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Biomedical subjects

S K Obaro

Publications and source records attributed to S K Obaro.

At least 19 recordsLinked to original sources
PubMed2000

Prospects for pneumococcal vaccination in African children.

Streptococcus pneumoniae (pneumococcus) remains a major cause of morbidity and mortality in both developed and undeveloped countries. Accurate disease burden estimates for developing countries and Africa in particular, where diagnostic facilities are less adequate and a disease surveillance system virtually non-existent, is difficult. However, from conservative estimates, the pneumococcus is probably responsible for at least 1 million of the 4 million deaths that occur from acute lower respiratory infections in children aged less than 5 years. The global burden of disease has been accentuated by the rising menace of multi-drug resistant strains, which defy geographic and racial borders. Thus, now more than ever before, there is an urgent need to identify and implement preventive measures to avert this problem. The currently licensed pneumococcal polysaccharide vaccine, comprises 23 capsular polysaccharides of the pneumococcus, many of which are poorly immunogenic in the very vulnerable age group of under-fives. A possible solution to the problem of poor immunogenicity is to use a protein/polysaccharide conjugate vaccine similar to that recently introduced successfully for Haemophilus influenzae type b (Hib) and using this approach, several workers have reported promising results from safety and immunogenicity studies. However, unlike Hib, the development of conjugate vaccine against pneumococcal disease is complicated by the existence of more serotypes than can be feasibly incorporated in a single conjugate vaccine formulation. Whilst this challenge has been taken on by some vaccine manufacturers, novel approaches such as the identification or construction of protective protein antigen, common to all clinically important strains are being explored. Novel application of the pneumococcal polysaccharide vaccines in pregnancy for protection of disease in early infancy is an approach that has not been evaluated. For maximum impact, the ultimate vaccine formulation should be affordable and available to resource poor countries where the burden of disease is highest. Establishing disease surveillance systems in such countries now will greatly facilitate the introduction of the vaccines.

Adhesins, Bacterial↗
PubMed2000

Diagnosis of childhood pneumonia in the tropics.

Recent global estimates indicate that there are 10 million deaths annually of children aged < 5 years and that 99% of these deaths occur in developing countries, with 70% caused by infections. Pneumonia is the leading cause of the infection-attributable mortality in this age-group, accounting for > 2 million of the deaths. These deaths are potentially preventable if appropriate clinical and laboratory tools are in place to facilitate early detection of the pneumonia, identification of the pathogen involved, and institution of appropriate therapy or, even better, implementation of appropriate vaccination schedules. The currently available tools for the diagnosis of acute, lower-respiratory-tract infections in children have low sensitivity and are, in any case, grossly underutilized. Consequently, there is a great shortage of the data necessary for implementing potentially effective, intervention measures. This review is of the common aetiological agents of childhood pneumonia in the tropics and of the clinical and laboratory techniques currently available for routine diagnosis. Although there are newer and more sensitive diagnostic tools, they are expensive and are not likely to be within reach of most developing countries in the tropics. There is, however, considerable scope to improve the use of the cheaper techniques, and so facilitate the development and implementation of effective control measures.

Child, Preschool↗
PubMed2000

Electrolyte derangement in cerebral malaria: a case for a more aggressive approach to the management of hyponatraemia.

Although hyponatraemia has been consistently shown to occur in a large proportion of children with cerebral malaria, no statistical relationship has been established between the incidence of hyponatraemia and that of malaria-attributable mortality. However, hyponatraemia is not a benign state in other conditions (such as meningitis) or in surgical patients, and is likely to add to malarial deaths. The high mortality rate seen among cases of cerebral malaria, despite all efforts to curb it, therefore calls for a more aggressive approach to the management of hyponatraemia. Current methods for the administration of hypotonic saline and isotonic glucose solutions need review. In addition, children admitted with cerebral malaria should have their electrolyte status monitored to identify new or ongoing hyponatraemia. When hyponatraemia is discovered, it should be quickly and actively corrected.

Child↗
PubMed2000

Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants.

BACKGROUND: Unrelenting high morbidity and mortality have mandated that immunogenic vaccines be used to combat pneumococcal disease in infants. OBJECTIVES: To evaluate the safety and immunogenicity of a nonavalent pneumococcal conjugate vaccine and the antigenic interaction when administered simultaneously with diphtheria, tetanus and pertussis vaccines. METHODS: Two hundred seven infants were randomized to receive three doses of either nonavalent protein conjugate pneumococcal vaccine (PnCV) or inactivated polio vaccine (IPV) at 2, 3 and 4 months of age with routine Expanded Program of Immunization vaccines as scheduled. Vaccinees were visited on Days 1, 2 and 7 to observe local and systemic adverse reactions. Blood was drawn before the first dose and 1 month after the third dose. Antibody concentrations in sera were measured by standardized enzyme-linked immunosorbent assay. Nasopharyngeal carriage of pneumococci was tested at 5 and 9 months of age. RESULTS: No serious reactions were observed. Local induration and tenderness were observed more commonly at the site of administration of diphtheria, tetanus and pertussis vaccines than at the site of administration of IPV or PnCV. Between 79 and 91% achieved >1 microg/ml antibody against specific pneumococcal serotypes. Antibody responses to diphtheria and pertussis antigens were similar in both groups; however, antibody response to tetanus toxoid was significantly lower in infants who received PnCV (geometric mean concentration, 11.1 vs. 17.4; P < 0.001). Nasopharyngeal carriage in PnCV-vaccinated children was reduced but not significantly different from those vaccinated with IPV. CONCLUSION: Simultaneous administration of PnCV with Expanded Program of Immunization vaccines is safe and immunogenic. immune response to the composite antigens is likely to confer protection.

Antibodies, Bacterial↗
PubMed1999

The host response in malaria and depression of defence against tuberculosis.

Malaria causes significant morbidity and mortality world-wide. Both asymptomatic and symptomatic malarial infections cause immune depression, which predisposes the host to infection with other microorganisms. Specific clinical investigations have shown, for example, that those with malaria-attributable anaemia are particularly likely to have Salmonella septicaemia, and that asymptomatic malarial infection causes diminished response to polysaccharide vaccine. The results of clinical studies and experiments with animal models have revealed that malarial parasites can decrease their vertebrate host's effective humoral and cellular immune responses. In this review, the possible ways in which this malaria-induced immune impairment could affect the host's response to Mycobacterium tuberculosis infection are considered. Could malarial infection be one of the reasons for the persistence of tuberculosis in malaria-endemic regions?

CD4-CD8 Ratio↗
PubMed1998

An efficacy trial of the malaria vaccine SPf66 in Gambian infants--second year of follow-up.

In 1994, 630 Gambian infants were immunized with three doses of the synthetic polypeptide malaria vaccine SPf66 or with a control vaccine. No significant protection against first or total attacks of malaria was observed among the children who received SPf66. However, the period of follow-up was short. Thus, 532 children were followed for a second malaria transmission season during which 291 episodes of malaria were detected. Protective efficacies of SPf66 against first attacks of malaria and against all attacks of malaria were 8% [95% CI-20%, 30%] and 2% [95% CI-26% 24%] respectively. SPf66 did not provide any significant degree of protection to Gambian infants during a second year of follow-up.

Animals↗
PubMed1997

Follow-up of Gambian children recruited to a pilot safety and immunogenicity study of the malaria vaccine SPf66.

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 was undertaken in The Gambia in 1993. One hundred and fifty infants aged 6-11 months were immunized with either 0.5 mg or 1.0 mg of SPf66 produced either in Colombia or in the USA or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance and the difference in incidence between children who had received high dose Colombian vaccine and the control children was statistically significant at the 5% level. During the 1995 malaria transmission season, 127 children from the original cohort of 150 were observed. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine (6.23 vs 4.89 clinical attacks per 1000 days at risk), the effect being most marked among children who were in the high dose groups, but differences between groups were now no longer statistically significant.

Child↗
PubMed1997

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↗
PubMed1996

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↗