AFIRE (INA-101) : The Etiology of Acute Febrile Illness Requiring Hospitalization

ClinicalTrials.gov: NCT02763462
Collaborator: NIAID -HIH
Status: Completed

https://clinicaltrials.gov/study/NCT02763462

The AFIRE prospective observational cohort study enrolled 1,492 acute febrile patients (864 adults, 628 children) requiring hospitalization from July 2013 to June 2016. Inclusion criteria consisted of axillary body temperature ≥38˚C, ≥1 year of age, and hospitalization within the past 24 hours. Demographic, clinical, and laboratory data, including hematology results, were collected at enrollment, once during days 14-28, and three months after enrollment. Blood and other biological specimens were collected at each study visit, and each participant had aerobic blood cultures performed at enrollment. Microbial etiologies were identified in 1,003 (67.5%) participants and included dengue virus (467, 46.6%), Salmonella spp. (103, 10.3%), Rickettsia spp. (103, 10.3%), influenza virus (68, 6.8%), Leptospira spp. (44, 4.4%), chikungunya virus (37, 3.7%), and others.

AFIRE SITES Ver 2

Associated Publications:

  • An observational prospective cohort study of the epidemiology of hospitalized patients with acute febrile illness in Indonesia. PLoS Negl Trop Dis. 2020 Jan 10;14(1):e0007927. doi: 10.1371/journal.pntd.0007927. PMID: 31923174.
  • The characteristics of bacteremia among patients with acute febrile illness requiring hospitalization in Indonesia. PLoS One. 2022 Sep 8;17(9):e0273414.         doi: 10.1371/journal.pone.0273414. PMID: 36074783. 
  • Underdiagnoses of Rickettsia in patients hospitalized with acute fever in Indonesia: observational study results. BMC Infect Dis. 2020 May 24;20(1):364.      doi: 10.1186/s12879-020-05057-9. PMID: 32448167. 
  • Dengue viral infection in Indonesia: Epidemiology, diagnostic challenges, and mutations from an observational cohort study. PLoS Negl Trop Dis. 2019 Oct 21;13(10):e0007785. doi: 10.1371/journal.pntd.0007785. PMID: 31634352. 
  • Comparison of Commercial Enzyme-Linked Immunosorbent Assay and Immunofluorescence Assay for Diagnosis of Acute Rickettsia typhi Infections. Vector-Borne, and Zoonotic Diseases. doi: 
  • Leptospirosis in Indonesia: Diagnostic challenges associated with atypical manifestations and limited laboratory capacity. BMC.
  • “Chikungunya in Indonesia: Epidemiology and diagnostic challenges” PLOS NTDs
  • Etiologies of severe acute respiratory infection (SARI) and misdiagnosis of influenza in Indonesia, 2013-2016. Influenza and Other Respiratory Viruses
  • Case report: two confirmed cases of human Seoul virus infections in Indonesia BMC Infect Dis.
  • Prevalence of HIV Infection and Resistance Mutations in Patients Hospitalized for Febrile Illness in Indonesia. Am J Trop Med Hyg. 
  • Clinical characteristics of enteric fever and performance of TUBEX TF IgM test in Indonesian hospitals PLOS NTDs

Associated Biorepository

Pathogen

(Cellular & Coinfection)

Baseline Day 14-28 Month 3
Buffy coat Plasma Urine NS swab Plasma Urine Plasma Urine
Acinetobacter baumanii 7 7 N/A 1 6 N/A 5 1
Amoeba 12 10 1 N/A 11 N/A 10 N/A

Ascaris lumbricoides

& Trichiuris trichiura

2 2 2 N/A 1 N/A 1 N/A

Bordetella pertusis

& Streptococcus pneumoniae

1 1 N/A 1 1 N/A 1 N/A
Escherichia coli 14 19 7 1 15 1 16 1
Klebsiella pneumoniae 13 12 1 2 10 N/A 9 N/A
Leptospira spp. 35 41 6 1 35 N/A 35 1

Moraxella catharrhalis

& Influenza B  virus

1 1 N/A N/A 1 N/A N/A N/A
Mycobacterium leprae 2 2 N/A N/A 2 N/A 1 N/A
Mycobacterium tuberculosis 18 19 2 N/A 11 N/A 11 N/A
Mycoplasma pneumoniae 1 1 N/A N/A 1 N/A 1 N/A
Plasmodium spp. 2 2 N/A N/A 1 N/A 1 N/A
Pseudomonas aeruginosa 7 8 1 NA 4 NA 5 NA
Rickettsia felis 1 1 N/A N/A 1 N/A 1 N/A
Rickettsia typhi 87 96 5 1 76 N/A 71 N/A
Salmonella spp. 54 91 9 2 78 2 67 N/A
Streptococcus pneumoniae 16 18 4 N/A 16 N/A 13 N/A
Toxoplasma gondii 1 1 N/A N/A 1 N/A 1 N/A
Other Bacteria 7 9 1 N/A 7 N/A 6 N/A
Pathogen (Viral) Baseline Day 14-28 Month 3
Buffy coat Plasma Urine NS swab Plasma Urine Plasma Urine
Adenovirus 1 1 N/A 1 1 N/A 1 N/A
Chikungunya virus 31 37 4 1 39 N/A 35 N/A
Coronavirus OC43 1 1 N/A 1 1 N/A 1 N/A
Dengue virus 375 415 19 11 318 N/A 294 N/A
Enterovirus 1 1 N/A 1 1 N/A 1 N/A
Hepatitis A Virus 3 4 N/A N/A 4 N/A 4 N/A
Human Herpes Virus  6 5 8 1 1 5 N/A 6 N/A
Human Metapneumovirus N/A 1 N/A 1 1 N/A 1 N/A
Influenza A virus 32 36 N/A 5 32 N/A 36 N/A
Influenza B virus 18 19 1 3 18 N/A 17 N/A
Measles virus 8 10 N/A 1 10 N/A 9 N/A
Respiratory Syncytial Virus 8 10 N/A 3 10 N/A 9 N/A
Seoul virus 2 2 N/A N/A 2 N/A 2 N/A
Unidentified 376 442 38 13 331 13 270 6
Other Categories  Baseline  Day 14-28 Month 3
Buffy coat  Plas ma  Urine  NS swab  Plas ma  Urine  Plas ma  Urine 
Adult 761 831 73 22 643 14 582 7
Paediatric 368 494 35 30 397 5 356 3
Comorbidities* 327 383 40 22 302 12 261 7
Fatal cases 73 81 10 3 28 1 6 0