Editing Fever Q (section)

== Diagnosis ==
[[File:Q fever management algorithm.gif|thumb|Q&nbsp;fever management algorithm from the [[wikipedia:Centers for Disease Control and Prevention|CDC]].]]
Several aspects of the disease make [[wikipedia:Medical diagnosis|diagnosis]] of Q&nbsp;fever a difficult and lengthy process, usually relying on [[wikipedia:Serology|serology]],<ref name="maurin">{{Cite journal|last1=Maurin|first1=M.|last2=Raoult|first2=D.|title=Q fever|url=https://journals.asm.org/doi/10.1128/cmr.12.4.518|journal=Clinical Microbiology Reviews|date=1999-10-01|volume=12|issue=4|pages=518–553|doi=10.1128/CMR.12.4.518|pmc=88923|pmid=10515901|access-date=2024-09-26|df=mdy-all}}</ref><ref name="scola">{{Cite journal|last=La Scola|first=Bernard|title=Current laboratory diagnosis of Q&nbsp;fever|journal=Seminars in Pediatric Infectious Diseases|date=October 2002|volume=13|issue=4|pages=257–262|doi=10.1053/spid.2002.127199|pmid=12491231}}</ref> after the onset of symptoms. The reference standard is an [[wikipedia:Immunofluorescence#Secondary (indirect)|indirect fluorescent antibody (IFA)]] test to look for an [[wikipedia:Immunoglobulin G|immunoglobulin G]] (IgG) [[wikipedia:Immune response|response]] to the infection, performed on [[wikipedia:Paired data|paired]] [[wikipedia:Serum (blood)|serum]] samples taken at least two weeks apart. A fourfold or greater rise in [[wikipedia:Titer#Antibody titer|antibody titers]] is needed for a positive result, with accuracy increasing commensurate to the interval between when the samples are taken, three to six weeks being optimal. [[wikipedia:Antibody|Antibodies]] to ''C. burnetii'' tend to remain elevated for many months and sometimes even years after the disease has resolved. [[wikipedia:Sampling (statistics)|Statistical sampling]] suggests that approximately 3% of healthy adults in the U.S. and up to 20% of people in high-risk professions—[[wikipedia:Veterinarian|veterinarians]], [[wikipedia:Ranch|ranchers]], etc.—have elevated titers from past Q&nbsp;fever infections, though the large majority of those prior infections will have been asymptomatic, and thus, untreated.<ref name="cdc_diagnosis">{{Cite web|title=Clinical and Laboratory Diagnosis for Q&nbsp;Fever|date=2024-05-15|url=https://www.cdc.gov/q-fever/hcp/diagnosis-testing/index.html|website=[[wikipedia:Centers for Disease Control and Prevention|CDC]]|archive-url=https://web.archive.org/web/20240927064825if_/https://www.cdc.gov/q-fever/hcp/diagnosis-testing/index.html|archive-date=2024-09-27|url-status=live|language=en-US|access-date=2024-09-26|df=mdy-all}}</ref>

If a more rapid determination of Q&nbsp;fever infection is needed during the [[wikipedia:Acute (medicine)|acute]] phase of the illness (such as when a [[wikipedia:Differential diagnosis|differential diagnosis]] cannot exclude other, more serious potential causes), a [[wikipedia:Polymerase chain reaction|polymerase chain reaction]] (PCR) [[wikipedia:Assay|assay]] can be performed on a sample of [[wikipedia:Whole blood|whole blood]]—or serum, at some laboratories—to detect the presence of ''C. burnetii'' [[wikipedia:Nucleic acid sequence|DNA sequences]] at the molecular level. This method is most sensitive in the first week of illness, before the appearance of detectable levels of organism-specific antibodies, and is quickly rendered mostly ineffective following the start of standard treatment regimens. While a positive PCR result can be a key element in diagnosis, particularly for patients suffering an extreme course of symptoms, a negative result does not rule out the infection and a serological result should be determined afterwards for greater certainty.<ref name="cdc_diagnosis" />

Diagnosis of the [[wikipedia:Chronic condition|chronic form]] of the infection relies on the two distinct [[wikipedia:Antigen|antigenic]] [[wikipedia:Phase variation|phases]] (I and II, corresponding to the more and less [[wikipedia:Virulence|virulent]] forms of the pathogen, respectively) of human antibody responses. In acute infections, the phase II antigen will be predominant, due to a combination of natural immune response as well as the necessary delay between patient samples for the test comparison. However, the reverse is true for chronic infections, which are associated with a rising phase I IgG titer (≥1:2<sup>10</sup>)—potentially higher than even phase II—showing the failure of the immune system to arrest the progression of the disease as expected.<ref name="cdc_diagnosis" />

Looking for the bacteria themselves in blood via [[wikipedia:Microbiological culture|culture isolation]] is both technically difficult and time consuming, and only available at specialized microbiology laboratories, making it ill-suited for routine diagnoses; common hospital [[wikipedia:Blood culture|blood cultures]] are unable to detect the organism.<ref name="cdc_diagnosis" />

When Q&nbsp;fever causes endocarditis, [[wikipedia:Echocardiography#Transesophageal echocardiogram|transesophageal echocardiography]] may be required to properly diagnose it. Q&nbsp;fever hepatitis manifests as an elevation of [[wikipedia:Alanine transaminase|alanine transaminase]] and [[wikipedia:Aspartate transaminase|aspartate transaminase]], but a definitive diagnosis is only possible on [[wikipedia:Liver biopsy|liver biopsy]], which shows the characteristic [[wikipedia:Fibrin ring granuloma|fibrin ring granulomas]].<ref name="veerdonk">{{Cite journal|last1=van de Veerdonk|first1=Frank Leo|last2=Schneeberger|first2=Peter Martin|title=Patient with Fever and Diarrhea|url=https://academic.oup.com/cid/article/42/7/1051/322183|journal=Clinical Infectious Diseases|date=2006-04-01|volume=42|issue=7|pages=1051–1052|archive-url=https://web.archive.org/web/20240928005750if_/https://academic.oup.com/cid/article/42/7/1051/322183|archive-date=2024-09-28|url-status=live|doi=10.1086/501027|doi-access=free|access-date=2024-09-27|df=mdy-all}}</ref>