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Pathology152 papers

Meningitis caused by Coxiella burnetii

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Pathophysiology

Being an intracellular pathogen, Coxiella burnetii relies heavily on cell-mediated immunity (CMI). Cytokines such as interferon-gamma (IFNγ), a pro-inflammatory cytokine, and interleukin 10 (IL10), with its dual role in both anti-inflammatory responses and stimulation of humoral immunity, are essential for managing infection, with dysregulation potentially linked to chronic disease progression in humans (O'Shannessy et al., 2026).

Epidemiology

A study conducted in the northern and southern regions of Maranhão State, Brazil, assessed C. burnetii infections in small ruminants, revealing increased exposure frequencies and shedding patterns through vaginal swabs, milk, and faeces, underscoring regional prevalence and transmission dynamics (PMID: 41631523).

The study emphasized the role of environmental contamination in Q fever transmission, noting that assessing and managing farm environments is crucial for controlling infections (PMID: 41631523).

A study in Kenya reported seroprevalence estimates ranging from 5% to 46% in humans, indicating substantial endemic presence of Coxiella burnetii across different livestock species such as goats, sheep, cattle, and camels (Mutisya et al., 2025; PMID: 41105740).

Risk factors for Coxiella burnetii infection among humans in Kenya include direct involvement in animal handling, herding activities, illiteracy, and keeping livestock, especially in rural settings (Mutisya et al., 2025; PMID: 41105740).

A first survey on seroprevalence of Coxiella burnetii in human patients from 2015 to 2024 in Sardinia, Italy, reveals persistent transmission risks linked to environmental contamination and animal reservoirs, underscoring the continuous zoonotic threat (PMID: 40872301).

The study indicates that in livestock, Coxiella burnetii infection often manifests clinically through reproductive issues such as abortions and stillbirths, highlighting its substantial epidemiological significance in animal health. [PMID: 35511819]

The study utilized latent class models (LCMs) to evaluate the diagnostic performances of three commercially available ELISA tests for detecting Coxiella burnetii-specific antibodies in domestic ruminants, highlighting the importance of understanding test characteristics like sensitivity and specificity for accurate seroprevalence assessments (PMID: 33853678).

Clinical Presentation

Although many infections in ruminants like sheep and goats are asymptomatic, these animals can excrete C. burnetii through milk, faeces, and vaginal discharge, contributing to environmental contamination and human risk (PMID: 41631523).

The acute form of Q fever, caused by Coxiella burnetii, manifests with symptoms such as influenza-like illness, hepatitis, headache associated with photophobia, and atypical pneumonia (Mutisya et al., 2025; PMID: 41105740).

Clinical presentations of acute Q fever include flu-like illness, pneumonia, and hepatitis, which can be non-specific and easily confused with other conditions, emphasizing the need for precise diagnostic testing (PMID: 40872301).

Apart from reproductive complications, infected cattle may exhibit clinical signs such as anorexia, suggesting a broader spectrum of clinical presentations in infected animals. [PMID: 35511819]

Primary human infections with C. burnetii are frequently asymptomatic, affecting about 60% of cases, complicating clinical diagnosis (Million et al., 2016; cited in Vourvidis et al., 2021; PMID: 32790038).

Diagnosis

Optimization of cytokine recall assays (CRAs) for whole-blood samples has been achieved for detecting interferon-gamma (IFNγ) and interleukin 10 (IL10) responses to Coxiella burnetii antigens in cattle, suggesting these assays could serve as a diagnostic tool for identifying infections (O'Shannessy et al., 2026).

Diagnosis of Q fever relies heavily on serological tests such as the indirect immunofluorescent assay (IFI), which is considered the gold standard due to its high sensitivity and specificity in detecting IgG and IgM antibodies against Coxiella burnetii (PMID: 40872301).

Meletis E et al. (2022) evaluated the sensitivity and specificity of three diagnostic tests for Coxiella burnetii infection in cattle and buffaloes using Bayesian latent class analysis, emphasizing the need for multi-modal testing strategies for accurate diagnosis. [PMID: 35511819]

Due to the absence of a gold standard test for serological diagnosis of Coxiella burnetii infection in animals, latent class models (LCMs) were employed to assess the diagnostic performances of ELISA tests, thereby offering a practical approach to estimating true sensitivity and specificity (PMID: 33853678).

Previous studies on seroprevalence often assumed perfect sensitivity and specificity for ELISA tests without validating these assumptions, potentially leading to overestimations or underestimations. LCMs address this issue by providing a more nuanced evaluation of test performance (PMID: 33853678).

Serological tests for diagnosing Coxiella burnetii infections include ELISA, which demonstrates slightly higher sensitivity than IFA for small ruminants, though IFA is considered better for detecting IgG and IgM in goat sera (Rousset et al., 2007; Muleme et al., 2016; PMID: 33645900).

Management

Given the role of environmental contamination and animal excretions in transmission, managing farm environments and regularly testing excretions (milk, faeces, vaginal swabs) are critical components of controlling Q fever outbreaks (PMID: 41631523).

The optimization of cytokine recall assays (CRAs) for detecting specific cytokine responses in cattle infected with Coxiella burnetii could provide insights into therapeutic targets and management strategies for chronic infections (O'Shannessy et al., 2026).

Given the high endemicity of Coxiella burnetii, enhancing surveillance systems and coordinated control measures across animal and human health sectors is crucial for effective management (Mutisya et al., 2025; PMID: 41105740).

Given that C. burnetii can be shed through multiple routes including milk, vaginal mucus, and feces, implementing multi-faceted testing protocols is essential for managing infections in livestock effectively. [PMID: 35511819]

Enhanced diagnostic accuracy achieved through the application of latent class models to ELISA tests can support more effective surveillance and management strategies for Coxiella burnetii infections in domestic ruminants (PMID: 33853678).

Prognosis & Follow-up

Studies indicate that chronically infected patients exhibit elevated spontaneous release of interleukin 10 (IL10) from peripheral blood mononuclear cells (PBMCs), which could serve as a biomarker for monitoring disease progression in Coxiella burnetii infections (O'Shannessy et al., 2026).

Special Populations

Unpublished data indicate that bovine infertility cases in Nepal frequently involve sub-clinical mastitis and brucellosis, suggesting a possible association with Coxiella burnetii infection, despite limited direct evaluation (corresponding author unpublished data; PMID: 33645900).

References

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