Anemia in Sri Lanka: A Literature Review.

Anemia is a global health problem. This paper reviews literature on the prevalence of anemia in Sri Lanka. We searched EBSCO (Elton Bryson Stephens Company), Cochrane Library, and Medline for articles on prevalence and molecular basis of anemia in Sri Lanka from January 2000 to May 2021. Forty articles were selected. Most of the studies were on prevalence of anemia among children and pregnant women. All the studies had restricted themselves to assess the contributing factors for anemia in limited age categories. Most articles had attempted to determine the overall prevalence of anemia and the contribution of iron deficiency to it. There were only a few studies on prevalence and molecular basis of hemoglobinopathies and even fewer on the prevalence of anemia of chronic disease. None of the studies had attempted to assess the national prevalence of red cell membranopathies and enzymopathies. The published data on prevalence of anemia in Sri Lanka are incomplete. This review emphasizes the value of a much broader survey on anemia covering all age categories including the elderly and conducting a national survey including anemia of chronic disease and on red cell membranopathies and enzymopathies in Sri Lanka.

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.

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.

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.

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.

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.

Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka.

INTRODUCTION: While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. METHODS: In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case-control study between lean NAFLD cases and lean non-NAFLD controls. RESULTS: Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. CONCLUSION: Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming.

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. SUMMARY: Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient.

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.

Effect of audio and visual distraction on patients undergoing colonoscopy: a randomized controlled study.

Background and study aims: Colonoscopy can cause anxiety and discomfort in patients. Sedation and analgesia as premedication can lead to complications in the elderly and those with comorbidities. This has led to an interest in the use of audio-visual distraction during the colonoscopy. We compared the effects of audio (AD) versus visual distraction (VD) in reducing discomfort and the need for sedation during colonoscopy. Patients and methods: Consecutive patients undergoing colonoscopy were randomized into three groups: one group was allowed to listen to the music of their choice (AD), the second group was allowed to watch a movie of their choice (VD), and the third group was not allowed either distraction during colonoscopy and acted as a control (C). Patient controlled analgesia and sedation were administered to all three groups. We used 25 mg of pethidine in 5-mg aliquots and 2.5 mg of midazolam in 0.5-mg aliquots. All patients were assessed for perceived pain and willingness to repeat the procedure. Number of "top-ups" of sedation and total dose of pethidine and midazolam were noted. Patient cooperation and ease of procedure were assessed by the colonoscopist. Results: In total, 200 patients were recruited [AD, n = 66 (32 males, median age 57 years); VD, n = 67 (43 males, median age 58 years); C, n = 67 (35 males, median age 59 years)]. The AD group had significantly less pain (P = 0.001), better patient cooperation (P = 0.001) and willingness to undergo a repeat procedure (P = 0.024) compared with VD and C groups. Conclusions: AD reduces pain and discomfort, improves patient cooperation and willingness to undergo a repeat procedure, and seems a useful, simple adjunct to low dose sedation during colonoscopy. STUDY REGISTRATION: SLCTR/2014/031.

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.

Association between road accidents and low-grade hepatic encephalopathy among Sri Lankan drivers with cirrhosis: a prospective case control study.

BACKGROUND: Low-grade hepatic encephalopathy (LGHE) comprises minimal hepatic encephalopathy (MHE) and grade 1 hepatic encephalopathy. LGHE has no or minimal recognizable symptoms but has mild cognitive and psychomotor deficits. Studies in Western countries have demonstrated increased road accidents (RA) among patients with MHE. Our objective was to investigate the association between Sri Lankan LGHE phenotype and RA. STUDY DESIGN AND METHODS: A prospective, case-control study was conducted in the University Medical Unit, North Colombo Teaching Hospital, Ragama Sri Lanka. Patients with cirrhosis of any aetiology, without OHE, who had been driving during previous 1 month were included. A similar number of age matched, healthy control drivers were also enrolled. Both groups were subjected to five pencil-paper based psychometric tests used to detect LGHE in cirrhotics. Self-reported RA during the previous 1 month were recorded: categorized as 'major' when resulted in hospitalization of the involved, 'minor' when there were injuries, but not serious enough for hospitalization of the involved and 'other' when limited to damages to vehicle or environment without injuries. RESULTS: Among 55 drivers with cirrhosis and LGHE [males, median age 53 years (range 30-60)], 7 (12.7 %) reported RA compared to 6 (10.9 %) among 55 controls [males; median age 51 years (range 30-60)]. There were no 'major' accidents in either group. 2/55 (3.6 %) cases and 2/55 (3.6 %) controls reported 'minor' accidents. CONCLUSION: There was no increased frequency of RA among Sri Lankan drivers with LGHE compared to healthy controls. This is with the limitation of the study based only on self reported RA.

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.

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.