• Retraction [1]

    17 July 2018

  • Contrasting spatial distribution and risk factors for past infection with scrub typhus and murine typhus in Vientiane City, Lao PDR.

    17 July 2018

    The aetiological diagnostic of fevers in Laos remains difficult due to limited laboratory diagnostic facilities. However, it has recently become apparent that both scrub and murine typhus are common causes of previous undiagnosed fever. Epidemiological data suggests that scrub typhus would be more common in rural areas and murine typhus in urban areas, but there is very little recent information on factors involved in scrub and murine typhus transmission, especially where they are sympatric - as is the case in Vientiane, the capital of the Lao PDR.We therefore determined the frequency of IgG seropositivity against scrub typhus (Orientia tsutsugamushi) and murine typhus (Rickettsia typhi), as indices of prior exposure to these pathogens, in randomly selected adults in urban and peri-urban Vientiane City (n = 2,002, ≥35 years). Anti-scrub and murine typhus IgG were detected by ELISA assays using filter paper elutes. We validated the accuracy of ELISA of these elutes against ELISA using serum samples. The overall prevalence of scrub and murine typhus IgG antibodies was 20.3% and 20.6%, respectively. Scrub typhus seropositivity was significantly higher among adults living in the periphery (28.4%) than in the central zone (13.1%) of Vientiane. In contrast, seroprevalence of murine typhus IgG antibodies was significantly higher in the central zone (30.8%) as compared to the periphery (14.4%). In multivariate analysis, adults with a longer residence in Vientiane were at significant greater risk of past infection with murine typhus and at lower risk for scrub typhus. Those with no education, living on low incomes, living on plots of land with poor sanitary conditions, living in large households, and farmers were at higher risk of scrub typhus and those living in neighborhoods with high building density and close to markets were at greater risk for murine typhus and at lower risk of scrub typhus past infection.This study underscores the intense circulation of both scrub and murine typhus in Vientiane city and underlines difference in spatial distribution and risk factors involved in the transmission of these diseases.

  • Molecular Characterization of Cryptosporidium Species and Giardia duodenalis from Symptomatic Cambodian Children.

    17 July 2018

    In a prospective study, 498 single faecal samples from children aged under 16 years attending an outpatient clinic in the Angkor Hospital for Children, northwest Cambodia, were examined for Cryptosporidium oocysts and Giardia cysts using microscopy and molecular assays.Cryptosporidium oocysts were detected in 2.2% (11/498) of samples using microscopy and in 7.7% (38/498) with molecular tests. Giardia duodenalis cysts were detected in 18.9% (94/498) by microscopy and 27.7% (138/498) by molecular tests; 82% of the positive samples (by either method) were from children aged 1-10 years. Cryptosporidium hominis was the most common species of Cryptosporidium, detected in 13 (34.2%) samples, followed by Cryptosporidium meleagridis in 9 (23.7%), Cryptosporidium parvum in 8 (21.1%), Cryptosporidium canis in 5 (13.2%), and Cryptosporidium suis and Cryptosporidium ubiquitum in one sample each. Cryptosporidium hominis and C. parvum positive samples were subtyped by sequencing the GP60 gene: C. hominis IaA16R6 and C. parvum IIeA7G1 were the most abundant subtypes. Giardia duodenalis was typed using a multiplex real-time PCR targeting assemblages A and B. Assemblage B (106; 76.8% of all Giardia positive samples) was most common followed by A (12.3%) and mixed infections (5.1%). Risk factors associated with Cryptosporidium were malnutrition (AOR 9.63, 95% CI 1.67-55.46), chronic medical diagnoses (AOR 4.51, 95% CI 1.79-11.34) and the presence of birds in the household (AOR 2.99, 95% CI 1.16-7.73); specifically C. hominis (p = 0.03) and C. meleagridis (p<0.001) were associated with the presence of birds. The use of soap was protective against Giardia infection (OR 0.74, 95% CI 0.58-0.95).This is the first report to describe the different Cryptosporidium species and subtypes and Giardia duodenalis assemblages in Cambodian children. The variety of Cryptosporidium species detected indicates both anthroponotic and zoonotic transmission in this population. Interventions to improve sanitation, increase hand washing after defecation and before preparing food and promote drinking boiled water may reduce the burden of these two parasites.

  • The Aetiologies and Impact of Fever in Pregnant Inpatients in Vientiane, Laos.

    17 July 2018

    Laos has the highest maternal mortality ratio in mainland Southeast Asia and a high incidence of infectious diseases. Globally, malaria has been the pathogen most intensively investigated in relation to impact on pregnancy, but there has been relatively little research on the aetiology and impact of other diseases. We therefore aimed to determine the causes and impact of fever in pregnant women admitted to two central hospitals in Vientiane City, Lao PDR (Laos).This hospital-based prospective study was conducted in Mahosot Hospital and the Mother and Child Hospital, Vientiane, between 2006 and 2010, with the aim to recruit 250 consenting pregnant women admitted with tympanic temperature ≥37.5°C. Primary outcome was the cause of fever and secondary outcomes were pregnancy outcomes. Specific investigations (culture, antigen, molecular and serological tests) were performed to investigate causes of fever. After discharge, all pregnant women were asked to return for review and convalescence serum on day 10-14 and were monitored until delivery.250 pregnant women were recruited to this study between February 2006 and November 2010. Fifty percent were pregnant for the first time. Their median (range) gestational age on admission was 24 (4-43) weeks. The median (range) tympanic admission temperature was 38.5°C (37.5-40.5°C). Fifteen percent of patients stated that they had taken antibiotics before admission. Headache, myalgia, back pain and arthralgia were described by >60% of patients and 149 (60%) were given a laboratory diagnosis. Of those with confirmed diagnoses, 132 (53%) had a single disease and 17 (7%) had apparent mixed diseases. Among those who had a single disease, dengue fever was the most common diagnosis, followed by pyelonephritis, scrub typhus, murine typhus and typhoid. Patients were also diagnosed with tuberculosis, appendicitis, Staphylococcus aureus septicemia, leptospirosis, Japanese encephalitis virus infection and Plasmodium falciparum malaria. Severe consequences, including maternal death, miscarriage, stillbirth, low birth weight and preterm birth, were found among 28 (78%) mothers with dengue fever, rickettsioses and typhoid.Fevers other than malaria, such as dengue, pyelonephritis, rickettsioses and typhoid are common causes of fever during pregnancy in the Asian tropics. Further investigations of their impact in the community on maternal death, fetal loss, vertical transmission, low birth weight and preterm birth are needed.

  • Ophthalmic infections in children presenting to Angkor Hospital for Children, Siem Reap, Cambodia.

    17 July 2018

    Ophthalmic infections cause significant morbidity in Cambodian children but aetiologic data are scarce. We investigated the causes of acute eye infections in 54 children presenting to the ophthalmology clinic at Angkor Hospital for Children, Siem Reap between March and October 2012.The median age at presentation was 3.6 years (range 6 days - 16.0 years). Forty two patients (77.8%) were classified as having an external eye infection, ten (18.5%) as ophthalmia neonatorum, and two (3.7%) as intra-ocular infection. Organisms were identified in all ophthalmia neonatorum patients and 85.7% of patients with an external eye infection. Pathogens were not detected in either of the intra-ocular infection patients. Most commonly isolated bacteria were Staphylococcus aureus (23 isolates), coagulase-negative staphylococci (13), coliforms (7), Haemophilus influenzae/parainfluenzae (6), Streptococcus pneumoniae (4), and Neisseria gonorrhoeae (2). Chlamydia trachomatis DNA was detected in 60% of swabs taken from ophthalmia neonatorum cases.This small study demonstrates the wide range of pathogens associated with common eye infections in Cambodian children. The inclusion of molecular assays improved the spectrum of detectable pathogens, most notably in neonates.

  • Exonic single nucleotide polymorphisms within TLR3 associated with infant responses to serogroup C meningococcal conjugate vaccine

    17 July 2018

    The introduction of the serogroup C meningococcal (MenC) conjugate vaccination has successfully controlled the burden of disease associated with this serogroup in many countries. However, considerable inter-individual variation is observed in immune responses to MenC vaccine, and little is understood of the determinants of this variability. Previously, we reported an association between single nucleotide polymorphisms (SNPs) in TLR3 and CD44 and the persistence of MenC vaccine immunity. Here we further examine polymorphisms within these two candidate genes and immune responses to MenC vaccine. MenC-specific IgG concentrations and serum bactericidal assay (SBA) titres were measured one month after a primary course of MenC vaccination in 318 human infants. Tagging SNPs (TagSNPs) within TLR3 and CD44 were genotyped and regional imputations carried out to screen these genes for variations associated with immunological responses to MenC vaccine. This study reports an association between an exonic variant (rs3775290, P= 0.025) in TLR3 and MenC IgG concentrations, as well as an association between three SNPs in CD44 (rs3794109, P= 0.021; rs3794110, P= 0.022; rs112762, P= 0.049) and MenC SBA titres. These data support our previous findings of an association between SNPs in TLR3 and CD44, and present novel findings implicating exonic variants in these genes with MenC vaccine responses. © 2014 Elsevier Ltd.

  • Seroprotection against serogroup C meningococcal disease in adolescents in the United Kingdom: observational study.

    17 July 2018

    To determine the persistence of bactericidal antibody titres following immunisation with serogroup C meningococcal glycoconjugate vaccine at age 6-15 years in order to examine changes in persistence of antibodies with age.Observational study.Secondary and tertiary educational institutions in the United Kingdom.Healthy adolescents aged 11-20 years previously immunised between 6 and 15 years of age with one of the three serogroup C meningococcal vaccines.Serum obtained by venepuncture.Percentage of participants with (rabbit complement) serum bactericidal antibody titres of at least 1:8; geometric mean titres of serogroup C meningococcal serum bactericidal antibody.Five years after immunisation, 84.1% (95% confidence interval 81.6% to 86.3%) of 987 participants had a bactericidal antibody titre of at least 1:8. Geometric mean titres of bactericidal antibody were significantly lower in 11-13 year olds (147, 95% confidence interval 115 to 188) than in 14-16 year olds (300, 237 to 380) and 17-20 year olds (360, 252 to 515) (P<0.0001 for both comparisons). Within these age bands, no significant difference in geometric mean titres of bactericidal antibody between recipients of the different serogroup C meningococcal vaccines was seen. More than 70% of participants had received a vaccine from one manufacturer; in this cohort, geometric mean titres were higher in those immunised at aged 10 years or above than in those immunised before the age of 10.Higher concentrations of bactericidal antibody are seen five years after immunisation with serogroup C meningococcal vaccine at age 10 years or above than in younger age groups, possibly owing to immunological maturation. This provides support for adolescent immunisation programmes to generate sustained protection against serogroup C meningococcal disease not only for the vaccine recipients but also, through the maintenance of herd immunity, for younger children.

  • First National Workshop on Antibiotic Resistance in Cambodia: Phnom Penh, Cambodia, 16-18 November 2011.

    17 July 2018

    The First National Workshop on Antibiotic Resistance in Cambodia was organised by the Cambodian Ministry of Health with support from several national and international partner institutions. It brought together policy-makers, clinicians, pharmacists, laboratory technicians and other professionals dealing with the problems of bacterial infection and antibiotic resistance across the country. Antibiotic resistance data from starting up and experienced laboratories were presented, showing high rates of resistance in key pathogens to most antibiotics currently available in Cambodia, e.g. 70-90% multidrug resistance and 70-80% decreased ciprofloxacin susceptibility in Salmonella enterica serovar Typhi, 20-40% meticillin resistance rates in Staphylococcus aureus and 30-50% extended-spectrum β-lactamase production in Escherichia coli. A five-point plan was discussed, which included initiatives from government and non-governmental partners, focusing on rational prescribing, clinical practice guidelines, improved laboratory services, infection prevention and enhanced education at all levels. Implementation, however challenging, is a priority given the high levels of resistance seen in key pathogens and the overall health needs in the country.

  • Pediatric suppurative parotitis in cambodia between 2007 and 2011

    17 July 2018

    The causes of suppurative parotitis in Cambodian children are not known. We describe 39 cases at the Angkor Hospital for Children, Siem Reap, between January 2007 and July 2011 (0.07/1000 hospital attendances). The median age was 5.7 years with no neonates affected. Burkholderia pseudomallei was cultured in 29 (74%) cases. No deaths occurred; 1 child developed facial nerve palsy. © 2012 by Lippincott Williams & Wilkins.