Biomedical subjects

Graham F Medley

Publications and source records attributed to Graham F Medley.

9 recordsLinked to original sources

PubMed2005

Molecular analysis of respiratory syncytial virus reinfections in infants from coastal Kenya.

BACKGROUND: Individuals are reinfected with respiratory syncytial virus (RSV) repeatedly. The nature of reinfection, in relation to RSV genetic and antigenic diversity, is ill defined and has implications for persistence and vaccine control. METHODS: We examined the molecular relatedness of RSV causing primary and repeat infections, by phylogenetic analysis of the attachment (G) gene in 12 infants from a birth cohort in rural Kenya, using nasal wash samples collected during a 16-month period in 2002-2003, which spanned 2 successive epidemics. RESULTS: Six infants were infected during both epidemics, 4 with RSV-A in the first epidemic followed by RSV-B during the second epidemic and 2 with RSV-A during both epidemics, with no significant G gene sequence variability between samples. Two infants were infected and reinfected with different RSV-A strains during the same epidemic. Possible viral persistence was suspected in the remaining 4 infants, although reinfection with the same variant cannot be excluded. CONCLUSIONS: These are the first data that specifically address strain-specific reinfections in infancy in relation to the primary infecting variant. The data strongly suggest that, following primary infection, some infants lose strain-specific immunity within 7-9 months (between epidemics) and group-specific immunity within 2-4 months (during an epidemic period).

Disease Outbreaks↗

PubMed2005

The reinfection threshold.

Thresholds in transmission are responsible for critical changes in infectious disease epidemiology. The epidemic threshold indicates whether infection invades a totally susceptible population. The reinfection threshold indicates whether self-sustained transmission occurs in a population that has developed a degree of partial immunity to the pathogen (by previous infection or vaccination). In models that combine susceptible and partially immune individuals, the reinfection threshold is technically not a bifurcation of equilibria as correctly pointed out by Breban and Blower. However, we show that a branch of equilibria to a reinfection submodel bifurcates from the disease-free equilibrium as transmission crosses this threshold. Consequently, the full model indicates that levels of infection increase by two orders of magnitude and the effect of mass vaccination becomes negligible as transmission increases across the reinfection threshold.

Disease Outbreaks↗

PubMed2005

Helminths of saiga antelope in Kazakhstan: implications for conservation and livestock production.

Saiga antelope (Saiga tatarica) graze extensively on livestock pasture, potentially enabling transmission of a wide range of parasitic helminths between saigas and domestic ruminants. Thirty-six of the 38 species of helminth that have been found in saigas in Kazakhstan in the past have been found also in domestic livestock. We examined 133 saigas culled for meat in autumn 1997, and found three species of cestode and 12 nematodes (nine in the abomasum), but no trematodes or lungworms. The most abundant species were Marshallagia marshalli, Marshallagia mongolica, and Nematodirus gazellae in the abomasum, Nematodirus gazellae in the small intestine, and Skrjabinema ovis in the large intestine. There was no clear relationship between intensities of abomasal nematodes and body condition. Age-intensity patterns differed between species: N. gazellae intensities were highest in saigas around 2-3 yr old, and declined in older animals, whereas the intensity of Marshallagia spp. rose asymptotically with age. Fecal egg density was directly proportional to adult worm intensity across ages for Marshallagia spp., but only in young animals for N. gazellae. There was no evidence that helminths, at the intensities observed, adversely affect saiga populations. The host range of many of the parasites found is broad, and transmission between saigas and livestock in both directions might become important to agriculture and conservation as livestock numbers recover. Simplified sampling techniques used in this study, and statistical analysis based on bootstrapping, could prove useful in other parasitologic surveys of wildlife in remote areas.

Age Factors↗

PubMed2004

Respiratory syncytial virus epidemiology in a birth cohort from Kilifi district, Kenya: infection during the first year of life.

We report estimates of incidence of respiratory syncytial virus (RSV) infection during the first year of life for a birth cohort from rural, coastal Kenya. A total of 338 recruits born between 21 January 2002 and 30 May 2002 were monitored for symptoms of respiratory infection by home visits and hospital referrals. Nasal washings were screened by use of immunofluorescence. From 311 child-years of observation (cyo), 133 RSV infections were found, of which 48 were lower respiratory tract infections (LRTIs) and 31 were severe LRTIs, resulting in 4 hospital admissions. There were 121 primary RSV infections (248 cyo), of which 45 were LRTIs and 30 were severe LRTIs, resulting in 4 hospital admissions; there was no association with age. RSV contributed significantly to total LRTI disease in this vaccine-target group.

Age Factors↗

PubMed2004

Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives.

The SIR (susceptible-infectious-resistant) and SIS (susceptible-infectious-susceptible) frameworks for infectious disease have been extensively studied and successfully applied. They implicitly assume the upper and lower limits of the range of possibilities for host immune response. However, the majority of infections do not fall into either of these extreme categories. We combine two general avenues that straddle this range: temporary immune protection (immunity wanes over time since infection), and partial immune protection (immunity is not fully protective but reduces the risk of reinfection). We present a systematic analysis of the dynamics and equilibrium properties of these models in comparison to SIR and SIS, and analyse the outcome of vaccination programmes. We describe how the waning of immunity shortens inter-epidemic periods, and poses major difficulties to disease eradication. We identify a "reinfection threshold" in transmission when partial immunity is included. Below the reinfection threshold primary infection dominates, levels of infection are low, and vaccination is highly effective (approximately an SIR model). Above the reinfection threshold reinfection dominates, levels of infection are high, and vaccination fails to protect (approximately an SIS situation). This association between high prevalence of infection and vaccine failure emphasizes the problems of controlling recurrent infections in high-burden regions. However, vaccines that induce a better protection than natural infection have the potential to increase the reinfection threshold, and therefore constitute interventions with a surprisingly high capacity to reduce infection where reduction is most needed.

Communicable Disease Control↗

PubMed2004

The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacy.

Population patterns of infection are determined largely by susceptibility to infection. Infection and vaccination induce an immune response that, typically, reduces susceptibility to subsequent infections. With a general epidemic model, we detect a 'reinfection threshold', above which reinfection is the principal type of transmission and, consequently, infection levels are much higher and vaccination fails. The model is further developed to address human tuberculosis (TB) and the impact of vaccination. The bacille Calmette-Guérin (BCG) is the only vaccine in current use against TB, and there is no consensus about its usefulness. Estimates of protection range from 0 to 80%, and this variability is aggravated by an association between low vaccine efficacy and high prevalence of the disease. We propose an explanation based on three postulates: (i) the potential for transmission varies between populations, owing to differences in socio-economic and environmental factors; (ii) exposure to mycobacteria induces an immune response that is partially protective against reinfection; and (iii) this protection is not significantly improved by BCG vaccination. These postulates combine to reproduce the observed trends, and this is attributed to a reinfection threshold intrinsic to the transmission dynamics. Finally, we demonstrate how reinfection thresholds can be manipulated by vaccination programmes, suggesting that they have a potentially powerful role in global control.

BCG Vaccine↗

PubMed2004

Molecular epidemiology of respiratory syncytial virus in Kilifi district, Kenya.

Respiratory syncytial virus (RSV) causes significant burden of disease during infancy and childhood. This study examined the genetic relatedness of RSV positive samples from child inpatients and outpatients and a birth cohort from a rural coastal district of Kenya and also the distribution of strains between these three groups. Clinical samples were collected over a 4-year period in Kilifi District, Kenya from community and hospital surveillance. Three hundred ninety seven of 1,044 nasal specimens from children (under 5 years old) attending Kilifi District Hospital, and from community-monitored infants, were positive for RSV by multiplex RT-PCR. Of these, 376 samples were analysed further by restriction fragment length polymorphisms (RFLP) of the nucleocapsid (N) and attachment (G) protein genes. The G gene was sequenced for 109 samples and phylogenetic analysis carried out. The group A samples from Kilifi fell into two clusters based on G gene sequences, while only one group B cluster was observed. One RSV-B sample from 2003 demonstrated the presence of a 60-nucleotide duplication within the G gene, clustering with similar isolates from Buenos Aries from 1999. All had similar sequences to isolates from the UK, USA, Spain, or Uruguay. The Kilifi District samples showed greater than 97% homology to isolates from South Africa and Mozambique and 91-94% homology to isolates from The Gambia. Samples from different sources, clearly differing in disease severity, did not differ in genotype characteristics, suggesting that disease causing variants are a general reflection of infections within this community.

Amino Acid Sequence↗

PubMed2004

Ruminating on complexity: macroparasites of wildlife and livestock.

Recent advances in ecology have improved our understanding of the role of parasites in the dynamics of wildlife populations. However, conditions that prevail in many wildlife systems, such as host movement, contact with livestock, and heterogeneity in the environment of the parasite outside of the host, have largely been ignored in existing models of macroparasite transmission. We need to refine these models if we are to stand a chance of developing effective parasite control strategies. New quantitative approaches enable us to address key complexities and make better use of scarce data, and these should enhance our efforts to understand and control emerging problems of interspecific parasite transmission.

Journal Article↗

PubMed2002

On the determinants of population structure in antigenically diverse pathogens.

Many pathogens exhibit antigenic diversity and elicit strain-specific immune responses. This potential for cross-immunity structure in the host resource motivates the development of mathematical models, stressing competition for susceptible hosts in driving pathogen population dynamics and genetics. Here we establish that certain model formulations exhibit characteristics of prototype pattern-forming systems, with pathogen population structure emerging as three possible patterns: (i) incidence is steady and homogeneous; (ii) incidence is steady but heterogeneous; and (iii) incidence shows oscillatory dynamics, with travelling waves in strain-space. Results are robust to strain number, but sensitive to the mechanism of cumulative immunity.

Animals↗