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1.
Community Dent Health ; 34(4): 208-225, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29119741

ABSTRACT

OBJECTIVE: In this article we report the findings of a scoping review that aimed to identify and summarise the range of programs and guidelines available for toothbrushing programs in schools and early childhood settings. Dental caries is one of the most common preventable diseases affecting children worldwide. Untreated caries can impact on child health and wellbeing, development, socialisation and school attendance. Supervised toothbrushing programs in schools and other early childhood settings can be effective in improving the oral health of young children. There is limited understanding of the salient issues to consider when developing such programs or how they are best implemented in real world settings. METHODS: A scoping review methodology was utilised to provide a summary of the guidelines and programs available. Key search terms were developed, mapped and utilised to identify guidelines and programs across 6 databases and key search engines. RESULTS: We located 26 programs and guidelines that met the inclusion and exclusion criteria for the review. These were collated and summarised across key countries and critical aspects of program development and implementation were identified. Toothbrush type and storage, toothpaste strength and method of dispensing, toothbrush storage, staff training and parental consent are key considerations that varied widely. CONCLUSIONS AND RECOMMENDATIONS: Guidelines for supervised toothbrushing programs vary within and across countries due to differences in water fluoridation and availability of low fluoride toothpastes. The results of this review provide critical information to be considered when establishing and implementing toothbrushing programs in these settings.


Subject(s)
Oral Health , Toothbrushing/standards , Child , Child, Preschool , Dental Caries/prevention & control , Guidelines as Topic , Humans , Schools
2.
mBio ; 7(4)2016 07 19.
Article in English | MEDLINE | ID: mdl-27435464

ABSTRACT

UNLABELLED: Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC50], <1:100 serum dilution; 18%) or moderate to high (EC50, >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV. IMPORTANCE: ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , Cross Reactions , Dengue Virus/immunology , Zika Virus Infection/therapy , Zika Virus/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Disease Models, Animal , Epitopes/immunology , Humans , Mice , Neutralization Tests , Treatment Outcome
3.
Community Dent Health ; 33(2): 100-6, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27352463

ABSTRACT

UNLABELLED: Early Childhood Caries (ECC) is the most common, preventable disease of childhood. It can affect children's health and wellbeing and children from migrant families may be at greater risk of developing ECC. OBJECTIVE: To describe ECC in children from migrant families, and explore possible influences. BASIC RESEARCH DESIGN: Cross-sectional analysis of caries data collected as baseline data for an oral health promotion study. PARTICIPANTS: The analysis sample included 630 1-4 year-old children clustered within 481 Iraqi, Lebanese and Pakistani families in Melbourne, Australia. METHOD: Child participants received a community-based visual dental examination. Parents completed a self-administered questionnaire on demographics, ethnicity, and oral health knowledge, behaviour and attitudes. MAIN OUTCOME MEASURE: Child caries experience. Bivariate associations between oral health behaviours and ethnicity were tested for significance using chi-square. Multivariate logistic regression analyses were performed to identify associations with ECC, adjusting for demographic variables and accounting for clustering by family. RESULTS: Overall, 34% of children in the sample experienced caries (both non-cavitated and cavitated). For all caries lesions, parent' length of residence in Australia, consumption of sweet drinks and parental education remained as independent predictors of child caries experience. Adding sugar to drinks was an additional risk factor for cavitation. Ethnicity was associated with some individual oral health behaviours suggesting cultural influences on health, however the relationship was not independent of other predictors. CONCLUSION: Culturally competent oral health promotion interventions should aim to support migrant families with young children, and focus on reducing sweet drink consumption.


Subject(s)
Dental Caries/epidemiology , Oral Health , Transients and Migrants , Adolescent , Adult , Attitude to Health , Beverages/statistics & numerical data , Child, Preschool , Cross-Sectional Studies , Diet, Cariogenic , Dietary Sucrose/administration & dosage , Educational Status , Female , Health Behavior , Health Knowledge, Attitudes, Practice , Humans , Infant , Iraq/ethnology , Lebanon/ethnology , Male , Middle Aged , Pakistan/ethnology , Parents/education , Parents/psychology , Risk Factors , Toothbrushing/statistics & numerical data , Victoria/epidemiology , Young Adult
4.
Aust Dent J ; 61(1): 84-92, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25892487

ABSTRACT

BACKGROUND: An important role for parents and caregivers in the prevention of dental caries in children is the early establishment of health promoting behaviours. This study aimed to examine mothers' views on barriers and facilitators to promoting child and family oral health. METHODS: Semi-structured interviews were undertaken with a purposive sample of mothers (n = 32) of young children. Inductive thematic analysis was conducted. RESULTS: Parental knowledge and beliefs, past experiences and child behaviour emerged as major influences on children's oral health. Child temperament and parental time pressures were identified as barriers to good oral health with various strategies reported for dealing with uncooperative children at toothbrushing time. Parental oral health knowledge and beliefs emerged as positive influences on child oral health; however, while most mothers were aware of the common causes of dental caries, very few knew of other risk factors such as bedtime feeding. Parents' own oral health experiences were also seen to positively influence child oral health, regardless of whether these were positive or negative experiences. CONCLUSIONS: Understanding parental oral health beliefs is essential to overcoming barriers and promoting enablers for good child oral health. Improving child oral health also requires consideration of child behaviour, family influences, and increasing awareness of lesser-known influencing factors.

5.
mBio ; 6(5): e01461-15, 2015 Oct 13.
Article in English | MEDLINE | ID: mdl-26463165

ABSTRACT

UNLABELLED: Dengue virus serotype 2 (DENV2) is widespread and responsible for severe epidemics. While primary DENV2 infections stimulate serotype-specific protective responses, a leading vaccine failed to induce a similar protective response. Using human monoclonal antibodies (hMAbs) isolated from dengue cases and structure-guided design of a chimeric DENV, here we describe the major site on the DENV2 envelope (E) protein targeted by neutralizing antibodies. DENV2-specific neutralizing hMAb 2D22 binds to a quaternary structure epitope. We engineered and recovered a recombinant DENV4 that displayed the 2D22 epitope. DENV2 neutralizing antibodies in people exposed to infection or a live vaccine tracked with the 2D22 epitope on the DENV4/2 chimera. The chimera remained sensitive to DENV4 antibodies, indicating that the major neutralizing epitopes on DENV2 and -4 are at different sites. The ability to transplant a complex epitope between DENV serotypes demonstrates a hitherto underappreciated structural flexibility in flaviviruses, which could be harnessed to develop new vaccines and diagnostics. IMPORTANCE: Dengue virus causes fever and dengue hemorrhagic fever. Dengue serotype 2 (DENV2) is widespread and frequently responsible for severe epidemics. Natural DENV2 infections stimulate serotype-specific neutralizing antibodies, but a leading DENV vaccine did not induce a similar protective response. While groups have identified epitopes of single monoclonal antibodies (MAbs), the molecular basis of DENV2 neutralization by polyclonal human immune sera is unknown. Using a recombinant DENV displaying serotype 2 epitopes, here we map the main target of DENV2 polyclonal neutralizing antibodies induced by natural infection and a live DENV2 vaccine candidate. Proper display of the epitope required the assembly of viral envelope proteins into higher-order structures present on intact virions. Despite the complexity of the epitope, it was possible to transplant the epitope between DENV serotypes. Our findings have immediate implications for evaluating dengue vaccines in the pipeline as well as designing next-generation vaccines.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Dengue Virus/immunology , Epitopes, B-Lymphocyte/immunology , Viral Envelope Proteins/immunology , Humans
6.
Br Dent J ; 218(11): 629-34, 2015 Jun 12.
Article in English | MEDLINE | ID: mdl-26068158

ABSTRACT

There is increasing importance placed on conducting clinical trials in dentistry to provide a robust evidence base for the treatment provided, and models of care delivered. However, providing the evidence upon which to base such decisions is not straightforward, as the conduct of these trials is complex. Currently, only limited information is available about the strategies to deliver successful clinical trials in primary care settings, and even less available on dental clinical trials. Considerable knowledge and experience is lost once a trial is completed as details about effective management of a trial are generally not reported or disseminated to trial managers and researchers. This leads to loss of vital knowledge that could assist with the effective delivery of new trials. The aim of this study is to examine the conduct and delivery of five dental clinical trials across both Australia and the UK and identify the various factors that impacted upon their implementation. Findings suggest that early stakeholder engagement, and well-designed and managed trials, lead to improved outcomes for researchers, clinic staff and patients, and increases the potential for future dissemination and translation of information into practice.


Subject(s)
Dental Care , Dental Research/methods , Randomized Controlled Trials as Topic/methods , Australia , Dental Care/methods , Dental Care/organization & administration , Dental Instruments , Dental Research/organization & administration , Humans , Multicenter Studies as Topic/methods , Patient Selection , Primary Health Care/methods , Resource Allocation , Scotland
7.
J Clin Microbiol ; 43(7): 3267-72, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16000446

ABSTRACT

Plaque assays for titrating dengue virus (DENV) are time-consuming and not suitable for strains that do not plaque. Fluorescence-activated cell sorting (FACS) has been used to detect DENV-infected cells. Here we describe a FACS-based assay for titrating DENV. We determined that at 24 h postinfection, the number of infected cells detected by FACS represented the first round of infection and therefore could be used as a readout of the number of infectious particles in the inoculum. When the titers of different laboratory and clinical strains of DENV were compared using FACS, plaque, and endpoint dilution assays, for most strains the FACS titers were comparable to titers obtained by plaque or endpoint dilution assays. The FACS assay is an improvement over the plaque assay because the infection period is reduced from 5 to 7 days to 24 h and the assay can be used to titrate clinical isolates that frequently do not form clear plaques on cell monolayers. The novel FACS-based methods described here will facilitate laboratory studies of dengue.


Subject(s)
Antibodies, Viral/immunology , Dengue Virus/isolation & purification , Dengue/diagnosis , Flow Cytometry/methods , Aedes , Animals , Cells, Cultured , Chlorocebus aethiops , Dengue/virology , Dengue Virus/immunology , Dengue Virus/pathogenicity , Humans , Neutralization Tests , Vero Cells , Viral Plaque Assay
8.
Obes Res ; 9(12): 733-40, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11743056

ABSTRACT

OBJECTIVE: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the beta-3 adrenergic receptor, tumor necrosis factor-alpha, leptin, and leptin receptor (Lepr) in a cohort of Australian women. RESEARCH METHODS AND PROCEDURES: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms. RESULTS: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the beta-3 adrenergic receptor (Trp64Arg), tumor necrosis factor-alpha promoter, or leptin genes in non-obese or obese women. DISCUSSION: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.


Subject(s)
Genetic Variation , Obesity/genetics , Receptors, Cell Surface , Absorptiometry, Photon , Adipose Tissue , Adult , Anthropometry , Australia , Body Composition , Body Mass Index , Carrier Proteins/genetics , Female , Gene Frequency , Genotype , Humans , Leptin/genetics , Middle Aged , Polymerase Chain Reaction , Promoter Regions, Genetic , Prospective Studies , Receptors, Adrenergic, beta-3/genetics , Receptors, Leptin , Tumor Necrosis Factor-alpha/genetics
9.
Infect Immun ; 69(6): 3536-41, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11349010

ABSTRACT

Here we describe a protocol for purifying Borrelia burgdorferi from feeding ticks by velocity centrifugation and Percoll density gradient centrifugation. The purified spirochetes were motile and 10- to 20-fold purer than the bacteria in crude tick homogenates. The purified bacteria were present in sufficient quantity for protein and gene expression studies. In comparison to culture-grown bacteria, tick-borne spirochetes had several proteins that were upregulated and a few that were downregulated. When the levels of B. burgdorferi outer surface proteins OspA and OspC were measured, OspC protein and mRNA levels were lower in cultured bacteria than in bacteria purified from ticks. Although differences in OspA mRNA levels were observed between cultured and tick-borne bacteria, no differences were observed at the protein level. These experiments demonstrate that tick-transmitted borreliae display a gene expression and antigen profile different from that of spirochetes cultured in vitro.


Subject(s)
Borrelia burgdorferi Group/isolation & purification , Ixodes/microbiology , Lipoproteins , Lyme Disease/transmission , Animals , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Antigens, Bacterial/metabolism , Antigens, Surface/genetics , Antigens, Surface/immunology , Antigens, Surface/metabolism , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/immunology , Bacterial Outer Membrane Proteins/metabolism , Bacterial Vaccines , Bacteriological Techniques , Borrelia burgdorferi Group/growth & development , Centrifugation, Density Gradient/methods , Culture Media , Feeding Behavior , Female , Ixodes/physiology , Lyme Disease/microbiology , Lyme Disease Vaccines/genetics , Lyme Disease Vaccines/immunology , Lyme Disease Vaccines/metabolism , Mice , Mice, Inbred C3H
10.
J Med Entomol ; 38(1): 99-107, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11268698

ABSTRACT

The blacklegged tick, Ixodes scapularis Say, transmits the Lyme disease spirochete Borrelia burgdorferi, whereas the American dog tick, Dermacentor variabilis (Say), is unable to transmit the bacterium. We compared the innate immune response of these ticks against spirochetes directly inoculated into the hemocoel cavity of ticks. In I. scapularis, some Borrelia were found associated with hemocytes, while numerous other spiral-shaped, intact bacteria remained free in the hemolymph. In contrast, in D. variabilis only remnants of the bacteria were evident in the hemolymph, indicating lysis; intact spirochetes were rare. Spirochetes were observed bound to or within the organs of both tick species, although many more spirochetes were found associated with the I. scapularis organs. The few spirochetes observed with the D. variabilis organs appeared to be dead because D. variabilis tissues rarely contained culturable bacteria, unlike I. scapularis tissues. When spirochetes were incubated with I. scapularis hemolymph plasma in vitro, bacterial survival and motility were not reduced. In contrast, incubation of spirochetes with D. variabilis hemolymph plasma resulted in > 50% of the spirochetes becoming nonmotile by 45 min. The differences in the responses of the two different tick species indicate that I. scapularis is immunotolerant when challenged with B. burgdorferi and dependent on a slow phagocytic response to clear Borrelia from the hemolymph. In contrast, D. variabilis is highly immunocompetent (i.e., innate immunity), using plasma borreliacidal factors and a rapid increase in phagocytic cells to clear the infection and limit tissue invasion.


Subject(s)
Borrelia burgdorferi Group/immunology , Dermacentor/immunology , Ixodes/immunology , Animals , Cell Count , Dermacentor/microbiology , Female , Hemocytes , Hemolymph , Immune Tolerance , Immunity, Innate , Immunocompetence , Ixodes/microbiology , Rabbits , Rats
11.
Proc Natl Acad Sci U S A ; 98(2): 670-5, 2001 Jan 16.
Article in English | MEDLINE | ID: mdl-11209063

ABSTRACT

The genome of Borrelia burgdorferi encodes a large number of lipoproteins, many of which are expressed only at certain stages of the spirochete's life cycle. In the current study we describe the B. burgdorferi population structure with respect to the production of two lipoproteins [outer surface protein A (OspA) and outer surface protein C (OspC)] during transmission from the tick vector to the mammalian host. Before the blood meal, the bacteria in the tick were a homogeneous population that mainly produced OspA only. During the blood meal, the population became more heterogeneous; many bacteria produced both OspA and OspC, whereas others produced only a single Osp and a few produced neither Osp. From the heterogeneous spirochetal population in the gut, a subset depleted of OspA entered the salivary glands and stably infected the host at time points >53 hr into the blood meal. We also examined genetic heterogeneity at the B. burgdorferi vlsE locus before and during the blood meal. In unfed ticks, the vlsE locus was stable and one predominant and two minor alleles were detected. During the blood meal, multiple vlsE alleles were observed in the tick. Tick feeding may increase recombination at the vlsE locus or selectively amplify rare vlsE alleles present in unfed ticks. On the basis of our data we propose a model, which is different from the established model for B. burgdorferi transmission. Implicit in our model is the concept that tick transmission converts a homogeneous spirochete population into a heterogeneous population that is poised to infect the mammalian host.


Subject(s)
Antigens, Bacterial/genetics , Antigens, Surface/genetics , Arthropod Vectors/microbiology , Bacterial Outer Membrane Proteins/genetics , Bacterial Proteins , Borrelia burgdorferi Group/genetics , Genes, Bacterial , Lipoproteins/genetics , Lyme Disease Vaccines/genetics , Lyme Disease/microbiology , Ticks/microbiology , Alleles , Animals , Antigenic Variation/genetics , Antigens, Surface/physiology , Bacterial Outer Membrane Proteins/physiology , Bacterial Vaccines , Bites and Stings/microbiology , Borrelia burgdorferi Group/immunology , Borrelia burgdorferi Group/isolation & purification , Borrelia burgdorferi Group/pathogenicity , Feeding Behavior , Genetic Variation , Intestines/microbiology , Lyme Disease/transmission , Mice , Mice, Inbred C3H , Phenotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Salivary Glands/microbiology , Skin/microbiology , Time Factors
12.
J Clin Invest ; 106(4): 561-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10953031

ABSTRACT

Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme disease vaccine that blocks transmission: OspA antibodies of immune hosts enter ticks during blood feeding and destroy spirochetes before transmission to the host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and many spirochetes repress OspA production during the feeding process. This preferential expression suggests that OspA may have an important function in the vector. Here we show that OspA mediates spirochete attachment to the tick gut by binding to an I. scapularis protein. The binding domains reside in the central region and COOH-terminus of OspA. OspA also binds to itself, suggesting that spirochete-spirochete interactions may further facilitate adherence in the gut. OspA-mediated attachment in the tick provides a possible mechanism for how stage-specific protein expression can contribute to pathogenesis during the B. burgdorferi natural cycle.


Subject(s)
Antigens, Surface/physiology , Bacterial Outer Membrane Proteins/physiology , Borrelia burgdorferi Group/physiology , Borrelia burgdorferi Group/pathogenicity , Ixodes/microbiology , Lipoproteins , Amino Acid Sequence , Animals , Antigens, Surface/genetics , Antigens, Surface/immunology , Arachnid Vectors , Bacterial Adhesion/genetics , Bacterial Adhesion/immunology , Bacterial Adhesion/physiology , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/immunology , Bacterial Vaccines , Base Sequence , Borrelia burgdorferi Group/genetics , DNA Primers/genetics , Digestive System/microbiology , Humans , Lyme Disease/etiology , Lyme Disease/prevention & control , Molecular Sequence Data , Mutagenesis, Site-Directed , Protein Binding
13.
Int J Obes Relat Metab Disord ; 23(8): 816-22, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10490782

ABSTRACT

OBJECTIVE: To investigate the relationship between polymorphisms in the OB-R and OB genes and metabolic markers for obesity and glucose intolerance in a population of Nauruan men. In addition, we examined the effect of the simultaneous presence of the three polymorphisms on the phenotype of individuals in this population. DESIGN AND SUBJECTS: This study was conducted in a population from the Pacific Island of Nauru. Populations in this region have some of the highest recorded rates of obesity and type 2 diabetes and are therefore of great interest in the genetic analysis of these diseases. Two hundred and thirty-two male subjects were examined in this cross-sectional study. All subjects were non-diabetic and the group had a mean age of 31 y and a mean body weight of 104 kg. MEASUREMENTS: Several phenotypic measures of body fatness and fat distribution (anthropometry), fasting plasma insulin, glucose and leptin concentrations, blood pressure and 2 h plasma glucose concentration, genotypes of subjects for the Gln223Arg, PRO1019pro (OB-R gene) and OB gene polymorphisms. RESULTS: Individually, the OB gene and Gln223Arg OB-R polymorphisms were not associated with the obese or glucose-intolerant phenotype in this population. Individuals with the PRO1019pro polymorphism were found to have elevated insulin concentrations and diastolic blood pressure (Pc = 0.04). In addition, individuals found to simultaneously exhibit homozygosity of the common allele of all three polymorphisms (genotypes: Arg/Arg, pro/pro and II/II) exhibited significantly elevated fasting insulin levels (Pc = 0.03). CONCLUSIONS: Pacific Island populations exhibit a remarkably high prevalence rate of obesity and type 2 diabetes and represent a unique population for genetic studies of obesity. In the present study we have revealed that a specific combination of alleles in OB and OB-R, two candidate genes for obesity, may confer an increased risk for the development of insulin resistance in Nauruan males.


Subject(s)
Carrier Proteins/genetics , Insulin Resistance/genetics , Obesity/genetics , Polymorphism, Genetic , Receptors, Cell Surface , Adult , Aged , Anthropometry , Asian People/genetics , Black People/genetics , Cross-Sectional Studies , Diabetes Mellitus, Type 2/genetics , Humans , Male , Micronesia , Middle Aged , Phenotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Receptors, Leptin , White People/genetics
14.
Am J Trop Med Hyg ; 60(2): 300-6, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10072155

ABSTRACT

Dengue is one of the most rapidly emerging diseases in the tropics. Humans are the principal reservoir of dengue viruses. It is unclear if nonhuman primates also serve as a reservoir of human dengue viruses under certain conditions. In this study, a cross-sectional serologic survey was carried out to characterize the pattern of transmission of a recently identified dengue virus among toque macaques in Sri Lanka. The results indicated that an epizootic dengue virus was active among the macaques. A single epizootic had taken place between October 1986 and February 1987 during which 94% of the macaques within the 3 km2 study site were exposed to the virus. The epizootic was highly focal in nature because macaques living 5 km from the study population were not exposed to the virus. The transmission of dengue viruses among macaques in the wild may have important public health implications.


Subject(s)
Dengue/epidemiology , Dengue/veterinary , Monkey Diseases/epidemiology , Animals , Antibodies, Viral/analysis , Dengue/transmission , Dengue/virology , Disease Outbreaks/veterinary , Disease Reservoirs , Enzyme-Linked Immunosorbent Assay , Humans , Macaca , Monkey Diseases/virology , Prevalence , Sri Lanka/epidemiology
15.
Infect Immun ; 67(1): 30-5, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9864192

ABSTRACT

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. When an infected nymphal tick feeds on a host, the bacteria increase in number within the tick, after which they invade the tick's salivary glands and infect the host. Antibodies directed against outer surface protein A (OspA) of B. burgdorferi kill spirochetes within feeding ticks and block transmission to the host. In the studies presented here, passive antibody transfer experiments were carried out to determine the OspA antibody titer required to block transmission to the rodent host. OspA antibody levels were determined by using a competitive enzyme-linked immunosorbent assay that measured antibody binding to a protective epitope defined by monoclonal antibody C3.78. The C3.78 OspA antibody titer (>213 microgram/ml) required to eradicate spirochetes from feeding ticks was considerably higher than the titer (>6 microgram/ml) required to block transmission to the host. Although spirochetes were not eradicated from ticks at lower antibody levels, the antibodies reduced the number of spirochetes within the feeding ticks and interfered with the ability of spirochetes to induce ospC and invade the salivary glands of the vector. OspA antibodies may directly interfere with the ability of B. burgdorferi to invade the salivary glands of the vector; alternately, OspA antibodies may lower the density of spirochetes within feeding ticks below a critical threshold required for initiating events linked to transmission.


Subject(s)
Antibodies, Bacterial/physiology , Antigens, Bacterial , Antigens, Surface/immunology , Arachnid Vectors/microbiology , Bacterial Outer Membrane Proteins/immunology , Borrelia burgdorferi Group/immunology , Ixodes/immunology , Ixodes/microbiology , Lipoproteins , Animals , Antibodies, Bacterial/biosynthesis , Antibodies, Bacterial/blood , Bacterial Outer Membrane Proteins/biosynthesis , Bacterial Vaccines , Borrelia burgdorferi Group/growth & development , Female , Host-Parasite Interactions , Lyme Disease/immunology , Lyme Disease/prevention & control , Lyme Disease/transmission , Mice , Salivary Gland Diseases/immunology , Salivary Gland Diseases/microbiology
16.
J Clin Microbiol ; 36(12): 3574-8, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9817875

ABSTRACT

The purpose of the present study was to investigate the transmission of a human isolate of the agent of human granulocytic ehrlichiosis (HGE agent) from infected mice to larval ticks and to examine the population kinetics of the HGE agent in different stages of the tick life cycle. The HGE agent was quantitated by competitive PCR with blood from infected mice and with Ixodes scapularis ticks. The median infectious dose for C3H mice was 10(4) to 10(5) organisms when blood from an infected severe combined immunodeficient mouse was used as an inoculum. Uninfected larval ticks began to acquire infection from infected mice within 24 h of attachment, and the number of HGE agent organisms increased in larval ticks during feeding and after detachment of replete ticks. Molted nymphal ticks, infected as larvae, transmitted infection to mice between 40 and 48 h of attachment. Onset of feeding stimulated replication of the HGE agent within nymphal ticks. These studies suggest that replication of the HGE agent during and after feeding in larvae and during feeding in nymphs is a means by which the HGE agent overcomes inefficiencies in acquisition of infection by ticks and in tick-borne transmission to mammalian hosts.


Subject(s)
Ehrlichiosis/transmission , Ixodes/microbiology , Tick-Borne Diseases/transmission , Animals , Ehrlichia/genetics , Ehrlichia/growth & development , Ehrlichia/isolation & purification , Humans , Larva/microbiology , Mice , Mice, Inbred C3H , Mice, SCID , Polymerase Chain Reaction
17.
Am J Trop Med Hyg ; 58(6): 780-5, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9660463

ABSTRACT

We examined the effect of repeated infestation of guinea pigs with Ixodes scapularis on the capacity of ticks to transmit Borrelia burgdorferi infection. Repeated challenges with nymphs or larvae lead to a reduction in duration of nymphal tick attachment and weight of recovered ticks consistent with the development of tick immunity. Only one of 18 I. scapularis-immune guinea pigs challenged with B. burgdorferi-infected nymphal ticks became infected, whereas 10 of 18 naive guinea pigs similarly challenged became infected. We conclude that tick immunity interferes with borrelial transmission.


Subject(s)
Arachnid Vectors/immunology , Ixodes/immunology , Lyme Disease/prevention & control , Tick Infestations/immunology , Animals , Antibodies, Bacterial/blood , Arachnid Vectors/microbiology , Borrelia burgdorferi Group/immunology , Female , Guinea Pigs , Immunoblotting , Ixodes/microbiology , Larva/immunology , Lyme Disease/transmission , Nymph/immunology , Nymph/microbiology , Skin/parasitology , Time Factors
18.
J Infect Dis ; 177(2): 395-400, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9466527

ABSTRACT

Immune sera from mice infected with the Lyme disease spirochete, Borrelia burgdorferi, have strong biologic activity against spirochetes cultured in vitro. Recent studies with rodents and ticks infected with B. burgdorferi indicate that spirochetes undergo major changes in protein expression as they adapt to the diverse environments encountered by a vectorborne pathogen. The purpose of this study was to explore the susceptibility of three different adaptive forms of B. burgdorferi (in vitro cultured, host-derived, and tickborne) to immune sera. Passive transfer of immune sera protected mice when they were challenged with spirochetes cultured in vitro. Immune sera did not protect mice from tickborne spirochetes or spirochetes derived from infected mice. These results indicate that spirochetes that have adapted within either the feeding tick or host are relatively invulnerable to the protective effects of immune sera, unlike spirochetes grown in vitro, which are highly susceptible.


Subject(s)
Antibodies, Bacterial/analysis , Antibodies, Bacterial/immunology , Borrelia burgdorferi Group/immunology , Host-Parasite Interactions/immunology , Lyme Disease/immunology , Animals , Borrelia burgdorferi Group/growth & development , Immunization, Passive , Ixodes/microbiology , Mice , Mice, Inbred C3H , Specific Pathogen-Free Organisms
19.
Eur J Clin Nutr ; 51(9): 625-32, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9306090

ABSTRACT

OBJECTIVES: This study investigated, on 53 Australians consuming a typical Western diet, the relationship between dietary intake, faecal excretion of carbohydrate and changes in faecal markers believed to be relevant to colon cancer risk, for example faecal output, transit time and concentrations of phenols, ammonia and butyrate. DESIGN: Fifty-three subjects consuming their usual diet were asked to record and weigh all food consumed for a seven day period, and to collect faeces for three days during this period. SETTING: Geelong, Victoria, Australia. SUBJECTS: All volunteers were either staff and students of the university, or associates of the authors. INTERVENTIONS: None. RESULTS: Volunteers had the following dietary intakes of carbohydrate (g/d; mean +/- s.d.); starch 131 +/- 41 (including resistant starch (RS), 5 +/- 2), sugar 108 +/- 37 and non-starch polysaccharides (NSP) 14 +/- 7. Daily faecal output was 127 +/- 70 g and transit time 47 +/- 19 h. Analysis of faecal samples found 0.8 +/- 1.2 g RS and significant relationship with the concentration (mmol/L) of butyrate excreted n faeces (r = 0.34, P < 0.05). Dietary intake of RS was associated with higher concentrations of faecal ammonia (r = 0.34, P < 0.05), but this association was reversed when RS was combined with NSP in the diet (r = 0.07, NS). In contrast to dietary intake, the faecal excretion of RS was negatively related to faecal ammonia concentration (r = -0.40, P < 0.01) and positively related to faecal output (r = 0.64, P < 0.01). Individuals who consumed more NSP in their diet (19 +/- 7 g/d) excreted more than 150 g faeces per day and had higher quantities of faecal-RS and -NSP; faster transit times; higher concentrations of short chain fatty acids and lower concentrations of potentially harmful ammonia and phenols. CONCLUSIONS: The combination of RS and NSP in the colon may be required to achieve an optimal luminal environment conducive to 'colonic health'. The results also support the suggestion that faecal output (< or > 150 g/d) may provide a useful index of colon cancer risk. High faecal outputs are achieved through higher intakes of NSP (the major component of dietary fibre).


Subject(s)
Biomarkers, Tumor , Colonic Neoplasms/diagnosis , Dietary Carbohydrates/administration & dosage , Dietary Carbohydrates/metabolism , Feces , Adolescent , Adult , Aged , Ammonia/analysis , Australia , Butyrates/analysis , Butyric Acid , Colonic Neoplasms/metabolism , Diet , Dietary Fiber/administration & dosage , Fatty Acids/analysis , Feces/chemistry , Female , Gastrointestinal Transit , Humans , Male , Middle Aged , Nitrogen/analysis , Phenols/analysis , Risk Factors
20.
Infect Immun ; 65(8): 3146-50, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9234767

ABSTRACT

Ixodes ticks are infected by Borrelia burgdorferi when larvae feed on spirochete-infected mice. We studied the acquisition of B. burgdorferi by larval ticks, characterized the production of outer surface protein A (OspA) by spirochetes entering larvae, and examined the effects of OspA antibodies on the establishment of B. burgdorferi infections in ticks. Most larvae were infected by spirochetes 24 to 48 h after placement on mice. OspA antibodies stained the first spirochetes observed in larvae, suggesting that OspA is synthesized early during the colonization of the vector. When OspA antibodies were administered to B. burgdorferi-infected mice and larvae were then placed on the animals, the severity of larval infection and the number of infected ticks (7 of 16) were decreased compared with that of controls (15 of 16). The inhibitory effects of OspA antibodies were observed with passive antibody transfer as well as active host-generated immunity. The lower larval infection rate observed in the presence of OspA antibodies was exacerbated after the larval molt since only 1 of 12 nymphs was infected, and none of the mice that were fed upon by these nymphs became infected with B. burgdorferi. Therefore, an OspA antibody response in mice altered the reservoir competence of the vertebrate host by inhibiting the movement of B. burgdorferi from the host to the vector.


Subject(s)
Antibodies, Bacterial/immunology , Antigens, Surface/immunology , Bacterial Outer Membrane Proteins/immunology , Borrelia burgdorferi Group/immunology , Ixodes/microbiology , Lipoproteins , Animals , Antigens, Surface/biosynthesis , Bacterial Outer Membrane Proteins/biosynthesis , Bacterial Vaccines , Immunization, Passive , Larva/microbiology , Mice , Mice, Inbred C3H
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