Performance of host-response biomarkers to risk-stratify children with pneumonia in Bhutan.

Pneumonia is the leading cause of post-neonatal death amongst children under five years of age; however, there is no simple triage tool to identify children at risk of progressing to severe and fatal disease. Such a tool could assist for early referral and prioritization of care to improve outcomes and enhance allocation of scarce resources. We compared the performance of inflammatory and endothelial activation markers in addition to clinical signs or scoring scales to risk-stratify children hospitalized with pneumonia at the national referral hospital of Bhutan with the goal of predicting clinical outcome. Of 118 children, 31 evolved to a poor prognosis, defined as either mortality, admission in the paediatric intensive care unit, requirement of chest drainage or requirement of more than five days of oxygen therapy. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) was the best performing biomarker and performed better than clinical parameters. sTREM-1 levels upon admission had good predictive accuracy to identify children with pneumonia at risk of poor prognosis. Our findings confirm that immune and endothelial activation markers could be proactively used at first encounter as risk-stratification and clinical decision-making tools in children with pneumonia; however, further external validation is needed.

Association of Clinical Signs, Host Biomarkers and Etiology With Radiological Pneumonia in Bhutanese Children.

Diagnosing pneumonia and identifying those requiring antibiotherapy remain challenging. Chest radiographs (CXR) are often used as the reference standard. We aimed to describe clinical characteristics, host-response biomarkers and etiology, and assess their relationship to CXR findings in children with pneumonia in Thimphu, Bhutan. Children between 2 and 59 months hospitalized with WHO-defined pneumonia were prospectively enrolled and classified into radiological endpoint and non-endpoint pneumonia. Blood and nasopharyngeal washing were collected for microbiological analyses and plasma levels of 11 host-response biomarkers were measured. Among 149 children with readable CXR, 39 (26.2%) presented with endpoint pneumonia. Identification of respiratory viruses was common, with no significant differences by radiological outcomes. No clinical sign was suggestive of radiological pneumonia, but children with radiological pneumonia presented higher erythrocyte sedimentation rate, C-reactive protein and procalcitonin. Markers of endothelial and immune activation had little accuracy for the reliable identification of radiological pneumonia.

Pneumococcal nasopharyngeal carriage among Bhutanese children hospitalized with clinical pneumonia: serotypes and viral co-infection.

BACKGROUND: Pneumococcal nasopharyngeal colonization (PNC) generally precedes pneumococcal disease. The purpose of this study was to determine the prevalence of PNC and to identify the pneumococcal serotypes circulating among Bhutanese children under five years of age admitted with clinical pneumonia, before the introduction of pneumococcal conjugate vaccine (PCV13) in the country. We also aimed to contribute to the understanding of the interplay between PNC and viral co-infection among this population. METHODS: This was a prospective study conducted at the Jigme Dorji Wangchuck National Referral Hospital in Bhutan over 12 consecutive months. Children aged 2 to 59 months admitted with WHO-defined clinical pneumonia were eligible for recruitment. We collected blood for bacterial culture and molecular identification of S. pneumoniae, and nasopharyngeal washing for screening of respiratory viruses, and for the detection and capsular typing of S. pneumoniae by real-time polymerase chain reaction (RT-PCR). RESULTS: Overall, 189 children were recruited, and PNC was tested in 121 of them (64.0%). PNC was found in 76/121 children (62.8%) and S. pneumoniae was identified in blood (both by culture and RT-PCR) in a single child. Respiratory viruses were detected in a similar proportion among children with (62/70; 88.6%) and without PNC (36/40; 90.0%; p = 1.000), but rhinovirus detection was less common among children with PNC (20/70; 28.6% versus 19/40; 47.5%; p = 0.046). Capsular typing identified 30 different serotypes. Thirty-nine children (51.3%) were colonised with two to five different serotypes. A third of the children presented with serotypes considered highly invasive. Over half of the children (44/76; 57.9%) were carrying at least one serotype included in PCV13. CONCLUSIONS: This study provides baseline information on the status of PNC among Bhutanese children admitted with clinical pneumonia prior to the introduction of PCV13, which is valuable to monitor its potential impact. PCV13 could theoretically have averted up to 58% of the pneumococcal infections among the children in this study, suggesting a future role for the vaccine to significantly reduce the burden associated with S. pneumoniae in Bhutan.

Clinical and Bacteriological Profile of Neonatal Sepsis: A Prospective Hospital-Based Study.

BACKGROUND: Neonatal sepsis remains one of the leading causes of mortality and morbidity in developing countries. With a dearth of data on neonatal sepsis in our country, this study was conducted to determine the incidence of clinical neonatal sepsis and evaluate the clinical, bacteriological, and antimicrobial susceptibility profile of organisms. Material and Methods. A prospective cross-sectional study was conducted in the Neonatal Unit of the National Hospital from 1st January to 31st December 2016. All neonates admitted with suspected clinical sepsis were included. Sepsis screens and cultures were sent under aseptic conditions. Data was analyzed using STATA™ version 12. Clinical features and neonatal and maternal risk factors were analyzed using chi-squared test. Bacteriological profile was analyzed with descriptive statistics. RESULTS: During the study period, incidence of culture positive neonatal sepsis was 19 per 1000 admissions with a blood culture positivity rate of 14%. 54.5% had culture-positive early-onset sepsis (EOS). Prematurity (p = 0.012), APGAR < 6 (p = 0.018), low birth weight (p < 0.001), and maternal intrapartum antibiotics (p = 0.031) significantly increased risk for culture-positive EOS. Prematurity (p < 0.001), low birth weight (p = 0.001), and parental nutrition (p = 0.007) were significantly associated with increased risk of culture-positive late-onset sepsis. A positive screen had sensitivity of 81.8% and negative predictive value of 87.7%. Gram-negative organisms were most commonly isolated (64.6%). Coagulase-negative Staphylococci (31%) were the commonest isolate followed by Klebsiella pneumoniae (27%) and Acinetobacter (18.8%). Ninety percent of Acinetobacter were carbapenem resistant. Gram-negative sepsis had mortality of 88.9%. CONCLUSION: Preterm, low birth weight, low APGAR scores, intrapartum antibiotics, and parental nutrition were significantly associated with neonatal sepsis. Coagulase-negative Staphylococci, Klebsiella pneumoniae, and Acinetobacter were the principal causative organisms. Gram-negative organisms had high resistance to commonly used antibiotics.

Pneumonia in children admitted to the national referral hospital in Bhutan: A prospective cohort study.

OBJECTIVES: The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. METHODS: This prospective study enrolled children aged 2-59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. RESULTS: From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). CONCLUSION: Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.

Antibiotic resistance in Neisseria gonorrhoea and treatment outcomes of gonococcal urethritis suspected patients in two large hospitals in Bhutan, 2015.

INTRODUCTION: Gonorrhea is a major sexually transmitted infection (STI) globally with increasing trends. Despite limited data, gonorrhea remains an important public health problem in Bhutan. METHODS: A descriptive study was carried out in two Bhutanese hospitals; Jigme Dorji Wangchuck National Referral Hospital and Phuentsholing General Hospital in 2015. Patients suspected of gonococcal urethritis were sampled, treated and followed up at two weeks. Gonococcal isolates were identified and tested for antibiotic susceptibility by the Calibrated Dichotomous Sensitivity Test (CDS) method. RESULTS: Of the 524 patients, 2.3% (12) were females. Most (46.6%) patients belonged to the 26-35 years age group. About 58% were lost to follow up; 62% (277) of males and all (12) females. N. gonorrhoea was positive in 76% (398) of microscopy and 73.1% (383) by culture. Resistance against ciprofloxacin, penicillin, tetracycline and nalidixic acid were 85.1%, 99.2%, 84.8% and 99.7% respectively. Nearly all the isolates were sensitive to cefpodoxime, ceftriaxone and azithromycin. Sixty-seven percent (350) were treated with injection ceftriaxone alone, 32% (169) with ceftriaxone and oral doxycycline and 1% (5) with ceftriaxone, doxycycline and metronidazole. Probable treatment failure was seen only in one patient (0.5%). CONCLUSIONS: Gonococcal resistance to currently used antibiotics was low and there was a high clinical cure rate. Compliance to treatment guidelines need reinforcement addressing antibiotic regimen, tracing sexual partners and addressing the social stigma. National STI programs should be more women-friendly for effective management, prevention and control of STIs. Laboratories must adopt more reliable susceptibility testing methods, the Minimum Inhibition Concentration method.

Scrub typhus in Bhutan: a synthesis of data from 2009 to 2014.

Scrub typhus is an acute, febrile illness, caused by the bacterium Orientia tsutsugamushi, that affects millions annually in the endemic Asia-Pacific region. In untreated cases, the case-fatality rates range from 6% to 35%. In Bhutan, there was a probable outbreak in Gedu in 2009, which resulted in heightened awareness of the disease. Nevertheless, information on scrub typhus in Bhutan is limited and scattered and the epidemiology has yet to be established. To report the current picture of scrub typhus in Bhutan, this review gathered data from scholarly databases, surveillance reports, the Annual health bulletin, research publications and laboratory test reports from hospitals. The weight of evidence indicates an increasing burden of scrub typhus since the Gedu incident, coupled with increased awareness and testing. Another outbreak in a rural primary school in 2014 resulted in two deaths. More hospitals now have testing facilities and laboratory-confirmed cases have been increasing since 2009, with seasonal trends. This review highlights the need for in-depth surveillance and reporting, increased awareness among health-care workers, and initiation of prevention and control programmes in the country.