Identification of Bulgarian Strain 258 of Enterovirus 71

Abstract

In 1975 in Bulgaria a severe epidemic of central nervous system (CNS) disease occurred. Clinically, histopathologically, and epidemiologically the cases resembled poliomyelitis, aseptic meningitis, meningoencephalitis, and, in some cases, encephalomyocarditis. About 21% of the 700 reported cases developed paralysis, 44 with fatal outcome [ref. 1]. In 65 cases, 92 strains of enterovirus of the same serologic type were isolated: 38 strains from the CNS, 10 from mesenteric lymph nodes and tonsils, and 44 from feces [ref. 1 2]. A typical representative strain, No. 258, isolated from the spinal cord of a 3-month-old baby who died on the 5th day of disease with signs of focal polioencephalitis, was selected for intensive study. Cross-neutralization tests established the antigenic identity of the Bulgarian 258 strain (Stanchev) with American strains of enterovirus type 71 (BrCr and JaFr strains) and Swedish strains of the same type (Nos. 52343, 52500, and 6041). From its biological [ref. 1,2], physicochemical [ref. 3], and antigenic properties, the etiological agent of this large epidemic can be classified as a member of enterovirus type 71, one of the most highly pathogenic of the recently recognized entero-viruses.

Incidence and case‐fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan

“…Several epidemics of enterovirus 71 have given us notice of how enterovirus 71 infection may be associated with even more severe manifestations, such as brain stem encephalitis, limb paralysis, pulmonary edema, and pulmonary hemorrhage. The 1998 epidemic in Taiwan was the fourth documented outbreak of enterovirus 71 infection causing rapid deterioration leading to death in young children; the first documented outbreak occurred in Bulgaria in 1975 [Melnick et al, 1979], the second in Hungary in 1978 [Nagy et al, 1982], and the third in Malaysia in 1997 [Ministry of Health of Malaysia, 1997]. The Bulgarian outbreak produced a disease characterized by a rapid onset of medullary involvement of the central nervous system.…”

“…Ever since Schmidt et al [1974] first identified this virus in 20 patients suffering from central nervous system disorders, enterovirus 71 has been associated with hand-foot-and-mouth disease, as well as with a variety of clinical syndromes worldwide [Hagiwara et al, 1978;Nagy et al, 1978;Melnick et al, 1979;Shindarov et al, 1979;Gilbert et al, 1988; Ministry of Health of Malaysia, 1997;Chang et al, 1998]. Some of these are serious or even life-threatening, including meningitis, encephalitis, poliomyelitislike syndrome and myocarditis.…”

Virological diagnosis of enterovirus type 71 infections: Experiences gained during an epidemic of acute CNS diseases in Hungary in 1978

“…258 and the prototype BrCr strain (13,18), as well as between the Japanese Nagoya and the BrCr strains (11). I t is of interest to note that two of our isolates, one from the brain of a patient with fatal encephalitis and another from the stool of a patient with poliomyelitis-like paralysis have been tested with anti-BrCr sera in Houston at the WHO Collaborating Centre for Virus Reference and Research.…”

“…It has elicited sporadic cases of meningitis, encephalitis, exanthematous and respiratory diseases in the U.S.A. (5,6,24), Australia (12) and Sweden (2,28); extensive mixed epidemics of hand, foot and mouth disease and aseptic meningitis with a predominance of the former in J a p a n (10,11,14) and of the latter in Sweden (2); and a severe epidemic of acute CNS diseases in Bulgaria (4,13,25). In Hungary a severe meningitis-encephalitis epidemic occurred in 1978 lasting from May to September.…”

An overview of the evolution of enterovirus 71 and its clinical and public health significance

“…Serological diagnosis was achieved by neutralisation assay with a total of 71.9% of clinically diagnosed cases having either a single high titre antibody level (38.8%) or a four-fold rise in antibody (33.2%). The initial identi¢cation of EV71 (strain 258) in the Bulgarian epidemic was made by Melnick et al [25] and a formalininactivated vaccine was prepared from this strain [22]. However, the vaccine was never put into use, as the epidemic declined before the vaccine was ready for use.…”