The role of imported cases in the epidemiology of urban Plasmodium falciparum malaria in Quibdó, Colombia.

OBJECTIVE: To assess the role of imported cases in the local epidemiology of malaria and population genetics of Plasmodium falciparum in an urban endemic area in Colombia. METHOD: A total of 679 P. falciparum cases presenting in the city were interviewed, mapped, and genotyped using msp1 and msp2 molecular markers. RESULTS: Among the cases, 75% were classified as imported and harboured single-clone infections. The P. falciparum parasite population had low genetic diversity with a preponderant haplotype (mean genetic diversity H = 0.36), even when microsatellite markers were used (H = 0.49), partly because of the small scale at which population movement was studied. Nevertheless, indigenous and potentially introduced cases were identified. CONCLUSION: Migration is a confounder in planning malaria control in this endemic urban area. Longitudinal studies which monitor the P. falciparum population in imported and autochthonous cases at larger spatial scales would be necessary to study the effect of population movement on malaria transmission and, with suitable molecular markers, on the spread of drug resistance.

Overview of management of atrial fibrillation in symptomatic elderly patients: pharmacologic therapy versus AV node ablation.

Atrial fibrillation is an abnormal heart rhythm affecting the upper chambers of the heart in which uncoordinated electrical depolarizations lead to ineffective contractions. Approximately five million patients in the US have atrial fibrillation, and this number is expected to double to 10 million over the next 30 years. Advancing age is a major risk factor for the development of atrial fibrillation; new cases of atrial fibrillation are diagnosed in men over age 80 at the rate of 2% per year. Although several drugs are available for management of atrial fibrillation, the efficacy of these drugs may be limited in elderly patients. In this review, we provide an overview of management of atrial fibrillation, with special emphasis on pharmacologic therapy versus arteriovenous (AV) node ablation in symptomatic elderly patients.

Radiofrequency ablation for supraventricular tachycardia in children < or =15 kg is safe and effective.

Risks associated with radiofrequency ablation (RFA) have been reported to be increased in children < or =15 kg. We sought to compare the safety and efficacy of RFA in children <15 kg with those between 15.1 and 20 kg. Clinical, electrophysiologic, and RFA data for all patients < or =20 kg who underwent RFA for supraventricular tachycardia between January 1994 and January 2003 were reviewed. Patients were divided into those < or =15 kg (group 1, n = 25) and those between 15.1 and 20 kg (group 2, n = 44). The two groups differed significantly in age and weight by design (group 1: mean weight, 11.9 +/- 3.0 kg; age, 2.8 +/- 1.9 years; group 2: weight, 18.0 +/- 1.5 kg; age, 5.1 +/- 1.1 years). There were no significant differences in other baseline characteristics except for incidence of structural heart disease (28% group 1 vs 7% group 2, p < 0.01). No significant differences in mechanism of tachycardia, arrhythmia cycle length, number of total and brief RFA applications, total RFA time, average and maximum RFA temperatures, total procedure duration, short-term success rate (96% group 1 vs 86% group 2, p = 0.17), long-term success rate (91% group 1 vs 89% group 2, p = 0.76), or major complications (8.0% group 1 vs 2.3% group 2, p = 0.39) were found. There were no procedure-related deaths in either group. These data suggest that, in two large volume electrophysiology centers, the procedural risks and outcomes of RFA are similar between patients weighing less than 15 kg and those between 15.1 and 20 kg.

Guidelines for malaria prevention in travellers from the United Kingdom for 2003.

This updated guidance from the Advisory Committee on Malaria Prevention for UK Travellers provides the essential information for healthcare workers who advise travellers. The many personal, visit and location-specific factors that need to be taken into account are discussed. Tables include the available antimalarials for prophylaxis and for standby treatment, appropriate choices of regimen by region and country for malarious areas, and the adjustments needed for children and in concomitant disease. There is greater emphasis on mefloquine, doxycycline and atovaquone/proguanil as the three options for highly chloroquine-resistant falciparum malarious areas, and changes in emergency standby medication.

Malaria prophylaxis for long-term travellers.

These guidelines are designed to assist healthcare workers who are advising long-term travellers on malaria prophylaxis, defined for the purpose of this document as those travelling for longer than 6 months. The document focuses on long-term use of antimalarials for adults, but also identifies specific issues for women and children. However, data on the long-term use of antimalarials is limited for all travellers and few data are available on the incidence of malaria in travellers overseas or, indeed, deaths overseas from malaria. Whilst all available evidence is taken into account, the advice provided also reflects experienced professional opinion. This document has been written on behalf of the Health Protection Agency's Advisory Committee on Malaria Prevention for UK Travellers, and is designed to act as a supplement to the 'Guidelines for malaria prevention in travellers from the United Kingdom for 2003'. The latter document contains a more complete description of antimalarials and additional preventive measures, together with recommendations for malaria chemoprophylaxis for individuals countries. Decisions on the terms under which different drugs are licensed for use are the responsibility of the Committee on Safety of Medicines. This paper should also, therefore, be used in conjunction with Summary of Product Characteristics (data sheets).

Modeling the potential radionuclide transport by the Ob and Yenisey Rivers to the Kara Sea.

A major portion of the former Soviet Union (FSU) nuclear program is located in the West Siberian Basin. Among the many nuclear facilities are three production reactors and the spent nuclear fuel reprocessing sites, Mayak, Tomsk-7, and Krasnoyarsk-26, which together are probably responsible for the majority of the radioactive contamination found in the Ob and Yenisey River systems that feed into the Arctic Ocean through the Kara Sea. This manuscript describes ongoing research to estimate radionuclide fluxes to the Kara Sea from these river systems. Our approach is to apply a hierarchy of simple models that use existing and forthcoming data to quantify the transport and fate of radionuclide contaminants via various environmental pathways. We present an initial quantification of the contaminant inventory, hydrology, meteorology, and sedimentology of the Ob River system and preliminary conclusions from portions of the Ob River model.

Guidelines for malaria prevention in travellers from the United Kingdom for 2001.

These guidelines on malaria prevention are designed to aid health care workers who advise travellers, particularly those who will be overseas for less than a year. The present, and any future, revisions are the responsibility of the Advisory Committee on Malaria Prevention in UK travellers (ACMP; membership given at the end of the Guidelines). This has replaced the consensus meetings which produced earlier versions from 1980 to the the 1997 version. The guidelines are in three parts. The first part is a summary that emphasises modifications to the advice given in the last set of guidelines, published in 1997. The second part discusses the issues addressed in formulating the guidelines. Oversimplified lists of recommendations by country can be misleading. The second part also addresses the health care worker's consultation with prospective travellers. Doctors, practice nurses and pharmacists are asked to read this section to ensure that due attention is paid to the traveller's history and destination. The third part gives specific recommendations for travellers to specific destinations and some details of individual drugs. Fuller information on some drugs now less used was given in earlier versions of the guidelines. These guidelines reflect experienced professional opinion. Data are inadequate for unequivocal views to be given on several issues, but all available evidence has been taken into consideration. There is often a range of acceptable options, but to meet the requests of general practitioners the guidelines aim to give one recommended option and state the alternatives, suggesting when and how different regimens can be used to good effect. However, there are now several options for effective prophylaxis of highly chloroquine-resistant falciparum malaria, and the choice between them will depend on details of the journey and individual preferences. Decisions on the terms under which different drugs are licensed for use are the responsibility of the Licensing Authority, advised by the Committee on Safety of Medicines and not of the ACMP. The guidelines should therefore be read as a supplement to and not as a substitute for the relevant data sheets. In concept and practice, chemoprophylaxis lies somewhere between vaccinations (for which people expect governments to lay down schedules) and treatment of ill people (which is determined by individual clinical need and choice). The risks of malaria need to be balanced against the risks of the preventive measures, on the basis of the data available. Travellers may ask for an explanation of these risks and doctors and practice nurses need to be well informed and able to present this information to travellers. The second part of these guidelines may also be of use to prospective travellers who wish to read about the options themselves. All readers are recommended to read part two in its entirety to get a balanced picture.

The clinical course of multifocal atrial tachycardia in infants and children.

OBJECTIVES: This study outlines the clinical course, treatment and the late outcome of infants and children with multifocal atrial tachycardia (MAT). BACKGROUND: Multifocal atrial tachycardia is defined by three distinct P-waveforms, irregular P-P intervals, isoelectric baseline between P-waves and rapid rate on an electrocardiogram. Several smaller prior reports have described pediatric patients with MAT, but their long-term outcome has not been fully assessed. METHODS: The clinical records, echocardiograms and long-term follow-up of patients with MAT were reviewed and compared to previous reports of MAT. RESULTS: Fourteen boys and seven girls (median age 1.8 months) presented with MAT. At diagnosis, six patients had respiratory illness, of whom two were critical. Ten were asymptomatic. Seven patients had structural heart disease (SHD), one of whom died. Four of 15 patients (27%) with echocardiograms had diminished ventricular function. Ventricular rates were 111 to 253 beats/min (mean 181 beats/min). Median duration of the arrhythmia was 4.9 months (mean 6.7 months). Electrical cardioversion was attempted in 4 patients without success and 15 patients received antiarrhythmic medication. Seventeen patients were followed for a mean of 60 months. Four patients were lost to follow-up. There were no late arrhythmias. CONCLUSIONS: The majority of children with MAT are healthy infants under one year of age; a few may exhibit mild to life-threatening cardiorespiratory disease. Less often, MAT accompanies SHD. Mild ventricular dysfunction may be observed in the presence of MAT, but symptoms are few and resolution is generally complete. Response to antiarrhythmic agents is mixed, and cardioversion is of no avail. Finally, long-term cardiovascular and developmental outcome depends principally on underlying condition; for otherwise healthy children, it is excellent.

Expression of CENTRORADIALIS (CEN) and CEN-like genes in tobacco reveals a conserved mechanism controlling phase change in diverse species.

Plant species exhibit two primary forms of flowering architecture, namely, indeterminate and determinate. Antirrhinum is an indeterminate species in which shoots grow indefinitely and only generate flowers from their periphery. Tobacco is a determinate species in which shoot meristems terminate by converting to a flower. We show that tobacco is responsive to the CENTRORADIALIS (CEN) gene, which is required for indeterminate growth of the shoot meristem in Antirrhinum. Tobacco plants overexpressing CEN have an extended vegetative phase, delaying the switch to flowering. Therefore, CEN defines a conserved system controlling shoot meristem identity and plant architecture in diverse species. To understand the underlying basis for differences between determinate and indeterminate architectures, we isolated CEN-like genes from tobacco (CET genes). In tobacco, the CET genes most similar to CEN are not expressed in the main shoot meristem; their expression is restricted to vegetative axillary meristems. As vegetative meristems develop into flowering shoots, CET genes are downregulated as floral meristem identity genes are upregulated. Our results suggest a general model for tobacco, Antirrhinum, and Arabidopsis, whereby the complementary expression patterns of CEN-like genes and floral meristem identity genes underlie different plant architectures.

Separation of shoot and floral identity in Arabidopsis.

The overall morphology of an Arabidopsis plant depends on the behaviour of its meristems. Meristems derived from the shoot apex can develop into either shoots or flowers. The distinction between these alternative fates requires separation between the function of floral meristem identity genes and the function of an antagonistic group of genes, which includes TERMINAL FLOWER 1. We show that the activities of these genes are restricted to separate domains of the shoot apex by different mechanisms. Meristem identity genes, such as LEAFY, APETALA 1 and CAULIFLOWER, prevent TERMINAL FLOWER 1 transcription in floral meristems on the apex periphery. TERMINAL FLOWER 1, in turn, can inhibit the activity of meristem identity genes at the centre of the shoot apex in two ways; first by delaying their upregulation, and second, by preventing the meristem from responding to LEAFY or APETALA 1. We suggest that the wild-type pattern of TERMINAL FLOWER 1 and floral meristem identity gene expression depends on the relative timing of their upregulation.

The last and the next hundred years of malariology.

The founding fathers of malariology combined scientific originality, perseverance in research, strong characters, breadth of interest and social concern. A hundred years later research and understanding has made immense progress but the world still bears a huge burden of malaria. For the next century research requires both more specialism and a holistic range if it is to be used in control, requiring multidisciplinary team work. Environmental changes and interventions produce a dynamic and changing pattern of malaria, not the static one of the past. From the original parasite life cycle, research has analysed a series of other cycles at electron microscope, biochemical and genome levels on decreasing size scales and quantitative epidemiological cycles for control. Recent additions to these concepts have been stage-specific antigens, cycles of disease rather than parasites alone, considering populations of parasites rather than just cases, and also genetic variation in each component of the parasite-human host-vector triad. In this volume there emerges for the first time a coherent overall picture of the biomedical aspects of basic malariology as the interacting population genetics of malaria parasites, anophelines and people. This provides a coherent model for the new century dealing with the great biological malaria problems of drug resistance, vaccine development, insecticidal and net control and can feed, with socio-economic work, into the gathering renewal of control efforts. New work on large-scale changes of malaria in space and time enables us to be precise about effects of local and global environmental changes to predict epidemics. Future research will be as much about linking these different scales of understanding as control will be about linking different levels of the health system. The grim situation in poor holoendemic countries also requires practical support of the type that the founders of malariology were involved in. A coherent understanding needs to feed into the new control efforts, from Roll Back Malaria onwards, for the next century.

The public health significance of urinary schistosomiasis as a cause of morbidity in two districts in Mali.

Schistosoma haematobium-related morbidity was studied in the perennial irrigation area of Office du Niger and the small reservoirs area of Plateau Dogon in Mali. Questionnaire, clinical, parasitologic, and ultrasound examination data were collected from 1,041 individuals at the baseline survey in 1991; 705 were re-examined one year after treatment. At baseline, the overall prevalence of S. haematobium infection was 55.2%; half of those infected had no clinical symptoms and 30% had pathologic lesions. Both infection and morbidity were more frequent in children than in adults, with a peak prevalence at 7-14 years of age. The rates of lesions were more than twice as high in those heavily infected as in lightly infected individuals. Reagent strip testing for microhematuria was more sensitive in detecting individuals with pathologic lesions than in detecting individuals with infection. One year after treatment with praziquantel, more than 80% of the urinary tract lesions had cleared. It is concluded that S. haematobium-related morbidity is frequent in Mali, but passive case detection for treatment would not cover a great deal of early stages of the disease; active intervention using reagent strip testing for microhematuria at the most peripheral levels would be an efficient system for morbidity control and monitoring of control operations.

The particular and the general. Issues of specificity and verticality in the history of malaria control.

Several ideas have currency through long periods of malaria control history and important issues in controlling many communicable diseases have often been fought out over malaria. Health administrators view complex problems of malaria control through these apparently simple ideas. The most important concepts concern the need for specific methods to combat particular features of the spread of malaria and how far this is reflected by the development of specific health services. This paper follows these ideas through the last century and argues that the dead hand of history has played too large a role in determining malaria control generally, and especially over the last two decades, while the whole period provides an illuminating commentary on conceptualization in tropical health and its evolution. The two decades following discovery of the mosquito transmission of malaria saw increasingly specific knowledge about the vectors and approaches to preventing breeding. This required "odd" health workers who poured oil on water and did fresh-water biology and later special engineers who could design reservoirs and irrigation systems hostile to anopheline breeding and apply "species sanitation". The expertise required lay outside the health sector. Later, the DDT phase focused on a single highly specialized control technique, total coverage house spraying, and led on to attempted eradication, whose activities were vertically grouped. Malaria eradication became autonomous within the health department. It became the archetypal vertical programme whose funding levels and early successes made it a model to be emulated. But the need for active case surveillance to be integrated with general health services was a major reason for failure in some countries. The subsequent reaction to failed eradication emphasized horizontal or general health services, and these are very relevant to current pre-occupations with morbidity and mortality reduction by early diagnosis and prompt treatment. The future needs a complex mixture of interventions that cut across traditional views of either specificity or of the horizontal/vertical split in programmes, and development of effective control with imperfect tools requires a more sophisticated analysis of control methods and organizations than is provided by a simple vertical/horizontal debate.

Cerebrospinal fluid profile in patients with acute Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood for which there is currently no diagnostic test. The clinical presentation of KD may initially resemble other infectious diseases, including bacterial or viral meningitis. For this reason lumbar puncture (LP) is sometimes performed during the evaluation of these patients. To understand the range of cerebrospinal fluid (CSF) changes that may be associated with acute KD, a retrospective review of unselected KD patients from three pediatric centers was performed. METHODS: Retrospective chart review was performed on KD patients evaluated during the first 10 days of illness who had an LP performed before the administration of intravenous gamma-globulin. RESULTS: During the 6.5-year study period, 46 KD patients underwent LP as part of their clinical evaluation. Of these patients 18 (39.1%) had CSF pleocytosis, 1 (2.2%) had a CSF glucose <45 mg/dl and 8 (17.4%) had an elevated CSF protein. Of the patients with CSF pleocytosis, the median white blood cell count was 22.5 cells (range, 7 to 320 cells), with a median of 6.0% neutrophils (range, 0 to 79%) and 91.5% mononuclear cells (range, 11 to 100%). CONCLUSIONS: In the present series approximately one-third of KD patients who underwent an LP had CSF pleocytosis with a mononuclear cell predominance. No patient had significant hypoglycorrhachia, and elevation of the CSF protein was uncommon. CSF abnormalities were similar between US and Japanese KD patients. The basis for the CSF pleocytosis in acute KD patients remains unknown.

A common mechanism controls the life cycle and architecture of plants.

The overall aerial architecture of flowering plants depends on a group of meristematic cells in the shoot apex. We demonstrate that the Arabidopsis TERMINAL FLOWER 1 gene has a unified effect on the rate of progression of the shoot apex through different developmental phases. In transgenic Arabidopsis plants which ectopically express TERMINAL FLOWER 1, both the vegetative and reproductive phases are greatly extended. As a consequence, these plants exhibit dramatic changes in their overall morphology, producing an enlarged vegetative rosette of leaves, followed by a highly branched inflorescence which eventually forms normal flowers. Activity of the floral meristem identity genes LEAFY and APETALA 1 is not directly inhibited by TERMINAL FLOWER 1, but their upregulation is markedly delayed compared to wild-type controls. These phenotypic and molecular effects complement those observed in the tfl1 mutant, where all phases are shortened. The results suggest that TERMINAL FLOWER 1 participates in a common mechanism underlying major shoot apical phase transitions, rather than there being unrelated mechanisms which regulate each specific transition during the life cycle.

Schistosomiasis haematobia in Mali: prevalence rate in school-age children as index of endemicity in the community.

In a nationwide survey of schistosomiasis conducted in Mali from 1984 to 1989, 56265 individuals from 323 villages had their urine examined parasitologically using a filtration technique. From a sample of 242 children in 3 villages, aged 7 to 14 years, urine samples were collected and tested for haematuria using reagent strips. Analysis of the age-specific prevalence rates of Schistosoma haematobium infection showed a strong positive correlation between the prevalence rate in the 7-14 year-old age group, and both the overall prevalence (r = 0.90; P < 0.001) and the prevalences at other ages. An index was derived from this relationship using the equation: overall prevalence = -1.14 + 0.74 (prevalence in 7-14 year-olds). The sensitivity and specificity of reagent strip testing for microhaematuria as compared to urine filtration were 73.3% and 83.2% respectively. We conclude that reagent strip testing of urine samples collected from a sample of individuals aged 7-14 years would be sufficient to estimate the overall prevalence of Schistosoma haematobium infection in a Malian community and suggest that this assessment procedure be used at the peripheral level of primary health care to decide on treatment regimes.

A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone.

A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while in combination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria.