Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Improving the quality of HIV rapid testing in Ghana using the dried tube specimen-based proficiency testing program.

BACKGROUND: The introduction of human immunodeficiency virus (HIV) antibody rapid testing (RT) in resource-limited settings has proven to be a successful intervention to increase access to prevention measures and improve timely linkage to care. However, the quality of testing has not always kept pace with the scale-up of this testing strategy. To monitor the accuracy of HIV RT test results, a national proficiency testing (PT) program was rolled out at selected testing sites in Ghana using the dried tube specimen (DTS) approach. METHODS: Between 2015 and 2018, 635 HIV testing sites, located in five regions and supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), were enrolled in the HIV PT program of the Ghana Health Service National AIDS/STI Control Programme. These sites offered various services: HIV Testing and Counselling (HTC), prevention of mother-to-child transmission (PMTCT) and Antiretroviral Treatment (ART). The PT panels, composed of six DTS, were prepared by two regional laboratories, using fully characterized plasma obtained from the regional blood banks and distributed to the testing sites. The results were scored by the PT providers according to the predefined acceptable performance criteria which was set at ≥ 95%. RESULTS: Seven rounds of PT panels were completed successfully over three years. The number of sites enrolled increased from 205 in round 1 (June 2015) to 635 in round 7 (December 2018), with a noticeable increase in Greater Accra and Eastern regions. The average participation rates of enrolled sites ranged from 88.0% to 98.0% across the PT rounds. By round 7, HTC (257/635 (40.5%)) and PMTCT (237/635 (37.3%)) had a larger number of sites that participated in the PT program than laboratory (106/635 (16.7%)) and ART (12/635 (1.9%)) sites. The average testing performance rate improved significantly from 27% in round 1 to 80% in round 7 (p < 0.001). The highest performance rate was observed for ART (100%), HTC (92%), ANC/PMTCT (90%) and Laboratory (89%) in round 5. CONCLUSION: The DTS PT program showed a significant increase in the participation and performance rates during this period. Sub-optimal performances observed was attributed to non-compliance to the national testing algorithm and testing technique. However, the implementation of review meetings, peer-initiated corrective action, supportive supervisory training, and mentorship proved impactful. The decentralized approach to preparing the PT panels ensured ownership by the region and districts.

Acute febrile illness among outpatients seeking health care in Bangladeshi hospitals prior to the COVID-19 pandemic.

Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged ≥2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (≥100.4°F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia (R/O) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever (Salmonella enterica serotype Typhi orSalmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli, and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O, 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8-23 years) and was detected more frequently in the 21-25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85-7.32) between July and December (aOR 2.01, 1.01-5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93-4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management.

Etiology of acute meningitis and encephalitis from hospital-based surveillance in South Kazakhstan oblast, February 2017-January 2018.

Encephalitis and meningitis (EM) are severe infections of the central nervous system associated with high morbidity and mortality. The etiology of EM in Kazakhstan is not clearly defined, so from February 1, 2017 to January 31, 2018 we conducted hospital-based syndromic surveillance for EM at the Shymkent City Hospital, in the South Kazakhstan region. All consenting inpatients meeting a standard case definition were enrolled. Blood and cerebrospinal fluid (CSF) samples were collected for bacterial culture, and CSF samples were additionally tested by PCR for four bacterial species and three viruses using a cascading algorithm. We enrolled 556 patients. Of these, 494 were of viral etiology (including 4 probable rabies cases), 37 were of bacterial etiology, 19 were of unknown etiology and 6 were not tested. The most commonly identified pathogens included enterovirus (73%, n = 406 cases), herpes simplex virus (12.8%, n = 71), and Neisseria meningitidis (3.8%, n = 21). The incidence rates (IRs) for enteroviral and meningococcal EM were found to be 14.5 and 0.7 per 100,000 persons, respectively. The IR for bacterial EM using both PCR and culture results was 3-5 times higher compared to culture-only results. Antibacterial medicines were used to treat 97.2% (480/494) of virus-associated EM. Incorporation of PCR into routine laboratory diagnostics of EM improves diagnosis, pathogen identification, ensures IRs are not underestimated, and can help avoid unnecessary antibacterial treatment.

Performance of tuberculosis drug susceptibility testing in U.S. laboratories from 1994 to 2008.

We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994 to 2008, implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line antituberculosis drugs used in the United States-isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI)-recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (Bactec), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (chi-square test, P < 0.0001). For resistant strains, overall agreement by methods was 91.3% for AP, 93.0% for Bactec, and 82.6% for MGIT and by drugs was 92.2% for INH, 91.5% for RMP, 79.0% for EMB, and 97.5% for PZA. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time revealed consistent performance even for strains with higher levels of interlaboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug-resistant M. tuberculosis in U.S. laboratories.

Amphotericin B microspheres: a therapeutic approach to minimize toxicity while maintaining antifungal efficacy.

Amphotericin B microsphere formulations with and without addition of polyethylene glycol 2000 in cross-linked bovine serum albumin were prepared. Amphotericin B microspheres were characterized for particle size (<5 microm), zeta potential (approximately 30 mV) and drug interaction by DSC and FTIR and were found to be stable formulations. Drug release profiles for these microspheres revealed that the release was primarily by diffusion. In vitro toxicity as assessed by release of haemoglobin and potassium demonstrated no toxic effect as compared with conventional solution formulation. Antifungal activity in vitro was comparable to solution formulation when tested by broth dilution method.

Pharmacokinetic and biodistribution studies of amphotericin B microspheres.

The pharmacokinetics of Amphotericin B (AmB) from polyethylene glycol 2000 (PEG 2000) entrapped cross-linked bovine serum albumin (BSA) microsphere formulations were investigated and compared with solution formulation. The microsphere preparations were characterized for particle size using electron microscopy, zeta potential and encapsulation efficiency. The microsphere formulations demonstrated a sustained release of AmB for a longer period of time, with no rise in plasma creatinine and potassium levels. The enhanced AmB accumulation in lungs was observed which could be of importance since lungs are the primary target in most fungal infections. The stealth property of submicron cross-linked BSA microspheres in formulations containing PEG 2000 (formulation F-2N) and without PEG 2000 (formulation F-1N) was also evaluated. There was no evidence that microspheres embedded with PEG remained longer in circulation; however, it was noticed that the internalization of formulation F-2N microspheres was delayed when compared with microspheres from formulation F-1N.