Safety and efficacy of purified Vero cell rabies vaccine given intramuscularly and intradermally. (Results of a prospective randomized trial)

OBJECTIVES: To determine adverse reactions as a result of pre- and post-exposure rabies vaccination, using the conventional intramuscular, and reduced dose intradermal regimens and purified Vero cell rabies vaccine. DESIGN: A prospective and randomized study of patients exposed to rabies and of subjects in need of pre-exposure rabies vaccination. SETTING: A metropolitan rabies control center in a canine rabies endemic country. PATIENTS: 1198 subjects were recruited between May, 1994 and March, 1996. They were divided into four groups. Patients with suspected or proven rabies exposures were given the vaccine intramuscularly using the conventional regimen, or intradermally using the World Health Organization approved Thai Red Cross schedule. Human or equine rabies immune globulin was administered where indicated. Pre-exposure and post-exposure vaccine recipients were divided randomly into two groups each and given the vaccine either by the intramuscular or intradermal schedules. MEASUREMENTS: All local and systemic adverse reactions were recorded and statistically analyzed. RESULTS: Pruritus at injection sites was the only significant local reaction. It was more common in the intradermal groups. Low-grade fever, the only significant adverse systemic event, was more common in the intramuscular groups and was noted in 8% of all subjects. Eighty-four patients bitten by proven rabid animals were found to be alive and well 3 years later. Forty-four of these had received the intramuscular and 40 the intradermal postexposure regimens with human or equine immune globulin injected into wounds on the first day of treatment. CONCLUSIONS: Purified Vero cell rabies vaccine is safe, carries a very low adverse reaction rate and is effective in preventing rabies in severely exposed subjects when used with human or equine rabies immune globulin.     

Rabies prophylaxis following the feeding of a rabid pony

A survey was performed to identify people who were exposed to a rabid pony and determine whether or not they received rabies postexposure prophylaxis (PEP). Sixty-one visitors who came in contact with the rabid pony were identified. These visitors heard about the rabid pony via the news media. Forty-five visitors were exposed during the 2 weeks before the pony died. Thirty-two of these 45 visitors received PEP. Thirty-one visitors had or may have had saliva contact to an open wound or mucosa and all 31 received PEP. Fourteen visitors had no saliva contact to a wound or mucosa and one received PEP. Sixteen visitors were exposed before the pony was potentially shedding rabies virus and one received PEP. No visitor was bitten by the pony. Most of the persons 31/33 (94%) who received PEP had an exposure for which PEP was indicated. Nonbite transmission of rabies is discussed.     

Rabies surveillance in the United States during 1997

In 1997, 49 states, the District of Columbia, and Puerto Rico reported 8,509 cases of rabies in nonhuman animals and 4 cases in human beings to the Centers for Disease Control and Prevention. Nearly 93% (7,899) were wild animals, whereas 7% (610) were domestic species. The total number of reported cases increased 19.4% from that of 1996 (7,128 cases). Increases were apparent in each of the major species groups, with the exception of cattle. The relative contributions of these groups to the total reported for 1997 were as follows: raccoons (50.5%; 4,300 cases), skunks (24.0%; 2,040), bats (11.3%; 958), foxes (5.3%; 448), cats (3.5%; 300), dogs (1.5%; 126), and cattle (1.4%; 122). The 958 cases of rabies reported in bats represented a 29.3% increase over the total reported for 1996 and the greatest number reported since 1984, with cases reported by 46 of the 48 contiguous states. The epizootic of rabies in raccoons expanded into Ohio in 1997 and now includes 19 states and the District of Columbia. Thirteen states, where rabies in raccoons is enzootic, reported increases over 1996 in total numbers of reported cases. New York (1,264 cases), North Carolina (879), Virginia (690), and Maryland (619) reported the greatest numbers of cases [corrected]. Five states reported increases that exceeded 50%, compared with cases reported in 1996: Ohio (673.3%; 15 cases in 1996 to 116 in 1997). Massachusetts (144.3%; 115 to 281), South Carolina (97.9%; 96 to 190), Connecticut (97.4%; 274 to 541), and Maine (86.3%; 131 to 244). Cases of rabies associated with foci of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas continued to decline, with this state reporting 78.3% fewer rabid foxes (13 cases), 26.7% fewer rabid dogs (11), and 63.2% fewer rabid coyotes (7) during 1997, compared with 1996. Reported cases of rabies in cats (300) and dogs (126) increased 12.8% and 13.5%, respectively, whereas cases in cattle (122) decreased by 6.9%. Thirty states, the District of Columbia, and Puerto Rico reported increases in rabies in animals during 1997, compared with decreases reported by 31 states and the District of Columbia in 1996. One state (Mississippi; 5 cases) remained unchanged. Hawaii was the only state that did not report a case of rabies in 1997. Four indigenously acquired cases of rabies reported in human beings were the result of infection with rabies virus variants associated with bats.     

The abbreviated 2-1-1 schedule of purified chick embryo cell rabies vaccination for rabies postexposure treatment

During August 1988 to January 1990, the immunogenicity and safety of purified chick embryo cell rabies vaccine (PCEC) given by the conventional and abbreviated regimens in 82 vaccinees moderately to severely exposed to laboratory proven rabid animals were studied. The 16 vaccinees received PCEC six doses as conventional schedule on days 0, 3, 7, 14, 28 and 90, the 11 vaccinees received six doses of PCEC plus human rabies immune globulin (HRIG) on day 0. The 29 vaccinees received an abbreviated schedule of PCEC as two doses on day 0, one dose each on days 7 and 21 and the 26 cases received PCEC abbreviated schedule plus HRIG on day 0. The kinetics of the neutralizing antibodies on days 0, 7, 14, 28, 56, 180 and 365 were studied for comparative purpose. All vaccinees had high antibody levels from day 14 which last longer than a year and were safe after one year follow up. The adverse reactions of the vaccine were mild and self-limited.     

Bats, cats, and rabies in an urban community

Bats are the primary vectors of rabies in humans in the United States. In the urban environment they generally are found within buildings where they may bite people or be attacked by cats or dogs. Given the high probability that any bat that bites a person may be rabid, antirabies prophylaxis should be administered as soon as possible after the incident. This should not be delayed pending laboratory results on the bat. Children should be taught to avoid contact with moribund bats. Cats are more likely to be involved with rabid bats than dogs, but they are less likely to be vaccinated against rabies. The occasional rabid cat in an urban community may have acquired its infection from a bat. Therefore, it is vital that communities enforce rabies vaccination for cats as well as dogs.     

Clinical presentation of experimentally induced rabies in horses

Twelve naive and nine test-vaccinated horses which developed clinical signs of rabies as a result of the required protocol of a vaccine trial were prospectively observed. Nineteen of the 21 cases were confirmed positive for rabies infection of the brain by fluorescent antibody test. The two horses with negative results had ganglioneuritis of the trigeminal ganglion or lymphocytic perivascular cuffing in the brain stem in addition to clinical signs. Average incubation period was 12.3 days and average morbidity was 5.5 days. Naive animals had significantly shorter incubation and morbidity periods (P < 0.05). Muzzle tremors were the most frequently observed (81%) and most common initial sign. Other common signs were pharyngeal spasm or pharyngeal paresis (71%), ataxia or paresis (71%), lethargy or somnolence (71%). The furious form was manifested in 43% of rabid horses and some of these furious animals initially manifested the dumb form. The paralytic form was not observed. Histopathology was characteristics for rabies. The results of this trial do not reflect on the efficacy of commercially licensed equine rabies vaccines.     

Public awareness of rabies and compliance with pet vaccination laws in Connecticut, 1993

OBJECTIVE: To determine the degree of public awareness of rabies and compliance with cat and dog vaccination laws in Connecticut in 1993. DESIGN: Monthly telephone surveys. SAMPLE POPULATION: 1,810 households. PROCEDURE: A telephone interview was conducted, using rables-related questions contained in the Behavioral Risk Factor Surveillance System, with an adult member from households randomly selected statewide by telephone number. Results of the surveys for the year were aggregated, and weighted data were analyzed. RESULTS: Ninety percent of respondents had heard about rabies during the preceding year, and 84% considered it a problem in Connecticut. Forty-seven percent of households surveyed owned dogs or cats. Ninety-three percent of dogs and 80% of cats were reported to be vaccinated against rabies. Twenty-two percent of households with cats had at least 1 cat that was not current on rabies vaccination. CLINICAL RELEVANCE: In Connecticut, an epizootic of rabies in raccoons was accompanied by a high degree of awareness of rabies and rate of reported vaccination of dogs and cats. However, vaccination of cats was less common than that of dogs. Public education efforts should emphasize the necessity to vaccinate cats and to avoid contact with unknown cats in rabies epizootic or enzootic areas. A surveillance system can be used to help evaluate public health programs.     

Persistence of antibodies in children after intradermal or intramuscular administration of preexposure primary and booster immunizations with purified Vero cell rabies vaccine

BACKGROUND: The use of intradermal (i.d.) injections of purified Vero cell rabies vaccine (PVRV) for preexposure prophylaxis has not been well-established. We studied the safety and immunogenicity of i.d. and intramuscular (i.m.) PVRV injections for primary and booster preexposure immunizations. METHODS: One of two rabies preexposure PVRV regimens comprising three doses of either 0.1 ml i.d. or 0.5 ml i.m. administered during 28 days was assigned at random to 190 school children. One booster dose was given 1 year later either i.d. or i.m., according to their initial randomization group. Serologic results were available from 155 (82%) children at 1 year after primary immunization and 118 (62%) children at 2 years after booster. RESULTS: Although children vaccinated i.d. had significantly lower rabies-neutralizing antibody titers after primary immunization as well as after booster than children vaccinated i.m. (P< 0.001 for all time points), there were no significant differences in the percentages of children with adequate titers (> or =0.15 IU/ml) between the i.d. and i.m. groups after both primary and booster immunizations. Mild local reactions were more frequent after i.d. vaccination. Mild or moderate systemic reactions were infrequent and similar after i.d. and i.m. vaccinations. Fever and headache were reported by < or =6%. The reactions after booster were not different from those of post-primary immunization. CONCLUSIONS: Purified Vero cell rabies vaccine appears to be safe and immunogenic for primary and booster preexposure immunizations. An i.d. PVRV preexposure regimen should be useful especially for rabies-endemic countries with low per capita income.     

Efficacy of an oral vaccinia-rabies glycoprotein recombinant vaccine in controlling epidemic raccoon rabies in New Jersey

A field trial to evaluate the efficacy of an oral vaccinia-rabies glycoprotein recombinant virus vaccine in controlling epidemic raccoon (Procyon lotor) rabies was conducted by distributing 180,816 doses (10(8.2)TCID50/ml) of vaccine in wax ampules within fish-meal polymer baits at a rate of 64 doses/km2/treatment throughout a 552 km2 area, forming an 18 km wide band across the northern Cape May Peninsula of New Jersey (USA). Vaccination treatments were conducted in the spring and fall between May 1992 and October 1994 from a helicopter along ecotones and from motor vehicles along roads. Vaccine-laden baits were removed by animals from tracking stations within 3 wk and 61% of the identifiable tracks were those of raccoons. Tetracycline incorporated in the baits as a biomarker was detected in 155 (73%) of the vaccination area raccoons following the fall 1993 and spring 1994 vaccinations. Eleven (61%) of the raccoons sampled in the same time period seroconverted (> or = 0.5 IU) in response to rabies virus glycoprotein. A raccoon diagnosed with rabies from the northern border of the vaccination area on 30 April 1993 provided the first evidence that the barrier was being challenged by the rabies epidemic. The prevalence of rabies in raccoons from the vaccination area for the first year (10%, n = 96) and second year (8%, n = 61) of challenge was reduced more than six-fold by vaccination compared to unvaccinated raccoons from northern adjacent surveillance areas during the corresponding first (65%, n = 189) and second years (53%, n = 43). Vaccination also effectively reduced by three-fold the rate at which the epidemic moved through the raccoon population (15 km/yr). The breach of the vaccination area resulted in a resumption of the high rate (43 km/yr) of epidemic movement and a significant nine-fold increase in rabies prevalence (77%, n = 47). The maximum linear movement (12.9 km) among five ear-tagged rabid raccoons in the study area was significantly greater than that of 19 normal radio-collared raccoons (2.58 km) in the area. These large movements of rabid raccoons, together with relocation of nuisance raccoons, spillover of raccoon rabies in skunks (Mephitis mephitis) and other species, insufficient funding and a decision to discontinue the program in 1994 (which could have resulted in insufficient population immunity among raccoons in the vaccination area) may have contributed to the eventual breach of the barrier.     

Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new, highly purified, heat-treated equine rabies immunoglobulin, administered either alone or in association with a purified, Vero-cell rabies vaccine

A clinical evaluation of a new, purified, heat-treated equine rabies immunoglobulin (PHT-Erig), F(ab')2 preparation, was carried out in Thailand and in the Philippines-two countries where rabies is endemic. An initial prospective, randomised, controlled trial (Study 1), compared the safety and pharmacokinetics (serum concentrations of rabies antibodies) after administration either of PHT-Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A second trial (Study 2) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV), administered in association with either Erig PMC or PHT-Erig. In Study 1, 27 healthy, Thai adults received a 40 IU kg(-1) dose of either Erig PMC (n = 12) or PHT-Erig (n = 15) via the intramuscular (i.m.) route; half of the dose was injected into the deltoid area and the other half into the buttocks. Serum for rabies antibody determination and F(ab')2 concentration was collected at hours (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were safe, with no serious adverse events, and in particular, no anaphylactic reactions or serum sickness was reported. A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products. Nonetheless, the relative bioavailability of 93% and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar. The antibody level in either group were low throughout the 15-day study period. The geometric mean titer (GMT) values ranged from group 0.027-0.117 IU ml(-1) in the Erig group and from 0.029 to 0.072 IU ml(-1) in the PHT-Erig. There was no significant difference between the evolution of GMT values for the two groups. In Study 2, 71 healthy volunteers received 40 IU kg(-1) via the intramuscular route of either Erig PMC (n = 36) or PHT-Erig (n = 35) on D0, in association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and D28. No serious reactions were reported in either group. In particular, no immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were observed. Over the 28-day follow-up period, GMT profiles of the two groups were statistically equivalent. On D14, 100% of the subjects had protective antibody titers (anti-rabies antibodies > or = 0.5 IU ml(-1), which is the WHO-recommended level of seroconversion), and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen. On D28, the GMT values were 33.2 IU ml(-1) (95% CI, 23.8-46.1 IU ml(-1)) in the Erig PMC/PVRV group and 31.4 IU ml(-1) (95% confidence interval, CI, 23.4-42.2 IU ml(-1)) in the PHT-Erig/PVRV group, showing evidence of adequate vaccine-induced antibody responses in both groups. The increased purity, the heat-treatment step introduced in the manufacturing process of PHT-Erig, and the good clinical results substantiate the use of this new generation, purified equine F(ab')2 preparation in the post-exposure prophylaxis of rabies.     

Chromosomal abnormalities and tumor development: from genes to therapeutic mechanisms

PURPOSE: To summarize the epidemiologic, diagnostic, and clinical features of the 32 laboratory-confirmed cases of human rabies diagnosed in the United States from 1980 to 1996. DATA SOURCES: Data were obtained from case reports of human rabies submitted to the Centers for Disease Control and Prevention by state or local health authorities. STUDY SELECTION: All cases of human rabies reported in the United States from 1980 to 1996 in which infection with rabies virus was confirmed by laboratory studies. DATA EXTRACTION: Patients were reviewed for demographic characteristics, exposure history, rabies prophylaxis, clinical presentation, treatment, clinical course, diagnostic laboratory tests, identification of rabies virus variants, and the number of medical personnel or family members who required postexposure prophylaxis after coming in contact with an exposed person. DATA SYNTHESIS: 32 cases of human rabies were reported from 20 states. Patients ranged in age from 4 to 82 years and were predominantly male (63%). Most patients (25 of 32) had no definite history of an animal bite or other event associated with rabies virus transmission. Of the 32 cases, 17 (53%) were associated with rabies virus variants found in insectivorous bats, 12 (38%) with variants found in domestic dogs outside the United States, 2 (6%) with variants found in indigenous domestic dogs, and 1 (3%) with a variant found in indigenous skunks. Among the 7 patients with a definite exposure history, 6 cases were attributable to dog bites received in foreign countries and 1 was attributable to a bat bite received in the United States. In 12 of the 32 patients (38%), rabies was not clinically suspected and was diagnosed after death. In the remaining 20 cases (63%), the diagnosis of rabies was considered before death and samples were obtained specifically for laboratory confirmation a median of 7 days (range, 3 to 17 days) after the onset of clinical signs. Of the clinical differences between patients in whom rabies was diagnosed before death and those in whom it was diagnosed after death, the presence of hydrophobia or aerophobia was significantly associated with antemortem diagnosis (odds ratio, 11.0 [95% CI, 1.05 to 273.34]). The median number of medical personnel or familial contacts of the patients who received postexposure prophylaxis was 54 per patient (range, 4 to 179). None of the 32 patients with rabies received postexposure prophylaxis before the onset of clinical disease. CONCLUSIONS: In the United States, human rabies is rare but probably underdiagnosed. Rabies should be included in the differential diagnosis of any case of acute, rapidly progressing encephalitis, even if the patient does not recall being bitten by an animal. In addition to situations involving an animal bite, a scratch from an animal, or contact of mucous membranes with infectious saliva, postexposure prophylaxis should be considered if the history indicates that a bat was physically present, even if the person is unable to reliably report contact that could have resulted in a bite. Such a situation may arise when a bat bite causes an insignificant wound or the circumstances do not allow recognition of contact, such as when a bat is found in the room of a sleeping person or near a previously unattended child.     

Comparative study of 2 variants of a modified esophageal transection in the Sugiura-Futagawa operation

From December of 1990 to December of 1997, 119 subjects visited to our hospital to receive post-exposure therapy using purified chick embryo cell rabies vaccine manufactured by the Chem-Sero-Theraptic Institute (Katestuken), because they had been bitten by supposed rabid animals abroad. The forty of the subjects (male: 25, female: 15) wished to have their anti-rabies antibody levels examined. The number of samples taken after 5 or 6 shots rabies vaccine were 30 and 15, respectively. The antibody levels after 6 shots of rabies vaccine varied from 1.0 IU/ml to 10.1 IU/ml. After 5 shots the antibody levels fluctuated from under 0.1 IU/ml to over 8.8 IU/ml, and 3 subjects were found to have antibody titers of under 0.5 IU/ml which is the WHO minimal protective level. Two of these 3 subjects found to have antibodies of 1.0 IU/ml and 3.1 IU/ml. after the 6th injection. However, these 3 subjects had the hazard to have rabies despite post-exposure immunization, because the incubation period of rabies is found to be 1-3 months in about 60% of the cases. The potency of Kaketsuken's rabies vaccine should be increased to provide higher antibody levels.     

Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a multicentre, placebo-controlled, dose-comparison study

OBJECTIVE: To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis. DESIGN: Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo. SETTING: European university hospitals. PATIENTS: A total of 103 patients with Raynaud's phenomenon secondary to systemic sclerosis. INTERVENTION: Patients received one of three treatments for 6 weeks: placebo, oral iloprost 50 microg or oral iloprost 100 microg. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 200 microg. MEASUREMENTS: The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient diary; physician's global assessment and adverse events were recorded at visits to the clinic. Analysis was performed on an intention-to-treat population. RESULTS: A total of 103 patients were recruited, 89 completed the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patients received placebo, 33 received iloprost 50 microg and 35 received iloprost 100 microg. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up. At the end of treatment (6 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.03), but not in the severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow-up (12 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but not in the frequency of attacks (P = 0.07). Percentages of patients improved at the end of treatment as assessed by the physician were 44% placebo, 57% iloprost 50 microg and 64% iloprost 100 microg (not significant). Side-effects were reported by 80% of patients on placebo, 85% on oral iloprost 50 microg and 97% on oral iloprost 100 microg. Premature discontinuations of treatment in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events. CONCLUSION: The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 microg iloprost dose was better tolerated in this patient group.     

Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis

BACKGROUND: Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial. METHODS: Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145). FINDINGS: 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]). INTERPRETATION: RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.     

Postexposure treatment of rabies in Pakistan

To evaluate compliance with current World Health Organization (WHO) guidelines for postexposure treatment (PET) of rabies, we interviewed all animal bite victims seeking treatment on the same day of each week from 28 December 1994 through 18 January 1995 at the Civil Hospital of Karachi (Pakistan), a major referral center. Of the 143 patients studied, 109 (76%) sustained bleeding transdermal bites (WHO category III). Overall, wounds were not washed with soap or an antiseptic in 69% of victims. All victims received 5% sheep brain-derived vaccine, and only three of the 109 victims with category III bites received rabies immune globulin. PET of rabies in Karachi was deficient by all WHO standards. Although there is a great urgency to improve PET, it will remain a costly and inefficient method of controlling rabies. Reduction of rabies reservoirs is required to decrease human deaths due to rabies in Pakistan and other developing countries in which canine rabies is endemic.     

Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD. METHODS: To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen. RESULTS: Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy. CONCLUSIONS: Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.     

Hong Kong''s eastern and western medical history

BACKGROUND: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions. OBJECTIVE: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks. RESULTS: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone. CONCLUSIONS: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.     

Prevention of the spread of rabies to wildlife by oral vaccination of raccoons in Massachusetts

OBJECTIVE: To evaluate the use of bait containing rabies vaccine to create a barrier of rabies-vaccinated raccoons in Massachusetts and to determine the effectiveness of various bait distribution strategies in halting the spread of rabies. DESIGN: Prospective study. SAMPLE POPULATION: Free-ranging raccoons. PROCEDURE: Baits were distributed twice yearly in a 207-km2 (80-mi2) area in the vicinity of the Cape Cod Canal. Bait density and distribution strategy varied among 3 treatment areas. Raccoons were caught in live traps after bait distribution and anesthetized; blood samples were obtained to measure serum antibody titers to rabies virus. Vaccination rates were determined by the percentage of captured raccoons with antibody titers to rabies virus > or = 1:5. In addition, raccoons with clinical signs of illness inside the vaccination zone and adjacent areas were euthanatized and submitted for rabies testing. RESULTS: The percentage of vaccinated raccoons differed significantly among the following 3 areas with various bait densities: high-density area with uniform bait distribution (103 baits/km2 [267 baits/mi2]) = 37%; low-density area with additional targeted bait distribution (93 baits/km2 [240 baits/mi2]) = 67%; and, high-density area with additional targeted bait distribution (135 baits/km2 [350 baits/mi2]) = 77%. Nineteen animals with rabies (15 raccoons, 3 skunks, 1 cat) were reported in the area just outside of the vaccination zone, but only 1 raccoon with rabies was reported from inside the vaccination zone. CLINICAL IMPLICATIONS: In this suburban study area, an approximate vaccination rate of 63% was sufficient to halt the spread of rabies in free-ranging raccoons. Compared with uniform bait distribution, targeting raccoon habitats increased vaccination rates.     

Stem cells of the central nervous system

BACKGROUND: The aim of the present study was to analyze whether minor differences in recipient body surface area have any predictive value on renal allograft evolution. METHODS: For this study, we considered 236 pairs of recipients who received a kidney from the same donor at our center between March 1985 and December 1995. Pairs in whom at least one patient presented any of the following events were excluded: graft loss during the first year of follow-up, diabetes mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or de novo glomerulonephritis. Recipients of each pair were classified as large or small according to their body surface area (BSA). The percentage difference of BSA in each pair was calculated, and two cohorts of pairs were defined: BSA difference < or = 10% (n=76 pairs) and BSA difference >10% (n=70 pairs). RESULTS: The large recipients of the cohort with a BSA difference >10% showed a higher incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075), hypertension at 1 year of follow-up (51/70 vs. 35/70, P=0.006), and a higher serum creatinine level at 1-year follow-up (173 vs. 142 micromol/L, P=0.003), whereas in the cohort with a BSA difference < or = 10%, posttransplant evolution in large and small recipients was not different. Multivariate analysis showed that recipient BSA was an independent predictor of delayed graft function, posttransplant hypertension, and serum creatinine at 1-year follow-up. CONCLUSIONS: Relatively small differences in recipient BSA influence renal allograft evolution. Consequently, our data support that recipient size should be taken into consideration for renal allograft allocation.