Stigma associated with cutaneous leishmaniasis in rural Sri Lanka: development of a conceptual framework.

BACKGROUND: There is limited knowledge about the stigma associated with cutaneous leishmaniasis (CL) in Sri Lanka. To ensure that leishmaniasis researchers focus on CL-associated stigma, we provide an evidence-based framework that can be used in future research. METHODS: We conducted a systematic review on CL-associated stigma using international evidence and carried out a multimethod qualitative study in the Anuradhapura district in Sri Lanka. Based on that, we identified manifestations of stigma, drivers and facilitators that we synthesised to develop a conceptual framework on CL-associated stigma. RESULTS: Our framework consists of drivers, facilitators and self-stigma experienced by people with CL. Stigma drivers included fear, misbeliefs and misconceptions about CL; the belief that wounds are disfiguring; the treatment burden and implied blame. Facilitators that reduced stigma included knowledge of the curability of CL and awareness that CL is not contagious. The nature of social interactions in rural communities enhanced stigma formation. We identified various enacted, felt and internalised stigma experiences of people with CL. CONCLUSIONS: We developed a conceptual framework of the stigma associated with CL that can be used to develop targeted interventions to increase CL awareness, address stigma and improve the quality of life for CL patients.

Levels of Cytokines in Leptospirosis Patients with Different Serovars and rfb Locus.

Leptospirosis has a wide spectrum of clinical manifestations ranging from mild to severe disease. The cytokine response is considered one of the key drivers for this varying manifestation. The different cytokine response observed in patients with leptospirosis could be due to the variation of infecting serovars. Since the rfb locus codes for the lipopolysaccharide synthesis of the bacterial cell wall, which also determines the serovar, this locus may play a role in driving a specific cytokine response in the host. We investigated 12 commonly used cytokine profiles in serum samples of culture, microscopic agglutination test (MAT), or polymerase chain reaction (PCR)-positive patients with leptospirosis. The sequences of the rfb locus in culture-positive samples were generated from whole genome sequencing and serovar status was drawn from original data published. Isolated cultures were subjected to whole genome sequencing using the PacBio RS II system, and the resulting data were used to determine the species. The recovered genomic data were annotated with the Rapid Annotation using Subsystem Technology (RAST) subsystem, and the rfb locus was extracted. The cytokine analysis was carried out using the Qiagen human ELISA kit. Eighteen samples were found to be positive by culture, while the other 7 samples were positive by PCR or MAT. Infections from Leptospira interrogans serovar Autumnalis (5), Pyrogens (3), Icterohaemorrhagiae (1) Leptospira borgpetersenii (all 7 samples clustered in same clonal group with serovar status not determined), Leptospira weilii (1 with serovar status not determined), and Leptospira kirschneri serovar Grippotyphosa (1) were included in the analysis. Three patients [infected with Leptospira interrogansserovar Autumnalis (2) and Pyrogens (1)] and 2 MAT-positive patients (highest titer against serovar Bratislava of L.interrognas) were reported to have severe clinical manifestations, while the rest had mild to moderate symptoms. Although the serum cytokine concentration of patients with severe clinical manifestation was comparatively higher, a statistically significant difference was observed only for interleukin (IL)-1ß (P < 0.05). IL-10/tumor necrosis factor-alpha (TNF-α) ratio was high in patients with severe complications. In general, patients infected with L. interrogans showed higher concentration of cytokines compared to L. borgpetersenii.

The psychosocial burden of cutaneous leishmaniasis in rural Sri Lanka: A multi-method qualitative study.

Leishmaniasis is a tropical infectious disease affecting some of the world's most economically disadvantaged and resource-poor regions. Cutaneous leishmaniasis (CL) is the most common out of the three clinical types of Leishmaniasis. Since 1904 this disease has been endemic in Sri Lanka. CL is considered a disfiguring stigmatising disease with a higher psychosocial burden. However, there needs to be a more in-depth, holistic understanding of the psychosocial burden of this disease, both locally and internationally. An in-depth understanding of the disease burden beyond morbidity and mortality is required to provide people-centred care. We explored the psychosocial burden of CL in rural Sri Lanka using a complex multimethod qualitative approach with community engagement and involvement. Data collection included participant observation, an auto-ethnographic diary study by community researchers with post-diary interviews, and a Participant Experience Reflection Journal (PERJ) study with post-PERJ interviews with community members with CL. The thematic analysis revealed three major burden-related themes on perceptions and reflections on the disease: wound, treatment, and illness-experience related burden. Fear, disgust, body image concerns, and being subjected to negative societal reactions were wound-related. Treatment interfering with day-to-day life, pain, the time-consuming nature of the treatment, problems due to the ineffectiveness of the treatment, and the burden of attending a government hospital clinic were the treatment-related burdens. Anxiety/worry due to wrongly perceived disease severity and negative emotions due to the nature of the disease made the illness experience more burdensome. Addressing the multifaceted psychosocial burden is paramount to ensure healthcare seeking, treatment compliance, and disease control and prevention. We propose a people-centred healthcare model to understand the contextual nature of the disease and improve patient outcomes.

Whole genome sequencing data of Leptospira weilii and Leptospira kirschneri isolated from human subjects of Sri Lanka.

Leptospirosis is a re-emerging zoonotic disease. This article reports the complete genome sequences of three novel strains of Genus Leptospira: two from the species Leptospira weilii (FMAS_RT1, FMAS_PD2) and one from Leptospira kirschneri (FMAS_PN5). These isolates were recovered from the blood samples of acute febrile patients in different geographical and climatic zones of Sri Lanka. High-quality genomic DNA was extracted from the three isolates in mid-log phase cultures. Whole genome sequencing was conducted using the PacBio Single Molecule Real-Time (SMRT) platform to identify the species, genome features, and novelty of the strains. The annotation was conducted using RAST (Rapid Annotation Using Subsystem Technology version 2.0) and the NCBI Prokaryotic Genome Annotation Pipeline. The genome sequences of three isolates have been deposited in the Mendeley data repository and the National Center for Biotechnology Information (NCBI) repository. This data will be useful for future researchers when conducting comparative genomic analysis, revealing the exact mechanism of pathogenesis of leptospirosis and developing molecular diagnostic tools for early detection.

Stigma associated with cutaneous and mucocutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous (CL) and mucocutaneous leishmaniasis (MCL) are parasitic diseases caused by parasites of the genus leishmania leading to stigma caused by disfigurations. This study aimed to systematically review the dimensions, measurement methods, implications, and potential interventions done to reduce the CL- and MCL- associated stigma, synthesising the current evidence according to an accepted stigma framework. METHODS: This systematic review followed the PRISMA guidelines and was registered in PROSPERO (ID- CRD42021274925). The eligibility criteria included primary articles discussing stigma associated with CL and MCL published in English, Spanish, or Portuguese up to January 2023. An electronic search was conducted in Medline, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library. The mixed methods appraisal tool (MMAT) was used for quality checking. A narrative synthesis was conducted to summarise the findings. RESULTS: A total of 16 studies were included. The studies report the cognitive, affective, and behavioural reactions associated with public stigma. Cognitive reactions included misbeliefs about the disease transmission and treatment, and death. Affective reactions encompass emotions like disgust and shame, often triggered by the presence of scars. Behavioural reactions included avoidance, discrimination, rejection, mockery, and disruptions of interpersonal relationships. The review also highlights self-stigma manifestations, including enacted, internalised, and felt stigma. Enacted stigma manifested as barriers to forming proper interpersonal relationships, avoidance, isolation, and perceiving CL lesions/scars as marks of shame. Felt stigma led to experiences of marginalisation, rejection, mockery, disruptions of interpersonal relationships, the anticipation of discrimination, fear of social stigmatisation, and facing disgust. Internalised stigma affected self-identity and caused psychological distress. CONCLUSIONS: There are various manifestations of stigma associated with CL and MCL. This review highlights the lack of knowledge on the structural stigma associated with CL, the lack of stigma interventions and the need for a unique stigma tool to measure stigma associated with CL and MCL.

Mitigating the effects of climate change on human health with vaccines and vaccinations.

Climate change represents an unprecedented threat to humanity and will be the ultimate challenge of the 21st century. As a public health consequence, the World Health Organization estimates an additional 250,000 deaths annually by 2030, with resource-poor countries being predominantly affected. Although climate change's direct and indirect consequences on human health are manifold and far from fully explored, a growing body of evidence demonstrates its potential to exacerbate the frequency and spread of transmissible infectious diseases. Effective, high-impact mitigation measures are critical in combating this global crisis. While vaccines and vaccination are among the most cost-effective public health interventions, they have yet to be established as a major strategy in climate change-related health effect mitigation. In this narrative review, we synthesize the available evidence on the effect of climate change on vaccine-preventable diseases. This review examines the direct effect of climate change on water-related diseases such as cholera and other enteropathogens, helminthic infections and leptospirosis. It also explores the effects of rising temperatures on vector-borne diseases like dengue, chikungunya, and malaria, as well as the impact of temperature and humidity on airborne diseases like influenza and respiratory syncytial virus infection. Recent advances in global vaccine development facilitate the use of vaccines and vaccination as a mitigation strategy in the agenda against climate change consequences. A focused evaluation of vaccine research and development, funding, and distribution related to climate change is required.

Out-of-Pocket Expenditure for Antenatal Care Amid Free Health Care Provision: Evidence From a Large Pregnancy Cohort in Rural Sri Lanka.

INTRODUCTION: Global evidence suggests that high out-of-pocket (OOP) expenditure negatively affects health service utilization and creates an economic burden on households during pregnancy. This study aimed to estimate the magnitude and associated factors of OOP expenditure for antenatal care (ANC) in a rural Sri Lankan setting by following up with a large pregnancy cohort (The Rajarata Pregnancy Cohort [RaPCo]) in Anuradhapura District, Sri Lanka. METHODS: Data were collected from July 2019 to May 2020. An interviewer-administered questionnaire was used to collect socioeconomic data and OOP expenditures in the first trimester. Self-administered questionnaires were used monthly to collect OOP expenditures in the second and third trimesters. In-depth financial information of 1,558 pregnant women was analyzed using descriptive statistics, nonparametric statistics, and a multiple linear regression model. RESULTS: The majority of participants used both government and private health facilities for ANC. The mean (standard deviation [SD]) OOP expenditure per ANC visit was US$4.18 (US$4.19), and the mean (SD) OOP expenditure for total ANC was US$57.74 (US$80.96). Pregnant women who used only free government health services also spent 28% and 14% of OOP expenditure on medicines and laboratory investigations. Household income (P<.001), household expenditure (P<.1), used health care mode (P<.05), maternal morbidities (P<.05), and the number of previous pregnancies (P<.1) were the statistically significant independent predictors of OOP expenditure. OOP expenditure per visit for ANC equals half of the daily household expenditure. CONCLUSION: Despite having freely available government health facilities, most pregnant women tend to use both government and private health facilities and incur higher OOP expenditure. Free government health care users also incur a direct medical OOP expenditure for medicines and laboratory investigations. Monthly household income, expenditure, used health care mode, maternal morbidities, and the number of previous pregnancies are independent predictors of OOP expenditure.

The Effect of Salacia Reticulata Extract Biscuits on Blood Sugar Control of Type 2 Diabetes Mellitus Patients: A Two-Period, Two-Sequence, Crossover, Randomized, Triple-Blind, Placebo-Controlled, Clinical Trial.

Background Traditional physicians in Sri Lanka and India use extracts from the plant Salacia reticulata,or Kothala Himbutu (KH) to treat diabetes. The effect of a KH biscuit, taken as a snack, on glycemic control was investigated in patients with type 2 diabetes. Methodology This triple-blind, randomized, placebo-controlled, two-period, two-sequence, crossover study was conducted in the Internal Medical Clinic, Teaching Hospital Anuradhapura. A research assistant opened computer-generated random numbers enclosed in a sealed envelope and performed treatment allocation. The group outcome was masked from the researchers, patients, and analysts. Both the placebo and the KH biscuit were identical. The primary outcome measure was HbA1c. Intention to treat analyses was used. Glycemic stability was assured in the run-in period, and patients with severe renal, liver, or heart disease were excluded. If patients needed insulin, they were withdrawn from the trial. Results From January 2014 to May 2016, 230 patients were screened, and 136 were randomized. Of them, 62 were allocated, 58 completed the placebo biscuit, 71 were allocated, and 69 completed the KH biscuit. After the washout period and crossover, 57 completed the KH and 65 completed the placebo biscuit. The baseline mean HbA1c level was 8.45% (68.9 mmol/mol) and 8.65% (71.0 mmol/mol) for the placebo-KH biscuit and KH-placebo biscuit groups. At the end of the trial, the HbA1c levels in the placebo-KH biscuit group and the KH-placebo biscuit group were 8.23% (66.4 mmol/mol) and 8.53% (69.3 mmol/mol), respectively. The unadjusted mean HbA1c reduced from the baseline with 0.10% (95% CI = -0.12, 0.32) after the placebo biscuit and 0.35% (95% CI = 0.10, 0.60) after the KH biscuit. After the placebo and KH biscuits, the HbA1c values were 8.46% (95% CI = 8.19, 8.73) (69 mmol/mol with 95% CI = 66, 72) and 8.19% (95% CI = 7.90, 8.48) (66 mmol/mol with 95% CI = 63, 69), respectively. The paired sample t-test shows that the reduction was not significant for placebo biscuits (p = 0.324), while it is significant for KH biscuits (p = 0.003). Analysis with multiple imputations confirmed a significant difference between the placebo and KH biscuit in reducing the HbA1c level. Conclusions KH biscuit taken as a snack reduces HbA1c by 0.25% compared to placebo without serious renal or liver adverse effects. The biscuit can be safely recommended as a snack to patients with type 2 diabetes.

Differences in the characteristics of people who purchase pesticides from shops for self-harm versus those who use pesticides available in the domestic environment in Sri Lanka.

OBJECTIVE: Data from South Asia indicate that for 15%-20% of suicide attempts, pesticides are purchased from shops; otherwise, pesticides are obtained from an individual's house or nearby environment. We aimed to investigate the difference between individuals who directly purchase pesticides from shops for suicide attempts and suicide deaths versus those related to accessing the pesticides from an individual's house or nearby environment. METHODS: We conducted two comparative studies in rural Sri Lanka: (1) non-fatal shop cases (n = 50) were survivors of self-poisoning with pesticides who ingested the pesticides after purchasing them from a shop; non-fatal domestic cases (n = 192) were survivors who accessed pesticides from their house or nearby environment. (2) fatal shop cases (n = 50) were individuals who died after ingesting pesticides they purchased for the act; fatal domestic cases (n = 102) were patients who died after ingesting pesticides they accessed at house or nearby environment. Logistic regression analysis was used to assess the characteristics which distinguished between the shop and domestic cases. RESULTS: Data indicate that 20.7% and 32.9% of individuals who used pesticides for suicide attempts and suicide deaths had purchased them from shops, respectively. Being a non-farmer was the main distinguishing characteristic of shop cases: adjusted odds ratios (AOR) 8.9, 95% confidence intervals (CI) 3.2-24.4 for non-fatal shop cases, and AOR 4.0, 95% CI 1.5-10.6 for fatal shop cases. Non-fatal shop cases also had higher suicide intent (AOR 3.0, CI 1.0-8.9), and ingesting an insecticide (AOR 4.8, CI 1.8-1.0-8.9) than non-fatal domestic cases. CONCLUSION: A high suicide intent of individuals who purchase pesticides for the event explains the high proportion of such fatal cases. Such high suicide intent makes the prevention implications difficult to spell out for those individuals who purchase pesticides for self-poisoning. However, our findings are valuable for clinicians to assess pesticide poisoning cases in hospitals.

Incorporating early pregnancy mental health screening and management into routine maternal care: experience from the Rajarata Pregnancy Cohort (RaPCo), Sri Lanka.

Early identification of mental health problems in pregnancy in low-income and middle-income countries is scarcely reported. We present the experience of a programme assimilating screening and management of antenatal anxiety and depression in conjunction with the Rajarata Pregnancy Cohort, in Sri Lanka. We adopted a two-stage screening approach to identify the symptoms and the reasons for anxiety and depression. Pregnant women (n=3074), less than 13 weeks of period of gestation underwent screening with the Edinburgh Postnatal Depression Scale (EPDS). Scores were positive among 23% and 14% of women in the first and second trimesters, respectively. Clinical (telephone) interviews (n=78, response 56.9%) were held for women having high EPDS scores to screen for clinical depression using the 'mental health GAP' tool. Targeted interventions including counselling, financial and social support and health education were employed. The procedure was repeated in the second trimester with in-person clinical interviews and inquiry into intentional self-harm. Our findings indicated that (1) the majority of mental health problems in early pregnancy were anxiety related to early pregnancy-associated conditions manageable at the primary healthcare level, (2) coupling mental health screening using psychometric tools with clinical interviews facilitates targeted patient-centred care, (3) the majority of intentional self-harm during pregnancy is not in the routine health surveillance system and (4) promoting women to attend the psychiatry clinic in tertiary care hospital has been difficult. Following the experience, we propose a model for mental health service provision in routine pregnancy care programme starting from early pregnancy.

Global, regional, and country-level cost of leptospirosis due to loss of productivity in humans.

BACKGROUND: Leptospirosis, a prevalent zoonotic disease with One Health priority and a disease of poverty, lacks global economic burden estimates. This study aims to determine the global, regional, and country-level cost of leptospirosis due to loss of productivity. METHODOLOGY/PRINCIPAL FINDINGS: The cost of leptospirosis due to loss of productivity (referred to as productivity cost hereafter) was estimated by converting the disability-adjusted life years (DALYs) lost due to leptospirosis to a monetary value using the per capita gross domestic product (GDP). The country-specific DALYs lost were obtained from the global burden of leptospirosis study published previously. Non-health GDP per capita (GDP- per capita health expenditure) was used for the cost conversion of DALYs. Country-specific GDP and health expenditure data were obtained from the World Bank data repositories. Estimates were done using both nominal and international dollars. The estimated global productivity cost of leptospirosis in 2019 was Int$ 29.3 billion, with low and high estimates ranging from Int$ 11.6 billion to 52.3 billion. China (Int$ 4.8 billion), India (Int$ 4.6 billion), Indonesia (Int$ 2.8 billion), Sri Lanka (Int$ 2.1 billion), and the United States (Int$ 1.3 billion) had the highest productivity cost due to leptospirosis. Eight out of 10 countries with the highest burden were in the Asia-Pacific region. In addition, lower-middle-income countries had an annual productivity cost of Int$ 13.8 billion, indicating that the disease is poverty-related. CONCLUSION: Although significant, the cost estimate due to loss of productivity is merely a fraction of the overall economic burden of this disease, which also includes other direct, indirect, and intangible costs. The existing partial estimates of the different components of economic cost suggest a profound economic burden that demands the inclusion of leptospirosis in the global health agenda for comprehensive disease control and prevention efforts, including vaccine development.

Heart disease complicating pregnancy as a leading cause of maternal deaths in LMIC settings: the Sri Lankan experience.

Background: Heart disease (HD) is one of the leading indirect causes of maternal deaths worldwide, both in high- and low- and middle-income countries (LMICs). This study aims to describe maternal deaths due to cardiovascular disease complicating pregnancy in Sri Lanka. Methods: The national Maternal Death Surveillance Response (MDSR) system in Sri Lanka investigates all female deaths during pregnancy and 12 months after delivery. These maternal death investigation records were perused in this analysis. Maternal deaths from 2006 to 2018 with HD complicating pregnancy as the immediate or underlying cause of death were re-coded using the ICD-11 classification. Findings: Of the 2855 pregnancy-related deaths reported to the MDSR from 2006 to 2018, 1646 (57.7%) were confirmed as maternal deaths. Of those, 284 (17.25%) were attributed to HD complicating pregnancy. The cause-specific maternal mortality ratio due to heart disease from 2006 to 2018 was 7.24 per 100,000 live births. Rheumatic heart disease was the leading cause of HD (60, 21.1%), while cardiomyopathies (59, 20.7%) and congenital anomalies (34, 12.0%) accounted for a sizeable share. Medically contraindicated pregnancies accounted for 54 (19%) deaths. Application of the 3-delay model identified 186 (65.5%) cases with possible delays. Out of all deaths, 158 (55.6%) cases were categorized as preventable. Interpretation: Preventing maternal mortality from HD in LMICs requires a lifecycle approach with situation-specific interventions and highly specialized care. Community awareness, capacity building related to management, and specific infrastructure development will be key strategies. Funding: None.

Complete genome sequences of twelve strains of Leptospira interrogans isolated from humans in Sri Lanka.

Leptospirosis, a major zoonotic disease caused by pathogenic Leptospira spp. is recognized globally as an emerging zoonotic disease. Whole-genome sequencing reveals hidden messages about Leptospira's pathogenesis. We used Single Molecule Real-Time (SMRT) sequencing to obtain complete genome sequences of twelve L. interrogans isolates from febrile patients from Sri Lanka for a comparative whole genome sequencing study. The sequence data generated 12 genomes with a coverage greater than X600 with sizes ranging from 4.62 Mb to 5.16 Mb, and a G + C content ranging from 35.00% to 35.42%. The total number of coding sequences predicted by the NCBI (National Center for Biotechnology Information) genome assembly platform ranged from 3845 to 4621 for the twelve strains. Leptospira serogroup with similar-sized LPS biosynthetic loci that belonged to the same clade had a close relationship in the phylogenetic analysis. Nonetheless, variations in the genes encoding sugar biosynthesis were found in the serovar determinant region (rfb locus). Type I and Type III CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems were found in all of the strains. Genome BLAST Distance Phylogeny of these sequences allowed for detailed genomic strain typing. These findings may help us better understand the pathogenesis, develop a tools for early diagnosis, comparative genomic analysis and evolution of Leptospira.

'We do not rush to the hospital for ordinary wounds (sulu tuvala)': A qualitative study on the early clinical manifestations of cutaneous leishmaniasis and associated health behaviours in rural Sri Lanka.

BACKGROUND: Knowledge of early clinical manifestations, people's perceptions and behaviours is crucial in preventing and controlling neglected tropical diseases (NTDs). Cutaneous leishmaniasis is an NTD that causes skin lesions and affects millions worldwide. Delayed healthcare-seeking behaviour leading to prolonged treatment periods and complications is rife among people with cutaneous leishmaniasis. This study examined the patient-reported early clinical manifestations of cutaneous leishmaniasis, local interpretations and associated health behaviours within the socio-cultural context of rural Sri Lanka. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a qualitative study among people with cutaneous leishmaniasis in three rural communities in the Anuradhapura district, Sri Lanka. Participants' experiences were explored through a study-bespoke participant experience reflection journal and in-depth interviews. We analysed the data using a narrative-thematic approach. The study included 30 people with cutaneous leishmaniasis (12 females and 18 males) aged between 18 and 75 years. We identified four major themes during the analysis: 1) patient-reported early clinical manifestations of cutaneous leishmaniasis, 2) local interpretations of the early skin lesion(s), 3) associated actions and behaviours, and 4) the time gap between the initial notice of symptoms and seeking healthcare for cutaneous leishmaniasis. Early clinical manifestations differed among the participants, while the majority misinterpreted them as a mosquito/ant bite, pimple, wart, eczema, macule, or worm infestation. Participants undertook different context-specific self-management actions to cure cutaneous leishmaniasis. We identified an average time gap between the notice of symptoms and the first visit to the healthcare facility ranging from three to twelve months. CONCLUSIONS/SIGNIFICANCE: Diverse early clinical manifestations, local interpretations, and associated behaviours of people with cutaneous leishmaniasis have led to a substantial delay in healthcare-seeking. The study sheds light on the importance of understanding the manifestations of NTDs within the social context. Our findings will inform designing context-specific health interventions to improve awareness and healthcare-seeking in cutaneous leishmaniasis in rural settings.

The stigma associated with cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL): A protocol for a systematic review.

Leishmaniasis is a neglected tropical disease with three main clinical types; cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). CL and MCL are considered to be highly stigmatizing due to potentially disfiguring skin pathology. CL and MCL-associated stigma are reported across the world in different contexts assimilating different definitions and interpretations. Stigma affects people with CL, particularly in terms of quality of life, accessibility to treatment, and psycho-social well-being. However, evidence on CL- and MCL-associated stigma is dispersed and yet to be synthesized. This systematic review describes the types, measurements, and implications of the stigma associated with CL and MCL and identifies any preventive strategies/interventions adopted to address the condition. This study was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement which is registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols PROSPERO (ID- CRD42021274925). We will perform an electronic search in MEDLINE, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library databases, and in Google Scholar, using a customized search string. Any article that discusses any type of CL- and/or MCL-associated stigma in English, Spanish and Portuguese will be included. Articles targeting veterinary studies, sandfly vector studies, laboratory-based research and trials, articles focusing only on visceral leishmaniasis, and articles on diagnostic or treatment methods for CL and MCL will be excluded. Screening for titles and abstracts and full articles and data extraction will be conducted by two investigators. The risk of bias will be assessed through specific tools for different study types. A narrative synthesis of evidence will then follow. This review will identify the knowledge gap in CL-associated stigma and will help plan future interventions.

Impact of COVID-19 pandemic on health service utilisation and household economy of pregnant and postpartum women: a cross-sectional study from rural Sri Lanka.

OBJECTIVES: This study aims to describe how household economies and health service utilisation of pregnant and postpartum women were affected during the pandemic. DESIGN: A cross-sectional study. SETTING: This study was conducted in the Anuradhapura district, Sri Lanka. PARTICIPANTS: The study participants were 1460 pregnant and postpartum women recruited for the Rajarata Pregnancy Cohort during the initial stage of the COVID-19 pandemic. PRIMARY AND SECONDARY OUTCOME MEASURES: Household economic (income, poverty, nutritional and health expenditures) and health service utilisation details during the COVID-19 pandemic were gathered through telephone interviews. Sociodemographic and economic data were obtained from the cohort baseline and analysed with descriptive and non-parametric analysis. RESULTS: Out of the 1460 women in the sample, 55.3% (n=807) were pregnant and 44.7% (n=653) were postpartum women. Of the total sample, 1172 (80.3%) women participated in the economic component. The monthly household income (median (IQR)=212.39 (159.29-265.49)) reduced (median (IQR)=159.29 (106.20-212.39)) in 50.5% (n=592) families during the pandemic (Z=-8.555, p<0.001). Only 10.3% (n=61) of affected families had received financial assistance from the government, which was only 46.4% of the affected income. The nutritional expenditure of pregnant women was reduced (Z=-2.023, p=0.043) by 6.7%. During the pandemic, 103 (8.8%) families with pregnant or postpartum women were pushed into poverty, and families who were pushed into poverty did not receive any financial assistance. The majority of women (n=1096, 83.3%) were satisfied with the free public health services provided by the public health midwife during the pandemic. CONCLUSION: During the early stages of the pandemic, healthcare utilisation of pregnant women was minimally affected. Even before the country's current economic crisis, the household economies of pregnant women in rural Sri Lanka were severely affected, pushing families into poverty due to the pandemic. The impact of COVID-19 and the aftermath on pregnant women will have many consequences if the policies and strategies are not revised to address this issue.

Early pregnancy metabolic syndrome and risk for adverse pregnancy outcomes: findings from Rajarata Pregnancy Cohort (RaPCo) in Sri Lanka.

BACKGROUND: Despite the intergenerational effects of metabolic disorders, evidence is greatly lacking on early pregnancy metabolic syndrome (MetS) and its effects on pregnancy outcomes from low- and middle-income countries. Thus, this prospective cohort of South Asian pregnant women aimed to evaluate how early pregnancy MetS would affect pregnancy outcomes. METHODS: A prospective cohort study was conducted among first-trimester (T1) pregnant women of Anuradhapura district, Sri Lanka recruited to the Rajarata Pregnancy Cohort in 2019. MetS was diagnosed by the Joint Interim Statement criteria before 13 weeks of gestational age (GA). Participants were followed up until their delivery, and the major outcomes measured were large for gestational age (LGA), small for gestational age (SGA), preterm birth (PTB) and miscarriage (MC). Gestational weight gain, gestational age at delivery and neonatal birth weight were used as measurements to define the outcomes. Additionally, outcome measures were re-assessed with adjusting fasting plasma glucose (FPG) thresholds of MetS to be compatible with hyperglycemia in pregnancy (Revised MetS). RESULTS: 2326 T1 pregnant women with a mean age of 28.1 years (SD-5.4), and a median GA of 8.0 weeks (IQR-2) were included. Baseline MetS prevalence was 5.9% (n = 137, 95%CI-5.0-6.9). Only 2027 (87.1%) women from baseline, had a live singleton birth, while 221(9.5%) had MC and 14(0.6%) had other pregnancy losses. Additionally, 64(2.8%) were lost to follow-up. A higher cumulative incidence of LGA, PTB, and MC was noted among the T1-MetS women. T1-MetS carried significant risk (RR-2.59, 95%CI-1.65-3.93) for LGA, but reduced the risk for SGA (RR-0.41, 95%CI-0.29-0.78). Revised MetS moderately increased the risk for PTB (RR-1.54, 95%CI-1.04-2.21). T1-MetS was not associated (p = 0.48) with MC. Lowered FPG thresholds were significantly associated with risk for all major pregnancy outcomes. After adjusting for sociodemographic and anthropometric confounders, revised MetS remained the only significant risk predictor for LGA. CONCLUSION: Pregnant women with T1 MetS in this population are at an increased risk for LGA and PTB and a reduced risk for SGA. We observed that a revised MetS definition with lower threshold for FPG compatible with GDM would provide a better estimation of MetS in pregnancy in relation to predicting LGA.

Serum creatinine and estimated glomerular filtration rate (eGFR) in early pregnancy and changes during the pregnancy.

Renal functions in pregnancy undergo rapid changes, and the thresholds for normal values are a major research gap and are still debatable. The lack of prospective population-based studies with early pregnancy recruitment hampered the decision-making process on the best thresholds to be used in clinical practice. We present the serum creatinine (sCr) and sCr-based estimated glomerular filtration rates (eGFR) in early pregnancy with changes over the gestational period in a large prospective, community-based cohort, the Rajarata Pregnancy Cohort (RaPCo). We carried out a community-based prospective cohort study with 2,259 healthy pregnant women with a gestation period of less than 13 weeks and without pre-existing medical conditions. Gestational period-specific sCr and sCr-based eGFR were calculated for different age strata, and the participants were followed up until the second trimester. Renal functions of pregnant women were compared with 2.012 nonpregnant women from the same geographical area. The mean (SD) sCr of the 2,012 nonpregnant women was 62.8(12.4) µmol/L, with the 97.5th percentile of 89.0 µmol/L. Among the pregnant women, mean (SD) sCr was 55.1(8.3), 52.7(8.1), 51.1(9.1), 47.1(7.2), and 49.3 (9.9), while the 97.5th percentile for sCr was 72.4, 69.1, 70.0, 63.6, and 66.0 µmol/L respectively during the 4-7, 8-9, 10-12, 24-27 and 28-30 weeks of gestation. The average sCr value was 84.7% and 76.4% of the nonpregnant group, respectively, in the first and second trimesters. The mean eGFR was 123.4 (10.7) mL/min/1.73 m2 in the first trimester and increased up to 129.5 mL/min/1.73 m2 in the 24th week of gestation. The analysis of cohort data confirmed a significant reduction in sCr with advancing pregnancy (p<0 .001). This study provides thresholds for renal functions in pregnancy to be used in clinical practice. Clinical validation of the proposed thresholds needs to be evaluated with pregnancy and newborn outcomes.