Non-invasive diagnosis of lung tuberculosis in children by single voxel 1H-magnetic resonance spectroscopy

Our previous study showed that 1H-magnetic resonance spectroscopy (1H-MRS) can detect lipid peaks characteristic for Mycobacterium tuberculosis infection in cerebral lesions of young children; therefore, we aimed to extend and validate the application of 1H-MRS for the diagnosis of active pulmonary tuberculosis lesions in three adolescent patients. Here, we document lipid peaks characteristic for M. tuberculosis infection by 1H-MRS from lung tissue surrounding lung cavities of two patients whose sputum samples were positive for acid-fast bacilli by microscopy and positive for M. tuberculosis by genetic testing, indicating active tuberculosis. A similar lipid peak was found also in the pleural effusion of a third patient with concurrent lung cavity compatible with active tuberculosis. However, in a patient with a pyogenic pulmonary abscess, 1H-MRS of the drained pus displayed different characteristic peaks but no lipid peak at all. Conclusion: Our findings further validate 1H-MRS as a rapid, non-invasive, and specific diagnostic tool for active tuberculosis in children with microbiologically documented infection outside the central nervous system, specifically in the lung

Non-invasive diagnosis of lung tuberculosis in children by single voxel ¹H-magnetic resonance spectroscopy

Our previous study showed that (1)H-magnetic resonance spectroscopy ((1)H-MRS) can detect lipid peaks characteristic for Mycobacterium tuberculosis infection in cerebral lesions of young children; therefore, we aimed to extend and validate the application of (1)H-MRS for the diagnosis of active pulmonary tuberculosis lesions in three adolescent patients. Here, we document lipid peaks characteristic for M. tuberculosis infection by (1)H-MRS from lung tissue surrounding lung cavities of two patients whose sputum samples were positive for acid-fast bacilli by microscopy and positive for M. tuberculosis by genetic testing, indicating active tuberculosis. A similar lipid peak was found also in the pleural effusion of a third patient with concurrent lung cavity compatible with active tuberculosis. However, in a patient with a pyogenic pulmonary abscess, (1)H-MRS of the drained pus displayed different characteristic peaks but no lipid peak at all. CONCLUSION: Our findings further validate (1)H-MRS as a rapid, non-invasive, and specific diagnostic tool for active tuberculosis in children with microbiologically documented infection outside the central nervous system, specifically in the lungs

A prospective, comparative study of severe neurological and uncomplicated hand, foot and mouth forms of paediatric enterovirus 71 infections

Objectives: In this study, we document the clinical characteristics and investigated risk factors for uncomplicated and severe forms of EV-A71 disease in Cambodian children. Methods: From March to July 2014 inclusive, all patients with suspicion of EV-A71 infection presenting to Kantha Bopha Hospitals in Phnom Penh and Siem Reap and confirmed by the Virology Unit at the Institut Pasteur du Cambodge were prospectively enrolled in this study. Throat swabs, rectal swabs and serum samples were collected from all consecutive patients with suspected EV-A71 infection. In addition, CSF was also collected from patients with suspected EV-A71 associated encephalitis. A total of 122 patients (29 with uncomplicated disease and 93 with severe disease) with confirmed EV-A71 infection with all available demographic and clinical data for clinical classification and further analysis were included in the study. Results: In this prospective EV-A71 study in Cambodia, we confirmed the previously reported association of male gender and absence of mouth or skin lesions with severe disease. We also highlighted the strong association of neutrophils in blood, but also in CSF in patients with pulmonary oedema. More importantly, we identified new putative nutrition-related risk factors for severe disease. Conclusions: EV-A71 is an important cause of encephalitis in the Asia-Pacific region. Further studies to determine the risk factors associated with severe EV-A71 disease are needed

The sensitivity of an interferon-γ release assay in microbiologically confirmed pediatric tuberculosis

This study aimed at determining the sensitivity of a whole blood interferon-γ release assay (IGRA) among children with microbiologically confirmed tuberculosis in a high-burden country. Children with a diagnosis of tuberculosis based on clinical and radiographic assessment were tested with an IGRA in addition to microbiologic examination of appropriate specimens for acid-fast bacilli, mycobacterial rRNA, and observation for growth of Mycobacterium tuberculosis on appropriate culture media. Of the 405 children with a clinical diagnosis of tuberculosis, 91 (22.5%) had microbiologically confirmed tuberculosis, of whom 81 were tested with an IGRA. A positive result was obtained in 43 (sensitivity 53.1%, 95% confidence interval 42.3 to 63.6%), uninfluenced by age, sex, or disease manifestation. Conclusions: The sensitivity of a whole blood interferon-γ release assay in microbiologically confirmed pediatric tuberculosis was low. An IGRA cannot, thus, be used as rule-in test, but it might be useful to rule in tuberculosis among children in whom tuberculosis is notoriously difficult to confirm microbiologically

Aetiology of acute meningoencephalitis in Cambodian children, 2010–2013

Acute meningoencephalitis (AME) is associated with considerable morbidity and mortality in children in developing countries. Clinical specimens were collected from children presenting with AME at two Cambodian paediatric hospitals to determine the major aetiologies associated with AME in the country. Cerebrospinal fluid (CSF) and blood samples were screened by molecular and cell culture methods for a range of pathogens previously associated with AME in the region. CSF and serum (acute and convalescent) were screened for antibodies to arboviruses such as Japanese encephalitis virus (JEV), dengue virus (DENV), and chikungunya virus (CHIKV). From July 2010 through December 2013, 1160 children (one month to 15 years of age) presenting with AME to two major paediatric hospitals were enroled into the study. Pathogens associated with AME were identified using molecular diagnostics, cell culture and serology. According to a diagnostic algorithm, a confirmed or highly probable aetiologic agent was detected in 35.0% (n=406) of AME cases, with a further 9.2% (total: 44.2%, n=513) aetiologies defined as suspected. JEV (24.4%, n=283) was the most commonly identified pathogen followed by Orientia tsutsugamushi (4.7%, n=55), DENV (4.6%, n=53), enteroviruses (3.5%, n=41), CHIKV (2.0%, n=23) and Streptococcus pneumoniae (1.6%, n=19). The majority of aetiologies identified for paediatric AME in Cambodia were vaccine preventable and/or treatable with appropriate antimicrobials

The sensitivity of an interferon-γ release assay in microbiologically confirmed pediatric tuberculosis

This study aimed at determining the sensitivity of a whole blood interferon-γ release assay (IGRA) among children with microbiologically confirmed tuberculosis in a high-burden country. Children with a diagnosis of tuberculosis based on clinical and radiographic assessment were tested with an IGRA in addition to microbiologic examination of appropriate specimens for acid-fast bacilli, mycobacterial rRNA, and observation for growth of Mycobacterium tuberculosis on appropriate culture media. Of the 405 children with a clinical diagnosis of tuberculosis, 91 (22.5 %) had microbiologically confirmed tuberculosis, of whom 81 were tested with an IGRA. A positive result was obtained in 43 (sensitivity 53.1 %, 95 % confidence interval 42.3 to 63.6 %), uninfluenced by age, sex, or disease manifestation. Conclusions: The sensitivity of a whole blood interferon-γ release assay in microbiologically confirmed pediatric tuberculosis was low. An IGRA cannot, thus, be used as rule-in test, but it might be useful to rule in tuberculosis among children in whom tuberculosis is notoriously difficult to confirm microbiologically

Molecular epidemiology of Orientia tsutsugamushi in Cambodia and Central Vietnam reveals a broad region-wide genetic diversity

Scrub typhus is an acute infectious disease caused by an obligate intracellular bacterium Orientia tsutsugamushi following the bite of infected trombiculid mites of the genus Leptotrombidium. This zoonotic disease is a major cause of febrile illness in the Asia-Pacific region, with a large spectrum of clinical manifestations from unapparent or mild disease to fatal disease. O. tsutsugamushi is characterized by a very high genomic plasticity and a large number of antigenic variants amongst strains. The 56-kDa type specific antigen (TSA) gene, encoding the major antigenic protein, was used as reference to investigate the genetic relationships between the strains and to genotype O. tsutsugamushi isolates. The open reading frame of the 56-kDa TSA gene of 41 sequences (28 Cambodian and 13 Vietnamese strains) from patient samples were sequenced and used for genotyping. The 28 Cambodian isolates clustered into 5 major groups, including Karp (43.5%), JG-v (25%), Kato/TA716 (21.5%), TA763 (3.5%) and Gilliam (3.5%). Karp (77%), TA763 (15.5%) and JG-v (7.5%) strains were identified amongst the 13 Vietnamese isolates. This is the first countrywide genotyping description in Cambodia and in Central Vietnam. These results demonstrate the considerable diversity of genotypes in co-circulation in both countries. The genotyping result might raise awareness amongst Cambodian and Vietnamese clinicians of the high genetic diversity of circulating O. tsutsugamushi strains and provides unique and beneficial data for serological and molecular diagnosis of scrub typhus infections as well as raw materials for future studies and vaccine development. (Résumé d'auteur

Seroprevalence and transmission of Human Influenza A(H5N1) virus before and after virus reassortment, Cambodia, 2006–2014

Thirty-five human influenza A(H5N1) cases were reported in Cambodia during 2013–2014 after emergence of a clade 1.1.2 reassortant virus. We tested 881 villagers and found 2 cases of pauci- or asymptomatic infection. Seroprevalence after emergence of the reassortant strain (0.2%) was lower than the aggregate seroprevalence of 1.3% reported in earlier studies