Dataset Information

Comparison of Commercial ELISA Kits to Confirm the Absence of Transmission in Malaria Elimination Settings.

ABSTRACT: Background: Antimalarial antibody measurements are useful because they reflect historical and recent exposure to malaria. As such, they may provide additional information to assess ongoing transmission in low endemic or pre-elimination settings where cases are rare. In addition, the absence of antibody responses in certain individuals can indicate the cessation of transmission. Commercial malaria enzyme-linked immunosorbent assays (ELISA) detect antimalarial antibodies and are commonly used to screen blood donations for possible malaria infection. However, there is no standardized test to detect antimalarial antibodies for epidemiological use. Here we compared five commercially available ELISA kits (Trinity Biotech, newbio, DiaPro, Cellabs, and NovaTec) in search of a standardized tool for supporting claims of absence of malaria transmission. For comparison, a research-based (RB) ELISA protocol was performed alongside the commercial kits. Results: The commercial kits were first compared using serum samples from known malaria-unexposed individuals (n = 223) and Toxoplasma-infected individuals (n = 191) to assess specificity and cross-reactivity against non-malaria infections. In addition, 134 samples from ?10-year-olds collected in a hyperendemic region in the Gambia in the early 1990s were used to assess sensitivity. Three out of five kits showed high sensitivity (90-92%), high specificity (98-99%), low cross-reactivity (0-3%) and were considered user-friendly (Trinity Biotech, newbio and NovaTec). Two of these kits (Trinity Biotech and NovaTec) were taken forward for epidemiological evaluation and results were compared to those using the RB-ELISA. Samples from two pre-elimination settings (Praia, Cape Verde; n = 1,396, and Bataan, the Philippines; n = 1,824) were tested. Serological results from both the Trinity Biotech kit and the RB-ELISA concurred with recent passively detected case counts in both settings. Results from the Trinity Biotech kit reflected a significant decrease in the number of reported cases in Bataan in the 1990s better than the RB-ELISA. Results from the NovaTec kit did not reflect transmission patterns in either setting. Conclusion: The Trinity Biotech commercial ELISA kit was considered reliable for epidemiological use and accurately described transmission patterns in two (previously) malaria endemic settings. The use of this simple and standardized serological tool may aid national control and elimination programs by confirming that regions are free from malaria.

SUBMITTER: van den Hoogen LL

PROVIDER: S-EPMC7509087 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comparison of Commercial ELISA Kits to Confirm the Absence of Transmission in Malaria Elimination Settings.

van den Hoogen Lotus L LL Bareng Paolo P Alves Joana J Reyes Ralph R Macalinao Malou M Rodrigues Júlio M JM Fernandes José M JM Goméz Lara F LF Hall Tom T Singh Susheel K SK Singh Susheel K SK Fornace Kimberly K Luchavez Jennifer J Kitchen Alan A Chiodini Peter P Espino Fe F Tetteh Kevin K A KKA Stresman Gillian G Sepúlveda Nuno N Drakeley Chris C

Frontiers in public health 20200909

<b>Background:</b> Antimalarial antibody measurements are useful because they reflect historical and recent exposure to malaria. As such, they may provide additional information to assess ongoing transmission in low endemic or pre-elimination settings where cases are rare. In addition, the absence of antibody responses in certain individuals can indicate the cessation of transmission. Commercial malaria enzyme-linked immunosorbent assays (ELISA) detect antimalarial antibodies and are commonly us ...[more]

PMID: 33014975

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Project description:BackgroundTransfusion with Plasmodium-infected blood represents a risk for malaria transmission, a rare but severe event. Several non-endemic countries implement a strategy for the screening of candidate blood donors including questionnaire for the identification of at-risk subjects and laboratory testing of blood samples, often serology-based, with temporary deferral from donation for individuals with a positive result. In Italy, the most recent legislation, issued in November 2015, introduced the use of serological tests for the detection of anti-Plasmodium antibodies.MethodsIn the absence of a gold standard for malaria serology, the aim of this work was to evaluate five commercial ELISA kits, and to determine their accuracy (sensitivity and specificity) in comparison to immuno-fluorescence antibody test (IFAT), and their agreement (concordance of results). Serum samples from malaria patients or from subjects with malaria history (N = 64), malaria naïve patients with other parasitic infections (N = 15), malaria naïve blood donors (N = 8) and malaria exposed candidate blood donors (N = 36) were tested.ResultsThe specificity of all ELISA kits was 100%, while sensitivity ranged between 53 and 64% when compared to IFAT on malaria patients samples. When tested on candidate blood donors' samples, ELISA kits showed highly variable agreement (42-94%) raising the possibility that the same individual could be included or excluded from donation depending on the test in use by the transfusion centre.ConclusionsThese preliminary results indicate how the lack of a gold standard for malaria serology must be taken into account in the application and future revision of current legislation. There is need of developing more sensitive serological assays. Moreover, the adoption of a unique serological test at national level is recommended, as well as the development of screening algorithms based on multiple laboratory tests, including molecular assays.

Project description:BACKGROUND: In malaria endemic areas, continuous exposure to Plasmodium parasites leads to asymptomatic carriers that provide a fundamental reservoir of parasites, contributing to the persistence of malaria transmission. Therefore, in the present investigation, the presence and prevalence of malaria asymptomatic cases were determined to evaluate the reservoir of infection in two malaria endemic areas with a previous history of malaria transmission in the south of Iran, Bashagard and Ghale-Ganj districts of Hormozgan and Kerman provinces, respectively, where malaria transmission has been drastically reduced in the recent years. METHODS: The population samples (n = 500 from each of the studied areas) were randomly collected from non-febrile, long-term residing, aged two to over 60 years, during 20092010. Three identical surveys were carried out in both study areas and in each phase all the consent participants were interviewed and clinically examined. In all, three surveys to detect hidden parasite reservoirs (both Plasmodium falciparum and Plasmodium vivax), thick and thin blood smears and a highly sensitive nested-PCR were applied. In addition, the sero-prevalence survey for detecting malaria exposure was done by using a serological marker. RESULTS: In this study, P. vivax and P. falciparum parasites were not detected by light microscopy and nested-PCR assay in all three surveys of samples. Antibody responses against P. vivax and P. falciparum were detected in 1% and 0.2% of the total examined individuals, respectively, in Bashagard district. Regarding to Ghale-Ganj district, about 0.9% of the individuals had IgG -specific antibody to P. vivax at the first and second surveys, but at the third survey 0.45% of the participants had positive antibody to P. vivax parasite. IgG -specific antibody to P. falciparum was detected in 0.2% of the participants at the first and follow-up surveys. The overall regional differences were not statistically significant (P > 0.05). CONCLUSION: Taken together, the lack of asymptomatic carrier with the evidence of extremely low sero-positive to both P. vivax and P. falciparum among examined individuals supported the limited recent transmission in the studied areas and, therefore, these parts of Iran have potential to eliminate the disease in the next few years. However, continued follow up and action are still needed in both studied areas and also in their neighbouring province, Sistan and Baluchistan, which has the highest reported cases of malaria in Iran and also, has the largest border line with Afghanistan and Pakistan, with no elimination activities. This data will provide useful information for managing elimination activities in Iran.

Project description:BackgroundReactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages.MethodsCommunities in Southern Province, Zambia, where elimination operations are currently underway, were used as representatives of three archetypes of malaria transmission: low-transmission, high household density; high-transmission, low household density; and high-transmission, high household density. Transmission at the spatially-connected household level was simulated with a dynamical model of malaria transmission, and local variation in vectorial capacity and intervention coverage were parameterized according to data collected from the area. Various potential intervention packages were imposed on each of the archetypical settings and the resulting likelihoods of elimination by the end of 2020 were compared.ResultsSimulations predict that success of elimination campaigns in both low- and high-transmission areas is strongly dependent on stemming the flow of imported infections, underscoring the need for regional-scale strategies capable of reducing transmission concurrently across many connected areas. In historically low-transmission areas, treatment of clinical malaria should form the cornerstone of elimination operations, as most malaria infections in these areas are symptomatic and onward transmission would be mitigated through health system strengthening; reactive case detection has minimal impact in these settings. In historically high-transmission areas, vector control and case management are crucial for limiting outbreak size, and the asymptomatic reservoir must be addressed through reactive case detection or mass drug campaigns.ConclusionsReactive case detection is recommended only for settings where transmission has recently been reduced rather than all low-transmission settings. This is demonstrated in a modelling framework with strong out-of-sample accuracy across a range of transmission settings while including methodologies for understanding the most resource-effective allocations of health workers. This approach generalizes to providing a platform for planning rational scale-up of health systems based on locally-optimized impact according to simplified stratification.

Project description:Background Targeted research on residual malaria transmission is important to improve strategies in settings pursuing elimination, where transmission reductions prove challenging. This study aimed to detect and characterize spatial heterogeneity and factors associated with Plasmodium falciparum infections and exposure, P. falciparum apical membrane antigen 1 (PfAMA1) antibody (Ab) response, in the Central Highlands of Madagascar (CHL). Methods From May to July 2014, a cross-sectional school-based survey was carried out in 182 fokontany (villages) within 7 health districts of the CHL. Rapid diagnostic tests (RDTs) and a bead-based immunoassay including PfAMA1 antigen biomarker were used to estimate malaria prevalence and seroprevalence, respectively. Local Moran’s I index was used to detect spatial “hotspots”. Remotely sensed environmental data—temperature, vegetation indices, land covers, and elevation—were used in multivariable mixed-effects logistic regression models to characterize factors associated with malaria infection and cumulative exposure. Results Among 6,293 school-children ages 2–14 years surveyed, RDT prevalence was low at 0.8% (95% CI 0.6–1.1%), while PfAMA1 Ab seroprevalence was 7.0% (95% CI 6.4–7.7%). Hotspots of PfAMA1 Ab seroprevalence were observed in two districts (Ankazobe and Mandoto). Seroprevalence increased for children living > 5 km from a health centre (adjusted odds ratio (OR) = 1.6, 95% CI 1.2–2.2), and for those experiencing a fever episode in the previous 2 weeks (OR 1.7, 95% CI 1.2–2.4), but decreased at higher elevation (for each 100-m increase, OR = 0.7, 95% CI 0.6–0.8). A clear age pattern was observed whereby children 9–10 years old had an OR of 1.8 (95% CI 1.2–2.4), children 11–12 years an OR of 3.7 (95% CI 2.8–5.0), and children 13–14 years an OR of 5.7 (95% CI 4.0–8.0) for seropositivity, compared with younger children (2–8 years). Conclusion The use of serology in this study provided a better understanding of malaria hotspots and associated factors, revealing a pattern of higher transmission linked to geographical barriers in health care access. The integration of antibody-assays into existing surveillance activities could improve exposure assessment, and may help to monitor the effectiveness of malaria control efforts and adapt elimination interventions. Supplementary Information The online version contains supplementary material available at 10.1186/s12936-022-04260-0.

Project description:BackgroundGene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa.MethodsUsing an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems-"classic" and "integral"-are evaluated. Various transmission regimes (low, moderate, and high-corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated.ResultsLocal elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80-90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80-90%.ConclusionA single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.

Dataset Information

Comparison of Commercial ELISA Kits to Confirm the Absence of Transmission in Malaria Elimination Settings.

Publications

Comparison of Commercial ELISA Kits to Confirm the Absence of Transmission in Malaria Elimination Settings.

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