Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 16;23(1):411.
doi: 10.1186/s12879-023-08335-4.

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

Brian K Kigozi  1   2 , Grishma A Kharod #  3 , Henry Bukenya #  4 , Sean V Shadomy  3 , Dana L Haberling  3 , Robyn A Stoddard  3 , Renee L Galloway  3 , Phionah Tushabe  4 , Annet Nankya  4 , Thomas Nsibambi  4   5 , Edward Katongole Mbidde  4 , Julius J Lutwama  4 , Jamie L Perniciaro  6 , William L Nicholson  7 , William A Bower  3 , Josephine Bwogi #  4 , David D Blaney #  3
Affiliations

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

Brian K Kigozi et al. BMC Infect Dis. .

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.

Keywords: Acute Febrile illness; Arboviral infections; Brucellosis; Leptospirosis; Malaria; Rickettsioses; Typhoid Fever; Uganda.

PubMed Disclaimer

Conflict of interest statement

Authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A map illustrating study clinics of the Uganda AFI prospective study
Fig. 2
Fig. 2
Study profile for participants recruited into the Uganda AFI study, April 2011 to January 2013
Fig. 3
Fig. 3
Clinical presentation during baseline visit of AFI study participants, April 2011 to January 2013
Fig. 4
Fig. 4
a Seasonal occurrence of AFI pathogens at St. Paul’s HC IV, April 2011 to January 2013. CHIKV: Chikungunya virus. HC: Health Centre. TF: Typhoid fever. SFGR: Spotted Fever Group Rickettsia. DENV: Dengue virus. TGR: Typhus Group Rickettsia. WNV: West Nile virus. b Seasonal occurrence of AFI pathogens at Ndejje HC IV, April 2011 to January 2013. CHIKV: Chikungunya virus. HC: Health Centre. TF: Typhoid fever. SFGR: Spotted Fever Group Rickettsia. DENV: Dengue virus. TGR: Typhus Group Rickettsia. WNV: West Nile virus. c Seasonal occurrence of AFI pathogens at Adumi HC IV, April 2011 to January 2013. CHIKV: Chikungunya virus. HC: Health Centre. TF: Typhoid fever. SFGR: Spotted Fever Group Rickettsia. DENV: Dengue virus. TGR: Typhus Group Rickettsia. WNV: West Nile virus
See this image and copyright information in PMC

References

    1. Prasad N, Murdoch DR, Reyburn H, Crump JA. Etiology of severe febrile illness in low- and middle-income countries: a systematic review. PLoS One. 2015;10(6):e0127962. doi: 10.1371/journal.pone.0127962. - DOI - PMC - PubMed
    1. Tun ZM, Moorthy M, Linster M, Su YC, Coker RJ, Ooi EE, et al. Characteristics of acute febrile illness and determinants of illness recovery among adults presenting to Singapore primary care clinics. BMC Infect Dis. 2016;16(1):612. doi: 10.1186/s12879-016-1958-4. - DOI - PMC - PubMed
    1. The World Health Organization . World malaria report. 2022.
    1. Crump JA, Kirk MD. Estimating the Burden of Febrile Illnesses. PLoS Negl Trop Dis. 2015;9(12):e0004040. doi: 10.1371/journal.pntd.0004040. - DOI - PMC - PubMed
    1. Prasad N, Sharples KJ, Murdoch DR, Crump JA. Community prevalence of fever and relationship with malaria among infants and children in low-resource areas. Am J Trop Med Hyg. 2015;93(1):178-80. - PMC - PubMed