Epidemic Vaccine Research Articles

Measles outbreak at the Val Thorens ski station, France, 2019

Abstract During the 2019 winter season, a measles outbreak occurred at the Val Thorens ski station in France, in an area frequented by over 300,000 holiday-makers (70% foreigners) and 2,500 seasonal workers. Between 24/01/2019 and 15/04/2019, 55 cases were reported (18 confirmed and 37 clinical). Apart from 5 infected children under 2 years old attending the same nursery, cases were mainly seasonal workers between 19 and 41 years old. Five cases were hospitalised, one with severe pneumonia. Of the 36 cases with known vaccination status, 25 (69%) had not completed 2-dose vaccination. Other confirmed cases in visitors to Val Thorens were reported in neighbouring valleys (n = 3), and in other French regions. One case was reported the French overseas territory Guadeloupe (WHO ‘Americas’ region where measles has been eradicated). British, Belgian, Danish, Dutch and Irish authorities reported 7 cases in people who had stayed in the area. The list of exported cases is non-exhaustive. The regional health agency (ARS) provided increased information on epidemic risk and vaccination recommendations, particularly to health professionals and the town council. Identifying all contacts was difficult because many had occurred with seasonal workers. In addition to the approximately 150 vaccinations carried out by the Val Thorens medical centre from the start of the outbreak, only 41 other people were vaccinated in 5 free vaccination sessions organized in situ by the ARS, and the local medical and immunization centres. The large attendance at the station favoured the outbreak and its extension in France and abroad. Due to low measles vaccine coverage in France (80.3% for 2-dose cover in 2 years in 2017), outbreaks in non-vaccinated and not fully vaccinated populations are increasing, as seen in Val Thorens. Key messages A major measles epidemic occurring in an undervaccinated population in frequent contact with tourists, led to the extension of cases in France and Europe. Despite 5 free in situ vaccination sessions, with the mobilisation of local health professionals, few seasonal workers came to be vaccinated.

A game theoretic approach to discuss the positive secondary effect of vaccination scheme in an infinite and well-mixed population

Abstract Pre-emptive vaccination policy used in controlling the rapid spreading of infectious diseases is considered as one of the most challenging issues imposed to mankind, causing enormous death tolls over the years. This paper dedicatedly studies the dilemma effect coming from the failure of getting perfect immunity to those individuals who committed vaccination earlier. Therefore, we propose a new theoretical model that slows down the infection spreading and also facilitates quicker recovery time than what the previous model does even if a vaccinator fails to obtain perfect immunity. We name this effect as the “positive secondary effect” of vaccination as it gives a second chance to the vaccinators which in return subdues the rapid spreading that helps in producing better social average payoff as well as keeping the final epidemic size smaller. Moreover, to address the positive secondary effect more precisely, we introduce two different parameters; namely, relaxation parameter (η) and foster parameter (δ) in two different directions to quantify the individual effects resulting from each of the parameter space as well as their superposition effect. An in-depth discussion focuses on the influential role played by our proposed model via discounting and faster recovery effects while a second chance is given to the vaccinators. In addition, we also examine the situation when discounting effect brought by η outperforms very much than its faster recovery controlled by δ as well as the superposition effects. Unlike all previous studies dealing with vaccination game, we pay much attention to investigating the secondary effect of imperfect vaccination policy. Our proposed theoretical scheme completely reproduces the decision-making process of choosing an imperfect provision based on evolutionary game theory entailed with the widely used SIR (Susceptible–Infected–Recovered) epidemic model. Without considering any spatial structure and perfect vaccination policy, our model presumes the population being infinite and well-mixed to represent the infection spreading dynamics mathematically. This study is conducted throughout using the so-called theoretical approach. Besides that, three different updating rules based on evolutionary game theory have also been considered to investigate all possible situations. Later on, we draw 2D full phase diagrams showing the final epidemic size, vaccination coverage, and average social payoff quantitatively. Finally, our theoretical result is compared with the counterpart result obtained from the multi-agent simulation (MAS) approach and a good agreement is found, hence the appropriateness of the proposed model is fully justified.

Epidemic size, duration and vaccine stockpiling following a large-scale attack with smallpox

On August 16th, 2018, we held Exercise Mataika to test preparedness for a worst-case scenario of a smallpox attack which begins in the Pacific and is followed by a larger scale attack in a highly populous Asian country. The exercise was underpinned by mathematical modelling which aimed to determine the duration and magnitude of the epidemic under different scenarios, the critical threshold for epidemic control, and scenarios where the current stockpile of vaccine is adequate. We constructed a modified SEIR model for smallpox transmission. We found that time to commencing the response, rates of contact tracing and ring vaccination, and rates of case isolation are all influential factors on epidemic size and duration. Ideally, the response should commence in 20 days after the attack, corresponding to 8 days after the first symptoms appear, given an average incubation period of 12 days. Every day of delay worsens the epidemic. The WHO stockpile of vaccine of 34 million doses is adequate if rates of case isolation and ring vaccination are maintained above 60%. If rates of contact tracing, ring vaccination and case isolation fall below 53%, epidemic control is lost. In such a scenario, the epidemic persists for longer than 10 years and over a billion doses of vaccine are needed for epidemic control. There are modifiable factors which can prevent a catastrophic scenario following smallpox re-emergence. These include very rapid response time and high rates of isolation and ring vaccination. Training and capacity building, as well as pre-vaccinated teams, can also assist with rapid response. In low income countries, a smallpox epidemic could overwhelm the health system and far exceed human resource capacity, so low rates of case isolation and contact tracing is a realistic possibility. The consequences of poor epidemic control are catastrophic if rates of case isolation and ring vaccination fall below 53%, the threshold for epidemic control. Global cooperation is also critical, to ensure that vaccine and other resources are directed quickly to affected areas.

Effect of information spreading to suppress the disease contagion on the epidemic vaccination game

The information awareness about contagious diseases have an influential effect on an individual's decision to suppress the diffusion of infections. In this work, a new mathematical framework for a vaccination game combined with susceptible-infected-recovered (SIR) and unaware-aware (UA) situation is considered. Altering wearing mask or taking protection against diseases, we consider the information spreading effect that might be represented the situation of self-protection. The information spreading is supposed only for local situation for a season, but has a very significant effect to reduce the infection through a generation. Within this concept, unaware and aware states are taken for susceptible, infected and vaccinated individuals for an infinite and well mixed population. Moreover, three different strategy updating rules concerning whether an individual committing or not vaccination: individual based, strategy based and direct selection are studied to show the comparison by depicting as full phase diagram. Finally, it can be seen that information spreading can subdue the spreading of epidemic within a population.

Complete sequence analysis of human norovirus GII.17 detected in South Korea.

Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI-GVII, with GII.4 being the most prevalent. However, in 2012-2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013-2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.

The impact of influenza vaccination on infection, hospitalisation and mortality in the Netherlands between 2003 and 2015

Influenza epidemics annually cause substantial morbidity and mortality. For this reason, vaccination is offered yearly to persons with an elevated risk for complications. Assessments of the impact of vaccination are, however, hampered by year-to-year variation in epidemic size and vaccine effectiveness.We estimate the impact of the current vaccination programme comparing simulations with vaccination to counterfactual simulations without vaccination. The simulations rely on an age- and risk-structured transmission model that tracks the build-up and loss of immunity over successive seasons, and that allows the vaccine match to vary between seasons. The model parameters are estimated with a particle Monte Carlo method and approximate Bayesian computation, using epidemiological data on vaccine effectiveness and epidemic size in the Netherlands over a period of 11 years.The number of infections, hospitalisations and deaths vary greatly between years because waning of immunity and vaccine match may differ every season, which is in line with observed variation in influenza epidemic sizes. At an overall coverage of 21%, vaccination has averted on average 13% (7.2–19%, 95% range) of infections, 24% (16–36%) of hospitalisations, and 35% (16–50%) of deaths. This suggests that vaccination is mainly effective in protecting vaccinees from infection rather than reducing transmission. As the Dutch population continues to grow and age, the vaccination programme is projected (up to 2025) to gain in impact, despite a decreasing infection attack rate.

Prevalence and genotypes of group A rotavirus among outpatient children under five years old with diarrhea in Beijing, China, 2011\u20132016

BackgroundRotavirus is a leading cause of severe diarrheal disease, and one of the common causes of death in children aged under five years old. The dominant epidemic strains may change in different years in the same area. In order to provide evidence for rotavirus epidemic control and inform vaccine development, we analyzed epidemiological patterns and genetic characteristics of rotavirus in Beijing during 2011–2016.MethodsStool specimens of outpatient children under five years old were collected from three children’s hospitals on a weekly basis. Group A rotavirus antigens were detected using enzyme-linked immunosorbent assay (ELISA) kit. The partial VP4 genes and VP7 genes of rotavirus were both amplified and sequenced. Genotyping and phylogenetic analyses were performed. Logistic regression and Chi-square tests were performed to determine differences across age groups, districts and years in rotavirus prevalence and genotype distribution.ResultsA total of 3668 stool specimens from children with acute diarrhea identified through hospital-based surveillance were collected from 2011 to 2016 in Beijing. A total of 762 (20.8%) specimens tested positive for rotavirus. The rotavirus-positive rate was highest among the 1–2 years old age group (29.0%, 310/1070). November, December and January were the highest rotavirus-positive rate months each year. G9 was the most common G genotype (64.4%, 461/716), and P [8] was the most common P genotype (87.0%, 623/716) among the 716 rotavirus-positive specimens. G9P [8], G3P [8] and G2P [4] were the most common strains. The rotavirus-positive rates of samples in 2012 and 2013 were higher than that in 2011, and the dominant genotype changed from G3P [8] to G9P [8] in 2012 and 2013. VP7 gene sequences of G9 strains in this study clustered into two main lineages. Most of the G9 strains exhibited the highest nucleotide similarity (99.1%~ 100.0%) to the strain found in Japan (MI1128). VP4 gene sequences of P [8] strains were almost P[8]b.ConclusionsRotavirus accounted for more than one fifth of childhood diarrhea in Beijing during the study period. Targeted measures such as immunization with effective rotavirus vaccines should be carried out to reduce the morbidity and mortality due to rotavirus.

Exploring voluntary vaccination with bounded rationality through reinforcement learning

Evidence shows that there exists a complex interaction between human vaccinating behaviors and disease prevalence during an epidemic. Usually, rational individuals make vaccinating decisions by strategically evaluating the cost of vaccination and the risk of infection. While in reality, individuals’ decisions can also be influenced by their social acquaintances. In this paper, we present a reinforcement learning-based mechanism to characterize human decision-making process with bounded rationality, which takes into consideration both individuals’ rational decisions and social influence from their neighbors. Specifically, we investigate human voluntary vaccinating behaviors in the face of flu-like seasonal diseases in locally-mixed social networks, where each individual together with his/her neighbors forms a well-mixed environment. Through carrying out simulations, we evaluate the performance of decision-making mechanisms with/without reinforcement learning in terms of vaccine coverage, final epidemic size, average payoff and vaccine effectiveness under different settings of relative cost of vaccination and infection. Simulation results show that reinforcement learning can improve the vaccine effectiveness through balancing individuals’ rationality and social influence. This emphasizes the importance of appropriately utilizing human bounded rationality in preventing disease epidemics through voluntary vaccination policies.

Ebola: Lessons on Vaccine Development.

The West African Ebola virus (EBOV) epidemic has fast-tracked countermeasures for this rare, emerging zoonotic pathogen. Until 2013-2014, most EBOV vaccine candidates were stalled between the preclinical and clinical milestones on the path to licensure, because of funding problems, lack of interest from pharmaceutical companies, and competing priorities in public health. The unprecedented and devastating epidemic propelled vaccine candidates toward clinical trials that were initiated near the end of the active response to the outbreak. Those trials did not have a major impact on the epidemic but provided invaluable data on vaccine safety, immunogenicity, and, to a limited degree, even efficacy in humans. There are plenty of lessons to learn from these trials, some of which are addressed in this review. Better preparation is essential to executing an effective response to EBOV in the future; yet, the first indications of waning interest are already noticeable.

Effectiveness and impact of a single-dose vaccine against chickenpox in the community of Madrid between 2001 and 2015

ABSTRACTBackground: Chickenpox is a contagious airborne disease. Immunization by varicella vaccine is an effective preventive measure. The objective of this study is to evaluate the impact and effectiveness of a single-dose vaccination against chickenpox at 15 months of age.Methods: Observational study based on data from the Epidemiological Surveillance System of the Autonomous Community of Madrid from 2001 to 2015. The years were grouped into 4 periods according to epidemic cycles and vaccination schedule: 2001–06, 2007–10, 2011–13 and 2014–15. The impact was calculated as Relative Risk (RR) between the incidence of chickenpox in children between 15 months and 13 years of age between 2011–13 and 2001–06 through Poisson regression using notifications made to the Diseases of Compulsory Declaration (DCD) system, the Sentinel Physicians Network (SPN) and hospital discharge records noted as Minimum Basic Data Set (MBDS). The vaccine effectiveness (VE) was calculated using the screening method and a 1:2 case-control study paired by age and paediatrician in population from 15 months to 13 years and between 2007 and 2015 using SPN source data.Results: The RR2011–13/2001–06 using data from the DCD was 0.14 (95% CI: 0.14 to 0.15), 0.07 (95% CI: 0.06 to 0.08) from SPN and 0.17 (95% CI: 0.15 to 0.20) from MBDS. A total of 338 cases were included in the VE screening obtaining an overall of 93.1 (90.9 to 94.8). For a case-control study, 120 cases and 247 controls were recruited obtaining a VE of 92.4% (IC 95%: 80.8 to 97.0%).Conclusions: The single-dose vaccination against chickenpox at 15 months of age has high impact and effectiveness.

Porcine epidemic diarrhea vaccine evaluation using a newly isolated strain from Korea

Porcine epidemic diarrhea virus (PEDV) infects pigs and causes an enteric disease that is characterized by vomiting and watery diarrhea. PEDV outbreaks have a tremendous financial impact on the worldwide pork industry. In South Korea, the incidence of PEDV has continued despite nationwide use of attenuated and inactivated vaccines, raising questions regarding the current vaccines’ efficacy and the need for new vaccine development. In the present study, we isolated a new Korean PEDV epidemic strain, PED-CUP-B2014, in Vero cells. Phylogenetic analysis of the spike gene demonstrated that the PED-CUP-B2014 belongs in genogroup G2b and is close to PEDVs currently circulating in many countries including the United States, and is distinct from many current vaccine strains. Upon serial passages into Vero cells, PED-CUP-B2014 adapted to Vero cells, which was evidenced as higher virus growth in Vero cells and confirmed lower virulence in suckling piglets. The administration of the inactivated 65-passaged PED-CUP-B2014 to sows greatly increased the survival rate of their offspring and significantly reduced diarrhea severity after PEDV challenge. Higher serum/colostrum PEDV-specific antibodies and higher neutralizing titers were shown in sows vaccinated with PED-CUP-B2014 compared to unvaccinated sows or sows administered commercial PEDV vaccine. Altogether, our data demonstrated that the newly isolated PEDV strain conferred critical passive immune protection to pigs against epidemic PEDV infection.

Porcine epidemic diarrhea vaccine efficacy evaluation by vaccination timing and frequencies

Porcine epidemic diarrhea (PED) virus is a causative agent of enteric disease characterized by watery diarrhea and dehydration. Because PED has high morbidity and mortality, especially in suckling piglets, it causes a great economic loss to swine farms worldwide. Although various PED vaccines have been developed and commercialized, their efficacies are still controversial. In particular, current PED vaccination protocol (vaccination at 2 and 4 weeks before farrowing) may cause stress in pregnant sows. In this study, we compared the effects of PED vaccination timing and frequency for its efficacy by measuring the PED virus-specific antibodies. We found that vaccination at early stages of pregnancy induces similar levels of serum and colostrum antibodies with those at late stages of pregnancy. As the number of vaccinations increased, the amounts of antibody in serum and colostrum, and neutralizing activities increased. Our results provide important information for establishing a more efficient PED vaccination protocol.

Selective epidemic vaccination under the performant routing algorithms

Despite the extensive research on traffic dynamics and epidemic spreading, the effect of the routing algorithms strategies on the traffic-driven epidemic spreading has not received an adequate attention. It is well known that more performant routing algorithm strategies are used to overcome the congestion problem. However, our main result shows unexpectedly that these algorithms favor the virus spreading more than the case where the shortest path based algorithm is used. In this work, we studied the virus spreading in a complex network using the efficient path and the global dynamic routing algorithms as compared to shortest path strategy. Some previous studies have tried to modify the routing rules to limit the virus spreading, but at the expense of reducing the traffic transport efficiency. This work proposed a solution to overcome this drawback by using a selective vaccination procedure instead of a random vaccination used often in the literature. We found that the selective vaccination succeeded in eradicating the virus better than a pure random intervention for the performant routing algorithm strategies.

Serum and mammary secretion antibody responses in porcine epidemic diarrhea-immune gilts following porcine epidemic diarrhea vaccination

Objective: In the sow herd, maintaining levels of immunity sufficient to protect neonatal pigs is an important aspect in porcine epidemic diarrhea virus (PEDV) control. This study compared anamnestic responses to two commercially available PEDV vaccines. Materials and methods: PEDV antibody-positive gilts (n = 36) in a commercial production system were each randomly (www.random.org) assigned to one of five vaccination protocols: no vaccine (controls); PEDV vaccine A (2 weeks pre-farrow); PEDV vaccine A (5 and 2 weeks pre-farrow); PEDV vaccine B (2 weeks pre-farrow); and PEDV vaccine B (5 and 2 weeks pre-farrow). Serum, colostrum, and milk samples collected over the course of the study were tested for PEDV IgG, IgA, and neutralizing antibody (NAb). Results: Analysis of the data from 32 animals completing the study found that vaccine induced a clear anamnestic response, ie, vaccinates had higher antibody concentrations than controls for most tests and specimens, but no difference was detected between one versus two doses of vaccine, and few differences in response were detected for vaccine A versus B. A positive but weak correlation was detected between IgG in serum and IgA in colostrum (P = .012; r = .44). Implications: Under the conditions of this study, PEDV-vaccinated gilts have higher IgG, IgA, and NAb responses than nonvaccinated controls in all diagnostic specimens tested. In breeding herds, direct measurement of PEDV IgA or NAb in colostrum and milk will provide a more accurate measurement of lactogenic immunity than serological testing.

Attitudes about vaccines to prevent Ebola virus disease in Guinea at the end of a large Ebola epidemic: Results of a national household survey.

In 2014-2016, an Ebola epidemic devastated Guinea; more than 3800 cases and 2500 deaths were reported to the World Health Organization. In August 2015, as the epidemic waned and clinical trials of an experimental, Ebola vaccine continued in Guinea and neighboring Sierra Leone, we conducted a national household survey about Ebola-related knowledge, attitudes, and practices (KAP) and opinions about "hypothetical" Ebola vaccines. Using cluster-randomized sampling, we selected participants aged 15+ years old in Guinea's 8 administrative regions, which had varied cumulative case counts. The questionnaire assessed socio-demographic characteristics, experiences during the epidemic, Ebola-related KAP, and Ebola vaccine attitudes. To assess the potential for Ebola vaccine introduction in Guinea, we examined the association between vaccine attitudes and participants' characteristics using categorical and multivariable analyses. Of 6699 persons invited to participate, 94% responded to at least 1 Ebola vaccine question. Most agreed that vaccines were needed to fight the epidemic (85.8%) and that their family would accept safe, effective Ebola vaccines if they became available in Guinea (84.2%). These measures of interest and acceptability were significantly more common among participants who were male, wealthier, more educated, and lived with young children who had received routine vaccines. Interest and acceptability were also significantly higher among participants who understood Ebola transmission modes, had witnessed Ebola response teams, knew Ebola-affected persons, believed Ebola was not always fatal, and would access Ebola treatment centers. In multivariable analyses of the majority of participants living with young children, interest and acceptability were significantly higher among those living with vaccinated children than among those living with unvaccinated children. The high acceptability of hypothetical vaccines indicates strong potential for introducing Ebola vaccines across Guinea. Strategies to build public confidence in use of Ebola vaccines should highlight any similarities with safe, effective vaccines routinely used in Guinea.

Emergence of mosaic recombinant strains potentially associated with vaccine JXA1-R and predominant circulating strains of porcine reproductive and respiratory syndrome virus in different provinces of China

BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) has caused several outbreaks in China since 2006. However, the genetic diversity of PRRSV in China has greatly increased by rapid evolution or recombination events. Modified live-attenuated vaccines are widely used to control this disease worldwide. Although the risk and inefficacy of the vaccine has been reported, the genetic diversity between epidemic field strains and vaccine strains in China has not been completely elucidated.MethodsA total of 293 clinical samples were collected from 72 pig farms in 16 provinces of China in 2015 for PRRSV detection. A total of 28 infected samples collected from 24 pig farms in nine provinces were further selected for immunohistochemical analysis and whole genome sequencing of PRRSV. Phylogenetic analysis and recombination screening were performed with the full genome sequences of the 28 strains and other 623 reference sequences of PRRSV.ResultsOf 293 clinical samples, 117 (39.93%) were positive for PRRSV by RT-PCR. Phylogenetic results showed that the 28 strains were nested into sublineage 10.5 (classic highly pathogenic [HP]-PRRSV), sublineage 10.6 (HP-PRRSV-like strains and related recombinants), sublineage 10.7 (potential vaccine JXA1-R-like strains), and lineage 9 (NADC30-like strains and recombinants of NADC30-like strains), respectively, suggesting that multiple subgenotypes of PRRSV currently circulate in China. Recombination analyses showed that nine of 28 isolates and one isolate from other laboratory were potential complicated recombinants between the vaccine JXA1-R-like strains and predominant circulating strains.ConclusionsThese results indicated an increase in recombination rates of PRRSV under current vaccination pressure and a more pressing situation for PRRSV eradication and control in China.

豚流行性下痢発生農場の疫学情報を用いた統計解析によるワクチンの有効性に関する考察

豚流行性下痢発生農場の疫学情報を用いた統計解析によるワクチンの有効性に関する考察

Development of an enzyme-linked immunosorbent assay for the monitoring and surveillance of antibodies to porcine epidemic diarrhea virus based on a recombinant membrane protein

The recent dramatic increase in reported cases of porcine epidemic diarrhea (PED) in pig farms is a potential threat to the global swine industry. Therefore, the accurate diagnosis, serological monitoring, and surveillance of specific antibodies in pigs resulting from porcine epidemic diarrhea virus (PEDV) infection or vaccination would be essential in helping to control the spread of PED. We developed and validated an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant membrane (M) protein of PEDV. To detect PEDV antibodies in eight herds, 382 serum samples were collected from sows that had been immunized with a PED vaccine, and screened using the developed ELISA in parallel with a serum neutralization (SN) assay. Of the tested samples, 276 were positive for the presence of PEDV antibodies according to both assays, while 98 were negative. An excellent agreement between the ELISA and the SN assay was observed (kappa=0.947; 95% confidence interval=0.910–0.984; McNemar's test, P=0.727). No cross-reaction was detected for the developed ELISA with other coronaviruses or other common pig pathogens. The developed ELISA could be used for serological evaluation and indirect diagnosis of PED infection.

Response Strategies against Meningitis Epidemics after Elimination of Serogroup A Meningococci, Niger.

To inform epidemic response strategies for the African meningitis belt after a meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared the effectiveness and efficiency of meningitis surveillance and vaccine response strategies at district and health area levels using various thresholds of weekly incidence rates. We analyzed reports of suspected cases from 3 regions in Niger during 2002-2012 (154,392 health area weeks), simulating elimination of serogroup A meningitis by excluding health area years with identification of such cases. Effectiveness was highest for health area surveillance and district vaccination (58-366 cases; thresholds 7-20 cases/100,000 doses), whereas efficiency was optimized with health area vaccination (5.6-7.7 cases/100,000 doses). District-level intervention prevented <6 cases (0.2 cases/100,000 doses). Reducing the delay between epidemic signal and vaccine protection by 2 weeks doubled efficiency. Subdistrict surveillance and response might be most appropriate for meningitis epidemic response after elimination of serogroup A meningitis.

Typing of Canine Parvovirus Strains Circulating in North-East China.

Canine parvovirus (CPV) is highly contagious and is a major cause of haemorrhagic enteritis and myocarditis in dogs. We investigated the genetic variation of emerging CPV strains by sequencing 64 CPV VP2 genes from 216 clinical samples of dogs from Heilongjiang, Jilin, Liaoning, Shandong and Hebei in 2014. Genetic analysis revealed that CPV-2b was predominant in Hebei and CPV-2a was predominant in the other four provinces. In addition, a CPV-2c strain has emerged in Shandong province. All samples had a Ser-Ala substitution at residue 297 and an Ile-Arg substitution at residue 324. Interestingly, in five separate canine samples, we found a mutation of Gln370 to Arg, until now detected only in isolates from pandas. The phylogenetic analysis showed clear distinctions between epidemic isolates and vaccine strains and between Chinese CPV-2c strains and CPV-2c strains found in other countries. Monitoring recent incidence of CPV strains enables evaluation and implementation of disease control strategies.