718
Pathology (2015), 47(7), December
CORRESPONDENCE
C. M. Florkowski P. M. George
Syphilis diagnosis algorithm Serum
Canterbury Health Laboratories, Christchurch, New Zealand
EIA
Contact A/Prof C. M. Florkowski. E-mail: [email protected]
POS
NEG No futher testing
Known positive?
1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551–67. 2. Thygesen K, Mair J, Giannitsis E, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012; 33: 2252–7. 3. Florkowski CM, Wallace J, Walmsley T, George P. The effect of hemolysis on current troponin assays – a confounding preanalytical variable. Clin Chem 2010; 56: 1195–7. 4. Lippi G, Avanzini P, Dipalo M, Aloe R, Cervellin G. Influence of hemolysis on troponin testing: studies on Beckman Coulter UniCel DxI 800 Accu-TnI and overview of the literature. Clin Chem Lab Med 2011; 49: 2097–100. 5. Koerbin G, Tate J, Potter JM, Cavanaugh J, Glasgow N, Hickman PE. Characterisation of a highly sensitive troponin I assay and its application to a cardio-healthy population. Clin Chem Lab Med 2012; 50: 871–8. 6. Meites S. Reproducibly simulating hemolysis, for evaluating its interference with chemical methods. Clin Chem 1973; 19: 1319. 7. Sawyer N, Blennerhassett J, Lambert R, Sheehan P, Vasikaran S. Outliers affecting cardiac troponin I measurement: comparison of a new high sensitivity assay with a contemporary assay on the Abbott ARCHITECT analyser. Ann Clin Biochem 2014; 51: 476–84. 8. Kavsak PA, Worster A, You JJ, et al. Ninety-minute vs 3-h performance of high-sensitivity cardiac troponin assays for predicting hospitalization for acute coronary syndrome. Clin Chem 2013; 59: 1407–10. 9. Krintus M, Kozinski M, Boudry P, et al. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay. Clin Chem Lab Med 2014; 52: 1657–65. 10. Dwyer DG, Fry M, Somerville A, Holdgate A. Randomised single blinded control trial comparing haemolysis rate between two cannula aspiration techniques. Emerg Med Aust 2006; 18: 484–8. 11. Ryan JB, Stuart LA, Southby SJ, et al. Comparison of BD Vacutainer Rapid Serum Tube and plasma for haemolysis markers in the emergency department. Ann Clin Biochem 2015; 52: 293–6.
DOI: 10.1097/PAT.0000000000000342
Evaluation of the Dual Path Platform syphilis point of care test in North Queensland Sir, The rate of diagnosis of syphilis in North Queensland Aboriginal and Torres Straight Islander populations has continued to rise over the past 6 years, from 16.1% in 2009 to 36.4% in 2013.1,2 In particular, the regions surrounding Mount Isa have been marked by ongoing syphilis outbreaks, with a total of 284 cases from January 2010 to March 2015. Of these cases, 99% occurred in patients of Indigenous origin, and 95% aged less than 35 years.1 Resurgence of disease in rural and remote communities has been attributed to geographical and sociocultural constraints delaying disease presentation.3 The current algorithm for diagnosis of infectious syphilis in Pathology Queensland (Fig. 1) uses two treponemal tests [enyme immunoassay IgG (EIA IgG; Abbott, USA) and the Treponema pallidum particle agglutination test (TPPA; Fujirebio, Japan)], and one non-treponemal antibody test [rapid plasma reagin (RPR; BD, USA)]. Non-treponemal tests, while non-specific, become elevated with acute infection and subsequently increase the sensitivity of diagnosis. This allows for the detection of active disease. Treponemal tests are utilised in
YES
Perform RPR
NO
Perform RPR and confirmatory TPPA TPPA NEG Confirmed positive
Apply comment reporting possible false positive result and suggest retesting in 2–4 weeks
Fig. 1 Townsville laboratory syphilis diagnosis algorithm. EIA, enzyme immunoassay IgG (Abbott, USA); RPR, rapid plasma reagin (BD, USA); TPPA, Treponema pallidum particle agglutination test (Fujirebio, Japan).
a confirmatory capacity.4 Treponemal antibody tests remain elevated for life, and therefore do not always reflect active infection.4,5 A positive TPPA test in conjunction with a positive RPR test is indicative of current infection with T. pallidum, while a positive TPPA test with a negative RPR test is indicative of inactive infection.3–5 A new point of care test (PoCT), the Dual Path Platform (DPP) Syphilis Screen and Confirm Assay (Chembio, USA) is based on the simultaneous detection of non-treponemal and treponemal antibodies. It improves on previous syphilis PoCT assays, with the additional ability to detect non-treponemal antibodies. This consequently allows for a differentiation between active infection and inactive disease, with the nontreponemal antibody decreasing or becoming absent in treated disease.4 Ethics approval was granted and a total of 449 stored frozen sera obtained during sexual health clinic screens over the last 12 months in North Queensland were tested with the DPP Syphilis PoCT. The DPP Syphilis PoCT consists of both a treponemal marker and non-treponemal marker (Fig. 2), in addition to a procedural control marker. The treponemal marker (line 1) detects IgG to T. pallidum, whilst the non-treponemal marker (line 2) detects IgM and IgG antibodies to lipoidal material and cardiolipin antibodies.6,7 If the antibodies to syphilis (treponemal and non-treponemal) are present, then two pink/purple lines are produced, in addition to the control line, and signify active infection. The absence of treponemal and/or non-treponemal antibodies results in no pink/purple lines in the test area.6 The test was performed according to instructions provided by the manufacturers, and interpreted by medical staff in the Townsville laboratory. Comparison was made with the gold standard tests EIA, TPPA, and RPR. Known positive and negative results were deidentified to ensure interpretation was non-biased, and a spectrum of serum titres ranging from 2 to 256 were tested. Discrepant results were retested with the DPP Syphilis PoCT, but the result of the gold standard was accepted over the result of the DPP Syphilis PoCT. Results were then entered into a central database. Each specimen had been previously tested according to the standard testing regimen at the Townsville laboratory to provide a comparison of PoCT to gold standard. Of the 449 specimens, 217 tested positive by the DPP Syphilis PoCT (non-treponemal line) compared to 227 by the comparator RPR test (Table 1). Analysis of these results
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
A
719
B
Fig. 2 Structure of the Chembio dual POC test for syphilis showing the locations of the antigen lines. (A) Dissected view following testing of reactive serum; (B) complete cassette following testing of reactive serum.
demonstrated a sensitivity of 95.6% and specificity of 66.2% when compared to the RPR gold standard. The sensitivity of the DPP Syphilis PoCT in this study compared to the manufacturer’s testing was equivalent (88.6–98.7%); however, it demonstrated a lower specificity when compared with the manufacturer’s testing (98.6%).6 Of the 449 specimens, 319 tested positive by the treponemal line of the DPP Syphilis PoCT compared to 341 by the comparator TPPA test (Table 2). This demonstrated a sensitivity of 93.5% and specificity of 87%, with a positive predictive value of 95.8%. The sensitivity and specificity were less than that achieved through the manufacturer’s testing (sensitivity 96.5%, specificity 95.5%)6 and comparable with independent, peer-reviewed testing (sensitivity 89.8%, specificity 98.3%).8 A recent study looking at the diagnosis of syphilis based solely on a treponemal PoCT demonstrated a sensitivity of 81.5% [95% confidence interval (CI) 76.6–86.4%], and a specificity of 100%.5 The study reported here showed an improved sensitivity with the additional detection of non-treponemal antibodies (95.6%). However it demonstrated a lower specificity (66.2%) when compared with the treponemal PoCT. Table 1 Results of the Chembio DPP Screen and Confirm Assay in comparison to the laboratory reference method Syphilis RPR status via reference method Syphilis RPR status via PoCT Positive Negative Total
Positive
Negative
Total
217 10 227
75 147 222
292 157 449
Limitations of the study included the use of stored serum over fresh serum or whole blood. This might have reduced the sensitivity and specificity of the test. The DPP Syphilis PoCT offers an alternative to laboratory diagnostic methods of syphilis diagnosis in rural and remote regions. It allows for diagnosis at the point of care, such as a primary healthcare clinic, where diagnosis is often delayed due to geographic isolation and poor access to laboratory services. Treatment of early syphilis is crucial in reducing the spread of disease in communities, and incidence of disease sequelae. The DPP Syphilis PoCT allows for simultaneous diagnosis and treatment, which is important in regions where patients are mobile and do not return to health clinics for test results. However, due to a lower specificity of the test compared to the gold standard testing regimen (Fig. 1), it would result in higher rates of unnecessary treatment. Biologically false positive results compared to true positive results would be impossible to separate based solely on the DPP Syphilis PoCT, increasing the need for parallel testing with the gold standard. It is important to note that diagnosis is never made based only on laboratory information, and that history and examination continue to form a large part of the clinical diagnosis. Current treatment of syphilis consists of one dose of intramuscular benzathine penicillin. The risk of treating biologically false positives is small when compared with the risks presented by failure to treat congenital syphilis.5 The ability of the DPP Syphilis PoCT to increase the time to diagnosis would consequently decrease the morbidity associated with infection, in addition to increasing contact tracing and spread of disease. While not currently licensed for use in Australia, it would help to reduce maternal spread of disease to neonates, as well as horizontal transmission. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose.
RPR, rapid plasma reagin.
Table 2 Results of the Chembio DPP Screen and Confirm Assay in comparison to the laboratory reference method
Linsey Skinner Gemma Robertson Robert Norton
Syphilis TPPA status via reference method Syphilis TPPA status via PoCT Positive Negative Total
James Cook University, Pathology Queensland, Qld, Australia Positive
Negative
Total
319 22 341
14 94 108
333 116 449
TPPA, Treponema pallidum particle agglutination.
Contact Ms Linsey Skinner. E-mail: [email protected] 1. The Department of Health, Public Health Laboratory Network. Syphilis Laboratory Case Definition. June 2012. http://www.health.gov.au/internet/ main/publishing.nsf/Content/cda-phln-syphilis.htm.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
720
CORRESPONDENCE
2. The Kirby Institute. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia. Annual Surveillance Report 2014. Sydney: The Kirby Institute, University of New South Wales, 2014. 3. Ratnam S. The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol 2005; 16: 41–5. 4. Yin YP, Chen XS, Wei WH, et al. A dual point-of-care test shows good performance in simultaneously detecting nontreponemal and treponemal antibodies in patients with syphilis: a multisite evaluation study in China. Clin Infect Dis 2013; 56: 659–65. 5. Robertson G. The utility of syphilis point of care testing in remote Queensland communities. Pathology 2014; 46: 348–72. 6. Chembio Diagnostic Systems. DPP Syphilis Screen and Confirm. 2012; cited 10 Mar 2015. http://chembio.com/wp-content/uploads/2012/05/DPP-Syphwhite-paper.pdf. 7. Larsen S, Creighton E. CDC Syphilis Manual. Atlanta: Centers for Disease Control and Prevention, 1998; Chapter 10, Rapid plasma reagin 18-MM circle card test RPR. 8. Causer LM, Kaldor JM, Fairley CK, et al. A laboratory-based evaluation of four rapid point-of-care tests for syphilis. PLoS One 2014; 11: e91504.
DOI: 10.1097/PAT.0000000000000334
Amoebic encephalitis in a farmer Sir, Balamuthia mandrillaris (B. mandrillaris) is the main pathogenic protozoa causing granulomatous amoebic encephalitis (GAE) in healthy individuals. GAE with B. mandrillaris is a rare and progressively fatal disease. Its mortality rate is more than 95%.1 Balamuthia mandrillaris has been found worldwide in soil and water.2 GAE with B. mandrillaris occurs in both immunocompetent and immunocompromised people.1,2 Balamuthia mandrillaris enters through the lower respiratory tract or through broken skin.2 It causes a subacute or chronic meningoencephalitis. Patients with GAE present with fever, headache, nausea, vomiting and a change in mental state.2 These symptoms are similar to patients with bacterial meningitis. If patients are not diagnosed and treated promptly with appropriate agents, they progress to death between one week and several months after the onset of neurological symptoms.2 Here we report a Japanese farmer with GAE due to B. mandrillaris. The patient died 8 weeks after the onset of symptoms, and GAE due to B. mandrillaris was revealed by an autopsy. A 57-year-old farming woman was admitted to our hospital in September 2013 complaining of a headache. During the summer months, she was using groundwater that had accumulated in tanks for irrigation. General findings and vital signs were unremarkable. Her past medical history was unremarkable and she had no evidence of immunodeficiency. Neurological examination did not show any major problems except for mild dysarthria. A computed tomography (CT) scan revealed a tumour-like lesion in the right frontal lobe of the cerebrum. Additionally, contrast enhanced magnetic resonance imaging (MRI) scan showed this lesion to have ring enhancement and associated vasogenic oedema (Fig. 1). Differential diagnosis included a glioma, metastatic tumour or abscess formation. Two weeks after admission, local resection of the right frontal lesion was done. Histological diagnosis was granulomatous necrotising encephalitis of unknown aetiology. After operation, intravenous cefazolin and dexamethasone were started. Two weeks after the operation, a T2 enhanced MRI of the brain showed several new
Pathology (2015), 47(7), December
high signal lesions appearing adjacent to the operative site. Antibiotics were changed to ceftriaxone and metronidazole which were recommended by Brouwer et al.3 as the standard antimicrobial therapy with brain abscess. Three weeks after the operation, the patient developed fever, headache and vomiting. A possibility of toxoplasmosis was raised because of equivocal positivity by immunohistochemistry. Thus, the antibiotics were changed to sulfamethoxazole trimethoprim and meropenem. The findings of CSF were unremarkable except for slightly raised total protein. No organisms were observed in the CSF on Gram, Grocott or Ziehl–Neelsen stainings, and CSF cultures were negative. Unfortunately amoebic culture was not done. Subsequently T2 emphasised imaging of MRI showed that new high signal lesions appeared at the left temporal lobe, brainstem and cerebellum. Quadriplegia and anisocoria appeared and the level of consciousness became worse. The patient progressed to coma and cardiac arrest on the 43rd hospitalised day. Autopsy was performed 9 h after death. The membranes surrounding the brain were thick and inflamed at the base of the brain, especially the ventral aspect of the pons, midbrain and anterior cerebellum. The brain weighed 1050 g. The gyri appeared wide and flat while the sulci were narrowed consistent with brain oedema. The pons and midbrain were extensively inflamed and covered by purulent materials resulting in severe flattening of the ventral aspect (Fig. 2A). Both cerebral peduncles of the midbrain were necrotic and friable. In addition, there was a necrotic area in the right cerebral convexity of the anterior temporal brain. Histologically the entire brain and the spinal cord showed severe amoebic meningitis containing numerous trophozoites and cysts, especially around the vessels (Fig. 2B,C). In addition, there was severe inflammation, necrosis and haemorrhage around the midbrain, pons, medulla oblongata and anterior cerebellum. The trophozoites appeared to extend from the leptomeninges into the brain parenchyma resulting in encephalitis, characterised by extensive degeneration and necrosis of neuronal tissue associated
Fig. 1 There is a tumour-like lesion with ring enhancement and oedema (contrasted MRI, T1 emphasised imaging).
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
Pathology (2015), 47(7), December
CORRESPONDENCE
C. M. Florkowski P. M. George
Syphilis diagnosis algorithm Serum
Canterbury Health Laboratories, Christchurch, New Zealand
EIA
Contact A/Prof C. M. Florkowski. E-mail: [email protected]
POS
NEG No futher testing
Known positive?
1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551–67. 2. Thygesen K, Mair J, Giannitsis E, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012; 33: 2252–7. 3. Florkowski CM, Wallace J, Walmsley T, George P. The effect of hemolysis on current troponin assays – a confounding preanalytical variable. Clin Chem 2010; 56: 1195–7. 4. Lippi G, Avanzini P, Dipalo M, Aloe R, Cervellin G. Influence of hemolysis on troponin testing: studies on Beckman Coulter UniCel DxI 800 Accu-TnI and overview of the literature. Clin Chem Lab Med 2011; 49: 2097–100. 5. Koerbin G, Tate J, Potter JM, Cavanaugh J, Glasgow N, Hickman PE. Characterisation of a highly sensitive troponin I assay and its application to a cardio-healthy population. Clin Chem Lab Med 2012; 50: 871–8. 6. Meites S. Reproducibly simulating hemolysis, for evaluating its interference with chemical methods. Clin Chem 1973; 19: 1319. 7. Sawyer N, Blennerhassett J, Lambert R, Sheehan P, Vasikaran S. Outliers affecting cardiac troponin I measurement: comparison of a new high sensitivity assay with a contemporary assay on the Abbott ARCHITECT analyser. Ann Clin Biochem 2014; 51: 476–84. 8. Kavsak PA, Worster A, You JJ, et al. Ninety-minute vs 3-h performance of high-sensitivity cardiac troponin assays for predicting hospitalization for acute coronary syndrome. Clin Chem 2013; 59: 1407–10. 9. Krintus M, Kozinski M, Boudry P, et al. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay. Clin Chem Lab Med 2014; 52: 1657–65. 10. Dwyer DG, Fry M, Somerville A, Holdgate A. Randomised single blinded control trial comparing haemolysis rate between two cannula aspiration techniques. Emerg Med Aust 2006; 18: 484–8. 11. Ryan JB, Stuart LA, Southby SJ, et al. Comparison of BD Vacutainer Rapid Serum Tube and plasma for haemolysis markers in the emergency department. Ann Clin Biochem 2015; 52: 293–6.
DOI: 10.1097/PAT.0000000000000342
Evaluation of the Dual Path Platform syphilis point of care test in North Queensland Sir, The rate of diagnosis of syphilis in North Queensland Aboriginal and Torres Straight Islander populations has continued to rise over the past 6 years, from 16.1% in 2009 to 36.4% in 2013.1,2 In particular, the regions surrounding Mount Isa have been marked by ongoing syphilis outbreaks, with a total of 284 cases from January 2010 to March 2015. Of these cases, 99% occurred in patients of Indigenous origin, and 95% aged less than 35 years.1 Resurgence of disease in rural and remote communities has been attributed to geographical and sociocultural constraints delaying disease presentation.3 The current algorithm for diagnosis of infectious syphilis in Pathology Queensland (Fig. 1) uses two treponemal tests [enyme immunoassay IgG (EIA IgG; Abbott, USA) and the Treponema pallidum particle agglutination test (TPPA; Fujirebio, Japan)], and one non-treponemal antibody test [rapid plasma reagin (RPR; BD, USA)]. Non-treponemal tests, while non-specific, become elevated with acute infection and subsequently increase the sensitivity of diagnosis. This allows for the detection of active disease. Treponemal tests are utilised in
YES
Perform RPR
NO
Perform RPR and confirmatory TPPA TPPA NEG Confirmed positive
Apply comment reporting possible false positive result and suggest retesting in 2–4 weeks
Fig. 1 Townsville laboratory syphilis diagnosis algorithm. EIA, enzyme immunoassay IgG (Abbott, USA); RPR, rapid plasma reagin (BD, USA); TPPA, Treponema pallidum particle agglutination test (Fujirebio, Japan).
a confirmatory capacity.4 Treponemal antibody tests remain elevated for life, and therefore do not always reflect active infection.4,5 A positive TPPA test in conjunction with a positive RPR test is indicative of current infection with T. pallidum, while a positive TPPA test with a negative RPR test is indicative of inactive infection.3–5 A new point of care test (PoCT), the Dual Path Platform (DPP) Syphilis Screen and Confirm Assay (Chembio, USA) is based on the simultaneous detection of non-treponemal and treponemal antibodies. It improves on previous syphilis PoCT assays, with the additional ability to detect non-treponemal antibodies. This consequently allows for a differentiation between active infection and inactive disease, with the nontreponemal antibody decreasing or becoming absent in treated disease.4 Ethics approval was granted and a total of 449 stored frozen sera obtained during sexual health clinic screens over the last 12 months in North Queensland were tested with the DPP Syphilis PoCT. The DPP Syphilis PoCT consists of both a treponemal marker and non-treponemal marker (Fig. 2), in addition to a procedural control marker. The treponemal marker (line 1) detects IgG to T. pallidum, whilst the non-treponemal marker (line 2) detects IgM and IgG antibodies to lipoidal material and cardiolipin antibodies.6,7 If the antibodies to syphilis (treponemal and non-treponemal) are present, then two pink/purple lines are produced, in addition to the control line, and signify active infection. The absence of treponemal and/or non-treponemal antibodies results in no pink/purple lines in the test area.6 The test was performed according to instructions provided by the manufacturers, and interpreted by medical staff in the Townsville laboratory. Comparison was made with the gold standard tests EIA, TPPA, and RPR. Known positive and negative results were deidentified to ensure interpretation was non-biased, and a spectrum of serum titres ranging from 2 to 256 were tested. Discrepant results were retested with the DPP Syphilis PoCT, but the result of the gold standard was accepted over the result of the DPP Syphilis PoCT. Results were then entered into a central database. Each specimen had been previously tested according to the standard testing regimen at the Townsville laboratory to provide a comparison of PoCT to gold standard. Of the 449 specimens, 217 tested positive by the DPP Syphilis PoCT (non-treponemal line) compared to 227 by the comparator RPR test (Table 1). Analysis of these results
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
A
719
B
Fig. 2 Structure of the Chembio dual POC test for syphilis showing the locations of the antigen lines. (A) Dissected view following testing of reactive serum; (B) complete cassette following testing of reactive serum.
demonstrated a sensitivity of 95.6% and specificity of 66.2% when compared to the RPR gold standard. The sensitivity of the DPP Syphilis PoCT in this study compared to the manufacturer’s testing was equivalent (88.6–98.7%); however, it demonstrated a lower specificity when compared with the manufacturer’s testing (98.6%).6 Of the 449 specimens, 319 tested positive by the treponemal line of the DPP Syphilis PoCT compared to 341 by the comparator TPPA test (Table 2). This demonstrated a sensitivity of 93.5% and specificity of 87%, with a positive predictive value of 95.8%. The sensitivity and specificity were less than that achieved through the manufacturer’s testing (sensitivity 96.5%, specificity 95.5%)6 and comparable with independent, peer-reviewed testing (sensitivity 89.8%, specificity 98.3%).8 A recent study looking at the diagnosis of syphilis based solely on a treponemal PoCT demonstrated a sensitivity of 81.5% [95% confidence interval (CI) 76.6–86.4%], and a specificity of 100%.5 The study reported here showed an improved sensitivity with the additional detection of non-treponemal antibodies (95.6%). However it demonstrated a lower specificity (66.2%) when compared with the treponemal PoCT. Table 1 Results of the Chembio DPP Screen and Confirm Assay in comparison to the laboratory reference method Syphilis RPR status via reference method Syphilis RPR status via PoCT Positive Negative Total
Positive
Negative
Total
217 10 227
75 147 222
292 157 449
Limitations of the study included the use of stored serum over fresh serum or whole blood. This might have reduced the sensitivity and specificity of the test. The DPP Syphilis PoCT offers an alternative to laboratory diagnostic methods of syphilis diagnosis in rural and remote regions. It allows for diagnosis at the point of care, such as a primary healthcare clinic, where diagnosis is often delayed due to geographic isolation and poor access to laboratory services. Treatment of early syphilis is crucial in reducing the spread of disease in communities, and incidence of disease sequelae. The DPP Syphilis PoCT allows for simultaneous diagnosis and treatment, which is important in regions where patients are mobile and do not return to health clinics for test results. However, due to a lower specificity of the test compared to the gold standard testing regimen (Fig. 1), it would result in higher rates of unnecessary treatment. Biologically false positive results compared to true positive results would be impossible to separate based solely on the DPP Syphilis PoCT, increasing the need for parallel testing with the gold standard. It is important to note that diagnosis is never made based only on laboratory information, and that history and examination continue to form a large part of the clinical diagnosis. Current treatment of syphilis consists of one dose of intramuscular benzathine penicillin. The risk of treating biologically false positives is small when compared with the risks presented by failure to treat congenital syphilis.5 The ability of the DPP Syphilis PoCT to increase the time to diagnosis would consequently decrease the morbidity associated with infection, in addition to increasing contact tracing and spread of disease. While not currently licensed for use in Australia, it would help to reduce maternal spread of disease to neonates, as well as horizontal transmission. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose.
RPR, rapid plasma reagin.
Table 2 Results of the Chembio DPP Screen and Confirm Assay in comparison to the laboratory reference method
Linsey Skinner Gemma Robertson Robert Norton
Syphilis TPPA status via reference method Syphilis TPPA status via PoCT Positive Negative Total
James Cook University, Pathology Queensland, Qld, Australia Positive
Negative
Total
319 22 341
14 94 108
333 116 449
TPPA, Treponema pallidum particle agglutination.
Contact Ms Linsey Skinner. E-mail: [email protected] 1. The Department of Health, Public Health Laboratory Network. Syphilis Laboratory Case Definition. June 2012. http://www.health.gov.au/internet/ main/publishing.nsf/Content/cda-phln-syphilis.htm.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
720
CORRESPONDENCE
2. The Kirby Institute. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia. Annual Surveillance Report 2014. Sydney: The Kirby Institute, University of New South Wales, 2014. 3. Ratnam S. The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol 2005; 16: 41–5. 4. Yin YP, Chen XS, Wei WH, et al. A dual point-of-care test shows good performance in simultaneously detecting nontreponemal and treponemal antibodies in patients with syphilis: a multisite evaluation study in China. Clin Infect Dis 2013; 56: 659–65. 5. Robertson G. The utility of syphilis point of care testing in remote Queensland communities. Pathology 2014; 46: 348–72. 6. Chembio Diagnostic Systems. DPP Syphilis Screen and Confirm. 2012; cited 10 Mar 2015. http://chembio.com/wp-content/uploads/2012/05/DPP-Syphwhite-paper.pdf. 7. Larsen S, Creighton E. CDC Syphilis Manual. Atlanta: Centers for Disease Control and Prevention, 1998; Chapter 10, Rapid plasma reagin 18-MM circle card test RPR. 8. Causer LM, Kaldor JM, Fairley CK, et al. A laboratory-based evaluation of four rapid point-of-care tests for syphilis. PLoS One 2014; 11: e91504.
DOI: 10.1097/PAT.0000000000000334
Amoebic encephalitis in a farmer Sir, Balamuthia mandrillaris (B. mandrillaris) is the main pathogenic protozoa causing granulomatous amoebic encephalitis (GAE) in healthy individuals. GAE with B. mandrillaris is a rare and progressively fatal disease. Its mortality rate is more than 95%.1 Balamuthia mandrillaris has been found worldwide in soil and water.2 GAE with B. mandrillaris occurs in both immunocompetent and immunocompromised people.1,2 Balamuthia mandrillaris enters through the lower respiratory tract or through broken skin.2 It causes a subacute or chronic meningoencephalitis. Patients with GAE present with fever, headache, nausea, vomiting and a change in mental state.2 These symptoms are similar to patients with bacterial meningitis. If patients are not diagnosed and treated promptly with appropriate agents, they progress to death between one week and several months after the onset of neurological symptoms.2 Here we report a Japanese farmer with GAE due to B. mandrillaris. The patient died 8 weeks after the onset of symptoms, and GAE due to B. mandrillaris was revealed by an autopsy. A 57-year-old farming woman was admitted to our hospital in September 2013 complaining of a headache. During the summer months, she was using groundwater that had accumulated in tanks for irrigation. General findings and vital signs were unremarkable. Her past medical history was unremarkable and she had no evidence of immunodeficiency. Neurological examination did not show any major problems except for mild dysarthria. A computed tomography (CT) scan revealed a tumour-like lesion in the right frontal lobe of the cerebrum. Additionally, contrast enhanced magnetic resonance imaging (MRI) scan showed this lesion to have ring enhancement and associated vasogenic oedema (Fig. 1). Differential diagnosis included a glioma, metastatic tumour or abscess formation. Two weeks after admission, local resection of the right frontal lesion was done. Histological diagnosis was granulomatous necrotising encephalitis of unknown aetiology. After operation, intravenous cefazolin and dexamethasone were started. Two weeks after the operation, a T2 enhanced MRI of the brain showed several new
Pathology (2015), 47(7), December
high signal lesions appearing adjacent to the operative site. Antibiotics were changed to ceftriaxone and metronidazole which were recommended by Brouwer et al.3 as the standard antimicrobial therapy with brain abscess. Three weeks after the operation, the patient developed fever, headache and vomiting. A possibility of toxoplasmosis was raised because of equivocal positivity by immunohistochemistry. Thus, the antibiotics were changed to sulfamethoxazole trimethoprim and meropenem. The findings of CSF were unremarkable except for slightly raised total protein. No organisms were observed in the CSF on Gram, Grocott or Ziehl–Neelsen stainings, and CSF cultures were negative. Unfortunately amoebic culture was not done. Subsequently T2 emphasised imaging of MRI showed that new high signal lesions appeared at the left temporal lobe, brainstem and cerebellum. Quadriplegia and anisocoria appeared and the level of consciousness became worse. The patient progressed to coma and cardiac arrest on the 43rd hospitalised day. Autopsy was performed 9 h after death. The membranes surrounding the brain were thick and inflamed at the base of the brain, especially the ventral aspect of the pons, midbrain and anterior cerebellum. The brain weighed 1050 g. The gyri appeared wide and flat while the sulci were narrowed consistent with brain oedema. The pons and midbrain were extensively inflamed and covered by purulent materials resulting in severe flattening of the ventral aspect (Fig. 2A). Both cerebral peduncles of the midbrain were necrotic and friable. In addition, there was a necrotic area in the right cerebral convexity of the anterior temporal brain. Histologically the entire brain and the spinal cord showed severe amoebic meningitis containing numerous trophozoites and cysts, especially around the vessels (Fig. 2B,C). In addition, there was severe inflammation, necrosis and haemorrhage around the midbrain, pons, medulla oblongata and anterior cerebellum. The trophozoites appeared to extend from the leptomeninges into the brain parenchyma resulting in encephalitis, characterised by extensive degeneration and necrosis of neuronal tissue associated
Fig. 1 There is a tumour-like lesion with ring enhancement and oedema (contrasted MRI, T1 emphasised imaging).
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
