Gorączka q – Diagnostyka i diagnoza

Gorączka q
Diagnostyka i diagnoza

Gorączka Q, wywoływana przez Coxiella burnetii, stanowi wyzwanie diagnostyczne ze względu na niespecyficzne objawy kliniczne przypominające inne infekcje, co wymaga wysokiego indeksu podejrzenia. Diagnostyka opiera się głównie na serologii, z testem immunofluorescencji pośredniej (IFA) jako złotym standardem, umożliwiającym wykrycie przeciwciał IgG i IgM fazy I i II. W ostrej fazie choroby potwierdzenie diagnozy wymaga czterokrotnego wzrostu miana IgG fazy II lub miana ≥ 1:200 (IgG) bądź ≥ 1:50 (IgM). W przewlekłej postaci istotne jest podwyższone miano IgG fazy I (≥ 1:1024 lub ≥ 1:800) oraz identyfikacja trwałej infekcji, np. zapalenia wsierdzia. PCR, szczególnie w pierwszym tygodniu choroby, wykazuje czułość 81% i swoistość 90%, stanowiąc cenne narzędzie diagnostyczne we wczesnym stadium, zwłaszcza w połączeniu z serologią. Nowoczesne metody, takie jak metagenomiczne sekwencjonowanie następnej generacji (mNGS) i targeted NGS (tNGS), umożliwiają szybką identyfikację patogenu w trudnych przypadkach.

Diagnostyka Gorączki Q

Gorączka Q, choroba odzwierzęca wywoływana przez bakterię Coxiella burnetii, stanowi istotne wyzwanie diagnostyczne dla klinicystów. Ze względu na niespecyficzne objawy kliniczne, które mogą naśladować wiele innych chorób zakaźnych, diagnoza często wymaga wysokiego indeksu podejrzenia oraz zastosowania odpowiednich testów laboratoryjnych. Świadomość epidemiologicznych i klinicznych cech gorączki Q jest niezbędna do postawienia szybkiej i prawidłowej diagnozy.¹²

Wyzwania diagnostyczne

Diagnoza gorączki Q jest często utrudniona z kilku powodów. Po pierwsze, objawy kliniczne są niespecyficzne i mogą przypominać wiele innych chorób, takich jak grypa, inne infekcje wirusowe, salmonelloza, malaria, zapalenie wątroby, bruceloza czy atypowe zapalenie płuc. Po drugie, w wielu krajach gorączka Q nie jest chorobą podlegającą obowiązkowi zgłaszania, co prowadzi do jej niedoszacowania i niedodiagnozowania. Badania seroprewalencji wykazały, że znacznie więcej osób jest zakażonych C. burnetii niż sugeruje liczba zgłoszonych objawowych przypadków.¹²³

W Chinach, gdzie gorączka Q nie jest uznawana za chorobę podlegającą obowiązkowemu zgłaszaniu, choroba jest często przeoczana i niedoszacowana w praktyce klinicznej, co prowadzi do opóźnienia diagnozy, niekiedy nawet o kilka miesięcy do roku od wystąpienia pierwszych objawów.¹

Metody diagnostyczne

Metody serologiczne

Diagnostyka gorączki Q opiera się głównie na serologii, a najczęściej stosowaną metodą jest test immunofluorescencji pośredniej (IFA). Serologia umożliwia wykrycie przeciwciał przeciwko antygenowi fazowemu I i II bakterii C. burnetii. Badania serologiczne powinny być zawsze wykonywane u pacjentów z gorączką i ujemnymi posiewami krwi.¹²

Najbardziej wiarygodne i powszechnie stosowane metody serologiczne obejmują:

Pośrednią immunofluorescencję (IFA) – metoda referencyjna¹²
Test wiązania dopełniacza (CFT)¹²
ELISA¹²
Mikroaglutynację¹

Interpretacja testów serologicznych

W przypadku ostrej gorączki Q, diagnozę potwierdza się poprzez:

Wykrycie czterokrotnego wzrostu miana przeciwciał IgG fazy II w teście IFA między próbkami surowicy z fazy ostrej i zdrowienia pobranymi w odstępie 3-6 tygodni¹²
Miano przeciwciał IgG fazy II ≥ 1:200 lub miano przeciwciał IgM ≥ 1:50 w pojedynczym badaniu¹
Wartość graniczna miana przeciwciał w teście IFA powinna być określona dla każdego obszaru geograficznego¹

W przypadku przewlekłej gorączki Q, diagnoza wymaga:

Wykazania podwyższonego miana przeciwciał IgG fazy I (≥ 1:1024 lub ≥ 1:800, w zależności od przyjętych kryteriów) oraz¹²
Identyfikacji trwałej infekcji (np. zapalenie wsierdzia)¹

Warto zauważyć, że serokonwersja występuje zwykle między 7 a 15 dniem choroby i jest prawie zawsze obecna do 21 dnia. Testy diagnostyczne oparte na serologii będą negatywne przez pierwsze 15 dni choroby, dlatego leczenie powinno się rozpocząć przed laboratoryjnym potwierdzeniem zakażenia C. burnetii.¹²

Diagnostyka molekularna

Badanie PCR (reakcja łańcuchowa polimerazy) jest coraz częściej stosowane w diagnostyce gorączki Q. PCR można wykonać na:

Krwi pełnej lub surowicy w ciągu pierwszego tygodnia choroby, przed rozwojem przeciwciał¹²
Tkankach zajętych przez infekcję (np. zastawki serca, biopsje wątroby)¹

PCR w połączeniu z serologią jest zalecany we wczesnych stadiach infekcji dla ostatecznej diagnozy ostrej gorączki Q. Test PCR powinien być wykonany podczas ostrej choroby (optymalnie w ciągu pierwszych 2 tygodni od wystąpienia objawów) i najlepiej przed lub krótko po podaniu antybiotyków.¹²

W jednym z badań koreańskich wykazano, że czułość PCR dla gorączki Q wynosi 81% (95% CI, 54-96), swoistość 90% (95% CI, 67-99), dodatnia wartość predykcyjna 87% (95% CI, 63-96) i ujemna wartość predykcyjna 85% (95% CI, 67-94), co czyni go użytecznym testem do wczesnej diagnostyki gorączki Q.¹

Nowe metody diagnostyczne

W ostatnich latach pojawiły się nowe podejścia diagnostyczne dla gorączki Q:

Metagenomic next-generation sequencing (mNGS) – umożliwia szybką identyfikację C. burnetii w próbkach krwi lub bioptatów. Ta metoda okazała się szczególnie przydatna w przypadkach trudnych do zdiagnozowania.¹²³
Targeted next-generation sequencing (tNGS) – obiecujące i znaczące narzędzie do szybkiego wykrywania zakażenia C. burnetii, o koszcie stanowiącym około jedną czwartą kosztu mNGS.¹²
Q-detect – pierwszy test immunologiczny oparty na komórkach dla C. burnetii. Infekcje mogą być wykrywane lata po ekspozycji na bakterie, nawet gdy przeciwciała zanikły.¹

Badania laboratoryjne wspomagające diagnozę

Pewne standardowe badania krwi, takie jak morfologia i testy funkcji wątroby, mogą wspierać diagnozę gorączki Q (i pomagać w decyzji o rozpoczęciu leczenia) przed zakończeniem testów potwierdzających.¹

Ostra gorączka Q – zmiany w badaniach laboratoryjnych

W ostrej gorączce Q mogą występować następujące nieprawidłowości w badaniach laboratoryjnych:

Morfologia krwi zwykle pokazuje prawidłową liczbę białych krwinek (70-90%) (podwyższona liczba WBC u 30% pacjentów)¹
Łagodna trombocytopenia (25%), a następnie reaktywna trombocytoza w okresie zdrowienia¹
W rzadkich przypadkach może wystąpić niedokrwistość hemolityczna¹
Testy funkcji wątroby zwykle wykazują łagodne podwyższenie transaminaz (2-3 razy powyżej normy u 70-85% pacjentów) i fosfatazy alkalicznej (2-3 razy powyżej normy) bez hiperbilirubinemii¹
OB jest zwykle podwyższone (55 mm/h ± 30 mm/h)¹
Mogą występować różne dodatnie przeciwciała autoimmunologiczne, w tym przeciwciała przeciw mięśniom gładkim i antyfosfolipidowe¹
Posiewy krwi są typowo ujemne¹

Przewlekła gorączka Q – zmiany w badaniach laboratoryjnych

W przewlekłej gorączce Q mogą występować następujące wyniki laboratoryjne:

Niedokrwistość chorób przewlekłych¹
Podwyższone OB¹
Podwyższone gamma globuliny (poliklonalne)¹
Podwyższony czynnik reumatoidalny (RF)¹
Zwiększone poziomy kreatyniny¹

Diagnostyka specyficznych form choroby

Zapalenie wsierdzia w gorączce Q

Diagnoza zapalenia wsierdzia w przebiegu gorączki Q może być niezwykle trudna, ponieważ zmiany wegetatywne na zastawkach serca są widoczne w echokardiografii u zaledwie około 12% pacjentów. W przypadku podejrzenia przewlekłej gorączki Q, należy wykonać badanie echokardiograficzne, aby wykluczyć zmiany w zastawkach serca.¹²

Zapalenie wsierdzia w przebiegu gorączki Q jest diagnozowane przy spełnieniu kryteriów klinicznych zapalenia wsierdzia wraz z dowodami serologicznymi lub izolacją C. burnetii. Pojedyncze miano przeciwciał IgG fazy I ≥ 800 jest uwzględnione w zmodyfikowanych kryteriach Duke’a.¹

Zapalenie wątroby w gorączce Q

Zapalenie wątroby w przebiegu gorączki Q objawia się podwyższeniem poziomu aminotransferazy alaninowej i asparaginianowej, ale ostateczna diagnoza jest możliwa tylko na podstawie biopsji wątroby, która pokazuje charakterystyczne ziarniniaki z pierścieniami fibrynowymi.¹

W przypadku pacjentów z FUO (gorączka nieznanego pochodzenia) oraz nieprawidłowościami funkcji wątroby przy braku przyczyn wirusowych lub immunologicznych, ważne jest rozważenie biopsji wątroby.¹

Zespół zmęczenia po gorączce Q

Diagnoza zespołu zmęczenia po gorączce Q opiera się na:

Utrzymywaniu się charakterystycznych objawów przez rok po objawowym ostrym zakażeniu gorączką Q¹
Podwyższonych mianach przeciwciał przeciwko antygenowi C. burnetii¹
Braku klinicznych i laboratoryjnych dowodów na przewlekłą gorączkę Q z zajęciem narządów¹

Nie istnieje wzorzec serologiczny, który korelowałby z zespołem zmęczenia po gorączce Q.¹

Zalecenia diagnostyczne

Kiedy podejrzewać gorączkę Q

Badanie serologiczne w kierunku gorączki Q powinno być zawsze wykonane u pacjenta z gorączkową chorobą i ujemnymi posiewami krwi. Zaleca się, aby wszyscy pacjenci z następującymi stanami przeszli badania serologiczne w kierunku gorączki Q:¹

Zapalenie wsierdzia z ujemnymi posiewami krwi¹
Pacjenci z gorączką i tętniakami aorty¹
Osoby z przedłużającą się gorączką¹
Ziarniniakowe zapalenie wątroby¹
Atypowe zapalenie płuc w obszarach, gdzie gorączka Q jest endemiczna¹
Osoby z objawami grypopodobnymi oraz narażeniem zawodowym lub związanym z podróżą na potencjalnie zakażone zwierzęta hodowlane¹

Postępowanie diagnostyczne

W przypadku podejrzenia gorączki Q, zaleca się następujące postępowanie:

Zebranie szczegółowego wywiadu, w tym narażenia zawodowego i kontaktu ze zwierzętami¹
Wykonanie podstawowych badań laboratoryjnych (morfologia, testy funkcji wątroby, CRP)¹²
Badanie PCR krwi pobranej najlepiej w ciągu pierwszego tygodnia choroby¹
Badania serologiczne z próbkami sparowanymi: ostra (pobrana w ciągu 7 dni od wystąpienia choroby) i zdrowienia (pobrana 7 dni po pierwszej próbce lub 2-3 tygodnie później)¹²
W przypadku podejrzenia przewlekłej gorączki Q, należy również wykonać badania w kierunku miana przeciwciał IgA fazy I metodą IFA¹

W nieskomplikowanych przypadkach zaleca się powtórzenie badań serologicznych w kierunku gorączki Q po 6 miesiącach, aby zidentyfikować potencjalną progresję do choroby przewlekłej.¹

Ograniczenia diagnostyczne

Interpretacja wyników badań serologicznych w kierunku gorączki Q może być trudna. Lekarze powinni zasięgnąć porady lokalnego oddziału chorób zakaźnych lub mikrobiologa w razie potrzeby.¹

Fałszywie dodatnie wyniki serologiczne mogą występować w przypadku legionellozy i leptospirozy.¹

Ujemny wynik PCR nie wyklucza diagnozy gorączki Q i może wystąpić z powodu:¹²

Inhibicji PCR¹
Zmienności sekwencji leżących u podstaw starterów lub sond¹
Obecności DNA C. burnetii w ilościach mniejszych niż granica wykrywalności testu¹

Wyniki testów powinny być wykorzystywane jako pomoc w diagnostyce i nie powinny być uważane za diagnostyczne same w sobie. Pojedynczy test nie powinien być stosowany jako jedyne kryterium do formułowania wniosku klinicznego, ale wyniki powinny być skorelowane z objawami i prezentacją kliniczną pacjenta.¹

Leczenie empiryczne

Ze względu na trudności w uzyskaniu szybkiej, ostatecznej diagnozy, leczenie empiryczne powinno być rozważone, jeśli prezentacja i wywiad kliniczny sugerują chorobę odzwierzęcą. Wczesne leczenie jest korzystne i może zapobiec komplikacjom.¹

Jeśli lekarz podejrzewa gorączkę Q, może zdecydować się na rozpoczęcie leczenia przed otrzymaniem wyników badań, szczególnie że wyniki testów na C. burnetii mogą zająć kilka tygodni.¹

Doksycyklina jest lekiem z wyboru w leczeniu gorączki Q i powinna być podawana przez 15-21 dni w przypadku ostrej infekcji. Leczenie przewlekłych infekcji, takich jak zapalenie wsierdzia, wymaga dłuższej antybiotykoterapii, często trwającej co najmniej 18 miesięcy.¹²

Wnioski

Diagnostyka gorączki Q wymaga wysokiego indeksu podejrzenia oraz zastosowania odpowiednich testów laboratoryjnych. Złotym standardem diagnostycznym pozostaje serologia, szczególnie test immunofluorescencji pośredniej (IFA), który pozwala na różnicowanie między ostrą i przewlekłą infekcją. PCR jest wartościowym narzędziem we wczesnej fazie choroby, przed rozwojem przeciwciał. Nowe metody diagnostyczne, takie jak mNGS i tNGS, oferują obiecujące podejście do szybkiej i dokładnej identyfikacji C. burnetii w trudnych przypadkach diagnostycznych.¹²

Ze względu na potencjalne poważne powikłania nieleczonej gorączki Q, szczególnie rozwój zapalenia wsierdzia u osób z predyspozycjami, wczesna diagnoza i leczenie są kluczowe. W przypadku silnego podejrzenia klinicznego, leczenie empiryczne powinno być rozpoczęte przed potwierdzeniem laboratoryjnym.¹

Dalsze badania i wysiłki międzynarodowych naukowców i ekspertów w dziedzinie gorączki Q są potrzebne, aby opracować ostateczne, oparte na dowodach kryteria diagnostyki i leczenia tej złożonej choroby.¹

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Materiały źródłowe

#1 Diagnosis and Management of Q Fever — United States, 2013
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6203a1.htm
Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause acute or chronic illness in humans. […] Establishing a diagnosis of Q fever often is challenging for clinicians. […] This report provides the first national recommendations issued by CDC for Q fever recognition, clinical and laboratory diagnosis, treatment, management, and reporting for health-care personnel and public health professionals. […] Laboratory diagnosis relies mainly on serology, and doxycycline is the most effective treatment for acute illness. […] Diagnosis of chronic Q fever endocarditis can be extremely difficult because vegetative lesions are visualized by echocardiography in approximately 12% of patients. […] Physician awareness of the epidemiologic and clinical characteristics of Q fever is required to make a prompt and correct diagnosis.
#1 Q Fever – Infectious Diseases – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/infectious-diseases/rickettsiae-and-related-organisms/q-fever
Diagnosis is confirmed by several serologic techniques, isolation of the organism, or polymerase chain reaction (PCR). […] Symptoms do not readily suggest the diagnosis of Q fever. Early on, Q fever resembles many infections (eg, influenza, other viral infections, salmonellosis, malaria, hepatitis, brucellosis). Later, it resembles many forms of bacterial, viral, and mycoplasmal and other atypical pneumonias. Contact with animals or animal products is an important clue. […] IFA of infected tissue is the diagnostic method of choice; alternatively, enzyme-linked immunosorbent assay (ELISA) may be done. Acute and convalescent serum specimens (typically complement fixation) may be used. Antibodies to phase II antigen are used to diagnose acute disease, and antibodies to both phase I and phase II antigens are used to diagnose chronic disease.
#1 Delayed diagnosis of persistent Q fever: a case series from China | BMC Infectious Diseases | Full Text
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09484-w
Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. […] In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. […] The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. […] Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. […] Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii. […] The definitive diagnosis was achieved through detection of the causative pathogen C. burnetii using metagenomic next-generation sequencing (mNGS) testing.
#1 Diagnosis of Q Fever
https://pmc.ncbi.nlm.nih.gov/articles/PMC104936/
Query (Q) fever, due to Coxiella burnetii, is a ubiquitous zoonosis. […] The diagnosis of Q fever relies mainly upon serology, the most commonly used method being the immunofluorescence assay. Serological testing for Q fever should always be done for a patient with a febrile illness and negative blood cultures. […] The most reliable and commonly used methods are indirect immunofluorescence, complement fixation, ELISA, and microagglutination. […] Currently, the immunofluorescence assay is the reference method for the serodiagnosis of Q fever. […] In case of acute Q fever, diagnosis would be confirmed by an immunofluorescence assay titer greater than or equal to the cutoff value (which must be determined for each geographical area) or by a fourfold increase in the antibody titer detected by immunofluorescence assay, complement fixation, ELISA, or microagglutination. […] We recommend that all patients with blood culture-negative endocarditis, febrile patients with aortic aneurysms, and those with prolonged fever, granulomatous hepatitis, or atypical pneumonia in areas where Q fever is endemic should at the very least undergo serological testing for Q fever.
#1 Diagnosis and Management of Q Fever — United States, 2013
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6203a1.htm
The most commonly used means of confirming the diagnosis of acute Q fever is demonstration of a fourfold rise in phase II IgG by IFA between serum samples from the acute and convalescent phases taken 3-6 weeks apart. […] Diagnosis of chronic Q fever requires demonstration of an increased phase I IgG antibody (1:1024) and an identifiable persistent infection (e.g., endocarditis). […] PCR, immunohistochemistry, or culture of affected tissue can provide definitive confirmation of infection by Coxiella burnetii. […] Diagnosis of post-Q fever fatigue syndrome relies on persistence of characteristic symptoms 1 year after a symptomatic acute Q fever infection, elevated antibody titers against Coxiella burnetii antigen, and a lack of clinical and laboratory evidence of chronic Q fever with organ involvement.
#1
https://journals.lww.com/md-journal/fulltext/2019/06070/diagnostic_usefulness_of_molecular_detection_of.6.aspx
Diagnosis of Q fever is difficult due to the lack of distinct clinical features that distinguish it from other febrile diseases. […] Serologic testing is the gold standard method for diagnosing Q fever, but antibody formation may not be detectable for 2 to 3 weeks from symptom onset, limiting early diagnosis. […] We thus evaluated the diagnostic utility of polymerase chain reaction (PCR) to detect Coxellia burnetii DNA in serum from patients with suspected acute Q fever. […] Acute Q fever was diagnosed using clinical and laboratory criteria: fever with at least one other symptoms (myalgia, headache, pneumonia, or hepatitis) and single phase II immunoglobulin G (IgG) antibody titers 1:200 or immunoglobulin M (IgM) antibody titer 1:50 (probable), or a fourfold increase or seroconversion in phase II IgG antibody titers as measured by indirect immunofluorescence assays between paired samples (confirmed).
#1 Q Fever Workup: Approach Considerations, Routine Laboratory Studies, Serology
https://emedicine.medscape.com/article/227156-workup
The diagnosis of Q fever relies on a high index of suspicion as suggested by the epidemiologic features and is proven by serologic analysis. The organism is very infectious, and isolation ought to be done in biosafety level 3 laboratories. […] If a clinician thinks Q fever is a likely diagnosis, the laboratory should be notified so that they can take appropriate precautions. […] Most cases of Q fever are diagnosed based on detection of phase I and II antibodies (between acute and convalescent paired sera); a 4-fold rise in complement-fixing antibody titer against phase II antigen occurs and yields the highest specificity. This requires a baseline sample and another sample in 3-4 weeks. Thus, serologic tests are not helpful acutely but may later confirm the diagnosis: Seroconversion generally occurs between days 7 and 15 and is almost always present by 21 days.
#1 Coxiella burnetii – Q Fever | Choose the Right Test
https://arupconsult.com/content/coxiella-burnetii
Serology is the most common diagnostic approach for C. burnetii infection, regardless of whether acute or chronic infection is suspected. […] The standard test for diagnosing acute C. burnetii infection is indirect fluorescent antibody (IFA) testing on paired acute and convalescent sera. […] A fourfold increase in phase II immunoglobulin G (IgG) concentration is considered diagnostic for Q fever. […] PCR testing on serum or whole blood can be used to detect C. burnetii within the first week of illness before antibodies develop, and PCR in combination with serology is recommended in the early stages of infection for a definitive diagnosis of acute Q fever. […] Chronic Q fever can be diagnosed when an individual exhibits both elevated phase I IgG antibody titers and a persistent focus of infection, such as endocarditis.
#1 Coxiella burnetii – Q fever – Swissticks
https://swissticks.ch/en/pathogens/coxiella-burnetii-q-fever/
Diagnosis is based on PCR or serology. […] PCR can be performed on whole blood or serum in the acute phase, and allows the diagnosis of acute Q fever within the first 2 weeks of infection. PCR can also be performed on infected tissues (heart valve samples, liver biopsies, bone biopsies). […] Serology can be performed using a highly sensitive screening test followed by an immunofluorescence test for confirmation which also allows serum titration. A fourfold increase in phase II IgG antibody titer by immunofluorescence between paired acute and convalescent specimens is the gold standard for confirming the diagnosis of acute Q fever. However, negative serology in the acute phase does not exclude Q fever. […] Diagnosis of chronic Q fever requires demonstration of a high phase I IgG antibody titer ( 1:800) greater than the phase II IgG titer and an identifiable focal infection (e.g., endocarditis, hepatitis, or spondylodiskitis).
#1
https://journals.lww.com/md-journal/fulltext/2019/06070/diagnostic_usefulness_of_molecular_detection_of.6.aspx
The Q fever PCR sensitivity was 81% (95% confidence interval [CI], 5496), specificity was 90% (95% CI, 6799), positive predictive value was 87% (95% CI, 6396), and negative predictive value was 85% (95% CI, 6794). […] Q fever PCR testing using blood from patients with suspected acute Q fever seems to be a rapid and useful test for early diagnosis of Q fever. […] Diagnosis of Q fever using only clinical, epidemiological, and routine laboratory findings is challenging. […] Therefore, polymerase chain reaction (PCR) detection of C. burnetii DNA directly from a single serum sample has recently been considered to be a confirmatory test for acute Q fever. […] Our in-house Q fever PCR detection method seems to have higher sensitivity (81%) and relatively high specificity when compared to those described in the previous studies.
#1 Clinical diagnosis of Q fever by targeted next-generation sequencing for identification of Coxiella burnetii | BMC Infectious Diseases | Full Text
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10437-6
Q fever is a zoonotic bacterial disease caused by Coxiella burnetii. Due to its variable and non-specific clinical symptoms, the disease is often overlooked and underreported. To date, the identification of C. burnetii as the causative pathogen of Q fever using targeted next-generation sequencing (tNGS) has not been previously documented. […] tNGS was performed on patients with acute fever of unknown etiology, and qPCR was confirmed for C. burnetii infection. […] tNGS was performed on 112 patients with acute fever of unknown etiology at Peking University Third Hospital between March 27 and September 20, 2024. C. burnetii was identified in blood samples from five patients, leading to a clinical diagnosis of Q fever. These diagnoses were subsequently confirmed by qPCR at the Beijing CDC.
#1 Q fever
https://www.innatoss.com/en/q-fever/
Innatoss Laboratories has launched a unique test for Q fever diagnosis: Q-detect is the first cell-mediated immunity test for Coxiella burnetii. Infections can be detected years after exposure to the bacteria, even when antibodies have decayed. […] It pleases me to see that specifically in our region a better diagnostic test was developed and is being performed. With the new cellular test we seem to have a better tool to trace persons infected with the Q fever bacterium Coxiella, who are running the risk of disease manifestations. […] Diagnosing an infection with Coxiella burnetii is important for many reasons: in the acute and chronic phase, for timely treatment with antibiotics; chronic fatigue patients may have Q fever Fatigue Syndrome; when treatment with immunesuppressive drugs is started, it is important to be aware of previous exposure to Coxiella. In case of unexpected febrile symptoms caused by activation of lingering Q fever, correct treatment can be initiated. […] Innatoss Laboratories has extensive knowledge and experience on Q fever diagnostics and the related immune response.
#1 Coxiella burnetii – Q Fever | Choose the Right Test
https://arupconsult.com/content/coxiella-burnetii
Coxiella burnetii, the causative agent for Q fever, is primarily transmitted to humans via inhalation of particles excreted by livestock such as cattle, sheep, and goats; other forms of transmission (eg, human to human) are rare. […] Laboratory testing for Q fever includes testing for antibody response to both phase I and phase II antigens. […] Because diagnostic serology tests will return negative results for the first 15 days of illness, treatment should begin before laboratory confirmation of Coxiella burnetii infection (Q fever). […] Certain standard blood tests, such as CBC and liver function tests, can support a diagnosis of Q fever (and assist in the decision to begin treatment) before confirmatory laboratory tests have been completed. […] Testing for acute Q fever (ie, C. burnetii infection) should be considered in individuals with flu-like symptoms (such as fever, headache, and chills) and occupational or travel-related exposure to potentially infected livestock.
#1 Q Fever: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/227156-overview
Lab tests […] Acute Q fever may present with the following laboratory results: […] A complete blood cell (CBC) count usually shows a normal white blood cell (WBC) count (70-90%) (elevated WBC in as many as 30%), mild thrombocytopenia (25%) (followed by a reactive thrombocytosis during the convalescent period [1]), and, in rare cases, hemolytic anemia. […] Liver function tests usually show mild elevation of transaminases (2-3 times the reference range in 70-85% of patient) and alkaline phosphatase (2-3 times the reference range) without hyperbilirubinemia. […] The erythrocyte sedimentation rate (ESR) usually is elevated (55 mm/h 30 mm/h). […] Several positive autoimmune antibodies, including antismooth muscle and antiphospholipid, may be seen. […] Blood cultures typically are negative (Note that, although possible, attempting to isolate the organism from blood is a dangerous practice; cases of Q fever have developed in laboratory technicians).
#1 Q Fever: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/227156-overview
In chronic Q fever, the following laboratory results may be observed: […] Anemia of chronic disease. […] Elevated ESR. […] Elevated gamma globulins (polyclonal). […] Elevated rheumatoid factor (RF). […] Increased creatinine levels. […] Serology […] The diagnosis of Q fever relies on a high index of suspicion as suggested by the epidemiologic features and is proven by serologic analysis. The 3 serologic techniques used for diagnosis are as follows: […] Indirect immunofluorescence (IIF) (method of choice). […] Complement fixation. […] Enzyme-linked immunosorbent assay (ELISA) (comparable to IIF). […] See Workup for more detail.
#1 Azthena logo with the word Azthena
https://www.news-medical.net/health/Q-Fever-Diagnosis.aspx
This condition is diagnosed by meeting clinical criteria for endocarditis along with serologic evidence or isolation of C. burnetii. A single-phase I IgG antibody titer of 800 or more is included in the modified Duke criteria, but if titers are low or absent, as may happen with concomitant immunosuppression, a PCR is invaluable in early diagnosis.
#1 Q fever – Wikipedia
https://en.wikipedia.org/wiki/Q_fever
Diagnosis is usually based on serology (looking for an antibody response) rather than looking for the organism itself. […] Serology allows the detection of chronic infection by the appearance of high levels of the antibody against the virulent form of the bacterium. […] Molecular detection of bacterial DNA is increasingly used. […] Contrary to most obligate intracellular parasites, Coxiella burnetii can be grown in an axenic culture, but its culture is technically difficult and not routinely available in most microbiology laboratories. […] Q fever can cause endocarditis (infection of the heart valves) which may require transoesophageal echocardiography to diagnose. […] Q fever hepatitis manifests as an elevation of alanine transaminase and aspartate transaminase, but a definitive diagnosis is only possible on liver biopsy, which shows the characteristic fibrin ring granulomas.
#1 Granulomatous hepatitis caused by Q fever: a differential diagnosis of fever of unknown origin | Annals of Hepatology
https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-granulomatous-hepatitis-caused-by-q-S1665268119313961
Serologic test confirms C. burnetii infection. […] In conclusion, we described a patient with acute Q fever and granulomatous hepatitis. It is one of the few cases of this disease reported in Mexico. In our country, Q fever is probably an underdiagnosed cause of fever of unknown origin and it is important to consider a liver biopsy in patients with UFO and liver function abnormalities in the absence of viral or immunological causes.
#1 Q fever: A rural disease with potential urban consequences
https://www1.racgp.org.au/ajgp/2018/march/q-fever
For suspected chronic Q fever, a request should also be made for phase 1 IgA titres by IFA. […] In uncomplicated cases, repeat Q fever serology at six months to identify potential progression to chronic disease. […] There is no serological pattern that correlates with the post-Q fever fatigue syndrome. […] Achieving a timely, definitive diagnosis is challenging, but as early treatment is beneficial, empirical antibiotic therapy should be considered if the presentation and clinical history suggest a zoonotic disease. […] Chronic Q fever requires long-term antimicrobial treatment and specialist input.
#1 Q fever: A rural disease with potential urban consequences
https://www1.racgp.org.au/ajgp/2018/march/q-fever
Q fever often presents as an undifferentiated febrile illness. […] Laboratory diagnosis is made by serology or polymerase chain reaction. […] Diagnosis of chronic Q fever can sometimes be made by real-time, quantitative polymerase chain reaction (qPCR) on the patients blood, but expert advice should be sought for interpretation. […] Because Q fever can be mistaken for other conditions, including other zoonotic diseases (eg leptospirosis, brucellosis), the work-up should be determined by a detailed history, examination and initial screening investigation. […] A useful algorithm for general practitioners (GPs) that describes the recommended approach to diagnostic tests has been previously reported. […] Full blood count, liver function tests and CRP can give some indication of infection, but are not specific.
#1 Q fever: A rural disease with potential urban consequences
https://www1.racgp.org.au/ajgp/2018/march/q-fever
Culture for C. burnetii should be avoided (outside of biosafety level 3 laboratory conditions) as it requires specialised culture techniques and, if successful, can be a high risk for laboratory-acquired infections. […] Serology, to demonstrate specific antibodies, or through specific bacterial nucleic acid detection are the preferred diagnostic tests. […] Ideally, blood should be collected within one week of disease onset to enable the detection of C. burnetii DNA in blood through Q fever PCR (5 mL EDTA). […] A positive PCR result is confirmatory alongside the clinical findings. […] Although a single, high phase 2 IgM antibody titre, in conjunction with a compatible clinical history, is suggestive of acute Q fever infection, it is preferable to demonstrate a fourfold rising antibody titre between an acute blood collection (within seven days of disease onset) and a convalescent specimen collected 7 days after the first collection.
#1
https://www.health.vic.gov.au/infectious-diseases/q-fever
PCR testing is less sensitive in chronic Q fever. Suitable specimens include blood and biopsy specimens of focally infected tissues such as heart tissue, bone or vascular graft. […] Diagnosis of chronic Q fever is usually made by detection of C. burnetii by PCR of heart tissue, bone or vascular graft and can be suggested by detection in blood. It is also suggested by the presence of IgG antibody to C. burnetii phase I antigen 1:1024 by IFA assay. […] The interpretation of Q fever serology results can be challenging. Clinicians should seek advice from their local infectious diseases service or microbiologist as required.
#1 Q Fever Workup: Approach Considerations, Routine Laboratory Studies, Serology
https://emedicine.medscape.com/article/227156-workup
The 3 serologic techniques used for diagnosis include indirect immunofluorescence (IIF) (method of choice), complement fixation, and enzyme-linked immunosorbent assay (ELISA) (comparable to IIF). […] Interpretation of Q fever serology is challenging in regard to discordance of the serologic results from different reference laboratories. […] None of these results should be used in isolation, and their interpretation should always be applied in the appropriate clinical context. False-positive serologic results may occur in legionellosis and leptospirosis. […] Rapid, sensitive, and quantitative polymerase chain reaction (PCR) testing can be done on either whole blood or serum. PCR testing should be obtained during the acute illness (optimally within the first 2 wk of symptom onset) and, preferably, before or shortly after antibiotic administration.
#1 CBBRP – Overview: Coxiella burnetii (Q fever), Molecular Detection, PCR, Blood
https://www.mayocliniclabs.com/test-catalog/overview/62248
Aiding in the diagnosis of Coxiella burnetii infection (eg, Q fever) […] Current diagnostic methods of Q fever endocarditis include serologic studies and histopathologic examination of excised cardiac tissue. These current methods are subjective and nonspecific, limiting usefulness in patient diagnostics. […] Evaluation of infected tissue, blood, or serum using polymerase chain reaction (PCR) has been shown to be an effective tool for diagnosing C burnetii infection. Mayo Clinic Laboratories has developed a real-time PCR test that permits rapid identification of C burnetii. […] A positive result indicates the presence of Coxiella burnetii DNA. […] A negative result indicates the absence of detectable C burnetii DNA but does not negate the presence of the organism and may occur due to inhibition of PCR, sequence variability underlying primers or probes, or the presence of C burnetii DNA in quantities less than the limit of detection of the assay.
#1 CBBRP – Overview: Coxiella burnetii (Q fever), Molecular Detection, PCR, Blood
https://www.mayocliniclabs.com/test-catalog/overview/62248
Test results should be used as an aid in diagnosis and not be considered diagnostic in themselves. A single assay should not be used as the only criteria to form a clinical conclusion, but results should be correlated with patient symptoms and clinical presentation. A negative result does not negate the presence of the organism or active disease.
#1 Q Fever: Causes, Symptoms, Diagnosis, Prevention & Treatment
https://my.clevelandclinic.org/health/diseases/17883-q-fever
Your healthcare provider will diagnose Q fever by asking you about your symptoms and medical history and by taking a blood sample. […] Test results for C. burnetii can take several weeks. If your provider suspects you have Q fever, they might decide to treat you before the results come back. […] To test for Q fever, your healthcare provider will take a sample of your blood with a small needle. Your sample will be sent to a lab to look for signs of an infection with C. burnetii (testing for antibodies). […] They may also try to grow (culture) C. burnetii from your sample. […] You may need to provide multiple samples over time to get a definitive diagnosis.
#1 Department of Health
https://www.health.ny.gov/diseases/communicable/q_fever/fact_sheet.htm
Laboratory diagnosis is accomplished through the identification of specific antibodies to Coxiella burnetii. […] Doxycycline is the treatment of choice for Q fever and should be administered for 15-21 days. […] Treatment of chronic infections like endocarditis require longer courses of antibiotic therapy.
#1 Chronic Q Fever DiagnosisâConsensus Guideline versus Expert Opinion
https://pmc.ncbi.nlm.nih.gov/articles/PMC4480373/
For possible chronic Q fever patients, antibiotic treatment should not be initiated, but follow-up is indicated. […] A critical difference in the diagnostic criteria proposed by Raoult and those of the Dutch Q Fever Consensus Group is the diagnostic value attributed to C. burnetii PCR positivity of blood samples. […] The alternative criteria also generally oppose the term chronic Q fever but makes a distinction in 2 manifestations: Q fever endocarditis and Q fever vascular infection. […] Our data illustrate that, when proven cases of chronic Q fever are missed, and patients are therefore not adequately treated, these patients are at high risk for severe complications and death. […] A single positive C. burnetii PCR of blood is highly suggestive for chronic Q fever when acute Q fever is excluded.
#1 Chronic Q Fever DiagnosisâConsensus Guideline versus Expert Opinion
https://pmc.ncbi.nlm.nih.gov/articles/PMC4480373/
We hope that, with the future results from the Dutch National Chronic Q Fever Database and joint efforts of international researchers and experts in the field of Q fever, these guidelines can be modified to provide definite evidence-based criteria for diagnosis and treatment of this complex disease.
#2 Diagnosis of Q Fever
https://pmc.ncbi.nlm.nih.gov/articles/PMC104936/
Query (Q) fever, due to Coxiella burnetii, is a ubiquitous zoonosis. […] The diagnosis of Q fever relies mainly upon serology, the most commonly used method being the immunofluorescence assay. Serological testing for Q fever should always be done for a patient with a febrile illness and negative blood cultures. […] The most reliable and commonly used methods are indirect immunofluorescence, complement fixation, ELISA, and microagglutination. […] Currently, the immunofluorescence assay is the reference method for the serodiagnosis of Q fever. […] In case of acute Q fever, diagnosis would be confirmed by an immunofluorescence assay titer greater than or equal to the cutoff value (which must be determined for each geographical area) or by a fourfold increase in the antibody titer detected by immunofluorescence assay, complement fixation, ELISA, or microagglutination. […] We recommend that all patients with blood culture-negative endocarditis, febrile patients with aortic aneurysms, and those with prolonged fever, granulomatous hepatitis, or atypical pneumonia in areas where Q fever is endemic should at the very least undergo serological testing for Q fever.
#2 Q fever: Epidemiology, microbiology, and diagnostic tests – UpToDate
https://www.uptodate.com/contents/q-fever-epidemiology-microbiology-and-diagnostic-tests
Q fever: Epidemiology, microbiology, and diagnostic tests […] Antibodies against these phases are used to diagnose the infection. […] This topic discusses the epidemiology, microbiology, and diagnostic test characteristics of Q fever. […] Seroprevalence studies demonstrate that many more people are infected with C. burnetii than the numbers of reported symptomatic Q fever cases suggest. […] Underreporting of Q fever cases probably results from a combination of subclinical infections and, in cases where infection does lead to disease, a failure to recognize it due to nonspecific clinical presentation. […] Q fever likely occurs throughout most of the world, although the incidence and prevalence of infection are unknown in many countries due to lack of surveillance.
#2 Coxiella burnetii – Q Fever | Choose the Right Test
https://arupconsult.com/content/coxiella-burnetii
Serology is the most common diagnostic approach for C. burnetii infection, regardless of whether acute or chronic infection is suspected. […] The standard test for diagnosing acute C. burnetii infection is indirect fluorescent antibody (IFA) testing on paired acute and convalescent sera. […] A fourfold increase in phase II immunoglobulin G (IgG) concentration is considered diagnostic for Q fever. […] PCR testing on serum or whole blood can be used to detect C. burnetii within the first week of illness before antibodies develop, and PCR in combination with serology is recommended in the early stages of infection for a definitive diagnosis of acute Q fever. […] Chronic Q fever can be diagnosed when an individual exhibits both elevated phase I IgG antibody titers and a persistent focus of infection, such as endocarditis.
#2 Q Fever Workup: Approach Considerations, Routine Laboratory Studies, Serology
https://emedicine.medscape.com/article/227156-workup
The 3 serologic techniques used for diagnosis include indirect immunofluorescence (IIF) (method of choice), complement fixation, and enzyme-linked immunosorbent assay (ELISA) (comparable to IIF). […] Interpretation of Q fever serology is challenging in regard to discordance of the serologic results from different reference laboratories. […] None of these results should be used in isolation, and their interpretation should always be applied in the appropriate clinical context. False-positive serologic results may occur in legionellosis and leptospirosis. […] Rapid, sensitive, and quantitative polymerase chain reaction (PCR) testing can be done on either whole blood or serum. PCR testing should be obtained during the acute illness (optimally within the first 2 wk of symptom onset) and, preferably, before or shortly after antibiotic administration.
#2 Chronic Q Fever DiagnosisâConsensus Guideline versus Expert Opinion
https://pmc.ncbi.nlm.nih.gov/articles/PMC4480373/
Literature-based consensus guideline is more sensitive and easier to use in clinical practice. […] We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 20062012. […] A PCR positive for C. burnetii or culture of the organism in blood or tissue, in the absence of acute Q fever, is a strong indicator for chronic Q fever. […] However, sensitivity on blood samples is only 50%60% for both PCR and culture in patients with chronic Q fever. […] Therefore, serologic testing is also valuable for the diagnosis of chronic Q fever. […] A phase I IgG cutoff titer of 1:800, which is based on an in-housedeveloped immunofluorescence assay (IFA), has been internationally accepted for the diagnosis of chronic Q fever and is included in the modified Duke criteria for diagnosis of endocarditis.
#2 Coxiella burnetii – Q Fever | Choose the Right Test
https://arupconsult.com/content/coxiella-burnetii
Coxiella burnetii, the causative agent for Q fever, is primarily transmitted to humans via inhalation of particles excreted by livestock such as cattle, sheep, and goats; other forms of transmission (eg, human to human) are rare. […] Laboratory testing for Q fever includes testing for antibody response to both phase I and phase II antigens. […] Because diagnostic serology tests will return negative results for the first 15 days of illness, treatment should begin before laboratory confirmation of Coxiella burnetii infection (Q fever). […] Certain standard blood tests, such as CBC and liver function tests, can support a diagnosis of Q fever (and assist in the decision to begin treatment) before confirmatory laboratory tests have been completed. […] Testing for acute Q fever (ie, C. burnetii infection) should be considered in individuals with flu-like symptoms (such as fever, headache, and chills) and occupational or travel-related exposure to potentially infected livestock.
#2 Diagnosis of Acute Q Fever | IDR
https://www.dovepress.com/diagnosis-of-acute-q-fever-in-a-patient-by-using-metagenomic-next-gene-peer-reviewed-fulltext-article-IDR
Q fever is a zoonotic disease caused by Coxiella burnetii infection, with domestic ruminants as the main source of infection and tick bites as one of the transmission vectors. The clinical manifestations of Q fever are varied and atypical. For the reason that C. burnetii is a strictly intracellular pathogen, it is difficult to be diagnosed by traditional culture methods. Additionally, serological and molecular diagnostic methods to assist in the diagnosis of Q fever are not routinely performed in most clinical laboratories. Therefore, early and rapid diagnosis of Q fever is a challenge. […] Metagenomic next-generation sequencing is a new diagnostic technology that provides rapid and accurate detection of unexplained infections, including Q fever. Its application plays a crucial role in clinical diagnosis for identifying elusive pathogens.
#2 Clinical diagnosis of Q fever by targeted next-generation sequencing for identification of Coxiella burnetii | BMC Infectious Diseases | Full Text
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10437-6
tNGS is a promising and significant tool for rapidly detecting C. burnetii infection. […] The diagnosis of Q fever primarily relies on laboratory methods due to its non-specific clinical presentation. Diagnostic tools include microbial culture, IFA, qPCR, and mNGS. […] In this study, tNGS was employed to identify C. burnetii, and the results were subsequently confirmed by qPCR at the Beijing CDC, ensuring diagnostic accuracy. […] Therefore, it is too expensive to be carried out to identify the causative pathogens in the fever of unknown cause. However, the cost of blood tNGS is about one-fourth of that of mNGS. […] Therefore, prospective observational studies are needed to evaluate pathogen detection rates and costs of tNGS versus multiplex PCR targeting similar pathogen panels in clinical settings. […] Taken together, since the clinical symptoms of Q fever vary and are non-specific, it is frequently neglected and poorly reported, and tNGS is a promising and significant tool for rapidly detecting C. burnetii infection.
#2 Q Fever Workup: Approach Considerations, Routine Laboratory Studies, Serology
https://emedicine.medscape.com/article/227156-workup
In cases of suspected chronic Q fever, whole blood or serum PCR testing should be performed because recurrent bacteremia may occur. […] Echocardiography is recommended to exclude underlying cardiac lesions. About 30% to 50% of patients with valvular lesions develop chronic endocarditis (most commonly, aortic valve; prosthetic valves are also prone to being affected).
#2 Q Fever â Serology | Public Health Ontario
https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Q-Fever-Serology
Q Fever serology testing is performed once per week. […] Turnaround time is up to 10 days from receipt by PHO laboratory. […] An acute (collected early after the onset of symptoms) and a convalescent (collected 2-3 weeks later) may be required for laboratory diagnosis. […] Q Fever (Coxiella burnetti) serology is performed using Indirect Immunofluorescence antibody (IFA) assay for IgG and IgM for both phase 1 and phase 2 antibodies. […] Results are reported to the ordering physician or health care provider as indicated on the requisition. […] Specimens that are positive for Q-Fever are reported to the Medical Officer of Health as per Health Protection and Promotion Act.
#2 CBBRP – Overview: Coxiella burnetii (Q fever), Molecular Detection, PCR, Blood
https://www.mayocliniclabs.com/test-catalog/overview/62248
Test results should be used as an aid in diagnosis and not be considered diagnostic in themselves. A single assay should not be used as the only criteria to form a clinical conclusion, but results should be correlated with patient symptoms and clinical presentation. A negative result does not negate the presence of the organism or active disease.
#2 Understanding Treatment for Q Fever | ID Care
https://idcare.com/infection/q-fever/
How does ID Care diagnose Q fever? Because the symptoms of Q fever can resemble those of other infectious diseases, an accurate diagnosis is crucial. ID Care physicians will come to an accurate Q fever diagnosis by sending a blood test to the laboratory to check for the Coxiella burnetii bacterium. […] Fortunately, Q fever is easily treated with the antibiotic doxycycline. Most times, ID Care specialists prescribe this antibiotic treatment for about two to three weeks â although the duration of your regimen depends on the severity of your diagnosis. If you have chronic Q fever, we may design a combination of antibiotics for at least 18 months with yearly follow-up tests to ensure youâre healthy and prevent Q fever from returning.
#3 Delayed diagnosis of persistent Q fever: a case series from China | BMC Infectious Diseases | Full Text
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09484-w
Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. […] In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. […] The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. […] Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. […] Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii. […] The definitive diagnosis was achieved through detection of the causative pathogen C. burnetii using metagenomic next-generation sequencing (mNGS) testing.
#3 Diverse and atypical manifestations of Q fever in a metropolitan city hospital: Emerging role of next-generation sequencing for laboratory diagnosis of Coxiella burnetii | PLOS Neglected Tropical Diseases
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010364
Diverse and atypical manifestations are associated with Q fever. […] Next-generation sequencing is becoming an important diagnostic modality for culture-negative infections, particularly those that the physicians fail to recognize clinically, such as Q fever. […] Traditionally, Q fever is diagnosed in the laboratory using serological test by detection of antibodies. Recently, molecular tests such as polymerase chain reaction (PCR) amplification of specific targets have also been employed for more rapid diagnosis of this condition. […] The diagnosis of acute, chronic and convalescent Q fever was made based on a combination of clinical presentation, inflammatory marker levels, echocardiographic findings and serological or molecular test results. […] Seven patients were diagnosed to have Q fever by serological test, nested real-time PCR and next-generation sequencing respectively.