https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673600020365.pdf

Neurological manifestations of dengue infection.

Of more than 500 arboviruses recognized worldwide, 5 were first isolated in Canada and 58 were first isolated in the United States. Six of these viruses are human pathogens: western equine encephalitis (WEE) and eastern equine encephalitis (EEE) viruses (family Togaviridae, genus Alphavirus), St. Louis encephalitis (SLE) and Powassan (POW) viruses (Flaviviridae, Flavivirus), LaCrosse (LAC) virus (Bunyaviridae, Bunyavirus), and Colorado tick fever (CTF) virus (Reoviridae, Coltivirus). Their scientific histories, geographic distributions, virology, epidemiology, vectors, vertebrate hosts, transmission, pathogenesis, clinical and differential diagnoses, control, treatment, and laboratory diagnosis are reviewed. In addition, mention is made of the Venezuelan equine encephalitis (VEE) complex viruses (family Togaviridae, genus Alphavirus), which periodically cause human and equine disease in North America. WEE, EEE, and SLE viruses are transmitted by mosquitoes between birds; POW and CTF viruses, between wild mammals by ticks; LAC virus, between small mammals by mosquitoes; and VEE viruses, between small or large mammals by mosquitoes. Human infections are tangential to the natural cycle. Such infections range from rare to focal but are relatively frequent where they occur. Epidemics of WEE, EEE, VEE, and SLE viruses have been recorded at periodic intervals, but prevalence of infections with LAC and CTF viruses typically are constant, related to the degree of exposure to infected vectors. Infections with POW virus appear to be rare. Adequate diagnostic tools are available, but treatment is mainly supportive, and greater efforts at educating the public and the medical community are suggested if infections are to be prevented.

https://cmr.asm.org/content/cmr/7/1/89.full.pdf

Medically important arboviruses of the United States and Canada.

Although considered by many in the west to be a rare and exotic infection, Japanese encephalitis is numerically one of the most important causes of viral encephalitis worldwide, with an estimated 50 000 cases and 15 000 deaths annually. 2 About one third of patients die, and half of the survivors have severe neuropshychiatric sequelae. Most of China, Southeast Asia, and the Indian subcontinent are aVected by the virus, which is spreading at an alarming rate. In these areas, wards full of children and young adults aZicted by Japanese encephalitis attest to its importance.

/pdf/neurological-aspects-of-tropical-disease-japanese-1sngp852vm.pdf

NEUROLOGICAL ASPECTS OF TROPICAL DISEASE: Japanese encephalitis

Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.

https://www.nejm.org/doi/pdf/10.1056/NEJM198809083191004?listPDF=true

Protection against Japanese Encephalitis by Inactivated Vaccines

Overview: Japanese encephalitis.

The distribution of virus and the composition of the mononuclear inflammatory response were studied in the brains of 7 children who died with Japanese encephalitis. Viral antigen was localized to neurons, with greatest involvement in the thalamus and brainstem. Quantitation of perivascular inflammatory responses showed a preponderance of T cells, but only 7 to 30% of these cells were T suppressor/cytotoxic cells. Inflammatory cells invading the parenchyma were predominantly macrophages with small numbers of T cells. B cells remained localized to perivascular cuffs. Viral antigen was progressively cleared in patients with survival of 6 days or more.

Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases.

Forty-nine consecutive patients with laboratory-confirmed acute Japanese encephalitis were studied to identify risk factors present at hospital admission which were associated with a fatal outcome. Sixteen patients (33%) died. The following constellation of findings correlated with a fatal outcome: infectious virus in cerebrospinal fluid (CSF), low levels of Japanese encephalitis virus-specific IgG and IgM in both CSF and serum, and a severely depressed sensorium. Age, sex, days ill before admission, distance from home to the hospital, past medical history, CSF protein content, and CSF leukocyte count were not significant risk factors.
Among patients hospitalized for acute Japanese encephalitis, a vigorous virus-specific immunoglobulin response, both systemically and locally within the central nervous system, is a good marker for survival, and may be an inherently important factor in recovery from illness.

Fatal outcome in Japanese encephalitis.

During an epidemic of Japanese encephalitis (JE) in northern Thailand, cerebrospinal fluid (CSF) leukocytes and blood leukocytes from 28 patients with suspected JE were tested for spontaneous in vitro synthesis of antibodies to JE virus (JEV). Sixteen patients were subsequently proven to be infected with JEV. Supernatant fluids of three-day cultures of unstimulated peripheral blood mononuclear leukocytes or unstimulated unfractionated CSF leukocytes were tested for JEV IgM and IgG antibodies with isotype-specific "antibody capture" radioimmunoassays. Blood-derived leukocytes from all sixteen JEV-infected patients and CSF-derived leukocytes from four JEV-infected patients synthesized JEV antibodies. Blood-derived and CSF-derived leukocytes from all 12 patients with central nervous system infections caused by agents other than JEV uniformly failed to synthesize JEV antibodies. Virus-specific antibody-producing cells can be detected in the blood and CSF early in the clinical course of acute JE.

Wanida Lorsomrudee

Papers

Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases.

Fatal outcome in Japanese encephalitis.

Virus-specific antibody-producing cells in blood and cerebrospinal fluid in acute Japanese encephalitis.