Healthcare Seeking Behavior and Disease Perception Toward Cholera and Acute Diarrhea Among Populations Living in Cholera High-Priority Hotspots in Shashemene, Ethiopia.

BACKGROUND: Healthcare seeking behavior (HSB) and community perception on cholera can influence its management. We conducted a cross-sectional survey to generate evidence on cholera associated HSB and disease perception in populations living in cholera hotspots in Ethiopia. METHODS: A total of 870 randomly selected households (HHs) in Shashemene Town (ST) and Shashemene Woreda (SW) participated in our survey in January 2022. RESULTS: Predominant HHs (91.0%; 792/870) responded "primary health center" as the nearest healthcare facility (HCF). Around 57.4% (247/430) of ST HHs traveled <30 minutes to the nearest HCF. In SW, 60.2% (265/440) of HHs travelled over 30 minutes and 25.9% (114/440) over 4 km. Two-thirds of all HHs paid

Coverage of Two-Dose Preemptive Cholera Mass Vaccination Campaign in High-Priority Hotspots in Shashemene, Oromia Region, Ethiopia.

BACKGROUND: Cholera is a public health priority in Ethiopia. The Ethiopian National Cholera Plan elaborates a multi-year scheme of oral cholera vaccine (OCV) use. Aligned with this, a preemptive OCV campaign was conducted under our Ethiopia Cholera Control and Prevention project. Here, we present the OCV vaccination outcomes. METHOD: Cholera high-priority hotspots in the Oromia Region, Shashemene Town (ST) and Shashemene Woreda (SW), were selected. Four kebelles (Abosto, Alelu, Arada, and Awasho) in ST and 4 clusters (Faji Gole, Harabate, Toga, and Chabi) in SW were study sites with OCV areas nested within. A total of 40 000 and 60 000 people in ST and SW, respectively, were targeted for a 2-dose OCV (Euvichol-Plus) campaign in 11-15 May (first round [R1]) and 27-31 May (second round [R2]) 2022. Daily administrative OCV coverage and a coverage survey in 277 randomly selected households were conducted. RESULTS: The administrative OCV coverage was high: 102.0% for R1 and 100.5% for R2 in ST and 99.1% (R1) and 100.0% (R1) in SW. The coverage survey showed 78.0% (95% confidence interval [CI]: 73.1-82.9) of household members with 2-dose OCV and 16.8% (95% CI: 12.4-21.3) with no OCV in ST; and 83.1% (95% CI: 79.6-86.5) with 2-dose OCV and 11.8% (95% CI: 8.8-14.8) with no OCV in SW. The 2-dose coverages in 1-4-, 5-14-, and ≥15-year age groups were 88.3% (95% CI: 70.6-96.1), 88.9% (95% CI: 82.1-95.7), and 71.3% (95% CI: 64.2-78.3), respectively, in ST and 78.2% (95% CI: 68.8-87.7), 91.0% (95% CI: 86.6-95.3), and 78.7% (95% CI: 73.2-84.1) in SW. CONCLUSIONS: High 2-dose OCV coverage was achieved. Cholera surveillance is needed to assess the vaccine impact and effectiveness.

Comprehensive Review on the Use of Oral Cholera Vaccine (OCV) in Ethiopia: 2019 to 2023.

BACKGROUND: Cholera outbreaks in Ethiopia necessitate frequent mass oral cholera vaccine (OCV) campaigns. Despite this, there is a notable absence of a comprehensive summary of these campaigns. Understanding national OCV vaccination history is essential to design appropriate and effective cholera control strategies. Here, we aimed to retrospectively review all OCV vaccination campaigns conducted across Ethiopia between 2019 and 2023. METHODS: The OCV request records from 2019 to October 2023 and vaccination campaign reports for the period from 2019 to December 2023 were retrospectively accessed from the Ethiopia Public Health Institute (EPHI) database. Descriptive analysis was conducted using the retrospective data collected. RESULTS: From 2019 to October 2023, Ethiopian government requested 32 044 576 OCV doses (31 899 576 doses to global stockpile; 145 000 doses to outside of stockpile). Around 66.3% of requested doses were approved; of which 90.4% were received. Fifteen OCV campaigns (12 reactive and 3 pre-emptive) were conducted, including five two-dose campaigns with varying dose intervals and single-dose campaigns partially in 2019 and entirely in 2021, 2022 and 2023. Overall vaccine administrative coverage was high; except for Tigray region (41.8% in the 1st round; 2nd round didn't occur). The vaccine administrative coverage records were documented, but no OCV coverage survey data was available. CONCLUSIONS: This study represents the first comprehensive review of OCV campaigns in Ethiopia spanning the last five years. Its findings offer valuable insights into informing future cholera control strategies, underscoring the importance of monitoring and evaluation despite resource constraints. Addressing the limitations in coverage survey data availability is crucial for enhancing the efficacy of future campaigns.

Dissecting Water, Sanitation, and Hygiene (WaSH) to Assess Risk Factors for Cholera in Shashemene, Oromia Region, Ethiopia.

BACKGROUND: Cholera outbreaks have afflicted Ethiopia, with nearly 100 000 cases and 1030 deaths reported from 2015 to 2023, emphasizing the critical need to understand water, sanitation, and hygiene (WaSH) risk factors. METHODS: We conducted a cross-sectional household (HH) survey among 870 HHs in Shashemene Town and Shashemene Woreda, alongside extracting retrospective cholera case data from the Ethiopian Public Health Institute database. Relationships between WaSH and sociodemographic/economic-levels of HHs were examined. WaSH status and cholera attack rates (ARs) were described at kebele-level using geospatial mapping, and their association was statistically analyzed. RESULTS: Access to basic drinking water, sanitation, and hygiene facilities was limited, with 67.5% (95% confidence interval, 64.4-70.6), 73.4% (70.3-76.3), and 30.3% (27.3-33.3) of HHs having access, respectively. Better WaSH practices were associated with urban residence (adjusted odds ratio, 1.7, [95% confidence interval, 1.1-2.7]), higher educational levels (2.7 [1.2-5.8]), and wealth (2.5 [1.6-4.0]). The association between cholera ARs and at least basic WaSH status was not statistically significant (multiple R2 = 0.13; P = .36), although localized effects were suggested for sanitation (Moran I = 0.22; P = .024). CONCLUSIONS: Addressing gaps in WaSH access and hygiene practices is crucial for reducing cholera risk. Further analyses with meaningful covariates and increased sample sizes are necessary to understand the association between cholera AR and specific WaSH components.

Retrospective Analysis of Cholera/Acute Watery Diarrhea Outbreaks in Ethiopia From 2001 To 2023: Incidence, Case Fatality Rate, and Seasonal and Multiyear Epidemic Patterns.

BACKGROUND: The Ethiopian government has developed the multisectoral cholera elimination plan (NCP) with an aim of reducing cholera incidence and case fatality rate (CFR). To better understand and monitor the progress of this plan, a comprehensive review of national cholera epidemiology is needed. METHODS: Reported data on cholera/acute watery diarrhea (AWD) cases in the past 20 years were extracted from the Ethiopian Public Health Institute and World Health Organization databases. Descriptive statistics, Pearson χ2, and logistic regression analyses were conducted. RESULTS: From January 2001 to November 2023, a total of 215 205 cholera/AWD cases, 2355 deaths with a cumulative CFR of 1.10% (95% confidence interval [CI], 1.092-1.095), and a mean annual incidence rate of 8.9/100 000 (95% CI, 6.5-11.3) were reported. Two major upsurges of cholera epidemics were found in the last two decades with mean attack rate (AR) of 20.57/100 000 in 2006-2010 and 14.83/100 000 in 2016-2020. Another resurgence of outbreaks occured in 2021-2023 (mean AR, 8.63/100 000). In 2015-2023, 54.0% (53 990/99 945) of cases were aged 15-44 years. National cholera CFR (3.13% [95% CI: 2.1-4.5]) was the highest in 2022. The 2015-2023 cumulative cholera CFR was different across regions: Benishangul Gumuz (6.07%), Gambela (1.89%), Sidama (1.42%), Southern Nation, Nationalities, and Peoples' (1.34%), Oromia (1.10%), and Amhara (1.09%). Cholera/AWD patients in older adults (≥45 years), severe dehydration, peak rainy season (June-August), and outpatients were associated with higher risk of death. CONCLUSIONS: Cholera has been a public health problem in Ethiopia with case fatalities still above the global target. Case management needs to be improved particularly in outpatients and older populations. Outbreak preparedness should be rolled out well in advance of the typical rainy seasons. Significant investments are essential to advance the cholera surveillance system at healthcare setting and community level. Underlying factors of cholera deaths per areas should be further investigated to guide appropriate interventions to meet the NCP target by 2028.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.

Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program.

Background: Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Methods: Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures. Results: A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5-14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation. Conclusions: Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.

Magnitude and Molecular Characterization of Extended-Spectrum ß-Lactamase Genes among Klebsiella pneumoniae Isolates in a Large Tertiary Hospital in Ethiopia.

Background Extended-spectrum ß-lactamases (ESBLs)-producing Klebsiella pneumoniae is reported worldwide increasingly. However, studies on ESBLs are still scarce in Ethiopia. Therefore, the current study aimed to determine the magnitude and resistance patterns of ESBL-producing K. pneumoniae as well as the frequency of ESBL-encoding genes.Methods A cross-sectional study was conducted from September 2018 to February 2019 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia among a total of 132 non-duplicate K. pneumoniae isolates. Phenotypic detection of ESBL production was done using Combined Disc Test. ESBL-encoding genes of blaCTX-M, blaTEM, and blaSHV were detected through multiplex PCR.Results The magnitude of ESBL production was 102/132 (77.3%). ESBL positive isolates were 100% resistant to ceftriaxone, cefotaxime, and cefuroxime. Co-resistance of ESBL-positive isolates to other non ß-lactam antimicrobials was high to trimethoprim-sulfamethoxazole (96.1%) followed by tetracycline (75.5%) and gentamicin (73.5%). However, these isolates showed high susceptibility to amikacin (96.1%) and meropenem (89.2%). From the total ESBL-positive isolates, 82.6%, 73.5%, and 75% carried blaCTX-M, blaTEM, and blaSHV genes, respectively. The majority 78/102 (76.5%) of ESBL-positive isolates harbored all three types of ESBL genes simultaneously.Conclusions The magnitude of ESBL-producing K. pneumoniae isolates was very alarming in the study area. The co-occurrence of blaCTX-M, blaTEM, and blaSHV genes is high, demanding large-scale studies to evaluate the presence of antimicrobial resistance super-clones. ESBL-producing isolates showed high resistance to most of the antimicrobials, needing phenotypic detection of ESBL regularly for better management of patients.

Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia.

BACKGROUND: We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia. METHODS: We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics. RESULTS: Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged < 15 years versus ≥ 15 years were detected for Vi (Odds Ratio (OR): 8.00, p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana. CONCLUSIONS: Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.

Occult hepatitis B virus infection among patients with chronic liver disease of unidentified cause, Addis Ababa Ethiopia.

Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg in the presence of HBV DNA in the serum and/or liver tissue remains a potential risk of transmission and diseases progression among different population groups. It could be associated with asymptomatic case up to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The objective of this study was to assess the magnitude and characteristics of OBI among patients with CLD of unidentified cause in Addis Ababa, Ethiopia. The study was conducted at the gastroenterology & hepatology referral clinic of three government and two private hospitals in Addis Ababa. Known CLD patients as evidenced by clinical and imaging criteria and/or with HBV surface antigen (HBsAg) negative results using rapid test kit were included. ELISA serological test to anti-HBc Ab, anti HBsAg Ab, and HBsAg were determined using BIORAD kits [ https://www.bio-rad.com ]. HBV-DNA was amplified, and viral loads were determined by quantitative real-time PCR using Abbott m2000rt platform following the manufacturer's instructions. Data analysis was done using SPSS version 20.A total of 48 CLD patients with no identified cause for their liver disease were identified during the study period. All the patients had evidence of CLD by clinical and imaging criteria and nine were excluded. Three (7.69%) of the 39 patients tested positive for HBsAg test done by ELISA making the negative predictive value of the rapid test kits 92.3% compared to ELISA. The remaining 36 patients had serology test for HBV and 16 (44.4%) had positive anti-HBV core antibody. Two (5.56%) of the 36 patients with HBV viral load determination had detectable HBV DNA suggesting presence of an occult hepatitis B infection. Occult hepatitis B infection is found to be an aetiology among CLD patients labelled as having no identified cause by the current standard of care using rapid HBsAg kits in a subset of patients in Ethiopia. This study signifies the high rate of OBI and past evidence of HBV infection among CLD patients and thus nucleic acid testing and/or anti-HBc shall be integrated to the routine health care system to minimize HBV infection risk of transmission and to enhance patient care.

Infectious Disease Control and Management in Ethiopia: A Case Study of Cholera.

Cholera remains a significant public health problem among the vulnerable populations living in many resource-limited settings with poor access to safe and clean water and hygiene practice. Around 2.86 million cholera cases and 95,000 deaths are estimated to occur in endemic countries. In Ethiopia, cholera has been one of the major epidemic diseases since 1634 when the first cholera outbreak was recorded in-country. Several cholera epidemics occurred with recent outbreaks in 2019-2021. Cholera has been often reported as acute watery diarrhea due to limited diagnostic capacity in remote areas in Ethiopia and sensitivities around cholera outbreaks. The government of Ethiopia has been executing several phases of multi-year health sector development plan in the past decades and has recently developed a national cholera control plan. Here, we aim to present the existing cholera control guidelines and health system in Ethiopia, including case detection and reporting, outbreak declaration, case management, and transmission control. Challenges and way forward on further research and public health interventions are also discussed to address the knowledge and health service gaps related to cholera control in Ethiopia.

Detection of blaKPC and blaNDM carbapenemase genes among Klebsiella pneumoniae isolates in Addis Ababa, Ethiopia: Dominance of blaNDM.

BACKGROUND: Infections caused by Klebsiella pneumoniae have been difficult to control because of the worldwide emergence of carbapenem-resistant isolates mainly due to carbapenemase production. Information regarding carbapenemase-producing K. pneumoniae is still scarce in Ethiopia. Therefore, the current study aimed to determine the prevalence of carbapenemase-producing K. pneumoniae and to assess the occurrence of blaNDM and blaKPC carbapenemase genes. METHODS: A cross-sectional study was conducted from September 2018 to February 2019 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A total of 132 non-duplicate K. pneumoniae isolates were studied. Phenotypic confirmation of carbapenemase production was done by modified Carbapenem Inactivation Method (mCIM). Multiplex PCR was performed for the detection of carbapenemase-encoding genes blaKPC, and blaNDM. RESULTS: Out of the total 132 K. pneumoniae isolates, 39 (29.6%) were non-susceptible to one or more carbapenems. The prevalence of carbapenemase-producing isolates from the total was 28 (21.2%) with mCIM of which the most dominant gene was blaNDM 26 (92.9%) and one isolate carried blaKPC concomitantly. Carbapenemase-producing K. pneumoniae isolates were 100% non-susceptible to half of the antimicrobials used in the study, including meropenem and ertapenem. Previous use of carbapenems was associated with carbapenemase production (P = 0.004). CONCLUSIONS: The prevalence of carbapenemase-producing K. pneumoniae isolates was worrying in the study area. To our knowledge, the study described the emergence of blaNDM and blaKPC gene carrying K. pneumoniae in Ethiopia for the first time. Further large-scale molecular-based studies, including other carbapenemase genes and sequencing of K. pneumoniae, are warranted to have a clear awareness about the presence of antimicrobial resistance high-risk clones in Ethiopia.

Prevalence and Molecular Characterization of Extended Spectrum ß-Lactamase and Carbapenemase-Producing Enterobacteriaceae Isolates from Bloodstream Infection Suspected Patients in Addis Ababa, Ethiopia.

Background: Production of Extended spectrum beta-lactamase (ESBL) and Carbapenemase is the most common strategy for drug resistance in clinical isolates of Enterobacteriaceae. This study was conducted to determine the magnitude of ESBL and Carbapenemase production (CPE) among clinical isolates of Enterobacteriaceae causing bloodstream infections (BSI) in Ethiopia. Methods: A cross-sectional study was performed from September 2018 to January 2019 in Ethiopia. A total of 2397 BSI suspected patients were enrolled and blood culture was performed using a BacT/Alert instrument in combination with conventional methods for identification. After antimicrobial susceptibility test, phenotypic confirmation of ESBLs was done by combined disc-diffusion. Meanwhile carbapenemase production was done by modified carbapenem inactivation method. Multiplex PCR was conducted to detect the presence of bla CTX-M,bla SHV, bla TEM, bla KPC and bla NDM genes. Results: A total of 104 (4.3%) Enterobacteriaceae were isolated from 2397 BSI suspected patients. Klebsiella pneumoniae (55/104, 52%) was the predominant isolate followed by E. coli, (19.2%, 20/104) and K.oxytoca (17.3%, 18/104). ESBL and carbapenemase production were observed from 70 (67.3%, 57.4 -76.2% at 95% CI) and 8 (7.7%, 3.4-14.6% at 95% CI) isolates respectively. The highest frequency of ESBL and carbapenemase production was observed in K. pneumoniae 78.2% (43/55) and 9.1% (5/55), respectively. All the 70 isolates confirmed as ESBL producers harbored at least one of the ESBL genes and the majority of them carried multiple beta-lactamase genes (84.3%), where bla CTX-M, type was the most predominant (67.3%). Similarly, the entire eight isolates positive for carbapenemase carried bla NDM but none of them carried bla KPC. Conclusion: In our study, the rate of ESBL production among BSI-causing Enterobacteriaceae was alarming and most of the isolates carried multiple types of ESBL genes. A significant magnitude of CPE isolates causing BSI was recorded.

The Magnitude of Carbapenemase and ESBL Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections at Tikur Anbessa Specialized Teaching Hospital, Addis Ababa, Ethiopia.

BACKGROUND: The emergence of multidrug-resistant organisms, such as extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), and carbapenemase-producing Enterobacteriaceae (CPE) is a public health concern. Therefore, this study aimed to determine the magnitude of carbapenemase and ESBL producing bacteria isolated from patients affected by Urinary Tract Infection (UTI). METHODS: A cross-sectional study was conducted from December 2018 to March 2019 at Tikur Anbessa Specialized Hospital. A total of 120 Enterobacteriaceae isolates from UTI patients were collected and identified on species level using standard microbiological methods. Antimicrobial susceptibility test was determined according to the guidelines of the Clinical and Laboratory Standards Institute. Detection of ESBL production was carried out by using ESBL ChromoSelect Agar medium and the combined disk diffusion. Production of carbapenemase was determined by using Hodge-test and modified carbapenem inactivation method as described in CLSI guidelines. RESULTS: Out of the total 120 Enterobacteriaceae isolates, 74 (61.7%) were ESBL-producers, and 8 (6.7%) were carbapenemase producers. The most common ESBL producing isolate was E.coli 38 (51.4%) and the most common carbapenemase-producing isolate was K.pneumoniae five (62.5%). Most of the ESBL and carbapenemase-producing isolates were recovered from hospitalized patients 46 (62.2%) and 7 (87.5%) respectively. The rate of ESBL and CPE production was observed high among patients taking antibiotics 64.8% (59/91) and 7.7% (7/91) respectively, but no significant association was observed p > 0.05. Furthermore, about 1.7% (2/120) isolates were found both ESBL and carbapenemase producers. Significant resistances rates were observed in ESBL and CPE isolates. CONCLUSION: Enterobacteriaceae isolates showed a significantly higher rate of ESBL production. A significant figure of carbapenemase production was observed among Enterobacteriaceae isolates causing UTI. The production of ESBL and CPE enhanced for an increased rate of MDR patterns. Efforts need to be made to introduce a system for tracking and detecting ESBL-PE and CPE-producing bacteria in hospitals, and monitoring dissemination of ESBL and CPE-producing Enterobacteriaceae is strongly recommended.

The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries.

BACKGROUND: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. METHODS: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. RESULTS: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries. CONCLUSIONS: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.

High Prevalence of Multidrug-Resistant Klebsiella pneumoniae in a Tertiary Care Hospital in Ethiopia.

Klebsiella pneumoniae poses an urgent public health threat, causing nosocomial outbreaks in different continents. It has been observed to develop resistance to antimicrobials more easily than most bacteria. These days, multidrug-resistant strains are being increasingly reported from different countries. However, studies on the surveillance of multidrug-resistant Klebsiella pneumoniae are very rare in Ethiopia. This study aimed to determine the antimicrobial resistance patterns and magnitude of MDR K. pneumoniae isolates from patients attending or admitted to Tikur Anbessa Specialized Hospital (TASH). A cross-sectional study was conducted from September 2018 to February 2019 at TASH, Addis Ababa, Ethiopia. Identification of K. pneumoniae was done by examining the Gram stain, colony characteristics on MacConkey agar and 5% sheep blood agar, as well as using a series of biochemical tests. Antimicrobial susceptibility testing of the isolates for 21 antimicrobials was done by the Kirby-Bauer disc diffusion technique. Data were double entered using Epidata 3.1 and exported to SPSS version 25 software for analysis. Among the total K. pneumoniae isolates (n = 132), almost all 130 (98.5%) were MDR. Two (1.5%) isolates showed complete non-susceptibility to all antimicrobial agents tested. Moreover, a high rate of resistance was observed to cefotaxime and ceftriaxone 128 (97%), trimethoprim-sulfamethoxazole 124 (93.9%), and cefepime 111 (84.1%). High susceptibility was recorded to amikacin 123 (93.2%), imipenem 107 (81.1%), meropenem 96 (72.7%), and ertapenem 93 (70.5%). K. pneumoniae isolates showed a high rate of resistance to most of the tested antimicrobials. The magnitude of MDR K. pneumoniae was very alarming. Therefore, strengthening antimicrobial stewardship programs and antimicrobial surveillance practices is strongly recommended in TASH.

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) for the Treatment of Uncomplicated Falciparum Malaria in Africa: A Systematic Review.

BACKGROUND: Africa still bears the largest burden of malaria as the majority of infections in the continent are caused by P. falciparum. Artemether-lumefantrine (AL, Coartem®) is the most widely used artemisinin-based combination therapy (ACT), for treating uncomplicated falciparum malaria globally. However, the development of resistance to antimalarial drugs is a major challenge for malaria control. In this review, the efficacy of AL for the treatment of uncomplicated falciparum malaria in Africa was evaluated. METHODS: Articles published between January 2015 and July 2019 were systematically searched using comprehensive search strings from PubMed/Medline, SCOPUS, and grey literature from Google Scholar. Interventional studies that followed patients for at least 28 days were included. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. All the included articles were measured to be good quality. While computing the efficacy of AL, polymerase chain reaction (PCR)-corrected cure rate (adequate clinical and parasitological response, ACPR) at day 28 was considered as the main endpoint. Meta-analysis was computed using STATA v 15 to calculate the pooled ACPR. RESULTS: In this review, 39 articles that reported the treatment outcome of 8,320 patients were included. After 28 days of follow-up, the pooled PCR uncorrected and corrected APCR was at 87% (95% CI: 85-90%) and 97.0% (95% CI: 96-98%), respectively. Moreover, the proportion of early treatment failure (ETF) was almost 0%, while most of the included articles reported <8% late treatment failures. The reinfection and recrudescence rate was less than 10% and 2.6%, respectively, within 28 days. We noted rapid fever and parasite clearance in which greater than 93% and 94% patients were parasite and fever free at day three following AL treatment. CONCLUSIONS: This review discovered that despite more than a decade since its introduction, Coartem® remains effective and thus could continue to be the drug of choice for the treatment of uncomplicated falciparum malaria for all age groups in Africa. However, the risk of new emerging resistance for this combination warrants regular monitoring of its efficacy across the continent.

Multicountry Distribution and Characterization of Extended-spectrum ß-Lactamase-associated Gram-negative Bacteria From Bloodstream Infections in Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum ß-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. METHODS: Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for ß-lactamase were performed on all pathogens. RESULTS: Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. CONCLUSIONS: Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.

Acute Febrile Illness Among Children in Butajira, South-Central Ethiopia During the Typhoid Fever Surveillance in Africa Program.

BACKGROUND: Clearly differentiating causes of fever is challenging where diagnostic capacities are limited, resulting in poor patient management. We investigated acute febrile illness in children aged ≤15 years enrolled at healthcare facilities in Butajira, Ethiopia, during January 2012 to January 2014 for the Typhoid Fever Surveillance in Africa Program. METHODS: Blood culture, malaria microscopy, and blood analyses followed by microbiological, biochemical, and antimicrobial susceptibility testing of isolates were performed. We applied a retrospectively developed scheme to classify children as malaria or acute respiratory, gastrointestinal or urinary tract infection, or other febrile infections and syndromes. Incidence rates per 100 000 population derived from the classification scheme and multivariate logistic regression to determine fever predictors were performed. RESULTS: We rarely observed stunting (4/513, 0.8%), underweight (1/513, 0.2%), wasting (1/513, 0.2%), and hospitalization (21/513, 4.1%) among 513 children with mild transient fever and a mean disease severity score of 12 (95% confidence interval [CI], 11-13). Blood cultures yielded 1.6% (8/513) growth of pathogenic agents; microscopy detected 13.5% (69/513) malaria with 20 611/µL blood (95% CI, 15 352-25 870) mean parasite density. Incidences were generally higher in children aged ≤5 years than >5 to ≤15 years; annual incidences in young children were 301.3 (95% CI, 269.2-337.2) for malaria and 1860.1 (95% CI, 1778.0-1946.0) for acute respiratory and 379.9 (95% CI, 343.6-420.0) for gastrointestinal tract infections. CONCLUSIONS: We could not detect the etiological agents in all febrile children. Our findings may prompt further investigations and the reconsideration of policies and frameworks for the management of acute febrile illness.

Correction to: Prevalence and phenotypic characterization of Enterococcus species isolated from clinical samples of pediatric patients in Jimma University Specialized Hospital, south west Ethiopia.

Following publication of the original article [1], the authors reported that one of the authors' names was spelled incorrectly. In this Correction the incorrect and correct author name are shown.