Helen E. Jenkins

Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings

Swine Flu Benchmark The World Health Organization (WHO) announced on 29 April 2009, a level-5 pandemic alert for a strain of H1N1 influenza originating in pigs in Mexico and transmitting from human to human in several countries. Fraser et al. (p. 1557, published online 11 May; see the cover) amassed a team of experts in Mexico and WHO to make an initial assessment of the outbreak with a view to guiding future policy. The outbreak appears to have originated in mid-February in the village of La Gloria, Veracruz, where over half the population suffered acute respiratory illness, affecting more than 61% of children under 15 years old in the community. The basic reproduction number (the number of people infected per patient) is in the range of 1.5—similar or less than that of the pandemics of 1918, 1957, and 1968. There remain significant uncertainties about the severity of this outbreak, which makes it difficult to compare the economic and societal costs of intervention with lives saved and the risks of generating antiviral resistance. An international collaborative effort has analyzed the initial dynamics of the swine flu outbreak. A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; ≥15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.

Positive and negative effects of widespread badger culling on tuberculosis in cattle.

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers (Meles meles) have been culled by the British government in a series of attempts to limit the spread of Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britains cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced or increased incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies but will present challenges for policy development.

Culling and cattle controls influence tuberculosis risk for badgers

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. In Britain, European badgers (Meles meles) are implicated in transmitting Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Badger culling has therefore been a component of British TB control policy for many years. However, large-scale field trials have recently shown that badger culling has the capacity to cause both increases and decreases in cattle TB incidence. Here, we show that repeated badger culling in the same area is associated with increasing prevalence of M. bovis infection in badgers, especially where landscape features allow badgers from neighboring land to recolonize culled areas. This impact on prevalence in badgers might reduce the beneficial effects of culling on cattle TB incidence, and could contribute to the detrimental effects that have been observed. Additionally, we show that suspension of cattle TB controls during a nationwide epidemic of foot and mouth disease, which substantially delayed removal of TB-affected cattle, was associated with a widespread increase in the prevalence of M. bovis infection in badgers. This pattern suggests that infection may be transmitted from cattle to badgers, as well as vice versa. Clearly, disease control measures aimed at either host species may have unintended consequences for transmission, both within and between species. Our findings highlight the need for policymakers to consider multiple transmission routes when managing multihost pathogens.

Implications of a Circulating Vaccine-Derived Poliovirus in Nigeria

BACKGROUNDnThe largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV).nnnMETHODSnWe identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared.nnnRESULTSnNo significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV.nnnCONCLUSIONSnThe attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge.

The Early Transmission Dynamics of H1N1pdm Influenza in the United Kingdom.

We analyzed data on all laboratory-confirmed cases of H1N1pdm influenza in the UK to 10th June 2009 to estimate epidemiological characteristics. We estimated a mean incubation period of 2.05 days and serial interval of 2.5 days with infectivity peaking close to onset of symptoms. Transmission was initially sporadic but increased from mid-May in England and from early June in Scotland. We estimated 37% of transmission occurred in schools, 24% in households, 28% through travel abroad and the remainder in the wider community. Children under 16 were more susceptible to infection in the household (adjusted OR 5.80, 95% CI 2.99-11.82). Treatment with oseltamivir plus widespread use of prophylaxis significantly reduced transmission (estimated reduction 16%). Households not receiving oseltamivir within 3 days of symptom onset in the index case had significantly increased secondary attack rates (adjusted OR 3.42, 95% CI 1.51-8.55).

The Duration of the Effects of Repeated Widespread Badger Culling on Cattle Tuberculosis Following the Cessation of Culling

Background In the British Isles, control of cattle tuberculosis (TB) is hindered by persistent infection of wild badger (Meles meles) populations. A large-scale field trial—the Randomised Badger Culling Trial (RBCT)—previously showed that widespread badger culling produced modest reductions in cattle TB incidence during culling, which were offset by elevated TB risks for cattle on adjoining lands. Once culling was halted, beneficial effects inside culling areas increased, while detrimental effects on adjoining lands disappeared. However, a full assessment of the utility of badger culling requires information on the duration of culling effects. Methodology/Principal Findings We monitored cattle TB incidence in and around RBCT areas after culling ended. We found that benefits inside culled areas declined over time, and were no longer detectable by three years post-culling. On adjoining lands, a trend suggesting beneficial effects immediately after the end of culling was insignificant, and disappeared after 18 months post-culling. From completion of the first cull to the loss of detectable effects (an average five-year culling period plus 2.5 years post-culling), cattle TB incidence was 28.7% lower (95% confidence interval [CI] 20.7 to 35.8% lower) inside ten 100 km2 culled areas than inside ten matched no-culling areas, and comparable (11.7% higher, 95% CI: 13.0% lower to 43.4% higher, p u200a=u200a 0.39) on lands ≤2 km outside culled and no-culling areas. The financial costs of culling an idealized 150 km2 area would exceed the savings achieved through reduced cattle TB, by factors of 2 to 3.5. Conclusions/Significance Our findings show that the reductions in cattle TB incidence achieved by repeated badger culling were not sustained in the long term after culling ended and did not offset the financial costs of culling. These results, combined with evaluation of alternative culling methods, suggest that badger culling is unlikely to contribute effectively to the control of cattle TB in Britain.

Effectiveness of Immunization against Paralytic Poliomyelitis in Nigeria

BACKGROUNDnThe number of cases of paralytic poliomyelitis has declined in Nigeria since the introduction of newly licensed monovalent oral poliovirus vaccines and new techniques of vaccine delivery. Understanding the relative contribution of these vaccines and the improved coverage to the decline in incident cases is essential for future planning.nnnMETHODSnWe estimated the field efficacies of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine, using the reported number of doses received by people with poliomyelitis and by matched controls as identified in Nigerias national surveillance database, in which 27,379 cases of acute flaccid paralysis were recorded between 2001 and 2007. Our estimates of vaccine coverage and vaccine-induced immunity were based on the number of doses received by children listed in the database who had paralysis that was not caused by poliovirus.nnnRESULTSnThe estimated efficacies per dose of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine against type 1 paralytic poliomyelitis were 67% (95% confidence interval [CI], 39 to 82) and 16% (95% CI, 10 to 21), respectively, and the estimated efficacy per dose of trivalent oral poliovirus vaccine against type 3 paralytic poliomyelitis was 18% (95% CI, 9 to 26). In the northwestern region of Nigeria, which reported the majority of cases during the study period, coverage with at least one dose of vaccine increased from 59 to 78%. Between 2005 and 2007, vaccine-induced immunity levels among children under the age of 5 years more than doubled, to 56%.nnnCONCLUSIONSnThe higher efficacy of monovalent type 1 oral poliovirus vaccine (four times as effective as trivalent oral poliovirus vaccine) and the moderate gains in coverage dramatically increased vaccine-induced immunity against serotype 1 in northern Nigeria. Further increases in coverage in Nigerian states with infected populations are required to achieve the levels of vaccine-induced immunity associated with the sustained elimination achieved in other parts of the country.

BOVINE TUBERCULOSIS IN CATTLE AND BADGERS IN LOCALIZED CULLING AREAS

Bovine tuberculosis (TB) is a zoonotic disease that can have serious consequences for cattle farming and, potentially, for public health. In Britain, failure to control bovine TB has been linked to persistent infection of European badger (Meles meles) populations. However, culling of badgers in the vicinity of recent TB outbreaks in cattle has failed to reduce the overall incidence of cattle TB. Using data from a large-scale study conducted in 1998–2005, we show that badgers collected on such localized culls had elevated prevalence of Mycobacterium bovis, the causative agent of bovine TB, suggesting that infections in cattle and badgers were indeed associated. Moreover, there was a high degree of similarity in the M. bovis strain types isolated from cattle and associated badgers. This similarity between strain types appeared to be unaffected by time lags between the detection of infection in cattle and culling of badgers, or by the presence of purchased cattle that might have acquired infection elsewhere. However, localized culling appeared to prompt an increase in the prevalence of M. bovis infection in badgers, probably by disrupting ranging and territorial behavior and hence increasing intraspecific transmission rates. This elevated prevalence among badgers could offset the benefits, for cattle, of reduced badger densities and may help to explain the failure of localized culling to reduce cattle TB incidence.

The effects of annual widespread badger culls on cattle tuberculosis following the cessation of culling

BACKGROUNDnThe effective control of human and livestock diseases is challenging where infection persists in wildlife populations. The Randomised Badger Culling Trial (RBCT) demonstrated that, while it was underway, proactive badger (Meles meles) culling reduced bovine tuberculosis (TB) incidence inside culled areas but increased incidence in neighboring areas, suggesting that the costs of such culling might outweigh the benefits.nnnOBJECTIVES AND DESIGNnThe objective of this study was to investigate whether culling impacts persisted more than one year following the cessation of culling (the post-trial period). We compared TB incidence in and around RBCT proactive culling areas with that in and around matched unculled areas.nnnRESULTSnDuring the post-trial period, cattle TB incidence inside culled areas was reduced, to an extent significantly greater (p=0.002) than during culling. In neighboring areas, elevated risks observed during culling were not observed post-trial (p=0.038). However, the post-trial effects were comparable to those observed towards the end of the trial (inside RBCT areas: p=0.18 and neighboring areas: p=0.14).nnnCONCLUSIONSnAlthough to-date the overall benefits of culling remain modest, they were greater than was apparent during the culling period alone. Continued monitoring will demonstrate how long beneficial effects last, indicating the overall capacity of such culling to reduce cattle TB incidence.

The prevalence, distribution and severity of detectable pathological lesions in badgers naturally infected with Mycobacterium bovis.

The Randomized Badger Culling Trial (RBCT) began in 1998 to determine the impact of badger culling in controlling bovine tuberculosis in cattle. A total of 1166 badgers (14% of total) proactively culled during the RBCT were found to be tuberculous, offering a unique opportunity to study the pathology caused by Mycobacterium bovis in a large sample of badgers. Of these, 39% of adults (approximately 6% of all adults culled) had visible lesions (detectable at necropsy) of bovine tuberculosis; cubs had a lower prevalence of infection (9%) but a higher percentage of tuberculous cubs (55.5%) had visible lesions. Only approximately 1% of adult badgers had extensive, severe pathology. Tuberculous badgers with recorded bite wounds (approximately 5%) had a higher prevalence of visible lesions and a different distribution of lesions, suggesting transmission via bite wounds. However, the predominance of lesions in the respiratory tract indicates that most transmission occurs by the respiratory route.