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Biomedical subjects

Tom Smith

Publications and source records attributed to Tom Smith.

At least 19 recordsLinked to original sources
PubMed2007

Attention problems among children with a positive family history of alcohol abuse or dependence and controls. Prevalence and course for the period from preteen to early teen years.

This longitudinal study investigated the scope and course of attention problems over a period of time from preteen (ages 7-12 years) to early teen years (ages 13-17 years). We compared symptoms in subjects with and without a family history (FH) of alcohol abuse or dependence from among families without evidence of antisocial personality disorder. Evaluations of attention problems for the offspring were based on the Child Behavior Checklist and a validated semistructured interview carried out with the mother. The findings indicate no higher risk for attention problems and attention-deficit hyperactivity disorder (ADHD)-like symptoms in the children of families with an alcohol use disorder. Regarding the course of problems, the ADHD symptom count tended to decrease over time, especially for children without a FH of alcohol abuse or dependence. Further research will be needed to determine whether results can be replicated with families from different social strata and including subjects with the antisocial personality disorder.

Adolescent↗
PubMed2006

Predictors of attention problems for the period from pre-teen to early teen years.

OBJECTIVE: This longitudinal study investigated the scope, persistence, and predictors of attention problems (AP) over a period of time from pre-teen (7-12 years) to early teen years (13-17 years). METHOD: AP evaluations used the Child Behavior Checklist (CBCL) and a semi-structured interview (C-SSAGA-P) with the parents. In addition, data relating to birth complications, family histories of affective disorders and alcohol-use disorders, home supervision, emotional, social and behavioral problems, school performance and school activities at two different measurement points were also collected. RESULTS: The findings indicate a high degree of comorbidity between AP and emotional and behavioral problems, difficulties in school, social problems and peer rejection. Furthermore, a cross-sectional association between childhood AP and parental affective disorders was also evident. Longitudinally, there was no increase in AP over the age span covered by the study, and symptoms often did not persist over time. Multiple regression analyses confirmed poorer school performance, problems with peers and AP at time point 15 as predictors for subsequent AP. CONCLUSION: The findings indicate that AP symptoms do not occur more frequently in early teen than in pre-teen years, and tend to be temporary phenomena. Difficulties in school and with peers were noted as particularly strong predictors of subsequent AP.

Adolescent↗
PubMed2006

Effect of the malaria vaccine Combination B on merozoite surface antigen 2 diversity.

Extensive genetic polymorphism is generally found in Plasmodium falciparum surface antigens. This poses a considerable obstacle to the development of a malaria vaccine. In order to assess possible effects of a polymorphic vaccine, we have analyzed the genetic diversity of parasites collected in the course of a phase 2b field trial of the blood stage vaccine Combination B in Papua New Guinea. The full-length 3D7 allele of the merozoite surface protein 2 (MSP2) was included in Combination B as one of three subunits. Vaccinees had a lower prevalence of parasites carrying a 3D7-type allele (corresponding to that in the vaccine) and selection appeared to favour the alternative FC27-type alleles resulting in a higher incidence of morbid episodes associated with FC27-type parasites. We sequenced MSP2 alleles detected in study participants after vaccination to identify breakthrough genotypes. Extensive genetic diversity of MSP2 was observed in both the repetitive and family-specific domains, but alleles occurring in vaccine recipients were no different from those found in placebo recipients. A phylogenetic analysis showed no clustering of 3D7-type breakthrough infections from vaccine recipients. The repeat unit present in the vaccine molecule occurred in a number of alleles from the trial area and was also observed in vaccinated individuals. Thus the anti-repeat immune response did not lead to elimination of parasites carrying the same repeat unit. We conclude that the conserved epitopes in the family-specific domain were the most important determinants of the vaccine effect against new 3D7-type infections and that the hypervariable domains were not subject to selective effects of the vaccine.

Animals↗
PubMed2006

Cause-specific mortality rates in sub-Saharan Africa and Bangladesh.

OBJECTIVE: To provide internationally comparable data on the frequencies of different causes of death. METHODS: We analysed verbal autopsies obtained during 1999 -2002 from 12 demographic surveillance sites in sub-Saharan Africa and Bangladesh to find cause-specific and age-specific mortality rates. The cause-of-death codes used by the sites were harmonized to conform to the ICD-10 system, and summarized with the classification system of the Global Burden of Disease 2000 (Version 2). FINDINGS: Causes of death in the African sites differ strongly from those in Bangladesh, where there is some evidence of a health transition from communicable to noncommunicable diseases, and little malaria. HIV dominates in causes of mortality in the South African sites, which contrast with those in highly malaria endemic sites elsewhere in sub-Saharan Africa (even in neighbouring Mozambique). The contributions of measles and diarrhoeal diseases to mortality in sub-Saharan Africa are lower than has been previously suggested, while malaria is of relatively greater importance. CONCLUSION: The different patterns of mortality we identified may be a result of recent changes in the availability and effectiveness of health interventions against childhood cluster diseases.

Adolescent↗
PubMed2006

Mapping malaria transmission in West and Central Africa.

We have produced maps of Plasmodium falciparum malaria transmission in West and Central Africa using the Mapping Malaria Risk in Africa (MARA) database comprising all malaria prevalence surveys in these regions that could be geolocated. The 1846 malaria surveys analysed were carried out during different seasons, and were reported using different age groupings of the human population. To allow comparison between these, we used the Garki malaria transmission model to convert the malaria prevalence data at each of the 976 locations sampled to a single estimate of transmission intensity E, making use of a seasonality model based on Normalized Difference Vegetation Index (NDVI), temperature and rainfall data. We fitted a Bayesian geostatistical model to E using further environmental covariates and applied Bayesian kriging to obtain smooth maps of E and hence of age-specific prevalence. The product is the first detailed empirical map of variations in malaria transmission intensity that includes Central Africa. It has been validated by expert opinion and in general confirms known patterns of malaria transmission, providing a baseline against which interventions such as insecticide-treated nets programmes and trends in drug resistance can be evaluated. There is considerable geographical variation in the precision of the model estimates and, in some parts of West Africa, the predictions differ substantially from those of other risk maps. The consequent uncertainties indicate zones where further survey data are needed most urgently. Malaria risk maps based on compilations of heterogeneous survey data are highly sensitive to the analytical methodology.

Africa, Central↗
PubMed2006

Picture this: the state of the art in visualization for complex adaptive systems.

Visualization has an increasingly important role to play in scientific research. Moreover, visualization has a special role to play within artificial life as a result of the informal status of its key explananda: life and complexity. Both are poorly defined but apparently identifiable via raw inspection. Here we concentrate on how visualization techniques might allow us to move beyond this situation by facilitating increased understanding of the relationships between an ALife system's (low-level) composition and organization and its (high-level) behavior. We briefly review the use of visualization within artificial life, and point to some future developments represented by the articles collected within this special issue.

Art↗
PubMed2006

Comparison of PCR-RFLP and Genescan-based genotyping for analyzing infection dynamics of Plasmodium falciparum.

Parameters describing the infection dynamics of Plasmodium falciparum are important determinants of the potential impact of interventions and are potential outcome measurements for malaria intervention trials. Low parasite densities, periodic sequestration of parasites, and the presence of multiple concurrent infections make it essential to use molecular techniques to estimate the force of infection and duration of infections in endemic areas. We now compare two approaches for tracking individual genotypes of the highly polymorphic merozoite surface protein 2: 1) fluorescence-labeled polymerase chain reaction (PCR) and GeneScan-sizing and 2) restriction fragment length polymorphism (RFLP). We analyze samples from a longitudinal field study in Ghana and use statistical approaches that allow for imperfect detectability. The two methods gave broadly similar estimates of parasite dynamics, but GeneScan is more precise and can achieve a higher throughput. The analysis of parasite dynamics indicated an average duration of infection of 210 days by GeneScan versus 152 days by PCR-RFLP in the study population in Kassena-Nankana, Northern Ghana. This reflects the good performance of GeneScan-based genotyping for studies of parasite infection dynamics.

Adolescent↗
PubMed2005

An immigration-death model to estimate the duration of malaria infection when detectability of the parasite is imperfect.

Immigration-death models are proposed to analyse the infection dynamics in longitudinal studies of panels of heavily parasitized human hosts where parasites have been typed at regular intervals by PCR. Immigration refers to the acquisition of a new parasitic genotype, occurring at rate lambda, and death refers to the clearance of a parasitic genotype (with rate mu). The models assume that corresponding to each observed process which is the detection or failure to detect a parasitic genotype, is an underlying true process which is hidden as a result of imperfect detection. We consider: (i) a model in which no distinction is made between the different members of the human population, who collectively represent the habitat of the parasites, and (ii) a model that allows for the accrual of infections with age. The models are fitted to a panel data set of malaria genotype of parasites belonging to the msp2 FC27 and 3D7 allelic families from a study of the dynamics of Plasmodium falciparum in Northern Ghana. Maximum likelihood estimates suggest that on average any individual residing in this holo-endemic area will acquire 16 new infections per year (95 per cent CI, 15-18) (defined by their single locus genotypes) and that infection with any of these genotypes lasts on average 152 days (95 per cent CI, 138-169). We estimate that an average of 47 per cent (95 per cent CI, 42-51) of the parasite types present in the host are detected in a finger-prick blood sample. This model provides a basis for analyses of how these quantities vary with the age, and hence the immune status of the host.

Adolescent↗
PubMed2005

An outbreak of serotype 1 Streptococcus pneumoniae meningitis in northern Ghana with features that are characteristic of Neisseria meningitidis meningitis epidemics.

BACKGROUND: The Kassena-Nankana District (KND) of northern Ghana lies in the African meningitis belt, where epidemics of bacterial meningitis have been reoccurring every 8-12 years. These epidemics are generally caused by Neisseria meningitidis, an organism that is considered to be uniquely capable of causing meningitis epidemics. METHODS: We recruited all patients with suspected meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were collected and analyzed by standard microbiological techniques. Bacterial isolates were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic-resistance testing. RESULTS: A continual increase in the incidence of pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited strong seasonality, a broad host age range, and clonal dominance, all of which are characteristic of meningococcal meningitis epidemics in the African meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%; the majority of pneumococcal isolates were antibiotic sensitive and expressed the serotype 1 capsule. MLST revealed that these isolates belonged to a clonal complex dominated by sequence type (ST) 217 and its 2 single-locus variants, ST303 and ST612. CONCLUSIONS: The S. pneumoniae ST217 clonal complex represents a hypervirulent lineage with a high propensity to cause meningitis, and our results suggest that this lineage might have the potential to cause an epidemic. Serotype 1 is not included in the currently licensed pediatric heptavalent pneumococcal vaccine. Mass vaccination with a less complex conjugate vaccine that targets hypervirulent serotypes should, therefore, be considered.

Drug Resistance, Bacterial↗
PubMed2005

Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria.

The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55-270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24-40% by microscopy and 55-83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on southeastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations.

Animals↗
PubMed2005

The added value of claims for cancer surveillance: results of varying case definitions.

OBJECTIVE: As cancer diagnosis and treatment has moved to the outpatient healthcare setting, traditional cancer surveillance tools are less effective for complete and unbiased capture of incident cases. This study evaluates the potential for Medicare data to supplement cancer surveillance in a unique manner by using a standard that is independent of a central cancer registry. DESIGN: State cancer registry records were matched with Medicare data. Case validation included inpatient record abstraction combined with a mail/telephone survey of treating physicians. The positive predictive value (PPV), sensitivity (capture rate), and potential additional cases were calculated for 6 Medicare claims-based case definitions. RESULTS: The PPV varied according to cancer site and definition, ranging from 70%-97% (prostate) to 87%-98% (breast). Sensitivity varied inversely with PPV, ranging from 51%-94% (breast) to 10%-88% (lung). The most important factors that predicted being missed by the registry were having no admission to an ACOS-certified hospital and no surgical treatment. CONCLUSION: Medicare data represent a valid resource for supplementing state cancer registries in surveillance efforts. This potential is especially applicable to cancers predominantly diagnosed and treated outside the hospital setting.

Aged↗
PubMed2005

Emergence of W135 meningococcal meningitis in Ghana.

Neisseria meningitidis serogroup W135, well known for a long time as a cause of isolated cases of meningococcal meningitis, has recently increasingly been associated with disease outbreaks of considerable magnitude. Burkina Faso was hit by W135 epidemics in the dry seasons of 2002-2004, but only four W135 meningitis cases were recorded between February 2003 and March 2004 in adjoining Ghana. This reconfirms previous findings that bottlenecks exist in the spreading of new epidemic N. meningitidis clones within the meningitis belt of sub-Saharan Africa. Of the four Ghanaian W135 meningitis patients one died and three survived, of whom one had profound neurosensory hearing loss and speech impairment. All four disease isolates were sensitive to penicillin G, chloramphenicol, ciprofloxacin and cefotaxime and had the multi-locus sequence type (ST) 11, which is the major ST of the ET-37 clonal complex. Pulsed-field gel electrophoresis (PFGE) profiles of the Ghanaian disease isolates and recent epidemic isolates from Burkina Faso were largely identical. We conducted meningococcal colonization surveys in the home communities of three of the patients and in the Kassena Nankana District located at the border to Burkina Faso. W135 carriage rates ranged between 0% and 17.5%. When three consecutive surveys were conducted in the patient community with the highest carrier rate, persistence of W135 colonization over a period of 1 year was observed. Differences in PFGE profiles of carrier isolates taken at different times in the same patient community were indicative of rapid microevolution of the W135 bacteria, emphasizing the need for innovative fine typing methods to reveal the relationship between W135 isolates.

Adolescent↗
PubMed2005

Effectively starting and titrating intrathecal analgesic therapy in patients with refractory cancer pain.

Patients continue to suffer from pain despite their analgesic regimen and frequently from symptoms related to these interventions. This article describes the role that intrathecal analgesia may play in improving comfort for individuals experiencing refractory pain and/or symptoms of opioid therapy. Patient selection, staff education, institution requirements, medications, and titration guidelines also will be reviewed. Patients with cancer clearly deserve to achieve comfort; therefore, intrathecal therapy, which is a safe intervention, must be considered when refractory pain or symptoms occur.

Algorithms↗
PubMed2004

A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma.

PURPOSE: P-glycoprotein (Pgp) inhibitors have been under clinical evaluation for drug resistance reversal for over a decade. Valspodar (PSC 833) inhibits Pgp-mediated efflux but delays drug clearance, requiring reduction of anticancer drug dosage. We designed an infusional schedule for valspodar and vinblastine to mimic infusional vinblastine alone. The study was designed to determine the maximally tolerated dose of vinblastine, while attempting to understand the pharmacokinetic interactions between vinblastine and valspodar and to determine the response rate in patients with metastatic renal cell cancer. PATIENTS AND METHODS: Thirty-nine patients received continuous infusion valspodar and vinblastine. Vinblastine was administered for 3 days to compensate for the expected delay in clearance and the required dose reduction. Valspodar was administered initially at a dose of 10 mg/kg/d; the dose of vinblastine varied. RESULTS: The maximum-tolerated dose of vinblastine was 1.3 mg/m(2)/d. As suggested previously, serum valspodar concentrations exceeded those needed for Pgp inhibition. Consequently, the dose of valspodar was reduced to 5 mg/kg, allowing a vinblastine dose of 2.1 mg/m(2)/d to be administered. Pharmacodynamic studies demonstrated continued inhibition of Pgp at lower valspodar doses by functional assay in Pgp-expressing CD56+ cells and by (99m)Tc-sestamibi imaging. A 15-fold range in cytochrome p450 activity was observed, as measured by midazolam clearance. No major responses were observed. CONCLUSIONS: These results suggest that the pharmacokinetic impact of cytochrome P450 inhibition by valspodar can be reduced although not eliminated, while preserving Pgp inhibition, thus separating the pharmacokinetic and pharmacodynamic activities of valspodar.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Strain-specific humoral response to a polymorphic malaria vaccine.

The 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum was one of three subunits of the malaria vaccine Combination B that were tested in a phase I/IIb double-blind randomized placebo-controlled trial, which was undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because only one variant of the highly polymorphic MSP2 was used for vaccination, we examined whether the elicited response was directed against conserved or strain-specific epitopes. Postvaccination (week 12) titers of antibody against recombinantly expressed individual domains of MSP2 were measured by enzyme-linked immunosorbent assay and compared to baseline values. We found that vaccination with the 3D7 form of MSP2 induced a significant strain-specific humoral response directed against the repetitive and semiconserved family-specific part. The conserved N- and C-terminal domains were not immunogenic. Titers of antibody against the alternate FC27 family-specific domain showed a tendency to increase in vaccinated children, but there was no increase in antibodies against FC27-type 32-mer repeats. These results indicate that vaccination with one MSP2 variant mainly induced a strain-specific response, which can explain the selective effect of vaccination with combination B on the genotypes of breakthrough parasites. These findings support the inclusion of both family-specific domains (3D7 and FC27) in an improved vaccine formulation.

Amino Acid Sequence↗
PubMed2004

Estimating the duration of Plasmodium falciparum infection from trials of indoor residual spraying.

We reviewed the use of simple mathematical models to estimate the duration of Plasmodium falciparum infection after transmission has been interrupted. We then fit an exponential decay model to repeated cross-sectional survey data collected from three historical trials of indoor residual spraying against malaria: one from two contiguous districts in Tanzania-Kenya (Pare Taveta) carried out in 1954, the others in West Papua (1953), and the Garki project in northern Nigeria (1972-1973). A cross-sectional analysis of these datasets gave overall estimates of 602 days (95% confidence interval [CI] = 581-625) for the infection duration in Pare Taveta, 734 days (95% CI = 645-849) in West Papua, and 1,329 days (95% CI =1,193-1,499) for Garki. These estimates are much greater than the most widely quoted figures for the duration of untreated P. falciparum infections. Although these may be exaggerated because some reinfections occurred despite intensive vector control, prevalence was still decreasing when all these projects ended. Longitudinal survival analysis of the Garki data gave much shorter estimates of duration (186 days, 95% CI = 181-191), but effects of imperfect detection of parasites by microscopy severely bias these estimates. Estimates of infection duration for different age groups showed considerable variation but no general age trend. There was also no clear relationship between malaria endemicity and infection duration. Analyses of successive sampling from the same individuals with parasite typing are needed to obtain more reliable estimates of infection duration in endemic areas. Periods of several years may be required to evaluate long-term effects of interventions on malaria prevalence.

Animals↗