Large-scale survey of adverse reactions to canine non-rabies combined vaccines in Japan

Canine non-rabies combined vaccines are widely used to protect animals from infectious agents, and also play an important role in public health. We performed a large-scale survey to investigate vaccine-associated adverse events (VAAEs), including anaphylaxis, in Japan by distributing questionnaires on VAAEs to veterinary hospitals from April 1, 2006 through May 31, 2007. Valid responses were obtained for 57,300 vaccinated dogs at 573 animal hospitals; we obtained VAAEs information for last 100 vaccinated dogs in each veterinary hospital. We found that of the 57,300, 359 dogs showed VAAEs. Of the 359 dogs, death was observed in 1, anaphylaxis in 41, dermatological signs in 244, gastrointestinal signs in 160, and other signs in 106. Onset of VAAEs was mostly observed within 12h after vaccination (n=299, 83.3%). In this study, anaphylaxis events occurred within 60 min after vaccination, and about half of these events occurred within 5 min (n=19, 46.3%). Furthermore, where anaphylaxis was reported, additional information to support the diagnosis was obtained by reinvestigation. Our resurvey of dogs with anaphylaxis yielded responses on 31 dogs; 27 of these demonstrated collapse (87.1%), 24 demonstrated cyanosis (77.4%), and both signs occurred in 22 (71.0%). Higher rates of animal VAAEs, anaphylaxis, and death were found in Japan than in other countries. Further investigations, including survey studies, will be necessary to elucidate the interaction between death and vaccination and the risk factors for VAAEs, and thus develop safer vaccines. Moreover, it may also be necessary to continually update the data of VAAEs.     

Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper,canine parvovirus infection and rabies

Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.     

Cell-mediated immune response to rabies virus in dogs following vaccination and challenge

Peripheral blood lymphocytes (PBL) from non-vaccinated dogs and from dogs either vaccinated intramuscularly (IM) or subcutaneously (SC) with an inactivated rabies virus vaccine (Rabguard-TC, Norden Laboratories, Lincoln, NE) or intramuscularly with an attenuated rabies virus vaccine (Endurall-R, Norden Laboratories, Lincoln, NE) were exposed in vitro to rabies virus. Blastogenesis of PBL was measured by incorporation of 3H-thymidine into the DNA of proliferating cells in the presence of a suboptimal concentration of phytohemagglutinin (PHA). Following the first vaccination, there was no difference in the blastogenic response of lymphocytes from dogs vaccinated IM with either the inactivated or attenuated rabies virus vaccines. The inactivated rabies vaccine stimulated as great or greater blastogenic response when it was given SC. The PBL from non-vaccinated control dogs were not stimulated by rabies virus. Dogs vaccinated with the inactivated vaccine developed a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus. Nonvaccinated control dogs did not develop a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus.     

Comparison of antibody responses after vaccination with two inactivated rabies vaccines

Thirty laboratory dogs were randomly assigned to two groups (A and B) of 15 dogs and subcutaneously vaccinated with a single dose of one of two commercially available monovalent inactivated rabies vaccines: RABISIN (Merial, France) (group A) and NOBIVAC Rabies (Intervet International) (group B). Rabies antibodies were measured over a period of 4 months using the fluorescent antibody virus neutralization (FAVN) test. The two vaccines performed differently in terms of magnitude and persistence of rabies antibodies titers in dogs. Two weeks after vaccination, average rabies antibody titers peaked at 2.53 IU/mL (range, 0.17-13.77 IU/mL) and 1.26 IU/mL (range, 0.50-4.56 IU/mL) in groups A and B dogs, respectively. The average FAVN antibody titres against rabies on D28, D56, D84, D112 and D120 were significantly higher in group A than in group B. Although all dogs from group B serologically responded to vaccination, the proportion of dogs with antibody titres >or=0.5 IU/mL dropped significantly after D28 and was statistically significantly lower on D56, D84 and D112 compared to group A dogs. In conclusion, in the context of international trade, the choice of the vaccine and the timing of blood tests are critical factors in achieving successful serological test results after rabies vaccination. RABISIN induces high and sustained antibody titres against rabies, increasing the flexibility for the time of blood sampling after primo-vaccination.     

Epidemiological situation of rabies in Lithuania from 1990 to 2000

The epidemiological situation of rabies was investigated in Lithuania. Over the last decade, 2277 cases of rabies were registered among wild and domestic animals (mean number of cases per districts was 44). The highest distribution of rabies was found in the districts of Lazdijai and Utena (116 and 81 cases, respectively), and the lowest in the Svencioniai and Zarasai districts (one and eight cases, respectively). It was found that rabies among wildlife comprised 54% with the majority of cases being registered in foxes (626 cases, 27%) followed by raccoon dogs (470 cases, 21%). Within the last 3 years, cases of rabies among foxes and raccoon dogs increased significantly (three and six times, respectively), compared with the period from 1990 to 1997. Among domestic animals, 46% cases of rabies were registered, with cattle comprising 27%, and the cases among cats and dogs at 9 and 8%, respectively. During the period from 1993 to 1997 in Lithuania, 11,385 of humans were attacked by domestic and wild animals, and 21,173 humans were vaccinated against rabies for prophylactic reasons. Our survey has shown that, during the period from 1997 to 2000, the number of people attacked has increased drastically-31,348 (60%), but only 8021 (18%) of them were vaccinated.     

Antibody response to an anti-rabies vaccine in a dog population under field conditions in Bolivia

Rabies remains an important public health issue in Bolivia, South America. Public concern and fears are most focussed on dogs as the source of rabies. The objective of the present study was to assess immunity of an inactivated suckling mouse brain vaccine against canine rabies used for the official vaccination campaigns under field conditions in an endemic area of rabies in Bolivia. A total of 236 vaccinated and 44 unvaccinated dogs in Santa Cruz de la Sierra, selected using stratified random sampling, were investigated in order to obtain owned dog characteristics and antibody titres against rabies in April 2007. The proportion of vaccinated dogs with an antibody titre exceeded the protection threshold value of 0.5 EU/ml was 58% [95% confidence intervals (CI): 52-65], indicating that vaccination is likely to elicit an antibody response (odds ratio 6.3, 95% CI: 1.2-11.5). The range of geometric mean of antibody titre for vaccinated dogs (0.89 EU/ml; 95% CI: 0.75-1.04) was considered to meet the minimal acceptable level indicating an adequate immune response to the vaccine. However, the titre level was not satisfactory in comparison with the results from other field investigations with inactivated tissue culture vaccines. It is recommended for public health authorities to (1) consider modernizing their vaccine manufacturing method because the level of immunity induced by the current vaccine is comparably low, (2) conduct frequent vaccination campaigns to maintain high levels of vaccination coverage, and (3) actively manage the domestic dog population in the study area, which is largely responsible for rabies maintenance.     

Rabies Vaccination: Higher Failure Rates in Imported Dogs than in those Vaccinated in Italy

The current European Union (EU) legislation decrees that pets entering the EU from a rabies‐infected third country have to obtain a satisfactory virus‐neutralizing antibody level, while those moving within the EU require only rabies vaccination as the risk of moving a rabid pet within the EU is considered negligible. A number of factors driving individual variations in dog vaccine response have been previously reported, including a high rate of vaccine failure in puppies, especially those subject to commercial transport. A total of 21 001 observations collected from dogs (2006–2012) vaccinated in compliance with the current EU regulations were statistically analysed to assess the effect of different risk factors related to rabies vaccine efficacy. Within this framework, we were able to compare the vaccination failure rate in a group of dogs entering the Italian border from EU and non‐EU countries to those vaccinated in Italy prior to international travel. Our analysis identified that cross‐breeds and two breed categories showed high vaccine success rates, while Beagles and Boxers were the least likely to show a successful response to vaccination (88.82% and 90.32%, respectively). Our analysis revealed diverse performances among the commercially available vaccines, in terms of serological peak windows, and marked differences according to geographical area. Of note, we found a higher vaccine failure rate in imported dogs (13.15%) than in those vaccinated in Italy (5.89%). Our findings suggest that the choice of vaccine may influence the likelihood of an animal achieving a protective serological level and that time from vaccination to sampling should be considered when interpreting serological results. A higher vaccine failure in imported compared to Italian dogs highlights the key role that border controls still have in assessing the full compliance of pet movements with EU legislation to minimize the risk of rabies being reintroduced into a disease‐free area.     

Patterns of rabies occurrence in Bhutan between 1996 and 2009

This study was conducted to evaluate incidence and seasonal trends of rabies in dogs and other domestic animals in Bhutan from 1996 to 2009. Time series analysis approach was used to determine the seasonal trend and temporal association between species-specific rabies cases in animals. A total of 814 rabies cases were reported during the 14-year period, of which cattle and domestic dogs accounted for 55% (447/814) and 39% (317/814) of the cases, respectively. The remaining 6% of the cases (50/814) were reported in horses (2%), cats (2%), pigs (1%) and goats (1%). Rabies cases were reported throughout the year with more reports during spring and summer months. The annual patterns of cases were stable from 1996 to 2005, but the incidence increased during 2006 and 2008. Fifty-nine of the 205 sub-districts reported rabies in animals from 1996 to 2009 with increased incidences in the four districts in southern Bhutan, an area located close to the border towns of India. A significant (P < 0.05) positive cross-correlation was observed between the number of cases in dogs and other domestic animals at time lags (months) 1-3 with the highest correlation (r = 0.94, P < 0.05) observed at time lag 0 (same month) indicating that the peak in rabies incidences occur in the same month when both dogs and other domestic animal cases are reported. Regression analysis predicted rabies in other domestic animal when there are reports of rabies in dogs during the previous months. This study provides useful information about the epidemiology of rabies that can be used to plan a rabies control programme in Bhutan.     

Rabies vaccination compliance following introduction of the triennial vaccination interval--the Texas experience

In 2003 the Texas Board of Health approved a modification to the Texas Administrative Code that permitted pet owners to have their dogs (Canis familiaris) and cats (Felis catus) vaccinated against rabies every 3 years, provided a triennial vaccine was used. The change had been opposed by hundreds in the veterinary community, some concerned that its implementation would be followed by a decrease in rabies vaccination rates. To determine if this decrease had occurred, rabies vaccination rates for 4 years before and after migration to the 3-year vaccination interval were examined. Data for dogs and cats, ≥ 4 months of age, were collected from the Texas Department of Health Rabies Incident Report database. Each animal's record included its current rabies vaccination status. The number of animals that were currently vaccinated against rabies was tallied and the percent vaccinated was calculated. From 1999 through 2002, 46% of dogs were vaccinated against rabies. From 2004 through 2007, 56% of dogs were vaccinated against rabies. From 1999 to 2002, 18% of cats were vaccinated against rabies. From 2004 to 2007, 30% of cats were vaccinated against rabies. There has been a significant increase in the numbers of dogs (P < 0.001), and cats (P < 0.001), vaccinated against rabies since the introduction of the triennial vaccination interval. This observational study documents the positive changes in rabies vaccination rates following migration from a 1-year to 3-year vaccination interval.     

Factors associated with the success of rabies vaccination of dogs in Sweden

Background

United Kingdom, Ireland, Malta and Sweden maintain their national provisions for a transitional period regarding rules concerning rabies vaccination and individual serological test for rabies neutralizing antibodies. The purpose of vaccinating dogs against rabies is to establish pre-exposure immunity and protect individual animals from contracting rabies.The aim of the study was to investigate factors associated with reaching the internationally accepted threshold antibody titre of 0.5 IU/mL after rabies vaccination of dogs.

Methods

The study was a prospective single cohort study including 6,789 samples from Swedish dogs vaccinated with commercially available vaccines in Sweden, and the dog''s antibody responses were determined by the OIE approved FAVN test. Information on potential risk factors; breed, age, gender, date of vaccination, vaccine label and the number of vaccinations, was collected for each dog. Associations between the dependent variable, serological response ≥ 0.5 IU/mL or < 0.5 IU/mL and each of the potential risk factors were investigated using logistic regression analysis.

Results

Of 6,789 vaccinated dogs, 6,241 (91.9%) had an approved test result of ≥ 0.5 IU/mL. The results of the multivariable logistic regression analysis showed that vaccinating with vaccine B reduced the risk of having antibody titres of < 0.5 IU/mL by 0.2 times compared with vaccination using vaccine A. Breed size was found significant as an interaction with number of vaccinations and age at vaccination as an interaction with day of antibody testing after last vaccination. In summary, larger breeds were at higher risk of having antibody titres of < 0.5 IU/mL but if vaccinated twice this risk was reduced. Moreover, there were a increased risk for dogs < 6 months of age and > 5 years of age to have antibody titres of < 0.5 IU/mL, but this was affected by number of days from vaccination till testing.

Conclusions

The probability of success of rabies vaccinations of dogs depends on type of vaccine used, number of rabies vaccinations, the breed size of the dog, age at vaccination, and number of days after vaccination when the antibody titres are tested. The need for a booster vaccination regimen is recommended for larger breeds of dog.     

Serological responses of adult dogs to revaccination against distemper, parvovirus and rabies

Serum antibody titres to canine distemper virus (CDV), canine parvovirus (CPV) and rabies were measured in dogs that had not been revaccinated annually and compared with the titres in a control group of regularly vaccinated animals; 83 per cent (171 of 207) of the dogs vaccinated against CDV one or more years earlier had serum neutralising antibody titres equal to or greater than 16; 64 per cent (136 of 213) of the dogs vaccinated against CPV one or more years earlier had haemagglutination inhibiting titres equal to or greater than 80; and 59 per cent (46 of 78) of the dogs vaccinated against rabies two or more years earlier had serum neutralising antibody titres equal to or greater than 0.5 iu/ml. Three weeks after a single booster vaccination the dogs' antibody titres against CDV had increased above the threshold level in 94 per cent of the dogs, against CPV in 68 per cent, and against rabies in 100 per cent.     

Control of rabies in Jaipur, India, by the sterilisation and vaccination of neighbourhood dogs

A programme to sterilise and vaccinate neighbourhood dogs against rabies was established in Jaipur, India. Neighbourhood dogs were captured humanely, sterilised surgically, vaccinated against rabies and, when they had recovered, released where they had been caught. Between November 1994 and December 2002, 24,986 dogs were treated in this way. Direct observational surveys of the local dog population indicated that 65 per cent of the females were sterilised and vaccinated, and that the population declined by 28 per cent. The records of human cases of rabies seen in the main government hospital of the city between January 1992 and December 2002 showed that the number of cases had declined to zero in the programme area but increased in other areas.     

Incidence of canine rabies in N'Djaména, Chad

This work describes for the first time the incidence risk of passively reported canine rabies, and quantifies reported human exposure in N'Djaména (the capital of Chad). To diagnose rabies, we used a direct immunofluorescent-antibody test (IFAT). From January 2001 to March 2002, we were brought 34 rabies cases in dogs and three cases in cats. Canine cases were geographically clustered. The annual incidence risk of canine rabies was 1.4 (95% CI: 1.2, 1.7) per 1000 unvaccinated dogs. Most of the rabid dogs were owned-although free-roaming and not vaccinated against rabies. Most showed increased aggressiveness and attacked people without being provoked. Eighty-one persons were exposed to rabid dogs and four persons to rabid cats (mostly children<15 years old). Most of the exposed persons were neighbours or family members of the animal owner. Most exposures were transdermal bites, but nearly half of all exposed persons did not apply any first wound care or only applied a traditional treatment. In N'Djaména, humans are often exposed to canine rabies but do not use the full-course post-exposure treatment and wound care is insufficient. Most rabid dogs would be accessible to parenteral vaccination. Pilot vaccination campaigns are needed to determine the success of dog mass vaccination in N'Djaména as a way to prevent animal and human rabies.     

Canine distemper virus neutralising antibodies in vaccinated dogs

The associations between the levels of canine distemper virus neutralising antibodies and vaccination history, age and gender were investigated in a cross-sectional study of a sample of 4627 dogs from the Finnish urban dog population. Dogs vaccinated with either Canlan (Langford Laboratories) or Dohyvac (Solvay Animal Health) or with both, had significantly lower titres than those vaccinated with Candur (Behringwerke), Duramune (Fort Dodge Laboratories) or Nobivac (Intervet), or with combinations including at least one of these. The vaccines were classified as having low and high immunogenicity on the basis of the geometric mean titre achieved by the vaccine when compared with the geometric mean titre of the entire dataset. The low geometric mean titre of Canlan, Dohyvac and their combination groups resulted from the large proportion of dogs without detectable titres, especially dogs under one year of age, rather than from uniformly low titres. An age-stratified comparison of vaccine usage and titres showed that the division of the vaccines into low and high immunogenicity vaccines was apparent in the dogs less than two years of age but not in the older dogs. The first vaccination with the high immunogenicity vaccines resulted in a higher proportion of dogs with detectable antibodies than even repeated vaccination with the low immunogenicity vaccines. Neither the time elapsed since the most recent vaccination nor the gender of the dogs was associated with the titre of antibody.     

Serosurveillance of rabies antibodies in dogs in Mumbai region by using indirect ELISA

Rabies is a highly fatal viral infection of the central nervous system affecting all warm-blooded animals including humans. To implement the preventive and control measures, it is important to decide the status of anti-rabies antibodies in dogs. Out of 120 serum samples, 47 (39.2 %) serum samples, showed an antibody titre equal to or above the cut off value of 0.5 IU/ml. The maximum number of dogs showed anti-rabies antibody titres equal to or above the cut-off value of 0.5 IU/ml after <1 month pre-exposure to the rabies vaccine. In 15 serum samples of pet dogs, we observed 13 (86.66 %) dogs with protective anti-rabies antibody titre. Statistical analysis suggests that the age of the animal had no significant effect on anti-rabies antibody titre in vaccinated pet dogs. The overall low seroprevalence of anti-rabies antibody in stray dogs indicates their susceptibility to rabies infection and thus posing a risk of rabies to other animals and humans.     

Rabies-vaccination coverage and profiles of the owned-dog population in Santa Cruz de la Sierra, Bolivia

The Bolivian government issued a regulation for rabies control in November 2005, owing to increasing the prevalence of dog and human rabies cases in recent years. An assessment of rabies-vaccination coverage and other factors that might influence the success of the on-going vaccination campaign was needed. The objective of this study was to investigate dog rabies vaccination coverage and risk factors associated with dogs being unvaccinated against rabies, and profiles of the owned-dog population in Santa Cruz de la Sierra, Bolivia, where dog rabies was endemic. Mainly due to logistical reasons, the WHO's expanded programme on immunization cluster-survey method was used. The 390 households were included in the study. Information about dog population and management characteristics was obtained for 542 dogs from 301 households. On average, households had 1.4 dogs and 1.8 dogs per dog-owning household (median = 1). The human-to-dog ratio was 4.6 : 1. During the last 1 year prior to the study, of the 539 dogs aged >or=1 month, 463 (85%; 95% CI 79-91; design effect 3.6) were classified as vaccinated. Amongst the study dogs, dogs aged 1-11 months were the higher risk of dogs not being vaccinated (OR = 8.2; 95% CI 4.3-15.6; P < 0.01). Almost two-thirds of the study dogs were allowed to roam freely throughout the day or in part. Community education efforts should address the importance of dog ownership and movement restriction, and the need to vaccinate young dogs.     

Vaccination coverage and epidemiological parameters of the owned-dog population in Thungsong District, Thailand

Canine rabies vaccination is delivered in Thungsong District, Thailand, as an annual campaign between March 1 and 31, and also at other times through private veterinary clinics, para-veterinarians and health-care staff residing in the villages. The current questionnaire-interview survey was conducted between June 23 and July 18, 2002 to determine: rabies-vaccination coverage amongst the owned-dog population; basic dog-population information; and community awareness about rabies. The modified expand programme on immunization cluster-survey method was used to collect information about dog demography and management characteristics. Household knowledge about rabies and sources of rabies information were assessed. Vaccinated dogs were identified from vaccine certificates or owner reports confirmed by vaccinators. Seventy percent (95%CI 62-78) of 364 eligible owned dogs were vaccinated within the 6 months prior to data collection. Of these 255 vaccinated dogs, 44, 21, 13, 17 and 5% were vaccinated through the annual vaccination campaign, veterinary clinics, para-veterinarians, other vaccinators and owners, respectively. Fifty-four percent of households owned dogs. The sex ratio in dogs was 2 males per female; the dog: human ratio was 1: 4.6 with an average of 0.9 dogs per household (1.7 dogs per dog-owning household). Most dogs roamed freely and these were less likely to be vaccinated compared to dogs being kept on premises or on a leash. Almost all households were aware of rabies and the need for dog rabies vaccination as a control method. Seventy-six percent believed that rabies only occurred in summer. There was little awareness about cat rabies amongst households. Vaccination coverage in the total dog population clearly has not yet reached the 80% target level set by Thailand's official rabies-control programme. Improved effectiveness of the owned-dog rabies-vaccination campaigns in each community is needed-perhaps by more community education about dog management or by better management of ownerless dogs.     

The ERA Strain of Rabies Vaccine

An antigenic extinction trial in cats showed that the ERA rabies vaccine had superior antigenic properties over Flury H.E.P. C.E.O. and killed tissue culture rabies vaccine.

Dogs and cats on a duration of immunity study of ERA rabies vaccine were challenged with fox salivary gland “street” rabies virus. The results of this challenge show a duration of immunity of five years in dogs and four years in cats.

Vaccination of dams in late pregnancy with ERA rabies vaccine resulted in transference of maternal antibody to the newborn, in both cattle and dogs. This maternally derived antibody interfered with the successful active immunization of the young calf. Calves free of antibodies for rabies could be successfully vaccinated as early as 17 days of age and were able to withstand a challenge with virulent “street” rabies virus two years later.

     

Community-based active surveillance for rabies in Machakos District, Kenya

The rabies problem in Kenya has been greatest in Machakos District where the disease has persisted endemically for over 40 years. This paper presents the results of a one-year community-based active surveillance for rabies in six randomly selected sublocations in the district for the period 1992-1993. Approximately 860 rabid dogs per 100000 dogs were confirmed in this study, compared to approximately 12 per 100000 confirmed rabid dogs reported by the existing passive-surveillance system. This active surveillance underestimated the true rabies incidence, because only 41% (130/317) of the potential specimens could be diagnosed. Dogs accounted for 92% (179/194) of primary animal-rabies suspects, 80% (66/83) of secondary suspects, and 81% of the confirmed animal-rabies cases. The annual incidence of animal-bites of humans was 234 per 100000 people and the point estimate of human-rabies incidence per year was 25 per million people. Almost all (97%) animal-bites of humans were due to dogs.The traditional passive-surveillance system grossly underestimated the importance of rabies as a public-health problem in Machakos District. Community-based active surveillance provides a potential cost-effective strategy for greatly improving estimates of rabies incidence and epidemiology to inform veterinary and policy decision-making.     

湖南部分地区犬狂犬病病毒的监测研究

对湖南部分地域的8个县(市、区)的8个城区、乡镇和农村的健康犬抽样采集脑组织标本142份,应用RT-PCR和直接荧光抗体试验(FAT)检测,检测结果142份犬脑样中均不含狂犬病病毒。调查上述监测点及周边近三年狂犬病的免疫情况,免疫率均超过70%。表明湖南部分犬免疫工作较好的地区,通过加大群免疫密度,可以使犬狂犬病病毒携带率降低,这可能与形成免疫屏障有关。