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

Abstract

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.

Widespread human exposure to ledanteviruses in Uganda: A population study

“…The findings of the Acute Febrile Illness (AFI) study including the detection of LDV have been reported previously [ 10 , 11 ]. Here we focus on the clinical presentation of the LDV patient.…”

Cross-sectional serosurvey of Leptospira species among slaughter pigs, goats, and sheep in Uganda

“…For East Sub-Saharan Africa, annual morbidity of 91,100 cases per 100,000 population has been reported [6]. In Uganda, Leptospira exposure has been shown in febrile patients from geographically distinct areas [7][8][9][10]. Domestic animals, particularly cattle and pigs are speculated as the source of these human Leptospira exposures [7,8,10], despite evidence of exposure in other main reservoirs such as wildlife [11].…”

“…In Uganda, Leptospira exposure has been shown in febrile patients from geographically distinct areas [7][8][9][10]. Domestic animals, particularly cattle and pigs are speculated as the source of these human Leptospira exposures [7,8,10], despite evidence of exposure in other main reservoirs such as wildlife [11]. This is possible since human-wildlife interactions are less common than interactions with domestic animals.…”

Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia

“…AFS diagnosis requires a comprehensive approach to each patient; the wide-ranging causes require detailed clinical methodologies and the diagnostic tests to support them. Diagnosis and treatment are adversely affected in regions where access to specialized tests is not immediately available [10,11].…”