Changing phenotype, early clinical course and clinical predictors of inflammatory bowel disease in Sri Lanka: a retrospective, tertiary care-based, multi-centre study.

BACKGROUND: Inflammatory bowel disease (IBD) is increasing in the Asia-Pacific region, with changes in disease phenotype and course. We aimed to assess the changing phenotypes of IBD over ten years, describe the early clinical course (ECC) and identify the clinical predictors (CP) of poor outcomes among a large, multi-centre, cohort of Sri Lankan IBD patients. METHODS: We included patients [diagnosed between June/2003-December/2009-Group-1(G1), January/2010-June/2016-Group-2(G2)] with ulcerative colitis (UC) and Crohn disease (CD) from five national-referral centres. Changing phenotype from G1 to G2, ECC (disease duration < 3-years) and CP of poor outcomes (disease duration ≥ 1-year) was assessed. Poor outcomes were complicated-disease (CompD-stricturing/penetrating-CD, extensive-UC/pancolitis, perforation/bleeding/colectomy/malignancy) and treatment-refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory and biologic use). RESULTS: 375 (UC-227, CD-148) patients were recruited. Both G1/G2 had more UC than CD (77% vs 23%, 54.5 vs 45.5 respectively, p < 0.01). Increase of CD from G1-to-G2 was significant (23-45.4%, p < 0.001). In both groups, left-sided colitis (E2) and ileo-colonic (L3)/non-stricturing, non-penetrating disease behaviour (B1) CD predominated. Extensive-colitis (E3) (36.4% vs 22.7, p < 0.05) and stricturing-CD (B2) (26.1% vs 4.0%, p < 0.01) was commoner in G1. ECC was assessed in 173-patients (UC-94, CD-79). Aggressive disease behaviour and TRD were low among both UC and CD. Immunomodulator use was significantly higher among CD than UC (61.5% vs 29.0% respectively, p < 0.01). Anti-TNF use was low among both groups (UC-3.2%, CD-7.7%). Disease complications among UC [bleeding (2.1%), malignancy-(1.1%), surgery-(2.1%)] and CD [stricture-(3.9%), perforation-(1.3%), malignancy-(1.3%), surgery-(8.9%)] were generally low. CPs were assessed in 271-patients (UC-163, CD-108). Having a family history of IBD (for UC), extraintestinal manifestation (EIM), severe disease at presentation, being in younger age categories and severe disease at presentation, (for both UC and CD) predicted poor outcomes. CONCLUSION: There was an increase in CD over time without change in disease phenotype for both UC and CD. A relatively benign ECC was observed. Family history (UC), EIMs (UC/CD), severe disease at presentation (UC/CD), younger age (CD/UC) CPs of poor outcomes.

COVID-19 and gastroenterology: clinical insights and recommendations for gastroenterology care providers.

While the COVID-19 pandemic evolves, we are beginning to understand the role the gastrointestinal tract plays in the disease and the impact of the infection on the care of patients with gastrointestinal (GI) and liver diseases. We review the data and understanding around the virus related to the digestive tract, impact of the pandemic on delivery of GI services and daily gastroenterology clinical practice, and the effects on patients with pre-existing GI diseases.

Percentage of small platelets on peripheral blood smear and Child-Turcott-Pugh class can predict the presence of oesophageal varices in newly diagnosed patients with cirrhosis: development of a prediction model for resource limited settings.

BACKGROUND: In cirrhosis upper-gastrointestinal-endoscopy (UGIE) identifies oesophageal varices (OV). UGIE is unavailable in most resource-limited settings. Therefore, we assessed prediction of presence of OV using hematological parameters (HP) and Child-Turcott-Pugh (CTP) class. METHODS: A prospective study was carried out on consecutive, consenting, newly-diagnosed patients with cirrhosis, in the University Medical Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka from April 2014-April 2016. All patients had UGIE to evaluate presence and degree of OV, prior to appropriate therapy. HP (full blood count with indices using automated analyzer and peripheral blood smear using Leishmann stain) and CTP class were assessed on admission. Linear logistic regression model was developed to predict OV using HP and CTP class. RESULTS: 54-patients with cirrhosis were included [14(26%), 24(44%) and 16(30%) belonged to CTP class A, B and C respectively]. 37 had varices [CTP-A 4/14(26.6%), CTP-B 19/24(79.2%), CTP-C 14/16(87.5%)] on UGIE. Generalized linear model fitting showed decreasing percentage of small platelets (%SP) (P = 0.002), CTP-B (P = 0.003) and CTP-C (P = 0.003) compared to CTP-A had higher probability of having OV. The model predicts the log odds for having OV = - 0.189 - (0.046*%SP) + 2.9 [if CTP-B] + 3.7 [if CTP-C]. Based on receiver operating characteristic (ROC) analysis, a model value > - 0.19 was selected as the cutoff point to predict OV with 89%-sensitivity, 76%-specificity, 89%-positive predictive value and 76%-negative predictive value. CONCLUSIONS: We constructed a model using %SP on peripheral blood smear and CTP class. This model may be used to predict the presence of OV, in newly diagnosed patients with cirrhosis, with acceptable sensitivity and specificity, to prioritize the patients who deserve early UGIE in limited resource settings.

Genotypic characterization of Orientia tsutsugamushi from patients in two geographical locations in Sri Lanka.

BACKGROUND: To date more than 20 antigenically distinct strains of Orientia tsutsugamushi (OT) reported within the tsutsugamushi triangle that cause an undifferentiated acute febrile illness in humans. Genotypic characterization of OT in different geographic regions or within the same country, is important in order to establish effective diagnostics, clinical management and to develop effective vaccines. Genetic and antigenic characterization of OT causing human disease in OT-endemic regions is not known for Sri Lanka. METHODS: Adult patients and children who were admitted with an acute febrile illness and presumed to having acute scrub typhus based on presence of an eschar and other supporting clinical features were recruited. Eschar biopsies and buffy coat samples collected from patients who were confirmed having OT by IFA were further studied by real time PCR (Orientia 47 kD) and nested PCR (Orientia 56 kD) amplification. DNA sequences were obtained for 56 kD gene amplicons and phylogenetic comparisons were analyzed using currently available data in GenBank [Neucleotide substitution per 100 residues, 1000 Bootstrap Trials]. RESULTS: Twenty eschar biopsies (Location1,19, Location 2,1) and eight buffy coat samples (Location1,6, Location2,2) examined by real time PCR revealed Orientia amplicons in 16 samples. DNA sequences were obtained for the 56 kD gene amplicons in 12 eschars and 4 buffy coat samples. The genotypes of the Location1 samples revealed that, 7 exhibiting close homology with JP1 [distantly related to UT177 Thai (Karp related)], five had close homology with Kato strain, two had close homology with JGv and JG AF [Distantly related to Kawasaki M63383] and one had close homology with Gilliam strain. The Location 2 strain was closely related to Kuroki-Boryong L04956, the genotype which is distributed in far eastern Asia. Similar to other patients in the cohort this patient also had never travelled out of Sri Lanka. CONCLUSIONS: We observed all three main OT genotypes in Sri Lanka, and the majority fell into Thai Karp related clade. These results demonstrate great antigenic diversity of OT in the studied areas of Sri Lanka.

The prevalence of upper respiratory symptoms in a cohort of adults presenting with symptoms of gastro-oesophageal reflux disease.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) is the pathological reflux of gastric contents into the oesophagus. The oesophagus and the upper respiratory tract have a common origin from the foregut. There is increasing evidence for multiple associations of GORD with the upper respiratory tract. OBJECTIVES: To study the presence of and association of upper respiratory symptoms (URS) with GORD. METHODS: Seventy adults scoring ≥12.5 on a previously validated GORD symptom score (GORD patients) and 70 healthy controls who had infrequent GORD symptoms or no upper gastro-intestinal complaints completed a pre-tested URS questionnaire on the frequency of 14 URS in 5 categories (laryngeal, nasal, pharyngeal, sinusal and aural). All GORD patients underwent upper gastro-intestinal endoscopy. The calculated URS score was correlated against the GORD symptom score and endoscopy findings. RESULTS: URS scores and individual symptom scores were higher in GORD patients compared to controls (mean ± SE, 4.7 ± 4.0; 1.9 ± 2.3). Individuals with higher GORD symptom scores reported more frequent URS. Pharyngeal symptoms had the highest correlation with the GORD symptom score (r=0.507, p<0.001). The presence of oeso-phagitis did not seem to influence the frequency of reporting URS. CONCLUSION: Upper respiratory symptoms are common in individuals with GORD symptoms though there appears to be no association with oesophageal mucosal damage.

Predicting acute liver failure in dengue infection.

In a retrospective study involving 240 patients with dengue infection, we attempted to identify early predictors of acute liver failure (ALF). Sixteen out of 41 patients with serum AST more than 1000 IU/ml developed ALF compared to none with serum AST less than 1000 IU/ml. Among patients with serum AST more than 1000 IU/ml, presence of two of the three following phenomena, within the first 5 days of illness: elevated serum bilirubin, elevated alkaline phosphatise or persistent nausea and vomiting, predicted development of ALF (93.8% sensitivity, 98.7% specificity, 83.3% positive predictive and 99% negative predictive value). The presence of elevated serum bilirubin, alkaline phosphatase and persistent nausea and vomiting in patients with very high serum AST during the early phase of dengue infection should alert the physician of impending ALF.

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

OBJECTIVE: The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. DESIGN: 442 incident cases (186 Crohn's disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. RESULTS: In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. CONCLUSIONS: This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem.

Two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. Thirty-one patients, hospitalized in Sri Lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with IgM ELISA for both pathogens. Of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. Moreover, in a retrospective study of 23 former patients, serologically confirmed for past leptospirosis, six (26·0%) were also positive in two different IgG ELISA hantavirus formats. Surprisingly, European Puumala hantavirus (PUUV) results were constantly higher, although statistically not significantly different, than Asian Hantaan virus (HTNV), suggesting an unexplained cross-reaction, since PUUV is considered absent throughout Asia. Moreover, RT-PCR on all hantavirus IgM ELISA positives was negative. Concomitant leptospirosis-hantavirus infections are probably heavily underestimated worldwide, compromising epidemiological data, therapeutical decisions, and clinical outcome.

Secondary bacteraemia in adult patients with prolonged dengue fever.

INTRODUCTION: Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. OBJECTIVES: To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. METHODS: A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. RESULTS: Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. CONCLUSIONS: A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.

Prevalence of hepatitis B and hepatitis C infections and their relationship to injectable drug use in a cohort of Sri Lankan prison inmates.

INTRODUCTION: Prisoners are considered to be at high risk for Hepatitis B (HBV) and Hepatitis C (HCV) virus infections. This is attributed to intravenous drug use and high-risk sexual behaviour. There are no published studies on HBV and HCV among prison inmates or injecting drug users in Sri Lanka. OBJECTIVES: To determine prevalence of HBV and HCV infections, and their relationship to injectable drug use among Sri Lankan prisoners. METHODS: We investigated 393 (median age 42 years (range 16 to 93); 82% males) randomly selected inmates of Mahara and Welikada prisons. RESULTS: Though 167 (42.5%) admitted drug abuse, only 17 (4.3%) had ever used intravenous drugs. Twelve (70.6%) of them reported sharing needles. One inmate was positive for HBsAg but was negative for HBV-DNA. Twenty seven (6.9%) were positive for anti-HCV antibodies, of whom only 2 (0.5%) were positive for HCV-RNA. None of the injecting drug users were positive for HBV-DNA or HCV-RNA. CONCLUSIONS: The prevalence of HBV and HCV infections as well as injecting drug use was very low among this cohort of Sri Lankan prison inmates.

Incidence of inflammatory bowel disease in Gampaha district: details of the Sri Lankan component of the Asia-Pacific Crohn's and colitis epidemiology study.

The aim of this report is to provide details of the methodology and results of the Sri Lankan component of the Asia-Pacific Crohn's and Colitis Epidemiology Study. Fourteen state and private hospitals with specialist services in the Gampaha and Colombo districts were kept under surveillance over a 12 month period to recruit patients with newly diagnosed Inflammatory Bowel Disease (IBD) who were permanent residents of the Gampaha district. Thirty five cases (ulcerative colitis-21, Crohn's disease-13, IBD-undetermined-1) were detected, giving a crude annual IBD incidence of 1.59 per 100,000 population.

Clinical profile and difficulties in diagnosis of central nervous system infections in adult patients in a tertiary care hospital.

OBJECTIVES: We aimed to describe the pattern of central nervous system (CNS) infections and accuracy of diagnosis in a Sri Lankan tertiary care hospital. METHODS: We prospectively studied all adult patients with suspected CNS infection admitted over a two-year period. Data were collected on demographic and clinical features, laboratory findings, treatment and immediate outcome. Diagnosis of CNS infection was categorized as definite, probable, possible and uncertain. RESULTS: We studied 215 patients [59.1% males; mean age (SD) 44 (20) years]. Blood cultures were done in 65 (30.2%) and only one was positive. Lumbar puncture was done in 146 (67.9%), and cerebrospinal fluid Gram stains, culture and acid-fast bacilli stains were all negative. Diagnosis of CNS infection was considered 'definite' in only one patient, 'probable' in 57.2%, 'possible' in 5.6%, and 'uncertain' in 26%. An alternative diagnosis was found in 23 patients (10.7%). Intravenous antibiotics and aciclovir were given on emperical grounds, largely without microbiological confirmation. CONCLUSIONS: Diagnosis of CNS infections is highly unsatisfactory with available facilities, even in a tertiary care setting.

Validation of the Sinhala version of the Chronic Liver Disease Questionnaire (CLDQ) for assessment of health related quality of life among Sri Lankan cirrhotics.

OBJECTIVES: The Chronic Liver Disease Questionnaire (CLDQ) is a validated tool measuring Health Related Quality of Life among patients with cirrhosis. The aim of this study was to validate a Sinhala version of the CLDQ (sCLDQ) and to test its correlation with the degree of liver dysfunction in a cohort of Sri Lankan patients with cirrhosis. METHODS: A standard translation method was used. Pilot testing was done with relevant cultural and language adaptations. The final version and the WHO Quality of Life-BREF (WHOQOL-BREF) validated Sinhala version were administered to patients with chronic lever disease (CLD). sCLDQ was re-administered 4 weeks later to test internal consistency and reliability. The validaty and reliability were assessed by Cronabach's alpha, intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. ANOVA and Pearson's correlation were used to assess correlation with the degree of liver dysfunction. RESULTS: Validation was done with 214 participants [mean age 55.6 years (SD 10.4) male 77.6%]. Cronabach's alpha was 0.926. Intra-class correlations varied from 0.431 to 0.912 and all were significant (p< 0.001). Retesting was done on a sub-sample of 18 participants. Test-retest correlation was 0.695 (p = 0.008). WHO-BREF was administered to a sub-sample of 48 subjects. There was a significant correlation (Pearson's r=0.391; p=0.004) between sCLDQ and WHOQOL BREF. sCLDQ was significantly associated with MELD (r=-0.13; p=0.038), MELD sodium (r=-0.223; p=0.002), serum bilirubin (r=-0.124; p=0.036), serum sodium (r=0.172; p=0.009), serum albumin (r=0.201; p=0.003) and Child grade (f=3.687; p=0.027). CONCLUSIONS: CLDQ is a reliable and valid tool to assess quality of life of Sri Lankan patients with cirrhosis and correlates well with known indices of disease severity.

Dengue and leptospirosis infection during the coronavirus 2019 outbreak in Sri Lanka.

A significant decrease in dengue fever cases and a contrasting increase in leptospirosis cases were reported for the second quarter of 2020 compared with 2019 in Sri Lanka. In the absence of significant environmental and weather-related differences to account for these changes in incidence, we investigated the possibility that the effects of the COVID-19 pandemic on public health, social behaviour and the restrictions imposed during the lockdown influenced the fluctuations in dengue and leptospirosis infections.

Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study.

INTRODUCTION AND OBJECTIVES: There are no cardiovascular (CV) risk prediction models for Sri Lankans. Different risk prediction models not validated for Sri Lankans are being used to predict CV risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected 40-64 year-old participants from the Ragama Medical Officer of Health (MOH) area in 2007 by stratified random sampling and followed them up for 10 years. Ten-year risk predictions of a fatal/non-fatal cardiovascular event (CVE) in 2007 were calculated using WHO/ISH (SEAR-B) charts with and without cholesterol. The CVEs that occurred from 2007-2017 were ascertained. Risk predictions in 2007 were validated against observed CVEs in 2017. RESULTS: Of 2517 participants, the mean age was 53.7 year (SD: 6.7) and 1132 (45%) were males. Using WHO/ISH chart with cholesterol, the percentages of subjects with a 10-year CV risk <10%, 10-19%, 20%-29%, 30-39%, ≥40% were 80.7%, 9.9%, 3.8%, 2.5% and 3.1%, respectively. 142 non-fatal and 73 fatal CVEs were observed during follow-up. Among the cohort, 9.4% were predicted of having a CV risk ≥20% and 8.6% CVEs were observed in the risk category. CVEs were within the predictions of WHO/ISH charts with and without cholesterol in both high (≥20%) and low(<20%) risk males, but only in low(<20%) risk females. The predictions of WHO/ISH charts, with-and without-cholesterol were in agreement in 81% of subjects (ĸ = 0.429; p<0.001). CONCLUSIONS: WHO/ISH (SEAR B) risk prediction charts with-and without-cholesterol may be used in Sri Lanka. Risk charts are more predictive in males than in females and for lower-risk categories. The predictions when stratifying into 2 categories, low risk (<20%) and high risk (≥20%), are more appropriate in clinical practice.

Ovarian lymphoma in a patient on long-term sulfasalazine for ulcerative colitis.

We report a case of ovarian lymphoma in a 59 year old woman with ulcerative colitis for over 20 years. She presented with intermittent high fever and right sided abdominal pain for 3 weeks. An ultrasound scan and CT scan revealed a right adnexal mass measuring 71 X 54 mm which was well defined with a thick wall and internal septations and enlarged pelvic and para aortic lymph nodes. The patient underwent bilateral salpingo oophorectomy and omentectomy. Histology confirmed a diffuse large B cell Non Hodgkin's lymphoma and she was referred for chemotherapy. After 6 cycles of chemotherapy she showed a good response. Lymphoma of the gastrointestinal tract arising in a background of ulcerative colitis has been known to occur, ovarian lymphoma with a background of ulcerative colitis has not been reported.

Acute Dermato-Lymphangio-Adenitis Following Administration of Infliximab for Crohn's Disease.

Tumor necrosis factor-α inhibitor (TNF-α) is frequently used for Crohn's disease and other autoimmune conditions. Increased risk of infection is an accepted adverse effect of TNF-α, and routine screening for potential infections are carried out before initiation of therapy. We report the case of a patient who developed a localized painful swelling near the injection site, which was diagnosed as acute dermato-lymphangio-adenitis due to filarial infection. This adds to the limited number of case reports on parasitic complications following TNF-α therapy.