[Prevention and therapy of virus diseases with interferon].
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Biomedical subjects
Publications and source records attributed to D Neumann-Haefelin.
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Human leukocyte interferon (HLI) was used for treatment of human diploid fibroblasts before and after infection with vaccinia virus, herpes simplex virus type 1 (HSV 1), herpes simplex virus type 2 (HSV 2), and varicella zoster virus (VZV). Vero cells were infected with Medical Lake macaque herpes virus (MLMV), and treated with HLI in the same way. In all of these systems HLI exhibited an antiviral effect when administered before infection, and this effect could be increased by additional HLI treatment after infection. In vivo studies with HLI treatment were performed in monkeys experimentally infected with vaccinia virus, HSV 1, and MLMV. Vaccinia and herpes keratitis were prevented by local, prophylactic administration of HLI. Generalized infections with vaccinia virus and MLMV in monkeys immunosuppressed by antilymphocyte globulin, were significantly modified by either prophylactic or therapeutic systemic treatment with HLI.
The prophylactic potency of topically applied human leukocyte interferon and human fibroblast interferon was compared in a monkey model with herpes simplex virus type 1-induced keratitis. Both interferons effectively prevented keratitis at 1.9 X 10(6) U of activity per ml but were ineffective at 1.9 X 10(3) U/ml. Slight differences between human leukocyte interferon and human fibroblast interferon observed at the level of 1.9 X 10(5) U/ml were not statistically significant.
Rubella virus and simina virus 40 (SV40) were isolated from a newborn child suffering from neurological and anatomical anomalies. The SV40 isolate was very similar to SV40 strain 777 by electron microscopic, biological, and immunological criteria.
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Ten cases of Thygeson's bilateral punctate epithelial keratitis were observed during a two year period. The diagnosis, therapy and prognosis are discussed. The common erroneous diagnosis of herpetic keratitis may lead to corneal damage as a result of too intensive therapy. Highly hydrophilic contact lenses have proven to be a valuable aternative to steroid therapy. The etiology remains obscure. Viruses were not detected with either tissue culture technique or with electron microscopy.
There were 40 virologically confirmed cases of dendritic keratitis treated in a randomized double-blind placebo-controlled study. After thermomechanical debridement of the corneal epithelium, the patients received two drops of human leukocyte interferon (HLI) twice daily. The activity was 3 X 10(-6) units/ml. HLI significantly accelerated healing and inhibited virus shedding. It remains to be studied whether HLI will be equally effective in the prophylaxis of late herpes recurrences.
The virological surveillance of poliomyelitis in 1974-1975 led to the detection of specific characteristics of wild viruses in 57 out of 221 cases of poliovirus isolation. The disease symptoms were typical for poliomyelitis in 36 of these cases, less characteristic in 13. Polio wildvirus was isolated 8 times from the surroundings of the patients. In 36 foreign patients and one German the causative agent was imported from an endemic area. In these cases and in a further 7 German patients the disease was sporadic. In contrast 5 cases in German children in late autumn 1975 constitute a local epidemic of poliomyelitis.
In the autumn of 1975 five cases of poliomyelitis occurred within 6 weeks in German children of families of low socioeconomic class. They lived in two districts of Freiburg with close familial and occupational contacts. One child had been immunised against polio once orally several years ago and none of the others were immunised. The clinical course and results of investigations of the environment are reported. Included is the state of immunisation of 472 school beginners in Freiburg schools and the antibody levels of 284 children aged 1 to 10 years from Freiburg and the adjoining areas.
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Seventy-three patients with herpetic epithelial keratitis were randomly divided into three groups and were treated by local applications of human leukocyte interferon, thermocautery plus human leukocyte interferon, or thermocautery plus mock human leukocyte interferon to obtain information on whether therapy with human leukocyte interferon can serve as a substitute for mechanical debridement of the involved epithelium or can improve the results when given as additional therapy. Fifty-five patients (75%) yielded herpes simplex virus before treatment, and only the results in these patients with keratitis of proved viral etiology were included in the analysis. These results indicated that mechanical debridement cannot be replaced with local application of human leukocyte interferon (3-4 X 10(4) units per day). When given in addition to thermocautery, human leukocyte interferon may have been of some value in a number of patients. However, the results were not statistically significant. A more potent dosage of human leukocyte interferon might provide better results.
Rhesus monkeys treated with antilymphocytic globulin were infected with vaccinia virus or with Medical Lake macaque Herpesvirus. At the sites of inoculation of vaccinia virus, animals not treated with interferon developed typical pustulous reactions and then smaller secondary lesions. Human leukocyte interferon (5 X 10(5) international units per day) injected intramuscularly, either from one day before to three days after infection or for seven days beginning on the first day of primary reaction, suppressed the development of secondary lesions but did not influence the primary reaction. Infection with Herpesvirus caused a vesicular rash similar to that of human varicella. Through prophylactic treatment with human leukocyte interferon, the disease was completely averted in two of four monkeys, and in the other two the rash was delayed. Therapy initiated when the first lesions appeared prevented the enlargement and generalization of lesions in all of four monkeys. Formation of serum antibodies was only slightly influenced by human leukocyte interferon. The results suggest that systemic treatment with interferon, begun either prophylactically or therapeutically with the first symptoms, can be effective in immunosuppressed patients.
2,277 specimens from 901 eyes were cultured for herpes simplex virus (HSV). 161 of 391 herpes-diseased eyes yielded HSV. The clinico-virological correlation led to a simple diagnostic and therapeutic scheme which is applicable by the ophthalmologist in his office without virological confirmation: 1. Superficial viral herpes (dendritic keratitis and allied disorders), HSV-isolating rate 96%. 2. Stromal herpes (disciform edema, different types of interstitial herpetic keratitis), only sporadical findings of HSV in the lacrimal fluid. The rate of virus-recovery increases, however, when an interstitial herpetic keratitis ulcerates. 3. Metaherpetic corneal disease = chronic or chronic recurrent superficial postherpetic disease without any detectable HSV-activity (main types: metaherpetic erosion, metaherpetic ulcer, metaherpetic bullous keratopathy). One of four superficial herpetic corneal diseases proved to be nonviral, i.e. metaherpetic in our series. Metaherpetic diseases may be widely considered as a therapeutic entity. The differential diagnosis with the slitlamp only and the proposed therapy (highly hydrophilic soft lenses plus adequate additional eye drops) are discussed in detail. Being aware of the diagnostic criteria and taking advantage of a combined soft lens therapy the treatment of metaherpetic corneal disease is easier and more successful than commonly accepted.
12 african green monkeys were inoculated in both eyes with herpes simplex virus typ 1 and 16 rhesus monkeys with vaccinia virus. The right eyes were treated with human leukocyte interferon (HIF) while the left eyes served as controls and showed the typical keratitis, 7 out of 8 herpes eyes and all 9 vaccinia eyes which were treated prophylactically or simultaneiously with HIF showed no signs of disease. When HIF was given later in the course of the infection the keratitis was either little influenced or not modified at all. The reasons are discussed.
The effectiveness of high-titre rubella immunoglobulin was tested on rubella-susceptible female juveniles or young adults after intranasal immunization with rubella strain RA 27/3, 20 ml of rubella immunoglobulin having been administered intramuscularly to 56 subjects at different times (1, 3 and 5 days) after the immunization. The effect was demonstrated by seroconversion and virus isolation from the throat. In the control subjects (26) the secroconversion was 96% and in 42% of subjects virus was demonstrated in the throat. Early administration of rubella immunoglobulin (up to three days after immunization) depressed the seroconversion rate to 55% and virus isolation rate to 17.5%. Later administration (five days after immunization) increased the conversion rate to 81%, the isolation rate to 31%. There were no serious side effects of the immunization and the injection of the immunoglobulin. The results indicate that on early administration of an adequate amount of high-titre rubella immunoglobulin a protective effect can be expected, although this favourable effect-obtained in the conditions of this study-cannot be unreservedly transposed to the situation in wild virus infections.
Six virus laboratories from various parts of the German Federal Republic and West Berlin undertook investigations into polio-myelitis immunity in 1972. A total of 267 persons aged up to 20 years were investigated for neutralizing antibodies against the three types of polio virus. The study showed that from the fourth year of life approximately 70% of the persons investigated had antibodies against all three types of polio virus. In some younger children the equivalent values were considerably lower. After the fourth year of life there were only slight differences in the humoral immunity against the three polio virus types. There was no evidence that the immunity level had deteriorated up to the 20th year of life and thus there is no indication of the necessity for a repeat immunisation at a certain time. The investigation confirmed that three oral administrations of trivalent vaccine, as are now generally recommended as basic immunization in the German Federal Republic, result in a conversion rate of over 90% against each of the three virus types.
Pretreatment of human fibroblast cultures with human leukocyte interferon (HIF, 1,000 IU/ml) resulted in a 24-h delay of virus replication after infection with vaccinia virus and herpes simplex virus type 1 and type 2. Additional HIF treatment 24 h after infection effectively lowered the maximum yield of viral infectivity. Equal results were obtained in simian cells with 3,000 IU of HIF per ml. The spread of two cell-bound herpesviruses, varicella zoster virus and Medical Lake macaque herpesvirus, was inhibited by 2,000 IU of HIF per ml in human fibroblasts and Vero cells, respectively. Varicella zoster virus infectivity was notably reduced by HIF, whereas the latter system showed a low sensitivity. To study the effect of HIF in the infected cornea, keratitis was induced experimentally in both eyes of 12 rhesus monkeys and 12 African green monkeys by inoculation with vaccinia virus and herpes simplex virus, respectively. In each monkey one eye served as a control for the full cycle of disease. In the other eye HIF treatment was initiated prophylactically 15 h before or simultaneously with the challenge virus infection or 6 to 20 h postinfectionally or therapeutically after onset of the disease, and the treatment was continued for 2 to 7 days. Prophylactic and simultaneous administration equally resulted in inhibition of both vaccinia and herpes keratitis. Postinfectional and therapeutic administration of interferon moderated the course of keratitis slightly and shortened the period of virus shedding.
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