Therapeutic and preventive vaccination of persons bitten by wolves in the Aktiubinsk region]

A total of 46 cases of wolves attacking people were registered in the Aktyubinsk region during the period of 1972--1976. These attacks resulted in 1 person dying of wounds and 2 persons being infected with rabies. In more than a half of the wolves available for examination after the attack rabies was confirmed by laboratory investigation. All the victims of such attacks received antirabies gamma globulin (0.25--0.5 ml per kg body weight) and the maximum doses of rabies vaccine (daily injections of 5 ml for 25 days, then 2 more injections in the same dose 10 and 20 days later). No complications were observed after the injections. The vaccination schedule recommended for use in the USSR for the prophylaxis of rabies proved to be effective.     

Rabies post-exposure prophylaxis in the Philippines: health status of patients having received purified equine F(ab')(2) fragment rabies immunoglobulin (Favirab)

Background

Recommended treatment for severe rabies exposure in unvaccinated individuals includes wound cleaning, administration of rabies immunoglobulins (RIG), and rabies vaccination. We conducted a survey of rabies treatment outcomes in the Philippines.

Methods

This was a case series involving 7,660 patients (4 months to 98 years of age) given purified equine RIG (pERIG) at the Research Institute for Tropical Medicine (Muntinlupa, Philippines) from July 2003 to August 2004 following Category II or III exposures. Data on local and systemic adverse reactions (AR) within 28 days and biting animal status were recorded; outcome data were obtained by telephone or home visit 6–29 months post-exposure.

Results

Follow-up data were collected for 6,464 patients. Of 151 patients with laboratory-confirmed rabies exposure, 143 were in good health 6–48 months later, seven could not be contacted, and one 4-year-old girl died. Of 16 deaths in total, 14 were unrelated to rabies exposure or treatment. Two deaths were considered PEP failures: the 4-year old girl, who had multiple deep lacerated wounds from a rabid dog of the nape, neck, and shoulders requiring suturing on the day of exposure, and an 8-year-old boy who only received rabies PEP on the day of exposure.

Conclusions

This extensive review of outcomes in persons with Category III exposure shows the recommended treatment schedule at RITM using pERIG is well tolerated, while survival of 143 laboratory-confirmed rabies exposures confirms the intervention efficacy. Two PEP intervention failures demonstrate that sustained education and training is essential in rabies management.     

Correction: Neutralizing Antibody Response after Intramuscular Purified Vero Cell Rabies Vaccination (PVRV) in Iranian Patients with Specific Medical Conditions

Objective

Post exposure prophylaxis using one of the WHO-approved vaccines is the method of choice for preventing rabies. Abnormal immune function in patients with some specific medical conditions, such as pregnancy, chronic hepatitis B virus infection, different types of cancers like lymphoma, diabetes I and II, corticosteroid consumption by patients with rheumatoid arthritis and lupus erythematosus, could impair the immunologic response to various vaccines. The immune response to rabies vaccination has never been examined in patients with any of these described medical conditions. This study purposed to evaluate the neutralyzing antibody response after vaccination with purified Vero cell rabies vaccine (PVRV) according to the WHO-recommended Post–Exposure Prophylaxis (PEP) "ESSEN" regimen.

Methods

Thirty healthy volunteers and 50 volunteers with different medical conditions who were exposed to a suspected rabid animal in the 2nd or 3rd category of exposure received 5 doses of PVRV under the ESSEN protocol. Three blood samples were collected on days 0 (before the first dose), 14, and 35. The anti-rabies antibody titer was measured using the Rapid Fluorescent Foci Inhibition Test (RFFIT) and an ELISA Bio-Rad, Platelia, Rabies II kit.

Results

All subjects reached NAb titers above 0.5 IU/ml by day 14 after vaccination. On day 35 (1 week after receiving the last rabies vaccine), anti-rabies antibodies were in the protective level (>0.5 IU/ml) in both groups. There was no statistically significant difference in anti-rabies antibody response due to the type of exposure (category 2 or 3), and successful seroconversion was confirmed in both groups.

Conclusion

In conclusion, the ESSEN protocol using the PVRV vaccine is sufficient for rabies prophylaxis in patients with specific medical conditions.     

Immunogenicity of inactivated seasonal influenza vaccine in adult and pediatric liver transplant recipients over two seasons

Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010–11 influenza season, and 53 adult and 21 pediatric recipients in the 2011–12 season, were investigated. Seroprotection rates (hemagglutinin‐inhibition [HI] antibody titer 1:40) were 50–94% to all three antigens among adults and 27–80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32–56% among adults and 13–67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011–12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010–11 and 0/53 vs. 3/21 in 2011–12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long‐term response to preceding vaccinations appeared to be insufficient in both groups.     

Essential Role of T Cells in the Postexposure Prophylaxis of Rabies in Mice

Athymic nude mice injected intramuscularly with a street strain of rabies virus were not protected against rabies by postexposure administration of beta-propiolactone-inactivated rabies vaccine. In contrast, their normal littermates were completely protected from death by the same vaccination regimens. Nude mice did not produce IgG antibody as a result of the vaccine during the test period of 15 days, whereas normal littermates produced IgG antibody from day 5 after vaccination. However, passive immunization with antirabies hyperimmune mouse ascites showed that antibody was completely ineffective in protecting either nude mice or their normal littermates against rabies when given later than 2 days after infection. No significant difference in the induction of circulating interferon by the vaccination was noted in these mice. Passive transfer of immune spleen cells to nude mice immediately after infection resulted in 30 to 37.5% protection of the mice. Passively transferred spleen cells did not produce detectable amounts of neutralizing antibody in the recipient mice except on day 2 after the transfer, when a low level of antibody was detected. These observations demonstrate the essential role of T cells in the postexposure prophylaxis of rabies in mice. The mechanisms of the failure of postexposure vaccination in nude mice are discussed.     

浓缩狂犬病疫苗接种后不良反应与血清抗体水平分析

报导了≥２．５ＩＵ浓缩狂苗人体接种后的不良反应其反应率为１．３１％与以往未浓缩常规苗的反应率为０．７３％比较两者具有显著性差异（Ｘ２＝６．９４,Ｐ＜０．０１）,浓缩苗以注射１～３针时的不良反应多,临床表现以局部极痛、红肿、瘙痒、急性荨麻疹和过敏性休克等。但其血清抗体阳转率７天时为４０．０％以上,１４天时为１００％,而常规苗仅是４０．０％,抗体滴度浓缩苗第７天时达到有效保护水平（中和试验）。显示了其抗体产生早,水平高特点,关于如何减少浓缩狂苗不良反应问题,作者提出了几点建议     

Immunization Against Rabies

The methods used for both pre-exposure and post-exposure immunization against rabies were studied. In pre-exposure immunization duck embryo vaccine should be used. In post-exposure immunization either duck embryo or Semple-type vaccine appears to be effective in stimulating antibody production. Both vaccines may cause neurological sequelae. A dose of vaccine should be given 20-50 days after completion of the primary course of vaccination. Immune serum should be used in all severe exposures especially of the head and neck, and in individuals in whom the commencement of vaccination has been unduly delayed. In individuals who have been previously vaccinated reinforcing doses have been found to be effective even as long as 20 years after the primary vaccination. A tissue culture vaccine has been developed and is about to undergo field trials.     

Loss of binding antibodies against rabies in a vaccinated dog population in Flores Island,Indonesia

Effective parenteral vaccines are available to control rabies in dogs. While such vaccines are successfully used worldwide, the period between vaccine boosters required to guarantee protection of the population against rabies varies between vaccines and populations. In Flores Island, Indonesia, internationally and locally produced rabies vaccines are used during annual vaccination campaigns of predominantly free-roaming owned domestic dogs. The study objective was to identify the duration of the presence and factors associated with the loss of adequate level of binding antibodies (≥0.5 EU/ml) following rabies vaccination in a domestic dog population on Flores Island. A total of 171 dogs that developed an antibody titre higher or equal to 0.5 EU/ml 30 days after vaccination (D30), were repeatedly sampled at day 90, 180, 270, and 360 after vaccination. On the day of vaccination (D0), an interview was performed with dog owners to collect information on dog characteristics (age, sex, body condition score (BCS)), history of rabies vaccination, kind of daily food, frequency of feeding, and origin of the dog. Serum samples were collected and the level of antibodies was quantitatively assessed using ELISA tests. Dogs were categorized as having an adequate level of binding antibodies (≥0.5 EU/ml) or inadequate level of binding antibodies (<0.5 EU/ml) at each time points examined. A total of 115, 72, 23, and 31 dogs were sampled at D90, D180, D270, and D360, respectively, with the highest proportion of antibodies ≥ 0.5 EU/ml (58%, 95% CI, 49–67%) at D90, which reduced gradually until D360 (35%, 95% CI, 19–52%). Multivariable logistic regression models showed that loss of adequate level of binding antibodies is significantly associated with dogs having no history of vaccination or vaccination applied more than 12 months before D0, being less than 12 months of age, and having a poor BCS. These results highlight the importance of BCS regarding the immune response duration and provide insights into frequency of vaccination campaigns required for the internationally available vaccine used on Flores Island. For dogs without vaccination history or vaccination being applied more than 12 months before D0, a booster is recommended within 3 months (a largest drop of antibodies was detected within the first 90 days) after the first vaccination to guarantee measurable protection of the population that lasts at least for one year.     

Antibody Response to a Human Diploid Cell Rabies Vaccine

An experimentally killed rabies virus vaccine prepared in a human diploid cell strain (WI-38)—Wyeth rabies vaccine (WRV)—was used by various injection schedules in two separate studies to define more closely in human volunteer subjects an effective vaccination schedule for pre- or postexposure immunization, particularly for donors of rabies-hyperimmune plasma. To permit valid comparisons between our results and those of other workers, antibody levels achieved were expressed in terms of international units (IU) per milliliter of serum. Antibody response of previously nonvaccinated persons were only modest after a single dose of WRV, never reaching a level higher than 0.80 IU/ml over a 56-day testing period. Moreover, antibody was not detected at 0.16 IU/ml before the 14th day, either after a single dose or after two doses given 3 days apart. The best response followed four doses of WRV given within 4 weeks. This schedule resulted in the highest rate of seroconversion to the ≥6 IU/ml antibody level required of potential rabies-immune plasma donors. Giving the first vaccine dose in aluminum hydroxide diluent did not enhance the antibody response. There was a definite suggestion in the various injection schedules that higher and more sustained antibody levels were reached when the interval between the first and second vaccine doses was longest. The greater immunogenicity of WRV as compared with duck embryo vaccine was best demonstrated by the fact that a single booster dose of duck embryo vaccine to previously vaccinated individuals resulted in only a sevenfold antibody rise during the following 56 days, whereas a booster dose of WRV elicited a 69-fold rise. Al(OH)₃ in the first dose of WRV had no effect, but the enhancing effect of a longer interval between vaccine doses was noted once again; 20 of 20 subjects who received three doses of WRV with 4 weeks between doses developed good levels of rabies antibody, and 19 exceeded 6 IU/ml.     

Immunogenicity and efficacy of two rabies vaccines in wild-caught, captive raccoons

The immunogenicity and efficacy of two rabies vaccines in wild-caught, captive raccoons (Procyon lotor) were investigated. Raccoons were fed Ontario Slim (OS) baits containing a recombinant vaccinia virus-rabies glycoprotein (VRG) oral rabies vaccine, or they were given an intramuscular (IM) injection of IMRAB(?) 3 rabies vaccine. Blood samples collected before treatment and from weeks 1 to 16 posttreatment were assessed for the presence of rabies virus antibody (RVA). There were significantly more positive responders in the group that received an IM injection of IMRAB 3 (18/27) than in the group that consumed VRG in OS baits (VRG-OS; 4/ 26). There were no significant associations among age, sex, and seroconversion. Of those animals that mounted a humoral immune response to vaccination, RVA was first detected between weeks 1 and 5, with the majority of initial seroconversions detectable at week 2. A subsample of 50 raccoons (19 VRG-OS, 18 IMRAB 3, and 13 controls) from the longitudinal serology study was challenged with live raccoon variant rabies virus 442 days after initial treatment. There were significantly more survivors in the group that received IMRAB 3 (13/18) than in the VRG-OS (5/19) or control (2/13) groups. All 15 raccoons that demonstrated a serologic response survived challenge regardless of treatment. Of the 35 raccoons with no detectable serologic response, 30 (86%) succumbed to rabies virus infection (14/15 VRG-OS, 5/7 IMRAB 3, and 11/13 controls).     

Immune response in cattle vaccinated against rabies

In order to determine the best type of rabies vaccine to use as a booster, 78 serological samples from singly vaccinated cattle were analyzed by counterimmunoelectrophoresis technique. The animals were divided into several groups, received the first vaccine dose with modified live virus vaccine (ERA strain) and were revaccinated with inactivated virus or modified live virus vaccines. Boosters were given at 2, 4, 8, 12 and 16 weeks following first vaccination. Results showed high titres in the cases of booster with inactivated vaccine. In all cases, however, detectable antibody titres declined quickly.     

Eliminating rabies in Estonia

The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV) campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania.     

A mouse model of the pathogenesis and postexposure prophylaxis of rabies

A mouse model for the study of postexposure prophylaxis of rabies was established. Mice injected intramuscularly with a street strain of rabies virus were significantly protected from death by five daily 0.2-ml doses of inactivated rabies vaccine of chick embryo cell culture origin initiated immediately or 3 hr after infection. In these mice, a large amount of circulating interferon was induced as early as 1 hr after the first dose of vaccine and lasted until at least 12 hr but no such amount of interferon was induced by additional doses of vaccine. Serum antibody was first detected in the mice on day 6. It was noted that some of the surviving mice manifested an ataxia or paralysis of the legs. Increasing mortality rates were shown in mice treated with decreasing doses of the vaccine. Passive protection tests using concentrated IgG and IgM antibodies with equivalent neutralization titers showed that IgG antibody gave total protection when given 24 hr before the infection, while it was almost totally ineffective in reducing the mortality when given 2 days or more after infection. IgM antibody did not protect the mice even when given 24 hr before infection. These results suggest that interferon production is more important than antibody production in the initial stages of protection by postexposure vaccination. However, the mechanisms of postexposure prophylaxis in this model could not be explained only by the interferon produced by the vaccine and the possible contributions of additional mechanisms were suggested.     

Safety of lyophilized SAG2 oral rabies vaccine in collared lemmings

Fifteen collared lemmings (Dicrostonyx groenlandicus) were exposed to a lyophilized oral rabies vaccine designed to immunize wild carnivore populations. No animals contracted rabies from the vaccine as determined by the absence of clinical signs after 37 days and lack of rabies virus in brain tissue determined by the fluorescent antibody (FA) test. These results suggest that collared lemmings would not contract rabies if they ingested this lyophilized vaccine in the wild during bait vaccination programs for arctic foxes (Alopex lagopus).     

Vaccination of free-ranging Pennsylvania raccoons (Procyon lotor) with inactivated rabies vaccine

Thirty-nine free-ranging raccoons (Procyon lotor) in an endemic rabies area of Pennsylvania (USA) were vaccinated with a single intramuscular inoculation of commercial inactivated rabies virus vaccine, 17 June to 23 August 1987. Paired serum samples, pre- and postvaccination, were obtained from eight raccoons and were analyzed in vitro for rabies virus neutralizing antibody using a modified rapid fluorescent focus inhibition test. Seven of eight (88%) recaptured raccoons demonstrated seroconversion within 15 to 26 days of vaccination. At 1 yr postvaccination, three vaccinated raccoons were recaptured and challenged in captivity with street rabies virus, resulting in the death of two of three vaccinates and five of five unvaccinated control raccoons.     

42例狂犬疫苗免疫后抗体水平监测

本文报告了42例狂犬疫苗免疫后抗体水平的监测,并将其抗体效价与性别、年令免疫的天数进行了比较,从几何平均滴度上看,抗体效价与性别、年令均无明显区别,而免疫后的天数,则直接影响着抗体水平的高低,提示:狂犬疫苗免疫后抗体水平的监测具有重要意义.     

Immunization of Cattle Against Rabies Using Inactivated Cell Culture Vaccines

Twenty-one heads of cattle were vaccinated with Madibovin, 31 with Rabdomun and 127 with Rabisin on 4 different farms. Rabies neutralizing antibody titre (≥0.5 IU/ml) was detected in 80% of 163 animals tested about 1 month and in 42% of 133 animals tested about 1 year after primary vaccination. On 3 of the farms 86 animals received booster vaccination about 1 year after primary vaccination. All these animals had antibody titre (≥0.5 IU/ml) about 1 month after booster and antibody levels were higher than after the primary vaccination. Rabies antibody titres (≥0.5 IU/ml) were detected in 96% of 50 animals tested 1 year after the booster. No significant differences (p>0.05) in antibody levels were detected between animals vaccinated with Madibovin or Rabisin (farm C) respectively with Rabisin or Rabdomun (farm D) at any collection time. Responses to rabies vaccines varied considerably between the farms. After primary vaccination of the animals on 2 farms with the same batch of Rabisin, the antibody levels clearly differed (p<0.0001) between the farms. Our results indicate that booster is always necessary after primary vaccination to ensure that all animals are protected.     

Experimental inoculation of raccoons (Procyon lotor) with rabies virus of skunk origin.

To determine raccoon (Procyon lotor) susceptibility and serum neutralizing antibody response to a skunk salivary gland rabies virus, raccoons were inoculated with a rabies virus isolated from a naturally-infected striped skunk (Mephitis mephitis). Raccoons were divided into four groups of three animals each. A dilution of the rabies virus suspension, 10(2.4), 10(3.4), or 10(4.8), mouse intracerebral lethal dose50 (MICLD50), was administered into the masseter muscles of each animal. Three negative control animals received only diluent. Saliva and sera were collected on post-inoculation days 35, 63 and 92 for virus isolation and determination of serum neutralizing antibody titer. All animals survived the 92 day observation period and none exhibited the behavioral changes classically associated with clinical rabies virus infections. Rabies virus was not detected in the saliva of any raccoon and two of the three animals receiving the highest inoculum developed serum neutralizing antibodies (SNA). On day 92, a challenge suspension of New York City/Georgia (NYC/GA) strain rabies virus in fox salivary glands (10(3.2) MICLD50) was administered to all 12 raccoons. All animals succumbed to rabies virus except the two animals that had earlier developed SNA. The results of this study provided evidence about the susceptibility of raccoons to a skunk rabies virus and demonstrated that exposed raccoons could survive for at least 92 days following exposure. Furthermore, animals developing SNA under such circumstances were capable of withstanding challenge with rabies virus that was fatal for seronegative raccoons.