Chikungunya in Jamaica: Public health effects and clinical features in children / Chikungunya en Jamaica ­ Efectos en la Salud Pública y Características Clínicas en Niños

Chikungunya virus (CHIKV) entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica. METHODS: This study reviewed the public health effects of the illness in Jamaica by reviewing available data sources and the clinical features in 210 children and adolescents meeting the case definition at two hospitals, Bustamante Hospital for Children and University Hospital of the West Indies between August 23 and October 31, 2014 by chart review. Descriptive analyses and comparisons between groups using the Mann-Whitney U test were performed with SPSS version 22. RESULTS: The majority of households were affected by the illness which caused widespread absenteeism from school and work, loss of productivity and economic losses estimated at 60 billion dollars. The health sector was impacted by increased numbers seen in clinics and emergency departments, increased need for bed space and pharmaceuticals. Ninety-nine per cent of the children were febrile with a median maximal temperature of 102.4 F. Ninety-three per cent had household contacts of 0­20 persons. In addition to fever, maculopapular rash and joint pains, infants six months and younger presented with irritability and groaning (p = 0.00) and those between six months and six years presented with febrile seizures (p = 0.00). Neurologic involvement was noted in 24%. Apart from anaemia, few had other laboratory derangements. Few had severe organ dysfunction and there were no deaths. CONCLUSION: The Chikungunya Fever epidemic had significant public health and economic impact in Jamaica. In children, there were characteristic presentations in neonates and young infants and in children six months to six years. Neurologic involvement was common but other organ dysfunction was rare. These findings underscore the need to prevent further epidemics and the quest for a vaccine.(AU)

Antecedentes: El virus de Chikungunya (CHIKV) entró en el Caribe por primera vez en 2013, y Jamaica experimentó su primera epidemia de fiebre de Chikungunya en 2014. Nos propusimos como objetivo describir sus efectos en la salud pública y describir sus características clínicas en niños y adolescentes en Jamaica. Métodos: Este estudio examinó los efectos de la enfermedad en la salud pública en Jamaica. El examen se realizó mediante la revisión de fuentes de datos disponibles y las características clínicas en 210 niños y adolescentes que cumplían con la definición del caso en dos hospitales ­ Hospital Pediátrico Bustamante y el Hospital Universitario de West Indies ­ entre el 23 de agosto y 31 de octubre de 201, según las historias clínicas. Se realizaron análisis descriptivos y comparaciones entre los grupos usando la prueba U de Mann-Whitney y la versión 22 de SPSS Resultados: La mayoría de los hogares fueron afectados por la enfermedad, que causó un ausentismo generalizado en escuelas y trabajos, pérdida de productividad, y pérdidas económicas estimadas en 60 billones de dólares. El sector de la salud fue afectado por un aumento del número de personas atendidas en clínicas y departamentos de urgencias, y una mayor necesidad de camas en los hospitales y productos farmacéuticos. Noventa y nueve por ciento de los niños presentaron un estado febril con una temperatura mediana máxima de 102.4 F. Un noventa y tres por ciento tuvo contactos domésticos de personas de 0­20. Además de fiebre, erupciones maculopapulares y dolores en las articulaciones, los niños de seis meses o menos edad, presentaron irritabilidad y quejidos (p = 0.00), y aquellos entre seis meses y seis años de edad presentaron convulsiones febriles (p = 0.00). Se observó compromiso neurológico en el 24%. Aparte de anemia, algunos tenían otros trastornos de laboratorio. Otros presentaban una disfunción orgánica severa y no hubo muertes. Conclusión: La epidemia de fiebre de Chikungunya tuvo un impacto significativo tanto en la salud pública como en la economía de Jamaica. Los niños presentaron manifestaciones características, observadas tanto en recién nacidos y bebés pequeños como en niños de seis meses a seis años. El compromiso neurológico fue común, pero cualquiera otra disfunción orgánica fue rara. Estos hallazgos subrayan la necesidad de hacer más por evitar las epidemias y buscar la solución de una vacuna.(AU)

Development of ideas on renovascular hypertension.

Stephen Hales was the first to measure blood pressure directly in the horse (1733), and the definitive studies on human nephrins by Richard Bright followed much later (1836). The relation between high blood pressure and renal disease was established by Mahomed (1872). The discovery of renin and its possible link with Bright's disease was made by Tigerstedt and Bergman (1898), but only the experimental production of renal hypertension by Goldblatt and his colleagues (1934) led to the delineation of the role of the kidney in human hypertension by a wide variety of methods.

Abdominal obesity, impaired nonesterified fatty acid suppression, and insulin-mediated glucose disposal are early metabolic abnormalities in families with premature myocardial infarction.

British Indian Asian men aged <40 years have a twofold to threefold increased risk of death from coronary heart disease (CHD) compared with British whites. Epidemiological studies have suggested an association between glucose intolerance and hyperinsulinemia with premature CHD in Indian Asians. We tested the association of insulin action with myocardial infarction (MI) by using the hyperinsulinemic-euglycemic clamp in 17 MI patients: 8 Punjabi Sikhs (PSMIs), 9 British whites (BWMIs), and 17 control subjects (9 PSCs and 8 BWCs). Metabolic factors associated with insulin resistance were investigated in 51 MI patients (24 PSMIs and 27 BWMIs) and 53 control subjects (28 PSCs and 25 BWCs). Familial aggregation of defective insulin action was examined by studying five pedigrees of Sikh survivors of MI. Sikh survivors of premature MI demonstrated impaired insulin-mediated glucose uptake (P<.001) by use of the clamp technique and nonesterified fatty acid (NEFA) suppression (P<.05) by using both clamp techniques and the oral glucose tolerance test, as compared with Sikh control subjects. White patients had impaired insulin-mediated glucose uptake but normal NEFA suppression. Metabolic factors usually associated with insulin resistance, including increased 2-hour post-oral glucose tolerance test triglycerides, smaller low density lipoprotein particle size, and increased plasminogen activator inhibitor-1, were present in white (all P<.05) but surprisingly absent in Sikh (all P>.05) MI patients compared with respective ethnic control subjects. Fasting glucose and total cholesterol levels did not differ between patients and control subjects. Abdominal obesity, impaired NEFA suppression after oral glucose, and fasting hyperinsulinemia were present in Sikh MI patients and their nondiabetic first-degree relatives compared with Sikh control subjects. PS survivors of premature MI demonstrated impaired insulin-mediated glucose disposal and NEFA suppression compared with ethnic control subjects. BWMI patients showed abnormalities of carbohydrate, but not of NEFA, metabolism compared with white control subjects. Defects of insulin action manifested as abdominal obesity, impaired NEFA suppression, and fasting hyperinsulinemia are present in Sikh MI patients and their asymptomatic, nondiabetic, first-degree relatives. We suggest that these defects may be early metabolic markers that predict risk of premature MI among PSs.

Is there any evidence for a protective effect of antithrombotic medication on cognitive function in men at risk of cardiovascular disease? Some preliminary findings.

To explore whether antithrombotic medication may protect against cognitive decline, tests of verbal memory, attention, abstract reasoning, verbal fluency, and mental flexibility were administered to 405 men at risk of cardiovascular disease. These subjects were a subgroup of those who had been participating in a randomised double blind factorial trial of low dose aspirin (75 mg daily) and low intensity oral anticoagulation with warfarin (international normalised ratio of 1.5) at 35 general practices across the United Kingdom for at least five years, were at least 55 years old at trial entry, and had been randomly allocated to one of four groups: active warfarin and active aspirin, active warfarin and placebo aspirin, placebo warfarin and active aspirin, and double placebo. Verbal fluency and mental flexibility were significantly better in subjects taking antithrombotic medication than in subjects taking placebo. Aspirin may have contributed more than warfarin to any beneficial effect. These results provide tentative evidence that antithrombotic medication may protect cognitive function in men at risk of cardiovascular disease.

Separation of peripheral and central cardiovascular actions of angiotensin II.

The pressor and vasoconstrictor action of angiotensin II (ANG II) is considered to be caused by a combination of its direct and indirect vascular effects, the latter mediated by the sympathetic nervous system. The purpose of this study was to determine the extent to which the direct and indirect actions of ANG II contribute to its pressor and vascular effects. Blood pressure, cutaneous vascular, and plasma norepinephrine responses to intravenous ANG II were measured in conscious rabbits before and after inhibition of central sympathetic outflow with intravenous and intracisternal clonidine and after ganglionic blockade with intravenous pentolinium. Intravenous ANG II caused a similar dose-related rise in blood pressure before and after sympathetic blockade with intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. In contrast, the dose-related fall in cutaneous ear blood flow and cutaneous ear temperature and rise in cutaneous ear vascular resistance induced by intravenous ANG II were abolished after intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. Heart rate was unchanged after ANG II. There were no changes in back skin or rectal temperature. There was a nonsignificant fall in plasma norepinephrine and no change in epinephrine after ANG II. These results demonstrate that the acute pressor response to intravenous ANG II is mediated by its direct vascular effects and is not dependent on central or ganglionic stimulation of the sympathetic nervous system, in contrast to the effect of ANG II on cutaneous ear vasoconstriction, which is predominantly caused by a centrally mediated increase in sympathetic nervous activity. Our results separate, in conscious rabbits, the direct vascular effects of ANG II from its indirect vascular actions, which are mediated by central sympathetic stimulation in the brain.

Do normal plasma neurotensin concentrations increase ileal output?

Infusions of neurotensin increase ileal secretion in experimental animals, and the volume of ileal effluent in patients with ileostomies. The aim of the present study was to determine whether normal postprandial plasma concentrations of neurotensin increase the volume of fluid leaving the ileum. Basal and peak postprandial plasma neurotensin concentrations were 23 (17-36) and 39 (25-43) pmol/l (median and range) respectively in five subjects with ileostomies and 15 (3-27) and 32 (15-82) pmol/l respectively in nine normal subjects. Infusion of neurotensin for 30 min at a rate of 6.3 pmol/kg/min into six patients with ileostomies increased ileostomy output about 10-fold, and produced a significant decrease in the concentration of solid material, but plasma neurotensin concentrations rose to 237 (82-422) pmol/l during infusion at this rate. Infusion of neurotensin at 2.3 pmol/kg/min, producing plasma levels of 60 (16-108), had no significant effect the amount or nature of ileostomy effluent. We conclude that normal postprandial plasma concentrations of neurotensin are unlikely to influence the volume of fluid leaving the ileum.

Relationship between splanchnic vasodilation and postprandial hypotension in patients with primary autonomic failure.

The haemodynamic responses to a standard liquid meal were measured in patients with autonomic failure and in normal subjects. Resting superior mesenteric artery blood flow was similar in both groups, but mean supine arterial pressure and the superior mesenteric artery vascular resistance were higher in the patients with autonomic failure than in the normal subjects. After the meal there was a rise in superior mesenteric artery blood flow and a fall in superior mesenteric artery vascular resistance in both groups. Mean arterial blood pressure fell substantially after food in the patients with autonomic failure but not in the normal subjects. The basal heart rate, stroke distance and cardiac index were higher in the patients with autonomic failure, and rose significantly after the meal only in the normal subjects. Forearm blood flow fell and the vascular resistance rose after the meal in the normal subjects but not in the patients with autonomic failure. We conclude that superior mesenteric artery blood flow rose and superior mesenteric artery vascular resistance fell after the meal in the normal subjects and in the patients with autonomic failure. However, in the normal subjects the blood pressure was maintained by factors which include a rise in the heart rate and cardiac output. The lack of such compensatory changes probably accounts for postprandial hypotension in patients with autonomic failure.

Angiotensin converting enzyme inhibition lowers blood pressure in patients with primary autonomic failure independently of plasma renin levels and sympathetic nervous activity.

The haemodynamic and neurohormonal responses to the angiotensin converting enzyme (ACE) inhibitor captopril were studied in 12 patients with primary autonomic failure; seven had multiple system atrophy and five had pure autonomic failure. Basal supine mean arterial blood pressure was higher in the patients with multiple system atrophy than in those with pure autonomic failure and the normal subjects. Basal plasma noradrenaline levels were normal in the patients with multiple system atrophy, but lower in those with pure autonomic failure. Captopril lowered the mean arterial pressure in the patients with multiple system atrophy and pure autonomic failure but not in the normal subjects. In the patients with multiple system atrophy and pure autonomic failure, captopril lowered the cardiac output and the stroke volume. Forearm vascular resistance was unchanged. No significant changes occurred in the normal subjects. Plasma renin activity was unchanged after captopril in the patients with autonomic failure, but rose in the normal subjects. Plasma noradrenaline was unchanged in all groups after the administration of captopril. We conclude that captopril lowers the mean arterial pressure in patients with multiple system atrophy and pure autonomic failure. After the administration of captopril there is a reduction in cardiac output, secondary to a fall in stroke volume. The vasodepressor response to captopril in patients with autonomic failure is not related to the basal level of plasma renin activity or sympathetic nervous activity, indicating that the hypotensive effects of bradykinin or prostaglandins, or both, may contribute.

Renin messenger RNA localization in congenital mesoblastic nephroma using in situ hybridization.

Renin messenger (m) RNA distribution was studied in congenital mesoblastic nephroma, a usually benign renal tumour of early infancy which may be associated with excess renin production and hypertension. Using in situ hybridization with synthetic radiolabelled oligonucleotide probes combined with immunohistochemical studies, renin expression was found in areas of tumours containing recognizable cortical structures including glomeruli and tubules. Renin mRNA was also detected in vessels and larger vascular spaces within the tumour not associated with cortical structures. Cells in the tumour vessel walls and sinusoids which expressed renin also stained positively for vascular smooth muscle-specific alpha actin.

Cardiovascular and neurohormonal changes following central sympathetic blockade with clonidine in human unilateral renal artery stenosis.

The role of central pressor mechanisms in the maintenance of blood pressure in six hypertensive patients with angiographically proven unilateral renal artery stenosis was investigated by studying the haemodynamic and hormonal responses before and after central sympathetic blockade with clonidine. To assess the dependency of blood pressure on the direct effects of angiotensin II, the same patients were studied on a separate occasion after administration of the angiotensin converting enzyme (ACE) inhibitor, captopril. There was a substantial fall in blood pressure after administration of clonidine with a smaller fall after captopril. Clonidine-induced hypotension was accompanied by a fall in cardiac output, through a reduction in the stroke volume and heart rate. Forearm vascular resistance was unchanged. There was a selective decrease in digital skin vascular resistance and plasma noradrenaline, indicating reduced sympathetic activity. Plasma renin activity and aldosterone levels did not fall. After administration of captopril, there was a fall in cardiac output due to a fall in the stroke volume but not in the heart rate. Forearm vascular resistance, digital skin vascular resistance and plasma noradrenaline were unchanged. Plasma renin activity rose and plasma aldosterone fell. We conclude that in our hypertensive patients with renal artery stenosis, clonidine lowered blood pressure by a reduction in central sympathetic activity independently of renin suppression. In these patients captopril had minimal hypotensive effects, indicating a smaller role for the direct vascular effects of angiotensin II.

Problems in the treatment of hypertension.

The major problems discussed and the responses are: (1) Is blood pressure measurement by ordinary sphygmomanometer still valid as a guide to decisions? Yes. (2) Is translation of population into individual risk based on blood pressure alone appropriate as the sole criterion for treatment? No. All risk factors and observation time are important. (3) Does a good response to medical treatment preclude full investigation? No. Knowledge is better than ignorance. (4) Are trial results useful clinically? Yes, if selection of subjects, major risk factors, and relative benefits of treatment are clearly presented. (5) Do some drugs have beneficial effects on stroke and myocardial infarct other than purely those due to lowering of pressure? Yes: bendrofluazide and stroke. (6) Can smoking interfere with beneficial effects? Yes: propranolol and stroke. (7) Have some drugs serious adverse effects? Possibly thiazide in myocardial ischaemia. (8) Is it dangerous to lower the diastolic pressure below 90 mmHg? Possibly. (9) Is there a hypertension treatment paradox in stroke and myocardial infarct? Yes.

Retinal arterial macroaneurysms: a retrospective study of 40 patients.

We studied 40 patients with a total of 44 retinal arterial macroaneurysms. All patients were followed up for at least six months. Macroaneurysms (MAs) have variable clinical presentations and are still frequently misdiagnosed before fluorescein angiography. Haemorrhagic MAs were most frequently misdiagnosed (75%), and had a sudden onset with a relatively poor visual outcome. Patients with these MAs had higher systolic blood pressures and significantly fewer associated retinal vein occlusions (p less than 0.05) than other types of MA. Exudative MAs caused a gradual onset of symptoms, were frequently associated with retinal vein occlusions, and were the most frequent indication for laser treatment. Only one of 10 quiescent MAs subsequently developed significant exudation or haemorrhage. We confirm the association of MAs with retinal and systemic vascular disease. In addition we found that MA patients had a significantly higher blood packed cell volume (haematocrit) than controls (p less than 0.05). Laser treatment significantly shortened the duration of MA patency (p = 0.006).

Results of MRC (UK) trial of drug therapy for mild hypertension.

The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events, in men and women aged 35-64 years. A total of 17,354 patients was recruited, and 85,572 patient-years of observation accrued. Patients were randomly allocated at entry to take bendrofluazide or placebo, or propranolol or placebo. The stroke rate was reduced with treatment (60 strokes, vs 109 in the placebo groups), being 1.4 and 2.6 per 1,000 patient-years of observation, respectively (p less than 0.01), but overall rates of coronary events were not different (222 with treatment and 234 with placebos). The incidence of all cardiovascular events was reduced with treatment (286 events, vs 352 with placebos; p less than 0.05). For rates of mortality from all causes, treatment made no difference. Several post hoc analyses of subgroup results were performed. The all-cause mortality was reduced in men on treatment (157 deaths, vs 181 in placebo groups) but increased in women on treatment (91 deaths, vs 72 with placebos); this difference between the sexes was significant (p = 0.05). The reduction in stroke rate was greater with bendrofluazide than with propranolol (p = 0.002). The rate of strokes was reduced in both smokers and non-smokers taking bendrofluazide, but only in non-smokers taking propranolol; this difference between the drugs was significant (p = 0.03). The coronary-event rate was not reduced by bendrofluazide, whatever the smoking habit, nor in smokers taking propranolol, but it was reduced in non-smokers taking propranolol. (ABSTRACT TRUNCATED AT 250 WORDS)