Fever Diagnostics Research Articles

Field evaluation of validity and feasibility of Pan-Lassa rapid diagnostic test for Lassa fever in Abakaliki, Nigeria: a prospective diagnostic accuracy study

Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria. We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity. Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read. The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings. Médecins Sans Frontières.

Analysis of Q Fever Incidence in the Russian Federation Between 1957 and 2019

Objective of the study was to analyze the long-term incidence of Q fever in the Russian Federation, to recommend approaches to improve epizootiological and epidemiological surveillance of this infection, taking into account the current state of laboratory diagnostics and monitoring of foci.Materials and methods. A retrospective epidemiological analysis of the Q fever incidence using the data contained in Form No 2 of the state statistical report «Information on infectious and parasitic diseases» was conducted in the Russian Federation for the period of 1957– 2019, by the Federal Districts (FD) and administrative territories, and based on the results of the research of the Reference Center for Rickettsioses of the Omsk Research Institute of Natural Focal Infections.Results and discussion. Between 1957 and 2019, 13 836 cases of Q fever were officially registered in the Russian Federation. The maximum value of the morbidity rate per 100 thousand of the population was registered in 1957 (1.0 0/0000), the minimum one – in 2008 (0.01 0/0000). From 1997 to 2019, out of 2672 registered in 24 entities of the Russian Federation cases of Q fever, 2224 (83.20 %) occurred in the Southern FD with 2106 (78.8 %) cases in the Astrakhan Region. In the Stavropol Territory of the North Caucasus FD, 173 (6.47 %) cases of the disease were detected. 112 (4.19 %) cases were registered in the Central FD, with the maximum number in the Voronezh Region (82). In the Volga FD, 81 (3.03 %) cases were identified, 54 of which in the Ulyanovsk Region. 42 (1.61 %) cases of the disease were registered in the North-Western FD, 33 – in the Leningrad Region and St. Petersburg. In the Siberian FD, 39 (1.46 %) cases of Q fever were reported, 24 were diagnosed in the Novosibirsk Region. In the Ural FD, 1 (0.04 %) case of infection was detected. In the Far Eastern FD, there is no registration of Q fever. Presented are medical products for Q fever diagnostics authorized in Russia. Sanitation of the foci among farm animals should be carried out in accordance with the current sanitary-epidemiological and veterinary-sanitary rules.

Circle-to-circle amplification coupled with microfluidic affinity chromatography enrichment for in vitro molecular diagnostics of Zika fever and analysis of anti-flaviviral drug efficacy

Sensitive viral diagnostic methods are increasingly in demand to tackle emerging epidemics. The Zika virus (ZIKV) is particularly relevant in tropical resource limited settings (RLS) and is associated with intermittent epidemics such as the recent 2016 ZIKV outbreak in South America, wherein Zika fever was classified by WHO as a public health emergency of international concern. Thus, there is an urgent need for widespread Zika fever diagnostics and efficient drug therapies. ZIKV diagnostics are typically performed using RT-qPCR in centralized laboratories. While extremely sensitive, RT-qPCR requires rapid heating-cooling cycles, combined with continuous fluorescence measurements to allow quantification, implying high costs and limiting availability of molecular diagnostics in RLS. Here, we report isothermal amplification of ZIKV cDNA using padlock probes followed by two rounds of Rolling Circle Amplification (RCA), termed as circle-to-circle amplification (C2CA), combined with a microfluidic affinity chromatography enrichment (μACE) platform. This platform allowed the detection of <17 vRNA copies per reaction mixture, equivalent to ∼3 aM, showed a positive correlation with RT-qPCR in both average (r = 0.80) and discrete (r = 0.95) signal modes, and was validated for drug efficiency tests using in vitro infected peripheral blood mononuclear cells from 3 healthy donors. This performance shows significant promise towards highly sensitive, albeit simple and cost-effective point-of-care viral diagnostics.

Analysis of recombinant proteins for Q fever diagnostics

Serology is essential for Q fever diagnostics, a disease caused by the bacterial pathogen Coxiella burnetii. The gold standard test is an immunofluorescence assay utilizing whole cell antigens, which are both dangerous and laborious to produce. Complexities of the antigen coupled with the subjective nature of the assay lead to decreased uniformity of test results and underscore the need for improved methodologies. Thirty-three C. burnetii proteins, previously identified as immunoreactive, were screened for reactivity to naturally infected goat serum. Based on reactivity, 10 proteins were analyzed in a secondary screen against human serum from healthy donors. Assay sensitivity and specificity ranged from 21 to 71% and 90 to 100%, respectively. Three promising antigens were identified based on receiver operating characteristic curve analysis (CBU_1718, CBU_0307, and CBU_1398). Five multiplex assays failed to outperform the individual proteins, with sensitivities and specificities ranging from 29 to 57% and 90 to 100%, respectively. Truncating the top antigen, CBU_1718, had no effect on specificity (90%); yet sensitivity decreased dramatically (71% to 21%). Through this study, we have expanded the subset of C. burnetii immunoreactive proteins validated by enzyme-linked immunosorbent assay and demonstrate the effect of novel antigen combinations and protein truncations on assay performance.

The Current Status of Enteric Fever Diagnostics and Implications for Disease Control.

Enteric (typhoid) fever remains a problem in low- and middle-income countries that lack the infrastructure to maintain sanitation and where inadequate diagnostic methods have restricted our ability to identify and control the disease more effectively. As we move into a period of potential disease elimination through the introduction of typhoid conjugate vaccine (TCV), we again need to reconsider the role of typhoid diagnostics in how they can aid in facilitating disease control. Recent technological advances, including serology, transcriptomics, and metabolomics, have provided new insights into how we can detect signatures of invasive Salmonella organisms interacting with the host during infection. Many of these new techniques exhibit potential that could be further explored with the aim of creating a new enteric fever diagnostic to work in conjunction with TCV. We need a sustained effort within the enteric fever field to accelerate, validate, and ultimately introduce 1 (or more) of these methods to facilitate the disease control initiative. The window of opportunity is still open, but we need to recognize the need for communication with other research areas and commercial organizations to assist in the progression of these diagnostic approaches. The elimination of enteric fever is now becoming a real possibility, but new diagnostics need to be part of the equation and factored into future calculations for disease control.

Rickettsial Diseases: Not Uncommon Causes of Acute Febrile Illness in India.

Rickettsial diseases (RDs) are major under-diagnosed causes of arthropod borne acute febrile illness (AFI) presenting with a range of symptoms from mild self-limiting fever to fatal sepsis. The spotted fever group (SFG) and typhus group (TG) are major RDs, which are commonly caused by Rickettsia conorii and Rickettsia typhi, respectively. The limited availability and role of serological tests in the acute phase of illness warrants rapid reliable molecular methods for diagnosis and epidemiological studies. Two hundred patients with AFI in whom the routine fever diagnostics were negative, were enrolled over a period of two months (April 2019 to May 2019). DNA was extracted and in-house nested PCR using primers specific for both SPG and TG pathogens was used. The positive amplified products were sequenced for species identification and phylogenetic analysis was performed using MEGA 7.0.14 software (iGEM, Temple University, Philadelphia, PA 19122, USA). The demographic details of the RD cases were documented. The prevalence of RD among AFI cases was 7% (14/200); SFG and TG were identified as the cause in 4% and 3% of AFI cases, respectively. The median age of the RD cases was 22 years (range 2–65). The median duration of fever was 3 days (range 1–12). The RD cases presented with respiratory symptoms or signs (44.44%), jaundice (22.22%), abdominal pain (22.22%), diarrhea (22.22), vesicular rash (11.11%), vomiting (11.11%), loss of appetite (11.11%), headache (11.11%), leukocytosis (88.88% with mean count 22,750/mm3), and thrombocytopenia (33.33%). The cases were treated empirically with piperacillin-tazobactam (66.66%), clindamycin (44.44%), cefotaxime (33.33%), meropenem (33.33%), metronidazole (33.33%), doxycycline (22.22%), azithromycin (22.22%), ceftriaxone (11.11%), and amoxicillin-clavulanic acid (11.11%). The mortality among the RD cases was 11.11%. The present pilot study shows that RD is not an uncommon cause of AFI in north India. The febrile episodes are usually transient, not severe and associated with heterogenous clinical presentation without documented history of tick exposure in the hospitalized patients. The transient, non-severe, febrile illness could be due to transient rickettsemia resulting from empirical antimicrobial therapy as the rickettsial organisms are expected to be more susceptible to higher doses of β-lactam antibiotics. The study emphasizes the molecular method as a useful tool to identify rickettsial etiology in AFI.

Typhoid Fever Diagnosis in Endemic Countries: A Clog in the Wheel of Progress?

Typhoid fever causes significant morbidity and mortality in developing countries, with inaccurate estimates in some countries affected, especially those situated in Sub-Saharan Africa. Disease burden assessment is limited by lack of a high degree of sensitivity and specificity by many current rapid diagnostic tests. Some of the new technologies, such as PCR and proteomics, may also be useful but are difficult for low-resource settings to apply as point-of-care diagnostics. Weak laboratory surveillance systems may also contribute to the spread of multidrug resistant Salmonella serovar Typhi across endemic areas. In addition, most typhoid-endemic countries employ serological tests that have low sensitivity and specificity making diagnosis unreliable. Here we review currently available typhoid fever diagnostics, and advances in serodiagnosis of S. Typhi.

Assessment and Translation of the Antibody-in-Lymphocyte Supernatant (ALS) Assay to Improve the Diagnosis of Enteric Fever in Two Controlled Human Infection Models and an Endemic Area of Nepal.

New diagnostic tests for enteric fever are urgently needed to assist with timely antimicrobial treatment of patients and to measure the efficacy of prevention measures such as vaccination. In a novel translational approach, here we use two recently developed controlled human infection models (CHIM) of enteric fever to evaluate an antibody-in-lymphocyte supernatant (ALS) assay, which can detect recent IgA antibody production by circulating B cells in ex vivo mononuclear cell culture. We calculated the discriminative ability of the ALS assay to distinguish diagnosed cases in the two CHIM studies in Oxford, prior to evaluating blood culture-confirmed diagnoses of patients presenting with fever to hospital in an endemic areas of Kathmandu, Nepal. Antibody responses to membrane preparations and lipopolysaccharide provided good sensitivity (>90%) for diagnosing systemic infection after oral challenge with Salmonella Typhi or S. Paratyphi A. Assay specificity was moderate (~60%) due to imperfect sensitivity of blood culture as the reference standard and likely unrecognized subclinical infection. These findings were augmented through the translation of the assay into the endemic setting in Nepal. Anti-MP IgA responses again exhibited good sensitivity (86%) but poor specificity (51%) for detecting blood culture-confirmed enteric fever cases (ROC AUC 0.79, 95%CI 0.70–0.88). Patients with anti-MP IgA ALS titers in the upper quartile exhibited a clinical syndrome synonymous with enteric fever. While better reference standards are need to assess enteric fever diagnostics, routine use of this ALS assay could be used to rule out infection and has the potential to double the laboratory detection rate of enteric fever in this setting over blood culture alone.

Considerations for an Access-Centered Design of the Fever Thermometer in Low-Resource Settings: A Literature Review

BackgroundThe lack of adequate information about fever in low-resource settings, its unreliable self-assessment, and poor diagnostic practices may result in delayed care and under-or-overdiagnosis of diseases such as malaria. The mismatches of existing fever thermometers in the context of use imply that the diagnostic tools and connected services need to be studied further to address the challenges of fever-related illnesses and their diagnostics.ObjectiveThis study aims to inform a product-service system approach to design a reliable and accessible fever thermometer and connected services, as well as contribute to the identification of innovative opportunities to improve health care in low-resource settings.MethodsTo determine what factors impede febrile people seeking health care to access adequate fever diagnostics, a literature search was conducted in Google Scholar and PubMed with relevant keywords. Next, these factors were combined with a patient journey model to design a new product-service system for fever diagnostics in low-resource settings.ResultsIn total, 37 articles were reviewed. The five As framework was used to categorize the identified barriers. The results indicate that there is a poor distribution of reliable fever diagnostic practices among remote communities. This paper speaks to the global public health and design communities. Three complementary considerations are discussed that support the idea of a more holistic approach to the design of fever diagnostics: (1) understanding of the fever diagnostics patient journey, (2) identifying user groups of the thermometers in a specific health care system, and (3) assessing different needs and interests of the different users.ConclusionsAccess to basic, primary health care may be enhanced with better information and technology design made through the involvement of system users.

First isolation of Coxiella burnetii from clinical material by cell-free medium (ACCM2).

A disadvantage in Q fever diagnostics and research is the insensitive and difficult culture of Coxiella burnetii. This intracellular organism can only be isolated using embryonated eggs, animal hosts, or mammalian cell culture. In consequence, it has only been possible to isolate a few strains from human patients. Here, we describe the first isolation of C. burnetii from a clinical specimen using the recently developed cell-free medium acidified citrate cysteine medium 2 (ACCM2). We screened the sera of 217 patients who had undergone valvular transplantation but detected one serum with an antibody constellation indicating chronic Q fever. Polymerase chain reaction (PCR) of the corresponding heart valve revealed 3.1 × 10(5) copies/rxn. The strain was successfully isolated using ACCM2. Genomic investigation by multilocus variable-number of tandem repeat (VNTR) analysis (MLVA) revealed the strain to be a new genotype, A10, closely related to one from sheep. As the sensitivity of ACCM2 for different human strains is unknown, we also investigated combining a robust test, egg propagation, with ACCM2. This combination produced four to six logs of growth of the bacteria. The use of ACCM2 in this combination simplified the otherwise elaborate purification steps. Cultivation in ACCM2 has the potential to simplify the isolation of C. burnetii in a clinical setting. As the success rates of cell culture for virulent C. burnetii strains are variable, the sensitivity of ACCM2 for different strains is unknown, and many specimens may contain much fewer bacteria than in our case, the combination of the robust method of egg propagation with ACCM2 is a good alternative to existing single methods for investigating critical specimens.

Immunogenicity of the Q fever skin test

The Q fever skin test is used to measure cell-mediated immunity to Coxiella burnetii in pre-vaccination screening to exclude individuals with pre-existing immunity. We investigated whether this in-vivo test influences subsequent measurements of immune response. We assessed the humoral and cellular immune responses before, and 6 and 12 months after skin testing in 63 individuals who were not vaccinated because of either a positive skin test or positive serology in screening. IgG anti-C. burnetii antibodies were measured using immune-fluorescence assay (IFA). The cellular immune response was assessed by measuring in-vitro C. burnetii-specific interferon (IFN)-γ production in blood. Of the 35 subjects with a positive skin test and negative serology, 15/35 (43%) showed seroconversion at 6 months, and 7/32 (22%) seropositivity at 12 months. The mean ± SE specific IFN-γ production in this group increased from 185 ± 88 pg/mL (at baseline) to 422 ± 141 pg/mL at 6 months (P = 0.009) and 223 ± 91 pg/mL at 12 months (P = 0.17). Of the 28 subjects with positive serology (and unknown skin test results), 21/28 (75%) showed an increase in IgG anti-phase I titres at 6 months, and 11/25 (44%) at 12 months. The mean ± SE specific IFN-γ production was significantly increased at 6 months, but not at 12 months. Q fever skin testing causes higher antibody titres and higher in-vitro IFN-γ to C. burnetii, and therefore affects subsequent Q fever diagnostics.

Quantitative real-time PCR and phase specific serology are mutually supportive in Q fever diagnostics in goats

This study presents results of quantitative pathogen detection by real-time PCR (qPCR) and phase-specific serology for complete Q fever diagnostics. For this, samples of 42 goats in total were taken during a Q fever outbreak.In the early phase of the Q-fever infection, 104–108Coxiella (C.) burnetii pathogens per vaginal swab and 102–106C. burnetii per ml milk were detected using quantitative real-time PCR (qPCR). Pathogen excretion decreased continuously within two months to less than 104 (vaginal swab) and 102 (milk) C. burnetii. At the end of the study there was a shift toward a 10 fold higher excretion of the pathogen via the genital tract and milk.At the start of the study, serological tests showed a dominance of the phase-2 antibody in 76% (22/29) of the goats in the MONA- (Multiple of Normal Activity) ELISA and 79% (23/29) in the IDEXX-ELISA, which was replaced by a phase-1 dominance in 85% (29/34) and 62% (21/34), of the animals respectively at the end of the study. Serum samples from 13 goats before lambing that excreted C. burnetii after lambing showed antibodies against phase 2 of 100% using MONA-ELISA and 77% in the IDEXX-ELISA.The most important diagnostic instrument for Q-fever infection in goats following birth is testing of vaginal swabs using qPCR. Phase-specific serology allows an estimation of possible pathogen excretion even before birth, as well as achieving valuable results for determination of the infection phase.

Localizing chronic Q fever: a challenging query

BackgroundChronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed.MethodsFifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded.ResultsAccording to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively.ConclusionsIf chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions.

FRI0198 The risk of chronic q fever in rheumatoid arthritis patients with and without anti-tnf therapy

BackgroundThe Netherlands faced a large Q fever outbreak from 2007-2010, during which many individuals have been infected with Coxiella burnetii, the intracellular bacterium causing Q fever. Initial infection is often...

Limitations of typhoid fever diagnostics and the need for prevention

Evaluation of: Siba V, Horwood PF, Vanuga K et al. Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea using a composite reference standard. Clin. Vaccine Immunol. 19(11), 1833–1837 (2012).The study under review evaluated serological tests for typhoid fever against PCR as a reference test. While laboratory testing is essential for the confirmation of this severe disease, the low bacterial load and the low level of specific antibodies in the blood of typhoid patients combined with its acute character make interpretation of laboratory testing cumbersome. Validation of an index test requires good understanding of the diagnostic performance and assay characteristics of the reference test, and criteria and principles for study design and reporting outlined by the Quality Assessment of Diagnostic Accuracy Studies and the Standards for Reporting Studies of Diagnostic Accuracy should be followed. Described PCR assays for typhoid fever have not been validated against bone marrow culture, the gold standard, and their diagnostic utility remains to be established.

Principles of Standardization of Crimean Hemorrhagic Fever Diagnostics and Its Present-Day Peculiarities in the Territory of the Russian Federation

It is stated that due to epidemic manifestations Crimean hemorrhagic fever (CHF) has recently become one of the most pressing issues in the South of the European part of the Russian Federation, the area where its integrated natural focus is situated. In this respect, analyzed are the data on CHF monitoring over the past decade (since 1999); determined are the main epidemiological peculiarities of the infection in the modern period. Furthermore, outlined are the basic principles of development of the unified standard concerning epidemiological and laboratory diagnostics of the disease. Emphasized is the importance of differentiation in scope and nomenclature of diagnostic investigations in laboratory facilities of different echelons, which makes it possible to increase plausibility and quality of the surveys conducted, and carry out verification of the results obtained.

The utility of diagnostic tests for enteric fever in endemic locations

Enteric fever, an infection caused by Salmonella enterica serovar Typhi and serovar Paratyphi A, is common and endemic in many areas of the Asian and African continents. In endemic areas, diagnostic tests are needed to diagnose acute cases for clinical management, to detect convalescent and chronic fecal carriage and for contact tracing. A suitable test may also allow an assessment of disease burden in a community to determine the need for vaccination programs. Each specific role may warrant a dedicated test, utilizing different samples, targets and methods to serve their respective purpose. Current diagnostic methods are poor. Blood culture is insufficiently sensitive and technically demanding, and bone marrow culture, although more sensitive, is infrequently performed. Antibody- and antigen-detection tests lend themselves to point-of-care format but remain insufficiently sensitive and specific for this role. There are concerns about the sensitivity of nucleic acid amplification tests and they have not become widely adopted. However, new approaches using genomics, proteomics, transcriptomics, in vivo-induced antigen and immunoaffinity proteomics-based technologies are being employed to identify new antigens, gene targets and metabolic products that could be used as a basis for more effective diagnostic tests. If novel tests are to be credible and widely used they require rigorous evaluation in endemic areas in studies with appropriate selection of patients, adequate sample sizes and proper attention to a gold standard reference. Here, we discuss the range of methods currently used for diagnosing enteric fever in endemic locations and we suggest new technologies which may improve enteric fever diagnostics over the coming years.

Evaluation of a Diagnostic Algorithm for Acute Q Fever in an Outbreak Setting

In the peak of the 2009 Q fever outbreak in the Netherlands, we introduced a diagnostic algorithm for acute Q fever with an enzyme-linked immunosorbent assay for immunoglobulin M antibodies to Coxiella burnetii phase II antigens (MII screen) as an initial step. Subsequently, an immunofluorescence assay or PCR was performed depending on the MII screen outcome, date of onset of disease, and inpatient or outpatient setting. The impact of MII screen on the number of immunofluorescence assays performed and the contribution of PCR to diagnosis were retrospectively evaluated in 825 patients referred in a 17-day period. Acute Q fever was diagnosed in 256 patients. The introduction of MII screen reduced the number of immunofluorescence assays performed by more than 80%. In 103 patients, PCR analysis contributed to the diagnosis of acute Q fever. Q fever diagnostics were hampered by the fact that for a high number of patients the date of onset of disease was not provided and the requested follow-up serum samples were not received.

Proteomics paves the way for Q fever diagnostics

Q fever is a worldwide zoonosis caused by Coxiella burnetii. The disease most frequently manifests clinically as a self-limited febrile illness, as pneumonia (acute Q fever) or as a chronic illness that presents mainly as infective endocarditis. The extreme infectivity of the bacterium results in large outbreaks, and the recent outbreak in the Netherlands underlines its impact on public health. Recent studies on the bacterium have included genome sequencing, the investigation of host-bacterium interactions, the development of cellular and animal models of infection, and the comprehensive analysis of different clinical isolates by whole genome and proteomic approaches. Current approaches for diagnosing Q fever are based on serological methods and PCR techniques, but the diagnosis of early stage disease lacks specificity and sensitivity. Consequently, different platforms have been created to explore Q fever biomarkers. Several studies using a combination of proteomics and recombinant protein screening approaches have been undertaken for the development of diagnostics and vaccines. In this review, we highlight advances in the field of C. burnetii proteomics, focusing mainly on the contribution of these technologies to the development and improvement of Q fever diagnostics.