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Biomedical subjects

M A Monteil

Publications and source records attributed to M A Monteil.

9 recordsLinked to original sources

Asthma in the English-speaking Caribbean.

The prevalence of asthma in the Caribbean is high and seems to be increasing. Asthma research in this region has been biased towards the paediatric population and there is little published on adult disease. There is a high prevalence of other allergic diseases in the patients studied, with skin reactivity to at least one allergen in 50-81% of subjects. Reactivity to house dust mite, especially Dermatophagoides pteronyssinus, occurred most commonly and sensitivity to this mite correlated with high levels of mite proteins in mattress and bedroom dust. Asthmatic admissions to hospitals are highest in the last quarter of the year but fall to their lowest levels in April. Admission rates are influenced by climatic variables such as relative humidity and wind speed. In some territories current management of asthma remains reliant on the use of oral bronchodilators with underutilization of inhaled beta-agonists and corticosteroid preparations.

Adolescent

A glycoprotein pneumococcal conjugate vaccine primes for antibody responses to a pneumococcal polysaccharide vaccine in Gambian children.

BACKGROUND: Streptococcus pneumoniae is a major cause of acute respiratory infections and acute bacterial meningitis in children. Pneumococcal polysaccharide vaccines are poorly immunogenic in this highly vulnerable group, but protein polysaccharide conjugate vaccines are likely to be more effective. OBJECTIVES: To determine whether immunization of infants with a pneumococcal conjugate vaccine induces immunologic memory. METHODS: Eighty-four Gambian children, who had been vaccinated previously with two or three doses of a pentavalent pneumococcal conjugate vaccine (CRM197) or with a Haemophilus influenzae type b (Hib) conjugate vaccine were immunized when approximately 2 years old with a 23-valent pneumococcal polysaccharide vaccine, and a blood sample was obtained 10 days later. Pneumococcal antibody titers in prevaccination and postvaccination sera were measured by enzyme-linked immunosorbent assay and by an opsonophagocytic assay. RESULTS: On revaccination with a pneumococcal polysaccharide vaccine, children who had previously received pneumococcal conjugate vaccine had higher antibody concentrations to each of the five polysaccharide components of the conjugate vaccine than did control children. For type 6B polysaccharide, which is poorly immunogenic in young children, postvaccination antibody concentrations were 0.37, 27.6 and 50.9 microg/ml in children who had received no previous pneumococcal immunization or two or three doses of conjugate vaccine, respectively. Type 14 antibodies produced after revaccination were of high avidity and had opsonic activity. CONCLUSION: Vaccination of young infants with two or three doses of a pneumococcal conjugate vaccine primes the immune system to respond strongly and rapidly on subsequent exposure to pneumococcal polysaccharide.

Antibodies, Bacterial

Defective antibody-mediated opsonisation of S. pneumoniae in high risk patients detected by flow cytometry.

Invasive pneumococcal infection continues to be a significant cause of morbidity and mortality especially in patients with antibody deficiencies and disorders affecting the reticulo-endothelial system. Current recommendations for prophylaxis in these patients include immunization with 23-valent pneumococcal polysaccharide capsular vaccines. Post-immunization responses are commonly assessed by measuring serum antibody levels. However, there is no defined protective antibody range and this approach fails to determine the functional capacity of the antibodies. A simple, reproducible flow cytometric method of assessing the antibody-mediated opsonic activity against S. pneumoniae is described. This assay detected defective opsonic function in post-immunized at-risk patients who developed invasive pneumococcal infection.

Adult

Mannose binding protein gene mutations associated with unusual and severe infections in adults.

A defect in opsonisation can cause a common immunodeficiency. A mutation in mannose binding protein (MBP) caused by point mutations in the MBP gene will lead to such a defect. This type of syndrome can cause recurrent infections in infants between 6 and 18 months of age but is not generally believed to predispose to adult infections. We looked at 4 patients with severe and unusual infections in whom MBP gene mutations were the only identified cause of immunodeficiency and one patient with combined MBP and IgA deficiency. We analysed the MBP genotypes of all the patients in whom we suspected an immunodeficiency because of their clinical history. Infections seen were recurrent skin abscesses, chronic cryptosporidial diarrhoea, meningococcal meningitis with recurrent herpes simplex, and fatal klebsiella lobar pneumonia. Both sexes were affected and ages ranged from 15 to 56 years. Two patients were homozygous for codon 54 mutations, one patient had codon 52 and codon 54 mutations and was phenotypically homozygous, and two patients were heterozygous for codon 54 mutations. Individuals homozygous for MBP mutations are unusual in the general population (approximate frequency 0.3%). The occurrence of three homozygotes for MBP mutations among these five infected patients suggests that MBP deficiency may confer a life-long risk of infection.

Adolescent

Relationship of in vitro phagocytosis of serotype 14 Streptococcus pneumoniae to specific class and IgG subclass antibody levels in healthy adults.

The role of specific IgG2 antibody in the protection against serious infection with Streptococcus pneumoniae is unclear. We therefore decided to investigate the relationship between serum antibody levels and opsonization and phagocytosis of this microorganism. We have measured serum IgM, IgA and IgG subclass antibody specific for pneumococcal capsular polysaccharide and in vitro phagocytosis of serotype 14 pneumococcus by polymorphs, in healthy adults before and after immunization with Pneumovax II. IgM and IgG2 were the predominant anti-pneumococcal antibodies seen, IgA and IgG1 being present at low titre. No significant relationship of phagocytosis with specific IgM and IgA antibodies was found. However, both specific IgG1 and IgG2 antibodies in post-immunization sera correlated significantly with phagocytosis of the pneumococcus in the presence of complement (r = 0.57, P = 0.029 and r = 0.59, P = 0.022 respectively). After heat-inactivation, the remaining opsonic activity of sera correlated only with levels of specific IgG2 antibody (r = 0.61, P = 0.0006). Whereas phagocytosis supported by specific IgG1 and IgG2 antibody to serotype 14 pneumococcus after immunization is mediated by complement activation, IgG2-specific antibody in high titre may also be able to function by complement-independent interaction with Fc gamma receptors on polymorphs.

Adult

Specific IgG subclass antibody levels and phagocytosis of serotype 14 pneumococcus following immunization.

Complement and specific antibody directed against capsular polysaccharide are necessary for efficient phagocytosis of pneumococci. In normal adults, specific antibody to pneumococci is predominantly of the IgG2 subclass. However, the role of IgG2 in bacterial clearance is debatable. We therefore decided to investigate the relationship between specific IgG subclass antibody levels and phagocytosis of serotype 14 pneumococcus, before and after immunization with a pneumococcal capsular polysaccharide vaccine. Specific IgG subclass antibody was measured by an ELISA technique and the effect of serum on phagocytosis of radiolabelled pneumococci by normal polymorphs was determined. We found that in the presence of complement, phagocytosis correlated significantly with both specific IgG1 and IgG2 antibody titres (r = 0.547, P = 0.002 and r = 0.464, P = 0.009, respectively). However, in decomplemented sera, the correlation with IgG1 antibody was lost, whereas that with IgG2 antibody was strengthened (r = 0.641, P = less than 0.001). The possibility that IgG2 binds to receptors on polymorphs should be considered.

Adult

Staphylococcal opsonization and anti-Staphylococcus aureus IgG subclass antibodies in patients with severe or recurrent S. aureus infections.

Opsonization of Staphylococcus aureus (Oxford strain) and specific IgG subclass antibodies against formalised staphylococci were measured in plasmas from 27 patients with significant S. aureus infections and 35 healthy adults and 15 children. There were no statistically significant differences in the IgG2 and IgG4 levels between two groups and IgG3 was not detected, but the median plasma IgG1 level was significantly higher in patients with staphylococcal infections (P less than 0.00003). The concentration of IgG2 anti-S. aureus antibodies was 25-47 times greater than that of IgG1. If plasmas were decomplemented, the raised IgG1 levels were associated with increased opsonophagocytosis by normal neutrophils (P less than 0.0002).

Abscess