Evidence of Coxiella burnetii and Bartonella species infections among patients with persistent febrile illness in four low- and middle-income countries

Carl Boodman; Sophie Edouard; Johan van Griensven; Kanika Deshpande Koirala; Basudha Khanal; Suman Rijal; Narayan Raj Bhattarai; Sayda El Safi; Thong Phe; Kruy Lim; Pascal Lutumba; François Chappuis; Cédric P Yansouni; Barbara Barbé; Marjan van Esbroeck; Tine Verdonck; Marleen Boelaert; Pierre-Édouard Fournier; Emmanuel Bottieau

doi:10.1016/j.cmi.2025.04.038

Evidence of Coxiella burnetii and Bartonella species infections among patients with persistent febrile illness in four low- and middle-income countries

Clin Microbiol Infect. 2025 May 6:S1198-743X(25)00220-4. doi: 10.1016/j.cmi.2025.04.038. Online ahead of print.

Authors

Carl Boodman¹, Sophie Edouard², Johan van Griensven³, Kanika Deshpande Koirala⁴, Basudha Khanal⁴, Suman Rijal⁴, Narayan Raj Bhattarai⁴, Sayda El Safi⁵, Thong Phe⁶, Kruy Lim⁶, Pascal Lutumba⁷, François Chappuis⁸, Cédric P Yansouni⁹, Barbara Barbé³, Marjan van Esbroeck³, Tine Verdonck³, Marleen Boelaert³, Pierre-Édouard Fournier², Emmanuel Bottieau³

Affiliations

¹ Division of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Medical Sciences, University of Antwerp, Antwerp, Belgium. Electronic address: cboodman@itg.be.
² Institut Hospitalo-Universitaire en Maladies infectieuses (IHU-Méditerranée Infection), Marseille, France; French Reference Center for Rickettsioses, Q Fever And Bartonelloses, IHU-Méditerranée Infection, Marseille, France.
³ Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
⁴ Internal medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal.
⁵ Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
⁶ Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia.
⁷ Infectious diseases, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo.
⁸ Division of Tropical and Humanitarian Medicine, Geneva University Hospitals (HUG), Geneva, Switzerland.
⁹ Divisions of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montréal, Québec, Canada; JD MacLean Centre for Tropical and Geographic Medicine, McGill University, Montréal, Québec, Canada.

PMID: 40339791
DOI: 10.1016/j.cmi.2025.04.038

Abstract

Objectives: This study investigated whether infections due to Coxiella burnetii, Bartonella species or Tropheryma whipplei could be identified among biobanked samples associated with persistent fever in four low- or middle-income countries.

Methods: The NIDIAG consortium ("Better DIAGnosis of Neglected Infectious Diseases") prospectively investigated in 2013-2014 the aetiological spectrum of 1922 patients with persistent febrile illness (fever greater than 7 days) in Cambodia, Nepal, Sudan, and the Democratic Republic of Congo (DRC). Our study retrospectively tested serum and blood samples from the 745 patients (38.8%) who remained without an identified cause of fever. Indirect immunofluorescent antibody assays (IFA) were performed (except in the DRC) to assess immunoglobulin response to C. burnetii and Bartonella antigens. DNA extracts from whole blood samples were tested for C. burnetii, Bartonella genus, B. quintana, B. henselae and T. whipplei by qPCR.

Results: Evidence of infection with C. burnetii or Bartonella sp. was found in 124 persistent fever cases (16.6%). IFA for IgG to C. burnetii phase I and II antigens identified 59 (7.9%) positive sera: 31/333 (9.3%) from Sudan, 16/278 (5.8%) from Nepal, and 12/54 (22.2%) from Cambodia. Eight individuals had C. burnetii anti-phase I IgG titres ≥ 1:800. Bartonella IFA identified 60 (8.1%) IgG positive sera, with 49/278 (17.6%) positive samples from Nepal, 7/333 (2.1%) from Sudan and 4/54 (7.4%) from Cambodia. One serum from Sudan had anti-Bartonella IgG titres of 1:800. C. burnetii DNA was detected from blood in 3 individuals from Sudan and one individual from the DRC, whereas B. quintana DNA was present in a blood sample from a Nepalese individual. All qPCR tests for T. whipplei were negative.

Discussion: Direct and indirect evidence of C. burnetii or Bartonella sp. infections was observed in persistent fever cases. Further studies are necessary to elucidate the burden of these diseases in low- or middle-income countries.

Keywords: Bacteraemia; Bartonellosis; Fever; Low-resource setting; PCR; Q fever; Serology; Whipple's disease.