scholarly journals Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand

2021 ◽  
Author(s):  
Zoe Shih-Jung Liu ◽  
Jetsumon Sattabongkot ◽  
Michael White ◽  
Sadudee Chotirat ◽  
Chalermpon Kumpitak ◽  
...  

Plasmodium vivax is the dominant Plasmodium spp. causing the disease malaria in low-transmission regions outside of Africa. These regions often feature high proportions of asymptomatic patients with sub-microscopic parasitaemia and relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. However, previous work has failed to address the presence and maintenance of such antibody responses to P. vivax particularly in low-transmission regions. We followed 34 patients in western Thailand after symptomatic P. vivax infections to monitor antibody kinetics over 9 months, during which no recurrent infections occurred. We assessed total IgG, IgG subclass and IgM levels to up to 52 P. vivax proteins every 2-4 weeks using a multiplexed Luminex assay, and identified protein-specific variation in antibody longevity. Generally, an increase in antibody level was observed within 1-week post symptomatic infection, followed by an exponential decay of different rates. We observed mostly IgG1 dominance and IgG3 sub-dominance in this population. IgM responses followed similar kinetic patterns to IgG, with some proteins unexpectedly inducing long-lived IgM responses. We also monitored antibody responses against 27 IgG-immunogenic antigens in 30 asymptomatic individuals from a similar region. Our results demonstrate that most antigens induced robust and long-lived total IgG responses following asymptomatic infections in the absence of (detected) boosting infections. Our work provides new insights into the development and maintenance of naturally acquired immunity to P. vivax and will guide the potential use of serology to indicate immune status and/or identify populations at risk.

2020 ◽  
Author(s):  
Jason Rosado ◽  
Michael T. White ◽  
Rhea J. Longley ◽  
Wuelton Monteiro ◽  
Marcus Lacerda ◽  
...  

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.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Majid Mahmood ◽  
Noor-ul-ain Ilyas ◽  
Muhammad Faraz Khan ◽  
Muhammad Naseem Hasrat ◽  
Nicholas Richwagen

Abstract Background The COVID-19 pandemic is a catastrophic global phenomenon, affecting human life in a way unseen since the 1918 influenza pandemic. Effective management of this threat requires halting transmission, a strategy requiring accurate knowledge of SARS-CoV-2 transmission patterns. Methods This was a retrospective contact study aiming to estimate the transmission rate of COVID-19 by tracing contacts in symptomatic, pre-symptomatic, and asymptomatic patients. History of patients’ contacts during 24 h before appearance of symptoms or infection confirmation was traced for disease transmission. Results Overall, a total of 201 COVID-19 patients had contact with 7168 people in 24 h with an average of 35.66 contacts per patient, ranging from a minimum of 4 to maximum of 87 contacts (meetings). Out of 7168 persons met, infection was detected in 64 (0.89%). For the 155 symptomatic patients, a total of 5611 contacted persons were traced before appearance of symptoms (pre-symptomatic) in last 24 h with an average of 36.20 meetings per patient. The infection was transmitted in 63 (1.12%) people with 5548 (98.88%) remaining uninfected. Out of the 63 transmissions, 62 (98.4%) were traced within 6 h before symptom onset, while only 1 was identified in the 6–12 h timeframe before symptoms. A total of 1557 persons were traced having meeting/contacts with asymptomatic cases in last 24 h before infection confirmation. Out of these 1557 persons, only 1 was found to be infected and the infection rate was calculated to be 0.06%. Statistically, the transmission rate by pre-symptomatic patients was found to be significantly higher than the transmission rate by asymptomatic individuals (P < 0.05). Conclusion In the studied population, the risk of pre-symptomatic and asymptomatic transmission of COVID-19 was low, with transmission risks of 1.12% and 0.06% respectively. Pre-symptomatic infection becomes very rare in contacts made longer than 6 h before onset of symptoms. The infection transmission is traced as long as about 9 h before the appearance of clear symptoms in the patients, but the incidence rate was as low as about 0.02% of the total contacts in that period.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allison N. Grossberg ◽  
Lilia A. Koza ◽  
Aurélie Ledreux ◽  
Chad Prusmack ◽  
Hari Krishnan Krishnamurthy ◽  
...  

AbstractThe COVID-19 pandemic affects more than 81 million people worldwide with over 1.7 million deaths. As the population returns to work, it is critical to develop tests that reliably detect SARS-CoV-2-specific antibodies. Here we present results from a multiplex serology test for assessing the antibody responses to COVID-19. In an initial large cohort, this test shows greater than 99% agreement with COVID-19 PCR test. In a second outpatient cohort consisting of adults and children in Colorado, the IgG responses are more robust in positive/symptomatic participants than in positive/asymptomatic participants, the IgM responses in symptomatic participants are transient and largely fall below the detection limit 30 days after symptom onset, and the levels of IgA against SARS-CoV-2 receptor binding domain are significantly increased in participants with moderate-to-severe symptoms compared to those with mild-to-moderate symptoms or asymptomatic individuals. Our results thus provide insight into serology profiling and the immune response to COVID-19.


2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Rhea J. Longley ◽  
Camila T. França ◽  
Michael T. White ◽  
Chalermpon Kumpitak ◽  
Patiwat Sa-angchai ◽  
...  

2015 ◽  
Vol 23 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Rhea J. Longley ◽  
Arturo Reyes-Sandoval ◽  
Eduardo Montoya-Díaz ◽  
Susanna Dunachie ◽  
Chalermpon Kumpitak ◽  
...  

ABSTRACTPlasmodium vivaxis now the dominantPlasmodiumspecies causing malaria in Thailand, yet little is known about naturally acquired immune responses to this parasite in this low-transmission region. The preerythrocytic stage of theP. vivaxlife cycle is considered an excellent target for a malaria vaccine, and in this study, we assessed the stability of the seropositivity and the magnitude of IgG responses to three different preerythrocyticP. vivaxproteins in two groups of adults from a region of western Thailand where malaria is endemic. These individuals were enrolled in a yearlong cohort study, which comprised one group that remainedP. vivaxfree (by quantitative PCR [qPCR] detection,n= 31) and another that experienced two or more blood-stageP. vivaxinfections during the year of follow up (n= 31). Despite overall low levels of seropositivity, IgG positivity and magnitude were long-lived over the 1-year period in the absence of qPCR-detectable blood-stageP. vivaxinfections. In contrast, in the adults with two or moreP. vivaxinfections during the year, IgG positivity was maintained, but the magnitude of the response toP. vivaxcircumsporozoite protein 210 (CSP210) decreased over time. These findings demonstrate that long-term humoral immunity can develop in low-transmission regions.


2021 ◽  
Vol 15 (2) ◽  
pp. e0009165
Author(s):  
Jason Rosado ◽  
Michael T. White ◽  
Rhea J. Longley ◽  
Marcus Lacerda ◽  
Wuelton Monteiro ◽  
...  

Background Antibody responses as serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors that 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. Methodology We validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using a multiplex 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 previous infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the previous 9 months. Principal findings Antibody titers were associated with age, the number of blood-stage infections, and time since previous P. vivax infection in all three study sites. The association between antibody titers and time since previous P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the higher transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance for 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. Conclusions In low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In higher transmission settings, the accuracy of this approach diminishes substantially. We recommend using P. vivax SEMs in low transmission settings pursuing malaria elimination, but they are likely to be less effective in high transmission settings focused on malaria control.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Chee Hong Wong ◽  
Chew Yee Ngan ◽  
Rachel L. Goldfeder ◽  
Jennifer Idol ◽  
Chris Kuhlberg ◽  
...  

Abstract Background It is estimated that up to 80% of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic and asymptomatic patients can still effectively transmit the virus and cause disease. While much of the effort has been placed on decoding single nucleotide variation in SARS-CoV-2 genomes, considerably less is known about their transcript variation and any correlation with clinical severity in human hosts, as defined here by the presence or absence of symptoms. Methods To assess viral genomic signatures of disease severity, we conducted a systematic characterization of SARS-CoV-2 transcripts and genetic variants in 81 clinical specimens collected from symptomatic and asymptomatic individuals using multi-scale transcriptomic analyses including amplicon-seq, short-read metatranscriptome and long-read Iso-seq. Results Here we show a highly coordinated and consistent pattern of sgRNA expression from individuals with robust SARS-CoV-2 symptomatic infection and their expression is significantly repressed in the asymptomatic infections. We also observe widespread inter- and intra-patient variants in viral RNAs, known as quasispecies frequently found in many RNA viruses. We identify unique sets of deletions preferentially found primarily in symptomatic individuals, with many likely to confer changes in SARS-CoV-2 virulence and host responses. Moreover, these frequently occurring structural variants in SARS-CoV-2 genomes serve as a mechanism to further induce SARS-CoV-2 proteome complexity. Conclusions Our results indicate that differential sgRNA expression and structural mutational burden are highly correlated with the clinical severity of SARS-CoV-2 infection. Longitudinally monitoring sgRNA expression and structural diversity could further guide treatment responses, testing strategies, and vaccine development.


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