkable achievement between 2000 and 2015. Malaria drug resistance, along with several other factors, presents a significant challenge to malaria control and elimination efforts. Numerous countries in sub-Saharan Africa have documented the presence of confirmed or potential markers of partial resistance against artemisinin, the drug of choice for the treatment of uncomplicated Plasmodium falciparum malaria. The World Health Organization (WHO) recommends regular surveillance of artemisinin therapeutic efficacy to inform policy decisions. METHODS: This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated P. falciparum malaria in Ethiopia since 2004. Using a single-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria in Metehara Health Centre, central-east Ethiopia. Out of 2332 malaria suspects (1187 males, 1145 females) screened, 80 (50 males, 30 females) were enrolled, followed up for 28 days, and 73 (44 males, 29 females) completed the follow up. The study was conducted and data was analysed by employing the per-protocol and Kaplan-Meier analyses following the WHO Malaria Therapeutic Efficacy Evaluation Guidelines 2009. RESULTS: The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitaemia and fever by day (D) 3. The prevalence of gametocytes decreased from 6.3% on D0 to 2.5% on D2, D3, D7, and ultimately achieving complete clearance afterward. CONCLUSION: The overall cure rate for AL treatment was 100%, demonstrating its high efficacy in effectively eliminating malaria parasites in patients. No serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that AL remains a highly efficacious treatment for uncomplicated P. falciparum malaria in the study site after 20 years of its introduction in Ethiopia.

Prevalence of Open Defecation Practice and Associated Factors Among Households in Geshiyaro Project Implementation Sites in Ethiopia: A Cross-Sectional Study.

Background: Open defecation is a significant global challenge, impacting public health, environmental sanitation, and social well-being, especially in low- and middle-income countries like Ethiopia. It is the second-largest cause of disease burden worldwide by facilitating the spread of germs that cause diarrhea diseases. Studies examining open defecation practices are insufficient, especially in areas implementing Ethiopia's Geshiyaro project. Therefore, this study aimed to assess the status of open defecation practice and associated factors in the study area. Method: A community-based cross-sectional study was conducted from June to July 2023. The total number of households included in this study was 7995. A structured questionnaire and observational checklist were used to collect data. Descriptive and multivariate logistic regression analyses were performed using STATA version 16. Results: The study found that 16.5% of households practiced open defecation. The following factors were significantly associated with the occurrence of open defecation: residence (AOR = 1.56, 95% CI: 1.26-1.92), education (AOR = 0.59, 95% CI: 0.49-0.72), age (AOR = 0.53, 95% CI: 0.41-0.69), knowledge on diarrhea prevention (AOR = 1.32, 95% CI: 1.17-1.50), marital status (AOR = 1.61, 95% CI: 1.32-1.97), and awareness creation about WASH services (AOR = 1.96, 95% CI: 1.71-2.25). On the other hand, no significant association was observed between the occurrence of open defecation and the household's income (AOR = 1.07, 95% CI: 0.93-1.23) or the head of household sex (AOR = 0.94, 95% CI: 0.78-1.12). Conclusion: Open defecation remains a critical public health concern in Ethiopia's Geshiyaro project sites. Various factors influencing this practice have been identified. Targeted interventions are needed to enhance access to safe sanitation facilities and promote awareness of WASH services, aligning with SDG 3 target 3, and SDG 6 target 2.

Widespread pfhrp2/3 deletions and HRP2-based false-negative results in southern Ethiopia.

BACKGROUND: Rapid diagnostic tests (RDTs) play a significant role in expanding case management in peripheral healthcare systems. Histidine-rich protein-2 (HRP2) antigen detection RDTs are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported. This study assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia. METHODS: A multi-health facilities-based cross-sectional study was conducted on self-presenting febrile patients seeking treatment in southern Ethiopia from July to September 2022. A purposive sampling strategy was used to enroll patients with microscopically confirmed P. falciparum infections. A capillary blood sample was obtained to prepare a blood film for microscopy and a RDT using the SD Bioline™ Malaria Pf/Pv Test. Dried blood spot samples were collected for further molecular analysis. DNA was extracted using gene aid kits and amplification was performed using nested PCR assay. Exon 2 of hrp2 and hrp3, which are the main protein-coding regions, was used to confirm its deletion. The diagnostic performance of RDT was evaluated using PCR as the gold standard test for P. falciparum infections. RESULTS: Of 279 P. falciparum PCR-confirmed samples, 249 (89.2%) had successful msp-2 amplification, which was then genotyped for hrp2/3 gene deletions. The study revealed that pfhrp2/3 deletions were common in all health centres, and it was estimated that 144 patients (57.8%) across all health facilities had pfhrp2/3 deletions, leading to false-negative PfHRP2 RDT results. Deletions spanning exon 2 of hrp2, exon 2 of hrp3, and double deletions (hrp2/3) accounted for 68 (27.3%), 76 (30.5%), and 33 (13.2%) of cases, respectively. The study findings revealed the prevalence of P. falciparum parasites lacking a single pfhrp2-/3-gene and that both genes varied across the study sites. This study also showed that the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% when PCR was used as the reference test. CONCLUSION: This study confirmed the existence of widespread pfhrp2/3- gene deletions, and their magnitude exceeded the WHO-recommended threshold (> 5%). False-negative RDT results resulting from deletions in Pfhrp2/3- affect a country's attempts at malaria control and elimination. Therefore, the adoption of non-HRP2-based RDTs as an alternative measure is required to avoid the consequences associated with the continued use of HRP-2-based RDTs, in the study area in particular and in Ethiopia in general.

Progress in controlling the transmission of schistosome parasites in Southern Ethiopia: the Geshiyaro Project in the Wolaita Zone.

BACKGROUND: This paper describes changes in the prevalence and intensity of schistosome parasite infections in a project integrating mass drug administration (MDA), water, sanitation, and hygiene (WaSH), and behavioral change interventions. METHODS: The Geshiyaro Project comprises three intervention arms. Arm 1 is subdivided into "Arm 1 pilot" (one district) and Arm 1 (four other districts), both receiving integrated community-wide MDA with intensive WaSH interventions. Arm 2 involves 17 districts with community-wide MDA interventions, while Arm 3 serves as a control with school-based MDA interventions in three districts. A total of 150 individuals, stratified by age group, were randomly selected from each of the 45 sentinel sites. Arm sizes were 584 (Arm 1 pilot), 1636 (Arm 1), 2203 (Arm 2), and 2238 (Arm 3). Statistical tests were employed to compare infection prevalence and intensity across the different arms. RESULTS: The prevalence of schistosome parasite infection ranged from 0% to 2.6% and from 1.7% to 25.7% across districts, employing the Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) diagnostics, respectively. The mean infection intensity level showed no marked difference between baseline and follow-up surveys when measured by KK, except in Arm 2 (t = 6.89, P < 0.0001). Infection prevalence decreased significantly in Arm 1 (t = 8.62, P < 0.0001), Arm 2 (t = 6.94, P < 0.0001), and Arm 3 (t = 8.83, P < 0.0001), but not in Arm 1 pilot (t = 1.69, P = 0.09) by POC-CCA, when trace was considered positive. The decrease was significant only in Arm 1 (t = 3.28, P = 0.0001) and Arm 2 (t = 7.62, P < 0.0001) when the trace was considered negative in POC-CCA. Arm 2 demonstrated a significant difference in difference (DID) compared to the control group, Arm 3, regardless of whether trace in POC-CCA was considered positive (DID = 3.9%, df = 8780, P = 0.025) or negative (DID = -5.2, df = 8780, P = 0.0004). CONCLUSIONS: The prevalence of schistosomiasis was low when employing the KK diagnostic but moderate in some locations by the POC-CCA diagnostic. The infection level had decreased across all arms of the Geshiyaro study at mid-term of the 7-year project, but further efforts are needed to reduce the rate of parasite transmission based on the POC-CCA diagnostic scores.

Association between helminth infection and allergic disorders among children in Batu, Ethiopia.

BACKGROUND: Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy-related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths,  atopy and allergic conditions. METHODS: A total of 461 school children participated in this cross-sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer-led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme-linked immunosorbent assay and eosinophil count were also measured. RESULTS: Overall sensitivity to both allergens was 2.4%. Self-reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p = .052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p = .268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p = .268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. CONCLUSION AND CLINICAL RELEVANCE: This study found a non-significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders.

Spatial heterogeneity in mass drug administration from a longitudinal epidemiological study assessing transmission interruption of soil transmitted helminths in the Wolaita zone of southern Ethiopia (Geshiyaro Project).

OBJECTIVES: Deworming programmes of soil-transmitted helminths are generally monitored and evaluated by aggregating drug coverage and infection levels at a district level. However, heterogeneity in drug coverage at finer spatial scales means indicators may remain above thresholds for elimination as a public health problem or of transmission in some areas. This paper aims to highlight the misleading information that aggregating data at larger spatial scales can have for programme decision making. METHODS: Drug coverage data from the Geshiyaro project were compared at two spatial scales with reference to the World Health Organisation's targets. District (woreda) and village (kebele) level were compared. The association between infection levels and drug coverage was analysed by fitting a weighted least-squares function to the mean intensity of infection (eggs per gram of faeces) against drug coverage. RESULTS: The data show clearly that when the evaluation of coverage is aggregated to the district level, information on heterogeneity at a finer spatial scale is lost. Infection intensity decreases significantly (p = 0.0023) with increasing drug coverage. CONCLUSION: Aggregating data at large spatial scales can result in prematurely ceasing deworming, prompting rapid infection bounce-back. There is a strong need to define context-specific spatial scales for monitoring and evaluating intervention programmes.

Antimicrobial susceptibility in Neisseria gonorrhoeae and epidemiological data of gonorrhoea patients in five cities across Ethiopia, 2021-22.

Introduction: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern and enhanced global gonococcal AMR surveillance is imperative. As in many African countries, regular, representative and quality-assured gonococcal AMR is lacking in Ethiopia. We describe the AMR in gonococcal isolates from five cities across Ethiopia, 2021-22, and patient epidemiological data. Methods: Urethral discharge from males and cervical discharge from females were collected from October 2021 to September 2022. Epidemiological data were collected using a questionnaire. MIC determination (ETEST; eight antimicrobials) was performed on gonococcal isolates and EUCAST breakpoints (v13.1) were used. Results: From 1142 urogenital swab samples, 299 species-identified gonococcal isolates were identified; 78.3% were from males and 21.7% from females. The median age for males and females was 25 and 23 years, respectively. Most isolates (61.2%) were identified in Addis Ababa, followed by Gondar (11.4%), Adama (10.4%), Bahir Dar (10.0%) and Jimma (7.0%). The resistance level to ciprofloxacin, tetracycline and benzylpenicillin was 97.0%, 97.0% and 87.6%, respectively, and 87.6% of isolates were producing ß-lactamase. All isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. Recommended therapy [ceftriaxone (250 mg) plus azithromycin (1 g)] was used for 84.2% of patients. Conclusions: We present the first national quality-assured gonococcal AMR data from Ethiopia. Resistance levels to ciprofloxacin, tetracycline and benzylpenicillin were exceedingly high. However, all isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. In Ethiopia, it is essential to strengthen the gonococcal AMR surveillance by including further epidemiological data, more isolates from different cities, and WGS.

Emergence of Plasmodium falciparum strains with artemisinin partial resistance in East Africa and the Horn of Africa: is there a need to panic?

The emergence and spread of artemisinin partial resistance in East and Horn of Africa is alarming. However, artemisinin-based combination therapy (ACT) generally remains efficacious for the treatment of falciparum malaria. The emergence of partial artemisinin resistance does not currently meet the criteria to initiate change on treatment guidelines nor affect ACT routine procurement and distribution. It is high time for scientists and transitional researchers to be more critical and vigilant on further changes so that national programmes will be able to make informed decisions as well as remain alert and prepared for any change that may be required in the future.

Reemergence of Human African Trypanosomiasis Caused by Trypanosoma brucei rhodesiense, Ethiopia.

We report 4 cases of human African trypanosomiasis that occurred in Ethiopia in 2022, thirty years after the last previously reported case in the country. Two of 4 patients died before medicine became available. We identified the infecting parasite as Trypanosoma brucei rhodesiense. Those cases imply human African trypanosomiasis has reemerged.

Antimicrobial resistance profiles of bacterial isolates from clinical specimens referred to Ethiopian Public Health Institute: analysis of 5-year data.

BACKGROUND: Antimicrobial resistance is one of the common global public health problems. The emergence of antimicrobial resistance is multifactorial, and tackling its development is challenging. Consequently, infections caused by resistant bacteria are unresponsive to conventional drugs, resulting in prolonged and severe illnesses, higher mortality rates, and considerable healthcare costs. Therefore, understanding the antimicrobial resistance profiles of bacterial pathogens is essential to optimize treatments and reduce the risks associated with infections. This study aimed to determine the antimicrobial resistance patterns of bacterial isolates from different clinical specimens at the Ethiopian Public Health Institute (EPHI). MATERIALS AND METHODS: The retrospective cross-sectional study was conducted on the bacterial culture and antibiotic susceptibility reports of different clinical specimens referred to the Bacteriology Laboratory of EPHI from September 2015 to August 2019. Standard bacteriological techniques were used for the isolation and identification of the bacteria. Data were extracted from 840 patients' records, which included the type of clinical sample cultured, the name of the bacteria, the representations of the antibiotics used for susceptibility testing, and the susceptibility results. Descriptive statistics were used to describe the bacterial isolates and the antimicrobial resistance profiles. RESULTS: Eight types of clinical specimens were analyzed for bacterial isolates and urine specimens were the most analyzed. Ten different genera of bacteria were identified by culture. Almost all the isolates were gram-negative bacteria, while only one species of gram-positive (Staphylococcus aureus) was reported. Antibiotic sensitivity patterns were tested on 840 culture isolates. Escherichia coli strains revealed more than 57% resistance to seventeen antibiotics. Klebsiella pneumoniae showed nearly 70% or greater resistance rates for 17 of the antibiotics used. The overall detected multidrug resistance (MDR) was 64.29%. The highest MDR was reported in Acinetobacter strains (84%) followed by K. pneumoniae (80%). CONCLUSIONS: The multidrug resistance rates found in this study were alarming. Strengthening antimicrobial resistance surveillance at the national level is mandatory, and antimicrobial sensitivity testing should be accessible at local diagnostic centers.

Baseline soil-transmitted helminth and schistosome infection in the Geshiyaro project, Ethiopia: A unique transmission interruption project using biometric fingerprinting for longitudinal individual analysis.

BACKGROUND: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. METHODS: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. RESULTS: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). CONCLUSIONS: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission.

Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia.

Diagnosis and treatment of Plasmodium falciparum infections are required for effective malaria control and are pre-requisites for malaria elimination efforts; hence we need to monitor emergence, evolution and spread of drug- and diagnostics-resistant parasites. We deep sequenced key drug-resistance mutations and 1,832 SNPs in the parasite genomes of 609 malaria cases collected during a diagnostic-resistance surveillance study in Ethiopia. We found that 8.0% (95% CI 7.0-9.0) of malaria cases were caused by P. falciparum carrying the candidate artemisinin partial-resistance kelch13 (K13) 622I mutation, which was less common in diagnostic-resistant parasites mediated by histidine-rich proteins 2 and 3 (pfhrp2/3) deletions than in wild-type parasites (P = 0.03). Identity-by-descent analyses showed that K13 622I parasites were significantly more related to each other than to wild type (P < 0.001), consistent with recent expansion and spread of this mutation. Pfhrp2/3-deleted parasites were also highly related, with evidence of clonal transmissions at the district level. Of concern, 8.2% of K13 622I parasites also carried the pfhrp2/3 deletions. Close monitoring of the spread of combined drug- and diagnostic-resistant parasites is needed.

Therapeutic efficacy of pyronaridine-artesunate (Pyramax®) against uncomplicated Plasmodium falciparum infection at Hamusit Health Centre, Northwest Ethiopia.

BACKGROUND: Early case detection and prompt treatment are important malaria control and elimination strategies. However, the emergence and rapid spread of drug-resistant strains present a major challenge. This study reports the first therapeutic efficacy profile of pyronaridine-artesunate against uncomplicated Plasmodium falciparum in Northwest Ethiopia. METHODS: This single-arm prospective study with 42-day follow-up period was conducted from March to May 2021 at Hamusit Health Centre using the World Health Organization (WHO) therapeutic efficacy study protocol. A total of 90 adults ages 18 and older with uncomplicated falciparum malaria consented and were enrolled in the study. A standard single-dose regimen of pyronaridine-artesunate was administered daily for 3 days, and clinical and parasitological outcomes were assessed over 42 days of follow-up. Thick and thin blood films were prepared from capillary blood and examined using light microscopy. Haemoglobin was measured and dried blood spots were collected on day 0 and on the day of failure. RESULTS: Out of 90 patients, 86/90 (95.6%) completed the 42-day follow-up study period. The overall PCR-corrected cure rate (adequate clinical and parasitological response) was very high at 86/87 (98.9%) (95% CI: 92.2-99.8%) with no serious adverse events. The parasite clearance rate was high with fast resolution of clinical symptoms; 86/90 (95.6%) and 100% of the study participants cleared parasitaemia and fever on day 3, respectively. CONCLUSION: Pyronaridine-artesunate was highly efficacious and safe against uncomplicated P. falciparum in this study population.

Prognostic Value of C-Reactive Protein in SARS-CoV-2 Infection: A Simplified Biomarker of COVID-19 Severity in Northern Ethiopia.

Purpose: To evaluate the role of C-reactive protein (CRP) in predicting severe COVID-19 patients. Methods: A prospective observational cohort study was conducted from July 15 to October 28, 2020, at Kuyha COVID-19 isolation and treatment center hospital, Mekelle City, Northern Ethiopia. A total of 670 blood samples were collected serially. SARS-CoV-2 infection was confirmed by RT-PCR from nasopharyngeal swabs and CRP concentration was determined using Cobas Integra 400 Plus (Roche). Data were analyzed using STATA version 14. P-value <0.05 was considered statistically significant. Results: Overall, COVID-19 patients had significantly elevated CRP at baseline when compared to PCR-negative controls [median 11.1 (IQR: 2.0-127.8) mg/L vs 0.9 (IQR: 0.5-1.9) mg/L; p=0.0004)]. Those with severe COVID-19 clinical presentation had significantly higher median CRP levels compared to those with non-severe cases [166.1 (IQR: 48.6-332.5) mg/L vs 2.4 (IQR: 1.2-7.6) mg/L; p<0.00001)]. Moreover, COVID-19 patients exhibited higher median CRP levels at baseline [58 (IQR: 2.0-127.8) mg/L] that decreased significantly to 2.4 (IQR: 1.4-3.9) mg/L after 40 days after symptom onset (p<0.0001). Performance of CRP levels determined using ROC analysis distinguished severe from non-severe COVID-19 patients, with an AUC value of 0.83 (95% CI: 0.73-0.91; p=0.001; 77.4% sensitivity and 89.4% specificity). In multivariable analysis, CRP levels above 30 mg/L were significantly associated with an increased risk of developing severe COVID-19 for those who have higher ages and comorbidities (ARR 3.99, 95% CI: 1.35-11.82; p=0.013). Conclusion: CRP was found to be an independent determinant factor for severe COVID-19 patients. Therefore, CRP levels in COVID-19 patients in African settings may provide a simple, prompt, and inexpensive assessment of the severity status at baseline and monitoring of treatment outcomes.