A Multi-Country, Single-Blinded, Phase 2 Study to Evaluate a Point-of-Need System for Rapid Detection of Leishmaniasis and Its Implementation in Endemic Settings

With the advancement of isothermal nucleic acid amplification techniques, detection of the pathogenic DNA in clinical samples at point-of-need is no longer a dream. The newly developed recombinase polymerase amplification (RPA) assay incorporated in a suitcase laboratory has shown promising diagnostic efficacy over real-time PCR in detection of leishmania DNA from clinical samples. For broader application of this point-of-need system, we undertook a current multi-country diagnostic evaluation study towards establishing this technique in different endemic settings which would be beneficial for the ongoing elimination programs for leishmaniasis. For this study purpose, clinical samples from confirmed visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) patients were subjected to both real-time PCR and RPA assay in Bangladesh, India, and Nepal. Further skin samples from confirmed cutaneous leishmaniasis (CL) patients were also included from Sri Lanka. A total of 450 clinical samples from VL patients, 429 from PKDL patients, 47 from CL patients, and 322 from endemic healthy/healthy controls were under investigation to determine the diagnostic efficacy of RPA assay in comparison to real-time PCR. A comparative sensitivity of both methods was found where real-time PCR and RPA assay showed 96.86% (95% CI: 94.45–98.42) and 88.85% (95% CI: 85.08–91.96) sensitivity respectively in the diagnosis of VL cases. This new isothermal method also exhibited promising diagnostic sensitivity (93.50%) for PKDL cases, when a skin sample was used. Due to variation in the sequence of target amplicons, RPA assay showed comparatively lower sensitivity (55.32%) than that of real-time PCR in Sri Lanka for the diagnosis of CL cases. Except for India, the assay presented absolute specificity in the rest of the sites. Excellent concordance between the two molecular methods towards detection of leishmania DNA in clinical samples substantiates the application of RPA assay incorporated in a suitcase laboratory for point-of-need diagnosis of VL and PKDL in low resource endemic settings. However, further improvisation of the method is necessary for diagnosis of CL

Two essays on regional differences in health outcomes of women and children: The role of female labour force participation

This thesis examines the relationship between female labour force participation and various chronic health outcomes among women and children using cross-country data over 42 years. The results suggest that in the high-income countries, higher female labour force participation is positively associated with the prevalence of obesity among women and negatively related with the prevalence of overweight/obesity among children and adolescents. However, the relationship between female labour force participation and the prevalence of other chronic diseases, such as hypertension and type 2 diabetes mellitus, is negative in these countries. The thesis uncovers interesting regional and gender variations in these relationships that are important for labour market policy

On the feasibility of an agricultural revolution: Sri Lanka’s move to go 100% organic

Paper presented at the Annual International Conference on Research in Tropical and Subtropical Agriculture, Natural Resource Management and Rural Development (Tropentag) on Competing Pathways for Equitable Food Systems Transformation: Trade-Offs and Synergies, Berlin, Germany, 20-22 September 2023In April 2021, the Sri Lankan Government banned imports of agrochemicals, including chemical fertilizers, to make Sri Lanka the first fully organic and chemical fertilizer-free country globally. The ban was justified by human and environmental health concerns, such as many cases of kidney failure in the central parts of Sri Lanka. While previous policies had envisioned a stepwise transition, the sudden ban jolted the agriculture sector. However, it was aligned with the emerging national economic crisis with drastically declining foreign exchange reserves that restricted the import of commodities, including fertilizer for distribution at subsidized prices. The ban was also opportune because fertilizer prices peaked on international markets in 2022. Without any transitional time, the thrust for organic fertilizers failed to satisfy demand or obtain the required crop nutrients resulting in severe agricultural losses. After the first data on decreasing yields were revealed, the government lifted the chemical fertilizer ban on December 1, 2021, but it was too late as the cropping season had arrived. Without financial reserves to import fertilizer, the donor community was urged to assist. This paper addresses: (1) justification of the ban, (2) the feasibility of transitioning to organic fertilizers based on the available biomass to replace chemical fertilizers; and (3) the related cost implications. The scenarios focus on irrigated paddy rice and the plantation sector that underpin the national economy. Undervalued nutrient sources are also considered as well as the constraints to and implications of such a transition beyond Sri Lanka’s frontiers

Mathematical modelling to explore the role of the female-sex-worker-client interaction for gonorrhoea transmission and prevention among Australian heterosexuals

Gonorrhoea notifications have been increasing among young Australian heterosexuals since 2009 and the reasons for this are unclear. Gonorrhoea incidence has also increased in female sex workers (FSW) since 2009. Previous studies indicate that condom-use among FSW-clients declined from 2009-2017, mainly for oral sex and a high proportion of infections in heterosexual males arise from condomless oral sex with FSW. Thus, we hypothesise that an increase in condomless sex by FSW-clients may have contributed to the rising incidence of gonorrhoea among heterosexuals in Australia. In this thesis, mathematical modelling is used to provide insights to the role of the FSW-client interaction for heterosexual gonorrhoea transmission, to explore whether the increasing notifications can be explained, even partly, by decreasing condom-use among FSW-clients, and to evaluate the potential impact of providing gonorrhoea vaccination for FSW on gonorrhoea incidence/prevalence.A deterministic compartmental model was developed to address the stated objectives and was calibrated to reported female notifications and FSW incidence data for 2009. Using adaptations of the model that included/excluded FSW-client strata, we evaluated the role of FSW-client interactions in model dynamics and sensitivity of the reproduction number (Rt) in this population to changes in key parameters. We then estimated the annual percentage decline in condom-use between 2009 and 2017 that resulted in a model-produced notification rate that is consistent with the reported increase in heterosexual notifications using the model with FSW-client strata. Finally, the potential impact of a gonococcal vaccine for FSW on heterosexual gonorrhoea rates was assessed under different assumptions regarding the mode of vaccine conferred protection.Our results suggest that Rt and the heterosexual notification rate are highly sensitive to changes in parameters that govern transmission in the model that accommodates FSW-client interactions and infection rates are consequently highly sensitive to changes in condom-use by FSW-clients. An annual decline of only 0.26% in condom-use by FSW-clients is predicted to lead to an increase in heterosexual notifications that is consistent with the observed increase in notifications. Vaccinating FSW with a partially efficacious vaccine has the potential to substantially reduce gonorrhoea prevalence over time in the heterosexual population in Australia.These findings suggest that increasing condomless sex among FSW-clients can result in marked increases in heterosexual notifications. Therefore, promoting condom-use in commercial sex may help reduce the gonorrhoea burden in young heterosexuals. Additionally, targeted vaccination of FSW may be an effective means of controlling gonorrhoea in this population

Importance of KIM-1 and MCP-1 in Determining the Leptospirosis-Associated AKI: A Sri Lankan Study

Background. Acute kidney injury (AKI) is one of most prevalent and serious complications of leptospirosis, a prevalent zoonotic disease in tropical countries. Prompt diagnosis of the leptospirosis-associated AKI is a challenge as there are no proper diagnostic tools that can identify patients in the early stage. Kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) are widely used novel AKI biomarkers that are studied in various disease conditions with AKI, but not in leptospirosis. Thus, this study is aimed at seeking the importance of KIM-1 and MCP-1 in determining the leptospirosis-associated AKI. Methods. Leptospirosis-suspected patients who were admitted to medical wards of two selected hospitals in the Western province of Sri Lanka were recruited. Leptospirosis was confirmed by three diagnostic tests: PCR, MAT, and culture, and the status of AKI was determined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results. Of 170 leptospirosis-suspected patients, 79 were leptospirosis confirmed, and among them, 24.05% of patients were diagnosed to have AKI according to KDIGO criteria. Median serum KIM-1 (p<0.0001), urine KIM-1 (0.0053), serum MCP-1 (0.0080), and urine MCP-1 (0.0019) levels in those developing AKI were significantly higher than in patients not developing AKI. The biomarker levels associated with leptospirosis AKI had AUC-ROC of 0.8565, 0.7292, 0.7024, and 0.7282 for serum KIM-1, urine KIM-1, serum MCP-1, and urine MCP-1, respectively. Conclusion. This study revealed serum KIM-1 as a promising marker for leptospirosis-associated AKI among the tested biomarkers. Thus, further validation is recommended with a larger study group

Protocol for a cluster-randomised controlled trial evaluating the impact of a preschool-based capacity building intervention on intimate partner violence and substance misuse in Sri Lanka

Background: Past research has identified links between intimate partner violence (IPV) and alcohol misuse and poverty in Sri Lanka. Services that address substance misuse are amongst the few interventions shown to reduce IPV in settings similar to Sri Lanka. This paper describes the protocol for a study examining the impact of a preschool-based capacity building intervention on the prevalence of IPV and substance misuse in parents with children attending preschools, including uptake of available government services. Methods: The study is a cluster randomised controlled trial. Government-managed preschools (n = 34) in Galle and Colombo municipalities will be randomly assigned to an intervention (n = 17) or control group (n = 17). Parents with children attending these preschools will be recruited to participate. The study intervention will build the capacity of selected community volunteers (parents) and preschool teachers in the provision of information and support to families affected by IPV and substance misuse. This intervention is directed at improving uptake, access and coordination of existing services. Data will be collected from all parents, and teachers in the intervention group, pre-intervention and 10 months post-intervention. The primary outcome for this study is experience of IPV amongst mothers of preschool-attending children. Secondary outcomes are substance misuse amongst fathers, measured via the locally adapted Alcohol Use Disorders Identification Test and Drug Abuse Screening Test; and awareness and uptake of services for these issues measured through locally-relevant tools. Demographic information and satisfaction with the intervention will also be assessed. Discussion: By intervening through preschools we aim to support high-risk families early enough to arrest the cycle of violence that results in children themselves becoming victims and perpetrators of such violence. The innovative project design will reach the most vulnerable sections of the community and will provide a sustainable and feasible strategy for scale-up of the intervention. Trial registration: This study is registered with the Sri Lankan Clinical Trials Registry (2017/038) and has been submitted to ClinicalTrials.gov (U.S National Institutes of Health) under the title "Randomized control trial: preschool-based training and support programs to reduce intimate partner violence (IPV) by addressing alcohol and drug misuse in young families in Sri Lanka

A Multi-Country, Single-Blinded, Phase 2 Study to Evaluate a Point-of-Need System for Rapid Detection of Leishmaniasis and Its Implementation in Endemic Settings

With the advancement of isothermal nucleic acid amplification techniques, detection of the pathogenic DNA in clinical samples at point-of-need is no longer a dream. The newly developed recombinase polymerase amplification (RPA) assay incorporated in a suitcase laboratory has shown promising diagnostic efficacy over real-time PCR in detection of leishmania DNA from clinical samples. For broader application of this point-of-need system, we undertook a current multi-country diagnostic evaluation study towards establishing this technique in different endemic settings which would be beneficial for the ongoing elimination programs for leishmaniasis. For this study purpose, clinical samples from confirmed visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) patients were subjected to both real-time PCR and RPA assay in Bangladesh, India, and Nepal. Further skin samples from confirmed cutaneous leishmaniasis (CL) patients were also included from Sri Lanka. A total of 450 clinical samples from VL patients, 429 from PKDL patients, 47 from CL patients, and 322 from endemic healthy/healthy controls were under investigation to determine the diagnostic efficacy of RPA assay in comparison to real-time PCR. A comparative sensitivity of both methods was found where real-time PCR and RPA assay showed 96.86% (95% CI: 94.45–98.42) and 88.85% (95% CI: 85.08–91.96) sensitivity respectively in the diagnosis of VL cases. This new isothermal method also exhibited promising diagnostic sensitivity (93.50%) for PKDL cases, when a skin sample was used. Due to variation in the sequence of target amplicons, RPA assay showed comparatively lower sensitivity (55.32%) than that of real-time PCR in Sri Lanka for the diagnosis of CL cases. Except for India, the assay presented absolute specificity in the rest of the sites. Excellent concordance between the two molecular methods towards detection of leishmania DNA in clinical samples substantiates the application of RPA assay incorporated in a suitcase laboratory for point-of-need diagnosis of VL and PKDL in low resource endemic settings. However, further improvisation of the method is necessary for diagnosis of CL

A Multi-Country, Single-Blinded, Phase 2 Study to Evaluate a Point-of-Need System for Rapid Detection of Leishmaniasis and Its Implementation in Endemic Settings

With the advancement of isothermal nucleic acid amplification techniques, detection of the pathogenic DNA in clinical samples at point-of-need is no longer a dream. The newly developed recombinase polymerase amplification (RPA) assay incorporated in a suitcase laboratory has shown promising diagnostic efficacy over real-time PCR in detection of leishmania DNA from clinical samples. For broader application of this point-of-need system, we undertook a current multi-country diagnostic evaluation study towards establishing this technique in different endemic settings which would be beneficial for the ongoing elimination programs for leishmaniasis. For this study purpose, clinical samples from confirmed visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) patients were subjected to both real-time PCR and RPA assay in Bangladesh, India, and Nepal. Further skin samples from confirmed cutaneous leishmaniasis (CL) patients were also included from Sri Lanka. A total of 450 clinical samples from VL patients, 429 from PKDL patients, 47 from CL patients, and 322 from endemic healthy/healthy controls were under investigation to determine the diagnostic efficacy of RPA assay in comparison to real-time PCR. A comparative sensitivity of both methods was found where real-time PCR and RPA assay showed 96.86% (95% CI: 94.45–98.42) and 88.85% (95% CI: 85.08–91.96) sensitivity respectively in the diagnosis of VL cases. This new isothermal method also exhibited promising diagnostic sensitivity (93.50%) for PKDL cases, when a skin sample was used. Due to variation in the sequence of target amplicons, RPA assay showed comparatively lower sensitivity (55.32%) than that of real-time PCR in Sri Lanka for the diagnosis of CL cases. Except for India, the assay presented absolute specificity in the rest of the sites. Excellent concordance between the two molecular methods towards detection of leishmania DNA in clinical samples substantiates the application of RPA assay incorporated in a suitcase laboratory for point-of-need diagnosis of VL and PKDL in low resource endemic settings. However, further improvisation of the method is necessary for diagnosis of CL

A Multi-Country, Single-Blinded, Phase 2 Study to Evaluate a Point-of-Need System for Rapid Detection of Leishmaniasis and Its Implementation in Endemic Settings

With the advancement of isothermal nucleic acid amplification techniques, detection of the pathogenic DNA in clinical samples at point-of-need is no longer a dream. The newly developed recombinase polymerase amplification (RPA) assay incorporated in a suitcase laboratory has shown promising diagnostic efficacy over real-time PCR in detection of leishmania DNA from clinical samples. For broader application of this point-of-need system, we undertook a current multi-country diagnostic evaluation study towards establishing this technique in different endemic settings which would be beneficial for the ongoing elimination programs for leishmaniasis. For this study purpose, clinical samples from confirmed visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) patients were subjected to both real-time PCR and RPA assay in Bangladesh, India, and Nepal. Further skin samples from confirmed cutaneous leishmaniasis (CL) patients were also included from Sri Lanka. A total of 450 clinical samples from VL patients, 429 from PKDL patients, 47 from CL patients, and 322 from endemic healthy/healthy controls were under investigation to determine the diagnostic efficacy of RPA assay in comparison to real-time PCR. A comparative sensitivity of both methods was found where real-time PCR and RPA assay showed 96.86% (95% CI: 94.45–98.42) and 88.85% (95% CI: 85.08–91.96) sensitivity respectively in the diagnosis of VL cases. This new isothermal method also exhibited promising diagnostic sensitivity (93.50%) for PKDL cases, when a skin sample was used. Due to variation in the sequence of target amplicons, RPA assay showed comparatively lower sensitivity (55.32%) than that of real-time PCR in Sri Lanka for the diagnosis of CL cases. Except for India, the assay presented absolute specificity in the rest of the sites. Excellent concordance between the two molecular methods towards detection of leishmania DNA in clinical samples substantiates the application of RPA assay incorporated in a suitcase laboratory for point-of-need diagnosis of VL and PKDL in low resource endemic settings. However, further improvisation of the method is necessary for diagnosis of CL