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Biomedical subjects

S Bennett

Publications and source records attributed to S Bennett.

At least 253 records · Page 14Linked to original sources

Analysis of survival data by the proportional odds model.

A model is presented for the analysis of lifetime data in which the rates of mortality for separate groups of patients converge with time. A non-parametric estimate is given for the survivor function. The theoretical basis for the model assumes that prognostic factors have a multiplicative effect on the odds against survival beyond any given time. The model is fitted to data using maximum likelihood estimation, and an example of its use in the analysis of a lung cancer trial is given.

Epidemiologic Methods↗

The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy.

A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult. Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies (87%) recorded in 16 villages over a 3-year period. Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo, and their babies were significantly heavier (6% low birth weight vs 22%). In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae. However, the mean birth weight of babies born to grandemultigravidae who received chemoprophylaxis was significantly higher than that of babies born to grandemultigravidae who did not.

Antimalarials↗

A comparative study of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine and dapsone) as chemoprophylactics against malaria in Gambian children.

A comparison has been made of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine +dapsone) as malaria chemoprophylactics when given every two weeks for 3 years to Gambian children under the age of 5 years. Both drugs produced falls in spleen and malaria parasite rates and an increase in packed cell volume. Maloprim, but not chlorproguanil, significantly reduced the incidence of episodes of fever accompanied by malaria parasitaemia. Children who received Maloprim, but not those who received chlorproguanil, grew better than children in the placebo group. This finding suggests that brief clinical episodes of malaria are more important in impairing growth than more prolonged periods of asymptomatic parasitaemia. No serious side-effect attributable to either drug was observed. After chemoprophylaxis had been given for 3 malaria transmission seasons the level of resistance of Plasmodium falciparum to pyrimethamine and to chlorproguanil was about 10%.

Animals↗

Recognition of dominant T cell-stimulating epitopes from the circumsporozoite protein of Plasmodium falciparum and relationship to malaria morbidity in Gambian children.

Cellular immune responses to the Plasmodium falciparum circumsporozoite (CS) protein were measured by proliferation and interferon-gamma production in a cohort of children aged 3 to 8 years, living in The Gambia. Anti-CS antibody titres, malariometric indices and sickle cell status were also determined. Malaria morbidity in the ensuing malaria transmission season was monitored by weekly health questionnaire, axillary temperature measurements and examination of blood films. Exposure to malaria was inferred from entomological data collected during the transmission season. Immunological and parasitological measurements were repeated at the end of the rainy season. Immunological findings were compared between children who experienced clinical malaria or asymptomatic infection and children who had no evidence of infection. No association was found between cellular immune responses to the CS protein at the beginning of the transmission season and subsequent susceptibility to infection except among children with high titres of antibody to (NANP)40. Seropositive children who did not become infected had a higher mean proliferative response to the Th3R epitope than seropositive children who did become infected. High titres of anti-(NANP)40 antibodies alone were not protective. Responses to the Th2R epitope were significantly higher at the end of the rainy season than at the beginning in children who experienced an asymptomatic infection. Responses to variant sequences of the 2 epitopes were highly correlated at an individual level but there was no correlation between proliferative and interferon responses to a particular epitope.

Animals↗

Differential antibody response of Gambian donors to soluble Plasmodium falciparum antigens.

A seroepidemiological and clinical study was performed in an area of West Africa (The Gambia) where Plasmodium falciparum is endemic with seasonal transmission. Plasma samples were tested by intermediate gel immunoelectrophoresis for antibodies against 7 soluble P. falciparum antigens. There were marked differences in the age-related pattern of antibody response to the different antigens. Antibodies to 4 of the antigens were acquired slowly with a maximum prevalence reached after 25-35 years of age. Antibodies against the 3 remaining antigens, including the endotoxin-like antigen, Ag7, were acquired earlier with a plateau of maximum prevalence reached after 5-11 years, i.e. at the time when morbidity due to malaria decreased. Children who had not appeared to be infected with malaria during the preceding transmission season had lower levels of antibodies to soluble antigens than did children who had had a documented attack of clinical malaria or parasitaemia. There was no difference in antibody profiles to soluble antigens between children with sickle cell trait and children with normal haemoglobin.

Adolescent↗

Association between immune recognition of the malaria vaccine candidate antigen Pf155/RESA and resistance to clinical disease: a prospective study in a malaria-endemic region of west Africa.

We have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen Pf155/RESA in a longitudinal, prospective study of clinical immunity to Plasmodium falciparum malaria in a cohort of 354 Gambian children aged 3-8 years. A significant association was observed between presence of antibodies to the 3' repeat region peptide (EENV)6 and resistance to clinical malaria. The prevalence of protective antipeptide antibodies varied significantly between different ethnic groups, suggesting that immune recognition of some Pf155/RESA epitopes may be genetically regulated. There was no obvious association between proliferative or interferon gamma responses to T cell epitopes of Pf155/RESA and resistance to malaria infection or disease. At an individual level, the presence of peptide-binding antibodies was associated with the induction of interleukin 4 messenger ribonucleic acid expression in T cells activated with the overlapping T cell epitope EENVEHDA(EENV)2. This suggests that measurement of interleukin 4 production by T cells may represent a functional assay for T helper activity.

Animals↗

Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia.

Morbidity from Plasmodium falciparum malaria and humoral and in vitro cellular immune responses to defined malaria antigens were measured in rural Gambian children with haemoglobin phenotype AS (HbAS) and in those with a normal haemoglobin (HbAA). In a survey undertaken during the dry season, HbAS children had a higher parasite rate than HbAA children but a lower prevalence of parasitaemia at a level of 500/microliters or greater. Malariometric indices measured during a rainy season survey were similar in the 2 groups of children. During the rainy season, the incidence of infection with P. falciparum did not vary with haemoglobin phenotype. However, in children aged 6 years or less, a significantly smaller proportion of HbAS children who acquired infection developed clinical symptoms than did HbAA children. During both the dry season and rainy season surveys, humoral and in vitro cellular immune responses to defined antigens from the sporozoite and merozoite stages of P. falciparum were similar in the 2 groups of children. Thus, despite the differences in parasite indices and morbidity from malaria between the 2 groups of children, we found no evidence of an enhanced immune response to malaria infection amongst HbAS children compared with normal children.

Amino Acid Sequence↗

Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children.

Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin-lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗

Human leucocyte antigen (HLA) and malaria morbidity in a Gambian community.

Human leucocyte antigen (HLA) class I and class II typing was performed on 177 children in a rural area of The Gambia who were followed for 2 years in a longitudinal study of malaria morbidity. A comparison was made between those who experienced an episode of clinical malaria in one or both years and those who showed no evidence of infection in either year. No convincing association was found between morbidity and class I phenotype. An overall association of morbidity with the distribution of class II haplotypes was seen, but association with individual DR-DQ haplotypes were not conclusive.

Animals↗

Malaria prevalence is inversely related to vector density in The Gambia, West Africa.

Baseline epidemiological and entomological studies were conducted in 5 different areas of The Gambia before the introduction of a national malaria control programme, the objective of which was to treat all the bed nets belonging to people living in primary health care villages with insecticide. All malariometric indices used (parasite density, parasite rates, splenomegaly, and packed cell volume) indicated that malaria transmission was more intense in the east of the country than elsewhere. High transmission in the east was associated with a high sporozoite rate but not with the greatest vector abundance; the lowest malaria prevalence rates were found in villages which were close to very productive breeding sites of Anopheles gambiae s.l. Bed net usage was strongly correlated with vector density and the highest malaria rates were found in villages where bed net usage was relatively low. These results suggest that in The Gambia malaria prevalence rates are reduced where nuisance biting by mosquitoes is sufficient to encourage the population to protect themselves with bed nets.

Animals↗

Low level ivermectin coverage and the transmission of onchocerciasis.

Regular collections of biting Simulium damnosum s.l. were carried out during a community-based trial of doses of ivermectin every 6 months for onchocerciasis in Sierra Leone. Over 64,000 blackflies were caught at 4 sites close to treated villages and one site near an untreated village. More than 17,000 of these blackflies were dissected during the 31 months of the study and 5 doses of ivermectin were distributed to about 30% of the human population in the treated villages. High annual biting rates (about 100,000 bites per year) and transmission potentials (about 5000 larvae per year) were found at all catching sites. Approximately 30% of parous blackflies carried Onchocerca volvulus larvae, and 8% had infective stage larvae. None of these indices appeared to be affected by the distribution of ivermectin. However, the mean number of larvae per infected blackfly fell from 8.7 to 5.8 during the study period in the treated villages, equivalent to a 21% decrease per year. No such reduction was seen in the control village. This study demonstrates that in areas where high capacity vectors predominate, the effect on transmission of even a low coverage of the human population with repeated doses of ivermectin may be detectable using the sensitive entomological index of intensity of infection in infected flies. Statistical analysis of onchocerciasis transmission data is a complex issue and ways of improving the design of trials and applying appropriate statistical methods are discussed.

Animals↗

A comparison of the efficacy of insecticide-treated and untreated bed nets in preventing malaria in Gambian children.

An evaluation of the Gambian national insecticide bed net programme, which has introduced insecticide treatment of bed nets into all primary health care (PHC) villages in The Gambia, provided an opportunity to compare the individual risk of malaria in children who slept under untreated or insecticide-treated bed nets. 2300 children 1-4 years old were selected for a survey at the end of the 1992 rainy season, 1500 from PHC villages and 800 from non-PHC villages. All malariometric indices were lower, and the mean packed cell volume was higher, in children who slept regularly under treated or untreated bed nets than in those who did not use a net. This study suggested that untreated bed nets provide some individual protection against malaria, although not as efficiently as that provided by insecticide-treated bed nets which were particularly effective at preventing infections accompanied by high parasitaemia.

Bedding and Linens↗

Socio-economic risk factors for malaria in a peri-urban area of The Gambia.

Successful control of malaria depends upon a detailed knowledge of its epidemiology, including knowledge of the social and economic factors that influence its prevalence. Little is known about the socio-economic factors that influence the prevalence of malaria in tropical Africa. Therefore, we undertook such a study in over 350 Gambian children with malaria resident in a peri-urban area with seasonal transmission, using the case-control approach. Malaria was associated with poor quality housing and crowding and with travel to rural areas, where the level of malaria transmission is higher than in urban centres. No association was found between the risk of malaria and the overall education level of parents or guardians of study children. However, the knowledge of malaria possessed by mothers of cases of malaria was less than that of controls, suggesting that further education of the study community on the causation of malaria and on ways of preventing it could be of value.

Case-Control Studies↗

Socio-economic determinants are not major risk factors for severe malaria in Gambian children.

Only a small proportion of subjects infected with Plasmodium falciparum develop severe disease. Why this should be is not fully understood. To investigate the possible importance of socio-economic variables on the severity of malaria in Gambian children we undertook a case-control study of 384 children with severe or mild malaria. Few differences were found between the 2 groups. Children with severe malaria had a longer duration of symptoms when recruited than mild cases but this difference was largely accounted for by the fact the most children with severe disease were recruited at a referral hospital, whilst mild cases were recruited at a primary health care facility nearer their home. There was no difference between groups in the time before mothers sought some form of health care. Mothers of children with severe disease were less ready to take their child to hospital than mothers of mild cases, suggesting that education on the importance of taking a child with features of malaria to a health centre as soon as possible might have some effect on the development of severe disease. However, overall, the results of this study suggested that socio-economic and behavioural factors are not the major determinants for severe malaria in African children.

Attitude to Health↗

The risk of enteric infections associated with wastewater reuse: the effect of season and degree of storage of wastewater.

The effect of season and wastewater storage on the risk of Ascaris lumbricoides infection and diarrhoeal disease associated with wastewater reuse was studied in Mexico in 1991. Data were collected from 10,489 individuals during a dry-season survey. Exposure was to untreated wastewater, or effluent from 1 reservoir (< or = 1 nematode egg/L), or no wastewater irrigation (control group). The results were compared with a previous rainy-season survey which included effluent from 2 reservoirs in series. Direct exposure to untreated wastewater was associated with an excess risk of A. lumbricoides infection in children aged < 5 years (OR = 18.0) and persons aged > 5 years (OR = 13.5) and an increased risk of diarrhoea, particularly to children aged < 5 years (OR = 1.75); effects were stronger in the dry than in the rainy season. There was also an excess risk associated with the 1-reservoir group for A. lumbricoides infection (OR = 21.2 and 9.4) and for diarrhoeal disease (OR = 1.1 and 1.5) but little excess associated with the 2-reservoirs group. Therefore, wastewater retention in 1 reservoir (quality 10(5) faecal coliforms/100 mL, < or = 1 egg/L) does not significantly reduce risks of Ascaris infection and diarrhoeal disease whereas retention in 2 reservoirs in series (quality 10(3) faecal coliforms/100 mL, no detectable eggs/L) does.

Adolescent↗

The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia.

In 1992, the Gambian national impregnated bed net programme (NIBP) introduced insecticide treatment of bed nets into half of the primary health care villages in The Gambia. One component of the evaluation of this programme was the determination of whether it had any impact on the outcome of pregnancy in primigravidae. From February 1992, 651 primigravidae were recruited into the study. Less than 50% of them used an insecticide-treated bednet. During the rainy season the prevalence of Plasmodium falciparum among primigravidae was lower, fewer babies were classified as premature, and the mean birth weight was higher in villages where treated bed nets were used than in control villages. Therefore, during the rainy season, despite the low use of insecticide-treated bed nets by Gambian primigravidae, the NIBP had some impact on the outcome of pregnancy, particularly on the percentage of premature babies, and this was probably due to the decreased risk of malaria infection achieved during this period.

Adolescent↗

The interaction between Plasmodium falciparum and P. vivax in children on Espiritu Santo island, Vanuatu.

Studies of the prevalence and incidence of malaria were conducted in children < 10 years old living in 10 rural villages on the island of Espiritu Santo, Vanuatu, south-west Pacific. Malaria prevalence remained stable at 30% throughout the year but the relative contributions of the 2 major species were highly dependent on season. Plasmodium falciparum predominated in the long wet season (November-May) and P. vivax in the dry season (June-October). Case definitions for malaria, derived using a multiple logistic regression method, showed that parasite densities associated with clinical disease were low; case definitions for P. falciparum (> 1000 parasites/microL in children > 1 year old and > 500 microL in infants) and P. vivax (> 500 parasites/microL at all ages) were both associated with a specificity and sensitivity of > 90%. Like prevalence data, malaria morbidity was highly seasonal; 80% of clinical P. falciparum infections occurred in the wet season and 66% of clinical P. vivax in the dry season. Mixed infections were rare. Malaria was important cause of morbidity with children < 5 years old experiencing 1.3-3.0 episodes of clinical malaria per year and 23% of fevers being attributable to malaria in this age group. Children aged 5-9 years continued to suffer one episode of clinical malaria per year. The peak incidence of P. vivax malaria occurred earlier in life than the peak incidence of P. falciparum malaria. The possible interactions between these 2 parasite species are discussed.

Animals↗

The Gambian National Impregnated Bed Net Programme: evaluation of effectiveness by means of case-control studies.

Two case-control studies, one on mortality and the other on malaria morbidity, were carried out in order to evaluate the impact of the Gambian National Insecticide Bed Net Programme during the second year of intervention and to explore the feasibility of such a study for the evaluation of programme effectiveness. For the mortality study, children 1-9 years old who died during the 1993 rainy season were matched by age and sex with 2 healthy controls from the same village. For the morbidity study, children 1-9 years old attending Fatoto or Jahalia Health Centres in The Gambia and who had fever and parasitaemia > or = 5000/microL were matched by age with a child attending the health centres without fever or parasitaemia. An additional healthy control was recruited from the case's village. No impact of insecticide-treated bed nets on mortality was detected and this was in keeping with the results obtained by prospective surveillance. A protective effect of insecticide-treated nets on malaria morbidity was detected when cases were compared with controls recruited at the health centres. However, this disappeared when cases were compared with controls recruited from the cases' villages. The mortality case-control study suggested that reducing the time between onset of disease and treatment may have an important impact on childhood mortality. In order to calculate programme cost-effectiveness, important for informed resource allocations to be made by health managers, it is essential to obtain evidence of effectiveness. This can be done by means of case-control studies, which are easier to carry out and require fewer resources than prospective surveillance. Nevertheless, it is necessary to be conscious of their pitfalls, particularly of the bias involved in the choice of cases and controls. The measurement of insecticide on the nets of the cases or controls is essential for such studies.

Case-Control Studies↗