scholarly journals Allelic diversity of MSP1 and MSP2 repeat loci correlate with levels of malaria endemicity in Senegal and Nigerian populations

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mary A. Oboh ◽  
Tolla Ndiaye ◽  
Khadim Diongue ◽  
Yaye D. Ndiaye ◽  
Mouhamad Sy ◽  
...  

Abstract Background Characterizing the genetic diversity of malaria parasite populations in different endemic settings (from low to high) could be helpful in determining the effectiveness of malaria interventions. This study compared Plasmodium falciparum parasite population diversity from two sites with low (pre-elimination) and high transmission in Senegal and Nigeria, respectively. Methods Parasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicated P. falciparum malaria infected patients in Senegal (94) and Nigeria (93). Allelic polymorphism at merozoite surface protein 1 (msp1) and merozoite surface protein- 2 (msp2) genes were assessed by nested PCR. Results The most frequent msp1 and msp2 allelic families are the K1 and IC3D7 allelotypes in both Senegal and Nigeria. Multiplicity of infection (MOI) of greater that 1 and thus complex infections was common in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 for msp1/2) than in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity of msp1 gene was higher in P. falciparum isolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles was associated with heavy than with moderate parasite density. Meanwhile, equal proportions of K1 were observed in both heavy and moderate infection types in Nigeria. The IC3D7 subtype allele of the msp2 family was the most frequent in heavily parasitaemic individuals from both countries than in the moderately infected participants. Conclusion The unexpectedly low genetic diversity of infections high endemic Nigerian setting compared to the low endemic settings in Senegal is suggestive of possible epidemic outbreak in Nigeria.

2021 ◽  
Author(s):  
Abeba Reda ◽  
Alebachew Messele ◽  
Hussein Mohammed ◽  
Ashenafi Assefa ◽  
Lemu Golassa ◽  
...  

Abstract Background: The complexity and quantity of parasite populations circulating in a specific location are reflected in the genetic diversity of malaria parasites (s). Between 2015 and 2019, this study in Metehara, South east, Ethiopia. set out to investigate the temporal dynamics of genetic diversity and multiplicity as a result of evolutionary change in the genes that contribute to Plasmodium falciparum infection elimination. Method: Between 2015 and 2019, a cross-sectional study was carried out. from eighty-three dry blood spots from malaria patients who were screened for P. falciparum mono-infection by QPCR. From this seventy confirmed P. falciparum were genotyping to merozoite surface protein 1,2 and glutamate-rich protein using nested PCR.Result: Between 2015 and 2019, seventy (84.3%) of the isolates were successfully genotyped for all three target genes in both years. In 2015 and 2019, the allelic distributions of the three genes differed significantly (P= 0.001). Overall, the most common allelic families for msp1 and msp2 were K1 and FC27 respectively. For glurp, eight distinct genotypes were identified. In 2015, the genotyping of msp1, msp2 and glurp was 25 (86.2%), 25 (86.2%) and 24 (82.2%) respectively. K1, MAD20 and RO33 all have 19(65.5%), 3(10.3%) and 3(10.3%) msp1 allelic families respectively. In 2019 the genes were 30 (73.2%), 39 (95.1%) and 30 (73.2%). K1, MAD20, and RO33 were genotyped for 6 (14.6 percent), 18 (43.9 percent) and 6 (14.6 percent) genotyping respectively. Over all the multiplicity of infection was 1.67 (95 percent CI 1.54-1.74) and the heterozygosity index for msp1, msp2, and glurp was 0.48, 0.70, and 0.55 respectively.Conclusion: This study provides current information on the genetic diversity of P. falciparum populations in Metehara over five-year intervals, The progression of the dominant K1 variant from 2015 to MAD20 variant in 2019 was observed in this study.


2020 ◽  
Author(s):  
Mary Aigbiremo Oboh ◽  
Tolla Ndiaye ◽  
Khadim Diongue ◽  
Yaye D Ndiaye ◽  
Mouhamad Sy ◽  
...  

Background: Characterization of malaria parasite populations in different endemic settings (from low to high) could be helpful for ascertaining the progress of malaria interventions in endemic settings. The present study aims to compare Plasmodium falciparum parasite population structure between two West African countries with very different level of endemicity using P. falciparum allelic polymorphic markers: msp1 and msp2. Methods: Parasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicated P. falciparum malaria infected patients in Senegal (94) being at the pre-elimination stage in most part of the country and Nigeria (93) which is still at the control stage. Allelic polymorphism of msp1 and msp2 genes were assessed by nested PCR. Results: In Senegal as well as in Nigeria, K1 and IC3D7 allelic families were the most represented for msp1 and msp2 genes respectively. A higher multiplicity of infection (MOI) was found in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 for msp 1/2) than from sites in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity of msp 1 gene was higher in P. falciparum isolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles were associated with heavy (28) than with moderate (18) infections, in Nigeria however, equal proportions of K1 were observed in both infection types. The IC3D7 subtype allele of the msp 2 family showed high occurrence in heavily infected individuals from both countries (Senegal- 32; Nigeria- 26) than in the moderately infected participants. Conclusion: With the unusual high genetic diversity obtained in low endemic setting in Senegal and low genetic diversity in a high endemic Nigerian setting, multiple holistic approach should be employed in evaluating the actual transmission of a place in order to effectively direct control measures.


2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Joshua Idakwo ◽  
Emmanuel T. Idowu ◽  
Kolapo M. Oyebola ◽  
Olubunmi A. Otubanjo

Introduction: Extensive genetic diversity of malaria parasites is a major draw back to ongoing control efforts. Population-specific investigation of genetic structure of the parasite is important for effective malaria intervention in endemic populations such as Nigeria where about one-third of the global burden of the disease is borne. This study describes the genetic diversity of Plasmodium falciparum isolates in the Niger River basins, North-Central Nigeria. Methodology: Parasite DNA w as extracted fr om finger -prick blood samples collected from eighty P. falciparum positive individuals. Polymerase Chain Reaction (PCR) genotyping was carried out to target K1, MAD20 and R033 allelic families of Merozoite Surface Protein (MSP) -1 gene and FC27 and 3D7 allelic families of MSP-2 gene. Results: Proportion of isolates with K1 family w as 28(70%) with two alleles in Idah and 16(40%) with two alleles in Ibaji. Proportion of isolates with MAD20 family was 8 (20%) and a total of two alleles were observed in Idah and 4(10%) with two alleles in Ibaji. RO33 proportion was 16 (40%) in Idah one allele and 8(20%) in Ibaji where the allelic family was also observed to be monomorphic. K1 was the most predominant MSP1 allele in the two parasite populations and the frequency of FC27 genotype was higher than 3D7 in both populations. Multiplicity of infection (Mol) with MSP-1 loci was higher in Ibaji (1.30) than Idah (1.05) while MoI with MSP-2 loci was lower in Ibaji (2.00) than Idah (2.13). However, there is no significant difference in the mean Mol between Idah and Ibaji (P > 0.05). The expected heterozygosity (HE) value was 0.56 for MSP-1 and 0.84 for MSP-2. Conclusion: Our findings revealed high levels of monoclonal infections with P. falciparum, suggesting low parasite diversity. This may be a pointer to a reduction in malaria transmission in the river basins.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Olof Hellgren ◽  
Victor Kelbskopf ◽  
Vincenzo A. Ellis ◽  
Arif Ciloglu ◽  
Mélanie Duc ◽  
...  

Abstract Background Although avian Plasmodium species are widespread and common across the globe, limited data exist on how genetically variable their populations are. Here, the hypothesis that the avian blood parasite Plasmodium relictum exhibits very low genetic diversity in its Western Palearctic transmission area (from Morocco to Sweden in the north and Transcaucasia in the east) was tested. Methods The genetic diversity of Plasmodium relictum was investigated by sequencing a portion (block 14) of the fast-evolving merozoite surface protein 1 (MSP1) gene in 75 different P. relictum infections from 36 host species. Furthermore, the full-length MSP1 sequences representing the common block 14 allele was sequenced in order to investigate if additional variation could be found outside block 14. Results The majority (72 of 75) of the sequenced infections shared the same MSP1 allele. This common allele has previously been found to be the dominant allele transmitted in Europe. Conclusion The results corroborate earlier findings derived from a limited dataset that the globally transmitted malaria parasite P. relictum exhibits very low genetic diversity in its Western Palearctic transmission area. This is likely the result of a recent introduction event or a selective sweep.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kurnia Fitri Jamil ◽  
Nandha Rizki Pratama ◽  
Sylvia Sance Marantina ◽  
Harapan Harapan ◽  
Muhammad Riza Kurniawan ◽  
...  

Abstract Background The malaria control programme in Indonesia has successfully brought down malaria incidence in many parts in Indonesia, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein 1 gene (msp1) and msp2 among the Plasmodium falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation. Methods Screening of over 500 malaria cases admitted to the hospitals in 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and polymerase chain reaction (PCR) amplified for the msp1 and msp2 allelic subfamilies. Results Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases were classified as severe and 71 as mild malaria. Analysis of msp1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of msp2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp1 alleles is slightly higher than msp2 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and msp1 and msp2 alleles revealed that liver function abnormal value was associated with the msp2 mixed alleles (odds ratio (OR):0.13; 95%CI: 0.03–0.53). Mixed msp1 of K1 + RO33 was associated with severe malaria (OR: 28.50; 95%CI: 1.59–1532.30). Conclusion This study found a strong association between severe malaria in Aceh with subjects carrying the msp1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the msp2 mixed allelic subfamilies. Further study in different geographic areas is recommended.


2005 ◽  
Vol 73 (9) ◽  
pp. 5928-5935 ◽  
Author(s):  
Kevin K. A. Tetteh ◽  
David R. Cavanagh ◽  
Patrick Corran ◽  
Rosemary Musonda ◽  
Jana S. McBride ◽  
...  

ABSTRACT Polymorphism in pathogen antigens presents a complex challenge for vaccine design. A prime example is the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP1), to which allele-specific antibodies have been associated with protection from malaria. In a Zambian population studied here, 49 of 91 alleles sampled were of the K1-like type (the most common of three block 2 types in all African populations), and most of these had unique sequences due to variation in tri- and hexapeptide repetitive motifs. There were significant negative correlations between allelic sequence lengths of different regions of the repeats, so the complete repeat sequence had less length variation than its component parts, suggesting a constraint on overall length. Diverse epitopes recognized by three murine monoclonal antibodies and 24 individual human sera were then mapped by using a comprehensive panel of synthetic peptides, revealing epitopes in all regions of the repeats. To incorporate these different epitopes in a single molecule, a composite sequence of minimal overall length (78 amino acids) was then designed and expressed as a recombinant antigen. More human immune sera reacted with this “K1-like Super Repeat” antigen than with proteins consisting of single natural allelic sequences, and immunization of mice elicited antibodies that recognized a range of five cultured parasite lines with diverse K1-like MSP1 block 2 repeat sequences. Thus, complex allelic polymorphism was deconstructed and a minimal composite polyvalent antigen was engineered, delivering a designed candidate sequence for inclusion in a malaria vaccine.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinwen Xu ◽  
Sihong Liu ◽  
Kokouvi Kassegne ◽  
Bo Yang ◽  
Jiachen Lu ◽  
...  

Abstract Background Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119. Methods A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp119 (pocmsp119) and P. ovale wallikeri (pow) msp119 (powmsp119) genes by polymerase chain reaction. The genetic diversity of pomsp119 was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP119 (rPoMSP119)-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays. Results Sequences of pomsp119 were found to be thoroughly conserved in all the clinical isolates. rPoMSP119 proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP119-GST were observed. rPoMSP119-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP119 and rPowMSP119, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively. Conclusions This study revealed highly conserved gene sequences of pomsp119. In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP119 in mice was also identified. These instructive findings should encourage further testing of PoMSP119 for rational vaccine design. Graphical abstract


2018 ◽  
Vol 14 (4) ◽  
pp. 106-109
Author(s):  
Rosye Hefmi Rechnelty Tanjung ◽  
Yulius Sarungu ◽  
Meidy Johana Imbiri ◽  
Ade Irma Resmol ◽  
Dirk Yanes Persius Runtuboi ◽  
...  

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Tolla Ndiaye ◽  
Mouhamad Sy ◽  
Amy Gaye ◽  
Katherine J. Siddle ◽  
Daniel J. Park ◽  
...  

Abstract Background Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum, which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology including understanding the genetic diversity of the parasite and performing molecular surveillance of transmission has been poorly documented in Senegal. Next Generation Sequencing (NGS) offers a practical, fast and high-throughput approach to understand malaria population genetics. This study aims to unravel the population structure of P. falciparum and to estimate the allelic diversity, multiplicity of infection (MOI), and evolutionary patterns of the malaria parasite using the NGS platform. Methods Multiplex amplicon deep sequencing of merozoite surface protein 1 (PfMSP1) and merozoite surface protein 2 (PfMSP2) in fifty-three P. falciparum isolates from two epidemiologically different areas in the South and North of Senegal, was carried out. Results A total of 76 Pfmsp1 and 116 Pfmsp2 clones were identified and 135 different alleles were found, 56 and 79 belonged to the pfmsp1 and pfmsp2 genes, respectively. K1 and IC3D7 allelic families were most predominant in both sites. The local haplotype diversity (Hd) and nucleotide diversity (π) were higher in the South than in the North for both genes. For pfmsp1, a high positive Tajima’s D (TD) value was observed in the South (D = 2.0453) while negative TD value was recorded in the North (D = − 1.46045) and F-Statistic (Fst) was 0.19505. For pfmsp2, non-directional selection was found with a highly positive TD test in both areas and Fst was 0.02111. The mean MOI for both genes was 3.07 and 1.76 for the South and the North, respectively, with a statistically significant difference between areas (p = 0.001). Conclusion This study revealed a high genetic diversity of pfmsp1 and pfmsp2 genes and low genetic differentiation in P. falciparum population in Senegal. The MOI means were significantly different between the Southern and Northern areas. Findings also showed that multiplexed amplicon deep sequencing is a useful technique to investigate genetic diversity and molecular epidemiology of P. falciparum infections.


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