BACKGROUND: The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic.
METHODS: We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase-polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria.
RESULTS: Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America.
CONCLUSIONS: The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.).
Note: Malaysia is a study site (CYD14 Primary Study Group authors: HIHJMI, Pediatric Institute, Kuala Lumpur Hospital, Kuala Lumpur; RN, Department of Paediatrics, Hospital Pulau Pinang, Pulau Pinang, Malaysia)
This paper examines the trend and possible contributing factors for the occurrence of the food borne diseases outbreaks in Malaysia. These diseases mainly are cholera, typhoid fever, hepatitis A, dysentery and food poisoning. The outbreaks still occur sporadically in certain high risk areas throughout the country. The incidence rate of all the other three major food borne diseases steadily declined from the year 1988 to 1997 except for food poisoning and cholera. Statistic of food poisoning from the year 1996 to 1997 showed that 66.5% of the outbreak occurred in schools whereas only 0.4% originated from the contaminated food sold at various public food outlets. The school age group is always more affected than the general population. Amongst the contributing factors identified are related to unhygienic food handling practices followed by inadequate safe water supply and poor environmental sanitation. A multisectoral approach between Ministry of Health and other government agencies or private agents needs to be undertaken in the management of the food borne diseases in order to curb the incidences of food borne diseases in Malaysia.
From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, Malaysia, died of rapidly progressive cardiorespiratory failure during an outbreak of hand, foot, and mouth disease caused primarily by enterovirus 71 (EV71). The case children were hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). The illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest radiographs showing pulmonary edema, and 24 had echocardiograms showing left ventricular dysfunction), resulting in cardiopulmonary arrest soon after hospitalization (median time, 9 h). Cardiac tissue from 10 patients showed normal myocardium, but central nervous system tissue from 5 patients showed inflammatory changes. Brain-stem specimens from 2 patients were available, and both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsible for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown cofactors are likely responsible for this rapidly fatal disease.
Fever is one of the most common symptoms of pediatric illnesses; it is an important early symptom of malaria. Fever had served as the entry point for presumptive treatment of malaria among children in Nigerian. Appropriate HSB is important when seeking treatment for fever among under-five children; this will help for better prognosis because treatment will be initiated early. This study attempted to identify caregiver's HSB for under-five children with fever. A cross-sectional study was conducted in Imo-State, Nigeria. Appropriate HSB was operationally defined as seeking treatment from health facility within 24 h of fever. Data were obtained using pretested self-administered questionnaire. Data were analyzed using SPSS version 22. Simple and multiple logistic regression were used to determine predictors of appropriate HSB. A total of 559 eligible respondents were recruited; 103 (18.6%) caregivers had appropriate HSB. The predictors of HSB are being male child (aOR = 2.760; 95% CI:1.536-4.958), the age of child younger than 27 months (aOR = 2.804; 95% CI:1.485-5.295), employed caregivers (aOR = 1.882; 95% CI:1.014-3.493), number of household members (aOR = 2.504; 95% CI:1.464-4.283), and caregivers who decided to seek treatment at early stage (aOR = 7.060; 95% CI:1.616-30.852). Only 18.6% caregivers practiced appropriate HSB for fever cases among under-five children. It is essential to educate caregivers and emphasise on early treatment of fever and appropriate use of health facilities for fever. The findings will be used to improve intervention at the community level and will be compared with follow-up data to evaluate their effectiveness.
Early and targeted antimicrobial therapy improves outcomes in patients with febrile neutropenia (FN). We evaluated the impact of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) on antimicrobial utilization in the management of FN. A cohort of patients with FN and hematological malignancy was identified. Cases (in whom FDG-PET was performed, n = 37) were compared with controls (in whom conventional investigations excluding FDG-PET were performed, n = 76). An underlying cause for FN was determined in 94.6% of cases, compared to 69.7% of controls. FDG-PET had a significant impact on antimicrobial utilization compared to conventional imaging (35.1% vs. 11.8%; p = 0.003), and was associated with shorter duration of liposomal amphotericin-B therapy for systemic fungal infection (median 4.0 days cases vs. 10.0 days controls; p = 0.001). Cases had a longer length of hospitalization (p = 0.016). In the management of patients with high-risk FN, FDG-PET improves diagnostic yield and allows rationalization of antifungal therapy. The impact upon healthcare costs associated with antimicrobial therapy for FN requires further evaluation.
Two hundred and eleven blood transfusions were administered to 26 multi-transfused thalassemic children (aged 9 months-13 years) over a 6-month period. Eighteen children were receiving buffy coat-poor packed red cells (PRC) prepared by centrifuge while 8 children received filtered blood through a leucocyte-filter (Sepacell R-500A). Transfusion reactions occurred in 8.5% (n = 18) of transfusions and in 42.3% (n = 11) of patients. 11.9% (n = 16) and 2.6% (n = 2) of reactions occurred in 50% (n = 9) and 25% (n = 2) of patients receiving buffy coat-poor PRC and filtered blood respectively. Transfusion reactions in toto were significantly reduced in the group receiving filtered blood (p < 0.05). However, febrile reaction alone was not significantly reduced (p > 0.1). The median onset and duration of reaction were 2 hours (range 10 minutes-18 hours) and 4 hours (range 1/2-24 hours) respectively. 72.2% (n = 13) of the reactions occurred occurred during transfusion. 88.8% (n = 16) of the reactions caused only one symptom. 19.2% (n = 5) of all patients had recurrent reactions, all of them receiving buffy coat-poor PRC. The commonest clinical manifestation was fever (n = 7), followed by urticaria (n = 5) and petechial rash (n = 2). The outcome was good, with no patient experiencing symptoms exceeding 24 hours. Only 0.9% (n = 2) of the transfusions were discontinued.
Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.
This study was performed out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of an aqueous extract of Dicranopteris linearis leaves in experimental animals. The antinociceptive activity was measured using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory and antipyretic activities were measured using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, obtained after 72 h soaking of the air-dried leaves in distilled water and then prepared in the doses of 13.2, 66.0, 132.0, and 660.0 mg/kg, was administered subcutaneously 30 min before subjecting the animals to the assays mentioned above. Generally, the extract, at all doses used, was found to have significant (P < 0.05) concentration-independent antinociceptive, anti-inflammatory, and anti-pyretic activity. In conclusion, the aqueous extract of D. linearis has antinociceptive, anti-inflammatory, and antipyretic activity, supporting previous claims of its traditional use by the Malays to treat various ailments, particularly fever.
The purpose of this study was to determine if the Multinational Association for Supportive Care in Cancer (MASCC) risk-index score is able to predict the outcome of febrile neutropenia in patients with underlying hematological malignancy and to look at the other possible predictors of outcome. A retrospective study of 116 episodes of febrile neutropenia in patients who were admitted to the hematology ward of a local medical center in Malaysia between January 1st 2004 and January 31st 2005. Patient characteristics and the MASCC score were compared with outcome. The MASCC score predicted the outcome of febrile neutropenic episodes with a positive predictive value of 82.9%, a sensitivity of 93%, and specificity of 67%. Other predictors of a favorable outcome were those patients who had lymphomas versus leukemias, duration of neutropenia of less than 7 days, low burden of illness characterized by the absence of an infective focus and absence of lower respiratory tract infection, a serum albumin of >25 g/l, and the absence of gram-negative bacteremia on univariate analysis but only serum albumin level, low burden of illness, and presence of respiratory infection were significantly associated with unfavorable outcome after multivariate analysis. The MASCC score is a useful predictor of outcome in patients with febrile neutropenia with underlying hematological malignancies. This scoring system may be adapted for use in local settings to guide the clinical management of patients with this condition.
An 18-year-old male adolescent presented with prolonged high spiking temperature, photosensitive rash, oral ulcers and reduced hearing bilaterally of recent onset. Examination revealed malar rash, vasculitis rash over bilateral palms and soles, oral and buccal ulcers, palpable posterior auricular and inguinal lymph nodes, and reduced hearing bilaterally. His further investigations noted pancytopaenia, elevated transaminases, hyperferritinaemia, low C3 and C4 levels, positive antinuclear antibody, double-stranded DNA and direct Coombs test, while bone marrow aspiration revealed active phagocytic activity suggestive of hemophagocytic syndrome. We made a diagnosis of systemic lupus erythematosus with macrophage activation syndrome. We treated him with pulse intravenous methylprednisolone and his condition improved drastically. Temperature resolved on the next day after intravenous methylprednisolone; bilateral sensorineural hearing loss improved to near-normal hearing after treatment. He remained well during follow-up with a tapering dose of prednisolone.
To study the distribution of presenting features and their prognostic significance in neuroblastoma treated in a single institution in Malaysia. A retrospective study was made of 78 neuroblastoma cases diagnosed and treated in the University Hospital, Kuala Lumpur, Malaysia between June 1982 and February 1997. Diagnosis was established by standard histological criteria. The presenting features were evaluated for their distribution and prognostic influence. Disease-free survival from diagnosis was the outcome variable of interest. The ages ranged from 0.1 to 11 years old (median: 3 years old). The tumor originated from the adrenal glands in 83% and the majority of cases presented in advanced stage (stage III 22%, stage IV 66%). Bone marrow was the commonest site of distant metastasis occurring in 45% of patients. The main presenting signs and symptoms in decreasing order were pallor, fever, abdominal mass, weight loss, and bone/joint pain. Univariate analysis conferred age, initial stage and Hb level as significant prognostic factors. No influence in disease-free survival was found for sex, race, primary site, urinary vanillylmandelic acid level, white cell count and platelet count. Overall 2-year disease-free survival was achieved in 27 (39%) patients. Four patients underwent bone marrow transplant, three of whom achieved 2-year disease-free survival. The results suggest that age, initial stage and hemoglobin level are significant prognostic factors based on univariate analysis. In addition, more Malaysian children presented with adrenal primary site and advanced disease compared to previous reported studies.
The incidence of infection following TEVAR is low. To the best of our knowledge, this is the first case report of post thoracic endovascular aortic repair (TEVAR) with Streptococcus viridans graft infection. A 54-year-old male underwent TEVAR for dissecting thoracic aneurysm with spinal ischaemia. He had an eventful recovery with prolonged period of stay in intensive care unit. Three months later, he presented with persistent chest discomfort and fever. Computed tomography (CT) of the thorax revealed evidence of graft infection and the blood culture grew Streptococcus viridans. The rarity of TEVAR graft infection due to Streptococcus viridans and its management are being discussed.