Background: Lymphatic filariasis (LF), a mosquito-transmitted parasitic disease caused by filarial worms, is a leading cause of disability worldwide. In 1997, at the 50th World Health Assembly, a resolution was passed to eliminate LF as a public health problem by 2020. To reach established elimination targets, LF programmes conduct annual community-wide mass drug administration (MDA). At the start of the Global Programme to Eliminate Lymphatic Filariasis (GPELF), an estimated 120 million individuals were infected, and approximately 1.4 billion people were at risk for filarial infection. Since then, mainly through MDA programmes, the number of people at risk of infection has been reduced to 856.4 million. By the end of 2016, MDA had been implemented in 63 of 72 LF-endemic countries. Demonstrating success of LF programmes depends on rigorous monitoring and evaluation (M&E) of programme activities. As prevalence declines, it is important to identify sensitive diagnostic tools and robust surveillance strategies to detect any possible recrudescence of infection as early as possible. Existing recommendations for LF surveillance are adequate for making the decision to stop MDA, but may not be sufficient for documenting that elimination endpoints have been met. Programme strategies need to be refined in order to establish a more robust M&E framework.
Goals and objectives: The overarching goal of this PhD thesis was to provide recommendations on approaches for conducting surveillance for LF elimination programmes. There were two interlinked objectives: (i) to determine the utility of serologic tools during the post-MDA surveillance period within communities that have received multiple rounds of LF MDA; and (ii) to determine the utility of the transmission assessment survey (TAS) and other activities during the post-MDA surveillance period as platforms for integrated disease surveillance. The specific aims were (i) to compare LF antigen and antifilarial antibody responses during the post-MDA surveillance period; (ii) to determine the appropriate age group(s) to monitor during the post-MDA period; (iii) to compare diagnostic tools for use during the surveillance period to determine the most appropriate diagnostic tool(s) to use for LF surveillance; and (iv) to assess the feasibility of using existing disease programme infrastructures as platforms for multi-disease surveillance.
Methods: To compare the utility of parasitological and serological indicators for measuring LF programme endpoints, samples from participants (2-100 years old) in 10 sentinel sites in coastal Kenya were examined for circulating filarial antigen (CFA) and filarial antibodies. To evaluate the use of antibody responses as a way to measure the impact of MDA, serum samples collected at three time points from children 1-5 years of age in western Kenya were tested for antibody responses to two schistosome antigens by multiplex bead assay (MBA). In American Samoa, CFA and antibody results from children enrolled in LF TAS conducted 4 years apart were analysed to determine whether interruption of LF transmission has been achieved. A study was carried out in The Gambia among populations living in 15 villages with a history of high LF prevalence. Samples were collected and tested for CFA and filarial antibodies to evaluate the use of serological tools to confirm interruption of LF transmission. Published data from previously conducted studies in American Samoa were analysed to evaluate the relationship between human serological indicators and filarial DNA in mosquitoes. In Haiti, to evaluate the feasibility of using TAS as a platform to collect information about other tropical diseases, samples were collected to test for LF and malaria. In addition to LF testing, samples collected during the sentinel site surveys in coastal Kenya were used for the detection of antibodies against antigens from several parasitic infections as well as markers for immunity to vaccine-preventable diseases to determine the utility of integrated serosurveillance.
Results: The overall prevalence of filarial antigenaemia in coastal Kenya was low (1.3%). CFA prevalence among children under 10 years old was very low (<1%). However, quantitative antibody levels among children were higher in areas with suspected LF transmission. Antibodies to Schistosoma spp. antigens among children declined after MDA. There was a significant decrease in the proportion of 1-year olds with positive antibody responses from 33.1% in year 1 to 13.2% in year 3. In American Samoa, a total of 1,134 and 864 children (5-10 years old) were enrolled in TAS 1 (2011) and TAS 2 (2015), respectively.
Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2. In 2011, overall prevalence of antibody responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively. In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% and 7.8%, respectively. However, there were persistent antibody responses in some schools. In The Gambia, a total of 2,612 dried blood spots (DBS) collected from individuals aged 1 year and above was tested for antibodies to Wb123 by enzyme-linked immunosorbent assay (ELISA). Overall, prevalence of Wb123 was low (1.5%). In seven of 15 villages, there were no Wb123-positive individuals identified. In American Samoa, there was a significant relationship between the presence of filarial DNA in mosquitoes and villages with individuals with responses to Wb123. It was feasible to add malaria testing to TAS in Haiti. A total of 16,655 children were tested for LF and 14,795 for malaria in 14 TAS. In Kenya, utilising a multiplex approach, antibody responses to 10 antigens representing six parasitic infections and three antigens to assess immunity to vaccine preventable diseases were generated from a single sample collected from each participant.
Conclusions: As prevalence declines, using parasitological indicators to determine LF programme endpoints becomes challenging and there is a need to identify alternative indicators to use during the surveillance period. Results from this PhD thesis support the use of antibody tools to determine the status of LF transmission and suggest that serological tools can have a role in guiding programmatic decision-making. The absence of antibody responses strongly suggests that LF transmission has been interrupted and, in contrast, the presence of antibody in children is an important indicator that programmes have not reached elimination. Finally, existing LF programme activities can provide a platform both to introduce the use of antibody testing into TAS and to conduct integrated assessments.
BT - University of Basel LA - eng M3 - Dissertation N2 -Background: Lymphatic filariasis (LF), a mosquito-transmitted parasitic disease caused by filarial worms, is a leading cause of disability worldwide. In 1997, at the 50th World Health Assembly, a resolution was passed to eliminate LF as a public health problem by 2020. To reach established elimination targets, LF programmes conduct annual community-wide mass drug administration (MDA). At the start of the Global Programme to Eliminate Lymphatic Filariasis (GPELF), an estimated 120 million individuals were infected, and approximately 1.4 billion people were at risk for filarial infection. Since then, mainly through MDA programmes, the number of people at risk of infection has been reduced to 856.4 million. By the end of 2016, MDA had been implemented in 63 of 72 LF-endemic countries. Demonstrating success of LF programmes depends on rigorous monitoring and evaluation (M&E) of programme activities. As prevalence declines, it is important to identify sensitive diagnostic tools and robust surveillance strategies to detect any possible recrudescence of infection as early as possible. Existing recommendations for LF surveillance are adequate for making the decision to stop MDA, but may not be sufficient for documenting that elimination endpoints have been met. Programme strategies need to be refined in order to establish a more robust M&E framework.
Goals and objectives: The overarching goal of this PhD thesis was to provide recommendations on approaches for conducting surveillance for LF elimination programmes. There were two interlinked objectives: (i) to determine the utility of serologic tools during the post-MDA surveillance period within communities that have received multiple rounds of LF MDA; and (ii) to determine the utility of the transmission assessment survey (TAS) and other activities during the post-MDA surveillance period as platforms for integrated disease surveillance. The specific aims were (i) to compare LF antigen and antifilarial antibody responses during the post-MDA surveillance period; (ii) to determine the appropriate age group(s) to monitor during the post-MDA period; (iii) to compare diagnostic tools for use during the surveillance period to determine the most appropriate diagnostic tool(s) to use for LF surveillance; and (iv) to assess the feasibility of using existing disease programme infrastructures as platforms for multi-disease surveillance.
Methods: To compare the utility of parasitological and serological indicators for measuring LF programme endpoints, samples from participants (2-100 years old) in 10 sentinel sites in coastal Kenya were examined for circulating filarial antigen (CFA) and filarial antibodies. To evaluate the use of antibody responses as a way to measure the impact of MDA, serum samples collected at three time points from children 1-5 years of age in western Kenya were tested for antibody responses to two schistosome antigens by multiplex bead assay (MBA). In American Samoa, CFA and antibody results from children enrolled in LF TAS conducted 4 years apart were analysed to determine whether interruption of LF transmission has been achieved. A study was carried out in The Gambia among populations living in 15 villages with a history of high LF prevalence. Samples were collected and tested for CFA and filarial antibodies to evaluate the use of serological tools to confirm interruption of LF transmission. Published data from previously conducted studies in American Samoa were analysed to evaluate the relationship between human serological indicators and filarial DNA in mosquitoes. In Haiti, to evaluate the feasibility of using TAS as a platform to collect information about other tropical diseases, samples were collected to test for LF and malaria. In addition to LF testing, samples collected during the sentinel site surveys in coastal Kenya were used for the detection of antibodies against antigens from several parasitic infections as well as markers for immunity to vaccine-preventable diseases to determine the utility of integrated serosurveillance.
Results: The overall prevalence of filarial antigenaemia in coastal Kenya was low (1.3%). CFA prevalence among children under 10 years old was very low (<1%). However, quantitative antibody levels among children were higher in areas with suspected LF transmission. Antibodies to Schistosoma spp. antigens among children declined after MDA. There was a significant decrease in the proportion of 1-year olds with positive antibody responses from 33.1% in year 1 to 13.2% in year 3. In American Samoa, a total of 1,134 and 864 children (5-10 years old) were enrolled in TAS 1 (2011) and TAS 2 (2015), respectively.
Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2. In 2011, overall prevalence of antibody responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively. In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% and 7.8%, respectively. However, there were persistent antibody responses in some schools. In The Gambia, a total of 2,612 dried blood spots (DBS) collected from individuals aged 1 year and above was tested for antibodies to Wb123 by enzyme-linked immunosorbent assay (ELISA). Overall, prevalence of Wb123 was low (1.5%). In seven of 15 villages, there were no Wb123-positive individuals identified. In American Samoa, there was a significant relationship between the presence of filarial DNA in mosquitoes and villages with individuals with responses to Wb123. It was feasible to add malaria testing to TAS in Haiti. A total of 16,655 children were tested for LF and 14,795 for malaria in 14 TAS. In Kenya, utilising a multiplex approach, antibody responses to 10 antigens representing six parasitic infections and three antigens to assess immunity to vaccine preventable diseases were generated from a single sample collected from each participant.
Conclusions: As prevalence declines, using parasitological indicators to determine LF programme endpoints becomes challenging and there is a need to identify alternative indicators to use during the surveillance period. Results from this PhD thesis support the use of antibody tools to determine the status of LF transmission and suggest that serological tools can have a role in guiding programmatic decision-making. The absence of antibody responses strongly suggests that LF transmission has been interrupted and, in contrast, the presence of antibody in children is an important indicator that programmes have not reached elimination. Finally, existing LF programme activities can provide a platform both to introduce the use of antibody testing into TAS and to conduct integrated assessments.
PY - 2018 EP - 230 T2 - University of Basel TI - New approaches for conducting surveillance for lymphatic filariasis elimination programmes and implications for other neglected tropical diseases. UR - https://edoc.unibas.ch/65770/1/Won_thesis_20181016_final_eDoc.pdf VL - PhD ER -