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Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 901 records · Page 50Linked to original sources

Evaluation of C-reactive protein and haptoglobin as malaria episode markers in an area of high transmission in Africa.

Field studies of malaria in endemic areas frequently use the presence or levels of parasitaemia, together with the measurement of fever, as the primary criteria with which to identify cases. However, since malaria cases do not always present with measurable fever, and since asymptomatic parasitaemia occurs, additional episode markers might be useful epidemiological tools. We have measured the C-reactive protein and haptoglobin levels in paediatric patients presenting to a village health post in the Kilombero District in Tanzania and in convalescent sera from the same patients, in order to evaluate these acute-phase reactants as alternative markers of Plasmodium falciparum episodes. Among afebrile patients, C-reactive protein levels were highly correlated with parasite density. High C-reactive protein levels are therefore probably indicative of recent clinical malaria episodes in currently afebrile individuals with high parasite densities. An appropriate case definition for malaria in epidemiological studies in endemic areas might therefore be hyperparasitaemia accompanied by either, or both, measurable fever and raised C-reactive protein levels. This would give less biased estimates of the overall burden of malaria morbidity than does a definition which requires measurable fever. Levels of haptoglobin were highly negatively correlated with parasitaemia, but did not appear to be useful episode markers because this correlation was probably not related to acute morbidity. However, haptoglobin can be useful to assess at community level the impact of interventions on parasitaemia.

Biomarkers↗

The response to iron supplementation of pregnant women with the haemoglobin genotype AA or AS.

The influence of haemoglobin genotype on the response to iron supplementation was studied in a randomized, double blind, placebo-controlled trial involving 497 multigravid pregnant women from a rural area of The Gambia. Women were randomly allocated to receive either oral iron (60mg elemental iron per day) or placebo. At 36 weeks of pregnancy, women who had received oral iron during pregnancy had higher mean haemoglobin, packed cell volume, plasma iron and ferritin levels than did women who received placebo. Iron supplementation of pregnant women with the AA haemoglobin genotype also resulted in increases in the packed cell volume (PCV) and haemoglobin level measured after delivery, and in the birth weight of the infant. However, in AS women PCV and haemoglobin level at delivery were lower in the supplemented group and supplementation was also associated with reduced birth weights. In malaria endemic areas, pregnant women with the haemoglobin genotype AS may not benefit from iron supplementation during pregnancy.

Adolescent↗

Cyclic adenosine 3',5'-monophosphate, adenylate cyclase and physical dependence on ethanol: studies with tranylcypromine.

Tranylcypromine, a monoamine oxidase inhititor, was administered to rats during chronic ethanol treatment. The severity of the hyperactive withdrawal behavior observed upon removal of ethanol was, during the first 60 hours of treatment, similar in both ethanol and ethanol + tranylcypromine treated animals. However, after 84 hours of ethanol treatment, tranylcypromine slightly depressed the withdrawal severity. Rises in cerebral cortical cyclic adenosine 3',5'-monophosphate (cAMP) levels and adenylate cyclase activity associated with withdrawal behavior in ethanol-treated rats, though, were not observed. (Adenylate cyclase activity used throughout this paper refers to % conversion of 3H-adenine into 3H-cAMP). Based on this and previous data, a model invoking two neurochemical adaptations--one in adenylate cyclase and one, as yet, unknown-is proposed for the mechanism of physical dependence.

Adenylyl Cyclase Inhibitors↗

Risk factors for meningococcal meningitis in northern Ghana.

Meningococcal meningitis is a major cause of morbidity and mortality in the meningitis belt of sub-Saharan Africa where it occurs in epidemics every 8-12 years. Risk factors for the disease in this setting remain largely unknown. We carried out a case-control study to investigate possible risk factors among survivors of a meningitis epidemic occurring in 1997 in northern Ghana. A structured questionnaire on socio-economic factors, housing and household overcrowding, smoking and exposure to smoke and close contact with a case was administered to 505 of the survivors and 505 of age-, sex- and location-matched controls. Cooking in kitchens with firewood stoves (OR 9.00, CI 1.25-395) and sharing a bedroom with a case (OR 2.18 CI 1.43-3.4) were found to be risk factors for disease. Socio-economic factors, overcrowding, smoking and passive exposure to tobacco smoke were not found to be risk factors. Exposure to smoke from cooking fires or close contact with a case puts people at risk of contracting meningococcal meningitis. In the hot dry months, exposure to smoke from cooking fires should be minimized by encouraging alternatives to cooking over wood fires, or cooking outside. If wood-burning stoves cannot be avoided, kitchens should be made larger with improved ventilation. Meningitis cases should be nursed in well-ventilated rooms and the number of people sharing a room with a case kept at a minimum.

Adolescent↗

Associations of peak shifts in age--prevalence for human malarias with bednet coverage.

Effects of bednet coverage (C) on prevalence of malaria were analysed using data from 1990-92 from 9 Papua New Guinean villages. Effects of coverage varied by age, resulting in a shift in age of peak prevalence from 4.7 (C = 0%) to 11.6 (C = 100%) years for Plasmodium falciparum, from 3.4 to 4.9 years for P. vivax and from 11.0 to 16.8 years for P. malariae. In small areas with no bednets the age distribution of P. falciparum parasitaemia was like that of a holoendemic area. Where coverage was complete the pattern corresponded to mesoendemicity. Thus, protracted use of bednets can result in profound changes in the endemicity of malaria even when coverage is incomplete and without insecticide treatment. Average entomological inoculation rates (EIRs) estimated from indoor landing rates on individuals without bednets were 35, 12 and 10 infectious bites per person per annum for P. falciparum, P. vivax and P. malariae, respectively. Logistic regression analyses indicated that the EIR estimate for P. falciparum was related to prevalence of this species independently of effects of bednet coverage. However, the recent EIR still accounted for much less variation than did the bednets. A similar pattern was seen for P. malariae, while there were no significant relationships between the recent EIR and the parasite positivity for P. vivax. It is concluded that short-term variations in inoculation rate are not important determinants of parasite prevalence in this population.

Adolescent↗

Area effects of bednet use in a malaria-endemic area in Papua New Guinea.

Relationships between area coverage with insecticide-free bednets and prevalence of Plasmodium falciparum were investigated in 7 community-based surveys over a 33-month period in 1990-93 in 6 villages in the Wosera area of Papua New Guinea. Spatial patterns in circumsporozoite rates for P. falciparum, P. vivax isomorphs K210 and K247, and P. malariae, and the proportions of mosquito blood meals positive for specific human, goat, cat, dog and pig antigens were determined using ELISAs. P. falciparum prevalence in humans was better explained by bednet coverage in the immediate vicinity than by personal protection alone. Circumsporozoite rates for both P. falciparum and P. vivax were also inversely related to coverage with bednets. There was some increase in zoophagy in areas with high coverage, but relatively little effect on the human blood index or on overall mosquito densities. In this setting, protracted use of untreated bednets apparently reduces sporozoite rates, and the associated effects on prevalence are greater than can be accounted for by personal protection. Even at high bednet coverage most anophelines feed on human hosts, so the decreased sporozoite rates are likely to be largely due to reduction of mosquito survival. This finding highlights the importance of local vector ecology for outcomes of bednet programmes and suggests that area effects of untreated bednets should be reassessed in other settings.

Adolescent↗

Mosquito nets for the elderly?

Nine-year follow-up (ending 1999) of survival of 3738 individuals in a malaria-endemic area of Papua New Guinea found that the use of mosquito nets was associated with a large reduction in mortality in people aged > or = 40 years as well as in children aged < 5 years. There may be substantial benefits of malaria transmission reduction for older people, that have been overlooked in public health programmes and burden of disease calculations.

Adolescent↗

Mortality in a seven-and-a-half-year follow-up of a trial of insecticide-treated mosquito nets in Ghana.

A 17% efficacy in preventing all-cause mortality in children aged 6-59 months was previously reported from a cluster-randomized controlled trial of insecticide-treated mosquito nets (ITNs) carried out in the Kassena-Nankana District of northern Ghana from July 1993-June 1995. A follow-up until the end of 2000 found no indication in any age group of increased mortality in the ITN group after the end of the randomized intervention. These results should further encourage the use of ITNs as a malaria control tool in areas of high endemicity of Plasmodium falciparum.

Bedding and Linens↗

Estimation of the infectious reservoir of Plasmodium falciparum in natural vector populations based on oocyst size.

A method for determining the infectious reservoir of malaria (K) and vector survival rate (P) by measuring oocyst size and discriminating between the most recent and other infections is described. In the laboratory the mean diameter of 3 d oocysts in Anopheles gambiae, kept at 26 degrees C, was 11.5 microns and the mean diameter at day 5 was 24.5 microns. Oocyst sizes in wild caught mosquitoes from southern Tanzania, that had fed on the occupants of bed nets with holes in the sides, were more variable. 2060 A. gambiae s.l. and 1982 A. funestus were examined for oocysts 3 d after feeding; 796 and 654 oocysts from the 153 and 170 infected females, respectively, were measured. Because of misclassification errors, the use of a simple cut-off model, in which all oocysts less than 17.5 microns in diameter were considered to have arisen from the most recent feed, was thought to overestimate K and underestimate P. A statistical model which allows for overlap in the oocyst size distributions is described. Estimates of the infectious reservoir derived from this model were 2.8% for A. gambiae s.l. and 4.2% for A. funestus, and the estimated survival rates per gonotrophic cycle were 65.5% and 52.9%, respectively. The utility of measuring oocyst size in naturally infected mosquitoes is discussed.

Animals↗

Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study.

A prospective community study in a highly malaria endemic area of Papua New Guinea found that infection with multiple Plasmodium falciparum genotypes was an indicator of lowered risk of subsequent clinical attack. The results suggest that concurrent or very recent infections provide protection from superinfecting parasites. The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozoite surface proteins.

Adolescent↗

Parent-directed, intensive early intervention for children with pervasive developmental disorder.

We examined parent-directed, intensive early intervention for children with Pervasive Developmental Disorder. Children's parents recruited paraprofessional therapists and requested consultations on how to implement the UCLA treatment model in their homes (Smith & Lovaas, 1998). Parents and therapists then received six one-day workshops over a five-month period, with additional consultations for the next 2-3 years. Six boys participated (intake age 35-45 months, intake IQ 45-60). The study addressed 1) the children's skill acquisition during the first five months of treatment; 2) outcome 2-3 years later; 3) treatment quality; and 4) parents' impressions. Five of 6 children rapidly acquired skills when treatment began, but only 2 clearly improved on standardized tests at the 2-3 year follow-up. Therapists usually employed correct treatment procedures but were less consistent than therapists employed at a clinic. Parents reported high satisfaction with treatment. These mixed results highlight the need for multimodal assessment of parent-directed treatment.

Behavior Therapy↗

Effect of strategic gastrointestinal nematode control on faecal egg count in traditional West African cattle.

This paper reports on the effect of strategic anthelmintic treatments and other determinants on faecal egg counts (FEC) of Trichostrongyles in N'Dama cattle of a west African village. Initially, 527 animals from 13 private N'Dama cattle herds were monitored in a longitudinal study from October 1989 to December 1994. Each herd was stratified by age and animals were sequentially allocated to two groups with similar age distributions. One group received a single anthelmintic treatment of fenbendazole (7.5 mg/kg BW), in October 1989 (n = 250), whereas the other group remained untreated (n = 277) throughout the study. In the next rainy season (June to October), the treated animals were treated twice (in July and September). The same treatment schedule was used in the subsequent rainy seasons until December 1994. Biannual anthelmintic treatments decreased the level of FEC between 31% (late dry season) and 57% (rainy season), when compared to untreated controls. The highest levels of FEC were found during the rainy season from June to October. FEC levels decreased until 4 years of age, after which they remained on a constant low level. The variability of returns to anthelmintic treatments between herds did not seem to be influenced by FEC at the herd level. The financial evaluation of anthelmintic interventions cannot be predicted from FEC and must necessarily rely on the direct monitoring of livestock productivity parameters.

Africa, Western↗

Spatial patterns of child growth in Papua New Guinea and their relation to environment, diet, socio-economic status and subsistence activities.

Anthropometric data from the 1982/83 Papua New Guinea (PNG) National Nutrition Survey were analysed to identify geographical patterns of child growth and investigate their relation to a wide range of environmental, dietary and socio-economic variables. Standardized growth scores for length-for-age (LAZ), weight-for-age (WAZ) and weight-for-length (WLZ) were calculated based on an internal PNG growth reference. Hierarchical Bayesian spatial models based on conditional autoregressive (CAR) priors were subsequently used to model spatial patterns in scores and their relation to different sets of covariates. The geographical differences were bigger for linear growth than for increases in weight. Growth was most reduced in parts of Milne Bay Province, Madang Province, the Torricelli/Prinz Alexander Ranges, and in the area occupied by Angan people. Socio-economic status was the most important factor determining variation in growth within populations. Differences in diet and, to a lesser extent, the physical environment were the main determining factor of differences among populations. Covariate adjustment accounted for more spatially structured variation in LAZ and WAZ than in WLZ. All variables indicating higher socio-economic status were correlated with better growth, as was a high consumption of imported and local high quality foods such as cereals, legumes, tinned fish/meat or fresh fish. This indicates that nutritional interventions in PNG should aim at promoting the consumption of such high energy and high protein foods as well as strengthening the general economic base of rural populations.

Analysis of Variance↗

What proportion of children have a growth deficit?

Cross-sectional anthropometric survey data are frequently summarized to present estimates of the proportion of a child population who might be considered malnourished. A very commonly used summary statistic is the prevalence of standard deviation scores less than -2 (Pz < -2). Pz < -2 is not equivalent to the prevalence of growth retardation in the population, lambda. Identical values of Pz < -2 can arise as a result of a relatively low prevalence of predominantly severe malnutrition, or of universal or near-universal mild growth retardation. Alternative estimators which have been proposed give biased estimates of lambda. In this paper a simple statistical procedure using density ratios is described for estimating lambda from cross-sectional anthropometric data and international growth standards. This gives nearly unbiased estimates of lambda and of the distribution of the growth deficit in the growth retarded sub-set of the population. The analysis provides estimates of the probability that an individual child's growth is retarded. This is illustrated with data from the 1982/3 National Nutrition Survey of Papua New Guinea. Estimation of lambda for different indicators and for different populations could be useful in planning whether interventions should be targeted at the smallest children, or aimed at the population in general. The same estimates might also be used to help determine whether heterogeneity between countries in the reported associations between morbidity or mortality risks and anthropometric indices can be accounted for by differences in the amount of intrapopulation variation in growth retardation.

Anthropometry↗

Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in Highland children of Papua New Guinea.

Acute lower respiratory tract infection (ALRI) is the major cause of death among children in Papua New Guinea. This longitudinal study reports the bacteriologic findings for children observed in their hamlets. A total of 1,449 nasal swab specimens from 158 children less than 5 years of age who were studied intensively for 18 months were examined. Non-serotypable strains of Haemophilus influenzae were isolated from 91% of specimens, and serotypable strains were isolated from 35% (8% H. influenzae type b) of specimens. All children had acquired Streptococcus pneumoniae by the age of 3 months. The most frequently occurring serotypes of S. pneumoniae were 6, 19, and 23. Children more frequently carried invasive pneumococci during an episode of ALRI than when they were healthy. Also, children more frequently carried serotypable strains of H. influenzae during the 2 weeks preceding an episode of ALRI than when they were healthy. Between-children analyses showed that children who were susceptible to attacks of ALRI and those who were not susceptible had similar rates of carriage of bacteria.

Age Factors↗

Early clinical experience with high-frequency oscillatory ventilation for ARDS in adult burn patients.

Lung protective ventilation strategies are recommended in acute respiratory distress syndrome to avoid ventilator associated lung injury, a recently characterized complication of mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is an unconventional ventilation strategy which may achieve this goal. We reviewed our experience with HFOV in six severely burned patients with acute respiratory distress syndrome. The mean age (+/- SD) of the patients was 34 +/- 13 years, and the mean TBSA burn was 52 +/- 10%, with a mean full-thickness injury of 49 +/- 12%. HFOV was initiated as "rescue therapy" in three patients with oxygenation failure (mean PaO2/FIO2 ratio of 71 +/- 8 and mean oxygenation index [OI] of 42 +/- 3) that was unresponsive to conventional ventilation (mean FIO2, 1.0 +/- 0; mean positive end expiratory pressure, 14.8 +/- 2.8 cm H2O; and mean inhaled nitric oxide, 20 +/- 0 ppm). In the other three cases, HFOV was initiated "prophylactically" as a lung protective ventilation strategy in an attempt to prevent further respiratory deterioration. All six patients showed a rapid and substantial improvement in oxygenation after initiation of HFOV, with significant improvements in the PaO2/FIO2 and OI by 12 hours (P = 0.02). In four patients HFOV was also used during anesthesia and surgery, where a total of 10 procedures involving a mean excision and closure of 15 +/- 7% TBSA burns was performed. Five of the six patients died, but none died because of oxygenation failure. In three patients death resulted from sepsis and multiple organ dysfunction syndrome; their mean PaO2/FIO2 was 107 +/- 31 and their mean OI was 30 +/- 11 immediately before death. Two patients with multiple organ dysfunction syndrome died after withdrawal of life support; their mean PaO2/FIO2 and OI were 178 +/- 31 and 18 +/- 2 respectively, at the time of this decision. Although HFOV had no impact on mortality, it played a useful role in the supportive management of burn patients with severe oxygenation failure unresponsive to conventional ventilation. Importantly, HFOV allowed surgery to proceed in patients who may have otherwise been too unstable to go to the operating room. As far as we are aware, this is the first report of the use of intraoperative HFOV in burn patients.

Adult↗