RESUMEN

The coxsackievirus A24 variant was implicated in four of six major acute hemorrhagic conjunctivitis outbreaks in Singapore since its discovery in 1970. Hela cell suspension in 24-well flat-bottom tissue culture plates was a satisfactory alternative to monolayer cells grown in test tubes for virus isolation. Respiratory illness occurred in 20 of 98 patients with acute hemorrhagic conjunctivitis. Apart from conjunctival secretions, respiratory and oral transmission of coxsackievirus A24 variant would explain the rapid and extensive spread of acute hemorrhagic conjunctivitis during an outbreak.

Asunto(s)

RESUMEN

Singapore participated in the WHO EPI protocol for rapid assessment of serological response to three doses of standard oral poliovirus vaccine. The 100% seropositive finding of thirty infants below one year old is no proof of seroconversion rate to the Trivalent Oral Poliovirus Vaccine (TOPV) administered. Investigation of 100 cord blood samples showed that passively transferred maternal poliovirus neutralising antibody cannot be relied upon for protection of infants against poliomyelitis. This paper emphasises the importance of vaccine potency testing and serves as a timely reminder that although the last case of indigenous poliomyelitis was recorded in 1974, non Sabin-like (wild) polioviruses are being isolated from imported cases and foreigners hospitalised in Singapore, and unexpectedly, from the conjunctiva and pharynx of Singaporeans treated for conjunctivitis. It discusses the WHO (World Health Organization) Plan of Action for Eradication of Polio in the Western Pacific Region which includes Singapore.

Asunto(s)

RESUMEN

Nucleotide substitutions in the viral-encoded proteinase 3C (3Cpro) region (549 nucleotides) of the RNA genome of a coxsackievirus A24 variant (CA24v), one of the agents causing acute hemorrhagic conjunctivitis (AHC), were studied using 32 isolates collected from the Eastern hemisphere in 1970-1989. Based on regression analysis of nucleotide differences among isolates, the nucleotide substitution rate of CA24v 3Cpro was estimated to be 3.7 x 10(-3)/nucleotide/year. A phylogenetic tree constructed by the modified unweighted pair group method using arithmetic averages (UPGMA) indicated that CA24v had evolved from a common ancestor which appeared in one focal place in November 1963 +/- 21 months, about 7 years before the first isolation of CA24v in Singapore. The tree also revealed that all the recent epidemic isolates in 1985-1989 including Asian and Ghanian strains diverged from each other after 1981. This finding is consistent with the evidence that AHC due to CA24v had been confined to Southeast Asia and the Indian subcontinent until 1985, then suddenly and explosively spread to other areas where no CA24v isolations had been reported.

Asunto(s)

RESUMEN

The evolution of the variant of Coxsackievirus A 24 (CA 24 v) which causes acute hemorrhagic conjunctivitis was explored. Using 15 isolates obtained from Southeast Asia during the period 1970-1986, the genetic distance between isolates was estimated from pairwise comparison of nucleotide changes deduced from common spots on oligonucleotide maps of the isolates. From regression analysis of the genetic distance and the time of isolation of the isolates, the evolutionary rate of CA 24 v was estimated to be 3.44 x 10(-4)/nucleotide/month. The phylogenetic relationship of these isolates was explored using the neighbor-joining method and the modified unweighted pair group method using arithmetic averages (UPGMA). The phylogenetic tree constructed indicates that CA 24 v appeared from one focal place in July 1968 +/- 25 months, very close to the time of the first world epidemic of, then newly recognized, acute hemorrhagic conjunctivitis.

Asunto(s)

RESUMEN

Natural human interferons (IFN) and recombinant human IFNs (rIFN-alpha and rIFN-beta) inhibited the production of virus in Chang's human conjunctival cell cultures infected with epidemic isolates of acute hemorrhagic conjunctivitis virus, Coxsackievirus type A 24 (CA24). Generally, natural and rIFN-alpha and rIFN-beta were equally effective in inhibiting CA24 infection. However, rIFN-alpha A was more effective than rIFN-alpha C, D, I, J, and K in reducing virus infection, cytopathogenesis, and virus production. Recombinant IFN-alpha J was least effective in inhibiting CA24 in human conjunctival cell cultures. Also, the IFN titer was reduced 10- to 1,000-fold when cells were infected with greater than or equal to 0.3-0.5 CA24/cell, suggesting a dose-dependent IFN resistance by CA24. These results suggest that the antiviral activity of IFN against acute hemorrhagic conjunctivitis in vivo may vary with the CA24 isolates, the MOI, the type of IFN, and the time of infection with respect to beginning IFN treatment.

Asunto(s)

RESUMEN

Stools from acute diarrhoea were investigated for bacterial and viral pathogens. In one study involving 63 young children in a paediatric ward, 70% of the stools were positive for the pathogens looked for of which 37% contained bacteria, 22% viruses and 11% mixed cultures of bacteria and viruses. In another study in which 130 watery stools from routine specimens of patients of all ages were investigated, 36% were positive for pathogens with 11% bacteria, 18% viruses and 7% mixed pathogens. The high incidence of bacterial diarrhoea in young children was attributed to gastroenteritis caused by Salmonella species. Salmonella and rotavirus were found the most common pathogens in bacterial and viral diarrhoeas, and the most susceptible age group was under 5 years-old.

Asunto(s)

RESUMEN

An account of the nature of enterovirus and enterovirus infections with special reference to experiences encountered in Singapore is presented. The most common of enterovirus epidemic diseases since 1970 is Acute Haemorrhagic Conjunctivitis caused by Coxsackievirus A24 variant and Enterovirus type 70. Enterovirus of various serotypes were isolated from a wide range of illnesses varying in severity throughout the year.

Asunto(s)

Asunto(s)

RESUMEN

A recent epidemic of acute conjunctivitis in Singapore showed again the importance of Coxsackie virus type A24 variant as a causative agent of acute haemorrhagic conjunctivitis (AHC). Although the ocular manifestations appeared similar to those described for the 1970 and 1975 outbreaks, a markedly higher rate of respiratory involvements was noted. Not observed in previous epidemics were herpes-like vesicles in the conjunctiva and eyelids of one patient and vesicles in the buccal mucosa and lips of another from whom Coxsackie virus A24 was isolated. The most interesting finding in this study was the isolation of five wild (non-Sabin) poliovirus type 1 strains. Three strains were obtained from conjunctival and two from throat swabs of patients with mild to severe conjunctivitis. It is conceivable that the rare reports of polio-like paralysis or radiculomyelitis accompanying or following AHC in a few Asian countries could be attributed to concurrent infections with a poliovirus and either enterovirus type 70 or Coxsackie virus type A24.

Asunto(s)

RESUMEN

A rabbit enterovirus 70 (EV70) model infection that closely mimics human enteroviral conjunctivitis was developed. Conjunctivitis occurred 24 hr following topical application of EV70. The conjunctivitis was characterized by tearing, redness, swelling of the eye lids, follicles in the superior palpebral conjunctiva, and dilatation of subconjunctival blood vessels. Histologic examination of conjunctival and corneal tissue taken 1 and 2 days after infection revealed numerous punctate areas devoid of squamous epithelium on the upper palpebral conjunctiva. Also, follicles without germinal centers were observed microscopically in the palpebral and tarsal conjunctiva. Fibroblast infiltration characteristic of wound healing and a sparse mononuclear infiltration was noted by the second day. Peak levels of virus [10(3) to 10(6.2) plaque forming units (PFU)/ml] were detected 1 to 2 days after infection and declined to undetectable levels after 3 to 5 days. Interestingly, antiserum to parental EV70 was less effective (8-10-fold) in neutralizing EV70 adapted to animal and tissue culture systems. This finding suggests that an antigenic variant of EV70 arose during adaptation. Fibroblast interferon (IFN beta), which is indicative of viral infection, was detected in tears from 6 of 16 rabbits and declined to undetectable levels 3 days after infection. Serum antibody to EV70 was detectable 8 to 10 days after infection. However, the level of serum antibody was highly variable. The results indicate that the clinical disease, virologic and immunologic courses were similar to that of the human infection. Results suggest that this animal model provides a system for studying the natural antigenic variation of EV70, the natural host defenses of the eye, and antiviral treatments against enteroviral conjunctivitis.

Asunto(s)

RESUMEN

Arildone (WIN 38020; 4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-heptanedione) inhibited the infectivity of acute hemorrhagic conjunctivitis viruses in tissue culture. Arildone did not inhibit interferon (IFN) production or IFN activity. Treatment of cultures with combinations of arildone and IFN resulted in an additive inhibition of acute hemorrhagic conjunctivitis virus production.

Asunto(s)

Asunto(s)

RESUMEN

Virus-specific, early appearing neutralizing activities (ENA) and interferon (IFN) were detected in tears collected from patients during epidemics of acute hemorrhagic conjunctivitis (AHC). In one study, ENA that neutralized enterovirus type 70 (EV70) was detected in tears collected from 114 of 130 AHC patients in Florida. In another study, ENA against coxsackievirus type A24 (CA24) was detected in tears collected from 39 of 57 patients in Singapore with AHC caused by CA24. No tear samples contained ENAs to both EV70 and CA24. Tear samples from uninfected eyes did not contain ENA to EV70 or CA24. ENA to EV70 was detected in 6 of 11 patients 1-6h before the onset of AHC. In addition, tears of 68% of patients seen on the day of onset produced tears that contained ENA to EV70. Thus, ENA to EV70 may be detected less than 24h after infection (based on 24h incubation period). IFN beta was detected in 30% of tear samples collected from patients on the day of onset of AHC caused by EV70. This finding suggested that ENA and IFN could act together to inhibit primary infections of AHC. It was found that the combination of ENA and IFN inhibited virus replication synergistically (greater than or equal to 300 fold reduction) in preinfected cells. Our findings suggest that ENA represents a previously unreported early defense mechanism of the eye, that endogenous ENA and endogenous IFN could inhibit viruses synergistically in vivo, and that ENA in tears could be useful in identifying the agent causing AHC.

Asunto(s)

RESUMEN

Picornavirus particles and serotype-specific neutralizing antibody were demonstrated in tears collected during early onset of acute haemorrhagic conjunctivitis. Virus particles deposited from tears by airfuge ultracentrifugation and stained with potassium phosphotungstate were easily recognized by electron microscopy. Tear neutralizing antibody in the ultracentrifuged supernatant was detected by the neutralization test in monolayer HeLa cells grown in microtitration plates. The presence of virus particles and specific neutralizing antibody in tear specimens correlated with the serological findings.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)