Viral burden and diversity in acute respiratory tract infections in hospitalized children in wet and dry zones of Sri Lanka.

The present study was done to identify the viral diversity, seasonality and burden associated with childhood acute respiratory tract infection (ARTI) in Sri Lanka. Nasopharyngeal aspirates (NPA) of hospitalized children (1 month-5 years) with ARTI were collected in 2 centers (wet and dry zones) from March 2013 to August 2014. Respiratory viral antigen detection by immunofluorescence assay (IFA) was used to identify the infecting viruses. IFA negative 100 NPA samples were tested for human metapeumovirus (hMPV), human bocavirus and corona viruses by polymerase chain reaction. Of the 443 and 418 NPAs, 37.2% and 39.4% were positive for any of the 8 different respiratory viruses tested from two centers studied. Viral co-infection was detected with respiratory syncytial virus (RSV) in both centers. Peak viral detection was noted in the wet zone from May-July 2013 and 2014 and in the dry zone from December-January 2014 suggesting a local seasonality for viral ARTI. RSV showed a clear seasonality with a direct correlation of monthly RSV infections with rainy days in the wet zone and an inverse correlation with temperature in both centers. The case fatality rate was 2.7% for RSV associated ARTI. The overall disability adjusted life years was 335.9 and for RSV associated ARTI it was 241.8. RSV was the commonly detected respiratory virus with an annual seasonality and distribution in rainy seasons in the dry and wet zones of Sri Lanka. Identifying the virus and seasonality will contribute to employ preventive measures and reduce the empirical use of antibiotics in resource limited settings.

Infected tricuspid valve myxoma with Kodamaea ohmeri: Case report.

A 46-year-old male was having un-resolving fever for six weeks. Trans-esophageal echocardiography showed tricuspid valve myxoma (TVM). Kodamaea ohmeri was identified in 2 blood cultures and confirmed by 28S rDNA sequencing. Over three weeks of liposomal Amphotericin-B, fever has subsided thus indicated a clinical response. Subsequent echocardiography revealed no regression of suspected vegetation, and it was removed, and TV replacement was done. Histopathology revealed an infected myxoma and K. omeri was detected following 28S rDNA sequencing. For cardiac myxoma, excision is offered while for IE prolonged use of antifungals with or without vegetectomy is offered. So proper identification is important.

Inhibition of penicillin-binding protein 2a (PBP2a) in methicillin resistant Staphylococcus aureus (MRSA) by combination of oxacillin and a bioactive compound from Ramalinaroesleri.

Lichens are known to be useful and important in ethanopharmacology since ages and still possess substantial interest in alternative medical practices around the world. The intent of this investigation was to evaluate and to understand the antibacterial potential of usnic acid which was isolated from Himalyan fruticose lichen Ramalina roesleri. Usnic acid is predicted for its pharmaceutical properties through in -silico studies. Binding efficiency of usnic acid with Penicillin binding protein-PBP2a, a protein which is responsible for conferring resistance in Staphylococcus aureus was accessed using in-silico interaction assays comparing with oxacillin and ceftaroline. Further, the validation of in-silico modelling was checked by determining the antibacterial potential of usnic acid against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. In total, 28 clinical isolates collected from hospitals/medical students were included in the study and the anti-Staphylococcal activity was determined using agar plate dilution method followed by time-kill kinetics and synergistic studies. The scanning electron microscopic (SEM) pictures were obtained to show the cell wall disruption of MRSA by usnic acid. Docking results clearly indicated the enhanced binding potential of usnic acid (Glide XP G Score: 10.968; Glide energy -64.869) with PBP2a which is better than the energy range of reference compound, oxacillin (Glide XP G Score: 6.596; Glide energy -53.285) and roughly comparable to the co-crystallized ligand ceftaroline (Glide XP G Score: 12.20; Glide energy -70.322). Cefteroline is known to be more active against MRSA compared to oxacillin. The minimum inhibitory concentrations (MICs) of usnic acid against the clinical isolates of MRSA and reference strain (NCTC-6571) were in the range of 32-128 µg/ml. The high affinity of usnic acid to bind with PBP2a which is demonstrated via in-silico studies is further confirmed by the impressive inhibitory activity of usnic acid on MRSA clinical isolates.

Association of Hantavirus Infections and Leptospirosis With the Occurrence of Chronic Kidney Disease of Uncertain Etiology in the North Central Province of Sri Lanka: A Prospective Study With Patients and Healthy Persons.

Chronic Kidney disease of uncertain etiology (CKDu) has become a significant disease burden, affecting farming community of Sri Lanka and the exact etiology, which could be multifactorial, is not hitherto established. This study is aimed to determine the association of past hantavirus infection and leptospirosis with the occurrence of CKDu. A cohort (n = 179) of known CKDu patients living in high-CKDu prevalent areas of Anuradhapura district of Sri Lanka was compared with a group of 49 healthy, sex-matched younger blood relatives of CKDu patients (control-1) and another 48 healthy, age, and sex-matched individuals living in low-CKDu prevalent area (control-2) of the same district where same life style and climate conditions prevail. Fifty out of 179 (27.9%) CKDu patients, 16/49 (32.7%) of control-1 and 7/48 (14.6%) of control-2 were found positive for IgG antibodies to Puumala, Hantaan or both strains of hantaviruses. Hantaan strain specificity was found to be predominant in all study groups. Hantavirus IgG sero-prevalence of healthy individuals living in low-CKDu prevalent area was significantly lower compared to CKDu patients and healthy younger blood relatives living in high-CKDu prevalent areas (p = 0.03). Past hantavirus infection possesses a significant risk for the occurrence of CKDu (OR = 4.5; 95% CI-3.1-5.4, p = 0.02). In contrast, IgG seroprevalence to hantaviruses was not significantly different in CKDu patients and healthy younger blood relatives living in high-CKDu prevalent areas indicating past hantavirus infection has no association with the occurrence of CKDu or possibly, younger relatives may develop CKDu in subsequent years. Seroprevalence to leptospirosis showed no significant difference between CKDu patients and healthy controls.

Asymptomatic central line-associated bloodstream infections in children implanted with long term indwelling central venous catheters in a teaching hospital, Sri Lanka.

BACKGROUND: Indwelling central venous catheters (CVC) are used to provide long term hemodialysis. The commonest and the severe complication of CVC is the central line-associated bloodstream infection (CLABSI). This study was done to assess the etiology and infectious complications of CVC in children on long term hemodialysis. METHODS: Children newly undergoing hemodialysis and having indwelling CVC were included. They were followed up to a period of 2-years to assess infectious complications. Catheter bundle care approach was employed to prevent infections and other complications. Automated culture from the central catheter and peripheral vein and 2D echocardiography were done in each hemodialysis. Serial procalcitonin (PCT) was measured. Differential time of positivity (DTP) was used to detect CLABSI. During homestay in weekly telephone conversations were done to assess features of infection, and whenever having, we have asked to admit to the tertiary care unit. Logistic regression was performed, and the significant outcome variable was considered following multivariable analysis as a risk factor. RESULTS: Blood cultures were positive in 1090 (74.5%) out of 1462 children. According to DTP, 410 (28%) were having CLABSI, while 520 (35.6%) were having bacteremia without CLABSI. Out of 410 CLABSI patients, 79 (19.2%) were asymptomatic. Coagulase-negative Staphylococcus spp. (CoNS) bacteremia was significantly associated with asymptomatic CLABSI. Right-sided infective endocarditis (RS-IE) was significantly associated with asymptomatic CLABSI and asymptomatic bacteremia without CLABSI. CoNS was associated significantly in RS-IE following asymptomatic CLABSI and asymptomatic bacteremia. PCT was in asymptomatic CLABSI was 1.8 ± 0.9 ng/mL while in symptomatic CLABSI was 11.3 ± 2.5 ng/ml (P = 0.02). CoNS bloodstream infection, tunneled CVC, peripherally inserted central catheter, femoral site, the number of line days > 90, receipt of vancomycin, meropenem, or linezolid in the 5 days before CLABSI diagnosis and recurrent bacteremia were risk factors for asymptomatic CLABSI. CONCLUSIONS: Asymptomatic CLABSI could be a rare occurrence. CoNS was predominantly isolated in patients with asymptomatic CLABSI. RS- IE is a well-known complication in long term indwelling CVC. CoNS was significantly associated with RS-IE following asymptomatic CLABSI. Regular procalcitonin, microbiological, and imaging studies would be essential to detect infectious complications in both symptomatic and asymptomatic patients implanted with long term indwelling CVCs.

Corrigendum: Association of Hantavirus Infections and Leptospirosis With the Occurrence of Chronic Kidney Disease of Uncertain Etiology in the North Central Province of Sri Lanka: A Prospective Study With Patients and Healthy Persons.

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The emergence of non-albicans candidemia and evaluation of HiChrome Candida differential agar and VITEK2 YST® platform for differentiation of Candida bloodstream isolates in teaching hospital Kandy, Sri Lanka.

BACKGROUND: Candidemia is an emerging hospital-acquired bloodstream infection (BSI). It is common among severely ill and immunocompromised patients. Even following appropriate therapy in candidemia, recent studies reveal relative high mortality (40%). The global incidence of candidemia shows an incline. In Sri Lanka, candida speciation often difficult where basic facilities are less available. We have compared the risk factors, epidemiology, demography, and performance of HiChrome Candida differential agar (HiCA) characteristics with the VITEK2 YST platform for differentiation of Candida albicans (CA) and non-albicans candida (NAC) from blood culture isolate. METHODS: This is a laboratory-based cross-sectional study. Positive aerobic BACTEC blood cultures having yeast were identified using HiCA and VITEK2® platform. Epidemiology, risk factors, and clinical outcomes were compared between CA and NAC bloodstream isolates. RESULTS: Out of 120 positive yeast samples, VITEK2® has identified 110 (92%) as Candida sp. From that CA-34 (31%) and NAC-76 (69%) were isolated. Candidemia following NCA in neonates (p = 0.02), infants (p = 0.04) and adults (p = 0.02) in ICU and immunocompromised patients were significantly higher. Compared to CA, NAC bacteremia period prevalence (0.00041%) and incidence (0.23 per 100,000-person-years) was significantly high (p = 0.03). NAC 48 (63%) isolates were resistance to azoles. Exposure to antifungals (odds ratio (OR); p = 0.03), prolonged intensive care stay > 14 days (OR-3.3; p = 0.04), having a central venous line for > 8 days (OR-4.3; p = 0.03) and on immunosuppressive treatment (OR-2.4; p = 0.04) was significantly poses risk for NAC candidemia. Sen day mortality was significant among non-albicans cases (p = 0.03) while 30-day mortality was significant among albicans cases (p = 0.04). Compared to VITEK2®, the HiCA method was 93% sensitive and 93% specific in detecting CA. CONCLUSION: Compared to CA, candidemia following NAC was high. NAC isolates were having a high percentage of fluconazole and voriconazole resistance. VITEK2 YST® platform provides antifungal susceptibility with minimal inhibitory concentration (MIC). Impact, this would highlight the use of rapid candida identification flat form with MIC to direct appropriate antifungals for candidemia. For that implementation of novel diagnostic facilities like the VITEK2 YST platform at a tertiary care facility is demanding.

Intravenously administered cloxacillin-induced neutropenia with eosinophilia in a patient with infective endocarditis: a case report.

BACKGROUND: Bacteremia following Staphylococcus aureus is a serious clinical condition which is often associated with distant metastatic infections. One of the most dreaded complications of Staphylococcus aureus bacteremia is infective endocarditis. Cloxacillin is a common antibiotic prescribed for suspected staphylococcal infections and confirmed methicillin-sensitive Staphylococcus aureus infections. Prolonged use of cloxacillin may lead to neutropenia. CASE PRESENTATION: A 38-year-old Sinhalese man presented to Teaching Hospital Kurunegala, Sri Lanka, complaining of a 3-week history of fever; he was found to have a pansystolic murmur over the apex of his heart. He had leukocytosis with predominant neutrocytosis. His C-reactive protein was 231 mg/l and erythrocyte sedimentation rate was 100 mm/first hour. Transthoracic two-dimensional echocardiography revealed prolapsed mitral valve with 7 × 13 mm vegetation over the posterior mitral valve. On the following day, three blood cultures became positive and were subsequently identified as Staphylococcus aureus. Intravenously administered cloxacillin 3 g 6 hourly was started. Following day 24 of intravenously administered cloxacillin, our patient developed high spike fever. His total white blood cells were: 990/mm3 with 34% neutrophils and 22% eosinophils. His hemoglobin concentration was 9.5 g/dL and platelet count remained normal (202 × 106/mm3). His C-reactive protein was 78 mg/l, erythrocyte sedimentation rate was 95 mm/first hour, and he was otherwise comfortable, showing no signs of sepsis beside the high grade fever. His serum was negative for filarial and Toxoplasma antibodies while stool was negative for oocytes and amoebic cysts. Further, his serum was negative for dengue virus, Epstein-Barr virus, cytomegalovirus, and hepatitis B antibodies. He was clinically well on day 6 after stopping cloxacillin with 44% neutrophils and 18% eosinophils. His C-reactive protein and erythrocyte sedimentation rate became normal, and there was no further plan for cardiothoracic intervention or administration of antimicrobials. He was discharged from hospital and remained well 6 months later. CONCLUSION: This case report signifies the potential fatal adverse effect of cloxacillin in methicillin-sensitive Staphylococcus aureus infections. Leukopenia is associated with prolonged use of high doses of cloxacillin. In addition to transthoracic two-dimensional echocardiography and inflammatory markers, sequential white blood cells and differential counts would help clinicians to assess the prognosis of patients with infective endocarditis.

Use of Ayurveda and Sri Lankan traditional medicine for healing shaft of humerus fracture following nonunion.

Sri Lanka comprises of a well-established traditional orthopedic treatment system. A 14 year old child had a compound fracture over shaft of humerus. The internal fixator Kirschner (k) wire was applied following allopathic treatment and after three weeks, it was removed as there was no healing of wound over fracture site. Patient was asked to follow orthopedic clinic but defaulted and presented to Ayurveda management. X-ray reports showed nonunion of the humerus. Initially, nonunion bone was immobilized for six months using bamboo splints. Prior to applying the splints, during every visit, herbal oil and herbal paste were applied. Subsequently up to six months, motor, sensory functions assessment and quality of life (QoL) assessment was done using Quality of Life of the International Osteoporosis Foundation (QLIOF) questionnaire. Initial power of wrist and fingers were graded 1 and in 6- months time, improved to grade 5. The difference in the QLIOF scores were analyzed using Wilcoxon signed rank test. There was a significant (p = 0.03) difference between the pre-treatment (14) and post-treatment (59) QLIOF scores. The anterior- posterior and lateral X-ray showed complete healing of the fracture. This report indicates that the methods and medicines in Ayurveda and traditional orthopedic system can successfully treat a nonunion of humerus fracture.

A case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in Sri Lanka.

OBJECTIVES: The prevalence of hMPV infections in Sri Lanka has not been reported and here we report a case series of hMPV infection in children less than 5 years. Patients with ARTI were included from Teaching Hospital, Anuradhapura from March 2013 to August 2014. Indirect fluorescence assay was performed on nasopharyngeal aspirates for the identification of respiratory viruses [respiratory syncytial virus (RSV), parainfluenza virus 1, 2 and 3, influenza A and B and hMPV]. Moreover, reverse transcriptase-polymerase chain reaction was done to further confirm the hMPV infection. RESULTS: In this case series, hMPV infection showed a range of respiratory symptoms from common cold to life threatening lower respiratory tract infections with varying severity. In some cases, the clinical presentation of hMPV infection was similar to the ARTI caused by RSV. hMPV co-infections with of RSV have also been seen in some cases of ARTI. A child delivered through cesarean section and birth order > 3 has an Odds ratio of 3.5 and 4.3 (95% CI) for developing co-infection with RSV compared to hMPV mono-infections. Lack of diagnostic facilities to identify the viral aetiology has contributed to the use of antibiotics indicating the need for establishing viral diagnostic facilities in the country.

Assessment of the outcome of Ayurvedic treatments for vertebral fracture with motor dysfunction.

Assessment of outcome following Ayurveda treatment protocol was done in a complicated case of spinal fracture with motor dysfunction and having a past history of Pott's disease. A 52-year-old man was suffering from motor dysfunction after a spinal fracture at D5/D6 level. The patient sought Ayurveda treatments because he did not gained any significant improvement according to mainstream medical treatments what he underwent for several years. According to Ayurveda, the patient was treated following immobilization, external and internal application of herbal preparations followed by physiotherapy. The outcome of the treatments were monitored by motor function assessment, quality of life assessment and computed tomography scan. Initial signs of improvement were observed just after 1 month of commencing Ayurveda treatments. Continuously following the treatments for 24-month duration, the patient was reverted back to his normal life. This complicated case of spinal fracture was successfully cured using Ayurveda treatment. Therefore, the observations made here would be useful for organizing a future clinical trial.

Dehydration and malaria augment the risk of developing chronic kidney disease in Sri Lanka.

Chronic kidney disease (CKD) of unknown etiology (CKDu) is a serious health issue in Sri Lanka. One-to-one age and sex-matched two sample comparative study was carried out in the Medawachchiya divisional secretariat area of the North Central Province (NCP) of Sri Lanka, by randomly selecting 100 CKDu patients and 100 age and sex-matched subjects from non-CKDu affected families from the same area. An interviewer-administered questionnaire was used for the collection of data pertaining to occupation, medical history and lifestyle. Data were analyzed using a conditional linear logistic model. Working for >6 h in the field per day, exposure to sun, drinking water only from well, consumption of <3 L of water per day, and having a history of malaria were found to be having significant (P < 0.05) likelihood toward the development of CKDu. Treatment of water prior to consumption had a significant protective effect against CKDu. Dehydration, history of malaria and drinking untreated well water from are likely contribute to the development of CKD of unknown etiology among the inhabitants of NCP, Sri Lanka.