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Article ; Online: Previous Malaria Exposures and Immune Dysregulation: Developing Strategies To Improve Malaria Vaccine Efficacy in Young Children.

Dobbs, Katherine R / Atieli, Harrysone E / Valim, Clarissa / Beeson, James G

The American journal of tropical medicine and hygiene

2024 Volume 110, Issue 4, Page(s) 627–630

Abstract: After several decades in development, two malaria vaccines based on the same antigen and with very similar constructs and adjuvants, RTS,S/AS01 (RTS,S) and R21/Matrix-M (R21), were recommended by the WHO for widespread vaccination of children. These ... ...

Abstract	After several decades in development, two malaria vaccines based on the same antigen and with very similar constructs and adjuvants, RTS,S/AS01 (RTS,S) and R21/Matrix-M (R21), were recommended by the WHO for widespread vaccination of children. These vaccines are much-needed additions to malaria control programs that, when used in conjunction with other control measures, will help to accelerate reductions in malaria morbidity and mortality. Although R21 is not yet available, RTS,S is currently being integrated into routine vaccine schedules in some areas. However, the efficacy of RTS,S is partial, short-lived, and varies widely according to age and geographic location. It is not clear why RTS,S induces protection in some individuals and not others, what the immune mechanisms are that favor protective immunity with RTS,S, and how immune mechanisms are influenced by host and environmental factors. Several studies suggest that higher levels of previous malaria exposure negatively impact RTS,S clinical efficacy. In this article, we summarize data suggesting that previous malaria exposures negatively impact the efficacy of RTS,S and other malaria vaccine candidates. We highlight recent evidence suggesting that increasing malaria exposure impairs the generation of functional antibody responses to RTS,S. Finally, we discuss how investigation of clinical and immune factors associated with suboptimal responses to RTS,S can be used to develop strategies to optimize RTS,S, which will remain relevant to R21 and next-generation vaccines.
MeSH term(s)	Child ; Humans ; Infant ; Child, Preschool ; Malaria Vaccines ; Malaria, Falciparum/prevention & control ; Malaria/prevention & control ; Treatment Outcome ; Vaccination ; Plasmodium falciparum
Chemical Substances	Malaria Vaccines
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.23-0696
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Article ; Online: Correction to: Enhancing SVM for survival data using local invariances and weighting.

Sanz, Hector / Reverter, Ferran / Valim, Clarissa

BMC bioinformatics

2020 Volume 21, Issue 1, Page(s) 371

Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

Abstract	An amendment to this paper has been published and can be accessed via the original article.
Language	English
Publishing date	2020-08-27
Publishing country	England
Document type	Published Erratum
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-020-03558-7
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Article ; Online: Enhancing SVM for survival data using local invariances and weighting.

Sanz, Hector / Reverter, Ferran / Valim, Clarissa

BMC bioinformatics

2020 Volume 21, Issue 1, Page(s) 193

Abstract: Background: The necessity to analyze medium-throughput data in epidemiological studies with small sample size, particularly when studying biomedical data may hinder the use of classical statistical methods. Support vector machines (SVM) models can be ... ...

Abstract	Background: The necessity to analyze medium-throughput data in epidemiological studies with small sample size, particularly when studying biomedical data may hinder the use of classical statistical methods. Support vector machines (SVM) models can be successfully applied in this setting because they are a powerful tool to analyze data with large number of predictors and limited sample size, especially when handling binary outcomes. However, biomedical research often involves analysis of time-to-event outcomes and has to account for censoring. Methods to handle censored data in the SVM framework can be divided into two classes: those based on support vector regression (SVR) and those based on binary classification. Methods based on SVR seem to be suboptimal to handle sparse data and yield results comparable to Cox proportional hazards model and kernel Cox regression. The limited work dedicated to assess methods based on of SVM for binary classification has been based on SVM learning using privileged information and SVM with uncertain classes. Results: This paper proposes alternative methods and extensions within the binary classification framework, specifically, a conditional survival approach for weighting censored observations and a semi-supervised SVM with local invariances. Using simulation studies and some real datasets, we evaluate those two methods and compare them with a weighted SVM model, SVM extensions found in the literature, kernel Cox regression and Cox model. Conclusions: Our proposed methods perform generally better under a wide variety of realistic scenarios about the structure of biomedical data. Specifically, the local invariances method using the conditional survival approach is the most robust method under different scenarios and is a good approach to consider as an alternative to other time-to-event methods. When analysing real data is a method to be considered and recommended since outperforms other methods in proportional and non-proportional scenarios and sparse data, which is something usual in biomedical data and biomarkers analysis.
MeSH term(s)	Humans ; Proportional Hazards Models ; Support Vector Machine ; Survival Analysis
Language	English
Publishing date	2020-05-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-020-3481-2
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Article ; Online: Correction to

Hector Sanz / Ferran Reverter / Clarissa Valim

BMC Bioinformatics, Vol 21, Iss 1, Pp 1-

Enhancing SVM for survival data using local invariances and weighting

2020 Volume 2

Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

Abstract	An amendment to this paper has been published and can be accessed via the original article.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enhancing SVM for survival data using local invariances and weighting

Hector Sanz / Ferran Reverter / Clarissa Valim

BMC Bioinformatics, Vol 21, Iss 1, Pp 1-

2020 Volume 20

Abstract: Abstract Background The necessity to analyze medium-throughput data in epidemiological studies with small sample size, particularly when studying biomedical data may hinder the use of classical statistical methods. Support vector machines (SVM) models ... ...

Abstract	Abstract Background The necessity to analyze medium-throughput data in epidemiological studies with small sample size, particularly when studying biomedical data may hinder the use of classical statistical methods. Support vector machines (SVM) models can be successfully applied in this setting because they are a powerful tool to analyze data with large number of predictors and limited sample size, especially when handling binary outcomes. However, biomedical research often involves analysis of time-to-event outcomes and has to account for censoring. Methods to handle censored data in the SVM framework can be divided into two classes: those based on support vector regression (SVR) and those based on binary classification. Methods based on SVR seem to be suboptimal to handle sparse data and yield results comparable to Cox proportional hazards model and kernel Cox regression. The limited work dedicated to assess methods based on of SVM for binary classification has been based on SVM learning using privileged information and SVM with uncertain classes. Results This paper proposes alternative methods and extensions within the binary classification framework, specifically, a conditional survival approach for weighting censored observations and a semi-supervised SVM with local invariances. Using simulation studies and some real datasets, we evaluate those two methods and compare them with a weighted SVM model, SVM extensions found in the literature, kernel Cox regression and Cox model. Conclusions Our proposed methods perform generally better under a wide variety of realistic scenarios about the structure of biomedical data. Specifically, the local invariances method using the conditional survival approach is the most robust method under different scenarios and is a good approach to consider as an alternative to other time-to-event methods. When analysing real data is a method to be considered and recommended since outperforms other methods in proportional and non-proportional scenarios and sparse data, which is ...
Keywords	Support vector machines ; Survival analysis ; Kernel ; Classification ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The RTS,S malaria vaccine: Current impact and foundation for the future.

Beeson, James G / Kurtovic, Liriye / Valim, Clarissa / Asante, Kwaku Poku / Boyle, Michelle J / Mathanga, Don / Dobano, Carlota / Moncunill, Gemma

Science translational medicine

2022 Volume 14, Issue 671, Page(s) eabo6646

Abstract: The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of vaccine protection and longevity, implementation considerations, and future research ...

Abstract	The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of vaccine protection and longevity, implementation considerations, and future research needed to increase the vaccine's health impact, including vaccine modifications for higher efficacy and longevity of protection.
MeSH term(s)	Humans ; Infant ; Child ; Malaria Vaccines/therapeutic use ; Malaria/prevention & control ; Malaria, Falciparum/prevention & control ; Plasmodium falciparum
Chemical Substances	Malaria Vaccines ; RTS malaria vaccine
Language	English
Publishing date	2022-11-16
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abo6646
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Article ; Online: Genotyping of Anopheles mosquito blood meals reveals nonrandom human host selection: implications for human-to-mosquito Plasmodium falciparum transmission.

Mbewe, Rex B / Keven, John B / Mangani, Charles / Wilson, Mark L / Mzilahowa, Themba / Mathanga, Don P / Valim, Clarissa / Laufer, Miriam K / Walker, Edward D / Cohee, Lauren M

Malaria journal

2023 Volume 22, Issue 1, Page(s) 115

Abstract: Background: Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human- ... ...

Abstract	Background: Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission. Methods: In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals. Results: Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31-75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6-15 years old). Conclusions: The results support the hypothesis that humans aged 6-15 years are the most important demographic group contributing to the transmission of P. falciparum to the Anopheles mosquito vectors. This conclusion suggests that malaria control and prevention programmes should enhance efforts targeting school-age children and males.
MeSH term(s)	Adolescent ; Adult ; Aged ; Animals ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Anopheles/parasitology ; DNA/blood ; Genotype ; Malaria/blood ; Malaria/parasitology ; Malaria/prevention & control ; Malaria/transmission ; Malaria, Falciparum/blood ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/prevention & control ; Malaria, Falciparum/transmission ; Meals ; Mosquito Vectors/parasitology ; Plasmodium falciparum/genetics ; Blood/parasitology ; Host-Seeking Behavior ; Malawi
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-04-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-023-04541-2
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Article ; Online: Genotyping of Anopheles mosquito blood meals reveals nonrandom human host selection

Rex B. Mbewe / John B. Keven / Charles Mangani / Mark L. Wilson / Themba Mzilahowa / Don P. Mathanga / Clarissa Valim / Miriam K. Laufer / Edward D. Walker / Lauren M. Cohee

Malaria Journal, Vol 22, Iss 1, Pp 1-

implications for human-to-mosquito Plasmodium falciparum transmission

2023 Volume 11

Abstract: Abstract Background Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to ... ...

Abstract	Abstract Background Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission. Methods In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals. Results Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31–75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6–15 years old). Conclusions The results support the ...
Keywords	Malaria parasite transmission ; Microsatellites ; Vector-borne disease prevention ; Age-specific risk ; Human reservoirs of infection ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Subject code	572
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Challenges of acute febrile illness diagnosis in a national infectious diseases center in Rio de Janeiro: 16-year experience of syndromic surveillance.

Bressan, Clarisse da Silveira / Teixeira, Maria de Lourdes Benamor / Gouvêa, Maria Isabel Fragoso da Silveira / de Pina-Costa, Anielle / Santos, Heloísa Ferreira Pinto / Calvet, Guilherme Amaral / Lupi, Otilia / Siqueira, Andre Machado / Valls-de-Souza, Rogério / Valim, Clarissa / Brasil, Patrícia

PLoS neglected tropical diseases

2023 Volume 17, Issue 4, Page(s) e0011232

Abstract: Introduction: Acute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. ... ...

Abstract	Introduction: Acute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. Understanding the distribution of causes of AFI can improve patient outcomes. This study aims to describe the most common etiologies diagnosed over a 16-years period in a national reference center for tropical diseases in a large urban center in Rio de Janeiro, Brazil. Methods: From August 2004-December 2019, 3591 patients > 12 years old, with AFI and/or rash were eligible. Complementary exams for etiological investigation were requested using syndromic classification as a decision guide. Results. Among the 3591 patients included, endemic arboviruses such as chikungunya (21%), dengue (15%) and zika (6%) were the most common laboratory-confirmed diagnosis, together with travel-related malaria (11%). Clinical presumptive diagnosis lacked sensitivity for emerging diseases such as zika (31%). Rickettsia disease and leptospirosis were rarely investigated and an infrequent finding when based purely on clinical features. Respiratory symptoms increased the odds for the diagnostic remaining inconclusive. Conclusions: Numerous patients did not have a conclusive etiologic diagnosis. Since syndromic classification used for standardization of etiological investigation and presumptive clinical diagnosis had moderate accuracy, it is necessary to incorporate new diagnostic technologies to improve diagnostic accuracy and surveillance capacity.
MeSH term(s)	Humans ; Child ; Sentinel Surveillance ; Travel ; Brazil/epidemiology ; Travel-Related Illness ; Communicable Diseases ; Zika Virus Infection/diagnosis ; Zika Virus Infection/epidemiology ; Zika Virus ; Dengue/diagnosis ; Dengue/epidemiology
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0011232
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Article ; Online: Challenges of acute febrile illness diagnosis in a national infectious diseases center in Rio de Janeiro

Clarisse da Silveira Bressan / Maria de Lourdes Benamor Teixeira / Maria Isabel Fragoso da Silveira Gouvêa / Anielle de Pina-Costa / Heloísa Ferreira Pinto Santos / Guilherme Amaral Calvet / Otilia Lupi / Andre Machado Siqueira / Rogério Valls-de-Souza / Clarissa Valim / Patrícia Brasil

PLoS Neglected Tropical Diseases, Vol 17, Iss 4, p e

16-year experience of syndromic surveillance.

2023 Volume 0011232

Abstract: Introduction Acute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. ... ...

Abstract	Introduction Acute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. Understanding the distribution of causes of AFI can improve patient outcomes. This study aims to describe the most common etiologies diagnosed over a 16-years period in a national reference center for tropical diseases in a large urban center in Rio de Janeiro, Brazil. Methods From August 2004-December 2019, 3591 patients > 12 years old, with AFI and/or rash were eligible. Complementary exams for etiological investigation were requested using syndromic classification as a decision guide. Results. Among the 3591 patients included, endemic arboviruses such as chikungunya (21%), dengue (15%) and zika (6%) were the most common laboratory-confirmed diagnosis, together with travel-related malaria (11%). Clinical presumptive diagnosis lacked sensitivity for emerging diseases such as zika (31%). Rickettsia disease and leptospirosis were rarely investigated and an infrequent finding when based purely on clinical features. Respiratory symptoms increased the odds for the diagnostic remaining inconclusive. Conclusions Numerous patients did not have a conclusive etiologic diagnosis. Since syndromic classification used for standardization of etiological investigation and presumptive clinical diagnosis had moderate accuracy, it is necessary to incorporate new diagnostic technologies to improve diagnostic accuracy and surveillance capacity.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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