Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda.

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Global knowledge gaps in acute febrile illness etiologic investigations: A scoping review.

BACKGROUND: Acute febrile illness (AFI), a common reason for people seeking medical care globally, represents a spectrum of infectious disease etiologies with important variations geographically and by population. There is no standardized approach to conducting AFI etiologic investigations, limiting interpretation of data in a global context. We conducted a scoping review to characterize current AFI research methodologies, identify global research gaps, and provide methodological research standardization recommendations. METHODOLOGY/FINDINGS: Using pre-defined terms, we searched Medline, Embase, and Global Health, for publications from January 1, 2005-December 31, 2017. Publications cited in previously published systematic reviews and an online study repository of non-malarial febrile illness etiologies were also included. We screened abstracts for publications reporting on human infectious disease, aimed at determining AFI etiology using laboratory diagnostics. One-hundred ninety publications underwent full-text review, using a standardized tool to collect data on study characteristics, methodology, and laboratory diagnostics. AFI case definitions between publications varied: use of self-reported fever as part of case definitions (28%, 53/190), fever cut-off value (38·0°C most commonly used: 45%, 85/190), and fever measurement site (axillary most commonly used: 19%, 36/190). Eighty-nine publications (47%) did not include exclusion criteria, and inclusion criteria in 13% (24/190) of publications did not include age group. No publications included study settings in Southern Africa, Micronesia & Polynesia, or Central Asia. We summarized standardized reporting practices, specific to AFI etiologic investigations that would increase inter-study comparability. CONCLUSIONS: Wider implementation of standardized AFI reporting methods, with multi-pathogen disease detection, could improve comparability of study findings, knowledge of the range of AFI etiologies, and their contributions to the global AFI burden. These steps can guide resource allocation, strengthen outbreak detection and response, target prevention efforts, and improve clinical care, especially in resource-limited settings where disease control often relies on empiric treatment. PROSPERO: CRD42016035666.

Postexposure Prophylaxis After Possible Anthrax Exposure: Adherence and Adverse Events.

Anthrax postexposure prophylaxis (PEP) was recommended to 42 people after a laboratory incident that involved potential aerosolization of Bacillus anthracis spores in 2 laboratories at the Centers for Disease Control and Prevention in 2014. At least 31 (74%) individuals who initiated PEP did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. Among the 29 that discontinued the antimicrobial component of PEP, most (38%) individuals discontinued PEP because of their low perceived risk of infection; 9 (31%) individuals discontinued prophylaxis due to PEP-related minor adverse events, and 10% cited both low risk and adverse events as their reason for discontinuation. Most minor adverse events reported were gastrointestinal complaints, and none required medical attention. Individuals taking ciprofloxacin were twice as likely (RR = 2.02, 95% CI = 1.1-3.6) to discontinue antimicrobial prophylaxis when compared to those taking doxycycline. In the event anthrax PEP is recommended, public health messages and patient education materials will need to address potential misconceptions regarding exposure risk and provide information about possible adverse events in order to promote PEP adherence.

Patterns of social support among lymphoma patients considering stem cell transplantation.

There is lack of literature addressing factors that influence the process of care for patients with hematological malignancies. We evaluated the forms of social support available for patients with relapsed lymphoma considering stem cell transplantation and examined the influence of support on treatment delay. Data were collected from 119 patients with relapsed lymphoma using a questionnaire to capture sociodemographic information and emotional, informational, and instrumental forms of social support. Sixty-four percent of the patients were married, 56% had children over 18 years of age, 43% were employed, and 72% had private health insurance. Family members formed a major source of emotional support (83%), while 47% of patients considered personal prayers to be important. While 79% of patients received clinical support from nurses, few received formal group support or formal peer support (6.7% and 1.7% respectively). Support from extended family and peer groups reduced the likelihood of treatment delays. The potential benefits of peer group support should be reinforced for patients considering transplantation given how infrequent this form of social support is utilized and its positive impact on the process of care. Future studies should test the impact of social support on health outcomes especially among the underserved population.