Assessment of fever of unknown origin in adults

Evidence of unrecognised pulmonary tuberculosis (TB) or evidence of old healed TB (e.g., upper lobe fibrosis) may be present; such abnormalities should prompt sputum collection for smear, culture, and nucleic acid amplification testing.

Testing of 3 specimens (minimum 8 hours apart, including an early morning specimen) is recommended in many countries; consult local guidance.[54]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5. https://academic.oup.com/cid/article/64/2/111/2811357 http://www.ncbi.nlm.nih.gov/pubmed/28052967?tool=bestpractice.com ​​

Sputum specimen should be tested in patients with suspected extrapulmonary TB, as active pulmonary TB is seen in 15% to 20% of patients with extrapulmonary TB.​[55]Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82. http://www.ncbi.nlm.nih.gov/pubmed/11948050?tool=bestpractice.com [56]Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78. http://www.ncbi.nlm.nih.gov/pubmed/4050833?tool=bestpractice.com [57]Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62. http://www.ncbi.nlm.nih.gov/pubmed/855317?tool=bestpractice.com

Culture of Mycobacterium tuberculosis typically takes several weeks (up to 8), decisions on treatment are usually made before culture results are known.​​​​

Microscopy should be performed on specimens collected from sites of suspected extrapulmonary TB.[54]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5. https://academic.oup.com/cid/article/64/2/111/2811357 http://www.ncbi.nlm.nih.gov/pubmed/28052967?tool=bestpractice.com ​​[58]Nataraj G, Kurup S, Pandit A, et al. Correlation of fine needle aspiration cytology, smear and culture in tuberculous lymphadenitis: a prospective study. J Postgrad Med. 2002 Apr-Jun;48(2):113-6. http://www.ncbi.nlm.nih.gov/pubmed/12215692?tool=bestpractice.com

Culture result may take several weeks.​

NAAT should be performed on at least one respiratory specimen (or specimen collected from sites of suspected extrapulmonary TB) when a diagnosis of TB is being considered.​ NAAT may speed the diagnosis in smear-negative cases and may be helpful to differentiate non-tuberculous mycobacteria when sputum is AFB smear positive but NAAT negative.​[59]Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. Jan 2009 [internet publication]. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5801a3.htm Genotyping might be considered useful in outbreaks of TB to identify transmission of TB, especially when contact had not been appreciated in the course of epidemiological investigations.​

Although NAATs were originally designed and approved for respiratory specimens, they may also be requested on specimens from other sites where involvement of TB is suspected (e.g., cerebrospinal fluid, lymph node aspirate, lymph node biopsy, pleural fluid, peritoneal fluid, pericardial fluid, synovial fluid or urine).[54]Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5. https://academic.oup.com/cid/article/64/2/111/2811357 http://www.ncbi.nlm.nih.gov/pubmed/28052967?tool=bestpractice.com [60]World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].​ https://www.who.int/publications/i/item/9789240089488 ​​​​​ In the US, use of NAATs for extrapulmonary specimens is not approved by the Food and Drug Administration, and use would be off-label. Several rapid NAATs are available for the diagnosis of TB and some are also able to detect genes encoding resistance to TB drugs.[60]World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].​ https://www.who.int/publications/i/item/9789240089488 ​​

Broncho-alveolar lavage may be indicated in patients in whom sputum induction is unsuccessful or in whom smear and NAAT are negative. Bronchoscopy is useful when other diagnoses are strongly considered or in patients in whom pulmonary TB is still suspected after other methods proved non-diagnostic.

Trans-bronchial lung biopsies are useful in the diagnosis of miliary disease as granulomas may be visible.

One Cochrane review found the lateral flow urine lipoarabinomannan (LF-LAM) assay to have a sensitivity of 42% in diagnosing TB in HIV-positive individuals with TB symptoms, and 35% in HIV-positive individuals not assessed for TB symptoms.[61]Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011420.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/31633805?tool=bestpractice.com [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in symptomatic HIV‐positive adults?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2824/fullShow me the answer [ ] What is the accuracy of lateral flow urine lipoarabinomannan (LF‐LAM) for detecting tuberculosis (TB) in unselected HIV‐positive adults (symptomatic or asymptomatic)?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2825/fullShow me the answer​​​ WHO recommends that LF-LAM can be used to assist in the diagnosis of active TB in HIV-positive adults, adolescents, and children with signs and symptoms of TB, or in those with advanced HIV or who are seriously ill.​[60]World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].​ https://www.who.int/publications/i/item/9789240089488

Culture would still be required for drug susceptibility testing (DST).

Bronchiectasis can be seen in chronic cases. Haemoptysis usually originates from bronchial arteries, but Rasmussen's aneurysms from a pulmonary artery adjacent to a cavity can be the source of bleeding.

Residual bronchiectasis from old TB can cause haemoptysis.

4th-generation tests detect both the p24 (HIV-1) antigen and the HIV-1/HIV-2Ab antibody.[62]Centers for Disease Control and Prevention. 2018 quick reference guide: recommended laboratory HIV testing algorithm for serum or plasma specimens. January 2018 [internet publication]. https://stacks.cdc.gov/view/cdc/50872 [63]Centers for Disease Control and Prevention. Laboratory testing for the diagnosis of HIV infection: updated recommendations. June 2014 [internet publication]. https://stacks.cdc.gov/view/cdc/23447  These antigens are useful for diagnosing very early HIV infections when antibody levels are still low.

Less sensitive than CT; can be performed if CT not available.

MRI may be needed to confirm sinusitis due to fungal infection or tumour. A low signal intensity suggests fungal process. MRI more sensitive than CT for soft tissue pathology.

Rarely needed.

Note that infective endocarditis due to aspergillus is usually characterised by negative blood cultures.[64]McCormack J, Pollard J. Aspergillus endocarditis 2003-2009. Med Mycol. 2011 Apr;49 Suppl 1:S30-4. https://academic.oup.com/mmy/article/49/Supplement_1/S30/980952 http://www.ncbi.nlm.nih.gov/pubmed/20608781?tool=bestpractice.com [65]Talha KM, DeSimone DC, Sohail MR, et al. Pathogen influence on epidemiology, diagnostic evaluation and management of infective endocarditis. Heart. 2020 Dec;106(24):1878-82. http://www.ncbi.nlm.nih.gov/pubmed/32847941?tool=bestpractice.com ​​ Real-time PCR may be considered in blood culture-negative endocarditis.[65]Talha KM, DeSimone DC, Sohail MR, et al. Pathogen influence on epidemiology, diagnostic evaluation and management of infective endocarditis. Heart. 2020 Dec;106(24):1878-82. http://www.ncbi.nlm.nih.gov/pubmed/32847941?tool=bestpractice.com

Typically elevated, but normal result does not exclude diagnosis if clinical picture suggestive.

May be necessary if transthoracic echocardiography not conclusive.[66]Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med. 1994 Mar;96(3):200-9. http://www.ncbi.nlm.nih.gov/pubmed/8154507?tool=bestpractice.com [67]Kupferwasser LI, Darius H, Muller AM, et al. Diagnosis of culture-negative endocarditis: the role of the Duke criteria and the impact of transesophageal echocardiography. Am Heart J. 2001 Jul;142(1):146-52. http://www.ncbi.nlm.nih.gov/pubmed/11431671?tool=bestpractice.com

Useful for diagnosis and monitoring disease progress.

Specialised panoramic x-ray looking at entire maxilla and mandible.

Decreased T1 signal, increased T2 signal represents marrow fat replaced by water due to oedema, exudates, or ischaemia.

Perform after prostate examination and milking.

Results take 3 weeks.

Detects the presence of CMV proteins in the peripheral smear; most useful in immunocompromised patients.

May be required for localised infection.

Test for heterophile antibody (Paul-Bunnell IgM). False negative common early in course. Antibodies usually persist for 3 months.

Indicated if monospot test is negative, to differentiate EBV infection from other infectious causes of mononucleosis.

Molecular testing is required to confirm the diagnosis. Priorities for testing depend on local guidelines and available resources.

Collect upper respiratory specimens (nasopharyngeal and oropharyngeal swab or wash) in ambulatory patients and/or lower respiratory specimens (sputum and/or endotracheal aspirate or bronchoalveolar lavage) in patients with more severe respiratory disease.

Associated with prolonged PR interval. Can help eliminate other causes of cardiac symptoms.

Use a sensitive EIA or IFA as a first step. Confirm positive or equivocal results with the standardised Western blot assay or second EIA.[68]Centers for Disease Control and Prevention (CDC). Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 1995 Aug 11;44(31):590-1. http://www.ncbi.nlm.nih.gov/pubmed/7623762?tool=bestpractice.com [69]Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703. https://www.cdc.gov/mmwr/volumes/68/wr/mm6832a4.htm?s_cid=mm6832a4_w http://www.ncbi.nlm.nih.gov/pubmed/31415492?tool=bestpractice.com ​​

In the US, some enzyme immunoassays have been approved by the Food and Drug Administration for serological diagnosis of Lyme disease and can be used in place of Western blot assays for the second step.[69]Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703. https://www.cdc.gov/mmwr/volumes/68/wr/mm6832a4.htm?s_cid=mm6832a4_w http://www.ncbi.nlm.nih.gov/pubmed/31415492?tool=bestpractice.com

Use a sensitive EIA or IFA as a first step. Confirm positive or equivocal results withthe standardised Western blot assay or second EIA.[68]Centers for Disease Control and Prevention (CDC). Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 1995 Aug 11;44(31):590-1. http://www.ncbi.nlm.nih.gov/pubmed/7623762?tool=bestpractice.com [69]Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703. https://www.cdc.gov/mmwr/volumes/68/wr/mm6832a4.htm?s_cid=mm6832a4_w http://www.ncbi.nlm.nih.gov/pubmed/31415492?tool=bestpractice.com

In the US, some enzyme immunoassays have been approved by the Food and Drug Administration for serological diagnosis of Lyme disease andcan be used in place of Western blot assays for the second step.[69]Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703. https://www.cdc.gov/mmwr/volumes/68/wr/mm6832a4.htm?s_cid=mm6832a4_w http://www.ncbi.nlm.nih.gov/pubmed/31415492?tool=bestpractice.com

Used to confirm the diagnosis if the IFA or ELISA are positive or equivocal.

Usually asymptomatic, so diagnosed on FBC.

Abnormalities include promyelocytes, myelocytes, metamyelocytes, and band forms.

Diagnosis is usually made through scanning and confirmed by biopsy.[70]Knockaert DC, Vanneste LJ, Bobbaers HJ. Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. Medicine (Baltimore). 1993 May;72(3):184-96. http://www.ncbi.nlm.nih.gov/pubmed/8502169?tool=bestpractice.com

Indicated when PET scan is not available. Diagnosis is usually confirmed by biopsy.[70]Knockaert DC, Vanneste LJ, Bobbaers HJ. Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. Medicine (Baltimore). 1993 May;72(3):184-96. http://www.ncbi.nlm.nih.gov/pubmed/8502169?tool=bestpractice.com

Diagnosis is usually made through scanning and confirmed by biopsy.[70]Knockaert DC, Vanneste LJ, Bobbaers HJ. Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. Medicine (Baltimore). 1993 May;72(3):184-96. http://www.ncbi.nlm.nih.gov/pubmed/8502169?tool=bestpractice.com

Diagnosis is usually made through CT scanning and confirmed by biopsy.[70]Knockaert DC, Vanneste LJ, Bobbaers HJ. Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. Medicine (Baltimore). 1993 May;72(3):184-96. http://www.ncbi.nlm.nih.gov/pubmed/8502169?tool=bestpractice.com

Diagnosis is usually made through CT scanning and confirmed by biopsy.[70]Knockaert DC, Vanneste LJ, Bobbaers HJ. Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. Medicine (Baltimore). 1993 May;72(3):184-96. http://www.ncbi.nlm.nih.gov/pubmed/8502169?tool=bestpractice.com

Diagnosis is based on the clinical presentation along with an elevated erythrocyte sedimentation rate and a prompt and dramatic response to corticosteroids.[71]Salvarani C, Cantini F, Boiardi L, et al. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002 Jul 25;347(4):261-71. http://www.ncbi.nlm.nih.gov/pubmed/12140303?tool=bestpractice.com ​​

Ultrasound is the preferred early imaging test in guidelines for patients with suspected giant cell arteritis.[72]Dejaco C, Ramiro S, Bond M, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update. Ann Rheum Dis. 2023 Aug 7;ard-2023-224543. https://ard.bmj.com/content/early/2023/08/07/ard-2023-224543 http://www.ncbi.nlm.nih.gov/pubmed/37550004?tool=bestpractice.com [73]Ponte C, Grayson PC, Robson JC, et al. 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis. Arthritis Rheumatol. 2022 Dec;74(12):1881-9. http://www.ncbi.nlm.nih.gov/pubmed/36350123?tool=bestpractice.com ​ Axillary arteries should be included in the standard examination.[73]Ponte C, Grayson PC, Robson JC, et al. 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis. Arthritis Rheumatol. 2022 Dec;74(12):1881-9. http://www.ncbi.nlm.nih.gov/pubmed/36350123?tool=bestpractice.com

If clinical suspicion is high, treatment should not be delayed while awaiting this test.[19]Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65. https://onlinelibrary.wiley.com/doi/10.1002/art.41774 http://www.ncbi.nlm.nih.gov/pubmed/34235884?tool=bestpractice.com [74]Younge BR, Cook BE Jr, Bartley GB, et al. Initiation of glucocorticoid therapy: before or after temporal artery biopsy? Mayo Clin Proc. 2004 Apr;79(4):483-91. http://www.ncbi.nlm.nih.gov/pubmed/15065613?tool=bestpractice.com ​​​​​

Often positive, but only moderate sensitivity and specificity for systemic lupus erythematosus.

May show proteinuria or casts if there is renal involvement.

Rheumatoid factor test is positive in about 75% of people with rheumatoid arthritis.[75]Saraux A, Berthelot JM, Chales G, et al. Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum. 2001 Nov;44(11):2485-91. http://www.ncbi.nlm.nih.gov/pubmed/11710704?tool=bestpractice.com

More specific than rheumatoid factor.

Can help to differentiate rheumatoid arthritis from other causes of joint swelling.

May help to exclude other causes of arthritis.

Sensitivity and specificity of this test are low.​ While HLA-B27 is not specific to, or required for, the diagnosis of ReA, its presence in the proper clinical context improves the accuracy of the diagnosis.[76]Sieper J, Rudwaleit M, Braun J, et al. Diagnosing reactive arthritis: role of clinical setting in the value of serologic and microbiologic assays. Arthritis Rheum. 2002 Feb;46(2):319-27. https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.504 http://www.ncbi.nlm.nih.gov/pubmed/11840434?tool=bestpractice.com [77]van der Linden SM, Valkenburg HA, de Jongh BM, et al. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum. 1984 Mar;27(3):241-9. https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.1780270301 http://www.ncbi.nlm.nih.gov/pubmed/6608352?tool=bestpractice.com [78]Omair MA, AlDuraibi FK, Bedaiwi MK, et al. Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia. Clin Rheumatol. 2017 Jul;36(7):1537-43. http://www.ncbi.nlm.nih.gov/pubmed/28456926?tool=bestpractice.com ​​​​

Withdrawal of medication usually results in resolution of fever within 48 to 72 hours.[79]Arnow PM, Flaherty JP. Fever of unknown origin. Lancet. 1997 Aug 23;350(9077):575-80. http://www.ncbi.nlm.nih.gov/pubmed/9284789?tool=bestpractice.com

Aspartate aminotransferase (AST) greater than alanine aminotransferase (ALT) in alcohol origin.

Hepatitis C antibody test is unreliable; if high clinical suspicion, obtain viral load.

In lupoid (autoimmune) hepatitis, autoantibody tests may detect ANA, antiliver kidney microsomal antibody, and elevated IgG levels.

Viral, alcohol, or autoimmune.

A marker of active disease, elevated in many patients. ACE levels cannot be used for diagnosis and may not reflect disease activity.[80]Thillai M, Atkins CP, Crawshaw A, et al. BTS Clinical Statement on pulmonary sarcoidosis. Thorax. 2021 Jan;76(1):4-20. http://www.ncbi.nlm.nih.gov/pubmed/33268456?tool=bestpractice.com ​ Biopsy is preferable.

Biopsy of lesions in the lungs, skin, lymph nodes, liver, or kidneys can confirm the diagnosis.

Acute-phase reactant and might remain elevated in between attacks. Not specific or diagnostic.

Acute-phase reactant and might remain elevated in between attacks. Not specific or diagnostic.

Good-quality thick and thin films should be assessed.[81]World Health Organization. WHO guidelines for malaria. 2023 [internet publication]. https://iris.who.int/bitstream/handle/10665/373339/WHO-UCN-GMP-2023.01-Rev.1-eng.pdf?sequence=1  Thin films should be stained with a Giemsa stain and thick films with either a Giemsa or a Field stain. Giemsa should be used at pH 7.2.[82]Rogers CL, Bain BJ, Garg M, et al. British Society for Haematology guidelines for the laboratory diagnosis of malaria. Br J Haematol. 2022 May;197(3):271-82. https://onlinelibrary.wiley.com/doi/10.1111/bjh.18092 http://www.ncbi.nlm.nih.gov/pubmed/35262915?tool=bestpractice.com

These immunochromatographic tests detect the presence of malaria antigen or enzyme and typically give a visible band after 15 minutes if positive.

Problems have included poor detection of species other than Plasmodium falciparum and false-negative results at lower parasite burden.[83]Pattanasin S, Proux S, Chompasuk D, et al. Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):672-4. http://www.ncbi.nlm.nih.gov/pubmed/16117960?tool=bestpractice.com [84]Ashley EA, Touabi M, Ahrer M, et al. Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria. Malar J. 2009 Oct 27;8:241. https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-8-241 http://www.ncbi.nlm.nih.gov/pubmed/19860920?tool=bestpractice.com [85]Yerlikaya S, Campillo A, Gonzalez IJ. A Systematic review: performance of rapid diagnostic tests for the detection of Plasmodium knowlesi, Plasmodium malariae, and Plasmodium ovale monoinfections in human blood. J Infect Dis. 2018 Jun 20;218(2):265-76. https://academic.oup.com/jid/article/218/2/265/4938977 http://www.ncbi.nlm.nih.gov/pubmed/29554284?tool=bestpractice.com ​​​​ However, some studies have shown that performance of RDTs can be equivalent to expert microscopy.[86]Stauffer WM, Cartwright CP, Olson DA, et al. Diagnostic performance of rapid diagnostic tests versus blood smears for malaria in US clinical practice. Clin Infect Dis. 2009 Sep 15;49(6):908-13. https://academic.oup.com/cid/article/49/6/908/334568 http://www.ncbi.nlm.nih.gov/pubmed/19686072?tool=bestpractice.com [87]Nicastri E, Bevilacqua N, Sañé Schepisi M, et al. Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR methods and evidence of antimalarial overprescription in non-severe febrile patients in two Tanzanian hospitals. Am J Trop Med Hyg. 2009 May;80(5):712-7. http://www.ncbi.nlm.nih.gov/pubmed/19407111?tool=bestpractice.com ​​​ 

RDTs should be used if quality-assured malaria microscopy is not readily available.[81]World Health Organization. WHO guidelines for malaria. 2023 [internet publication]. https://iris.who.int/bitstream/handle/10665/373339/WHO-UCN-GMP-2023.01-Rev.1-eng.pdf?sequence=1

Creatinine level must be included to ensure adequate urine collection.

If clinical suspicion high; has high false-positive rate.

All laboratory tests typically normal.

All laboratory tests typically normal.

Rapid decrease in platelet count and elevated haematocrit is a warning sign that indicates a patient with dengue infection is about to enter the critical phase of infection, i.e., develop dengue haemorrhagic fever.[88]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication]. https://iris.who.int/bitstream/handle/10665/204894/B4751.pdf?sequence=1&isAllowed=y [89]Teixeira MG, Barreto ML. Diagnosis and management of dengue. BMJ. 2009 Nov 18;339:b4338. http://www.ncbi.nlm.nih.gov/pubmed/19923152?tool=bestpractice.com

Hypoalbuminaemia suggests plasma leakage.

IgM and IgG in a single serum sample (highly suggestive of infection); IgM or IgG seroconversion in paired sera or a fourfold IgG titre increase in paired sera (confirms infection); IgM:IgG ratio <1.2 (suggests secondary infection); negative result does not exclude infection unless paired sera are tested.

Serology may be negative in the first 5 days of illness; therefore, IgM enzyme-linked immunosorbent assay (ELISA) and IgG ELISA are the serological tests of choice after the first 5 days of illness (polymerase chain reaction [PCR] is more sensitive in the first 5 days). The presence of IgG in the first few days of infection strongly suggests a secondary infection.[88]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication]. https://iris.who.int/bitstream/handle/10665/204894/B4751.pdf?sequence=1&isAllowed=y

Test of choice for viral nucleic acid detection and can be ordered within the first 5 days of illness.[90]Centers for Disease Control and Prevention. CDC DENV-1-4 real-time RT-PCR multiplex assay. Jun 2023 [internet publication]. https://www.cdc.gov/dengue/healthcare-providers/testing/molecular-tests/realtime.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdengue%2Fclinicallab%2Frealtime.html [91]Centers for Disease Control and Prevention. CDC DENV-1-4 rRT-PCR multiplex and trioplex rRT-PCR assays. Jan 2020 [internet publication]. https://www.cdc.gov/dengue/healthcare-providers/testing/molecular-tests/assays.html Cerebrospinal fluid, whole blood, serum, or plasma specimen can be used.[90]Centers for Disease Control and Prevention. CDC DENV-1-4 real-time RT-PCR multiplex assay. Jun 2023 [internet publication]. https://www.cdc.gov/dengue/healthcare-providers/testing/molecular-tests/realtime.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdengue%2Fclinicallab%2Frealtime.html [91]Centers for Disease Control and Prevention. CDC DENV-1-4 rRT-PCR multiplex and trioplex rRT-PCR assays. Jan 2020 [internet publication]. https://www.cdc.gov/dengue/healthcare-providers/testing/molecular-tests/assays.html ​​

Detection of the non-structural protein 1 (NS1) using ELISA or rapid test kits is useful in early diagnosis and can be ordered from days 1 to 9 of the illness.[92]Lima Mda R, Nogueira RM, Schatzmayr HG, et al. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis. 2010 Jul 6;4(7):e738. https://www.doi.org/10.1371/journal.pntd.0000738 http://www.ncbi.nlm.nih.gov/pubmed/20625558?tool=bestpractice.com A serum specimen should be used.

Not required for diagnosis but may play a useful role in the management of infection in patients with haemorrhagic signs.

A lateral decubitus chest x-ray of the right-hand side of the chest can be ordered to detect clinically undetectable pleural effusion in the early phase of plasma leakage.