1) A study of 210 patients with infectious acute encephalitis syndrome (AES) in India found that 62% had a specific etiological diagnosis. The most common causes were herpes virus (12 patients) and Japanese encephalitis virus (8 patients) for neurological AES, and scrub typhus (42 patients) and dengue virus (20 patients) for systemic AES. 2) Using a syndromic approach, neurological AES could be differentiated from systemic AES with 100% specificity based on the absence of myalgia or rash. Thalamic involvement on imaging predicted Japanese encephalitis with 100% specificity for neurological AES cases. 3) Targeted testing and treatment based on the syndromic approach substantially reduced

1. A mosquito larva up close

2. Eur Neurol | Posted 6 days ago
A Cost-Effective Approach to the Diagnosis and Management of Acute Infectious Encephalitis; Misra U,
Mani V, Kalita J; European Neurology 77 (1-2), 66-74 (Dec 2016)
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SETTING A tertiary care teaching hospital in India.
OBJECTIVE To report a syndromic approach to acute encephalitis syndrome (AES) and propose a cost-effective
model.
STUDY DESIGN AES patients were categorized by the presence or absence of myalgia/rash into systemic and
neurological AES. The patients with systemic AES were investigated for dengue, scrub typhus, leptospira,
chikungunya, and malaria, and those with neurological AES were investigated for herpes and Japanese
encephalitis (JE). Sensitivity and specificity of syndromic categorization were tested, and cost effectiveness was
calculated.
RESULTS There were 210 patients with infectious AES; neurological in 45 and systemic in 165. Specific etiology
could be found in 130 (62%) patients, and after excluding 36 patients with co-infections, 94 patients were tested
for sensitivity and specificity. Twenty patients had neurological AES (herpes 12, JE 8), and 74 systemic (scrub
typhus 42, dengue 20, malaria 6, leptospira 6). The absence of myalgia/rash categorized neurological AES with
100% specificity. In neurological AES, thalamic involvement predicted JE with 100% specificity. In systemic AES,
differentiation could not be made between etiologies based on hypotension, thrombocytopenia, and muscle, liver,
and kidney dysfunction. In these patients, MRI and acyclovir therapy were warranted, saving cost. By targeted
investigations and treatment, the cost was reduced by 70%.
CONCLUSIONS A syndromic approach to AES and goal-directed investigations and treatment substantially
reduces the cost of management.

3. A study of dengue encephalitis in tertiary center of North India
Praveen Sharma UP India
Objectives: dengue infection caused by a flavivirus is endemic in more than hundred countries
including India. With expanding clinical spectrum encephalitis has been documented with increased
frequency. This study evaluate the incidence of Dengue encephalitis (DE) and correlates their out
come with clinical laboratory and Neuroinaing (MRI/CT) profile in patients with dengue virus
infection.
Methods:It’s a hospital based prospective cohort study conducted at King George’s Medical
University in Luckhnow India over a period of 2 years (August2012 to July2014) which included
laboratory confirmed DE.We estimated incidence and analyzed clinical laboratory and
neuroimaging data on admission discharge and follow-up for 3 months to assess outcome
predictors of DE
Results: Out of screened 540 confirmed Dengue cases 27patients had DE representing 5%
incidence. Two third were 20 years of age or younger with male preponderace (75%)Fever
Headache Seizure and Altered sensorium was present in >90% while 8(29.63%) patients had poor
glssgow coma scale (GCS). Rashes and Bleeding manifestations were present in only 3(11%) while
thrombocytopenia and liver dysfunction in 10 and 3 cases respectively. Cerebrospinal fluid (CSF)
was abnormal in 23(85%) and cerebral edema on neuroimaing in 16(59%) one third patients died
during hospital course and at 3 months follow up remainder were recovered.
Conclusion: an increasingly higher incidence rate with high mortality of DE is reported. Clinical
and laboratory parameters such as poor GCS dngue shock syndrome thrombocytopenia liver
dysfunction and abnormal Neuroimaging are poor outcome predictors. Keywords: Dengue
Flavivirus Dengue encephalitis.

4. Neurologic complications in dengue virus infection
by Ritesh Sahu, Rajesh Verma, Amita Jain, Ravindra K. Garg, Maneesh K.
Singh, Hardeep S. Malhotra, Praveen K. Sharma, and Anit Parihar
Neurology
Volume 83(18):1601-1609
October 28, 2014
© 2014 American Academy of Neurology

5. Figure 1 Schematic diagramPNS = peripheral nervous system.
Sahu R et al. Neurology 2014;83:1601-1609
© 2014 American Academy of Neurology

6. Figure 2 Bar diagramSpectrum and frequency of neurologic manifestations of dengue
infection (also see table e-1 on the Neurology® Web site at Neurology.org).
Sahu R et al. Neurology 2014;83:1601-1609
© 2014 American Academy of Neurology

7. Figure 3 MRI brain of a 28-year-old man with dengue encephalitis(A) T2-weighted and
(B) fluid-attenuated inversion recovery axial image show bilateral basal ganglia
hyperintensities.
Sahu R et al. Neurology 2014;83:1601-1609
© 2014 American Academy of Neurology

8. table e-1: Spectrum and frequency of neurological manifestations
of dengue infection.
Neurological presentation No. of cases (%) (n=45)
Encephalitis 15 (33)
Encephalopathy 10(22)
Myelitis 03(7)
GB Syndrome 04(9)
Neuralgic amyotrophy 03(7)
Myositis 06(13)
Hypokalemic paralysis 04(9)
Abbreviation: n, total number of cases.
Sahu R et al. Neurology 2014;83:1601-1609

9. The typical rash seen in dengue fever

10. Schematic depiction of the symptoms of dengue fever

11. A TEM micrograph showing dengue virus virions (the cluster of dark dots
near the center

12. The mosquito Aedes aegypti feeding on a human host

13. Clinical course of dengue fever

14. When laboratory tests for dengue fever become positive where day zero is the start of
symptoms, 1st refers to in those with a primary infection, and 2nd refers to in those with
a secondary infection

15. A 1920s photograph of efforts to disperse standing water and thus decrease mosquito
populations

16. Dengue distribution in 2006.
Epidemic dengue and A. aegypti
A. aegypti, without epidemic dengue

17. Public health officers releasing P. reticulata fry into an artificial lake in the Lago Norte
district of Brasília, Brazil, as part of a vector control effort

19. Puccioni-Sohler, M. et al. Neurology 2009;73:1413-1417
Clinical and CSF findings of 10 patients with neurologic manifestations associated with dengue
infection

20. Freedman D et al. N Engl J Med 2006;354:119-130

21. Freedman D et al. N Engl J Med 2006;354:119-130
Regions of Travel Exposure among Ill Travelers Returning from the Developing World

22. Freedman D et al. N Engl J Med 2006;354:119-130
Characteristics of Ill Travelers Returning from the Developing World, According to Region Visited

23. Freedman D et al. N Engl J Med 2006;354:119-130
Etiologic Diagnoses within Selected Syndrome Groups, According to Travel Region
Freedman D et al. N Engl J Med 2006;354:119-130

24. Rare Diagnoses
Clinicians evaluating returned travelers frequently entertain rare or exotic diagnoses.
Travel-related cases of Ebola virus disease, Japanese encephalitis, rabies, tetanus,
diphtheria, plague, tularemia, murine typhus, Rift Valley fever, poliomyelitis, primary
amebic meningoencephalitis, anthrax, or yellow fever are reported sporadically in the
literature. No cases of any of these diagnoses occurred among the 17,353 travelers
whose data were analyzed in this study or among any of the 25,023 patients whose
records were included in any category in our database but were excluded from this
study. Among the 17,353 patients in our cohort, each of the following diagnoses
occurred only once: Angiostrongylus cantonensis infestation, A. costaricensis infestation,
hantavirus infection, cholera, melioidosis, Ross River virus infection, African
trypanosomiasis, legionellosis, and meningococcal meningitis.
Freedman D et al. N Engl J Med 2006;354:119-130

25. Freedman D et al. N Engl J Med 2006;354:119-130
Proportionate Morbidity among Ill Travelers Returning from the Developing World, According to
Region of Travel

26. .
Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges.
Guzman MG, Kouri G.
Virology Department, PAHO/WHO Collaborating Center for Viral Diseases, Pedro Kouri
Tropical Medicine Institute, Autopista Novia del Mediodía, Km 6 P.O. Box Marianao 13,
Havana, Cuba. lupe@ipk.sld.cu
The incidence of dengue and dengue hemorrhagic fever (DF/DHF) has increased
significantly over the last decades. Yearly, an estimated 50-100 million cases of DF and
about 250000-500000 cases of DHF occur worldwide. The epidemiological situation in
Latin America now resembles that in Southeast Asia. Here, the main clinical,
epidemiological and virological observations in the American region are presented and
compared with those previously reported from Southeast Asia. During 2002, more than 30
Latin American countries reported over 1000000 DF cases. DHF occurred in 20 countries
with more than 17000 DHF cases, including 225 fatalities. The co-circulation of multiple
serotypes has been reported from many countries. In the Americas, DHF is observed both
in children and adults; secondary infection by a different dengue virus serotype has been
confirmed as an important risk factor for this severe form of the disease. However, some
new risk factors such as the interval of dengue virus infections and the ethnicity and
underlying chronic conditions of the patient have also been identified. The sequence of
dengue virus infections and association with certain genotypes are further factors of
importance. We also discuss the control and prevention strategies. In conclusion, without
urgent action for the prevention and control of dengue/DHF and its vector, the current
situation will worsen and, more dramatical, there is a risk of the urbanization of yellow
fever.
J Clin Virol. 2003 May;27(1):1-13.

27. Rev Panam Salud Publica. 2007 Nov;22(5):358-63.
Dengue viruses in Brazil, 1986-2006.
Nogueira RM, de Araújo JM, Schatzmayr HG.
Flavivirus Laboratory, Department of Virology, Instituto Oswaldo Cruz/ FIOCRUZ, Avenida
Brasil 4365, 21040-190, Rio de Janeiro, RJ, Brasil. rita@ioc.fiocruz.br
A total of 4,243,049 dengue cases have been reported in Brazil between 1981 and 2006,
including 5,817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)
and a total of 338 fatal cases. Although all Brazilian regions have been affected, the
Northeast and Southeast regions have registered the highest number of notifications.
DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981
and 1982. The disease became a nationwide public health problem following outbreaks of
DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The
introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe
epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were
typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus
serotypes and entered new areas, a finding that warrants closer evaluation. Unusual
clinical symptoms, including central nervous system involvement, have been observed in
dengue patients in at least three regions of the country.

29. Am. J. Trop. Med. Hyg., 54(3), 1996, pp. 256-259
Dengue Encephalitis: A True Entity?
L. C. S. Lum, S. K. Lam, Y. S. Choy, R. George AND F. Harun

30. Am. J. Trop. Med. Hyg., 54(3), 1996, pp. 256-259
Dengue Encephalitis: A True Entity?
L. C. S. Lum, S. K. Lam, Y. S. Choy, R. George AND F. Harun

31. Am. J. Trop. Med. Hyg., 54(3), 1996, pp. 256-259
Dengue Encephalitis: A True Entity?
L. C. S. Lum, S. K. Lam, Y. S. Choy, R. George AND F. Harun

32. Am. J. Trop. Med. Hyg., 54(3), 1996, pp. 256-259
Dengue Encephalitis: A True Entity?
L. C. S. Lum, S. K. Lam, Y. S. Choy, R. George AND F. Harun

33. Lancet. 2000 Mar 25;355(9209):1053-9.
Neurological manifestations of dengue infection.
Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B, Loan HT, Day NP,
Farrar J, Myint KS, Warrell MJ, James WS, Nisalak A, White NJ.
Wellcome Trust Clinical Research Unit, Cho Quan Hospital, Ho Chi Minh City, Vietnam.
BACKGROUND: Severe forms of dengue, the most important arboviral infection of man, are
associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of
dengue as a cause of neurological disease is uncertain. METHODS: During 1995, all patients with
suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by
culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses.
FINDINGS: Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%)
of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients
with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified.
Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had
dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21
had no characteristic features of dengue on admission. The most frequent neurological
manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No
patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2
strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic
fever, and with other strains previously isolated in southern Vietnam. INTERPRETATION: In dengue
endemic areas patients with encephalitis and encephalopathy should be investigated for this
infection, whether or not they have other features of the disease.

34. J Neurol Sci. 2006 May 15;244(1-2):117-22. Epub 2006 Mar 9.
Neurological manifestations of dengue virus infection.
Misra UK, Kalita J, Syam UK, Dhole TN.
Department of Neurology, Sanjay Gandhi PGIMS, Lucknow 226014, India. AIM: Paucity of studies on
neurological manifestations in dengue virus infection prompted this study. We aim to
correlate clinical, radiological and neurophysiological changes in dengue patients with
neurological manifestations. METHOD: Consecutive IgM seropositive dengue patients
admitted in neurology ward during 2003-2005 have been prospectively evaluated. They
were subjected to detailed clinical evaluation, blood counts, coagulation profile, serum
chemistry including creatine kinase (CK), cerebrospinal fluid (CSF), cranial CT and/or MRI,
electroencephalogram (EEG), nerve conduction and needle electromyography (EMG).
RESULTS: There were 17 patients, aged 5 to 56 years; 11 presented with encephalopathy
and 6 with acute motor weakness. In the patients with encephalopathy, seizures were
present in 3, myoclonus in 1, CSF pleocytosis and EEG slowing in 8 each and globus
pallidus and thoracic spinal cord involvement on MRI in 1 patient each. In the pure motor
weakness group, CK was elevated in 5 and EMG and muscle biopsy were consistent with
myositis in 1 patient each. The patients with pure motor weakness improved completely
but in the encephalopathy group 3 died, 2 had partial, 1 poor and 5 complete recovery by
1 month. CONCLUSION: Dengue patients presenting with encephalopathy had more
severe illness and worse outcome compared to acute pure motor weakness.

35. Clin Neuropathol. 1997 Jul-Aug;16(4):204-8.
Retrospective study on dengue fatal cases.
Miagostovich MP, Ramos RG, Nicol AF, Nogueira RM, Cuzzi-Maya T, Oliveira AV, Marchevsky RS,
Mesquita RP, Schatzmayr HG.
Departamento de Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Immunohistochemical procedure (avidin biotin peroxidase complex) was applied in formalin-fixed and
paraffin-embedded tissues obtained from 5 fatal cases of dengue infection associated with
encephalopathy. Dengue virus antigen was demonstrated in the cytoplasm of phagocytic
mononuclear cells from liver, spleen, and lung. Moreover, dengue viral antigens were here, to our
knowledge, first demonstrated in the central nervous system (CNS) and numerous immunolabelled
cells were found in brain sections from 3 cases. Extended immunohistochemical studies carried out in
1 case showed virus-positive cells mostly located within Virchow Robin space of medium size and
small veins, infiltrating the white and grey matter, and often situated close to neurons displaying
apparent cytopathic features. Furthermore, immunostaining for CD68 antigens demonstrated that
most CD68+ macrophages and dengue antigen-positive cells share similar morphology and
localization, suggesting a unique identity for at least part of these cells. Since in dengue fever, virus
replicates mostly in cells of macrophage lineage, our results seem to indicate that infiltration of virus-
infected macrophages could be one of the pathways by which viruses enter the brain in dengue
encephalitis. Whether bone marrow-derived infected macrophages and viral-free particles induce
CSN lesions through immune, metabolic, and/or direct viral-induced mechanisms will be essential to
better understand the pathogenesis and provide new therapeutic strategies for dengue-associated
encephalitis. As the evidence of tissue damage was nonspecific, the detection of virus antigen by
immunoperoxidase technique appeared to be highly reliable for dengue diagnosis.

36. Southeast Asian J Trop Med Public Health. 2001 Jun;32(2):341-5.
Neurological manifestations in dengue patients.
Pancharoen C, Thisyakorn U.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
To determine the frequency and the natural history of neurological manifestations of dengue infection
in Thai children, 1,493 children diagnosed with dengue infection by serology and admitted to the
Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand from 1987 to 1998 were
reviewed from prospectively recorded medical charts. There were 80 children identified with
neurological manifestations, an incidence of 5.4% of all dengue patients. Of these, there were 41
males and 39 females, with ages ranging from 3 months to 14 years. They were categorized into 20
cases of dengue fever, 26 cases of dengue hemorrhagic fever and 34 cases of dengue shock
syndrome. All cases experienced the neurological manifestations during the febrile stage of the
illness. The patients were classified into an encephalitic group (called "dengue encephalopathy") (42),
a seizure group (35) and a miscellaneous group (3). Encephalitic patients presented with alteration of
consciousness (83.3%), seizure (45.2%), mental confusion (23.8%), nuchal rigidity (21.4%), spasticity
of limbs (9.5%), positive clonus (4.8%), hemiplegia (2.4%) and positive kernig (2.4%), and were older
than those in the other groups. Patients in the seizure group presented with seizure (100%) and
positive clonus (2.9%). Abnormal laboratory findings included hyponatremia, abnormal liver enzymes
and CSF pleocytosis. Dengue IgM and dengue PCR were not demonstrated in 16 CSF specimens.
An autopsy finding of a child in the encephalitic group showed histologic evidence of encephalitis, the
only case of confirmed dengue encephalitis in this study. One patient with encephalitic symptoms
suffered from long-term neurological sequelae. The overall mortality rate was 5%. In conclusion,
neurological manifestations including seizure and encephalopathy in children with dengue are not
uncommon whereas dengue encephalitis is a rare entity.

37. Southeast Asian J Trop Med Public Health. 1999 Sep;30(3):504-6.
Dengue infection with central nervous system manifestations.
Thisyakorn U, Thisyakorn C, Limpitikul W, Nisalak A.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok,
Thailand.
A prospective observational study was conducted over a seven years period to determine
the clinical and laboratory findings of dengue patients with central nervous system
manifestations. Thirty serologically confirmed dengue infected patients with central
nervous system manifestations were seen at the Department of Pediatrics, Faculty of
Medicine, Chulalongkorn University, Bangkok and at Songkhla Hospital, Songkhla,
Thailand. The age ranged between 3 months and 14 years with a mean age of 6.2 years.
Seventeen were boys and thirteen were girls. The central nervous system manifestations
included alteration of consciousness 76.7%, seizures 63.3%, pyramidal tract signs 36.7%,
meningeal signs 30% and headache 26.7%. Eleven patients had primary while 19 had
secondary dengue infection. Cerebrospinal fluid examination showed lymphocytic
pleocytosis in 6 out of 28 patients while presence of anti-dengue IgM antibodies was
detected in 2 out of 19 specimens of cerebrospinal fluid tested. Two patients died, autopsy
was done on one patient and examination of the brain was compatible with viral
encephalitis.

38. J Infect Chemother. 2002 Jun;8(2):175-7.
Acute disseminated encephalomyelitis following dengue fever.
Yamamoto Y, Takasaki T, Yamada K, Kimura M, Washizaki K, Yoshikawa K, Hitani A,
Nakamura T, Iwamoto A.
Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical
Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
A58-year-old man suffered from acute disseminated encephalomyelitis (ADEM) after
dengue fever. ADEM has not been described as the cause of neurological complications in
dengue fever. However, the increasing use of magnetic resonance imaging in endemic
areas may help to identify ADEM as being responsible for neurological complications in
dengue fever.

39. J Neurol Sci. 2006 Nov 1;249(1):19-24. Epub 2006 Jul 25.
Dengue infection: neurological manifestations and cerebrospinal fluid (CSF)
analysis.
Soares CN, Faria LC, Peralta JM, de Freitas MR, Puccioni-Sohler M.
Neurology Service, HUAP/UFF (Hospital Universitário Antônio Pedro/Universidade
Federal Fluminense), Niterói, RJ, Brazil. crist_nsoares@yahoo.com.br
Neurological manifestation is considered a rare complication of dengue infection.
Neurological and cerebrospinal fluid (CSF) findings of 13 patients with dengue infection
were studied. Seven patients had encephalitis, two had myelitis and four showed Guillain-
Barré syndrome (GBS). No alteration in CSF was found from 57% of those with
encephalitis. Patients with GBS and myelitis showed a CSF-blood barrier dysfunction. The
differences in the CSF may be related to the location of the lesion and multiple
mechanisms of the disease in the nervous system.

40. J Infect Chemother. 2006 Dec;12(6):396-8. Epub 2007 Jan 18.
Post-dengue neuromyelitis optica: case report of a Japanese-descendent Brazilian
child.
Miranda de Sousa A, Puccioni-Sohler M, Dias Borges A, Fernandes Adorno L,
Papais Alvarenga M, Papais Alvarenga RM.
Centro de Neurologia e Reabilitação de Rondônia, Porto Velho, Brazil.
Monophasic neuromyelitis optica (NMO) is a rare form of post-infection acute
disseminated encephalomyelitis (ADEM). Cases occurring after dengue virus infection are
rare, despite the high prevalence of this disease in tropical and subtropical countries. We
report a female patient, 11 years old, of Japanese ancestry and living in North Brazil, who
developed NMO 1 week after having had a benign form of dengue fever. The disease was
confirmed by the detection of dengue IgM antibodies in serum and cerebrospinal fluid
(CSF). Restricted distribution of the lesions in the optic nerve and spinal cord was
confirmed by ophthalmological evaluation and magnetic resonance imaging of the brain
and spinal cord. Therapeutic intervention with corticotherapy resulted in benign evolution.
This is the second report of optic spinal syndrome following dengue virus infection in
patients of Japanese ancestry, suggesting an influence of the genetic background in the
susceptibility to post-dengue NMO.

41. Epidemiol Infect. 2006 Aug;134(4):820-5. Epub 2005 Dec 22.
Specific IgM and IgG responses in primary and secondary dengue virus infections determined
by enzyme-linked immunosorbent assay.
Sa-Ngasang A, Anantapreecha S, A-Nuegoonpipat A, Chanama S, Wibulwattanakij S, Pattanakul K,
Sawanpanyalert P, Kurane I.
National Institute of Health, Department of Medical Science, Ministry of Public Health, Nonthaburi,
Thailand. areerat@dmsc.moph.go.th
IgM- and IgG-capture ELISAs are widely used as diagnostic tests for confirmation of dengue virus
infection. The positive rate of anti-dengue IgM and IgG detection was examined in primary and
secondary dengue virus infections in the setting of a provincial hospital using IgM- and IgG-capture
ELISAs. Disease day 1 was defined as the day of onset of symptoms. In total, 232 plasma samples
were collected from 106 confirmed dengue cases consisting of 12 primary and 94 secondary
infections. In primary infection, anti-dengue IgM was detected in 4 out of 5 samples collected on
disease day 5 and in all the 21 samples collected on disease day 6 or later. Specific IgG was
detected in 2 out of 5 samples collected on day 12, and in 5 out of 6 samples collected on disease
days 13-15, but was not detected in samples collected on disease day 10 or earlier. In secondary
infection, IgM was not detected in the samples on disease days 2 and 3, but detected in 20 out of 79
samples collected on days 4-6, in 44 out of 65 on disease days 7-11 and in 40 out of 51 samples on
disease days 12-14. In contrast, specific IgG was detected in 21 out of 60 samples on disease days 4
and 5, in 13 out of 19 on disease day 6, in 62 out of 65 on disease days 7-11 and in all the samples
collected on disease day 12 or later. The result indicate that seroconversion rates of IgM and IgG are
different between primary and secondary infections, and suggest that detection of specific IgM and
IgG is necessary for determining dengue virus infection and for differentiating primary and secondary
dengue infections.

42. Clin Neuropathol. 1990 May-Jun;9(3):157-62.
Dengue: neuropathological findings in 5 fatal cases from Brazil.
Chimelli L, Hahn MD, Netto MB, Ramos RG, Dias M, Gray F.
Departmento de Patologia (Neuropatologia), Universidade Federal Fluminense, Niteroi,
RJ, Brasil.
Neuropathological examination of 5 patients with dengue who died of shock in Rio de
Janeiro during an outbreak in summer 1987, showed nonspecific lesions (edema, vascular
congestion, hemorrhagic foci and perivascular lymphocytic infiltrates). In one case with
delayed marked neurological symptoms, several foci of perivenous demyelination were
observed. Neurological manifestations are various and not uncommon in dengue, but their
anatomical substratum is not known. An immunopathological mechanism has been
postulated in some cases but has never been demonstrated morphologically. The
perivenous leukoencephalitis observed in one of our cases could represent the
morphological substratum of such an immunological mechanism