Successful Management of Neutropenic Sepsis Is Key to Better Survival of Patients With Blood Cancer in Sri Lanka: Real-World Data From the Resource-Limited Setting.

PURPOSE: Sepsis is the main cause of nonrelapse mortality, and there are no published data on applicability of supportive care protocols from high-income countries such as Sri Lanka. The aim of the study was to investigate management and mortality of neutropenic episodes among Hemato-Oncology patients. MATERIALS AND METHODS: Retrospective analysis of clinical characteristics, management, morbidity, and mortality of neutropenic Hemato-Oncology patients presented to the Lanka Hospital Blood Cancer Centre from January 1, 2019 to December 31, 2019 was performed. RESULTS: A total of 169 neutropenic episodes were identified; 115 (68%) of such episodes were related to chemotherapy. Acute leukemia, lymphoproliferative disorders, and plasma cell disorders accounted for 23%, 69%, and 8% of patients, respectively. The median age of patients who had sepsis was 56 years, whereas that of those who had no sepsis was 53 years (P = .49). The median time to neutropenia was 9 days for those in the sepsis group compared with 8 days in the group that had no sepsis (0.64). The median neutrophil count in the group that had sepsis was 0.06, whereas it was 0.69 in the group that had no sepsis (P ≤ .05). The median time to commencement of antibiotics was 20 minutes. CONCLUSION: To our knowledge, this is the only documented study related to outcome and successful applicability of western supportive care protocols to Sri Lankan patients with neutropenia. In this study, we have shown that neutropenic sepsis can be successfully managed in the setting of limited resources with service development, following guidelines and staff training.

ASVAC2022 : 8th Asian Vaccine Conference.

Aiming to further the Immunization Partners in Asia Pacific (IPAP)'s vision of a world where no one suffers from a vaccine preventable disease, the 8th Asian Vaccine Conference (ASVAC 2022) was held in Colombo, Sri Lanka and virtually from 15 to 18, September 2022 (www.asianvaccine.com). This conference followed those held in Siem Reap, Cambodia (2009), Manila, Philippines (2010), Jakarta, Indonesia (2011), Cebu, Philippines (2013), Hanoi, Vietnam (2015), Singapore (2017) and Naypyidaw and Yangon, Myanmar (2019). The ASVAC2022 themed "Immunization: in Era of Pandemics," commenced with the EPI Managers' Workshop, followed by pre-conference workshops and Vaccinology Masterclass, followed by the main conference featuring 5 plenary lectures, 6 partner-led symposia, free paper and poster presentations, and industry-supported lunch and evening sessions. There were over 1830 registered participants, with 112 attending in person and 998 virtually from 63 countries. The conference was organized by IPAP and hosted by the Vaccine and Infectious Disease Forum of Sri Lanka, Sri Lanka College of Pediatricians, Sri Lanka College of Microbiologists and College of General Practitioners of Sri Lanka, with the support of the Ministry of Health, Sri Lanka. The 9th ASVAC is scheduled to be held in Davao City, Philippines in late 2023.

Response and Survival Estimates of Patients With Plasma Cell Myeloma in a Resource-Constrained Setting Using Protocols From High-Income Countries: A Single-Center Experience From Sri Lanka.

PURPOSE: There is a significant disparity in global cancer care and outcome between countries. Progress in the treatment of symptomatic plasma cell myeloma (PCM) in high-income countries is not seen in low- and middle-income countries. MATERIALS AND METHODS: This is was a retrospective cohort study of all patients diagnosed with PCM between May 1, 2013, and September 30, 2021, at the first hemato-oncology center in Sri Lanka. We aimed to provide data on clinicopathologic characteristics, response, and survival estimates. RESULTS: A total of 79 patients with PCM received first-line therapy during the study period. The median age was 64 years, and approximately one third (33%) of patients were older than 70 years. There were 42 (53%) males and 37 females. Hypercalcemia, renal impairment, anemia, and bone disease were detected in 36.7%, 38%, 72.1%, and 81%, respectively. Thirty-nine, 34, and six patients received a combination of cyclophosphamide, thalidomide, and dexamethasone; bortezomib, thalidomide, and dexamethasone; and other treatments, respectively. The overall response rate (≥ partial response) was approximately 97% for both cyclophosphamide, thalidomide, and dexamethasone and bortezomib, thalidomide, and dexamethasone. Twenty-three (29%) of these patients died during the study period, but only 14 (18%) died due to PCM or associated sepsis. After a median follow-up of 40.6 months (range, 35.2-59.07 months), the median overall survival was 84.2 months (95% CI, 60.87 to not available). The 5-year estimated overall survival was 65%. CONCLUSION: To our knowledge, this is the only well-characterized study on long-term survival of patients with PCM in Sri Lanka. We have shown that it is possible to successfully apply Western treatment and supportive care protocols to the local population. These published data will help to benchmark and improve the treatment and develop blood cancer care in the local setting.

Hantavirus Hemorrhagic Fever with Renal Syndrome - Suspected Cases in Sri Lanka: Clinical Picture and Epidemiology from 2013-2021.

Hantavirus hemorrhagic fever with renal syndrome (HFRS) is an emerging zoonotic disease in Europe and Asia, which is clinically indistinguishable from leptospirosis. A total of 1,032 patients with clinical suspicion of HFRS-like illness were included in the analysis from March 2013 to March 2021. Of these, 168 were positive for hantavirus immunoglobulin M (IgM) antibodies. Thirty-one of 35 patients had a 4-fold increase in IgG antibody titer with paired serum, confirming acute hantavirus infections. The detected antibodies showed a diverse pattern, strongly cross-reacting with the Seoul, Hantaan, and Puumala virus antigens. All the IgM-positive patients had no serological evidence of acute dengue or leptospirosis and had classical features of HFRS, including fever, thrombocytopenia, and renal involvement. More than 90% of patients had a history of rodent exposure 2-3 weeks prior to the onset of the fever. The highest number of positive cases was diagnosed in the Western and North Central Provinces of Sri Lanka during the paddy harvesting seasons. A significant number of patients develop severe complications with high mortality rates. Therefore, hantavirus infection should be considered as a differential diagnosis for leptospirosis-like illnesses in Sri Lanka.

Blood cancer care in a resource limited setting during the Covid-19 outbreak; a single center experience from Sri Lanka.

BACKGROUND: The Covid-19 pandemic has caused significant morbidity and mortality among patients with cancer. Most countries employed measures to prevent spread of Covid-19 infection which include shielding, quarantine, lockdown, travel restrictions, physical distancing and the use of personal protective equipment. This study was carried out to assess the change in patient attendance and the efficacy of newly implemented strategies to mitigate the impact of Covid-19 on services at the Lanka Hospital Blood Cancer Centre (LHBCC) in Colombo, Sri Lanka. METHODOLOGY: Telephone consultation, infection control, personal protective measures and emergency admission policy were implemented with the aim of having a Covid-19 free ward and to prevent cross-infections. This descriptive cross-sectional study was conducted with 1399 patient episodes (in-patient care or day-case review). We analysed patients treated as in-patient as well as day-case basis between 01st April 2020 and 31st December 2020. RESULTS: There were 977 day-case based episodes and 422 in-patient based episodes. There was a 14% drop in episode numbers compared to same period in 2019. There was no cross infection and no patients with Covid-19 related symptoms or positive test results entered the LHBCC during the study period. CONCLUSION: Services in blood cancer care were maintained to prevent late stage presentation and adverse outcome. Measures implemented to prevent Covid-19 were effective to allow continuation of treatment. This study highlights the importance of implementing strict protocols, clinical screening, use of appropriate personal protective equipment in delivering blood cancer care during the Covid-19 pandemic. This is the only documented study relating to outcome and successful applicability of measures to prevent spread of Covid-19 infection and maintaining services among blood cancer patients in Sri Lanka.

Applicability of protocols from high-income countries in a resource limited setting; real world data of histopathology, clinical features and long-term outcome of Hodgkin Lymphoma in Sri Lanka.

Background:: There is a significant disparity in global cancer care and out-come between countries. We aimed to provide data on characteristics, average cost of treatment and survival estimates in patients with Hodgkin Lymphoma in Sri Lanka. Methods: All patients diagnosed with Hodgkin Lymphoma between 01.05.2013 and 01.10.2020 were included in the analysis. Findings: Classical Hodgkin Lymphoma(cHL) diagnosed in 85%; 68% presented with B symptoms and 61% had advanced stage of disease. Treatment was discontinued by 23% either before or just after starting treatment of whom 72% percent were females. The complete response (CR) rate of patients who continued treatment was 86% while the estimated five-year survival rate is 92%. Seventeen percent of these patients died but only two percent due to Hodgkin Lymphoma or associated treatment in the group which continued treatment compared to 45% in the group who defaulted treatment (p-value 0.0002). Five-year survival rate of patients who defaulted treatment was 50% while patients who continued treatment have an estimated five-year survival rate of 90%. Average cost of first line treatment was between US$ 2280 and US$ 7642. First treatment failure may incur substantially higher health care costs. Interpretation: This is the only well characterized study on long-term survival of patients with Hodgkin Lymphoma in Sri Lanka. We have shown that it is possible to successfully apply western treatment and supportive care protocols to the local population. This published data will help to bench mark and improve the treatment and develop blood cancer care in the local setting.

Dynamics of maternally transferred antibodies against measles, mumps, and rubella in infants in Sri Lanka.

BACKGROUND: Determining the dynamics of maternally transferred antibodies against measles, mumps, and rubella infections in infants is important for making evidence-based policy decisions regarding the timing of vaccination. METHODS: The levels of serum immunoglobulin G (IgG) developed against measles, mumps, and rubella infections were assessed using commercial ELISA kits in mother-newborn pairs (n = 294) and 6-12-month-old infants (n = 280) recruited from Colombo District, Sri Lanka. Antibody levels of mothers and their newborns were assessed with respect to sex and parity. Antibody levels and the protection conferred were assessed in a sample of infants who completed 6-12 months of age in relation to their age and sex. Antibody levels were compared between different age and sex groups using the Mann-Whitney U-test, and correlations of antibody titers were performed using the Spearman correlation test. RESULTS: The prevalence rates of seropositivity for measles, mumps, and rubella were 91.5%, 89%, and 88%, respectively, in mothers, and 95%, 91.5%, and 93%, respectively, in their newborns. The newborns had mean IgG levels exceeding those of the mothers (P < 0.001). Mothers with natural infections had higher antibody levels compared to vaccinated mothers, which resulted in a higher level of maternal transfer. All of the infants who were 9-10 months of age or older were seronegative for measles, all of those who were 10-11 months of age or older were seronegative for rubella, and all of those who were 11-12 months old were seronegative for mumps. CONCLUSIONS: The maternal transfer of antibodies to newborns is efficient and renders protection until the infants are 6-7 months old in the case of mumps and rubella and 7-8 months old in the case of measles. Hence infants remain vulnerable to infections before the first dose of the MMR vaccine.

Rotavirus infection among hospitalized children under five years of age with acute watery diarrhea in Sri Lanka.

BACKGROUND: Rotavirus is the leading cause of acute watery diarrhoea among children and is vaccine preventable. The aim of this hospital-based sentinel surveillance was to study the prevalence, demographic and clinical characteristics of rotavirus infections and to describe rotavirus genotype distribution patterns among children under five years of age hospitalized for acute watery diarrhea during the period of 2009-2016. METHODS: Prospective, sentinel hospital-based surveillance was conducted in Lady Ridgeway Hospital (LRH) from 2009 to 2016. Stool samples of children admitted with acute watery diarrhea were tested by rotavirus antigen detection 'ProSpecT' Enzyme Immunoassay (EIA) at Department of Virology, Medical Research Institute, Colombo. Specimens that tested positive for rotavirus were further analyzed at the Regional Reference Laboratory (RRL) participating in the World Health Organization (WHO)-coordinated Global Rotavirus Surveillance Network (GRSN) to determine the genotype of strains by reverse-transcriptase polymerase chain reaction. RESULTS: Of the 6090 children with diarrhea admitted, 1801 (29.5%) had stools taken and tested. In years with at least 11 months of data (2010 and 2013) rotavirus was detected in 36.5% (228/624) of specimens. Genotype G1P[8] was the most common genotype detected throughout the surveillance period (30.1%; 123/408) with G2P [8], G9P[8] and G3P[8] also detected. CONCLUSIONS: Rotavirus is a common cause of pediatric diarrhea hospitalizations in Sri Lanka. National introduction of rotavirus vaccine could reduce the burden of pediatric diarrhea.

Molecular epidemiology of rotaviruses in the south-east Asian region from 2009 to 2015.

BACKGROUND: In Asia, rotavirus accounts for approximately 45% of admissions due to acute gastroenteritis in children <5 years, and causes about 145,000 deaths every year. We studied the distribution of rotavirus strains from Myanmar, Sri Lanka, and Nepal during 2009-2015. METHODS: Stool samples collected from children <5 years of age hospitalized with acute diarrhea in the three sites and positive for rotavirus antigen by enzyme immunoassay (EIA) were sent to the Christian Medical College, Vellore from 2009 to 2015. G and P typing of rotavirus strains were performed using reverse-transcription polymerase chain reaction (RT-PCR). RESULT: Of the 2354 EIA positive samples tested, G12P[8] (36.8%), G1P[8] (30.1%), and G12P[6] (41.3%) were the most common strains isolated from Myanmar, Sri Lanka, and Nepal respectively. CONCLUSION: There was substantial diversity of rotavirus genotypes, and continued surveillance in developing countries of Asia will help in understanding the epidemiology of rotavirus before and after introduction of vaccines.

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction.

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

Impact of rubella vaccination on elimination of congenital rubella syndrome in Sri Lanka: progress and challenges.

Rubella infection in pregnancy can lead to pathologies, including miscarriage, stillbirth and congenital rubella syndrome (CRS) in the neonate. Rubella vaccination can prevent all occurrences of CRS. In Sri Lanka, significant outbreaks of CRS occurred in 1994 and 1995, with 275 and 212 reported cases. In 1996, Sri Lanka introduced rubella vaccination for women aged 16-44 years, to stop CRS. Measles-rubella vaccine was introduced into the routine immunization schedule in 2001 and additional campaigns were carried out in 2003 (all 11-15 year olds) and 2004 (all 16-20 year olds). Reported immunization coverage with a single dose of a rubella-containing vaccine has been more than 95% since 2000. Laboratory-supported surveillance for rubella and CRS was started in 1992. Reported rubella cases fell from 364 (incidence 19/million population) in 1999 to 96 cases (incidence 5/million population) in 2002 and further to 12 cases (incidence 0.6/ million population) in 2014. Laboratory-supported CRS surveillance was started in 1990 and the highest number of CRS cases, 275 (incidence 77/100 000 live births), was diagnosed in 1994. Reported CRS cases fell from 22 cases (incidence 7/100 000 live births) in 2002 to 3 cases (incidence <1/100 000 live births) in 2014. Almost 20 years of routine rubella vaccination has resulted in >96% reduction in reported rubella cases and a corresponding >98% reduction in CRS cases. Despite this great achievement, work remains to eliminate rubella and CRS from Sri Lanka.

Rotavirus infections with multiple emerging genotypes in Sri Lanka.

Rotavirus diarrhea is an important cause of child mortality in developing countries, but studies on this diarrhea are scarce in Sri Lanka. A prospective study conducted in Sri Lanka on rotavirus infection among children in a hospital setting (n = 611) versus children residing in tsunami camps (n = 52) showed that prevalence of rotavirus infection was comparable, 21.9 and 20%, respectively. The hospital and camps were located in different districts. Analysis of the genotypes of 122 rotaviruses from the hospital and 12 from the camps indicated that G9P[8] was associated with 35 and 33%; G12P[8/nt] with 14.7 and 33%; G3P[8/4/nt] with 17 and 8% and G1P[8/4] with 6.5 and 16.7%. Rotaviruses with G2P[8/4/6] and G4P[8/4] were hospital-associated only, and some rotaviruses (9 and 8% from the hospital and the camps, respectively) were G- and P-nontypable. We conclude from the present study that multiple emerging genotypes were prevalent in Sri Lanka, and children in camps were at risk of developing diarrhea due to rotaviruses.

Epidemiology of rotavirus diarrhea in mongolia and sri lanka, march 2005-february 2007.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among children. We conducted hospital-based surveillance to estimate the burden of hospitalizations for rotavirus among children aged <5 years and to describe strain distribution patterns during the 2-year study period. METHODS: Children aged <5 years with diarrhea were prospectively enrolled and evaluated by trained pediatricians at representative hospitals in Mongolia and Sri Lanka. Fecal specimens were tested by rotavirus antigen detection enzyme immunoassay. Specimens that tested positive for rotavirus were further characterized to determine the genotype of strains by reverse-transcriptase polymerase chain reaction. RESULTS: From 1 March 2005 through 28 February 2007, a total of 1277 hospitalized children with diarrhea were enrolled in Mongolia, and 1916 were enrolled in Sri Lanka. Of the 1152 children in Mongolia who had samples tested, 458 (40%) had results positive for rotavirus, and in Sri Lanka, 428 (24%) of 1806 children with samples tested had positive results. G3P[8] was the most common genotype among rotavirus strains in Mongolia (68%) and Sri Lanka (15%). CONCLUSIONS: Rotavirus causes 40% and 24% of hospitalizations for diarrhea among children in Mongolia and Sri Lanka, respectively. Each study site will continue surveillance of rotavirus, and additional laboratory testing will be performed to provide additional information on the distribution of rotavirus strains by G and P genotype.