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Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6/71); p < 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: As a consequence of the improved availability of combined antiretroviral therapy (cART) in resource‐limited countries, an emergence of HIV drug resistance (HIVDR) has been observed. We assessed the prevalence and spectrum of HIVDR in patients with failure of second‐line cART at two HIV clinics in central Ethiopia. Methods: HIV drug resistance was analysed in HIV‐1‐infected patients with virological failure of second‐line cART using the geno2pheno application. Results: Among 714 patients receiving second‐line cART, 44 (6.2%) fulfilled the criteria for treatment failure and 37 were eligible for study inclusion. Median age was 42 years [interquartile range (IQR): 20–45] and 62.2% were male. At initiation of first‐line cART, 23 (62.2%) were WHO stage III, mean CD4 cell count was 170.6 (range: 16–496) cells/µL and median (IQR) HIV‐1 viral load was 30 220 (7963–82 598) copies/mL. Most common second‐line cART regimens at the time of failure were tenofovir disoproxil fumarate (TDF)‐lamivudine (3TC)‐ritonavir‐boosted atazanavir (ATV/r) (19/37, 51.4%) and zidovudine (ZDV)‐3TC‐ATV/r (9/37, 24.3%). Genotypic HIV‐1 resistance testing was successful in 35 (94.6%) participants. We found at least one resistance mutation in 80% of patients and 40% carried a protease inhibitor (PI)‐associated mutation. Most common mutations were M184V (57.1%), Y188C (25.7%), M46I/L (25.7%) and V82A/M (25.7%). High‐level resistance against the PI ATV (10/35, 28.6%) and lopinavir (LPV) (5/35, 14.3%) was reported. As expected, no resistance mutations conferring integrase inhibitor resistance were detected. Conclusions: We found a high prevalence of resistance mutations, also against PIs (40%), as the national standard second‐line cART components. Resistance testing before switching to second‐ or third‐line cART is warranted. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases are among the leading causes of death in many low-income countries, such as Ethiopia. Without reliable local data concerning causative pathogens and antimicrobial resistance, empiric treatment is suboptimal. The objective of this study was to characterize gram-negative bacteria (GNB) as pathogens and their resistance pattern in hospitalized patients with infections in central Ethiopia. Methods: Patients ≥ 1 year of age with fever admitted to the Asella Referral and Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were collected and cultured on appropriate media. Antibiotic susceptibility testing (AST) was performed using the Kirby–Bauer method and VITEK® 2. Species identification and detection of resistance genes were conducted using MALDI-ToF MS (VITEK® MS) and PCR, respectively. Results: Among the 684 study participants, 54.2% were male, and the median age was 22.0 (IQR: 14–35) years. Blood cultures were positive in 5.4% (n = 37) of cases. Among other clinical samples, 60.6% (20/33), 20.8% (5/24), and 37.5% (3/8) of swabs/pus, urine and other body fluid cultures, respectively, were positive. Among 66 pathogenic isolates, 57.6% (n = 38) were GNB, 39.4% (n = 26) were gram-positive, and 3.0% (n = 2) were Candida species. Among the isolated GNB, 42.1% (16/38) were Escherichia coli, 23.7% (9/38) Klebsiella pneumoniae and 10.5% (4/38) Pseudomonas aeruginosa. In total, 27/38 gram-negative isolates were available for further analysis. Resistance rates were as follows: ampicillin/sulbactam, 92.6% (n = 25); cefotaxime, 88.9% (n = 24); ceftazidime, 74.1% (n = 20); cefepime, 74.1% (n = 20); gentamicin, 55.6% (n = 15); piperacillin/tazobactam, 48.1% (n = 13); meropenem, 7.4% (n = 2); and amikacin, 3.7% (n = 1). The blaNDM-1 gene was detected in one K. pneumoniae and one Acinetobacter baumannii isolate, which carried an additional blaOXA-51 gene. The ESBL enzymes were detected in 81.5% (n = 22) of isolates as follows: TEM, 77.2% (n = 17); CTX-M-1 group, 68.2% (n = 15); SHV group, 27.3% (n = 6); and CTX-M-9 group, 9.1% (n = 2). Based on the in vitro antimicrobial susceptibility results, empiric treatment initiated in 13 of 18 (72.2%) patients was likely ineffective. Conclusion: We report a high prevalence of ESBL-producing bacteria (81.5%) and carbapenem resistance (7.4%), with more than half of GNB carrying two or more ESBL enzymes resulting in suboptimal empiric antibiotic therapy. These findings indicate a need for local and national antimicrobial resistance surveillance and the strengthening of antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Ticks will diminish productivity among farm animals and transmit zoonotic diseases. We conducted a study to identify tick species infesting slaughter bulls from Adama City and to screen them for tick-borne pathogens. In 2016, 291 ticks were collected from 37 bulls in Adama, which were ready for slaughter. Ticks were identified morphologically. Total genomic DNA was extracted from ticks and used to test for Rickettsia spp. with real-time PCR. Species identification was done by phylogenetic analysis using sequencing that targeted the 23S-5S intergenic spacer region and ompA genes. Four tick species from two genera, Amblyomma and Rhipicephalus, were identified. Amblyomma cohaerens was the dominant species (n = 241, 82.8%), followed by Amblyomma variegatum (n = 22, 7.5%), Rhipicephalus pulchellus (n = 19, 6.5%), and Rhipicephalus decoloratus (n = 9, 3.0%). Among all ticks, 32 (11%) were positive for Rickettsia spp. and 15 (5.2%) of these were identified as R. africae comprising at least two genetic clades, occurring in A. variegatum (n = 10) and A. cohaerens (n = 5). The remainder of Rickettsia-positive samples could not be amplified due to low DNA yield. Furthermore, another 15 (5.2%) samples carried other pathogenic bacteria: Ehrlichia ruminantium (n = 9; 3.1%) in A. cohaerens, Ehrlichia sp. (n = 3; 1%) in Rh. pulchellus and A. cohaerens, Anaplasma sp. (n = 1; 0.5%) in A. cohaerens, and Neoehrlichia mikurensis (n = 2; 0.7%) in A. cohaerens. All ticks were negative for Bartonella spp., Babesia spp., Theileria spp., and Hepatozoon spp. We reported for the first time E. ruminatium, N. mikurensis, Ehrlichia sp., and Anaplasma sp. in A. cohaerens. Medically and veterinarily important pathogens were mostly detected from A. variegatum and A. cohaerens. These data are relevant for a One-health approach for monitoring and prevention of tick-borne disease transmission. [ABSTRACT FROM AUTHOR]

Background: Local data from the Asella Teaching and Referral Hospital in the town of Asella, Ethiopia reveal a high prevalence of extended-spectrum β-lactamase- (ESBL) producing Gram-negative bacteria (GNB) in clinical isolates. To investigate a possible route of transmission, we determined the proportions ESBL-producing GNB in isolates from flies caught in the hospital and in the town of Asella. Methods: Flies were collected in August 2019 from the neonatal intensive care unit (NICU), the orthopedic ward, the hospital's waste disposal area, and from a butchery situated 1.5 km from the hospital. After trapping, the flies were macerated and suspended in sterile normal saline. The suspensions were inoculated on MacConkey agar and incubated overnight. Species identification and antimicrobial susceptibility testing were performed using Vitek®-MS and VITEK® 2. Results: In total, 103 bacterial isolates were obtained from 85 flies (NICU: 11 isolates from 20 flies, orthopedic ward: 10 isolates from 12 flies, waste disposal area: 37 isolates from 26 flies, butchery: 45 isolates from 27 flies). The proportions of ESBL-producing bacteria among isolates obtained from flies collected in the hospital compound were significantly higher (82%, 90%, and 57% in NICU, orthopedic ward and waste disposal area, respectively) compared to flies collected outside of the hospital compound (2% (@1/45) in the butchery) (p ≤ 0.001). The proportion of ESBL was 67% (6/9) among Raoultella spp. 67% (4/6) among Kluyvera spp., 56% (5/9) among Enterobacter spp., 50% (5/10) among E. coli, and 44% (8/18) among Klebsiella spp.. Of the 40 ESBL-genes detected, 85% were CTX-M-like, 83% TEM-like, 23% SHV-like, and 2% CTX-M-2-like. ESBL-producing bacteria showed higher rates of resistance against ciprofloxacin (66% vs. 5%), gentamicin (68% vs. 3%), piperacillin-tazobactam (78% vs. 5%), and trimethoprim-sulfamethoxazole (88% vs. 16%), compared to non-ESBL-producing bacteria. Conclusion: A high proportion of ESBL was identified in isolates from flies caught in the hospital compound compared with isolates of flies collected at a distance of 1.5 km from the hospital. Flies can be potential vectors for transmission of multidrug-resistant (MDR) bacteria within hospitals. Further studies are needed to determine the source of MDR colonization in flies and possible impact of MDR for nosocomial infections. [ABSTRACT FROM AUTHOR]

Background Acute infectious diseases and sepsis are among the leading causes of mortality in Ethiopia. The lack of local data concerning causative pathogens and resistance patterns results in suboptimal empirical treatment and unfavorable clinical outcome. The objective of this study was the characterization of bacterial pathogens in hospitalized patients with febrile infections in Central Ethiopia. Methods In total, 684 patients ≥1 year of age with fever admitted to the Asella Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were cultured. Susceptibility testing was performed using the Kirby–Bauer method and VITEK2. Confirmation of species identification and identification of resistance genes were conducted using MALDI-ToF and PCR at a microbiology laboratory in Düsseldorf, Germany. Results In total, 684 study participants were included; 54% were male and mean age was 26.7 years. Thus, the overall culture positivity rate was 7.5%. Of the 83 cultured organisms, 38(46%) were Gram-negative, 43(52%) Gram-positive, and 2(2%) Candida species. Among the 38 Gram-negative isolates, 16(42%) were E. coli , 15(39%) K. pneumoniae , and 4(11%) P. aeruginosa. Resistance against commonly used antibiotics for Gram-negative at the study site was: piperacillin/tazobactam 48%(13), ampicillin/sulbactam 93% (25), cefotaxime 89%(24), ceftazidime 74%(20), Cefipime 74%(20), meropenem 7%(2), amikacin 4% (1) and gentamicin 56%(15). Of 27 Gram-negative available for resistance-gene detection, blaNDM-1 was detected in one K. pneumoniae isolate and blaNDM-1 plus blaOXA-51 in A. baumannii. 81%(22/27) of the Gram-negative rods were confirmed to contain ESBL-genes as follows: TEM 17(77%), CTX-M-1-group 15(68%), SHV-6(27%) and CTX-M-9-group 2(9%). Among isolated S.aureus, 1(5%) was confirmed to be Methicillin-resistant S. aureus. Conclusion We found a high prevalence (81%) of ESBL-producing bacteria and 7.4% carbapenem resistance at the study site. More than half of Gram-negative isolates had two or more mobile resistance genes. These findings warrant the need for local national multidrug-resistant surveillance. Strengthening of antimicrobial stewardship programs is needed in order to face the threat of multidrug-resistant bacteria. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

In resource-limited settings, intestinal Cryptosporidial or coccidian infections are common causes of chronic diarrhea but usually remain undiagnosed by routine stool investigation. Here, the addition of the Kinyoun staining technique after stool concentration was evaluated as an easy and inexpensive method for diagnosis of intestinal parasitic infection in patients with HIV. This cross-sectional study investigated patients with HIV with diarrhea and randomly selected patients with HIV without diarrhea as controls. Stool samples were examined by wet mount microscopy and Kinyoun staining after stool concentration. Clinical, sociodemographic, and behavioral data were collected. Statistical analysis was performed using chi-squared test and multivariate regression analysis. In total, 163 participants were included (62.0% female, mean age 38.2 [SD ± 10.7] years). Diarrhea was present in 52.1% (85/163). The prevalence of intestinal parasites was 18.4% (30/163). Cryptosporidial infections were more frequent among patients with diarrhea (12.9% [11/85] vs 1.3% [1/78], P = 0.005) and in patients with CD4+ cell count <200 cells/µl (25.9% [7/27] vs 3.7% [5/136], P = 0.001). Risk factors for intestinal parasitic infections were diarrhea and the habit of regularly eating uncooked food. Kinyoun staining was necessary for the detection of cryptosporidiosis. In our cohort, the prevalence of intestinal parasitic infection was high, especially after additional use of Kinyoun staining for detection of Cryptosporidia or intestinal coccidia. Considering its clinical relevance, particularly in individuals at risk, the implementation of this technique should be considered in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Despite the necessity of early recognition for an optimal outcome, sepsis often remains unrecognized. Available tools for early recognition are rarely evaluated in low- and middle-income countries. In this study, we analyzed the spectrum, treatment and outcome of sepsis at an Ethiopian tertiary hospital and evaluated recommended sepsis scores., Methods: Patients with an infection and ≥2 SIRS criteria were screened for sepsis by SOFA scoring. From septic patients, socioeconomic and clinical data as well as blood cultures were collected and they were followed until discharge or death; 28-day mortality was determined., Results: In 170 patients with sepsis, the overall mortality rate was 29.4%. The recognition rate by treating physicians after initial clinical assessment was low (12.4%). Increased risk of mortality was significantly associated with level of SOFA and qSOFA score, Gram-negative bacteremia (in comparison to Gram-positive bacteremia; 42.9 versus 16.7%), and antimicrobial regimen including ceftriaxone (35.7% versus 19.2%) or metronidazole (43.8% versus 25.0%), but not with an increased respiratory rate (≥22/min) or decreased systolic blood pressure (≤100mmHg). In Gram-negative isolates, extended antimicrobial resistance with expression of extended-spectrum beta-lactamase and carbapenemase genes was common. Among adult patients, sensitivity and specificity of qSOFA score for detection of sepsis were 54.3% and 66.7%, respectively., Conclusion: Sepsis is commonly unrecognized and associated with high mortality, showing the need for reliable and easy-applicable tools to support early recognition. The established sepsis scores were either of limited applicability (SOFA) or, as in the case of qSOFA, were significantly impaired in their sensitivity and specificity, demonstrating the need for further evaluation and adaptation to local settings. Regional factors like malaria endemicity and HIV prevalence might influence the performance of different scores. Ineffective empirical treatment due to antimicrobial resistance is common and associated with mortality. Local antimicrobial resistance statistics are needed for guidance of calculated antimicrobial therapy to support reduction of sepsis mortality., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The physiological range of different vital signs is dependent on various environmental and individual factors. There is a strong interdependent relationship between vital signs and health conditions. Deviations of the physiological range are commonly used for risk assessment in clinical scores, e.g. respiratory rate (RR) and systolic blood pressure (BPsys) in patients with infections within the quick sequential organ failure assessment (qSOFA) score. A limited number of studies have evaluated the performance of such scores in resource-limited health care settings, showing inconsistent results with mostly poor discriminative power. Divergent standard values of vital parameters in different populations, e.g. could influence the accuracy of various clinical scores., Methods: This multisite cross-sectional observational study was performed among Ethiopians residing at various altitudes in the cities of Asella (2400m above sea level (a.s.l.)), Adama (1600m a.s.l.), and Semara (400m a.s.l.). Volunteers from the local general population were asked to complete a brief questionnaire and have vital signs measured. Individuals reporting acute or chronic illness were excluded., Results: A positive qSOFA score (i.e. ≥2), indicating severe illness in patients with infection, was common among the studied population (n = 612). The proportion of participants with a positive qSOFA score was significantly higher in Asella (28.1%; 55/196), compared with Adama, (8.3%; 19/230; p<0.001) and Semara (15.1%; 28/186; p = 0.005). Concerning the parameters comprised in qSOFA, the thresholds for RR (≥22/min) were reached in 60.7%, 34.8%, and 38.2%, and for BPsys (≤100 mmHg) in 48.5%, 27.8%, and 36.0% in participants from Asella, Adama, and Semara, respectively., Discussion: The high positivity rate of qSOFA score in the studied population without signs of acute infection may be explained by variations of the physiological range of different vital signs, possibly related to the altitude of residence. Adaptation of existing scores using local standard values could be helpful for reliable risk assessment., Competing Interests: The authors have declared that no competing interests exist.