Search PubMed⌕ Search

Biomedical subjects

Brian Greenwood

Publications and source records attributed to Brian Greenwood.

11 recordsLinked to original sources
PubMed2003

Maternal immunisation in developing countries.

Maternal immunisation could help to prevent the 2-3 million neonatal and early infant deaths that occur in the developing world each year. Determining the causes of neonatal and early infant deaths in developing countries is difficult as most occur at home. However, it is likely that at least half are due to infections, several of which might be prevented by maternal immunisation. Even in poor countries with few health facilities, a high percentage of pregnant women attend an antenatal clinic at least once during pregnancy. Thus, an effective delivery system for maternal immunisation already exists and, because of the success of maternal tetanus immunisation, this approach to the prevention of serious illness or death in young infants is widely accepted by the general population. However, the high prevalence of HIV and malaria found in pregnant women in some parts of the developing world, especially sub-Saharan Africa, could have an effect on the efficacy of maternal immunisation as both of these infections adversely affect placental function. Nevertheless, the potential of maternal immunisation to prevent early infant deaths in developing countries needs to be fully explored. The incidence of pneumococcal infections is high in many developing countries and about 25% of these infections occur at an age before protection could be anticipated following vaccination with a pneumococcal conjugate vaccine in infancy. Thus, a strong case can be made for a trial of the effectiveness of maternal immunisation with a pneumococcal vaccine in preventing serious illness or death in young infants in developing countries.

Adult↗
PubMed2003

The development of Lapdap, an affordable new treatment for malaria.

There is much discussion on how new drugs can be developed for use in developing countries at a price that makes them accessible to those who need them most. The development of a new antimalarial, chlorproguanil/dapsone (Lapdap), provides an example of a way this can be achieved. The idea of combining chlorproguanil with dapsone came from studies done in east Africa in the 1980s. These studies showed, both in vivo and in vitro, that chlorproguanil/dapsone had advantages over sulphadoxine/pyrimethamine. A public-private partnership was established subsequently to manage a development programme of a fixed ratio tablet of this drug combination. The partnership comprised GlaxoSmithKline (formerly SmithKline Beecham), the World Health Organization (WHO), and the UK's Department for International Development (DFID). All clinical, toxicological, and pharmaceutical chemistry studies are complete and the findings have been submitted for regulatory approval. The question now is how Lapdap might be used safely and appropriately if it receives regulatory approval. A public-health group has been formed by WHO (with funding from DFID and the Gates Foundation) to research into this issue. The Lapdap development team completed its objective of submitting Lapdap for drug registration within a period of 5 years and at a low cost. Experience with the development of Lapdap may provide a model for the introduction of other new drugs developed primarily for use in developing countries.

Animals↗
PubMed2003

A health facility based case-control study of effectiveness of insecticide treated nets: potential for selection bias due to pre-treatment with chloroquine.

Case control studies offer an attractive way to assess the effectiveness of insecticide treated nets (ITN) under programme conditions but have the drawback of being susceptible to bias in the choice of controls. We evaluated the potential for pre-treatment with chloroquine to result in misclassification of cases and controls and affect estimates of ITN effectiveness in case control studies in urban and rural clinics in Eastern Afghanistan. During the one-month study, use of ITN showed no effect against malaria in the urban clinic (adjusted odds ratio OR 1.08; 95% CI 0.73-1.6) and the protective effect seen in the rural clinic was not significant (OR 0.62; 95% CI 0.2-2.4). Levels of pre-treatment were high in both clinics: 24% in urban and 19% in rural clinic attenders. In the urban clinic attenders the level of pre-treatment between bed net users and non-users was not significantly different (OR 1.07, 95% CI 0.70-1.64); therefore the misclassification of cases as controls did not introduce any selection bias. Amongst rural clinic attenders, bed net users were less likely to pre-treat with chloroquine than users (OR 0.33, 95% CI 0.14-0.77); this introduced a selection bias that resulted in an underestimation of the effectiveness of bed nets. Case control studies using health facility data are liable to selection bias especially in areas of high pre-treatment rates with chloroquine. Generalisation of results over a wide geographic region, or between urban and rural settings, may not be appropriate.

Adolescent↗
PubMed2003

Effects of misclassification of causes of death on the power of a trial to assess the efficacy of a pneumococcal conjugate vaccine in The Gambia.

BACKGROUND: A reduction in cause-specific mortality may be the most important public health measure of the efficacy of a new vaccine. However, in developing countries, assignment of causes of deaths occurring outside hospitals can be assessed often only through the questioning of relatives about the signs and symptoms leading to death ('post-mortem questionnaire'). Causes assigned in this way have poor sensitivity and specificity. We illustrate the effects of this misclassification on the power of a large trial of a pneumococcal polysaccharide/protein conjugate vaccine with a mortality endpoint. METHODS: Required sample sizes to achieve a study with specified power were calculated for all-cause and acute lower respiratory tract infection (ALRI) mortality for different levels of sensitivity and specificity of post-mortem questionnaires. Data from active community-based surveillance and post-mortem questionnaires collected 1989-1993 from the study area were used in the calculations. FINDINGS: The mortality rate among children aged 6-29 months from all causes was 34.2 per 1000 child-years; 19% of deaths were attributable to ALRI. Assuming that pneumococci would be responsible for 50% of ALRI deaths and that the vaccine would cover 70% of disease serotypes and would be 90% effective against these serotypes, the expected efficacy of the vaccine would be 6.0% (19% x 50% x 70% x 90%) against all causes combined and 31.5% (50% x 70% x 90%) against deaths from ALRI. If, as suggested by various reports, the sensitivity and specificity of assigning a death to ALRI by post-mortem questionnaire are about 40% and 90% respectively, then the observed vaccine efficacy against ALRI (as classified using the post-mortem questionnaire) would fall to 20%, and the power to detect this would be reduced by approximately 40%. Furthermore, low sensitivity of diagnosis would lead to a falsely low estimate of the burden of ALRI mortality in the population and the trial might have greater power to detect a reduction in mortality from all causes combined than that estimated at the outset. CONCLUSIONS: Low sensitivity and specificity of diagnosis by post-mortem questionnaire may mean that the power of a trial to detect a reduction in all-cause mortality is similar to that to detect a reduction in ALRI mortality. Since the latter is more susceptible to bias from misclassification of cause of death, all-cause mortality may be the most suitable endpoint. Similar considerations apply to trials of interventions against other diseases for which a cause-specific endpoint is subject to substantial misclassification.

Africa↗
PubMed2002

Treatment uptake by individuals infected with Plasmodium falciparum in rural Gambia, West Africa.

OBJECTIVE: To find out what proportion of Plasmodium falciparum infections are treated in rural Gambia. METHODS: Subjects from four villages in the Gambia were followed over nine months through visits to village health workers. Monthly cross-sectional malaria surveys measured the prevalence of P. falciparum infection. Linked databases were searched for treatment requests. Treated cases were individuals with parasitaemia who requested treatment during narrow or extended periods (14 or 28 days, respectively) before or after a positive blood film was obtained. FINDINGS: Parasite prevalence peaked in November 1998, when 399/653 (61%) individuals had parasitaemia. Parasite prevalence was highest throughout the study in children aged 5-10 years. Although access to treatment was better than in most of sub-Saharan Africa, only 20% of infected individuals sought medical treatment up to 14 days before or after a positive blood film. Within two months of a positive blood film, 199/726 (27%) individuals with parasitaemia requested treatment. Despite easy access to health care, less than half (42%) of those with parasite densities consistent with malaria attacks (5000/ l) requested treatment. High parasite density and infection during October-November were associated with more frequent treatment requests. Self-treatment was infrequent in study villages: in 3/120 (2.5%) households antimalarial drugs had been used in the preceding malaria season. CONCLUSION: Many P. falciparum infections may be untreated because of their subclinical nature. Intermittent presumptive treatment may reduce morbidity and mortality. It is likely that not all untreated infections were asymptomatic. Qualitative research should explore barriers to treatment uptake, to allow educational interventions to be planned.

Adolescent↗
PubMed2002

Malaria--a shadow over Africa.

Reduction in severe disease and death from falciparum malaria in Africa requires new, more effective and inexpensive public health measures. The completed genomes of Plasmodium falciparum and its vector Anopheles gambiae represent a big step toward the discovery of these needed tools.

Africa South of the Sahara↗
PubMed2002

Malaria in 2002.

The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used.

Africa↗
PubMed2002

Use of clinical algorithms for diagnosing malaria.

Several attempts have been made to identify symptoms and signs based algorithms for diagnosing malaria. In this paper, we review the results of published studies and assess the risks and benefits of this approach in different epidemiological settings. Although in areas with a low prevalence the risk of failure to treat malaria resulting from the use of algorithms was low, the reduction in the wastage of drugs was trivial. The odds of wastage of drugs increased by 1.49 (95% confidence limit 1.45-1.51) for each 10% decrease in the prevalence of malaria. In highly endemic areas the algorithms had a high risk of failure to treat malaria. The odds of failure to treat increased by 1.57 (95% confidence limit 1.50-1.65) for each 10% increase in the prevalence. Furthermore, the best clinical algorithms for diagnosing malaria were site-specific. We conclude that the accuracy of clinical algorithms for diagnosing malaria is not sufficient to determine whether antimalarial drugs should be given to children presenting with febrile illness. In highly endemic areas where laboratory support is not available, the policy of offering antimalarial drugs to all children presenting with a febrile illness recommended by the integrated child management initiative is appropriate.

Algorithms↗
PubMed2002

The molecular epidemiology of malaria.

This review discusses how the use of molecular genetic techniques such as the polymerase chain reaction are helping in the management and prevention of malaria.

Animals↗