Ayalew Jejaw Zeleke

The rise of antimalarial drug-resistant Plasmodium falciparum threatens malaria elimination efforts. Mutations in the gene kelch13 ( k13 ) confer artemisinin partial resistance (ART-R), compromising the efficacy of frontline artemisinin-based combination therapies (ACTs). The validated mutation k13 R622I has emerged and expanded rapidly in the Horn of Africa. We conducted a year-long genomic surveillance study in Gondar Zuria and Tach Armachiho, two ecologically distinct districts in northwestern Ethiopia where R622I was first identified. A total of 903 P. falciparum infections were sequenced using molecular inversion probe (MIP) panels targeting major drug resistance mutations and genome-wide informative SNPs. The R622I mutation was found in 44.3% of samples, more frequent in Gondar Zuria than Tach Armachiho (52% vs. 35%; p < 0.001 ), and persisted year-round in nearly all sites, indicating stable transmission with minimal seasonal variation. Histidine-rich protein 2 (HRP2) based rapid diagnostic test (RDT) negativity was also prevalent (39.3%), with significant district-level variation (48.7% vs. 27.6%; p < 0.001 ). Concerningly, R622I and HRP2-RDT co-occured in 22% of samples, higher in Gondar Zuria than in Tach Armachiho (28.9% vs. 12.9%; p < 0.00 1). Overall, HRP2-RDT negativity was significantly more common among R622I mutant parasites than wild-type (48.3% vs. 30.7%; p < 0.05). The k13 C580Y mutation was also detected at very low frequency (0.4%) in Gondar Zuria, representing the first report of this mutation in the Horn of Africa. Long-read whole-genome sequencing showed k13 flanking haplotypes of C580Y isolates were distinct from Southeast Asian lineages, suggesting a local, de novo emergence of African origin. These findings highlight the increasing prevalence and types of ART-R mutations, persistence of k13 R622I and its increasing association with HRP2-RDT negativity, representing a double threat to malaria control and elimination efforts.

The rise of antimalarial drug-resistant Plasmodium falciparum poses a major threat to malaria treatment, control, and elimination efforts. Mutations in the kelch13 ( k13 ) gene confer artemisinin partial resistance (ART-R), compromising the efficacy of combination therapies. In the Horn of Africa, the validated mutation k13 R622I has rapidly emerged in parallel with other mutations elsewhere in Eastern Africa. To monitor and inform control efforts, we conducted in-depth sampling where R622I was first detected, using molecular inversion probe (MIP) targeted sequencing of key resistance mutations and informative SNPs across the genome. Samples were collected for a year within two districts, Gondar Zuria and Tach Armachiho, representing different ecological zones in northwest Ethiopia. Among 903 people with P. falciparum malaria, we observed a markedly higher prevalence of R622I (44.3%) compared to earlier reports, with significantly higher prevalence in Gondar Zuria (52%) than in Tach Armachiho (40%; pk13 C580Y mutation in two patients (0.4%) from Gondar Zuria, the first report in the Horn of Africa. Identity-by-descent (IBD) analysis showed C580Y mutant parasites were likely clonal (IBD=1). Whole-genome sequencing confirmed their clonal nature and revealed flanking haplotypes distinct from those seen in Southeast Asia where the mutation was first observed, suggesting a local, de novo emergence. These findings highlight increasing prevalence and types of ART-R mutations and the concerning association now with RDT negativity that will further challenge malaria control and elimination efforts.

Background. In Ethiopia, despite various public health intervention approaches have been implemented to eliminate malaria, its public health problem remains considerable. There are such numerous studies; however, investigating the trend of malaria infection in various settings is paramount for area-specific evidence-based interventions, evaluating ongoing malaria control programs. Hence, since the trend of malaria infection in Maksegnit has not yet been documented, this study is aimed at assessing the seven-year trend of malaria in Maksegnit Health Center. Methods. An institutional-based retrospective study was conducted to assess the trend of malaria prevalence over the last seven years (2014-2020) using recorded blood smear reports in the laboratory logbook in Maksegnit Health Center, Northwest Ethiopia. Result. Over the last seven years, a total of 28217 clinically malaria-suspected individuals were requested for blood film examination at Maksegnit Health Center. Of whom, microscopically confirmed malaria case was found in 4641/28217 (16.4%). A significant seasonal and interannual variation of malaria cases was observed ( P < 0.001 ). The highest prevalence was observed in years 2014 (25.5%) and 2020 (25.1%), while the minimum annual prevalence was seen in 2017/18 (6.4%). The month of October (25.5%) had the highest number of malaria cases documented, while February had the least (4.7%). Males and individuals under the age group of 15-45 were the most affected segments of the population. A significant interannual fluctuating prevalence of malaria cases was recorded ranging from 25.5% to 6.4% ( P < 0.001 ). Conclusion. Malaria is still a public health threat in the study area despite significant fluctuating patterns of malaria was observed in the last seven years. In particular, a bounced back trend of malaria from 2018 to 2020 is alarming. Thus, the implementation of ongoing intervention approaches should be reconsidered, and uninterrupted efforts of the concerned bodies are still needed.

Background: The usefulness of histidine-rich protein-2/3 (HRP2/3)-based rapid diagnostic tests of malaria due to Plasmodium falciparum has been threatened by the appearance of mutant PfHRP2/3 genes. This study was undertaken to determine the global pooled estimates of PfHRP2/3gene deletions. Methods: Relevant publications were identified from electronic databases such as; PubMed, EMBASE, and MEDLINE online. Besides, all the relevant literatures were retrieved through Google and Google Scholar. STATA software was used for data analysis. The pooled estimates were calculated using random effect model. The summary estimates were presented using forest plots and tables. Results: A total of 27 studies were included in the systematic review. However, only 24 and 17 studies were included for PfHRP2 and 3 gene deletion meta-analysis, respectively. The prevalence of PfHRP2 gene deletion across the individual studies ranged from the highest 100% to the lowest 0%. However, the meta-analysis result showed that the global pooled prevalence of PfHRP2 and PfHRP3 gene deletions were 21.30% and 34.50%, respectively. The pooled proportion of PfHRP2 gene deletion among false negative PfHRP2-based RDTs results was found to be 41.10%. The gene deletion status was higher in South America and followed by Africa. The pooled estimate of PfHRP2 gene deletion among studies, which did not follow the WHO PfHRP2/3 gene deletion analysis protocol was higher than their counter parts (21.3% vs 10.5%). Conclusions: This review showed that there is a high pooled prevalence of PfHRP2/3 gene deletions in Plasmodium falciparum confirmed isolates and also a high proportion of their deletions among false-negative malaria cases using PfHRP2-based RDT results. Hence, malaria diagnosis based on PfHRP2-based rapid tests seems to be less sensitive and warrants further evaluation of PfHRP2/3 gene deletions.

Background. Inappropriate diagnosis could intimidate the prevention and control of hookworm infection. Thus, this study was aimed at evaluating the performance of hookworm diagnosis methods. Methods. An institution-based cross-sectional study was conducted from patients in Debre Elias and Sanja districts of the Amhara region, Ethiopia, from November 2019 to January 2020. The study subjects were selected conveniently. After the data was entered into Statistical Package for the Social Sciences (SPSS), sensitivity, specificity, predictive values, test accuracy, and agreement of the different hookworm diagnosis methods, namely, test tube flotation technique (TFT), McMaster (MM), formol-ether concentration (FEC), Kato-Katz (KK), and direct wet mount microscopy (DWMM), were calculated by using SPSS software. The composite reference standard (CRS) was used as the gold standard method. The kappa () test was used to measure the level of agreement between diagnosis tests. Result. A total of 389 stool samples were collected from patients in the study. The overall prevalence of hookworm was 63.24%. The test tube flotation technique (TFT) was found to be the highest both in terms of sensitivity and diagnostic accuracy (100%). McMaster (MM) was the second most sensitive test (68.7%), followed by FEC (44.3%) and KK (38.2%). On the other hand, DWMM had the lowest sensitivity (37.4%), and its diagnostic accuracy was also the least (60%). Only TFT had a perfect agreement ( , ) with the CRS. The sensitivity of DWMM, KK, and FEC showed a kind of linear function with the intensity of infection, but TFT and MM methods were not affected by the infection intensity. Conclusion. Hookworm is still a public health problem in the study area. TFT is by far more sensitive than MM, FEC, KK, and DWMM techniques.

Background. Cutaneous leishmaniasis (CL), which is one form of leishmaniasis, may show variations over years across regions, and epidemiological studies are crucial to estimate the cases of the disease status over a long time. This study is aimed at determining the trend of CL among patients at the University of Gondar Leishmaniasis Research and Treatment Center, northwest Ethiopia between 2009 and 2018 years. Methods. A ten-year data were extracted retrospectively. We included all patients who were visiting the center for CL diagnosis during the last ten years. Giemsa-stained skin slit microscopy was used to diagnose the disease. A chi-square test was used to compare the proportions of patients infected across years, seasons, months, sex, and age groups. Result. During the 10 years, a total of 1079 samples were requested for the diagnosis of CL. The cumulative average annual prevalence was found to be 55.4 (598/1079). The highest and lowest proportions of CL cases were recorded in 2014 (69.5) and 2018 (35.4), respectively. However, the percentage of CL cases did not show any significant differences over the study period. The number of suspected patients was significantly increased over the years (being lowest in 2009 and highest in 2017). The proportion of CL cases showed a remarkable difference across months but not seasons. CL was the highest within 15-49 years of age and males. Conclusion. The prevalence of CL did not show any significant differences over the last ten years. However, a remarkable increase of CL suspected cases was observed across the years. The disease showed significant association with age, sex, and months, but not seasons.

Background: Intestinal parasitic infections (IPIs) are small organisms that infect the gastro-intestinal tract of human beings. Causes malnutrition, iron deficiency anemia, impairment of physical and mental development in children. The aim of this study was to determine the prevalence of intestinal helminthiasis and associated factors among Kindergarten (KG) children in Gondar Town, northwest Ethiopia. Methods: Institution-based cross-sectional study was conducted on 390 Kindergarten children in Gondar town, Northwest, Ethiopia from March to May 2019. Study subjects were selected using systematic random sampling method. Data were gathered through direct interview by using a pretested questionnaire. Stool specimens were collected and examined using Kato Katz technique. Chi square was used to assess the association between variables and p-value less than 0.05 was taken as a statistical significance. Results: The overall prevalence of intestinal helminthiasis was 16.7%, while those of participants infected by soil-transmitted helminths (STHs) and intestinal Schistosomiasis were 13.8% and 5.9%, respectively. Ascaris lumbricoides was the predominant STHs (9%) followed by Trichuris trichiura (2.3%) and hookworm (1.5%). Light infection was observed in almost all of the infected study participants. Intestinal helminthiasis was found to be significantly associated with age, KG level of children, maternal occupation, and educational status of parents. Conclusion: A significant number of children were infected by intestinal parasites in the study area. A. lumbricoides and intestinal Schistosomiasis were the most predominant of the isolated parasites.

Background: Globally, soil-transmitted helminths affect beyond a billion people and cause 1.9 million disability-adjusted life years worldwide. It affects children disproportionately due to their unaware activities like walking barefoot, playing with dirty objects that might be contaminated with feces. The control of soil-transmitted helminths principally relies on periodic deworming using either a single dose of albendazole/mebendazole. To assure the effectiveness of this measure, performing continuous parasitological survey is necessary. Herein, the prevalence, intensity and associated factors of soil-transmitted helminth infections were assessed among school-aged children in northwest Ethiopia. Methods: A cross-sectional study design was conducted among school-aged children (6-14 years old) from January 21st to February 21st/2019. Multistage sampling technique was employed. A Kato-Katz concentration technique was utilized to detect STHs in stool samples. Moreover, risk factors for STH infections were assessed using well-structured questionnaire. Bivariate and multivariate analyses were used to assess the association between explanatory and the outcome variables. The magnitude of the association was measured using the adjusted odds ratio (AOR) and 95% confidence interval (CI). A P-value <0.05 was considered statistically significant. Results: The overall STHs prevalence in this study was 32.3% (95% CI: 29-35.6%) with Ascaris lumbricoides being the predominant species (24.3%) followed by hookworm (8.9%) and Trichuris trichiura (1%). Most (80.3%) of the infected school-aged children had light-intensity infections. Age of 11 years and above (AOR, 12.9, 95% CI, 1.6-103.6, P=0.004), being residing in Chuahit district (AOR, 3.9, 95% CI, 2.3-6.5, P<0.001), and untreated water supply (AOR, 1.7, 95% CI, 1.1-2.7, P=0.018) were identified as predictors for the overall STH prevalence. Conclusion: Our findings revealed STH infections are considerable health problems in the study areas. Thus, public health interventions such as provision of safe water supply, health education, and de-worming programs should be regularly implemented in the study areas.

Background. Worldwide, more than one-sixth of the population is infected by intestinal parasites, of which the majority live in developing countries. On the other hand, the prevalence of diabetes mellitus has been increasing over recent decades in developing countries. Patients with diabetes mellitus encountered impaired immunity and suffer from the consequences of infection particularly intestinal parasitic infection. Objective. This study is aimed at assessing the prevalence of intestinal parasites and associated factors among diabetes mellitus patients at the University of Gondar Referral Hospital, Northwest Ethiopia. Methods and Materials. An institutional-based cross-sectional study was conducted at the University of Gondar Comprehensive Specialized Referral Hospital from February 15 to March 30, 2018. A total of 234 diabetes mellitus patients were enrolled. A systematic random sampling technique was used to select study participants. Sociodemographic and clinical data were collected using a semistructured questionnaire. A 5-gram stool sample was collected to identify parasitic infection using a direct wet mount and formal-ether concentration technique. Data was entered and analyzed by using SPSS version 20. A p value of ≤0.05 was considered as statistically significant. Result. In the current study, the overall prevalence of intestinal parasite infection among diabetics was 45 (19.2%). The parasites identified in this study were Ascaris lumbricoides 15 (6.41%), Entamoeba histolytica/dispar 9 (3.85%), Hookworm 9 (3.85%), Schistosoma mansoni 7 (3%), Enterobius vermicularis 3 (1.3%), and Giardia lamblia 2 (0.9%). Poor educational background ( AOR = 3.62 ; 95% CI (1.038, 12.65); p = 0.043 ), poor hygiene and sanitation ( AOR = 4.67 ; 95% CI (1.82, 12.07); p = 0.001 ), and inappropriate latrine usage ( AOR = 5.41 ; 95% CI (1.43, 20.56); p = 0.013 ) were significantly associated with the prevalence of intestinal parasitic infection among diabetes mellitus patients. Conclusion. The overall prevalence of intestinal parasitic infection among diabetes mellitus patients was relatively high. There should be continued prevention, control, and management of intestinal parasitic infection in such a study population.

Background. Schistosomiasis is one of the Neglected Tropical Diseases in Ethiopia, and its burden may show variations from time to time across different regions. Thus, this study was aimed at determining the prevalence, intensity, and associated risk factors of Schistosoma mansoni (S. mansoni) among schoolchildren in Northwest Ethiopia. Methods. A school-based cross-sectional study was conducted. A multistage sampling technique was used to select the study participants. Stool specimens were collected and examined using two-slide Kato-Katz method. Data were analyzed using SPSS version 20 software. Multivariate logistic regression analysis was used to identify risk factors. values less than 0.05 were taken as statistically significant. Result. A total of 786 schoolchildren were participated in this study. The prevalence of S. mansoni was 33.5%. The mean egg count of the parasite among the infected study participants was 523.665 eggs per gram (epg) of stool. Thirty-seven, 42, and 21 percent of the study participant’s infection were due to light, moderate, and heavy infection intensities, respectively. Age of 8-11 years old ( , ), 5^th-8^th grade level ( , ), residing in Chuahit District ( , ), and using untreated water for domestic supply ( , ) were found to be risk factors for S. mansoni infection. Conclusion. High prevalence of S. mansoni and relatively higher proportion of moderate intensity of infection in this study imply that schistosomiasis is still one of the major public health problems in...