Patricia M. Graves

Description:Objective: The first round of triple-drug mass drug administration (MDA) for lymphatic filariasis (LF) in Samoa was in 2018. This study aims to i) examine progression of LF antigen (Ag) and microfilaria (Mf) in Ag-positive individuals from 2019-2023; and ii) compare Ag/Mf prevalence in household members of Mf-positive vs Mf-negative participants. Methods: In 2023, we tested Ag-positive participants (indexes) from a 2019 survey in Samoa, and their household members. We tested for Ag (Alere/Abbott Filariasis Test Strip) and Mf. We examined changes in Ag/Mf status in index participants and compared Ag/Mf prevalence between household members of Mf-positive and Mf-negative indexes. Results: We recruited 91 indexes and 317 household members. In 2023, all 17 Mf-positive indexes remained Ag-positive and 11/15 with Mf results (73.3%) were Mf-positive. Of 74 Mf-negative indexes, 79.7% remained Ag-positive in 2023 and 31.1% became Mf-positive. Household members of Mf-positive indexes were more likely to be Ag-positive (odds ratios 3.3, 95% CI 1.0-10.3) compared to those of Mf-negative indexes. Conclusions: Our results raise concerns regarding long-term effectiveness of a single-dose of triple-drug MDA for sustained clearance of Mf in Samoa. Guidelines for follow-up and treatment of Ag/Mf-positive people and household members are urgently required.

Description:Accurate rapid diagnostic tests (RDTs) are needed to diagnose lymphatic filariasis (LF) in global elimination programmes. We evaluated the performance of the new STANDARD Q Filariasis Antigen Test (QFAT) against the Bioline Filariasis Test Strip (FTS) for detecting W. bancrofti antigen (Ag) in laboratory conditions, using serum (n = 195) and plasma (n = 189) from LF-endemic areas (Samoa, American Samoa and Myanmar) and Australian negative controls (n = 46). The prior Ag status of endemic samples (54.9% Ag-positive) was determined by rapid test (ICT or FTS) or Og4C3 ELISA. The proportion of samples testing positive at 10 min was similar for QFAT (44.8%) and FTS (41.3%). Concordance between tests was 93.5% (kappa 0.87, n = 417) at 10 min, and it increased to 98.8% (kappa 0.98) at 24 h. The sensitivities of QFAT and FTS at 10 min compared to the prior results were 92% (95% CI 88.0-96.0) and 86% (95% CI 80.0-90.0), respectively, and they increased to 97% and 99% at 24 h. Specificity was 98% for QFAT and 99% for FTS at 10 min. Both tests showed evidence of cross-reaction with Dirofilaria repens and Onchocerca lupi but not with Acanthochilonema reconditum or Cercopithifilaria bainae. Under laboratory conditions, QFAT is a suitable alternative RDT to FTS.

Description:Objective: Contrasting evidence is emerging on the long-term effectiveness of triple-drug therapy for elimination of lymphatic filariasis (LF) in the Pacific region. We evaluated the effectiveness of ivermectin, diethylcarbamazine and albendazole (IDA) for sustained clearance of microfilariae (Mf) in Samoa. Methods: We enrolled two cohorts of Mf-positive participants. Cohort A were Mf-positive participants from 2018, who received directly observed triple-drug therapy in 2019 and were retested and retreated in 2023 and 2024. Cohort B were Mf-positive and treated in 2023 and retested in 2024. Participants were tested for LF antigen and Mf. Results: In Cohort A, eight of the 14 participants from 2018/2019 were recruited in 2023; six were Mf-positive. In 2024, six participants were retested, and two were Mf-positive. Cohort B included eight participants, and two remained Mf-positive in 2024. Mf prevalence in 2023 for Cohort A (71.4%, 95% CI 29.0%-96.3%) was significantly higher than among their household members (12.0%, 95% CI 2.5%-31.2%). Conclusions: One or two doses of directly observed IDA was not sufficient for sustained clearance of Wuchereria bancrofti Mf in Samoa. The high Mf prevalence in treated individuals compared to household members suggests recrudescence rather than reinfection.

Description:The elimination of lymphatic filariasis (LF) as a public health problem remains an ongoing challenge in the Pacific region. This study reports on antigen (Ag) and microfilaria (Mf) prevalence in Samoa in 2019, 7-9 months after the completion of the first round of triple-drug mass drug administration (MDA). It evaluates the effectiveness of the intervention for reducing Ag prevalence to below a 2% threshold, and how this differs between 5-9-year-olds and ≥10-year-olds. We surveyed 30 randomly selected and five purposefully selected primary sampling units (PSUs) in Samoa in 2018 (1-3 months post-triple-drug MDA) and, again, in 2019. In each PSU, we conducted a community survey of 15-20 households and a convenience survey of 5-9-year-old children. A finger-prick blood sample was collected from all participants to test for Ag and Mf. Demographic details were also collected. There was no significant change in adjusted Ag prevalence in the 30 randomly selected PSUs between 2018 (3.9% [95% CI: 2.7-5.6%]) and 2019 (4.1% [95% CI 2.7-5.9%]). Significantly higher Ag prevalence was observed in participants aged ≥10 years (4.6%, 95% CIs 3.0-6.7%) compared to 5-9-year-olds (1.1%, 95% CIs 0.5-2.2%), supporting existing evidence that post-MDA surveillance should not be based on Ag prevalence among 6-7-year-olds. A single round of triple-drug MDA was insufficient to break LF transmission in Samoa 7-9 months post-MDA.

Description:Background: Lymphatic filariasis (LF) is a globally significant, vector-borne, neglected tropical disease that can result in severe morbidity and disability. As the World Health Organization (WHO) Global Programme to Eliminate Lymphatic Filariasis makes progress towards LF elimination, there is greater need to develop sensitive strategies for post-intervention surveillance. Molecular xenomonitoring (MX), the detection of pathogen DNA in vectors, may provide a sensitive complement to traditional human-based surveillance techniques, including detection of circulating filarial antigen and microfilaraemia (Mf). This study aims to explore the relationship between human Mf prevalence and the prevalence of polymerase chain reaction (PCR)-positive mosquitoes using MX. Methods: This study compared Mf and MX results from a 2019 community-based survey conducted in 35 primary sampling units (PSUs) in Samoa. This study also investigated concordance between presence and absence of PCR-positive mosquitoes and Mf-positive participants at the PSU level, and calculated sensitivity and negative predictive values for each indicator using presence of any Mf-positive infection in humans or PCR-positive mosquitoes as a reference. Correlation between prevalence of filarial DNA in mosquitoes and Mf in humans was estimated at the PSU and household/trap level using mixed-effect Bayesian multilevel regression analysis. Results: Mf-positive individuals were identified in less than half of PSUs in which PCR-positive mosquito pools were present (13 of 28 PSUs). Prevalence of PCR-positive mosquitoes (each species separately) was positively correlated with Mf prevalence in humans at the PSU level. Analysed at the species level, only Aedes polynesiensis demonstrated strong evidence of positive correlation (r) with human Mf prevalence at both PSU (r: 0.5, 95% CrI 0.1-0.8) and trap/household levels (r: 0.6, 95% CrI 0.2-0.9). Conclusions: Findings from this study demonstrate that MX can be a sensitive surveillance method for identifying residual infection in low Mf prevalence settings. MX identified more locations with signals of transmission than Mf-testing. Strong correlation between estimated PCR-positive mosquitoes in the primary vector species and Mf in humans at small spatial scales demonstrates the utility of MX as an indicator for LF prevalence in Samoa and similar settings. Further investigation is needed to develop MX guidelines to strengthen the ability of MX to inform operational decisions.