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1.
Am J Trop Med Hyg ; 107(2): 393-396, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35895426

RESUMO

Melioidosis is reported to cause a high fatality rate in children, even in the absence of risk factors for disease. The aim of this study was to identify characteristics of fatal pediatric melioidosis infection. We performed a retrospective analysis of children aged < 15 years with culture-confirmed melioidosis admitted to Bintulu Hospital in Sarawak, Malaysian Borneo, from January 2011 to December 2020. Forty-one children had culture-confirmed melioidosis. Nine (22%) had a fatal outcome; 8 (89%) had no predisposing risk factors. Bacteremia, septic shock, and acute respiratory distress syndrome were present in all fatalities. Demographic characteristics, presenting manifestation, and disseminated infection were not significantly associated with mortality, whereas the presence of splenomegaly, cytopenia, disseminated intravascular coagulation, and hepatobiliary dysfunction, all of which are features of hyperferritinemic sepsis-induced multiple-organ dysfunction syndrome, were associated with mortality. Hyperferritinemic sepsis-induced multiple-organ dysfunction syndrome may be a key component in the pathogenesis of fatal pediatric melioidosis.


Assuntos
Melioidose , Sepse , Choque Séptico , Humanos , Criança , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Retrospectivos , Sepse/complicações , Choque Séptico/complicações
3.
Open Forum Infect Dis ; 8(10): ofab460, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34646909

RESUMO

BACKGROUND: Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a broad range of antibiotics, including aminoglycosides. In Sarawak, Malaysia, a high proportion of melioidosis cases are caused by gentamicin-susceptible isolates. There are limited epidemiological and clinical data on these infections. METHODS: We conducted a retrospective study of culture-confirmed melioidosis among adults admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2016. RESULTS: One hundred forty-eight adults with culture-confirmed melioidosis were identified. Of 129 (87%) tested, 84 (65%) had gentamicin-susceptible B pseudomallei. The average annual incidence of melioidosis was 12.3 per 100 000 population, with marked variation between districts ranging from 5.8 to 29.3 per 100 000 population. Rural districts had higher incidences of melioidosis and overwhelmingly larger proportions of gentamicin-susceptible B pseudomallei infection. Significantly more patients with gentamicin-susceptible infection had no identified risk factors, with diabetes less frequently present in this group. Ninety-eight percent had acute presentations. Pneumonia, reported in 71%, was the most common presentation. Splenic abscesses were found in 54% of those imaged. Bacteremia was present in 88%; septic shock occurred in 47%. Forty-five (35%) patients died. No differences in clinical, laboratory, or outcome characteristics were noted between gentamicin-susceptible and gentamicin-resistant infections. CONCLUSIONS: Gentamicin-susceptible B pseudomallei infections are common in Sarawak and dominate in the high-incidence rural interior regions. Clinical manifestations and outcomes are the same as for gentamicin-resistant B pseudomallei infections. Further studies are required to determine if all gentamicin-susceptible B pseudomallei infections in Sarawak are clonal and to ascertain their environmental drivers and niches.

4.
BMC Infect Dis ; 21(1): 1069, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654392

RESUMO

BACKGROUND: Melioidosis, the infection caused by Burkholderia pseudomallei, is associated with a high case fatality rate, due in part to difficulties in clinical recognition and diagnostic confirmation of the disease. Although head and neck involvement is common in children, specific disease manifestations differ between geographic regions. The aim of this study was to provide a detailed description of melioidosis of the head and neck among children in Sarawak, Malaysia, and determine if fine-needle aspiration of suspected head or neck lesions could improve melioidosis diagnosis. METHODS: We conducted a retrospective descriptive study of all children aged < 12 years with culture-confirmed melioidosis presenting with head and neck manifestations and admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2020. Fine-needle aspiration of head and neck lesions suspected to be due to melioidosis with inoculation in blood culture bottles (FNA + BCB) was used from the beginning of 2016. RESULTS: Of 34 children with culture-confirmed melioidosis, 20 (59%) had an infection involving one or more sites in the head and neck. Of these, 17 (85%) were diagnosed in or after 2016. Cervical lymph nodes were the most common organ or site affected, involved in 19 (95%) children. Clinical presentations of B. pseudomallei lymph node infections were highly variable. Five (25%) children had salivary gland involvement. Lacrimal gland involvement (dacryocystitis) and skin or soft tissue infection (scalp abscess) were less frequent. B. pseudomallei was isolated from the head or neck using FNA + BCB in 15 (75%) children and by standard culture methods of direct plating of pus on agar following incision and drainage in only 2 (10%) children. B. pseudomallei was isolated from non-head or neck specimens or blood in 3 (15%) children. CONCLUSIONS: Manifestations of pediatric head and neck melioidosis in Sarawak, Malaysia, differ from those of other regions. Fine-needle aspiration, mainly of affected cervical lymph nodes, facilitates B. pseudomallei detection and enables confirmation of melioidosis infections.


Assuntos
Burkholderia pseudomallei , Melioidose , Biópsia por Agulha Fina , Criança , Humanos , Malásia/epidemiologia , Melioidose/diagnóstico , Melioidose/epidemiologia , Estudos Retrospectivos
5.
Int J Infect Dis ; 98: 59-66, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32535300

RESUMO

OBJECTIVES: Melioidosis is associated with extremely high case fatality ratios. The aim of this study was to determine whether detection of abdominal visceral abscesses can facilitate diagnosis of melioidosis in children. METHODS: We conducted a retrospective analysis of all children who had liver and/or spleen abscesses on abdominal ultrasonography admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2014 until December 2018. RESULTS: Fifty-three children had liver and/or spleen abscesses. Spleen abscesses were present in 48 (91%) cases; liver abscesses in 15 (28%). Melioidosis was confirmed by culture in 9 (17%) children; small occult splenic abscesses were present in all cases. In 78% of these cases, the lesions were detected before any positive culture (or serology) results were available. Four (8%) children had bacteriologically-confirmed tuberculosis. Two (4%) had Staphylococcus aureus infection. Of the remaining 38 (72%) culture-negative cases, 36 (95%) had clinical and imaging characteristics similar to that of children with culture-confirmed melioidosis and improved with empirical melioidosis antibiotic therapy. CONCLUSIONS: A large number of children in Bintulu Hospital in Sarawak, Malaysia, were found to have spleen abscesses. Melioidosis was the most common etiology identified in these children. Abdominal ultrasonography is extremely useful in facilitating the diagnosis of pediatric melioidosis.


Assuntos
Melioidose/diagnóstico , Esplenopatias/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Infecções Intra-Abdominais , Abscesso Hepático/diagnóstico , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/epidemiologia , Malásia/epidemiologia , Masculino , Melioidose/diagnóstico por imagem , Melioidose/epidemiologia , Estudos Retrospectivos , Esplenopatias/diagnóstico por imagem , Esplenopatias/epidemiologia , Ultrassonografia
6.
BMC Infect Dis ; 19(1): 330, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999894

RESUMO

BACKGROUND: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited. METHODS: A retrospective study identifying all children aged < 15 years with invasive Salmonella infections from 2011 to 2016 was conducted in Bintulu Hospital in Sarawak. Population incidences, clinical and bacterial characteristics were examined. RESULTS: Forty-four patients were identified during the 6-year study period: 43 had iNTS infection and 1 had typhoid fever. The average annual iNTS incidence was 32.4 per 100,000 children aged < 5 years. None of the children had malaria or HIV infection, and only 7% were severely malnourished. Salmonella Enteritidis and Salmonella Java were the commonest NTS serovars identified. Pneumonia was the most common manifestation of iNTS disease, present in 20 (47%) children. Other manifestations included gastroenteritis, fever without a source, septic arthritis and meningitis. Salmonella Enteritidis was identified in 76% of those with pneumonia, significantly more frequently than in children with other manifestations. Over 25% of children with iNTS developed severe disease and nearly 10% suffered long term morbidity or mortality. While 78% of Salmonella Java isolates were multi-drug resistant, nearly all other isolates were susceptible to most antimicrobials, including ampicillin. CONCLUSIONS: Bintulu Division in Sarawak observed a very high incidence of childhood iNTS infections. Enteric fever was uncommon. The epidemiology of invasive Salmonella infections in Malaysian Borneo differs considerably from that of neighbouring countries in Asia.


Assuntos
Infecções por Salmonella/diagnóstico , Adolescente , Anti-Infecciosos/farmacologia , Bornéu/epidemiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Lactente , Malásia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Estudos Retrospectivos , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Infecções por Salmonella/epidemiologia , Salmonella enteritidis/efeitos dos fármacos , Salmonella enteritidis/isolamento & purificação , Sorogrupo , Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia
7.
Trop Med Infect Dis ; 3(1)2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30274422

RESUMO

Malaysia is an endemic hot spot for melioidosis; however, a comprehensive picture of the burden of disease, clinical presentations, and challenges faced in diagnosis and treatment of melioidosis is not available. This review provides a nonexhaustive overview of epidemiological data, clinical studies, risk factors, and mortality rates from available literature and case reports. Clinical patterns of melioidosis are generally consistent with those from South and Southeast Asia in terms of common primary presentations with diabetes as a major risk factor. Early diagnosis and appropriate management of Malaysian patients is a key limiting factor, which needs to be addressed to reduce serious complications and high mortality and recurrence rates. Promoting awareness among the local healthcare personnel is crucial to improving diagnostics and early treatment, as well as educating the Malaysian public on disease symptoms and risk factors. A further matter of urgency is the need to make this a notifiable disease and the establishment of a national melioidosis registry. We also highlight local studies on the causative agent, Burkholderia pseudomallei, with regards to bacteriology and identification of virulence factors as well as findings from host⁻pathogen interaction studies. Collectively, these studies have uncovered new correlations and insights for further understanding of the disease.

8.
Front Microbiol ; 8: 2249, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29238324

RESUMO

Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans. In this review the role of the host-viral interactions of EV71 are discussed together with the various models available to examine: how EV71 utilizes its proteins to cleave host factors and proteins, aiding virus replication; how EV71 uses its own viral proteins to disrupt host immune responses and aid in its immune evasion. These discoveries along with others, such as the EV71 crystal structure, have provided possible targets for treatment and drug interventions.

9.
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
10.
Antimicrob Agents Chemother ; 58(1): 162-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24145517

RESUMO

Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Burkholderia pseudomallei/efeitos dos fármacos , Macrolídeos/farmacologia , Gentamicinas/farmacologia , Malásia , Testes de Sensibilidade Microbiana
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