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Biomedical subjects

R J Hayes

Publications and source records attributed to R J Hayes.

At least 91 records · Page 5Linked to original sources

Evaluation of a primary health care programme in The Gambia. II. Its impact on mortality and morbidity in young children.

Mortality and morbidity in children under 5 years of age were measured in 41 villages and hamlets in a rural area of The Gambia for a 1-year period before and for a 3-year period after the introduction of a primary health care (PHC) programme into 15 of the larger villages in the area. Both infant mortality and child mortality rates fell during the post-intervention period but declines were similar in PHC and in non-PHC villages suggesting that factors such as an up-grading of the Farafenni dispensary, improvements in transport and the survey itself may have played an important part in bringing about these changes. Measurements of morbidity showed a lower prevalence of diarrhoea, vomiting or severe cough in PHC villages after the introduction of the PHC programme. Introduction of the PHC programme had no significant effect on nutritional status or on vaccine coverage. Significant improvements in the health of children in the Farafenni study area have taken place during the past 5 years but the PHC programme is probably only one of the factors that have brought about these changes.

Child Health Services↗

Replication of tomato golden mosaic virus DNA B in transgenic plants expressing open reading frames (ORFs) of DNA A: requirement of ORF AL2 for production of single-stranded DNA.

Tomato golden mosaic geminivirus has a genome of two single-stranded (ss) DNA components, A and B. An almost identical 'common' region in DNA A and DNA B is thought to contain sequence elements controlling replication and transcription. Hence investigation of sequences important for DNA replication by in vitro mutagenesis is complicated by possible effects on the transcription of genes for replication proteins. To overcome this problem, transgenic plants expressing open reading frames (ORFs) of DNA A from an enhanced cauliflower mosaic virus 35S RNA promoter were constructed and tested for their ability to support the replication of DNA B and DNA B mutants. The results show that plants transgenic for ORF AL1 are able to support the replication of the double-stranded (ds) forms of DNA B, but that ORF AL2 is required in addition to produce ssDNA B. ORFs AL3, BL1 or BR1 were not required for replication of ds or ssDNA B. To the best of our knowledge this is the first time that essential replication proteins of a geminivirus have been expressed constitutively from a plant genome without giving rise to replicating DNA A molecules, thereby allowing DNA B to replicate alone. Such transgenic plants should enable not only the mutational analysis of sequence elements within the replication origin region, but also the construction of a new generation of vectors for gene amplification in plants, based on a minimal virus replicon.

DNA Probes↗

Stability and expression of bacterial genes in replicating geminivirus vectors in plants.

Bacterial beta-glucuronidase (gus) and neomycin phosphotransferase (neo) genes were introduced into coat protein replacement vectors based on DNA A of tomato golden mosaic virus (TGMV). Recombinant gus and neo vectors up to 1.1 kbp larger than DNA A were shown to replicate stably in transgenic plants containing partial dimers (master copies) of the vectors integrated into their chromosomal DNA in the absence of DNA B. Beta-glucuronidase and neomycin phosphotransferase activities in independently transformed plants were proportional to the copy number of the double-stranded forms of the vector. Deletion analysis has shown that an essential part of the TGMV coat protein promoter, including a TATA box, lies within 76 nt upstream of the initiation codon of the gene. An increase in expression of a neo gene was obtained by replacing this 76 nt sequence by an 800 nt sequence containing a cauliflower mosaic virus 35S RNA promoter with no effect on the ability of the vector to replicate or on its stability in transgenic plants. Systemic infection of plants by agroinoculation with TGMV vectors larger than DNA A in the presence of DNA B resulted in deletions in the vector DNA in some, but not all, plants. Possible reasons for vector instability in systemically infected plants, and vector stability in transgenic plants containing master copies of the vector, are discussed.

Chromosome Deletion↗

Leptospiral infection in school-children from Trinidad and Barbados.

A serological survey for leptospiral agglutinins was undertaken between 1980 and 1983 in over 500 Barbadian and 500 Trinidadian school-children aged 7-14 years. The children were selected randomly from urban and rural schools, and examined three times at approximately annual intervals. A total of 12.5% of the Barbadian children and 9.5% of the Trinidadian children were seropositive at a titre of 50 using the microscopic agglutination test. On both islands, seroprevalence was higher in males than females, the difference being significant in rural schools. There was no evidence of a difference in prevalence between urban and rural schools, or between junior and secondary age-ranges. Analysis of the association of serology with socio-economic and behavioural factors showed a significant association in Trinidad with father's occupation, but most other variables on both islands showed only weak non-significant associations. Fourteen children in Trinidad and three in Barbados seroconverted. Seroconversion in Trinidad occurred at a rate of 1.6% per annum and was significantly associated with livestock contact and with absence of a tapped water supply. In Trinidad, Autumnalis was the most commonly recorded serogroup, but this accounted for less than a quarter of seropositives. In Barbados, Panama accounted for over half the seropositives and was about four times more common than the next most common serogroup, Autumnalis. In Barbados, 39 persons aged 19 or less were hospitalized with leptospirosis between November 1979 and December 1986. Average annual incidence rates were 2.2, 4.9 and 13.3 per 100,000 in the 5-9, 10-14 and 15-19 age-groups, respectively.

Adolescent↗

Iron-deficiency anaemia and its response to oral iron: report of a study in rural Gambian children treated at home by their mothers.

Haematological and iron parameters, measured in 907 children aged from 6 months to 5 years in rural Gambia at the start of the rainy season, differed from those in American reference populations as follows: mean haemoglobin levels were much lower at ages 1 and 2 years and mean levels of mean corpuscular volume (MCV) were lower at all ages (at age 1 year mean haemoglobin was 11.2 g/dl and mean MCV 68.2 fl); in a sample of 249 children randomly selected from the whole study population, mean serum iron levels were similar but mean transferrin saturation and mean serum ferritin levels were lower, especially at ages 1-3 years (at age 1 year mean serum iron was 11.1 mumol/l, mean transferrin saturation 16.9%, and geometric mean serum ferritin 8.8 ng/ml. A total of 213 children (23%) whose haemoglobin and mean corpuscular volume were both less than the 3rd percentile of the reference population received oral iron or placebo from their mothers during the rainy season when malaria transmission is maximal. Mean levels of haemoglobin, mean corpuscular volume, serum iron, transferrin saturation and serum ferritin rose in the iron-treated group and fell in the placebo group at all ages, except under 1 year for serum ferritin, to produce significant differences between the groups by the end of the study. Total iron-binding capacity showed no significant changes during the study. We concluded that oral iron given by the mother during the rainy season can be used to treat iron-deficiency anaemia in Gambian children who would otherwise become more anaemic.

Administration, Oral↗

The effects on malaria of treatment of iron-deficiency anaemia with oral iron in Gambian children.

In order to determine whether giving iron to iron-deficient children increases their susceptibility to malaria, 213 Gambian children aged between 6 months and 5 years with iron-deficiency anaemia were randomized to receive either oral iron or placebo during the rainy season when malaria transmission is maximal. Haematological and iron measurements improved significantly in the group given iron. Regular morbidity surveys showed that fever associated with parasitaemia occurred more frequently in the iron-treated group than in the placebo group. This difference was not significant for all parasitaemias grouped together, but became significant and progressively larger for parasitaemias of ten or more positive fields per 100 high power fields (P less than 0.025), and for parasitaemias of 50 or more positive fields per 100 high power fields (P less than 0.01). Three children in the iron-treated group but none in the placebo group had more than one episode of fever and parasitaemia. Splenomegaly rates rose appreciably during the study in both groups, but in children at age 2 years the splenomegaly rate at the end of the study was significantly greater in the iron-treated group. We concluded that there is a significantly increased risk of fever associated with severe malarial parasitaemia for children with iron-deficiency anaemia given iron during the season of maximal malaria transmission in this part of The Gambia.

Administration, Oral↗

Comparison of two strategies for control of malaria within a primary health care programme in the Gambia.

Two drug strategies for the control of malaria in children aged 3-59 months have been compared in a rural area of The Gambia--treatment of presumptive episodes of clinical malaria with chloroquine by village health workers, and treatment combined with fortnightly chemoprophylaxis with 'Maloprim' (pyrimethamine/dapsone) which was also given by village health workers. Treatment alone did not have any significant effect on mortality or morbidity from malaria. In contrast, treatment and chemoprophylaxis reduced overall mortality in children aged 1-4 years, mortality from probable malaria, and episodes of fever associated with malaria parasitaemia. A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed.

Antimalarials↗

Methods for assessing whether change depends on initial value.

Statistical analysis of whether the change in a variable depends on its initial value, in clinical trials and other studies, is complicated by the phenomenon of regression to the mean. We review this problem and examine some approaches for handling it. MacGregor's log-log plot fails to correct for the regression effect, while Oldham's method of plotting the change against the average of initial and final values is shown to give misleading results when the effect of treatment varies between subjects, or when subjects are selected for study if their initial observations fall above or below a specified cut-off point. These results are illustrated by computer simulations. We prefer the use of Blomqvist's method of correcting the association between change and initial value to allow for the regression effect.

Blood Pressure↗

Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children.

The incidence of clinical attacks of malaria was significantly less in Gambian children aged 1-9 years who slept in villages where all the bed nets (mosquito nets) were treated with permethrin than in children who slept in control villages with placebo-treated nets. Significant differences in changes in spleen size and in packed cell volume were also observed between the 2 groups during the course of a rainy season. No side effect was noted. Treatment of bed nets with insecticide is a form of malaria control that is well suited to community participation and can readily be incorporated into primary health care programmes. Insecticide-treated nets may be more effective in areas of seasonal or low intensity transmission than in areas with heavy perennial challenge.

Animals↗

The effects of antimalarials and folate supplements on haematological indices and red cell folate levels in Gambian children.

Haematological indices and red cell folate levels (RCF) were measured during two annual surveys in a group of Gambian children aged 3 months-5 years who were participating in a trial of malaria chemoprophylaxis with Maloprim or chlorproguanil given with or without folate supplements. Chlorproguanil was given in an adult dose of 20 mg, Maloprim as one quarter or one half of the adult dose of 25 mg pyrimethamine and 100 mg dapsone. Antimalarials and folate supplements were given fortnightly. About 20% of children had low RCF levels (less than 100 ng/ml). Among children who did not receive supplementation with folate there were no significant differences in mean RCF levels between children who received Maloprim, chlorproguanil or placebo. Among children who received folate supplements, the mean RCF was significantly lower among those receiving chlorproguanil than among the controls. Mean RCF values were similar in children who received Maloprim or placebo. If chlorproguanil is used for malaria chemoprophylaxis in young children an age-related dose should be used.

Antimalarials↗

The quality of care is related to death rates: hospital inpatient management of infants with acute gastroenteritis in Jamaica.

The quality of care of random samples of about 40 infants admitted with acute gastroenteritis to each of five hospitals in Jamaica was assessed. Low levels of adherence to consensus care criteria appeared to be correlated with high levels of hospital-specific severity standardized mortality ratios X100 (SSMRs); poor adherence, SSMR 127-230; intermediate adherence, SSMR 95; good adherence, SSMR 14. The main deficiencies in care at certain hospitals were: non-weighing of infants, incomplete physical examination, inadequate estimation of fluid requirements, and irregular recording of fluid intake. To improve the effective care of infants with gastroenteritis, a quality assurance program is required.

Acute Disease↗

Alternative measures of diarrhoeal morbidity and their association with social and environmental factors in urban children in The Gambia.

Diarrhoeal morbidity was studied during a 15-week period of the rainy season in 244 children aged 6 to 35 months in an urban Gambian community. The average prevalence of diarrhoea was 12.0% and the mean number of episodes per child varied between 2.4 and 2.9 depending on the definition of an episode. The number of chronic episodes lasting 14 d or more was tripled when 7 rather than one diarrhoea-free days were required to define a new episode. Neither prevalence nor the number of episodes varied significantly with age or sex. There was little association between the social and environmental characteristics of the children and diarrhoeal morbidity. The implications of using differing measures of diarrhoeal morbidity are discussed.

Child, Preschool↗

Resistance to reinfection after treatment of urinary schistosomiasis.

The process of reinfection after treatment was studied in a cohort of subjects in a focus of intense Schistosoma haematobium infection. Detailed observations were made at water contact sites of cercarial densities and of water contact by members of the cohort. Individual values of a cumulative index of exposure to infection were calculated using these observations and assumptions which were made about the effect of different water contact activities on the entry of cercariae into the skin. Among groups of subjects with an apparently similar intensity of exposure to infection, reinfection tended to be much heavier in children under 10 years of age than in 10 to 14-year-olds, while only light infections were found in the few adults who became reinfected. This trend for reinfection to decrease with increasing age, after an allowance for variation in exposure, was highly significant (p less than 0.001). These observations suggest that subjects in this area slowly acquire an increasing degree of immunity to the acquisition of S. haematobium infection which is effective in the absence of a mature egg laying infection.

Adolescent↗

Resistance to reinfection with Schistosoma haematobium in Gambian children: analysis of their immune responses.

The relationship between reinfection with Schistosoma haematobium and immunological parameters was studied in a group of Gambian children aged from 8 to 13 years. Each individual's exposure to infection was assessed from observations of water contact, cercarial densities and infected snail densities at water contact sites. Eosinophil counts were made and responses to egg antigen (SEA) and adult worm antigen (WWH) measured by ELISA. Low levels of reinfection were associated with a high eosinophil count, high levels of antibodies against WWH and SEA, increased age and low exposure. In a multiple regression analysis of the association of reinfection with eosinophil count, antibody levels, exposure, age and sex, the effects of eosinophil count and exposure were still very significant after allowing for all the other variables. The effects of the antibody levels were close to significance after allowance for exposure and eosinophil count (for WWH: P = 0.09; for SEA: P = 0.07), although the evidence was less clear after additional allowance was made for age and sex. The ability of sera from the children to recognize different parasite antigens was also examined by immunoprecipitation of labelled schistosomulum surface, WWH, SEA and S. haematobium adult worm mRNA in vitro translation products. Schistosomulum surface antigens were recognized by all the sera and there was little variation in this response. There was more variation in their responses to SEA and WWH and a marked heterogeneity in the response to in vitro translation products. However, the pattern of antigen recognition appeared unrelated to susceptibility to reinfection.

Adolescent↗

Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West Africa.

A study was made of factors that influenced susceptibility to group A meningococcal disease during an epidemic that affected The Gambia, West Africa during the dry season of 1982-83. No explanations were found for the distribution of cases between villages or within affected villages. Socio-economic status, crowding, nutrition and previous exposure to meningococcal disease all appeared to be unimportant. Examination of serum samples obtained before the outbreak from a few children who subsequently became patients and from an equal number of age-matched controls from the same village showed a higher mean serum IgA value in children who became patients than in controls. There were not, however, any significant differences found in the concentrations of IgG, IgM, complement or meningococcal antibody between the two groups. Four children who developed culture-proven group A meningococcal disease had raised titres of bactericidal antibody to the epidemic strain 2-3 months before their illnesses. Our findings suggest that some important risk factors for group A meningococcal disease remain to be identified.

Adolescent↗

The haematology of steady state homozygous sickle cell disease: interrelationships between haematological indices.

The interrelationships between steady state haematological variables in 825 patients with homozygous sickle cell (SS) disease have been examined. On simple correlation coefficient analysis HbA2 correlated negatively with both HbF and MCV, red cell count (RBC) correlated positively with total haemoglobin and negatively with MCV and reticulocytes, and MCV correlated positively with reticulocytes. Less consistent were positive correlations between HbA2 and RBC, between HbF and both MCV and haemoglobin, between MCHC and MCV, and a negative relationship between haemoglobin and reticulocyte count. Partial correlation coefficient analysis clarified some of these relationships. In principal component analysis, the first component weighted positively on Hb and RBC and negatively on reticulocytes and possibly reflected the haemolytic rate. The second component weighted positively on HbF and MCV and negatively on HbA2 and may be related to alpha thalassaemia status. The third component weighted almost exclusively on MCHC and may relate to the degree of intracellular polymerization of HbS. These three components accounted for approximately 75% of the total variation in the haematological data.

Adolescent↗