Coxiella burnetii and Bartonella species serology of febrile patients with an established infectious or inflammatory diagnosis in Sudan, Nepal, and Cambodia

ABSTRACT Coxiella burnetii and Bartonella species cause febrile illness and infective endocarditis in low- and middle-income countries (LMICs). This study investigated whether seropositivity to C. burnetii or Bartonella could be detected among patients with persistent fever for which an infectious or inflammatory etiological diagnosis had been previously established in three LMICs. Our study tested sera from Cambodian, Nepalese, and Sudanese participants using indirect immunofluorescent antibody assays (IFA) for C. burnetii and Bartonella . Seropositivity rates for both pathogens were assessed across tropical and inflammatory etiologies of fever and compared to ubiquitous bacterial infections considered as a “reference group,” as they were not expected to cause serologic cross-reactivity. A total of 1,313 individuals underwent IFA, including 560/1,313 (42.7%) from Sudan, 432 (32.9%) from Nepal, and 321 (24.5%) from Cambodia. Overall, 57 (4.3%) and 60 (4.6%) participants tested positive for C. burnetii and Bartonella species, respectively. Forty-four (3.4%) individuals tested positive for both C. burnetii and Bartonella species (75.4% positive agreement). C. burnetii positivity did not differ significantly between the three countries ( P = 0.44), while Bartonella seropositivity was predominantly identified in Nepal ( P < 0.001). Compared to the reference group, C. burnetii and Bartonella seropositivity were more common among participants with visceral leishmaniasis, P. falciparum malaria, leptospirosis, brucellosis, scrub typhus, and systemic lupus erythematosus (SLE), though only statistically significant for the latter two diagnoses. Further studies are necessary to investigate C. burnetii and Bartonella seropositivity in LMICs and to disentangle cross-reactivity, previous infection, or co-infection. IMPORTANCE Coxiella burnetii and Bartonella spp. are important but under-recognized causes of febrile illness and infective endocarditis in low- and middle-income countries (LMICs). This study evaluated the seroprevalence of these pathogens among patients with confirmed causes of persistent fever in Sudan, Nepal, and Cambodia. Despite the diagnostic utility of serologic testing for these infections, its performance in LMICs—where co-infections and background seropositivity are common—remains poorly characterized. The findings suggest notable seropositivity for C. burnetii and Bartonella among patients with a set of tropical and inflammatory diagnoses, including visceral leishmaniasis, Plasmodium falciparum malaria, leptospirosis, brucellosis, scrub typhus, and systemic lupus erythematosus. These results highlight the potential for cross-reactivity and underscore the need for context-specific validation. Enhanced understanding of serologic test characteristics is essential for accurate diagnosis in resource-limited settings.