scholarly journals Distinct Antibody Signatures Associated with Different Malaria Transmission Intensities in Zambia and Zimbabwe

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Tamaki Kobayashi ◽  
Aarti Jain ◽  
Li Liang ◽  
Joshua M. Obiero ◽  
Harry Hamapumbu ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Control ◽  
Protein Microarray ◽  
Small Sample ◽  
Antibody Responses ◽  
Transmission Intensity ◽  
Community Based ◽  
Content Type ◽  
Recent Exposure ◽  
Accurate Picture

ABSTRACT Antibodies to Plasmodium falciparum are specific biomarkers that can be used to monitor parasite exposure over broader time frames than microscopy, rapid diagnostic tests, or molecular assays. Consequently, seroprevalence surveys can assist with monitoring the impact of malaria control interventions, particularly in the final stages of elimination, when parasite incidence is low. The protein array format to measure antibodies to diverse P. falciparum antigens requires only small sample volumes and is high throughput, permitting the monitoring of malaria transmission on large spatial and temporal scales. We expanded the use of a protein microarray to assess malaria transmission in settings beyond those with a low malaria incidence. Antibody responses in children and adults were profiled, using a P. falciparum protein microarray, through community-based surveys in three areas in Zambia and Zimbabwe at different stages of malaria control and elimination. These three epidemiological settings had distinct serological profiles reflective of their malaria transmission histories. While there was little correlation between transmission intensity and antibody signals (magnitude or breadth) in adults, there was a clear correlation in children younger than 5 years of age. Antibodies in adults appeared to be durable even in the absence of significant recent transmission, whereas antibodies in children provided a more accurate picture of recent levels of transmission intensity. Seroprevalence studies in children could provide a valuable marker of progress toward malaria elimination. IMPORTANCE As malaria approaches elimination in many areas of the world, monitoring the effect of control measures becomes more important but challenging. Low-level infections may go undetected by conventional tests that depend on parasitemia, particularly in immune individuals, who typically show no symptoms of malaria. In contrast, antibodies persist after parasitemia and may provide a more accurate picture of recent exposure. Only a few parasite antigens—mainly vaccine candidates—have been evaluated in seroepidemiological studies. We examined antibody responses to 500 different malaria proteins in blood samples collected through community-based surveillance from areas with low, medium, and high malaria transmission intensities. The breadth of the antibody responses in adults was broad in all three settings and was a poor correlate of recent exposure. In contrast, children represented a better sentinel population for monitoring recent malaria transmission. These data will help inform the use of multiplex serology for malaria surveillance.

scholarly journals Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

2020 ◽  
Vol 5 ◽  
pp. 136
Author(s):  
Tony I. Isebe ◽  
Joel L. Bargul ◽  
Bonface M. Gichuki ◽  
James M. Njunge ◽  
James Tuju ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
The Gambia ◽  
Antibody Responses ◽  
Transmission Intensity ◽  
Parasite Development ◽  
Natural Immunity ◽  
Malaria Transmission Intensity ◽  
Transmission Region ◽  
Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

scholarly journals Malaria Transmission, Infection, and Disease at Three Sites with Varied Transmission Intensity in Uganda: Implications for Malaria Control

2015 ◽  
Vol 92 (5) ◽  
pp. 903-912 ◽  
Author(s):  
Moses R. Kamya ◽  
Maxwell Kilama ◽  
Steve W. Lindsay ◽  
Bryan Greenhouse ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Control ◽  
Transmission Intensity

scholarly journals Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

2021 ◽  
Vol 5 ◽  
pp. 136
Author(s):  
Tony I. Isebe ◽  
Joel L. Bargul ◽  
Bonface M. Gichuki ◽  
James M. Njunge ◽  
James Tuju ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Negative Correlation ◽  
The Gambia ◽  
Antibody Responses ◽  
Transmission Intensity ◽  
Parasite Development ◽  
Malaria Transmission Intensity ◽  
Transmission Region ◽  
Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in Gambia, compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses indicate negative correlation between antibody levels and malaria transmission intensity for Pf3D7_1102500 and Pf3D7_1401600. We report a correlation in antibody responses between schizont and gametocyte extract, but this is not statistically significant (cor=0.102, p=0.2851, CI=95%) and, Pf3D7_0532400 (cor=0.11, p=0.249, CI=95%) and Pf3D7_1401600 (cor=0.02, p=0.7968, CI=95%). We report a negative correlation in antibody responses between schizont and Pf3D7_1102500 (cor=-0.008, p=0.9348, CI=95%). There is a correlation between gametocyte extract and Pf3D7_1401600 (cor=-0.0402, p=0.6735, CI=95%), Pf3D7_1102500 (cor=0.0758, p=0.4271, CI=95%) and Pf3D7_0532400 (cor=0.155, p=0.1028, CI=95%). Acquisition of anti-PHIST antibodies correlates with exposure to malaria for Pf3D7_0532400 (p=0.009) but not Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels which do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore their potential as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

scholarly journals Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections

2020 ◽  
Author(s):  
Jason Rosado ◽  
Michael T. White ◽  
Rhea J. Longley ◽  
Wuelton Monteiro ◽  
Marcus Lacerda ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Antibody Responses ◽  
Blood Stage ◽  
Transmission Intensity ◽  
Low Transmission ◽  
Recent Exposure ◽  
High Transmission ◽  
Antibody Titers

AbstractBackgroundAntibody responses to serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors which affect antibody responses in naturally infected people from endemic settings. To address this question, we studied IgG responses to novel serological exposure markers (SEMs) of P. vivax in three settings with different transmission intensity.MethodologyWe validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using the Luminex® platform and compared results to data from cohorts in Thailand and Brazil. Linear regression models were used to characterize the association between antibody responses and age, the number of detected blood-stage infections during follow-up, and time since the last infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the last 9 months.Principal findingsAntibody titers were associated with age, the number of blood-stage infections, and time since last P. vivax infection in all three study sites. The association between antibody titers and time since last P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the high transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance of classifying recent exposure in all sites, with area under the ROC curve (AUC) = 0.83 in Thailand, AUC = 0.79 in Brazil, and AUC = 0.68 in Peru.ConclusionsIn low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In high transmission settings, the accuracy of this approach diminishes substantially. We recommend the application of P. vivax SEMs for use in low transmission settings pursuing malaria elimination, but they appear less useful in high transmission settings focused on malaria control.Author SummaryPlasmodium vivax still poses a threat in many countries due to its ability to cause recurrent infections. Key to achieving the goal of malaria elimination is the ability to quickly detect and treat carriers of relapsing parasites. Failing to identify this transmission reservoir will hinder progress towards malaria elimination. Recently, novel serological markers of recent exposure to P. vivax (SEM) have been developed and validated in low transmission settings. It is still poorly understood what factors affect the antibody response to these markers when evaluated in contrasting endemic contexts. To determine the factors that influence the antibody response to SEM, we compare the antibody levels in three sites with different transmission intensity: Thailand (low), Brazil (moderate) and Peru (high). In this study, we found that transmission intensity plays a key role in the acquisition of the antibody repertoire to P. vivax. In highly endemic sites, the immunological memory resulting from a constant and sustained exposure will impact the performance of SEMs to detect individuals with recent exposure to P. vivax. In summary, SEMs that perform well in low transmission sites do not perform as well in high transmission regions.

scholarly journals Vector composition, abundance, biting patterns and malaria transmission intensity in Madang, Papua New Guinea: assessment after 7 years of an LLIN-based malaria control programme

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
John B. Keven ◽  
Michelle Katusele ◽  
Rebecca Vinit ◽  
Daniela Rodríguez-Rodríguez ◽  
Manuel W. Hetzel ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Papua New Guinea ◽  
Malaria Control ◽  
New Guinea ◽  
Control Programme ◽  
Transmission Intensity ◽  
Bed Nets ◽  
Malaria Control Programme ◽  
Malaria Transmission Intensity ◽  
Vector Abundance

Abstract Background A malaria control programme based on distribution of long-lasting insecticidal bed nets (LLINs) and artemisinin combination therapy began in Papua New Guinea in 2009. After implementation of the programme, substantial reductions in vector abundance and malaria transmission intensity occurred. The research reported here investigated whether these reductions remained after seven years of sustained effort. Methods All-night (18:00 to 06:00) mosquito collections were conducted using human landing catches and barrier screen methods in four villages of Madang Province between September 2016 and March 2017. Anopheles species identification and sporozoite infection with Plasmodium vivax and Plasmodium falciparum were determined with molecular methods. Vector composition was expressed as the relative proportion of different species in villages, and vector abundance was quantified as the number of mosquitoes per barrier screen-night and per person-night. Transmission intensity was quantified as the number of sporozoite-infective vector bites per person-night. Results Five Anopheles species were present, but vector composition varied greatly among villages. Anopheles koliensis, a strongly anthropophilic species was the most prevalent in Bulal, Matukar and Wasab villages, constituting 63.7–73.8% of all Anopheles, but in Megiar Anopheles farauti was the most prevalent species (97.6%). Vector abundance varied among villages (ranging from 2.8 to 72.3 Anopheles per screen-night and 2.2–31.1 Anopheles per person-night), and spatially within villages. Malaria transmission intensity varied among the villages, with values ranging from 0.03 to 0.5 infective Anopheles bites per person-night. Most (54.1–75.1%) of the Anopheles bites occurred outdoors, with a substantial proportion (25.5–50.8%) occurring before 22:00. Conclusion The estimates of vector abundance and transmission intensity in the current study were comparable to or higher than estimates in the same villages in 2010–2012, indicating impeded programme effectiveness. Outdoor and early biting behaviours of vectors are some of the likely explanatory factors. Heterogeneity in vector composition, abundance and distribution among and within villages challenge malaria control programmes and must be considered when planning them.

scholarly journals Novel serologic biomarkers provide accurate estimates of recentPlasmodium falciparumexposure for individuals and communities

2015 ◽  
Vol 112 (32) ◽  
pp. E4438-E4447 ◽  
Author(s):  
Danica A. Helb ◽  
Kevin K. A. Tetteh ◽  
Philip L. Felgner ◽  
Jeff Skinner ◽  
Alan Hubbard ◽  
...  
Keyword(s):  
Malaria Control ◽  
Malaria Incidence ◽  
Low Cost ◽  
Protein Microarray ◽  
Area Under The Curve ◽  
Antibody Responses ◽  
Selection Strategy ◽  
Small Subset ◽  
Cross Sectional ◽  
Epidemiologic Surveillance

Tools to reliably measurePlasmodium falciparum(Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals.Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates ofPfexposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856Pfantigens by protein microarray in 186 Ugandan children, for whom detailedPfexposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual’s recent exposure. Responses to three novelPfantigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86–0.93), whereas responses to six antigens accurately estimated an individual’s malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.

scholarly journals Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses

2016 ◽  
Vol 23 (8) ◽  
pp. 717-724 ◽  
Author(s):  
Mohan Natesan ◽  
Stig M. Jensen ◽  
Sarah L. Keasey ◽  
Teddy Kamata ◽  
Ana I. Kuehne ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protein Microarray ◽  
Disease Outbreaks ◽  
Cross Reactivity ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Diagnostic Methods ◽  
Virus Infections ◽  
Content Type ◽  
Reactive Antibody

ABSTRACTA detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections byMarburg marburgvirus(MARV) species were least cross-reactive, while those from survivors of infections bySudan virus(SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses.

Immunity to malaria in an era of declining malaria transmission

Parasitology ◽  
2016 ◽  
Vol 143 (2) ◽  
pp. 139-153 ◽  
Author(s):  
FREYA J. I. FOWKES ◽  
PHILIPPE BOEUF ◽  
JAMES G. BEESON
Keyword(s):  
Immune Responses ◽  
Malaria Transmission ◽  
Malaria Control ◽  
Malaria Elimination ◽  
Research Priorities ◽  
Repeated Exposure ◽  
Antibody Responses ◽  
Acquired Immunity ◽  
Effective Response ◽  
Malaria Exposure

SUMMARYWith increasing malaria control and goals of malaria elimination, many endemic areas are transitioning from high-to-low-to-no malaria transmission. Reductions in transmission will impact on the development of naturally acquired immunity to malaria, which develops after repeated exposure toPlasmodiumspp. However, it is currently unclear how declining transmission and malaria exposure will affect the development and maintenance of naturally acquired immunity. Here we review the key processes which underpin this knowledge; the amount ofPlasmodiumspp. exposure required to generate effective immune responses, the longevity of antibody responses and the ability to mount an effective response upon re-exposure through memory responses. Lastly we identify research priorities which will increase our understanding of how changing transmission will impact on malarial immunity.

scholarly journals Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs

2014 ◽  
Vol 21 (6) ◽  
pp. 838-846 ◽  
Author(s):  
Elisabeth Baum ◽  
Deborah A. Grosenbaugh ◽  
Alan G. Barbour
Keyword(s):  
Borrelia Burgdorferi ◽  
Binding Protein ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Domestic Dog ◽  
Beagle Dogs ◽  
Effective Population ◽  
Content Type ◽  
Immunogenic Proteins ◽  
Antibody Levels

ABSTRACTLyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agentBorrelia burgdorferi. While immunoassays based on individual subunits have mostly supplanted the use of whole-cell preparations for canine serology, only a limited number of informative antigens have been identified. To more broadly characterize the antibody responses toB. burgdorferiinfection and to assess the diversity of those responses in individual dogs, we examined sera from 32 adult colony-bred beagle dogs that had been experimentally infected withB. burgdorferithrough tick bites and compared those sera in a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encodedB. burgdorferiproteins, including 24 serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural-reservoir rodents; these proteins included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, the fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals studied here demonstrated diversity in antibody responses in measures of antibody levels and specificities for conserved proteins, such as DbpB, and polymorphic proteins, such as OspC.

scholarly journals Determination of Specific Antibody Responses to the Six Species of Ebola and Marburg Viruses by Multiplexed Protein Microarrays

2014 ◽  
Vol 21 (12) ◽  
pp. 1605-1612 ◽  
Author(s):  
Teddy Kamata ◽  
Mohan Natesan ◽  
Kelly Warfield ◽  
M. Javad Aman ◽  
Robert G. Ulrich
Keyword(s):  
Rhesus Macaques ◽  
Protein Microarray ◽  
Serum Antibody ◽  
Protein Microarrays ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Diagnostic Methods ◽  
Virion Protein ◽  
Content Type ◽  
Antibody Recognition

ABSTRACTInfectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e.,Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e.,Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed inEscherichia coliwas compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses.

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