Different Genetic Characteristics of Plasmodium falciparum Isolates Collected During Successive Clinical Malaria Episodes in Senegalese Children

Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

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Interferon-γ and Interleukin-10 Responses during Clinical Malaria Episodes in Infants Aged 0–2 Years Prenatally Exposed to Plasmodium falciparum: Tanzanian Birth Cohort

Journal of Tropical Medicine ◽

10.1155/2018/6847498 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Boniphace Sylvester ◽

Dinah B. Gasarasi ◽

Said Aboud ◽

Donath Tarimo ◽

Siriel Masawe ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Prenatal Exposure ◽

Geometric Mean ◽

Placental Malaria ◽

Clinical Malaria ◽

Interleukin 10 ◽

Interferon Γ ◽

Enzyme Linked Immunosorbent Assay ◽

Prenatally Exposed ◽

Malaria Episodes

Background. Infants born to mothers with placental malaria are prenatally exposed to Plasmodium falciparum antigens. However, the effect of that exposure to subsequent immune responses has not been fully elucidated. This study aimed at determining the effect of prenatal exposure to P. falciparum on Interleukin-10 and Interferon-γ responses during clinical malaria episodes in the first 24 months of life. Methods. This prospective cohort study involved 215 infants aged 0-2 years born to mothers with or without placental malaria. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of IL-10 and IFN-γ in infants and detect IgM in cord blood. Data were analyzed using SPSS version 20. Findings. Geometric mean for IFN-γ in exposed infants was 557.9 pg/ml (95% CI: 511.6-604.1) and in unexposed infants it was 634.4 pg/ml (95% CI: 618.2-668.5) (P=0.02). Mean IL-10 was 22.4 pg/ml (95% CI: 19.4-28.4) and 15.1 pg/ml (95%CI: 12.4-17.6), respectively (P=0.01). Conclusions. Prenatal exposure to P. falciparum antigens significantly affects IL-10 and IFN-γ responses during clinical malaria episodes in the first two years of life.

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Seasonal changes in the Plasmodium falciparum population in individuals and their relationship to clinical malaria: a longitudinal study in a Sudanese village

Parasitology ◽

10.1017/s0031182098002650 ◽

1998 ◽

Vol 116 (6) ◽

pp. 501-510 ◽

Cited By ~ 45

Author(s):

C. ROPER ◽

W. RICHARDSON ◽

I. M. ELHASSAN ◽

H. GIHA ◽

L. HVIID ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Clinical Malaria ◽

Dry Season ◽

Malaria Episode ◽

Allelic Polymorphism ◽

Cross Sectional ◽

Increased Risk ◽

Risk Of Disease ◽

Polymerase Chain ◽

Malaria Episodes

Residents of Daraweesh village in Sudan were monitored for Plasmodium falciparum infection and malaria morbidity in 3 malaria seasons from 1993 to 1996. Malaria parasites were detected microscopically and by polymerase chain reaction (PCR) in a series of cross-sectional surveys. PCR revealed submicroscopical infections during the dry season, particularly among individuals who had recovered from a malaria episode following successful drug treatment. Clinical and subclinical infections were contrasted by assaying for allelic polymorphism at 2 gene loci, MSP-1 and GLURP and 2 hypotheses examined with reference to these data: that clinical malaria is associated with infection with novel parasite genotypes not previously detected in that host, or alternatively, that clinical malaria episodes are associated with an increased number of clones in an infection. We detected more mixed infections among clinical isolates, but people carrying parasites during the dry season were not found to have an increased risk of disease in the following malaria season. There was a clear association of disease with the appearance of novel parasite genotypes.

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Genetic Diversity and Complexity of Plasmodium Falciparum Infections in the Microenvironment Among Siblings of the Same Household in North-central Nigeria

10.21203/rs.3.rs-30643/v1 ◽

2020 ◽

Author(s):

Segun Isaac Oyedeji ◽

Peter Usman Bassi ◽

Samuel Adeola Oyedeji ◽

Olusola Ojurongbe ◽

Henrietta Oluwatoyin Awobode

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Complex Mixture ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Clinical Malaria ◽

Genetic Characteristics ◽

North Central ◽

Allele Type ◽

Allele Specific

Abstract Background: Plasmodium falciparum parasites are known to exhibit extensive genetic diversity in areas of high transmission intensity and infected individuals in such communities often harbour several complex mixture of parasite clones with different genetic characteristics. However, in the microenvironment, the extent of genetic diversity of the P. falciparum parasites remain largely unknown. In this study therefore, we investigated the complexity of P. falciparum infections in households, among symptomatic siblings living under the same roof in North-central Nigeria.Methods: Children were enrolled into the study if they were at least two from a household and presented with symptoms of uncomplicated malaria. Clinical malaria was confirmed by light microscopy of Giemsa stained thick and thin blood films. Genomic DNA was isolated from blood spots on filter paper. Molecular characterization of P. falciparum isolates was done by allele-specific nested PCR of the highly polymorphic merozoite surface protein-2 (MSP-2) gene.Results: 93 children from 43 households were enrolled into this study. A total of 26 different MSP-2 alleles were identified from 215 fragments (range: 180-480bp). Majority of the isolates [65.6% (n=61)] were polyclonal infections consisting of 2-6 clones and were significantly more common with the FC27 allelic family (p = 0.036). The multiplicity of infection (MOI) per household ranged from 1.0 to 4.5 while the overall MOI in the study population was 2.31. The pattern of distribution of MSP-2 allele types among the households fell into two categories: households where both MSP-2 allele types (FC27 and 3D7) were present; and households where only one MSP-2 allele type (FC27 or 3D7) was present. Majority of the households [88.4% (n=38)], had both MSP-2 allele types but they were disproportionately distributed among the children while in a few households [11.6% (n=5)], all the children were infected with only one type of MSP-2 allele.Conclusion: Our findings showed that P. falciparum isolates exhibit remarkable degree of genetic diversity in the microenvironment and are composed mainly of multiclonal infections, which is an indication of a high ongoing parasite transmission. This suggests that the microenvironment is an important area of focus for malaria control interventions and for evaluating intervention programmes.

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Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study

BMC Infectious Diseases ◽

10.1186/1471-2334-13-535 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 21

Author(s):

Alfred B Tiono ◽

Moussa W Guelbeogo ◽

N Falé Sagnon ◽

Issa Nébié ◽

Sodiomon B Sirima ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

Randomized Study ◽

Clinical Malaria ◽

Asymptomatic Carriers ◽

Cluster Randomized ◽

Malaria Episodes

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Genetic diversity and complexity of Plasmodium falciparum infections in the microenvironment among siblings of the same household in North-Central Nigeria

Malaria Journal ◽

10.1186/s12936-020-03415-1 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Segun Isaac Oyedeji ◽

Peter Usman Bassi ◽

Samuel Adeola Oyedeji ◽

Olusola Ojurongbe ◽

Henrietta Oluwatoyin Awobode

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Clinical Malaria ◽

Genetic Characteristics ◽

North Central ◽

Allele Type ◽

Allele Specific ◽

Study Population

Abstract Background Plasmodium falciparum parasites are known to exhibit extensive genetic diversity in areas of high transmission intensity and infected individuals in such communities often harbour several complex mixtures of parasite clones with different genetic characteristics. However, in the micro-environment, the extent of genetic diversity of P. falciparum parasites remain largely unknown. In this study therefore, the complexity of P. falciparum infections in households was investigated among symptomatic siblings, living under the same roof in north-central Nigeria. Methods Children were enrolled into the study if they were at least two from a household and presented with symptoms of uncomplicated malaria. Clinical malaria was confirmed by light microscopy of Giemsa-stained thick and thin blood films. Genomic DNA was isolated from blood spots on filter paper. Molecular characterization of P. falciparum isolates was done by allele-specific nested PCR of the highly polymorphic merozoite surface protein-2 (msp-2) gene. Results Ninety-three children from 43 households were enrolled into this study. A total of 26 different msp-2 alleles were identified from 215 fragments (range: 180–480 bp). Majority of the isolates [65.6% (n = 61)] were polyclonal infections consisting of 2–6 clones and were significantly more common with the FC27 allelic family (p = 0.036). The multiplicity of infection (MOI) per household ranged from 1.0 to 4.5 while the overall MOI in the study population was 2.31. The pattern of distribution of msp-2 allele types among the households fell into two categories: households where both msp-2 allele types (FC27 and 3D7) were present; households where only one msp-2 allele type (FC27 or 3D7) was present. Majority of the households [88.4% (n = 38)], had both msp-2 allele types but they were disproportionately distributed among the children while in a few households [11.6% (n = 5)], all the children were infected with only one type of msp-2 allele. Conclusion These findings showed that P. falciparum isolates exhibit remarkable degree of genetic diversity in the micro-environment and are composed mainly of multiclonal infections, which is an indication of a high ongoing parasite transmission. This suggests that the micro-environment is an important area of focus for malaria control interventions and for evaluating intervention programmes.

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Genetic diversity and complexity of Plasmodium falciparum infections in the microenvironment among siblings of the same household in North-Central Nigeria

10.21203/rs.3.rs-30643/v2 ◽

2020 ◽

Author(s):

Segun Isaac Oyedeji ◽

Peter Usman Bassi ◽

Samuel Adeola Oyedeji ◽

Olusola Ojurongbe ◽

Henrietta Oluwatoyin Awobode

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Clinical Malaria ◽

Genetic Characteristics ◽

North Central ◽

Allele Type ◽

Allele Specific ◽

Study Population

Abstract Background Plasmodium falciparum parasites are known to exhibit extensive genetic diversity in areas of high transmission intensity and infected individuals in such communities often harbour several complex mixtures of parasite clones with different genetic characteristics. However, in the micro-environment, the extent of genetic diversity of P. falciparum parasites remain largely unknown. In this study therefore, the complexity of P. falciparum infections in households was investigated among symptomatic siblings, living under the same roof in north-central Nigeria.Methods Children were enrolled into the study if they were at least two from a household and presented with symptoms of uncomplicated malaria. Clinical malaria was confirmed by light microscopy of Giemsa-stained thick and thin blood films. Genomic DNA was isolated from blood spots on filter paper. Molecular characterization of P. falciparum isolates was done by allele-specific nested PCR of the highly polymorphic merozoite surface protein-2 (msp-2) gene.Results Ninety-three children from 43 households were enrolled into this study. A total of 26 different msp-2 alleles were identified from 215 fragments (range: 180-480 bp). Majority of the isolates (65.6% (n=61)) were polyclonal infections consisting of 2-6 clones and were significantly more common with the FC27 allelic family (p = 0.036). The multiplicity of infection (MOI) per household ranged from 1.0 to 4.5 while the overall MOI in the study population was 2.31. The pattern of distribution of msp-2 allele types among the households fell into two categories: households where both msp-2 allele types (FC27 and 3D7) were present; households where only one msp-2 allele type (FC27 or 3D7) was present. Majority of the households (88.4% (n=38)), had both msp-2 allele types but they were disproportionately distributed among the children while in a few households (11.6% (n=5)), all the children were infected with only one type of msp-2 allele.Conclusion These findings showed that P. falciparum isolates exhibit remarkable degree of genetic diversity in the micro-environment and are composed mainly of multiclonal infections, which is an indication of a high ongoing parasite transmission. This suggests that the micro-environment is an important area of focus for malaria control interventions and for evaluating intervention programmes.

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10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity

Wellcome Open Research ◽

10.12688/wellcomeopenres.16562.1 ◽

2021 ◽

Vol 6 ◽

pp. 79

Author(s):

John W.G. Addy ◽

Yaw Bediako ◽

Francis M. Ndungu ◽

John Joseph Valetta ◽

Adam J. Reid ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Clinical Symptoms ◽

Clinical Malaria ◽

Multiple Infections ◽

Acquired Immunity ◽

Large Variability ◽

Antibody Titres ◽

Using Data ◽

Malaria Episodes

Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

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