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1.
Influenza Other Respir Viruses ; 17(7): e13176, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37502622

RESUMO

Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment. Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score. Clinical Trials Registration: NCT02654171.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Lactente , Humanos , Pré-Escolar , Infecções por Vírus Respiratório Sincicial/epidemiologia , Sulfonas/farmacologia , Sulfonas/uso terapêutico , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico
2.
BMJ Case Rep ; 14(4)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910804

RESUMO

We report a term newborn who presented on day 3 of life with unilateral, tender scrotal swelling with skin discolouration, which was subsequently diagnosed as haemophilia A at about 6 months of age. He received intramuscular vitamin K and hepatitis B vaccine at birth uneventfully. The scrotal swelling was treated as an infected hydrocoele, considering the absence of a family history of bleeding disorder and other risks of bleeding tendency, as well as the ultrasonographic features. He also had congenital pneumonia requiring venepuncture, non-invasive oxygen supplementation and intravenous antibiotics, without any complication. The swelling slowly improved over 2 months. He later developed post-trial vaccine injection haematoma at 4 months of age, and multiple non-traumatic bruises when he was 6 months old, leading to the diagnosis. This case demonstrates an uncommon, but a possible, early manifestation of haemophilia A at birth with a unilateral scrotal haematoma.


Assuntos
Doenças dos Genitais Masculinos , Hemofilia A , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hemofilia A/complicações , Hemofilia A/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-877032

RESUMO

@#Introduction: Sarawak has a population that is geographically and characteristically widely varied. This study aimed to determine the demographic profile of patients in Sarawak, Malaysia. Materials and Methods – A cross-sectional study was conducted in 2019 at four major haemophilia treatment centres in Kuching, Sibu, Bintulu and Miri Hospitals, Sarawak. Demographic and clinical data were collected with consents from patients. Results and Discussion: Ninety-six haemophilia patients were identified - 79(82.3%) haemophilia A(HA) and 17(17.7%) haemophilia B(HB). Severe haemophilia patients were noted in 45.6% (36/79) of HA and 64.7% (11/17) of HB. In all 44.3% of the HA and 52.9% of the HB population had no identifiable family history of haemophilia. Two-thirds of the patients with severe HA were on prophylaxis [24/36 (66.7%)] and only onethird [4/11 (36.4%)] in severe HB. Inhibitors developed in 9/79 (11.4%) of the HA population [3/79 (3.8%) high responders]. The median inhibitor titre was not significantly different between the different treatment groups – on demand versus prophylaxis (1.0BU versus 2.0BU; z statistic -1.043, p-value 0.297, Mann-Whitney test). None of the patients developed inhibitory alloantibodies to factor IX. Four HA patients (5.1%) underwent immune tolerance induction where one case had a successful outcome. Three severe HA patients received emicizumab prophylaxis and showed remarkable reduction in bleeding events with no thromboembolic events being reported. One female moderate HA patient received PEGylated recombinant anti-haemophilic factor. Eleven patients underwent radiosynovectomy. One mild HB patient succumbed to traumatic intracranial bleeding. Our data reported a prevalence (per 100,000 males) of 5.40 cases for all severities of HA, 2.46 cases for severe HA; 1.16 cases for all severities of HB, and 0.75 cases for severe HB. The overall incidence of HA and HB was 1 in 11,500 and 1 in 46,000, respectively. Conclusion: This study outlines the Sarawakian haemophilia landscape and offers objective standards for forward planning. Shared responsibilities among all parties are of utmost importance to improve the care of our haemophilia population.

4.
BMJ Case Rep ; 13(5)2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32430349

RESUMO

Children with Down syndrome have a higher risk of stroke. Similarly, intravenous immunoglobulin (IV Ig) is also known to cause a stroke. We reported a 3-year-old boy with Down syndrome who presented with severe pneumonia and received IV Ig. He developed right hemiparesis 60 hours after the infusion. Blood investigations, echocardiography and carotid Doppler did not suggest vasculitis, thrombophilia or extracranial dissection. Brain computerised tomography (CT) showed acute left frontal and parietal infarcts. Initial magnetic resonance angiography (MRA) of cerebral vessels showed short segment attenuations of both proximal middle cerebral arteries and reduction in the calibre of bilateral supraclinoid internal carotid arteries. The boy was treated with enoxaparin and aspirin. He only had partial recovery of the hemiparesis on follow-up. A repeat MRA 13 months later showed parenchymal collateral vessels suggestive of moyamoya disease. We recommend imaging the cerebral vessels in children with a high risk of moyamoya before giving IV Ig.


Assuntos
Imunoglobulinas Intravenosas/efeitos adversos , Doença de Moyamoya/diagnóstico por imagem , Paresia/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Pré-Escolar , Síndrome de Down/complicações , Fibrinolíticos/uso terapêutico , Seguimentos , Humanos , Angiografia por Ressonância Magnética , Masculino , Doença de Moyamoya/tratamento farmacológico , Paresia/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
5.
PLoS Negl Trop Dis ; 11(6): e0005650, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28599008

RESUMO

BACKGROUND: Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak. METHODS: A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics. FINDINGS: Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster. CONCLUSIONS: Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor.


Assuntos
Melioidose/epidemiologia , Melioidose/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Malásia/epidemiologia , Masculino , Estudos Prospectivos , Chuva , Estudos Retrospectivos , Fatores de Tempo
6.
BMC Infect Dis ; 9: 3, 2009 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-19152683

RESUMO

BACKGROUND: Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity. METHODS: We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD. RESULTS: Total duration of fever >or= 3 days, peak temperature >or= 38.5 degrees C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (>or= 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79-6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature >or= 38.5 degrees C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of >or= 2 risk factors predictive of CSF pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively. CONCLUSION: Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for hospitalization and further investigation, including cerebrospinal fluid examination, and close monitoring for disease progression in children with HFMD.


Assuntos
Doenças do Sistema Nervoso Central/etiologia , Enterovirus Humano A/patogenicidade , Doença de Mão, Pé e Boca/complicações , Doenças do Sistema Nervoso Central/virologia , Criança , Surtos de Doenças , Feminino , Febre/virologia , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Malásia/epidemiologia , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
7.
Clin Infect Dis ; 47(4): 458-68, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18616397

RESUMO

BACKGROUND: Japanese encephalitis is a major public health problem in Asia. However, there is little data on the long-term outcome of Japanese encephalitis survivors. METHODS: We prospectively evaluated children with serologically confirmed Japanese encephalitis over an 8.3-year period. The patients were assessed and their outcomes were graded with a functional outcome score at hospital discharge and at follow-up appointments. We examined how patient outcome at hospital discharge compared with that at long-term follow-up visits, when changes in outcome occurred, and the prognostic indicators of the eventual outcome. RESULTS: One hundred and eighteen patients were recruited into the study, and 10 (8%) died during the acute phase of illness. At hospital discharge, 44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae. Eighty six of the 108 patients were followed up for a median duration of 52.9 months (range, 0.9-114.9 months). During follow-up, 31 patients experienced improvement, but 15 patients experienced deterioration in their outcome grade. In most cases, assessment during the first 3-6 months after hospital discharge was predictive of the long-term outcome. More than one-half of the patients continued to experience neuropsychological sequelae and behavioral disorders. A combination of poor perfusion, Glasgow coma score < or =8, and > or =2 witnessed seizures predicted a poor long-term outcome with 65% sensitivity and 92% specificity. CONCLUSIONS: Neurological assessment of Japanese encephalitis survivors at hospital discharge does not predict long-term outcome. Seizures and shock are treatable risk factors for a poor outcome at hospital discharge and at long-term follow-up visits.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Criança , Pré-Escolar , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/mortalidade , Encefalite Japonesa/fisiopatologia , Encefalite Japonesa/virologia , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Malásia/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/fisiopatologia , Exame Neurológico , Prognóstico , Fatores de Tempo
8.
J Clin Microbiol ; 45(6): 1858-66, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17446325

RESUMO

Human enterovirus 71 and coxsackievirus A16 are important causes of hand-foot-and-mouth disease (HFMD). Like other enteroviruses, they can be isolated from a range of sterile and nonsterile sites, but which clinical sample, or combination of samples, is the most useful for laboratory diagnosis of HFMD is not clear. We attempted virus culture for 2,916 samples from 628 of 725 children with HFMD studied over a 3 1/2-year period, which included two large outbreaks. Overall, throat swabs were the single most useful specimen, being positive for any enterovirus for 288 (49%) of 592 patients with a full set of samples. Vesicle swabs were positive for 169 (48%) of 333 patients with vesicles, the yield being greater if two or more vesicles were swabbed. The combination of throat plus vesicle swabs enabled the identification of virus for 224 (67%) of the 333 patients with vesicles; for this patient group, just 27 (8%) extra patients were diagnosed when rectal and ulcer swabs were added. Of 259 patients without vesicles, use of the combination of throat plus rectal swab identified virus for 138 (53%). For 60 patients, virus was isolated from both vesicle and rectal swabs, but for 12 (20%) of these, the isolates differed. Such discordance occurred for just 11 (10%) of 112 patients with virus isolated from vesicle and throat swabs. During large HFMD outbreaks, we suggest collecting swabs from the throat plus one other site: vesicles, if these are present (at least two should be swabbed), or the rectum if there are no vesicles. Vesicle swabs give a high diagnostic yield, with the added advantage of being from a sterile site.


Assuntos
Infecções por Enterovirus/diagnóstico , Enterovirus/classificação , Enterovirus/isolamento & purificação , Doença de Mão, Pé e Boca/diagnóstico , Adolescente , Sangue/virologia , Líquido Cefalorraquidiano/virologia , Criança , Pré-Escolar , Surtos de Doenças , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Feminino , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Masculino , Faringe/virologia , Reto/virologia , Manejo de Espécimes/métodos , Úlcera/virologia , Cultura de Vírus
9.
Clin Infect Dis ; 44(5): 646-56, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17278054

RESUMO

BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear. METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates. RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P<.0001); children with HEV-71 genogroup B5 were more likely to be part of a family cluster (OR, 6.26; 95% CI, 2.77-14.18; P<.0001). Children with HEV-71 and coinfected with another enterovirus or adenovirus were no more likely to have CNS disease. CONCLUSIONS: Genogroups of HEV-71 may differ with regard to the risk of causing CNS disease and the association with family clusters. Dual infections are common, and all possible causes should be excluded before accepting that the first virus identified is the causal agent.


Assuntos
Enterovirus/genética , Doença de Mão, Pé e Boca/epidemiologia , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/virologia , Criança , Pré-Escolar , Enterovirus/classificação , Enterovirus/isolamento & purificação , Genótipo , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Malásia/epidemiologia , Filogenia , Estudos Prospectivos , Fatores de Risco
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