scholarly journals Genetic diversity of Plasmodium falciparum populations in three malaria transmission settings in Madagascar

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fanomezantsoa Ralinoro ◽  
Tovonahary Angelo Rakotomanga ◽  
Rianasoambolanoro Rakotosaona ◽  
Danielle A. Doll Rakoto ◽  
Didier Menard ◽  
...  

Abstract Background Assessment of the genetic diversity of Plasmodium falciparum parasites from various malaria transmission settings could help to define tailored local strategies for malaria control and elimination. Such assessments are currently scarce in Madagascar. The study presented here aimed to bridge this gap by investigating the genetic diversity of P. falciparum populations in three epidemiological strata (Equatorial, Tropical and Fringes) in Madagascar. Methods Two-hundred and sixty-six P. falciparum isolates were obtained from patients with uncomplicated malaria enrolled in clinical drug efficacy studies conducted at health centres in Tsaratanana (Equatorial stratum), Antanimbary (Tropical stratum) and Anjoma Ramartina (Fringes) in 2013 and 2016. Parasite DNA was extracted from blood samples collected before anti-malarial treatment. Plasmodium species were identified by nested PCR targeting the 18 S rRNA gene. The genetic profiles of P. falciparum parasites were defined by allele-specific nested PCR on the polymorphic regions of the msp-1 and msp-2 genes. Results Fifty-eight alleles were detected in the P. falciparum samples tested: 18 alleles for msp-1 and 40 for msp-2. K1 (62.9%, 139/221) and FC27 (69.5%, 114/164) were the principal msp-1 and msp-2 allele families detected, although the proportions of the msp-1 and msp-2 alleles varied significantly between sites. Polyclonal infections were more frequent at sites in the Equatorial stratum (69.8%) than at sites in the Tropical stratum (60.5%) or Fringes (58.1%). Population genetics analyses showed that genetic diversity was similar between sites and that parasite flow within sites was limited. Conclusions This study provides recent information about the genetic diversity of P. falciparum populations in three transmission strata in Madagascar, and valuable baseline data for further evaluation of the impact of the control measures implemented in Madagascar.

2021 ◽  
Author(s):  
Fanomezantsoa Ralinoro ◽  
Tovonahary Angelo Rakotomanga ◽  
Riana Rakotosaona ◽  
Danielle A. Doll Rakoto ◽  
Didier Menard ◽  
...  

Abstract BackgroundThe assessment of the genetic diversity of Plasmodium falciparum parasites from various malaria transmission settings could help to define tailored and dedicated local strategies for malaria control and elimination. To date, this information is scarce in Madagascar. To fill this gap, a study aiming at investigating the genetic diversity of P. falciparum populations in three epidemiological facies (Equatorial, Tropical and Fringes) in Madagascar was conducted.MethodsTwo hundred sixty-six P. falciparum isolates were obtained from patients with uncomplicated malaria enrolled in clinical drug efficacy studies conducted in health centers at Tsaratanana (Equatorial facies), Antanimbary (Tropical facies) and Anjoma Ramartina (Fringes) in 2013 and 2016. Parasite DNA was extracted from blood samples collected prior antimalarial treatment. Plasmodium species were identified by nested-PCR targeting 18S rRNA gene. The genetic profiles of P. falciparum parasites were defined by assessing the polymorphic regions of the msp-1 and msp-2 genes using allele-specific nested-PCR.ResultsA total of 58 alleles were detected for msp-1 (18 alleles) and msp-2 (40 alleles) among P. falciparum samples tested. K1 (62.9%, 139/221) and FC27 (69.5%, 114/164) were the most predominant msp-1 and msp-2 allelic families, although the proportions of the msp-1 and msp-2 alleles varied significantly between sites. Polyclonal infections were more frequent in site located in the Equatorial facies (69.8%) compared to sites in the Tropical facies (60.5%) and Fringes (58.1%). Population genetic measures showed that the genetic diversity was similar between sites and the parasite flow within sites was limited.ConclusionThis study provides recent information on the genetic diversity of P. falciparum populations in three transmission facies in Madagascar and valuable baseline data to further evaluate the impact of the control measures implemented in Madagascar.


2021 ◽  
Author(s):  
Anne L Wilson ◽  
Steve W Lindsay ◽  
Alfred Tiono ◽  
Jean Baptiste Yaro ◽  
Hilary Ranson ◽  
...  

Abstract Background Burkina Faso has one of the highest malaria burdens in sub-Saharan Africa despite the mass deployment of insecticide-treated nets (ITNs) and use of seasonal malaria chemoprevention (SMC) in children aged up to 5 years. Identification of risk factors for Plasmodium falciparum infection in rural Burkina Faso could help to identify and target malaria control measures. Methods A cross-sectional survey of 1,199 children and adults was conducted during the peak malaria transmission season in south-west Burkina Faso in 2017. Logistic regression was used to identify risk factors for microscopically confirmed P. falciparum infection. A malaria transmission dynamic model was used to determine the impact on malaria cases averted of administering SMC to children aged 5–15 year old. Results P. falciparum prevalence was 32.8% in the study population. Children aged 5 to < 10 years old were at 3.74 times the odds (95% CI = 2.68–5.22, p < 0.001) and children aged 10 to 15 years old at 3.14 times the odds (95% CI = 1.20–8.21, p = 0.02) of P. falciparum infection compared to children aged less than 5 years old. Administration of SMC to children aged up to 10 years is predicted to avert an additional 57 malaria cases per 1000 population per year (9.4% reduction) and administration to children aged up to 15 years would avert an additional 89 malaria cases per 1000 population per year (14.6% reduction) in the Cascades Region, assuming coverage of pyrethroid-piperonyl butoxide ITNs. Conclusion Malaria infections were high in all age strata, although highest in children aged 5 to 15 years, despite roll out of core malaria control interventions. Given the burden of infection in school-age children, extension of the eligibility criteria for SMC could help reduce the burden of malaria in Burkina Faso and other countries in the region.


2019 ◽  
Author(s):  
Metoh Theresia Njuabe ◽  
Jun-Hu Chen ◽  
Philip Fon Gah ◽  
Zhou Xia ◽  
Somo.Roger Moyou ◽  
...  

Abstract Background Plasmodium falciparum is the number one cause of malaria morbidity and mortality. Several methods of intervention have been deployed in Cameroon with an attempt to reduce malaria transmission. But evaluation methods mostly based on microscopy and immunology have proven to be cumbersome and expensive. This study aimed at analyzing the genetic diversity of P.falciparum and the impact of ACTs deployment on MOI Method 350 clinical isolates were collected between 2012 and 2013 and, three P. falciparum loci namely, msp-1(block2), msp-2 (block3), and glurp, (region II) characterized by nested PCR and DNA sequencing. Results From this study, a total of 16 different pfmsp1 were identified, including K1, MAD20 and RO33 allelic families. The K1 and MAD20 were the predominant polymorphic allelic types at the msp-1 gene, whereas alleles belonging to 3D7/IC were more frequent at the msp-2 gene. A peculiarity of this study is that RO33 revealed a monomorphic pattern among the msp-1 allelic type. Msp-1 and msp-2 revealed considerably greater parasite diversity than glurp. A total of 27 different msp-2 genotypes were recorded of which 15 belonged to the 3D7-type and 12 to the FC27 allelic families. Alignment of peptides encoded by pfmsp1 and Pfmsp2 reveals that K1 polymorphism had the highest similarity in the P.fmsp1 and Pfmsp2 clade followed by MAD20 with 93% to 100% homology. Indicating that P. falciparum isolates from Cameroon present high identity with allelic sequences from other areas in Africa, suggesting that vaccine developed with k1 and MAD20 of Pfmsp1 allelic variant could be protective for Africa children. The MOI ranged from 2.51 for msp1 to 3.82 for msp2. The overall heterozygosity ranged from 0.55 for msp-1 to 0.96 for msp-2 consistent with the genetic pattern observed in hyperendemic areas. Conclusion The present study reveals that isolates from South West Region of Cameroon are mainly polyclonal with high MOI and highly diverse in respect to both msp-1 and msp-2 despite ACTs deployment aiming at reducing malaria transmission. This study lays emphasis on the use of MOI and genotyping of both msp-1 and msp-2 in the evaluation of malaria control intervention in malaria endemics countries.


2020 ◽  
Author(s):  
Himanshu Gupta ◽  
Beatriz Galatas ◽  
Arlindo Chidimatembue ◽  
Wilson Simone ◽  
Gloria Matambisso ◽  
...  

Abstract Large-scale programs targeting Plasmodium falciparum (Pf) elimination can exert strong selection pressures on the parasite population. To better understand the impact that elimination initiatives can have on Pf genetic structure and gametocyte carriage, we applied amplicon-based sequencing of two polymorphic Pf genes and quantitative reverse-transcription PCR targeting gametocyte-specific genes to Pf isolates collected in Magude District (Southern Mozambique) before and after an elimination initiative. The 71% reduction of Pf prevalence achieved in 2 years was followed by reductions in Pf genetic diversity and increases in between-infection similarity. These genetic shifts were accompanied by increases in the relative transcript number of the female mature gametocyte marker pfs25, the pfap2g transcription factor that drives gametocytogenesis and the sexual ring marker pfgexp02, suggesting the parasite ability of adapting its sexual investment during elimination initiatives. Reactive interventions that target Pf sexual stages may be required to achieve complete interruption of transmission.


2021 ◽  
Author(s):  
Muzafar Shah ◽  
Ibrar Ullah ◽  
Sahib Gul Afridi ◽  
Muhammad Israr ◽  
Asifullah Khan ◽  
...  

Plasmodium falciparum, the main causative agent of malaria is an important public health vector in Khyber Pakhtunkhwa, Pakistan. Identification of the genetic diversity of malaria parasites can inform the intensity of transmission and identify potential deficiencies in malaria control programs. The aim of this study was to investigate the genetic diversity, allele frequencies and multiplicity of infection (MOI) of P. falciparum in Khyber Pakhtunkhwa, Pakistan. Methods: A total of 85 isolates from patients presenting to the local health centers with P. falciparum species were collected from 2017 to 2019. Parasite DNA was extracted from a total of 200 micro litter whole blood per patient using the Qiagen DNA extraction kit according to manufactures instructions. The polymorphic region of msp-1, msp-2 and glurp loci were genotyped by using nested polymerase chain reactions followed by gel electrophoresis for fragment analysis. Results: Genetic diversity and allelic frequencies of msp-1, msp-2 and glurp were identified in 85 blood samples. A total of 62 msp alleles were detected in which 30 for msp-1 and 32 for msp-2. For msp-1 the successful amplification occurred in (75/85) 88.23% isolates for msp-1, 78.9% (67/85) for msp-2 and 70% (60/85) for glurp. For msp-1, the K1 allelic family was predominant at 66.66% (50/75), followed by RO33 and MAD20. The frequency of samples having only K1, MAD20 and RO33 were 21.34% (16/75), 8% (6/75) and 10.67% (8/75) respectively. In msp-2, the FC27 allelic family was the most abundant with 70.14% (47/67) compared to 3D7 with 67.16% (45/67). Nine glurp RII region genotypes were identified. The overall mean multiplicity of infection was 2.6 with1.8 and 1.4 for msp-1 and msp-2 respectively while for glurp RII genes (MOI=1.03). There was no significant association between multiplicity of infection and age group (Spearman rank coefficient = 0.050; P = 0.6). There was significant correlation between MOI and parasite density for msp-2 allelic family. Conclusion: Our study showed high genetic diversity and allelic frequency with multiple clones of msp-1, msp-2 and glurp in P. falciparum isolates from malaria patients in Khyber Pakhtunkhwa Pakistan. In the present study the genotype data provided the valuable information which is essential for monitoring the impact of malaria eradication efforts in this region.


2010 ◽  
Vol 78 (11) ◽  
pp. 4625-4633 ◽  
Author(s):  
Faith H. A. Osier ◽  
Gareth D. Weedall ◽  
Federica Verra ◽  
Linda Murungi ◽  
Kevin K. A. Tetteh ◽  
...  

ABSTRACT Although Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate, extensive allelic diversity may compromise its vaccine potential. We have previously shown that naturally acquired antibodies to AMA1 were associated with protection from clinical malaria in this Kenyan population. To assess the impact of allelic diversity on naturally acquired immunity, we first sequenced the ectodomain-encoding region of P. falciparum ama1 from subjects with asymptomatic, mild, and severe malaria and measured allele frequency distributions. We then measured antibodies to three allelic AMA1 proteins (AMA1_3D7, AMA1_FVO, and AMA1_HB3) and used competition enzyme-linked immunosorbent assays (ELISAs) to analyze allele-specific antibodies. Seventy-eight unique haplotypes were identified from 129 alleles sampled. No clustering of allelic haplotypes with disease severity or year of sampling was observed. Differences in nucleotide frequencies in clinical (severe plus mild malaria) versus asymptomatic infections were observed at 16 polymorphic positions. Allele frequency distributions were indicative of balancing selection, with the strongest signature being identified in domain III (Tajima's D = 2.51; P < 0.05). Antibody reactivities to each of the three allelic AMA1 proteins were highly correlated (P < 0.001 for all pairwise comparisons). Although antibodies to conserved epitopes were abundant, 48% of selected children with anti-AMA1 IgG (n = 106) had detectable reactivity to allele-specific epitopes as determined by a competition ELISA. Antibodies to both conserved and allele-specific epitopes in AMA1 may contribute to clinical protection.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Miracle Amadi ◽  
Anna Shcherbacheva ◽  
Heikki Haario

Abstract Background Increasingly complex models have been developed to characterize the transmission dynamics of malaria. The multiplicity of malaria transmission factors calls for a realistic modelling approach that incorporates various complex factors such as the effect of control measures, behavioural impacts of the parasites to the vector, or socio-economic variables. Indeed, the crucial impact of household size in eliminating malaria has been emphasized in previous studies. However, increasing complexity also increases the difficulty of calibrating model parameters. Moreover, despite the availability of much field data, a common pitfall in malaria transmission modelling is to obtain data that could be directly used for model calibration. Methods In this work, an approach that provides a way to combine in situ field data with the parameters of malaria transmission models is presented. This is achieved by agent-based stochastic simulations, initially calibrated with hut-level experimental data. The simulation results provide synthetic data for regression analysis that enable the calibration of key parameters of classical models, such as biting rates and vector mortality. In lieu of developing complex dynamical models, the approach is demonstrated using most classical malaria models, but with the model parameters calibrated to account for such complex factors. The performance of the approach is tested against a wide range of field data for Entomological Inoculation Rate (EIR) values. Results The overall transmission characteristics can be estimated by including various features that impact EIR and malaria incidence, for instance by reducing the mosquito–human contact rates and increasing the mortality through control measures or socio-economic factors. Conclusion Complex phenomena such as the impact of the coverage of the population with long-lasting insecticidal nets (LLINs), changes in behaviour of the infected vector and the impact of socio-economic factors can be included in continuous level modelling. Though the present work should be interpreted as a proof of concept, based on one set of field data only, certain interesting conclusions can already be drawn. While the present work focuses on malaria, the computational approach is generic, and can be applied to other cases where suitable in situ data is available.


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