Understanding the processes underpinning IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) in primary care: study protocol for a process evaluation within a cluster randomised controlled implementation trial.

BACKGROUND: Providing supported self-management for people with asthma can reduce the burden on patients, health services and wider society. Implementation, however, remains poor in routine clinical practice. IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) is a UK-wide cluster randomised implementation trial that aims to test the impact of a whole-systems implementation strategy, embedding supported asthma self-management in primary care compared with usual care. To maximise opportunities for sustainable implementation beyond the trial, it is necessary to understand how and why the IMP2ART trial achieved its clinical and implementation outcomes. METHODS: A mixed-methods process evaluation nested within the IMP2ART trial will be undertaken to understand how supported self-management was implemented (or not) by primary care practices, to aid interpretation of trial findings and to inform scaling up and sustainability. Data and analysis strategies have been informed by mid-range and programme-level theory. Quantitative data will be collected across all practices to describe practice context, IMP2ART delivery (including fidelity and adaption) and practice response. Case studies undertaken in three to six sites, supplemented by additional interviews with practice staff and stakeholders, will be undertaken to gain an in-depth understanding of the interaction of practice context, delivery, and response. Synthesis, informed by theory, will combine analyses of both qualitative and quantitative data. Finally, implications for the scale up of asthma self-management implementation strategies to other practices in the UK will be explored through workshops with stakeholders. DISCUSSION: This mixed-methods, theoretically informed, process evaluation seeks to provide insights into the delivery and response to a whole-systems approach to the implementation of supported self-management in asthma care in primary care. It is underway at a time of significant change in primary care in the UK. The methods have, therefore, been developed to be adaptable to this changing context and to capture the impact of these changes on the delivery and response to research and implementation processes.

Approaching the community about screening children for a multicentre malaria vaccine trial.

Community sensitisation, as a component of community engagement, plays an important role in strengthening the ethics of community-based trials in developing countries and is fundamental to trial success. However, few researchers have shared their community sensitisation strategies and experiences. We report on our perspective as researchers on the sensitisation activities undertaken for a phase II malaria vaccine trial in Kilifi District (Kenya) and Korogwe District (Tanzania), with the aim of informing and guiding the operational planning of future trials. We report wide variability in recruitment rates within both sites; a variability that occurred against a backdrop of similarity in overall approaches to sensitisation across the two sites but significant differences in community exposure to biomedical research. We present a range of potential factors contributing to these differences in recruitment rates, which we believe are worth considering in future community sensitisation plans. We conclude by arguing for carefully designed social science research around the implementation and impact of community sensitisation activities.

Working with Concepts: The Role of Community in International Collaborative Biomedical Research.

The importance of communities in strengthening the ethics of international collaborative research is increasingly highlighted, but there has been much debate about the meaning of the term 'community' and its specific normative contribution. We argue that 'community' is a contingent concept that plays an important normative role in research through the existence of morally significant interplay between notions of community and individuality. We draw on experience of community engagement in rural Kenya to illustrate two aspects of this interplay: (i) that taking individual informed consent seriously involves understanding and addressing the influence of communities in which individuals' lives are embedded; (ii) that individual participation can generate risks and benefits for communities as part of the wider implications of research. We further argue that the contingent nature of a community means that defining boundaries is generally a normative process itself, with ethical implications. Community engagement supports the enactment of normative roles; building mutual understanding and trust between researchers and community members have been important goals in Kilifi, requiring a broad range of approaches. Ethical dilemmas are continuously generated as part of these engagement activities, including the risks of perverse outcomes related to existing social relations in communities and conditions of 'half knowing' intrinsic to processes of developing new understandings.

Contamination of food products with Mycobacterium avium paratuberculosis: a systematic review.

Although a causal link between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease has not been proved, previous studies suggest that the potential routes of human exposure to MAP should be investigated. We conducted a systematic review of literature concerning the likelihood of contamination of food products with MAP and the likely changes in the quantity of MAP in dairy and meat products along their respective production chains. Relevant data were extracted from 65 research papers and synthesized qualitatively. Although estimates of the prevalence of Johne's disease are scarce, particularly for non-dairy herds, the available data suggest that the likelihood of contamination of raw milk with MAP in most studied regions is substantial. The presence of MAP in raw and pasteurized milk has been the subject of several studies which show that pasteurized milk is not always MAP-free and that the effectiveness of pasteurization in inactivating MAP depends on the initial concentration of the agent in raw milk. The most recent studies indicated that beef can be contaminated with MAP via dissemination of the pathogen in the tissues of infected animals. Currently available data suggests that the likelihood of dairy and meat products being contaminated with MAP on retail sale should not be ignored.

The cost-effectiveness of improving malaria home management: shopkeeper training in rural Kenya.

Home management is a very common approach to the treatment of illnesses such as malaria, acute respiratory infections, tuberculosis, diarrhoea and sexually transmitted infections, frequently through over-the-counter purchase of drugs from shops. Inappropriate drugs and doses are often obtained, but interventions to improve treatment quality are rare. An educational programme for general shopkeepers and communities in Kilifi District, rural Kenya was associated with major improvements in the use of over-the-counter anti-malarial drugs for childhood fevers. The two main components were workshop training for drug retailers and community information activities, with impact maintained through on-going refresher training, monitoring and community mobilization. This paper presents the cost and cost-effectiveness of the programme in terms of additional appropriately treated cases, evaluating both its measured cost-effectiveness in the first area of implementation (early implementation phase) and the estimated cost-effectiveness of the programme recommended for district-level implementation (recommended district programme). The proportion of shop-treated childhood fevers receiving an adequate amount of a recommended antimalarial rose from 2% to 15% in the early implementation phase, at an economic cost of 4.00 US dollars per additional appropriately treated case (2000 US dollars). If the same impact were achieved through the recommended district programme, the economic cost per additional appropriately treated case would be 0.84 US dollars, varying between 0.37 US dollars and 1.36 US dollars in the sensitivity analysis. As with most educational approaches, the programme carries a relatively high initial financial cost, of 11,477 US dollars (0.02 per capita US dollars) for the development phase and 81,450 US dollars (0.17 per capita US dollars) for the set up year, which would be particularly suitable for donor funding, while the annual costs of 18,129 US dollars (0.04 per capita US dollars) thereafter could be contained within the budget of a typical District. To reach the Abuja target of 60% of those suffering from malaria in sub-Saharan Africa having access to affordable and appropriate treatment within 24 hours, improvements in community-based malaria treatment are urgently required. From these results, policymakers can estimate costs for district-scale shopkeeper training programmes, and will be able to assess their relative cost-effectiveness as comparable evaluations become available from home management interventions in the future. Extrapolation of the results using a simple decision tree model to estimate the cost per DALY averted indicates that the intervention is likely to be considered highly cost-effective in comparison with standard benchmarks for interventions in low-income countries.

Improving malaria home treatment by training drug retailers in rural Kenya.

Recent global malaria control initiatives highlight the potential role of drug retailers to improve access to early effective malaria treatment. We report on the findings and discuss the implications of an educational programme for rural drug retailers and communities in Kenya between 1998 and 2001 in a study population of 70,000. Impact was evaluated through annual household surveys of over-the-counter (OTC) drug use and simulated retail client surveys in an early (1999) and a late (2000) implementation area. The programme achieved major improvements in drug selling practices. The proportion of OTC anti-malarial drug users receiving an adequate dose rose from 8% (n = 98) to 33% (n = 121) between 1998 and 1999 in the early implementation area. By 2001, and with the introduction of sulphadoxine pyrimethamine group drugs in accordance with national policy, this proportion rose to 64% (n = 441) across the early and late implementation areas. Overall, the proportion of shop-treated childhood fevers receiving an adequate dose of a recommended anti-malarial drug within 24 h rose from 1% (n = 681) to 28% (n = 919) by 2001. These findings strongly support the inclusion of private drug retailers in control strategies aiming to improve prompt effective treatment of malaria.

Lack of effect of tryptophan depletion on the loudness dependency of auditory event related potentials in healthy volunteers.

It has previously been suggested that auditory event related potentials (AEPs) are a potential marker of central serotonergic (5-HT) activity in man, with the slope of the AEP amplitude stimulus intensity function (ASF-slope) inversely correlating with 5-HT activity. However, two recent studies investigating this hypothesis in healthy subjects by rapidly lowering central 5-HT concentrations using the acute tryptophan depletion paradigm have found no effect on ASF-slope [Biological Psychology, 59 (2002) 121; Psychopharmacology (Berl), 146 (1999) 101]. These studies employed a 50g tryptophan depletion drink, which has been argued may not lower central 5-HT concentrations sufficiently. We here report the effect of tryptophan depletion on the AEP ASF-slope using 100g amino acid drinks with and without tryptophan in 14 healthy male subjects, employing a within subject, double blind, random, balanced order, cross-over design. No significant effect of tryptophan depletion was found on ASF-slope. These negative findings cast further doubt on the hypothesis that the ASF-slope is an indicator of central 5-HT function.

Quality of care provided to febrile children presenting in rural private clinics on the Kenyan coast.

BACKGROUND: Private sector health facilities are diverse in nature, and offer widely varying quality of care (QOC). OBJECTIVES: The study aimed to describe the QOC provided to febrile children at rural private clinics on the Kenyan coast and stakeholder perspectives on standards of practice and opportunities for change. METHODS: Data collection methods were structured observations of consultations; interviews with users on exit from clinic and at home and in depth interviews with private practitioners (PP) and district health managers. FINDINGS: Private clinics have basic structural features for health care delivery. The majority of the clinics in this study were owned and run by single-handed trained medical practitioners. Amongst 92 observed consultations, 62% of diagnoses made were consistent with the history, examinations and tests performed. 74% of childhood fevers were diagnosed as malaria, and 88% of all prescriptions contained an antimalarial drug. Blood slides for malaria parasites were performed in 55 children (60%). Of those whose blood slide was positive (n=27), 52% and 48% were treated with a nationally recommended first or second line antimalarial drug, respectively. Where no blood slide was done (n=37), 73% were prescribed a nationally recommended first line and 27% received a second line antimalarial drug. Overall, 68 % of antimalarial drugs were prescribed in an appropriate dose and regime. Both private practitioners and district health managers expressed the view that existing linkages between the public and private health sectors within the district are haphazard and inadequate. CONCLUSIONS: Although rural PPs are potentially well placed for treatment of febrile cases in remote settings, they exhibit varying QOC. Practitioners, users and district managers supported the need to develop interventions to improve QOC. The study identifies the need to consider involvement of the for-profit providers in the implementation of the IMCI guidelines in Kenya.

Electroencephalograph effects of single doses of Ginkgo biloba and Panax ginseng in healthy young volunteers.

Both Ginkgo biloba and Panax ginseng exert a number of physiological effects and have been shown to modulate aspects of cognitive performance. Whilst a number of studies have examined ginkgo's effects on electroencephalograph (EEG) recordings, to date, none have investigated the EEG effects of ginseng. In this double-blind, placebo-controlled, balanced crossover experiment, the effects of single doses of G. biloba (360 mg GK501), P. ginseng (200 mg G115), and an identical placebo, on auditory-evoked potentials, contingent negative variation (CNV), and resting power within the delta, theta, alpha, and beta wavebands, were assessed in 15 healthy volunteers. Each participant was assessed on three separate occasions 4 h after consuming that day's treatment. The order of presentation of the treatments was dictated by a Latin square with 7 days between testing sessions. The results showed that ginseng led to a significant shortening of the latency of the P300 component of the evoked potential. Both ginseng and ginkgo also led to significant reductions in frontal 'eyes closed' theta and beta activity, with additional reduction for ginseng in the alpha waveband. These findings demonstrate for the first time that P. ginseng can directly modulate cerebroelectrical activity, and that these effects are more pronounced than those following G. biloba.

DNA replication in the hyperthermophilic archaeon Sulfolobus solfataricus.

Studies of the DNA-replication machinery of Archaea have revealed striking similarities to that of eukaryotes. Indeed, it appears that in most cases Archaea possess a simplified version of the eukaryotic replication apparatus. Studies of Archaea are therefore shedding light on the fundamental processes of DNA replication in both domains of life.

Acute tryptophan depletion attenuates auditory event related potentials in bipolar disorder: a preliminary study.

BACKGROUND: 5-HT modulates electroencephalographic (EEG) activity, which is abnormal in bipolar disorder and EEG abnormalities persist in euthymic bipolar patients. The EEG may therefore be a sensitive marker of 5-HT function in bipolar disorder. We examined the effects of acute tryptophan depletion (ATD) on EEG activity in bipolar patients. METHODS: Fourteen patients with DSM IV Bipolar 1 disorder participated in a within-subject, double-blind, placebo-controlled, random-order crossover study. Following ATD quantitative power spectrum brain mapping and measurement of auditory evoked potentials were carried out. RESULTS: ATD produced a significant fall in the amplitude of N1P2 and P300 components of the auditory evoked potential, but no significant changes in the power spectrum. There was an 83% reduction in plasma tryptophan after the depleting but not the control drink. LIMITATIONS: The effect of ATD on brain 5-HT levels was not directly measured. The number of patients is relatively small. The control condition may alter these electrophysiological measures. CONCLUSIONS: ATD attenuates auditory evoked potentials in bipolar disorder with the distribution of this effect being towards the front of the brain. These changes are not related to any change in mood. This is a potential trait marker of bipolar disorder, however there needs to be further exploration of this paradigm in controls and other patient groups.

Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach.

Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54 microM) for a second generation series of heterocyclic urea raf kinase inhibitors.

Electrophysiological and cognitive function in young euthymic patients with bipolar affective disorder.

OBJECTIVES: EEG abnormalities and neurocognitive deficits have been reported in patients with bipolar affective disorder. The aim of this study was to ascertain whether brain function remains impaired in young bipolar patients who have become euthymic in response to treatment. METHODS: Brain function was assessed by quantitative electroencephalographic (EEG) power-spectral mapping and by a battery of neuropsychological tests. The subjects were 29 euthymic bipolar patients aged 18-40 years and 26 healthy volunteers of similar age, IQ and socioeconomic status. RESULTS: Grand means of spectral power of the resting EEG showed significantly (from p < 0.01 to p < 0.0001) greater power in all wave bands (delta, theta, alpha and beta) in patients compared with controls. The most marked increases were in right temporal theta and left occipital beta power (with eyes open) encompassing brain areas concerned in visuospatial processing. Neurocognitive performance was significantly impaired in the patients compared with controls in a range of visuospatial tasks. CONCLUSIONS: The findings show significant disturbance of EEG activity and deficits in visuospatial processing in young bipolar patients despite clinical euthymia. The abnormalities were not related to age of onset or duration of illness and do not appear to be attributable to medication. The cognitive impairments were associated with the number of previous affective episodes.

Subchronic hydrocortisone treatment alters auditory evoked potentials in normal subjects.

RATIONALE: Abnormalities of cortical evoked potentials and background electroencephalographic (EEG) frequencies occur in several psychiatric disorders, some of which, especially depression, are associated with hypercortisolaemia. However, there have been few investigations of the effects of exogenously administered cortisol on waking EEG measures. OBJECTIVES: To examine the effects of subchronic hydrocortisone administration on auditory evoked potentials and background EEG activity. METHODS: Hydrocortisone, 20 mg twice daily, or placebo was administered to 30 normal male volunteers for 7 days in a between-subjects, double-blind trial. Auditory evoked potentials and EEG frequencies were measured on the last day. RESULTS: Hydrocortisone significantly increased the amplitudes of the N1P2 and P300 components of the auditory evoked response, but there was no change in background EEG. CONCLUSION: The results indicate that subchronic hydrocortisone treatment in normal subjects increases the amplitude of auditory evoked potentials, possibly reflecting a central alerting effect.

Changing home treatment of childhood fevers by training shop keepers in rural Kenya.

BACKGROUND: Malaria control in Africa relies primarily on early effective treatment for clinical disease, but most early treatments for fever occur through self-medication with shop-bought drugs. Lack of information to community members on over-the-counter drug use has led to widespread ineffective treatment of fevers, increased risks of drug toxicity and accelerating drug resistance. We examined the feasibility and measured the likely impact of training shop keepers in rural Africa on community drug use. METHODS: In a rural area of coastal Kenya, we implemented a shop keeper training programme in 23 shops serving a population of approximately 3500, based on formative research within the community. We evaluated the training by measuring changes in the proportions of drug sales where an adequate amount of chloroquine was purchased and in the percentage of home-treated childhood fevers given an adequate amount of chloroquine. The programme was assessed qualitatively in the community following the shop keeper training. RESULTS: The percentage of drug sales for children with fever which included an antimalarial drug rose from 34.3% (95% CI 28.9%-40.1%) before the training to a minimum of 79.3% (95% CI 71.8%-85.3%) after the training. The percentage of antimalarial drug sales where an adequate amount of drug was purchased rose from 31.8% (95% CI 26.6%-37.6%) to a minimum of 82.9% (95% CI 76.3%-87.3%). The percentage of childhood fevers where an adequate dose of chloroquine was given to the child rose from 3.7% (95% CI 1.2%-9.7%) before the training to a minimum of 65.2% (95% CI 57.7%-72.0%) afterwards, which represents an increase in the appropriate use of over-the-counter chloroquine by at least 62% (95% CI 53.7%-69.3%). Shop keepers and community members were strongly supportive of the aims and outcome of the programme. CONCLUSIONS: The large shifts in behaviour observed indicate that the approach of training shop keepers as a channel for information to the community is both feasible and likely to have a significant impact. Whilst some of the impact seen may be attributable to research effects in a relatively small scale pilot study, the magnitude of the changes support further investigation into this approach as a potentially important new strategy in malaria control.

Structural and functional abnormalities in elderly patients clinically recovered from early- and late-onset depression.

BACKGROUND: Structural and functional brain changes have been described in elderly patients with unipolar affective disorder. Changes appear to be more marked in patients with late-onset depression, but the reversibility of such changes after clinical recovery is not known. METHODS: Magnetic resonance imaging, electroencephalography (EEG), and cognitive tests were performed in 23 elderly patients (mean age 66.5 years) clinically recovered from major depression. Twelve had late-onset depression (first episode over 55 years of age); 11 had early onset (first episode before 50 years). EEG and cognitive testing were also performed on 15 control subjects. RESULTS: Patients with late-onset depression had larger third and lateral ventricles, increased ventricular-brain ratio, and greater frequency and severity of subcortical white matter lesions than those with early onset. There was no difference between early- and late-onset patients in EEG and cognitive measures, but compared with controls patients showed significant changes in EEG evoked potentials and increased slow-wave activity, slowed reaction times, and global impairments in cognitive function. CONCLUSIONS: These results suggest that structural changes are greater in patients with late-onset depression, and that EEG and cognitive impairments persist after recovery, regardless of age of onset of depression, and are independent of structural changes.

Assessment of the effects of combination therapy with ciprofloxacin and fenbufen on the central nervous systems of healthy volunteers by quantitative electroencephalography.

The potential effects of concurrent administration of fenbufen and ciprofloxacin on central nervous system activity in healthy young subjects were investigated by electroencephalography (EEG). Visual analog scales (VAS) were used to assess subjective measures of concentration, vigilance, tension, and irritability. When ciprofloxacin was administered in combination with fenbufen, none of the EEG parameters or VAS ratings measured were significantly different from those measured when the drugs were administered alone.

Retrospective perceptions of parents' child-rearing conduct by same-sex sibling trios in African American and European American families.

Adult (M = 33 years) trios of 20 sisters and 6 brothers from 15 African American and 11 European American intact families retrospectively described their parents' child-rearing conduct on the Parent-Child Relations Questionnaire II (Siegelman & Roe, 1979). Respondents' mean education (15.1 years) and family size exceeded U.S. averages. Fitting cultural stereotypes, mothers were depicted as more loving, more attentive, and less rejecting than fathers. African American parents were described as more demanding and less lenient than European American parents, although this finding was confounded with the latter's greater education (M = 14.4 years vs. 10.9 years). Daughter trios tended to differ more than son trios on their ratings of each parent, suggesting that daughters may be more attentive to intrafamilial events. The uniqueness of the sample and the small number of brother trios limit the generalizability of these findings.

Evaluating the community education programme of an insecticide-treated bed net trial on the Kenyan coast.

Increased interest in the potential contribution of insecticide-impregnated bed nets (ITBN) to malaria control has led to research efforts to determine the impact and sustainability of ITBN programmes in differing environments. There is a need to develop effective, feasible educational strategies that will both inform and motivate community members, and thus maximize the correct usage of ITBN. This is especially true in communities where indigenous usage of bed nets is low. This paper describes the educational component of a randomized controlled community intervention trial of ITBN, with childhood malaria morbidity as an outcome. The educational approach and messages for the ITBN trial were developed from anthropological survey data collected 4 years before the trial, and from community surveys conducted by project researchers. Low levels of understanding amongst mothers of the aetiological link between mosquitos and malaria led to the exclusion of the term 'malaria' from the initial educational messages promoting the use of ITBN. Appropriate individuals within the existing district health care structure were trained as community educators in the project. These educators conducted intensive teaching in the community through public meetings and group teaching in the first 6 months of the trial. The impact of these initial activities was assessed through interviews with a random sample of 100 mothers and 50 household heads. This allowed the identification of messages which had not been well understood and further educational methods were chosen to address the areas pinpointed. The community assessment also demonstrated that, in 1994, over 90% of mothers understood a protective role for bed nets against malaria and the ITBN education messages were changed to take account of this. The school programme was evaluated through determining outreach (the number of households accessed), changes in participant children's knowledge, post-teaching assessment of mothers' knowledge and discussions with parent-teacher associations. It was shown that 40% of intervention homes with children in the target group were accessed, participant children learned the educational messages well (scores increased from a pre-teaching mean of 59% to a post-teaching mean of 92%) and a high level of awareness of the ITBN trial was achieved in these homes (75%). However, specific messages of the education programmed were not well transferred to the home (30%). The discussion emphasises the need for allocation of adequate resources for education in programmes dependent on achieving a change in community practices. We also describe the value of ongoing communication between programme planners and a target population in maximizing the effectiveness of messages and methods used.

PIP: In Kenya, public health officers, public health technicians, and field staff implemented the education component of the insecticide-treated bed net (ITBN) trial in Kilifi District along the coast. The education strategy was based on anthropological survey data collected 4 years before the trial and from community surveys. It included teaching about the intervention to household heads at public meetings (June 1993), individual instruction at the time of bed net delivery (June-July 1993), follow-up education with bed net contacts in a small group format after net delivery (June-August 1993), follow-up education with mothers in a small group format after net delivery (September 1993), house-to-house education at the time of ITBN redipping (April-May 1994), and a teaching program in primary schools (June-July 1994). In September 1993, 98% of mothers understood the important of using bed nets year-round but 29% would not use them when it was too hot. Educators changed ITBN education messages to account for the high level of understanding about the importance of bed net use. Since mothers had low levels of understanding of the etiological link between mosquitoes and malaria, the educators excluded the term malaria from the initial educational messages promoting ITBN use. The researchers evaluated the school program through determining outreach (the number of households accessed), changes in participant children's knowledge, post-teaching assessment of mothers' knowledge, and discussions with parent-teacher associations. 40% of the intervention homes were accessed. Learning the educational messages progressed well with the participant children (mean score, 59% at pre-test and 92% at post-test). At the end of the school program, members of 75% of intervention homes were aware of the ITBN trial. Yet, only 30% of homes understood specific messages of the school program. In conclusion, there is a need for allocation of adequate resources for education to achieve a change in community practices and for ongoing communication to maximize the effectiveness of messages and methods used.

Chronic salicylate poisoning and severe malaria.

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.