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

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

Research output: Contribution to journal › Article › peer-review

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 (LMICs).

METHODS: The NIDIAG consortium prospectively investigated in 2013-2014 the etiological 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 Coxiella burnetii, Bartonella genus, Bartonella quintana, Bartonella henselae and Tropheryma whipplei by quantitative polymerase chain reaction (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 titers ≥ 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 titers 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.

CONCLUSIONS: 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 LMICs.

Original language	English
Journal	Clinical Microbiology and Infection
ISSN	1198-743X
DOIs	https://doi.org/10.1016/j.cmi.2025.04.038
Publication status	E-pub ahead of print - 6-May-2025

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Boodman, C., Edouard, S., van Griensven, J., Koirala, K. D., Khanal, B., Rijal, S., Bhattarai, N. R., El Safi, S., Phe, T., Lim, K., Lutumba, P., Chappuis, F., Yansouni, C. P., Barbé, B., van Esbroeck, M., Verdonck, T., Boelaert, M., Fournier, P.-É., & Bottieau, E. (2025). Evidence of Coxiella burnetii and Bartonella species infections among patients with persistent febrile illness in four low- and middle-income countries. Clinical Microbiology and Infection. Advance online publication. https://doi.org/10.1016/j.cmi.2025.04.038

@article{5503782fa4ea458c9a00a56e649a7650,

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

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 (LMICs).METHODS: The NIDIAG consortium prospectively investigated in 2013-2014 the etiological 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 Coxiella burnetii, Bartonella genus, Bartonella quintana, Bartonella henselae and Tropheryma whipplei by quantitative polymerase chain reaction (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 titers ≥ 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 titers 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.CONCLUSIONS: 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 LMICs.",

author = "Carl Boodman and Sophie Edouard and {van Griensven}, Johan and Koirala, {Kanika Deshpande} and Basudha Khanal and Suman Rijal and Bhattarai, {Narayan Raj} and {El Safi}, Sayda and Thong Phe and Kruy Lim and Pascal Lutumba and Fran{\c c}ois Chappuis and Yansouni, {C{\'e}dric P} and Barbara Barb{\'e} and {van Esbroeck}, Marjan and Tine Verdonck and Marleen Boelaert and Pierre-{\'E}douard Fournier and Emmanuel Bottieau",

note = "Copyright {\textcopyright} 2025. Published by Elsevier Ltd.",

year = "2025",

month = may,

day = "6",

doi = "10.1016/j.cmi.2025.04.038",

language = "English",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier",

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Boodman, C, Edouard, S, van Griensven, J, Koirala, KD, Khanal, B, Rijal, S, Bhattarai, NR, El Safi, S, Phe, T, Lim, K, Lutumba, P, Chappuis, F, Yansouni, CP, Barbé, B , van Esbroeck, M , Verdonck, T, Boelaert, M, Fournier, P-É & Bottieau, E 2025, 'Evidence of Coxiella burnetii and Bartonella species infections among patients with persistent febrile illness in four low- and middle-income countries', Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2025.04.038

TY - JOUR

T1 - Evidence of Coxiella burnetii and Bartonella species infections among patients with persistent febrile illness in four low- and middle-income countries

AU - Boodman, Carl

AU - Edouard, Sophie

AU - van Griensven, Johan

AU - Koirala, Kanika Deshpande

AU - Khanal, Basudha

AU - Rijal, Suman

AU - Bhattarai, Narayan Raj

AU - El Safi, Sayda

AU - Phe, Thong

AU - Lim, Kruy

AU - Lutumba, Pascal

AU - Chappuis, François

AU - Yansouni, Cédric P

AU - Barbé, Barbara

AU - van Esbroeck, Marjan

AU - Verdonck, Tine

AU - Boelaert, Marleen

AU - Fournier, Pierre-Édouard

AU - Bottieau, Emmanuel

PY - 2025/5/6

Y1 - 2025/5/6

N2 - 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 (LMICs).METHODS: The NIDIAG consortium prospectively investigated in 2013-2014 the etiological 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 Coxiella burnetii, Bartonella genus, Bartonella quintana, Bartonella henselae and Tropheryma whipplei by quantitative polymerase chain reaction (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 titers ≥ 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 titers 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.CONCLUSIONS: 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 LMICs.

AB - 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 (LMICs).METHODS: The NIDIAG consortium prospectively investigated in 2013-2014 the etiological 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 Coxiella burnetii, Bartonella genus, Bartonella quintana, Bartonella henselae and Tropheryma whipplei by quantitative polymerase chain reaction (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 titers ≥ 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 titers 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.CONCLUSIONS: 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 LMICs.

U2 - 10.1016/j.cmi.2025.04.038

DO - 10.1016/j.cmi.2025.04.038

M3 - Article

C2 - 40339791

SN - 1198-743X

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

ER -