Satzke C.,Murdoch Childrens Research Institute |
Satzke C.,University of Melbourne |
Turner P.,Angkor Hospital for Children |
Turner P.,University of Oxford |
And 13 more authors.
Vaccine | Year: 2013
In 2003 the World Health Organization (WHO) convened a working group and published a set of standard methods for studies measuring nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus). The working group recently reconvened under the auspices of the WHO and updated the consensus standard methods. These methods describe the collection, transport and storage of nasopharyngeal samples, as well as provide recommendations for the identification and serotyping of pneumococci using culture and non-culture based approaches. We outline the consensus position of the working group, the evidence supporting this position, areas worthy of future research, and the epidemiological role of carriage studies. Adherence to these methods will reduce variability in the conduct of pneumococcal carriage studies undertaken in the context of pneumococcal vaccine trials, implementation studies, and epidemiology studies more generally so variability in methodology does not confound the interpretation of study findings. © 2013 Elsevier Ltd.
PubMed | National Hospital for Tropical Diseases, Hospital for Tropical Diseases, Brac University, Childrens Hospital Number 2 and 14 more.
Type: | Journal: BMC infectious diseases | Year: 2016
The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course.This is a prospective multi-centre observational study aiming to enrol 7-8000 participants aged 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later.Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for Integrated Management of Childhood Illness used in dengue-endemic countries.NCT01550016. Registration Date: March 7, 2012.
Cornick J.E.,Malawi Liverpool Wellcome Trust Clinical Research Programme |
Cornick J.E.,University of Liverpool |
Everett D.B.,Malawi Liverpool Wellcome Trust Clinical Research Programme |
Everett D.B.,University of Liverpool |
And 8 more authors.
Emerging Infectious Diseases | Year: 2011
Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible.
Croucher N.J.,Imperial College London |
Mostowy R.,Imperial College London |
Wymant C.,Imperial College London |
Turner P.,Angkor Hospital for Children |
And 3 more authors.
PLoS Biology | Year: 2016
Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell–cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing “arms race.” Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic’s effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell–cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated. © 2016 Croucher et al.
Owusu-Ofori A.K.,Komfo Anokye Teaching Hospital |
Betson M.,Royal Veterinary College |
Parry C.M.,Angkor Hospital for Children |
Stothard J.R.,Disease Control Strategy Group |
Bates I.,Disease Control Strategy Group
Clinical Infectious Diseases | Year: 2013
Background. In sub-Saharan Africa, the prevalence of malaria parasitemia in blood donors varies from 0.6% to 50%. Although the burden of TTM in malaria-endemic countries is unknown, it is recommended that all donated blood is screened for malaria parasites. This study aimed to establish the incidence of TTM and identify a suitable screening test.Methods. Pregnant women, children, and immunocompromised malaria-negative transfusion recipients in a teaching hospital in Ghana were recruited over the course of 1 year. Parasites detected in recipients within 14 days of the transfusion were genotyped and compared to parasites in the transfused blood. The presence of genotypically identical parasites in the recipient and the transfused blood confirmed transfusion-transmitted malaria. Four malaria screening tests were compared to assess their usefulness in the context of African blood banks.Results. Of the 50 patients who received transfusions that were positive for Plasmodium falciparum by polymerase chain reaction (PCR), 7 recipients developed PCR-detectable parasitemia. In only 1 of the 50 recipients (2%) was the parasite identical to that in the transfused blood. The prevalence of P. falciparum malaria in transfused blood was 4.7% (21/445) by microscopy, 13.7% (60/440) by rapid diagnostic test, 18% (78/436) by PCR, and 22.2% (98/442) by enzyme immunoassay.Conclusions. Although malaria parasites are commonly detected in blood donors in malaria-endemic areas, transfusion-transmitted malaria occurs infrequently. Policies recommend screening blood donors for malaria, but none of the commonly used methods is sufficiently sensitive to be used by blood banks in malaria-endemic countries. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
PubMed | Angkor Hospital for Children, Angkor University, Mahidol University and 0000 0004 0418 5364Grid459332Aangkor Hospital For Children
Type: | Journal: Antimicrobial resistance and infection control | Year: 2017
Healthcare associated infections (HAI) are the most common preventable adverse events following admission to healthcare facilities. Data from low-income countries are scarce. We sought to prospectively define HAI incidence at Angkor Hospital for Children (AHC), a Cambodian pediatric referral hospital.Prospective HAI surveillance was introduced for medical admissions to AHC. Cases were identified on daily ward rounds and confirmed using locally adapted Centers for Disease Control and Prevention (CDC) definitions. During the surveillance period, established infection prevention and control (IPC) activities continued, including hand hygiene surveillance. In addition, antimicrobial stewardship practices such as the creation of an antimicrobial guideline smartphone app were introduced.Between 1st January and 31st December 2015 there were 3,263 medical admissions and 102 HAI cases. The incidence of HAI was 4.6/1,000 patient-days (95% confidence interval 3.8-5.6) and rates were highest amongst neonates. Median length of stay was significantly longer in HAI cases: 25days versus 5days for non-HAI cases (Prospective HAI surveillance can form part of routine practice in low-income healthcare settings. HAI incidence at AHC was relatively low, but human and financial costs remained high due to increased carbapenem use, prolonged admissions and higher mortality rates.
Coetzer M.,The Miriam Hospital |
Westley B.,The Miriam Hospital |
Delong A.,Brown University |
Tray C.,Angkor Hospital for Children |
And 4 more authors.
AIDS Research and Human Retroviruses | Year: 2013
Antiretroviral therapy in resource-limited settings is monitored clinically and immunologically according to WHO guidelines. Frequent misclassification of virologic failure is reported, mostly in adults, leading to early therapy switch or late failure diagnosis. Pediatric treatment monitoring and resistance data upon first-line failure are limited, particularly when the 2010-WHO pediatric guidelines are used without routine viral load monitoring. We previously reported high treatment failure misclassification rates by pediatric 2010 guidelines in Cambodian children on first-line therapy. Here we determine the extent and patterns of resistance, with yearly viral load and 6-monthly CD4. Drug resistance mutations were determined using the IAS-USA 2011 list. Predicted resistance interpretation was determined with Stanford Database tools. Fifty-one children with available genotypes met inclusion criteria. All but one (subtype B) were CRF01-AE. The most common regimen was stavudine, lamivudine, and nevirapine (96%), taken for a median of 2.2 years. Resistance was seen in 98%; 96% to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs); 51% with ≥4 mutations. The most common NRTI mutations were 184V/I and 67N and the most common NNRTI mutations were 181C/Y/I/V and 190A/S. A total of 22% had multiresistant mutations and 18% had predicted high-level resistance to subsequent therapy options didanosine, abacavir, etravirine, and tenofovir. In 98% of Cambodian children misclassified as nonfailing first-line therapy by 2010 guidelines, 51% had extensive drug resistance to current and 18% to subsequent antiretroviral therapy. Affordable routine viral load monitoring allowing for early and more accurate treatment failure diagnosis is desperately needed in resource-limited settings. © 2013, Mary Ann Liebert, Inc.
Merali H.S.,MassGeneral Hospital for Children |
Sing H.,Angkor Hospital for Children
American Journal of Tropical Medicine and Hygiene | Year: 2014
A 4-year-old Cambodian male presented to the emergency room with 2 weeks of gradually increasing leg weakness until he could no longer stand. He was also reported to have a deformity on his back, intermittent fevers and cough. His physical exam was notable for a 2 cm x 1 cm bony protrusion at his T4 vertebrae, and 2/5 strength and positive Babinski reflexes in his lower extremities. A chest x-ray showed a 3.2 cm x 2.9 cm mass in the middle mediastinum extending to the posterior mediastinum. A purified protein derivative test was positive. A computed tomography scan showed findings consistent with pulmonary tuberculosis and a paravertebral mass with amorphous calcifications, which involved destruction of the T4-T5 vertebrae and evidence of cord compression. These findings were all consistent with tuberculous spondylitis (Pott's disease). Copyright © 2014 by The American Society of Tropical Medicine and Hygiene.
Copelovitch L.,Angkor Hospital for Children |
Copelovitch L.,Children's Hospital of Philadelphia |
Sam Ol O.,Angkor Hospital for Children |
Taraquinio S.,Angkor Hospital for Children |
Chanpheaktra N.,Angkor Hospital for Children
Journal of Pediatrics | Year: 2010
Objectives: To describe childhood nephrotic syndrome (NS) in Cambodia and to evaluate whether initial presentation or relapse is associated with gastrointestinal parasitic infection. Study design: We reviewed the records of 112 children with NS. A retrospective cross-sectional study compared 99 stool exams from 63 children with NS with 12 365 stool exams from 9495 controls. Results: The male-to-female ratio was 1.7; the mean age of presentation was 8.95 years--44% were hypertensive, 44% had microscopic hematuria, 40% had eosinophilia, and 41% had acute renal failure; 92.7% were steroid sensitive, 12.7% were steroid dependent, and 8.9% were frequent relapsers. Peritonitis and death were rare outcomes. Giardia lamblia (OR, 3.62; 95% CI, 2.0 to 6.1), Strongyloides stercoralis (OR, 3.59; 95% CI, 1.3 to 8.2), and Hookworm species (OR, 2.57; 95% CI, 1.0 to 5.5) were more likely to be isolated from the children with NS than the controls. Conclusions: The clinical course of childhood NS in Cambodia is similar to the developed world. Differences at presentation included older age and increased prevalence of microscopic hematuria, hypertension, eosinophilia, and acute renal failure. This study demonstrates an association between G lamblia, S stercoralis, and possibly Hookworm species and the onset of NS. © 2010 Mosby, Inc. All rights reserved.
Pagnarith Y.,Angkor Hospital for Children |
Kumar V.,Angkor Hospital for Children |
Thaipadungpanit J.,Mahidol University |
Wuthiekanun V.,Mahidol University |
And 4 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2010
We describe the first cases of pediatric melioidosis in Cambodia. Thirty-nine cases were diagnosed at the Angkor Hospital for Children, Siem Reap, between October 2005 and December 2008 after the introduction of microbiology capabilities. Median age was 7.8 years (range = 1.6-16.2 years), 15 cases were male (38%), and 4 cases had pre-existing conditions that may have pre-disposed the patient to melioidosis. Infection was localized in 27 cases (69%) and disseminated in 12 cases (31%). Eleven cases (28%) were treated as outpatients, and 28 (72%) cases were admitted. Eight children (21%) died a median of 2 days after admission; seven deaths were attributable to melioidosis, all of which occurred in children receiving suboptimal antimicrobial therapy and before bacteriological culture results were available. Our findings indicate the need for heightened awareness of melioidosis in Cambodia, and they have led us to review microbiology procedures and antimicrobial prescribing of suspected and confirmed cases. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene.