Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England.

BACKGROUND: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. METHODS: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts' vaccination status as the main exposure while adjusting for confounders. RESULTS: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35-0.72) and 0.69 (0.53-0.90) for receipt of two doses 8-90 and >90 days ago, respectively, and 0.34 (0.23-0.50) for vaccination with three doses 8-151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts' infection risk: 0.45 (0.23-0.89). CONCLUSIONS: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose.

Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission: a prospective cohort study in England.

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Households were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Results: Between 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 - 2.20) of transmission than Alpha; contacts older than 18 years old were 1.48 (1.20 - 1.91) and 1.02 (0.93 - 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1. Conclusions: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low.

Potential drivers for schistosomiasis persistence: Population genetic analyses from a cluster-randomized urogenital schistosomiasis elimination trial across the Zanzibar islands.

The World Health Organization's revised NTD Roadmap and the newly launched Guidelines target elimination of schistosomiasis as a public health problem in all endemic areas by 2030. Key to meeting this goal is elucidating how selective pressures imposed by interventions shape parasite populations. Our aim was to identify any differential impact of a unique cluster-randomized tri-armed elimination intervention (biannual mass drug administration (MDA) applied alone or in association with either mollusciciding (snail control) or behavioural change interventions) across two Zanzibarian islands (Pemba and Unguja) on the population genetic composition of Schistosoma haematobium over space and time. Fifteen microsatellite loci were used to analyse individual miracidia collected from infected individuals across islands and intervention arms at the start (2012 baseline: 1,522 miracidia from 176 children; 303 from 43 adults; age-range 6-75, mean 12.7 years) and at year 5 (2016: 1,486 miracidia from 146 children; 214 from 25 adults; age-range 9-46, mean 12.4 years). Measures of genetic diversity included allelic richness (Ar), Expected (He) and Observed heterozygosity (Ho), inbreeding coefficient (FST), parentage analysis, estimated worm burden, worm fecundity, and genetic sub-structuring. There was little evidence of differential selective pressures on population genetic diversity, inbreeding or estimated worm burdens by treatment arm, with only the MDA+snail control arm within Unguja showing trends towards reduced diversity and altered inbreeding over time. The greatest differences overall, both in terms of parasite fecundity and genetic sub-structuring, were observed between the islands, consistent with Pemba's persistently higher mean infection intensities compared to neighbouring Unguja, and within islands in terms of infection hotspots (across three definitions). These findings highlight the important contribution of population genetic analyses to elucidate extensive genetic diversity and biological drivers, including potential gene-environmental factors, that may override short term selective pressures imposed by differential disease control strategies. Trial Registration: ClinicalTrials.gov ISRCTN48837681.

Sustained Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis in Vaccinated and Unvaccinated Individuals During the 5 Years Since Rotavirus Vaccine Introduction in England.

BACKGROUND: The introduction of an oral live-attenuated monovalent rotavirus vaccine (Rotarix®) into the UK infant immunization program in July 2013 was associated with large reductions in laboratory-confirmed rotavirus infections and hospitalizations due to acute gastroenteritis (AGE) within 12 months. Here we report the 5-year impact of the program in England. METHODS: Individuals with laboratory-confirmed rotavirus infections during 2000-2018 and all-cause hospitalizations for AGE during 2007-2018 were identified using national electronic records. Age-specific incidence rate ratios (IRR) and estimated numbers of cases averted in each of the 5 postvaccination years were calculated. RESULTS: There were 206 389 laboratory-confirmed rotavirus infections and 3 657 651 hospitalizations for all-cause AGE. Reductions of 69-83% in laboratory-confirmed rotavirus infections in all age groups and 77-88% in infants aged <1 year in each of the 5 postvaccine years are reported, with 11 386-11 633 cases averted annually. All-cause AGE hospitalizations were reduced by 12-35% across all age-groups and by 25-48% in <1 year-olds in the 5 postvaccine years, with 24 474-49 278 hospitalizations averted annually. There was strong evidence of indirect (herd) protection, with at least 50% and up to 80% of the non-specific end point of all-cause gastroenteritis (AGE) hospitalizations averted being in unvaccinated age-groups, primarily older adults. Seasonal changes include a possible shift from annual to biennial peaks with lower peak incidence and longer seasons. CONCLUSIONS: There were large and sustained declines in both laboratory-confirmed rotavirus infections and AGE hospitalizations across all age groups in each of the 5 years since the introduction of the UK rotavirus program.

Seroprevalence of SARS-CoV-2 among Blood Donors and Changes after Introduction of Public Health and Social Measures, London, UK.

We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17-69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15-16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays.

Revisiting density-dependent fecundity in schistosomes using sibship reconstruction.

The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.

The changing epidemiology of diphtheria in the United Kingdom, 2009 to 2017.

BackgroundDiphtheria is a potentially fatal disease caused by toxigenic strains of Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis.AimOur objective was to review the epidemiology of diphtheria in the United Kingdom (UK) and the impact of recent changes in public health management and surveillance.MethodsPutative human toxigenic diphtheria isolates in the UK are sent for species confirmation and toxigenicity testing to the National Reference Laboratory. Clinical, epidemiological and microbiological information for toxigenic cases between 2009 and 2017 are described in this population-based prospective surveillance study.ResultsThere were 33 toxigenic cases of diphtheria aged 4 to 82 years. Causative species were C. diphtheriae (n = 18) and C. ulcerans (n = 15). Most C. diphtheriae cases were cutaneous (14/18) while more than half of C. ulcerans cases had respiratory presentations (8/15). Two thirds (23/33) of cases were inadequately immunised. Two cases with C. ulcerans infections died, both inadequately immunised. The major risk factor for C. diphtheriae aquisition was travel to an endemic area and for C. ulcerans, contact with a companion animal. Most confirmed C. diphtheriae or C. ulcerans isolates (441/507; 87%) submitted for toxigenicity testing were non-toxigenic, however, toxin positivity rates were higher (15/23) for C. ulcerans than C. diphtheriae (18/469). Ten non-toxigenic toxin gene-bearing (NTTB) C. diphtheriae were also detected.ConclusionDiphtheria is a rare disease in the UK. In the last decade, milder cutaneous C. diphtheriae cases have become more frequent. Incomplete vaccination status was strongly associated with the risk of hospitalisation and death.

Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda.

BACKGROUND: A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. METHODS: We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. RESULTS: Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. CONCLUSIONS: Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

Examining human paragonimiasis as a differential diagnosis to tuberculosis in The Gambia.

OBJECTIVE: Paragonimiasis is a foodborne trematode infection of the lungs caused by Paragonimus spp., presenting clinically with similar symptoms to active tuberculosis (TB). Worldwide, an estimated 20.7 million people are infected with paragonimiasis, but relatively little epidemiological data exists for Africa. Given a recently reported case, we sought to establish whether paragonimiasis should be considered as an important differential diagnosis for human TB in The Gambia, West Africa. RESULTS: We developed a novel PCR-based diagnostic test for Paragonimus species known to be found in West Africa, which we used to examine archived TB negative sputum samples from a cross-sectional study of volunteers with tuberculosis-like symptoms from communities in the Western coastal region of The Gambia. Based on a "zero patient" design for detection of rare diseases, 300 anonymised AFB smear negative sputum samples, randomly selected from 25 villages, were screened for active paragonimiasis by molecular detection of Paragonimus spp. DNA. No parasite DNA was found in any of the sputa of our patient group. Despite the recent case report, we found no evidence of active paragonimiasis infection masking as TB in the Western region of The Gambia.

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme.

BACKGROUND: Schistosoma mansoni is a parasite of profound medical importance. Current control focusses on mass praziquantel (PZQ) treatment of populations in endemic areas, termed Preventative Chemotherapy (PC). Large-scale PC programmes exert prolonged selection pressures on parasites with the potential for, direct and/or indirect, emergence of drug resistance. Molecular methods can help monitor genetic changes of schistosome populations over time and in response to drug treatment, as well as estimate adult worm burdens through parentage analysis. Furthermore, methods such as in vitro drug sensitivity assays help phenotype in vivo parasite genotypic drug efficacy. METHODS: We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ. RESULTS: We demonstrated that there were individual parasites with reduced PZQ susceptibility in the 2010 collections, as evidenced by our in vitro larval behavioural phenotypic assay. There was no evidence, however, that miracidia showing phenotypically reduced susceptibility clustered together genetically. Molecular analysis also demonstrated a significant reduction of adult worm load over time, despite little evidence of reduction in parasite infection intensity, as measured by egg output. Genetic diversity of infections did not reduce over time, despite changes in the genetic composition of the parasite populations. CONCLUSIONS: Genotypic and phenotypic monitoring did not indicate a selective sweep, as may be expected if PZQ treatment was selecting a small number of related "resistant" parasites, but there was evidence of genetic changes at the population level over time. Genetic data were used to estimate adult worm burdens, which unlike parasite infection intensity, showed reductions over time, suggesting the relaxation of negative density-dependent constraints on parasite fecundity with PZQ treatment. We thereby demonstrated that density-dependence in schistosome populations may complicate evaluation and monitoring of control programmes.

Should we be treating animal schistosomiasis in Africa? The need for a One Health economic evaluation of schistosomiasis control in people and their livestock.

A One Health economic perspective allows informed decisions to be made regarding control priorities and/or implementation strategies for infectious diseases. Schistosomiasis is a major and highly resilient disease of both humans and livestock. The zoonotic component of transmission in sub-Saharan Africa appears to be more significant than previously assumed, and may thereby affect the recently revised WHO vision to eliminate schistosomiasis as a public health problem by 2025. Moreover, animal schistosomiasis is likely to be a significant cost to affected communities due to its direct and indirect impact on livelihoods. We argue here for a comprehensive evaluation of the economic burden of livestock and zoonotic schistosomiasis in sub-Saharan Africa in order to determine if extending treatment to include animal hosts in a One Health approach is economically, as well as epidemiologically, desirable.

Optimising cluster survey design for planning schistosomiasis preventive chemotherapy.

BACKGROUND: The cornerstone of current schistosomiasis control programmes is delivery of praziquantel to at-risk populations. Such preventive chemotherapy requires accurate information on the geographic distribution of infection, yet the performance of alternative survey designs for estimating prevalence and converting this into treatment decisions has not been thoroughly evaluated. METHODOLOGY/PRINCIPAL FINDINGS: We used baseline schistosomiasis mapping surveys from three countries (Malawi, Côte d'Ivoire and Liberia) to generate spatially realistic gold standard datasets, against which we tested alternative two-stage cluster survey designs. We assessed how sampling different numbers of schools per district (2-20) and children per school (10-50) influences the accuracy of prevalence estimates and treatment class assignment, and we compared survey cost-efficiency using data from Malawi. Due to the focal nature of schistosomiasis, up to 53% simulated surveys involving 2-5 schools per district failed to detect schistosomiasis in low endemicity areas (1-10% prevalence). Increasing the number of schools surveyed per district improved treatment class assignment far more than increasing the number of children sampled per school. For Malawi, surveys of 15 schools per district and 20-30 children per school reliably detected endemic schistosomiasis and maximised cost-efficiency. In sensitivity analyses where treatment costs and the country considered were varied, optimal survey size was remarkably consistent, with cost-efficiency maximised at 15-20 schools per district. CONCLUSIONS/SIGNIFICANCE: Among two-stage cluster surveys for schistosomiasis, our simulations indicated that surveying 15-20 schools per district and 20-30 children per school optimised cost-efficiency and minimised the risk of under-treatment, with surveys involving more schools of greater cost-efficiency as treatment costs rose.

One health - an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases.

Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions. In particular, we consider whether preventive chemotherapy, the current mainstay of NTD control, can be successful without a One Health approach. Transmission within and between animal reservoirs and humans can have important ecological and evolutionary consequences, driving the evolution and establishment of drug resistance, as well as providing selective pressures for spill-over, host switching, hybridizations and introgressions between animal and human parasites. Our aim here is to highlight the importance of both elucidating disease ecology, including identifying key hosts and tailoring control effort accordingly, and understanding parasite evolution, such as precisely how infectious agents may respond and adapt to anthropogenic change. Both elements are essential if we are to alleviate disease risks from NZDs in humans, domestic animals and wildlife.

Population genetic structure of Schistosoma mansoni and Schistosoma haematobium from across six sub-Saharan African countries: implications for epidemiology, evolution and control.

We conducted the first meta-analysis of ten Schistosoma haematobium (one published and nine unpublished) and eight Schistosoma mansoni (two published and six unpublished) microsatellite datasets collected from individual schistosome-infected school-children across six sub-Saharan Africa countries. High levels of genetic diversity were documented in both S. haematobium and S. mansoni. In S. haematobium populations, allelic richness did not differ significantly between the ten schools, despite widely varying prevalences and intensities of infection, but higher levels of heterozygote deficiency were seen in East than in West Africa. In contrast, S. mansoni populations were more diverse in East than West African schools, but heterozygosity levels did not vary significantly with geography. Genetic structure in both S. haematobium and S. mansoni populations was documented, at both a regional and continental scale. Such structuring might be expected to slow the spread to new areas of anti-schistosomal drug resistance should it develop. There was, however, limited evidence of genetic structure at the individual host level, which might be predicted to promote the development or establishment of drug resistance, particularly if it were a recessive trait. Our results are discussed in terms of their potential implications for the epidemiology and evolution of schistosomes as well as their subsequent control across sub-Saharan Africa.

Genetic consequences of mass human chemotherapy for Schistosoma mansoni: population structure pre- and post-praziquantel treatment in Tanzania.

Recent shifts in global health policy have led to the implementation of mass drug administration (MDA) for neglected tropical diseases. Here we show how population genetic analyses can provide vital insights into the impact of such MDA on endemic parasite populations. We show that even a single round of MDA produced a genetic bottleneck with reductions in a range of measures of genetic diversity of Schistosoma mansoni. Phylogenetic analyses and indices of population differentiation indicated that schistosomes collected in the same schools in different years were more dissimilar than those from different schools collected within either of the study's 2 years, in addition to distinguishing re-infection from non-clearance (that might indicate putatively resistant parasites) from within those children infected at both baseline and follow-up. Such unique results illustrate the importance of genetic monitoring and examination of long lived multi-cellular parasites such as these under novel or increased chemotherapeutic selective pressures.

Schistosome genomes: a wealth of information.

The blood flukes Schistosoma japonicum and Schistosoma mansoni are the first major human platyhelminth pathogens to have their genome sequences published. The work of two large international consortia offers draft sequence information and detailed analyses presenting a wealth of information addressing, in particular, metabolic and signalling pathways, host-parasite interactions and potential new drug targets. We comment on these breakthroughs and their potential applications in the study and control of schistosomes.

Evolutionary concepts in predicting and evaluating the impact of mass chemotherapy schistosomiasis control programmes on parasites and their hosts.

Schistosomiasis is a parasitic disease of significant medical and veterinary importance in many regions of the world. Recent shifts in global health policy have led towards the implementation of mass chemotherapeutic control programmes at the national scale in previously 'neglected' countries such as those within sub-Saharan Africa. Evolutionary theory has an important role to play in the design, application and interpretation of such programmes. Whilst celebrating the rapid success achieved to date by such programmes, in terms of reduced infection prevalence, intensity and associated human morbidity, evolutionary change in response to drug selection pressure may be predicted under certain circumstances, particularly in terms of the development of potential drug resistance, evolutionary changes in parasite virulence, transmission and host use, and/or competitive interactions with co-infecting pathogens. Theoretical and empirical data gained to date serve to highlight the importance of careful monitoring and evaluation of parasites and their hosts whenever and wherever chemotherapy is applied and where parasite transmission remains.

Bovine tuberculosis (Mycobacterium bovis) in British farmland wildlife: the importance to agriculture.

Bovine tuberculosis (bTB) is an important disease of cattle and an emerging infectious disease of humans. Cow- and badger-based control strategies have failed to eradicate bTB from the British cattle herd, and the incidence is rising by about 18%per year. The annual cost to taxpayers in Britain is currently 74 million UK pounds. Research has focused on the badger as a potential bTB reservoir, with little attention being paid to other mammals common on farmland. We have conducted a systematic survey of wild mammals (n=4393 individuals) present on dairy farms to explore the role of species other than badgers in the epidemiology of bTB. Cultures were prepared from 10397 samples (primarily faeces, urine and tracheal aspirates). One of the 1307 bank voles (Clethrionomys glareolus) live-sampled, and three of the 43 badgers (Meles meles), yielded positive isolates of Mycobacterium bovis. This is the first time the bacterium has been isolated from the bank vole. The strain type was the same as that found in cattle and badgers on the same farm. However, our work indicates that the mean prevalence of infectious individuals among common farmland wildlife is extremely low (the upper 95% confidence interval is < or =2.0 for all of the abundant species). Mathematical models illustrate that it is highly unlikely the disease could be maintained at such low levels. Our results suggest that these animals are relatively unimportant as reservoirs of bTB, having insufficient within-species (or within-group) transmission to sustain the infection, though occasional spill-overs from cattle or badgers may occur.

Mate choice, frequency dependence, and the maintenance of resistance to parasitism in a simultaneous hermaphrodite.

Biomphalaria glabrata are simultaneous hermaphroditic freshwater snails that act as intermediate hosts for the macroparasitic trematode Schistosoma mansoni, a causative agent of schistosomiasis. Heritability and strain-specificity of both snail resistance and susceptibility to schistosome infection have been demonstrated, genetic variability for which is maintained, in part, through trade-offs between high fitness costs associated with infection and those associated with resistance. However, despite such a high cost of resistance and a low prevalence of infection in natural snail populations, genes for resistance are maintained within snail populations over successive generations, including in the complete absence of parasite pressure in laboratory populations. This may be indicative of alternative benefits of resistance genes, in addition to parasite defense, such as differential mating success between genotypes. Here we examined the mate and gender choice of snails across a multi-factorial range of potential partner combinations. These included host-resistance or susceptibility genotype, host genotype frequency within the population, current parasite infection status, and parasite genotype. We demonstrate recognition and discrimination by host snails depending on host and/or parasite genotype for each of these factors. In particular, our results suggest that a rare mating advantage to resistant genotypes may be a potential explanation for the maintenance of highly costly resistance genes within intermediate host populations under conditions of low or zero parasite pressure.

Intraspecific competition and the evolution of virulence in a parasitic trematode.

Intrahost competition between parasite genotypes has been predicted to be an important force shaping parasite ecology and evolution and has been extensively cited as a mechanism for the evolution of increased parasite virulence. However, empirical evidence demonstrating the existence and nature of intraspecific competition is lacking for many parasites. Here, we compared within-host competitiveness between genetic strains of Schistosoma mansoni with high (HIGH-V) or low (LOW-V) virulence to their intermediate snail host, Biomphalaria glabrata. Groups of snails were exposed to either one or the other of two parasite strains, or a mixed infection of both strains, and the resulting progeny were identified using a molecular marker. In two separate experiments investigating simultaneous and sequential infections, we demonstrated that the lifetime reproductive success of parasite strain HIGH-V was reduced in the presence of a faster replicating parasite genotype, LOW-V, regardless of whether it was in a majority or minority in the initial inoculum of the simultaneous exposure or of its relative position in the sequential exposure experiment. Thus, we demonstrate competition between parasite genotypes and asymmetry in competitive success between parasite strains. Moreover, since the less virulent strain investigated here had a competitive advantage, we suggest that a high frequency of multiple infections could favor the evolution of less, rather than more, virulent parasites in this system.