Lymphatic filariases and soil-transmitted helminthiases in Sri Lanka: the challenge of eliminating residual pockets of transmission.

Sri Lanka has successfully met the challenge of controlling both lymphatic filariasis (LF) and soil-transmitted helminthiases (STH) as public health problems. The primary public health strategy for combatting both conditions has been preventive chemotherapy. The national programme for the elimination of LF implemented five annual rounds of mass chemotherapy in the endemic districts from 2002 to 2006 using a combination of diethylcarbamazine and albendazole. The overall microfilaria rate declined from 0.21% in 2001 before the mass chemotherapy, to 0.06% in 2016, at declaration of elimination of LF as a public health problem by the World Health Organization. Currently Sri Lanka is in the phase of post-validation surveillance. Achieving control of STH has been more difficult. Mass deworming programmes have been implemented for nearly a century, and national-level surveys reported prevalence rates declining from 6.9% in 2003 to 1% in 2017. However, neither of these infections has been completely eliminated. A situation analysis indicates continued transmission of both among high-risk communities. This paper explores the reasons for persistence of transmission of both LF and STH in residual pockets and the measures that are required to achieve long-term control, or perhaps even interrupt transmission in Sri Lanka. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Molecular Characterization of a Reemergent Brugia malayi Parasite in Sri Lanka, Suggestive of a Novel Strain.

Sri Lanka achieved elimination status for lymphatic filariasis in 2016; still, the disease remains a potential public health issue. The present study is aimed at identifying a subperiodic Brugia sp. parasite which has reemerged in Sri Lanka after four decades via molecular-based analysis. Polymerase chain reaction performed with pan-filarial primers specific for the internal transcribed spacer region-2 (ITS-2) of the rDNA of Brugia filarial parasites isolated from human, canine, and feline blood samples yielded a 615 bp band establishing the species identity as Brugia malayi. Comparison of the ITS2 sequences of the reemerged B. malayi isolates with GenBank sequences revealed a higher sequence homology with B. pahangi than B. malayi with similar phylogenetic evidence. However, the mean interspecies Kimura-2-parameter pairwise divergence between the generated Brugia sequences with B. malayi and B. pahangi was less than 3%. During the analysis of parsimony sites of the new ITS2 sequences, substitutions at A36T, A296G, T373A, and G482A made the sequences different from both B. pahangi and B. malayi suggesting the possibility of a new genetic variant or a hybrid strain of B. malayi and B. pahangi. Mosquito dissections and xenomonitoring identified M. uniformis and M. annulifera as vectors of this novel strain of B. malayi circulating among cats, dogs, and humans in Sri Lanka.

Biochemical and histopathological changes in Wistar rats after consumption of boiled and un-boiled water from high and low disease prevalent areas for chronic kidney disease of unknown etiology (CKDu) in north Central Province (NCP) and its comparison with low disease prevalent Colombo, Sri Lanka.

BACKGROUND: Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water. METHOD: Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method. RESULTS: Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na+:Ca2+ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals. CONCLUSIONS: Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.

The Diversity of Human Dirofilariasis in Western Sri Lanka.

BACKGROUND: Human dirofilariasis is an emerging zoonosis in many countries. Dirofilariasis caused by Dirofilaria repens may present with diverse clinical manifestations in humans due to aberrant localization of worm lesions causing diagnostic dilemmas. The aim of this retrospective study was to describe and update the demography and clinical spectrum of human dirofilariasis in western Sri Lanka. Nematode or nematode fragments isolated from excision biopsies that were confirmed as D. repens at the Department of Parasitology, Faculty of Medicine, University of Kelaniya, Sri Lanka, between 2012 and 2018 were included. Data on age, gender, and clinical details were obtained from case files. Identity of worms was established by morphometry and cuticle characteristics on wet-mount preparation. Specimens from unusual case presentations were further analyzed by PCR with specific primers for internal transcribed spacer region 2 (ITS2) of the ribosomal DNA. RESULTS: Sixteen nematode specimens isolated from subconjunctiva (n=2), subcutaneous (n=13) and intramuscular (n=1) locations were identified as D. repens by morphometry (average length 11.5 cm) and the characteristic longitudinal striations on cuticle visualized by microscopy. The age distribution of cases ranged from 1 to 65 years with a mean of 21.5. Females were more frequently affected (n=10, 62.5%) and worm locations were commonest in the orbital region (5/16) and scrotum (3/16). Imaging techniques were of use in detecting infections in deeper tissue levels. PCR analysis of DNA extracted from a worm in an intramuscular granuloma of the temporal region elicited the expected band at 484bp for D. repens. CONCLUSIONS: Human dirofilariasis is on an upward trend in incidence. Imaging techniques were of use in clinical diagnosis and molecular speciation in establishing the species identity in unusual case presentations. We suggest a more conservative approach in the management of human dirofilariasis and recommend a one health approach for control.

Genetics of common variable immunodeficiency: role of transmembrane activator and calcium modulator and cyclophilin ligand interactor.

Common variable immunodeficiency (CVID) is the most common clinically manifested primary immunodeficiency, which represents a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. The hallmark of the disease is the elevated susceptibility to recurrent infections of respiratory and gastrointestinal tract, mainly due to encapsulated bacteria while a significant proportion of patients with CVID develop autoimmune and lymphoproliferative complications. The primary cause of CVID is still not known. However, a number of distinct genetic defects including in inducible co-stimulator (ICOS), B-cell-activating factor receptor (BAFFR) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been identified in a minority of patients with CVID. Mutations in tumour necrosis factor receptor superfamily (TNFRSF) member, TACI, are more frequently found to be associated to the disease in about 10% of patients with CVID, but may require additional immunologic defects for complete expression of the phenotype, as unaffected heterozygotes have also been described. Clinically, patients with TACI mutations could present with the complete spectrum of complications seen in CVID. Recent animal studies have provided substantial information on TACI signalling, yet it still offers an outstanding opportunity for further exploration of the aetiology, as a large part of it remains poorly understood. In this review, we aim at giving an insight into the genetics underlying the CVID and particularly at outlining the role of TACI and its relative contribution to the development of CVID-like phenotypes in human.

Prevalence of enterobiasis among primary school children in Ragama, Sri Lanka.

OBJECTIVES: To determine the prevalence of enterobiasis among school children in Ragama Medical Officer of Health (MOH) region and the association between clinical features, potential risk factors and infection status. DESIGN: Cross sectional study. SETTING: School based. Participants 260 school children aged 5-7 years, attending five state schools in the Ragama MOH region. MAIN OUTCOME MEASURES: Prevalence of Enterobius vermicularis infection as diagnosed using adhesive cellophane tapes on the perianal skin on 2 consecutive days. RESULTS: The overall prevalence of enterobiasis was 38%. The risk factors significant on a univariate analysis were male gender, maternal under-education, non-permanency of paternal employment, more household members, more siblings in a family, more persons sleeping with an index child and lack of recent deworming. On a multivariate model more household members, more children in a household, more persons sleeping with the index child, non-permanency of paternal employment and lack of recent deworming were significantly associated with infection. None of the clinical manifestations evaluated (peri-anal itching, insomnia, abdominal pain, and enuresis) showed a significant association with enterobiasis. CONCLUSIONS: Enterobiasis is highly prevalent among primary school children in Ragama.

Selection of medical students in Sri Lanka: time to re-think criteria?

OBJECTIVE: To examine the validity of selected entry level characteristics in relation to the GCE A/L examination as independent predictors of performance of students in medical school. METHODS: A retrospective, analytical study was done at the Faculty of Medicine, University of Kelaniya. Student characteristics at entry were described by sex, the average z-score, General English grade and attempt at GCE A/L examination, and average mark obtained at the English placement test on registration to medical school. Average marks at three summative examinations were used as indicators of performance in medical school. Multivariate analysis using multiple linear regression was carried out using these three outcome measures in relation to four entry point variables as predictors of performance in medical school. Causal path diagrams were constructed using standardised regression coefficients for the whole group and for male and female students separately. RESULTS: The A/L z-score, A/L attempt and English placement test marks were all significant predictors of outcome at the First Examination. Of the variables relating to the A/L examination, the attempt had a much higher path coefficient with performance at the First Examination than the A/L z-score, as did the English marks. Separate path analyses for male and female students showed that while the significance of the relationships remained the same, the magnitude of the correlation was different. CONCLUSIONS: Students who gain admission on their 3rd attempt at the AL examination fare much worse than those admitted to medical school on their 1st attempt. Differences between sexes in examination performance are probably linked to both A/L attempt and English language proficiency.

Prevalence of childhood atopic diseases in the Western Province of Sri Lanka.

BACKGROUND: Atopic diseases in children are major public health problems around the world and the prevalence is increasing. Our objective was to assess the prevalence of atopic diseases in schoolchildren in the Western Province of Sri Lanka. METHODS: Children attending grade 5 in 17 schools in the Western Province of Sri Lanka were recruited to the study. Data were collected using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which was filled by the parent/guardian of the selected children. RESULTS: A total of 640 schoolchildren were recruited. Their mean age was 10 years (SD +/- 0.5) and 55.9% of the study population was boys. Prevalence (95% CI) of asthma, rhinitis and eczema was 17% (13.7-20.3), 21.4% (17.8-25.1) and 5% (3.1-7.0) respectively, while 33.7% (29.6-37.9) had one or more diseases. Only the prevalence of allergic rhinitis showed a statistically significant difference between the two sexes, being more common in boys. Less than 30% of affected children's parents recognised that their child had either asthma or rhinitis, whereas a higher number of parents (54.2%) recognised that their child had eczema. Among children with asthma, 44.4% had rhinitis. CONCLUSIONS: The prevalence of atopic diseases in schoolchildren in grade 5 in the Western Province of Sri Lanka is as common as in other countries in the south Asian region. Parental recognition of these conditions was not satisfactory.

A case of imported malaria: the first report of a Plasmodium malariae infection in Sri Lanka after 37 years.

We report a case of Plasmodium falciparum and P. malariae mixed infection in a patient who had been living in Malawi. This is the first case of P. malariae reported in Sri Lanka in 4 decades. The presence of both parasites was confirmed by microscopy and polymerase chain reaction (PCR). The history strongly indicated that the infection had been acquired from Malawi. The patient had liver dysfunction and a transient glomerulonephritis, both of which subsided with antimalarial treatment.

Effect of repeated mass chemotherapy for filariasis control on soil-transmitted helminth infections in Sri Lanka.

BACKGROUND: In July 2006 Sri Lanka completed 5 rounds of annual mass drug administration (MDA) with diethylcarbamazine citrate (DEC) and albendazole as part of its national programme for elimination of lymphatic filariasis (LF). Albendazole is highly effective against soil-transmitted helminths (STH). This study was carried out to assess the effect of repeated annual MDA on STH infections in the Western Province of Sri Lanka, an area co-endemic for LF and STH. METHODS: Faecal samples were obtained (during August-September 2006), from grade 5 students in 17 schools in the Western Province that were included in a national survey of schoolchildren's health in 2003, and examined using the modified Kato-Katz technique. The prevalence and intensity of roundworm, whipworm and hookworm infections in 2003 and 2006 were compared. RESULTS: Faecal samples from 255 children were examined in 2003; 448 were examined in 2006. Roundworm prevalence was marginally lower in 2006 (4.0%) than in 2003 (4.7%), as was hookworm (0.2% vs 0.4%), whereas whipworm prevalence was higher (13.8% vs 9.4%). These differences as well as that between the geometric mean egg counts were not statistically significant. Compliance with MDA in 2006, as reported by the schoolchildren examined, was only 59%. CONCLUSIONS: Four annual rounds of MDA with DEC and albendazole had virtually no effect on STH infections in the study area.

Emergence of inflammatory bowel disease 'beyond the West': do prosperity and improved hygiene have a role?

Inflammatory bowel disease (IBD) is increasing in many countries 'beyond the West'. This increase may be due to an increased rate of diagnosis but might also represent a true increase in incidence. Economic development, leading to improved hygiene and other changes in lifestyle, may play a role in the increase in IBD. However, the marked difference in prevalence between ethnic groups suggests that the genetic background of populations may also be relevant and supports the current hypothesis that IBD represents an interaction between environmental factors and a genetically susceptible host. Investigating the early stages of IBD as it emerges in new populations may provide new clues to its pathophysiology.

Intestinal parasites and the growth status of internally displaced children in Sri Lanka.

The growth status and intestinal parasitic infections among a group of children displaced by war in Sri Lanka was investigated. There was a high prevalence of growth retardation (wasting, stunting and underweight being 41%, 28% and 69.9%, respectively) and intestinal parasitic infections (40.2%) among the study population. Provision of adequate food, purified drinking water, sanitation and broad-spectrum anthelmintics is recommended.

Modified Dermatology Life Quality Index as a measure of quality of life in patients with filarial lymphoedema.

The quality of life (QoL) and correlates of the QoL of lymphoedema patients attending filariasis clinics and a hospital outpatient department were studied using a Life Quality Index (LQI) in a region endemic for Bancroftian filariasis in Sri Lanka. The index was derived by modifying a previously validated Dermatology Life Quality Index (DLQI) to focus on the oedematous limb rather than the skin. The index was scored from 0 (normal) to 30 (severely affects QoL). Lymphoedema was graded using criteria recommended by the WHO. Another semi-structured questionnaire was used to assess the patient's socioeconomic status, frequency of acute adenolymphangitis attacks (ADLA) and measures practiced for morbidity control. Ninety-one patients (62 females, 29 males; mean age 50.4 years) were studied. A single lower limb, both lower limbs or a single upper limb were affected in 78 (85.7%), 10 (11.0%) and 3 (3.3%) patients, respectively. The severity of lymphoedema ranged from stage 1 (mild) to stage 6 (severe). The mean LQI was 8.2 (SD 5.2, range 0-20). The modified DLQI scores showed a significant positive correlation with severity of lymphoedema and a negative correlation with age (R=0.59 and R=-0.1, respectively). The frequency of ADLAs correlated with an increased modified DLQI score. Local pain, embarrassment and limitations of physical activities were the most distressing aspects of lymphoedema. Disease severity and early onset lymphoedema were found to be significantly associated with poorer QoL in filarial lymphoedema.