An epidemiological analysis of severe imported malaria infections in Sri Lanka, after malaria elimination.

BACKGROUND: Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria. METHODS: Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients' general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented. RESULTS: 532 imported malaria cases were diagnosed over 11 years (2013-2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26-60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died. CONCLUSIONS: The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.

msp1, msp2, and glurp genotyping to differentiate Plasmodium falciparum recrudescence from reinfections during prevention of reestablishment phase, Sri Lanka, 2014-2019.

BACKGROUND: Sri Lanka after eliminating malaria in 2012, is in the prevention of re-establishment (POR) phase. Being a tropical country with high malariogenic potential, maintaining vigilance is important. All malaria cases are investigated epidemiologically and followed up by integrated drug efficacy surveillance (iDES). Occasionally, that alone is not adequate to differentiate Plasmodium falciparum reinfections from recrudescences. This study evaluated the World Health Organization and Medicines for Malaria Venture (MMV) recommended genotyping protocol for the merozoite surface proteins (msp1, msp2) and the glutamate-rich protein (glurp) to discriminate P. falciparum recrudescence from reinfection in POR phase. METHODS: All P. falciparum patients detected from April 2014 to December 2019 were included in this study. Patients were treated and followed up by iDES up to 28 days and were advised to get tested if they develop fever at any time over the following year. Basic socio-demographic information including history of travel was obtained. Details of the malariogenic potential and reactive entomological and parasitological surveillance carried out by the Anti Malaria Campaign to exclude the possibility of local transmission were also collected. The msp1, msp2, and glurp genotyping was performed for initial and any recurrent infections. Classification of recurrent infections as recrudescence or reinfection was done based on epidemiological findings and was compared with the genotyping outcome. RESULTS: Among 106 P. falciparum patients, six had recurrent infections. All the initial infections were imported, with a history of travel to malaria endemic countries. In all instances, the reactive entomological and parasitological surveillance had no evidence for local transmission. Five recurrences occurred within 28 days of follow-up and were classified as recrudescence. They have not travelled to malaria endemic countries between the initial and recurrent infections. The other had a recurrent infection after 105 days. It was assumed a reinfection, as he had travelled to the same malaria endemic country in between the two malaria attacks. Genotyping confirmed the recrudescence and the reinfection. CONCLUSIONS: The msp1, msp2 and glurp genotyping method accurately differentiated reinfections from recrudescence. Since reinfection without a history of travel to a malaria endemic country would mean local transmission, combining genotyping outcome with epidemiological findings will assist classifying malaria cases without any ambiguity.

Initial response to SARS-CoV-2 (COVID-19) outbreak in Sri Lanka; views of public health specialists through an International Health Regulations lens.

The COVID-19 pandemic affected Sri Lanka despite having developed an International Health Regulations (IHR) steering committee in 2016 and a national action plan for health security following the Joint External Evaluation in 2018. Many steps were taken to improve the disaster management skills of healthcare workers even before the COVID-19 outbreak. We interviewed seven public health specialists to obtain their views on the country's response to the pandemic. A thematic analysis was conducted, leading to the emergence of three major themes and seven subthemes. The major themes included health security preparedness; COVID-19 management; and effects of COVID-19. The subthemes were; preparedness prior to pandemic and gaps in the preparedness (under health security preparedness); dual burden for the curative sector, strategies to reduce transmission and barriers to managing COVID-19 (under COVID-19 management) and negative and positive effects of COVID-19 (under effects of COVID-19). When COVID-19 reached Sri Lanka, healthcare workers, border control authorities and those involved with infectious disease control were overwhelmed by the magnitude of the pandemic. Healthcare workers' hesitation to work amidst the pandemic due to fear of infection and possible transmission of infection to their families was a major issue; the demand for personal protective equipment by health workers when stocks were low was also a contributory factor. Lockdowns with curfew and quarantine at government regulated centers were implemented as necessary. Perceptions of the public including permitting healthcare workers to perform field public health services, logistical barriers and lack of human resources were a few of the barriers that were expressed. Some persons did not declare their symptoms, fearing that they would have to be quarantined. The pandemic severely affected the economy and Sri Lanka relied on donations and loans to overcome the situation. Pandemic also brought about innovative methods to maintain and upgrade health service provision. Individuals with non-communicable diseases received their regular medications through the post which reduced their risk of being infected by visiting hospitals. Improvement of laboratory services and quarantine services, a reduction of acute respiratory infections and diarrhoeal diseases, improved intersectoral coordination and public philanthropic response were other positive effects.

A malaria death due to an imported Plasmodium falciparum infection in Sri Lanka during the prevention of re-establishment phase of malaria.

BACKGROUND: Sri Lanka has maintained a rigorous programme to prevent the re-establishment of malaria ever since the disease was eliminated in October 2012. It includes efforts to sustain case surveillance to ensure early diagnosis and management of malaria. Yet, in April of 2023 the death occurred of an individual with imported malaria. CASE PRESENTATION: The deceased was a 37-year-old Sri Lankan male who returned to Sri Lanka on the 10th of April after a business trip to several countries including Tanzania. He was febrile on arrival and consulted three Allopathic Medical Practitioners in succession in his home town in the Western Province of Sri Lanka, over a period of 5 days starting from the very day that he arrived in the country. Malaria was not tested for at any of these consultations and his clinical condition deteriorated. On the evening of 14th of April he was admitted to the medical intensive care unit of a major private hospital in the capital city of Colombo with multiple organ failure. There, on a request by the treating physician blood was tested for malaria and reported early the next morning as Plasmodium falciparum malaria with a high parasitaemia (> 10%). The patient died shortly after on the 15th of April before any anti-malarial medication was administered. The deceased had been a frequent business traveller to Africa, but with no past history of malaria. He had not taken chemoprophylaxis for malaria on this or previous travels to Africa. DISCUSSION: The patient's P. falciparum infection progressed rapidly over 5 days of arriving in Sri Lanka leading to severe malaria without being diagnosed, despite him seeking healthcare from three different Medical Practitioners. Finally, a diagnosis of malaria was made on admission to an intensive care unit; the patient died before anti-malarial medicines were administered. CONCLUSIONS: This first death due to severe P. falciparum malaria reported in Sri Lanka after elimination of the disease was due to the delay in diagnosing malaria.

Genomic Surveillance of Recent Dengue Outbreaks in Colombo, Sri Lanka.

All four serotypes of the dengue virus (DENV1-4) cause a phenotypically similar illness, but serial infections from different serotypes increase the risk of severe disease. Thus, genomic surveillance of circulating viruses is important to detect serotype switches that precede community outbreaks of disproportionate magnitude. A phylogenetic analysis was conducted on near full length DENV genomes sequenced from serum collected from a prospective cohort study from the Colombo district, Sri Lanka during a 28-month period using Oxford nanopore technology, and the consensus sequences were analyzed using maximum likelihood and Bayesian evolutionary analysis. From 523 patients, 328 DENV sequences were successfully generated (DENV1: 43, DENV2: 219, DENV3:66). Most circulating sequences originated from a common ancestor that was estimated to have existed from around 2010 for DENV2 and around 2015/2016 for DENV1 and DENV3. Four distinct outbreaks coinciding with monsoon rain seasons were identified during the observation period mostly driven by DENV2 cosmopolitan genotype, except for a large outbreak in 2019 contributed by DENV3 genotype I. This serotype switch did not result in a more clinically severe illness. Phylogeographic analyses showed that all outbreaks started within Colombo city and then spread to the rest of the district. In 2019, DENV3 genotype I, previously, rarely reported in Sri Lanka, is likely to have contributed to a disease outbreak. However, this did not result in more severe disease in those infected, probably due to pre-existing DENV3 immunity in the community. Targeted vector control within Colombo city before anticipated seasonal outbreaks may help to limit the geographic spread of outbreaks.

Development of a machine learning model for early prediction of plasma leakage in suspected dengue patients.

BACKGROUND: At least a third of dengue patients develop plasma leakage with increased risk of life-threatening complications. Predicting plasma leakage using laboratory parameters obtained in early infection as means of triaging patients for hospital admission is important for resource-limited settings. METHODS: A Sri Lankan cohort including 4,768 instances of clinical data from N = 877 patients (60.3% patients with confirmed dengue infection) recorded in the first 96 hours of fever was considered. After excluding incomplete instances, the dataset was randomly split into a development and a test set with 374 (70%) and 172 (30%) patients, respectively. From the development set, five most informative features were selected using the minimum description length (MDL) algorithm. Random forest and light gradient boosting machine (LightGBM) were used to develop a classification model using the development set based on nested cross validation. An ensemble of the learners via average stacking was used as the final model to predict plasma leakage. RESULTS: Lymphocyte count, haemoglobin, haematocrit, age, and aspartate aminotransferase were the most informative features to predict plasma leakage. The final model achieved the area under the receiver operating characteristics curve, AUC = 0.80 with positive predictive value, PPV = 76.9%, negative predictive value, NPV = 72.5%, specificity = 87.9%, and sensitivity = 54.8% on the test set. CONCLUSION: The early predictors of plasma leakage identified in this study are similar to those identified in several prior studies that used non-machine learning based methods. However, our observations strengthen the evidence base for these predictors by showing their relevance even when individual data points, missing data and non-linear associations were considered. Testing the model on different populations using these low-cost observations would identify further strengths and limitations of the presented model.

Biology, bionomics and life-table studies of Anopheles stephensi (Diptera: Culicidae) in Sri Lanka and estimating the vectorial potential using mathematical approximations.

BACKGROUND: Anopheles stephensi is an invasive mosquito in Sri Lanka that can potentially transmit malaria. The transmission intensity is linked with biology, bionomic and behavioral aspects of a vector that are associated with the Vectorial Capacity (VC). However, the influence of larval conditions eventually affects the vectorial potential of An. stephensi are not well understood. METHODS: A colony of An. stephensi was established at the Regional Centre of the Open University of Sri Lanka, Jaffna District. The colony was maintained under confined conditions according to standard protocols. Biotypes of An. stephensi were characterized by referring to the number of egg ridges. Information on (a) biological aspects of eggs (duration for egg hatching, egg development and hatchability), (b) larval development time, larval survivorship pupation success, resting depth of larvae), (c) pupae (adult emergence rate, average time for adult emergence) and (d) adults (biting frequency, mating success gonotrophic cycle, fecundity, duration for egg-laying, percentage of sexes, adult survival/longevity) were evaluated under life-table analysis. Further, selected morphometric characters of each life cycle stage were recorded from the eggs (length and breadth), larvae (head length, width of head, length of thorax, width of thorax, length of abdomen, width of abdomen, and the total length of larvae), pupae (cephalothoracic length and width) and adults (length & width of wing, thorax and abdomen). The VC was calculated using a mathematical-based approach. Descriptive statistics, General Linear Model (GLM) and independent-sample t-test were used for the statistical analysis. RESULTS: All three biotypes were identified based on egg morphology. Mysorensis biotype (47%; n = 470) was predominant followed by type (38.1%; n = 381) and intermediate (14.9%; n = 149). The mean egg length (F(2,997) = 3.56; P = 0.029) and breadth (F(2,997) = 4.57; P = 0.011) denoted significant differences among the three biotypes. The mating success of females observed was 80.7 ± 4.45%. The mean hatching period was 1.9 ± 0.03 days, with a hatching rate of 86.2 ± 0.77%. Overall, 8.0 ± 0.14 days were required for larval development and 30.3 ± 0.14 h were spent in the pupal stage. The pupation success was 94.5 ± 0.37%, and the majority were males (53.1 ± 0.73%). The mean fecundity was 106.5 ± 6.38 eggs and a gonotrophic cycle of 3.4 ± 0.06 days. The female survival rate was 43.2 ± 2.4%, with a mean biting frequency of 66.6 ± 3.5%. The average VC of adult An. stephensi was estimated to be 18.7. CONCLUSIONS: The type biotype, which is an effective vector in the Indian subcontinent is present in Sri Lanka. According to the mathematical approximation, An. stephensi found locally has a vectorial capacity of over 18. Therefore, this study warrants the health authorities and vector control programmes to continue the entomological surveys, monitoring of vector densities and implementing appropriate vector control interventions based on biology and bionomic information of vectors.

Comparative analysis of the larvicidal activity of temephos (EC50) and novaluaron (EC10) to control Anopheles stephensi in Sri Lanka.

BACKGROUND: Anopheles stephensi was first recorded in the coastal area of Mannar District, Sri Lanka, in December 2016. Since then, this vector has been isolated from other districts in the Northern and Eastern Provinces of Sri Lanka. Chemical control is the main arm of vector control that can be used to reduce the vector densities within a short period. Thus, the present study aimed at evaluating the efficacy of using selected insecticides for the control of An. stephensi larvae. METHOD: The third and fourth instar larval stages of An. stephensi (F2 generation) of field mosquitoes that were caught using cattle baited net trap collections from Columbuthurai, Kurunagar, and Navanthurai areas in Jaffna District, Sri Lanka, were obtained from the laboratory colony established at Jaffna. Batches of 100 larvae were taken for experiments and introduced separately to a concentration series of temephos and novaluron (0.04-400 ppm). A control test was also performed at each setup without introducing insecticides. The mortality rates of An. stephensi larvae exposed to different concentrations of larvicides were recorded at 1, 24 and 48-h intervals. The experiment was replicated five times at individual concentrations for each selected chemical. Data were analyzed using the General Linear Model (GLM) and Probit analysis. RESULTS: The highest mortality rate (100%) at a 1-h exposure period was observed from temephos at >100 ppm. The mortality rates varied significantly for different concentrations and larvicides (p < 0.05). At 24-h of the exposure period, the 100% mortality of An. stephensi larvae were observed from both temephos and novaluron even at 0.04 ppm. CONCLUSION: Both temephos and novaluron reported 100% mortality rates in An. stephensi larvae at 1-h and 24-h exposure periods. Based on the findings, temephos and novaluron can be recommended as effective larvicides for chemical-based control of An. stephensi in Jaffna, Sri Lanka. Further, it is recommended to conduct a field-based study, where habitat types and water quality are highly heterogeneous and may affect the residual activity.

Immunopathology of Cutaneous Leishmaniasis in a Cohort of Sri Lankan Patients.

Introduction and objectives: Leishmania donovani is the causative organism of leishmaniasis in Sri Lanka. Studies on the immunopathology of leishmaniasis due to L. donovani are limited. The objective of this study was to describe the immunopathological characteristics of cutaneous leishmaniasis in a cohort of Sri Lankan patients. Methodology: Fifty skin biopsies of cutaneous leishmaniasis confirmed by detection of organisms by histology, culture, slit-skin smear, and/or polymerase chain reaction were reviewed. The inflammatory infiltrate was characterized by immunohistochemical staining for CD4, CD8, CD20, and CD68. Associations and correlations between immunohistochemical staining pattern and the parasitic load, and patterns of inflammation were determined. Results: The majority of biopsies showed a CD8+/CD4- T lymphocyte predominant infiltrate (84%, n = 42). A CD68 predominant infiltrate was seen in 16%(n = 8). The mean percentage of CD8+, CD4+, CD20+, and CD68+ inflammatory cells in the biopsies were 56.1% (SD = 16.5%), 2.6% (SD = 4.5%), 12.3% (SD = 10.9%), and 25.7% (SD = 15.8%) respectively. There was no association between the predominant inflammatory cell and the degree of inflammation (P = .173), presence of high RPI (P = .922), MRI(P = .367) or presence of granuloma (P = .247).The percentage of CD4+ cells showed a positive correlation with granuloma formation (Correlation coefficient = .411, P = .03). The percentage of CD20+ cells in the infiltrate showed a positive correlation with the degree of inflammation (Correlation coefficient = .491, P = .02) and the RPI (Correlation coefficient = .334, P = .018). Discussion and Conclusion: Skin biopsies from cutaneous leishmaniasis due to L. donovani infection showed a CD8+/CD4- predominant infiltrate. This is similar to the findings of studies on cutaneous leishmaniasis due to some other species and suggests that the cytotoxic T cell response plays a role in infections due to L. donovani.

Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults.

Given the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fever. Anti-Dengue Envelope and anti-Zika NS1 IgG antibodies were tested by ELISA (Euroimmun, Lubeck, Germany) in all recruited patients. Associations between pre-morbid seroprevalence for either or both infections and adverse clinical outcomes of the current dengue infection were explored. A total of 507 dengue infected patients were assessed of whom 342 (68%) and 132 (26%) patients had anti-dengue IgG and anti-Zika IgG respectively. People with combined prior dengue and zika exposure as well as prior dengue exposure alone, were at increased risk of plasma leakage, compensated and uncompensated shock, and severe dengue (p < 0·05), compared to people without prior exposure to either infection. The effect of prior Zika exposure alone could not be established due to the small the number of primary dengue infections with prior Zika exposure.

Malaria Control, Elimination, and Prevention as Components of Health Security: A Review.

International travel, a major risk factor for imported malaria, has emerged as an important challenge in sustaining malaria elimination and prevention of its reestablishment. To make travel and trade safe, the WHO adopted the International Health Regulations (IHR) which provides a legal framework for the prevention, detection, and containment of public health risks at source. We conducted a systematic review to assess the relevance and the extent of implementation of IHR practices that can play a role in reducing malaria transmission. Selected studies addressed control, elimination, and prevention of reestablishment of malaria. Study themes focused on appraisal of surveillance and response, updating national policies to facilitate malaria control and elimination, travel as a risk factor for malaria and risk mitigation methods, vector control, transfusion malaria, competing interests, malaria in border areas, and other challenges posed by emerging communicable diseases on malaria control and elimination efforts. Review results indicate that malaria has not been prioritized as part of the IHR nor has the IHR focused on vector-borne diseases such as malaria. The IHR framework in its current format can be applied to malaria and other vector-borne diseases to strengthen surveillance and response, overcome challenges at borders, and improve data sharing-especially among countries moving toward elimination-but additional guidelines are required. Application of the IHR in countries in the malaria control phase may not be effective until the disease burden is brought down to elimination levels. Considering existing global elimination goals, the application of IHR for malaria should be urgently reviewed and included as part of the IHR.

Evaluation of a haemozoin-based rapid diagnostic test for diagnosis of imported malaria during the phase of prevention of reestablishment in Sri Lanka.

BACKGROUND: Sri Lanka, an island nation, has eliminated endemic malaria transmission. Maintaining elimination in the continued presence of vectors requires vigilance in screening people travelling from high malaria-risk areas and a rapid response with focal screening for infections identified in the community. Such screening requires accurate and very rapid assays that enable an immediate response. Both microscopy and rapid diagnostic tests (RDTs) have limitations including sensitivity and speed in screening large numbers, while polymerase chain reaction (PCR) is practical only as laboratory confirmation. This study assessed the utility of 'Gazelle', a novel rapid malaria assay based on magneto-optical detection of haemozoin, a by-product of malaria parasite metabolism. METHODS: Between October 2020 and March 2021, two groups of individuals were screened for malaria by four methods, namely, microscopy, Rapid Diagnostic Test (RDT), Gazelle and PCR. Passive case detection was carried out for confirmation of diagnosis amongst individuals suspected of having malaria. Individuals at high-risk of acquiring malaria, namely persons returning from malaria endemic countries, were screened by active case detection. RESULTS: Of the 440 individuals screened for malaria, nine malaria positives were diagnosed by PCR, microscopy and the HRP2 band of RDT, which included five Plasmodium falciparum infections, two Plasmodium ovale, and one each of Plasmodium vivax and Plasmodium malariae. Gazelle correctly detected the P. vivax, P. ovale and P. malariae infections within the 2 min test time, but did not detect two P. falciparum infections giving a sensitivity of 77.8%. Specificity was 100%. DISCUSSION: The Gazelle, a portable bench top device proved useful to screen a large number of blood samples for non-falciparum parasites within 5 minutes of sample input. Species differentiation, and improvement in P. falciparum detection, will be important to broaden utility.

Treatment of chikungunya-associated joint pain: a systematic review of controlled clinical trials.

Post-chikungunya joint pain (arthritis or arthralgia) is a clinical concern in endemic regions as it may cause a debilitating illness sometimes years after the acute infection. This systematic review analyses evidence from controlled clinical trials regarding the efficacy of pharmacological and non-pharmacological interventions to treat post-chikungunya joint pain. PubMed, EMBASE, Scopus, Cochrane library and Web of Science were searched for eligible studies without any language or time limits, excluding retrospective studies, and prospective observational studies without a control group. Eleven studies met the inclusion criteria. Seven assessed pharmacological interventions and four assessed non-pharmacological interventions (exercise, neuromodulation). The number of participants in each intervention arm varied from 10 to 75 and, given the heterogeneity of interventions, a meta-analysis was not possible. Available evidence does not show any added benefit of chloroquine, hydroxychloroquine, stand-alone methotrexate or ribavirin compared with anti-inflammatory drugs or placebo/no treatment. Non-steroidal anti-inflammatory drugs may reduce pain up to 24 wk of treatment but long-term residual impact after stopping treatment is unassessed. Currently, there is also no high certainty evidence to recommend non-pharmacological methods such as exercise and neuromodulation.

Developmental responses and survival of Anopheles stephensi larval stages at different salinity levels.

BACKGROUND: Anopheles stephensi is a newly invaded vector in Sri Lanka. It has been identified in coastal areas in the northern and eastern parts of the country and evidences the ability to breed in brackish water environments. METHODS: Laboratory investigations were conducted with batches of 100 first and third instar larvae exposed to a salinity gradient (0-40 ppt). Survival rates at 1 h, 24 h and until pupation were recorded for first and third instar larvae at different salinity levels. The experiment was repeated four times for both instars. Data were analysed using the general linear model and probit analysis. RESULTS: Significant variations in adult emergence were observed from both larval stages at different salinity levels (p<0.05). The highest pupation rates were observed at 2.5 ppt salinity. The survival rate of first instar larvae after 24 h of salinity exposure was >80% up to 12.5 ppt, while 100% mortality was observed for from the ≥25 ppt level of salinity. More than 90% of the third instar larvae pupated from salinity levels <15 ppt. The lowest survival rate was reported as 15.8±2.47% at 25 ppt. CONCLUSIONS: This indicates a high potential of increasing density of A. stephensi in coastal ecosystems in lagoons and other saline water bodies. Hence it is high time to redesign vector control interventions for vector breeding in coastal ecosystems.

Epidemiological profile of imported malaria cases in the prevention of reestablishment phase in Sri Lanka.

Sri Lanka reported the last case of indigenous malaria in October 2012, and received malaria-free certification from WHO in September 2016. Malaria cases have since, shifted from indigenous to imported, and the country remains receptive and vulnerable to malaria. A case-based epidemiological study was conducted on all imported malaria cases reported in the country in 2015 and 2016 with the aim of profiling imported malaria to improve the effectiveness of the surveillance and case management system for malaria. Data were obtained from case reports of the Anti Malaria Campaign, hospital records and laboratory registers. Over the 2 years, 77 imported malaria infections were diagnosed in 54 Sri Lankans and 23 foreign nationals. A majority of the infections were reported among males (93%) in the age group of 21-50 years (85.8%), and all were recent travelers overseas. Most patients were detected by passive case detection, but 10% of cases were detected by Active Case Detection. Only 25% of patients were diagnosed within 3 days of the onset of symptoms. In 32% of patients, the diagnosis was delayed by more than 10 days after the onset of symptoms. Plasmodium falciparum infections manifested significantly earlier after arrival in Sri Lanka than did P.vivax infections. The majority of patients (74%) were diagnosed in the Western Province, which was not endemic for malaria. A third of patients were diagnosed in the private sector. The shift in the epidemiology of malaria infection from before to after elimination has implications for preventing the reestablishment of malaria.

Plasma leakage in dengue: a systematic review of prospective observational studies.

Plasma leakage is a precursor to life-threatening complications of dengue, but this group is poorly defined and not often reported in literature. Patients with Dengue haemorrhagic fever (DHF) as defined in the 1997 World Health Organization classification are often reported, and they all have plasma leakage, but some patients with plasma leakage do not meet the definition of DHF. The study aims to estimate the frequency of plasma leakage and DHF (as a surrogate of plasma leakage) in dengue and its variations based on virus serotype, geography, patient gender and pre-existing immunity to dengue. PUBMED, Scopus, EMBASE, CINAHL and Web of Science were searched for prospective observational studies reporting on plasma leakage or DHF. Quality of data was assessed using the NIH quality assessment tool for cohort studies. Forty-three studies that recruited 15,794 confirmed dengue patients were eligible. Cumulative frequency of plasma leakage was 36.8% (15 studies, 1642/4462, 95% CI 35.4-38.2%), but surprisingly the estimated cumulative frequency of DHF was higher (45.7%, 32 studies, 4758/10417, 95% CI 44.7-46.6%), indicating that current medical literature over-reports DHF or under-reports plasma leakage. Therefore, a reliable estimate for the proportion of dengue patients developing plasma leakage cannot be derived from existing medical literature even after applying rigorous inclusion criteria to select homogenous studies. Plasma leakage is an important marker of "at-risk" dengue patients and standardizing its definition, diagnosis and reporting should be a priority in research and global policy.

Direct costs of managing in-ward dengue patients in Sri Lanka: A prospective study.

INTRODUCTION: The cost in managing hospitalised dengue patients varies across countries depending on access to healthcare, management guidelines, and state sponsored subsidies. For health budget planning, locally relevant, accurate costing data from prospective studies, is essential. OBJECTIVE: To characterise the direct costs of managing hospitalised patients with suspected dengue infection in Sri Lanka. METHODS: Colombo Dengue Study is a prospective single centre cohort study in Sri Lanka recruiting suspected hospitalised dengue fever patients in the first three days of fever and following them up until discharge. The diagnosis of dengue is retrospectively confirmed and the cohort therefore has a group of non-dengue fever patients with a phenotypically similar illness, managed as dengue while in hospital. The direct costs of hospital admission (base and investigation costs, excluding medication) were calculated for all recruited patients and compared between dengue and non-dengue categories as well as across subgroups (demographic, clinical or temporal) within each of these categories. We also explored if excluding dengue upfront, would lead to an overall cost saving in several hypothetical scenarios. RESULTS: From October 2017 to February 2020, 431 adult dengue patients and 256 non-dengue fever patients were recruited. The hospitalisation costs were USD 18.02 (SD: 4.42) and USD 17.55 (SD: 4.09) per patient per day for dengue and non-dengue patients respectively (p>0.05). Laboratory investigations (haematological, biochemical and imaging) accounted for more than 50% of the total cost. The costs were largely homogenous in all subgroups within or across dengue and non-dengue categories. Excluding dengue upfront by subsidised viral genomic testing may yield overall cost savings for non-dengue patients. CONCLUSION: As non-dengue patients incur a similar cost per day as the dengue patients, confirming dengue diagnosis using subsidised tests for patients presenting in the first three days of fever may be cost-efficient.

Transfusion-induced Plasmodium falciparum malaria in a beta thalassaemia patient during the prevention of re-establishment phase in Sri Lanka.

BACKGROUND: Malaria was eliminated from Sri Lanka in 2012, and since then 50-60 imported malaria cases have been reported yearly. The country has remained malaria-free since, except for a single case of indigenous malaria in 2018. Blood donors are routinely screened for malaria, and transfusion malaria has not been reported in the country since 1966. CASE PRESENTATION: A 17-year-old splenectomized beta thalassaemia patient developed a transfusion-induced Plasmodium falciparum malaria infection following a blood transfusion 18 days earlier. The blood donor was an armed forces personnel who returned from South Sudan following a United Nations peace-keeping mission. The blood recipient's malaria infection took a complicated clinical course with elevated liver enzymes, lowered blood pressure and a prolonged parasite clearance time of 7 days but he recovered fully after two courses of artemether-lumefantrine interrupted by a course of intravenous artesunate. The prolonged parasite clearance is likely due to lack of splenic clearance of dead or damaged intra-erythrocytic parasites (due to a splenectomy) rather than to the parasite strain being resistant to artemisinin or the partner drug. This is corroborated by the fact that the blood donor's infection responded to artemether-lumefantrine with parasites being cleared on day 3. The blood donor who had not displayed signs or symptoms of malaria, had been screened for malaria on arrival in Sri Lanka and was negative on both microscopy and RDT. At the point of blood donation a blood smear examined microscopically was also reported negative for malaria, but retrospectively, the preserved smear of the donor's blood was found to contain P. falciparum parasites at a very low density. The donor when tested after the transfusion-induced case was diagnosed, also tested positive for malaria and was treated. CONCLUSIONS: After malaria elimination, transfusion-induced malaria from blood donors returning from malaria endemic countries poses a threat to preventing the re-establishment of the disease. Improved surveillance of arrivals in Sri Lanka from malaria endemic countries using more sensitive methods for screening than microscopy may be required to reduce this risk. More stringent criteria for selecting blood donors, and more effective methods of screening donors for malaria than microscopy may also be necessary.

A comparative analysis of the outcome of malaria case surveillance strategies in Sri Lanka in the prevention of re-establishment phase.

BACKGROUND: Sri Lanka sustained its malaria-free status by implementing, among other interventions, three core case detection strategies namely Passive Case Detection (PCD), Reactive Case Detection (RACD) and Proactive Case Detection (PACD). The outcomes of these strategies were analysed in terms of their effectiveness in detecting malaria infections for the period from 2017 to 2019. METHODS: Comparisons were made between the surveillance methods and between years, based on data obtained from the national malaria database and individual case reports of malaria patients. The number of blood smears examined microscopically was used as the measure of the volume of tests conducted. The yield from each case detection method was calculated as the proportion of blood smears which were positive for malaria. Within RACD and PACD, the yield of sub categories of travel cohorts and spatial cohorts was ascertained for 2019. RESULTS: A total of 158 malaria cases were reported in 2017-2019. During this period between 666,325 and 725,149 blood smears were examined annually. PCD detected 95.6 %, with a yield of 16.1 cases per 100,000 blood smears examined. RACD and PACD produced a yield of 11.2 and 0.3, respectively. The yield of screening the sub category of travel cohorts was very high for RACD and PACD being 806.5 and 44.9 malaria cases per 100,000 smears, respectively. Despite over half of the blood smears examined being obtained by screening spatial cohorts within RACD and PACD, the yield of both was zero over all three years. CONCLUSIONS: The PCD arm of case surveillance is the most effective and, therefore, has to continue and be further strengthened as the mainstay of malaria surveillance. Focus on travel cohorts within RACD and PACD should be even greater. Screening of spatial cohorts, on a routine basis and solely because people are resident in previously malarious areas, may be wasteful, except in situations where the risk of local transmission is very high, or is imminent. These findings may apply more broadly to most countries in the post-elimination phase.

Thrombocytopenia in Malaria: A Red-Herring for Dengue, Delaying the Diagnosis of Imported Malaria.

INTRODUCTION: Fever and thrombocytopenia, often presenting features of malaria, are also the hallmarks of dengue infections. This study examines the degree and duration of thrombocytopenia in imported malaria infections in Sri Lanka and the extent to which this could provide a false trail in favor of a dengue diagnosis. METHODS: The data of all confirmed malaria cases reported in Sri Lanka from 2017 to 2019 were extracted from the national malaria database. These included detailed histories, the time to malaria diagnosis, platelet counts, and in 2019, the trail of diagnostic procedures. RESULTS: Over the 3 years, 158 malaria cases (157 imported and one introduced) were reported. Platelet counts were available in 90.5% (n = 143) of patients among whom 86% (n = 123) showed a thrombocytopenia (<150,000 cells/µl) and in nearly a third (n = 52) a severe thrombocytopenia (<50,000 cells/µl). Only 30% of patients (n = 48) were diagnosed with malaria within 3 days of the onset of symptoms, while in 37% (n = 58) it took 7 or more days. Platelet counts where significantly higher in patients who had symptoms for 7 days or more compared to those who had symptoms for <7 days (χ2 = 6.888, P = 0.009). Dengue fever was suspected first in 30% (n = 16) of the total malaria patients reported in 2019. CONCLUSIONS: Low platelet counts could delay suspecting and testing for malaria. Eliciting a history of travel to a malaria-endemic country could provide an important and discerning clue to suspect and test for malaria in such patients.