Faculty Opinions recommendation of Major Threat to Malaria Control Programs by Plasmodium falciparum Lacking Histidine-Rich Protein 2, Eritrea.

Author(s):  
Audrey Odom John
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tobias Schindler ◽  
Anna C. Deal ◽  
Martina Fink ◽  
Etienne Guirou ◽  
Kara A. Moser ◽  
...  

Abstract The rapid and accurate diagnosis of Plasmodium falciparum malaria infection is an essential factor in malaria control. Currently, malaria diagnosis in the field depends heavily on using rapid diagnostic tests (RDTs) many of which detect circulating parasite-derived histidine-rich protein 2 antigen (PfHRP2) in capillary blood. P. falciparum strains lacking PfHRP2, due to pfhrp2 gene deletions, are an emerging threat to malaria control programs. The novel assay described here, named qHRP2/3-del, is well suited for high-throughput screening of P. falciparum isolates to identify these gene deletions. The qHRP2/3-del assay identified pfhrp2 and pfhrp3 deletion status correctly in 93.4% of samples with parasitemia levels higher than 5 parasites/µL when compared to nested PCR. The qHRP2/3-del assay can correctly identify pfhrp2 and pfhrp3 gene deletions in multiple strain co-infections, particularly prevalent in Sub-Saharan countries. Deployment of this qHRP2/3-del assay will provide rapid insight into the prevalence and potential spread of P. falciparum isolates that escape surveillance by RDTs.


2020 ◽  
Author(s):  
Ana Alvarez-Fernandez ◽  
María J. Bernal ◽  
Isabel Fradejas Villajos ◽  
Alexandra Martín Ramírez ◽  
Noor Azian Md Yu ◽  
...  

Abstract BackgroundThe emergence and spread of antimalarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known antimalarials. This antimalarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorfisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programs. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum.MethodsThree SNPs involved in most cases of resistance to the most widespread antimalarial treatments have been analyzed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analyzed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method.ResultsThe KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analyzed.ConclusionsThe KASP assays developed in our study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.


2020 ◽  
Author(s):  
Ana Alvarez-Fernandez ◽  
María J. Bernal ◽  
Isabel Fradejas Villajos ◽  
Alexandra Martín Ramírez ◽  
Noor Azian Md Yu ◽  
...  

Abstract Background The emergence and spread of antimalarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known antimalarials. This antimalarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorfisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programs. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum. Methods Three SNPs involved in most cases of resistance to the most widespread antimalarial treatments have been analyzed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analyzed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method. Results The KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analyzed. Conclusions The KASP assays developed in our study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.


2018 ◽  
Vol 24 (3) ◽  
pp. 462-470 ◽  
Author(s):  
Araia Berhane ◽  
Karen Anderson ◽  
Selam Mihreteab ◽  
Karryn Gresty ◽  
Eric Rogier ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ruth Ayanful-Torgby ◽  
Esther Sarpong ◽  
Hamza B. Abagna ◽  
Dickson Donu ◽  
Evans Obboh ◽  
...  

AbstractSubclinical infections that serve as reservoir populations to drive transmission remain a hurdle to malaria control. Data on infection dynamics in a geographical area is required to strategically design and implement malaria interventions. In a longitudinal cohort, we monitored Plasmodium falciparum infection prevalence and persistence, and anti-parasite immunity to gametocyte and asexual antigens for 10 weeks. Of the 100 participants, only 11 were never infected, whilst 16 had persistent infections detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and one participant had microscopic parasites at all visits. Over 70% of the participants were infected three or more times, and submicroscopic gametocyte prevalence was high, ≥ 48% of the parasite carriers. Naturally induced responses against recombinant Pfs48/45.6C, Pfs230proC, and EBA175RIII–V antigens were not associated with either infection status or gametocyte carriage, but the antigen-specific IgG titers inversely correlated with parasite and gametocyte densities consistent with partial immunity. Longitudinal analysis of gametocyte diversity indicated at least four distinct clones circulated throughout the study period. The high prevalence of children infected with distinct gametocyte clones coupled with marked variation in infection status at the individual level suggests ongoing transmission and should be targeted in malaria control programs.


2021 ◽  
Author(s):  
Mario JC Ayala ◽  
Leonardo S Bastos ◽  
Daniel A.M. Villela

Background: Malaria incidence in Brazil reversed its decreasing trend when cases from recent years, as recent as 2015, exhibited an increase in the Brazilian Amazon basin, the area with highest transmission of Plasmodium vivax and Plasmodium falciparum. In fact, an increase of more than 20% in the years 2016 and 2017 revealed possible vulnerabilities in the national malaria-control program. Methods: We studied factors that are potentially associated with this reversal, including migration, economical activities, and deforestation, and weakening of investment in control programs. We analyze past incidences of malaria cases due to Plasmodium vivax and Plasmodium falciparum with a spatio-temporal Bayesian model using more than 5 million individual records of malaria cases from January of 2003 to December of 2018 in the Brazilian Amazon to establish the municipalities with unexpected increases in cases. Results: We observe an increase in imported cases from border countries in Roraima state and found small effects due to deforestation and change of occupations. Also, an overall funding reduction from 2013 to 2016 happened before an increase in malaria cases in five regions in Amazon basin, markedly for P. vivax incidence and especially, in Pará and Roraima States. Conclusion: Urban developments, discontinued funding for control programs, migration from border areas, deforestation activities, and different economic activities such as mining and agriculture appear linked to the rebound on malaria incidence. These multifactorial drivers show that malaria control programs require permanent attention towards elimination.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Vicente Urbano Nsue Ndong Nchama ◽  
Ali Hamad Said ◽  
Ali Mtoro ◽  
Gertrudis Owono Bidjimi ◽  
Marta Alene Owono ◽  
...  

Abstract Background Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. Methods A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. Results There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6–59-month-olds, 0.26 in 5–17-year-olds, 0.20 in 18–45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6–59-month-olds, 0.10 in 5–17-year-olds, 0.11 in 18–45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. Conclusion Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Micaela Finney ◽  
Benjamin A. McKenzie ◽  
Bernadette Rabaovola ◽  
Alice Sutcliffe ◽  
Ellen Dotson ◽  
...  

Abstract Background Malaria is a top cause of mortality on the island nation of Madagascar, where many rural communities rely on subsistence agriculture and livestock production. Understanding feeding behaviours of Anopheles in this landscape is crucial for optimizing malaria control and prevention strategies. Previous studies in southeastern Madagascar have shown that Anopheles mosquitoes are more frequently captured within 50 m of livestock. However, it remains unknown whether these mosquitoes preferentially feed on livestock. Here, mosquito blood meal sources and Plasmodium sporozoite rates were determined to evaluate patterns of feeding behaviour in Anopheles spp. and malaria transmission in southeastern Madagascar. Methods Across a habitat gradient in southeastern Madagascar 7762 female Anopheles spp. mosquitoes were collected. Of the captured mosquitoes, 492 were visibly blood fed and morphologically identifiable, and a direct enzyme-linked immunosorbent assay (ELISA) was used to test for swine, cattle, chicken, human, and dog blood among these specimens. Host species identification was confirmed for multiple blood meals using PCR along with Sanger sequencing. Additionally, 1,607 Anopheles spp. were screened for the presence of Plasmodium falciparum, P. vivax-210, and P. vivax 247 circumsporozoites (cs) by ELISA. Results Cattle and swine accounted, respectively, for 51% and 41% of all blood meals, with the remaining 8% split between domesticated animals and humans. Of the 1,607 Anopheles spp. screened for Plasmodium falciparum, Plasmodium vivax 210, and Plasmodium vivax 247 cs-protein, 45 tested positive, the most prevalent being P. vivax 247, followed by P. vivax 210 and P. falciparum. Both variants of P. vivax were observed in secondary vectors, including Anopheles squamosus/cydippis, Anopheles coustani, and unknown Anopheles spp. Furthermore, evidence of coinfection of P. falciparum and P. vivax 210 in Anopheles gambiae sensu lato (s.l.) was found. Conclusions Here, feeding behaviour of Anopheles spp. mosquitoes in southeastern Madagascar was evaluated, in a livestock rich landscape. These findings suggest largely zoophagic feeding behaviors of Anopheles spp., including An. gambiae s.l. and presence of both P. vivax and P. falciparum sporozoites in Anopheles spp. A discordance between P. vivax reports in mosquitoes and humans exists, suggesting high prevalence of P. vivax circulating in vectors in the ecosystem despite low reports of clinical vivax malaria in humans in Madagascar. Vector surveillance of P. vivax may be relevant to malaria control and elimination efforts in Madagascar. At present, the high proportion of livestock blood meals in Madagascar may play a role in buffering (zooprophylaxis) or amplifying (zoopotentiation) the impacts of malaria. With malaria vector control efforts focused on indoor feeding behaviours, complementary approaches, such as endectocide-aided vector control in livestock may be an effective strategy for malaria reduction in Madagascar.


2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Peter M. Macharia ◽  
Emanuele Giorgi ◽  
Abdisalan M. Noor ◽  
Ejersa Waqo ◽  
Rebecca Kiptui ◽  
...  

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