Journal of Clinical Virology 58 (2013) 752

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Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv

Letter to the Editor

Comment on: Fulminant myocarditis and viral infection Keywords: Dengue virus Fulminant myocarditis In situ PCR Rapid diagnosis Emergency setting

To the Editor, We compliment the multi-disciplinary team of investigators from the University of S˘ao Paulo, Brazil for their studies on the Dengue virus (DENV) type 1 (DENV-1) associated case of fatal myocarditis [1]. We think that like the myocardial tissue, immunohistochemistry studies should be carried out on pulmonary tissues for phenotypic markers for lymphocytes (CD-3 and CD-8), plasmocytes (CD-38), macrophages (CD-68), and natural killer cells (CD-57). Such a workout would establish if the pulmonary tissues had also manifested a cytokine-mediated immunological response resulting in bilateral pleural effusion with congested and oedematous lungs. The post-mortem-tissues [1] could be examined for DENV-1 replication sites in the myocardium using an in situ RT-PCR. After five-year storage, tissues from an 11-year-old boy, who died in Thailand in 1987 with clinical diagnosis of dengue haemorrhagic fever were processed by transcribing the dengue viral RNA to DNA followed by its amplification using the polymerase chain reaction. During an in situ hybridization viral RNA was detected in hepatocytes in the mid-zonal region of the liver and was scattered macrophages in skin and lymph nodes [2]. Furthermore, RT-PCR was more sensitive than the most sensitive virus isolation technique for detecting DENV or its components in autopsy tissues from 18 children who were believed to have died of dengue haemorrhagic fever in Rangoon during 1976. It was possible to detect DENV- RNA in 14 of 18 liver specimens, 13 of 18 spleen specimens and in 7 of 16 mesenteric lymph node specimens. On the other hand, no DENV-RNA was detected in 44 samples of brain tissue from 15 individuals whose one or more other tissues had yielded DENV-RNA [3]. The facilities for an earlier diagnosis of DENV infection in the emergency rooms in Ribeir˘ao Preto in S˘ao Paulo state, Brazil [1] or elsewhere could be strengthened by availability of point-ofcare (POC) assay kits to detect any circulation of DENV NS1, IgM and IgG concurrently. POC are user friendly and do not require highly trained personnel or costly laboratory equipment. During such an exercise for a simulations serologic search, NS1would be detectable during the earlier phase of illness in primary and secondary infection though the only serologic marker detectable later

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might be IgM (in primary infections) or IgG (in secondary infection). Obviously, such a diagnostic protocol would enable a disease diagnosis in patients reporting in emergency rooms during various phases of illness. That was evident in Malaysia, during the 2006 to 2007 outbreak of dengue when the molecular and serologic response in ten adults with secondary infection and a fatal outcome were intriguing. All were positive for dengue NS1 and IgG. DENV RNA was detected in one (of the seven cases) case who was co-positive for NS1, IgM and IgG. There were three cases that were positive for NS1 and IgG but negative for IgM [4]. Last but not least, it would be important to follow the recommended 12-lead ECG in all patients with DENV infection [1] universally as that would ensure a rational case management during the acute stage of illness. Funding None. Competing interests None. Ethical approval Not required. References [1] Daniel RA, Silva AR, Neppelenbroek VB, Feres O, Bestetti RB. Fulminant myocarditis and viral infection. J Clin Virol 2013;58(September (1)):1–3. [2] Kangwanpong D, Bhamarapravati N, Lucia HL. Diagnosing dengue virus infection in archived autopsy tissues by means of the in situ PCR method: a case report. Clin Diagn Virol 1995;3(February (2)):165–72. [3] Rosen L, Drouet MT, Deubel V. Detection of dengue virus RNA by reverse transcription-polymerase chain reaction in the liver and lymphoid organs but not in the brain in fatal human infection. Am J Trop Med Hyg 1999;61(November (5)):720–4. [4] Sam SS, Omar SF, Teoh BT, Abd-Jamil J, AbuBakar S. Review of dengue hemorrhagic fever fatal cases seen among adults: a retrospective study. PLoS Negl Trop Dis 2013;7(May (5)):e2194, http://dx.doi.org/10.1371/journal.pntd.0002194.

Subhash C. Arya ∗ Nirmala Agarwal Sant Parmanand Hospital, Delhi, India ∗ Corresponding

author at: Sant Parmanand Hospital, 18 Alipore Road, Delhi 110054, India. Tel.: +91 119810642269. E-mail addresses: [email protected], [email protected] (S.C. Arya) 20 September 2013

Comment on: Fulminant myocarditis and viral infection.

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