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Malaria Journal Jun 2022Immunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful...
BACKGROUND
Immunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful epidemiological tools for rapid diagnostic test evaluation. This study presents the comparative evaluation of two multiplex platforms in identifying Plasmodium falciparum with presence or absence of HRP2/HRP3 expression as being indicative of hrp2/hrp3 deletions and other Plasmodium species. Moreover, correlation between the malaria antigen measurements performed at these platforms is assessed after calibrating with either assay standards or international standards and the cross-reactivity among Plasmodium species is examined.
METHODS
A 77-member panel of specimens composed of the World Health Organization (WHO) international Plasmodium antigen standards, cultured parasites for P. falciparum and Plasmodium knowlesi, and clinical specimens with mono-infections for P. falciparum, Plasmodium vivax, and Plasmodium malariae was generated as both whole blood and dried blood spot (DBS) specimens. Assays for HRP2, P. falciparum-specific pLDH (PfLDH), P. vivax-specific pLDH (PvLDH), and all human Plasmodium species Pan malaria pLDH (PanLDH) on the Human Malaria Array Q-Plex and the xMAP platforms were evaluated with these panels.
RESULTS
The xMAP showed a higher percent positive agreement for identification of hrp2-deleted P. falciparum and Plasmodium species in whole blood and DBS than the Q-Plex. For whole blood samples, there was a highly positive correlation between the two platforms for PfLDH (Pearson r = 0.9926) and PvLDH (r = 0. 9792), moderate positive correlation for HRP2 (r = 0.7432), and poor correlation for PanLDH (r = 0.6139). In Pearson correlation analysis between the two platforms on the DBS, the same assays were r = 0.9828, r = 0.7679, r = 0.6432, and r = 0.8957, respectively. The xMAP HRP2 assay appeared to cross-react with HRP3, while the Q-Plex did not. The Q-Plex PfLDH assay cross-reacted with P. malariae, while the xMAP did not. For both platforms, P. knowlesi was detected on the PvLDH assay. The WHO international standards allowed normalization across both platforms on their HRP2, PfLDH, and PvLDH assays in whole blood and DBS.
CONCLUSIONS
Q-Plex and xMAP show good agreement for identification of P. falciparum mutants with hrp2/hrp3 deletions, and other Plasmodium species. Quantitative results from both platforms, normalized into international units for HRP2, PfLDH, and PvLDH, showed good agreement and should allow comparison and analysis of results generated by either platform.
Topics: Antigens, Protozoan; Diagnostic Tests, Routine; Humans; Immunoassay; L-Lactate Dehydrogenase; Malaria; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium knowlesi; Protozoan Proteins; Sensitivity and Specificity
PubMed: 35672772
DOI: 10.1186/s12936-022-04203-9 -
The Journal of Infectious Diseases Jan 2022Plasmodium falciparum malaria dominates throughout sub-Saharan Africa, but the prevalence of Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax...
BACKGROUND
Plasmodium falciparum malaria dominates throughout sub-Saharan Africa, but the prevalence of Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax increasingly contribute to infection in countries that control malaria using P. falciparum-specific diagnostic and treatment strategies.
METHODS
We performed quantitative polymerase chain reaction (qPCR) on 2987 dried blood spots from the 2015-2016 Malawi Demographic and Health Survey to identify presence and distribution of nonfalciparum infection. Bivariate models were used to determine species-specific associations with demographic and environmental risk factors.
RESULTS
Nonfalciparum infections had broad spatial distributions. Weighted prevalence was 0.025 (SE, 0.004) for P. malariae, 0.097 (SE, 0.008) for P. ovale spp., and 0.001 (SE, 0.0005) for P. vivax. Most infections (85.6%) had low-density parasitemias ≤ 10 parasites/µL, and 66.7% of P. malariae, 34.6% of P. ovale spp., and 40.0% of P. vivax infections were coinfected with P. falciparum. Risk factors for P. malariae were like those known for P. falciparum; however, there were few risk factors recognized for P. ovale spp. and P. vivax, perhaps due to the potential for relapsing episodes.
CONCLUSIONS
The prevalence of any nonfalciparum infection was 11.7%, with infections distributed across Malawi. Continued monitoring of Plasmodium spp. becomes critical as nonfalciparum infections become important sources of ongoing transmission.
Topics: Adolescent; Adult; Female; Humans; Malaria; Malaria, Vivax; Malawi; Male; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Real-Time Polymerase Chain Reaction; Young Adult
PubMed: 34244739
DOI: 10.1093/infdis/jiab353 -
Current Research in Parasitology &... 2021and are protozoan parasites that can cause malaria in humans. They are genetically indistinguishable from, respectively, and , i.e. parasites infecting New World...
and are protozoan parasites that can cause malaria in humans. They are genetically indistinguishable from, respectively, and , i.e. parasites infecting New World non-human primates in South America. In the tropical rainforests of the Brazilian Atlantic coast, it has long been hypothesized that . and . in platyrrhine primates originated from . and . in humans. A recent hypothesis proposed the inclusion of into the transmission dynamics between humans and non-human primates in the Brazilian Atlantic tropical rainforest. Herein, we assess the occurrence of human malaria in simians and sylvatic anophelines using field-collected samples in the Capivari-Monos Environmental Protection Area from 2015 to 2017. We first tested simian blood and anopheline samples. Two simian () blood samples (18%, = 11) showed DNA sequences, one for . and another for . . From a total of 9,416 anopheline females, we found 17 pools positive for species with a qPCR assay. Only three showed DNA sequence, one for . and the others for rodent malaria species (similar to and ). Based on these results, we tested 25 rodent liver samples for the presence of and obtained . DNA sequence in a rodent ( sp.) liver. The findings of this study indicate complex malaria transmission dynamics composed by parallel spillover-spillback of human malaria parasites, i.e. . , . , and . , in the Brazilian Atlantic forest.
PubMed: 35284897
DOI: 10.1016/j.crpvbd.2021.100032 -
ACS Infectious Diseases Nov 2021and cultivation of has facilitated active research into the malaria parasite toward the quest for basic knowledge and the discovery of effective drug treatments. Such...
and cultivation of has facilitated active research into the malaria parasite toward the quest for basic knowledge and the discovery of effective drug treatments. Such a drug discovery program is currently difficult for simply because of the absence of and cultivation system for its asexual blood stages supporting antimalarial evaluation. Despite availability of artemisinin combination therapies effective on , is being increasingly detected in malaria endemic countries. is responsible for chronic infections and is associated with a high burden of anemia and morbidity. Here, we optimized and adapted conditions under which can be cultured and used for screening antimalarial drugs. Subsequently, this enabled us to test compounds such as artemether, chloroquine, lumefantrine, and quinine for antimalarial activity against .
Topics: Antimalarials; Humans; Lumefantrine; Malaria, Falciparum; Plasmodium falciparum; Plasmodium malariae
PubMed: 34711047
DOI: 10.1021/acsinfecdis.1c00262 -
Malaria Journal Nov 2014Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used... (Review)
Review
BACKGROUND
Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.
METHODS
A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014.
RESULTS
The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi.
CONCLUSION
ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority.
TRIAL REGISTRATION
CRD42014009103.
Topics: Antimalarials; Artemisinins; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Malaria; Treatment Outcome
PubMed: 25428624
DOI: 10.1186/1475-2875-13-463 -
Open Forum Infectious Diseases May 2020We assessed the efficacy of artemisinin-based combination therapies for treatment of uncomplicated malaria, with or without co-infecting spp., in Sumatera, Indonesia.
BACKGROUND
We assessed the efficacy of artemisinin-based combination therapies for treatment of uncomplicated malaria, with or without co-infecting spp., in Sumatera, Indonesia.
METHODS
Febrile patients aged >6 months with uncomplicated were randomized to receive dihydroartemisinin-piperaquine or artemether-lumefantrine, plus single-dose primaquine, and were followed for 42 days. Mixed infections were included; infections received 14 days of primaquine. We retrospectively restricted the analysis to cases with polymerase chain reaction (PCR)-confirmed parasitemia. Recurrent parasitemia in follow-up was identified by species-specific nested PCR.
RESULTS
Of the 3731 participants screened, 302 were enrolled and randomized. In the dihydroartemisinin-piperaquine arm, infections were confirmed by PCR in 59 participants, with mixed infections in 23 (39.0%). In the artemether-lumefantrine arm, infections were confirmed by PCR in 55 participants, with mixed infections in 16 (29.0%). Both regimens were well tolerated, and symptoms improved rapidly in all treated participants. In the dihydroartemisinin-piperaquine arm, 1 recurrence (on day 7) and 6 recurrences (1 had a mixed infection with ) were identified during days 3-42 of follow-up. In the artemether-lumefantrine arm, 1 recurrence occurred on day 35. Submicroscopic persistence occurred during follow-up in 21 (37%) of 57 receiving dihydroartemisinin-piperaquine and 20 (39%) of 51 receiving artemether-lumefantrine.
CONCLUSIONS
In Sumatera, both regimens effectively cleared initial parasitemia, but and persisted in some individuals. Molecular species detection should be deployed in antimalarial efficacy trials in Indonesia.
TRIAL REGISTRATION
NCT02325180.
PubMed: 32420402
DOI: 10.1093/ofid/ofaa116 -
Bulletin of the World Health... Sep 2012To synthesize findings from recent studies of strategies to deliver insecticide-treated nets (ITNs) at scale in malaria-endemic areas. (Review)
Review
OBJECTIVE
To synthesize findings from recent studies of strategies to deliver insecticide-treated nets (ITNs) at scale in malaria-endemic areas.
METHODS
Databases were searched for studies published between January 2000 and December 2010 in which: subjects resided in areas with endemicity for Plasmodium falciparum and Plasmodium vivax malaria; ITN delivery at scale was evaluated; ITN ownership among households, receipt by pregnant women and/or use among children aged < 5 years was evaluated; and the study design was an individual or cluster-randomized controlled design, nonrandomized, quasi-experimental, before-and-after, interrupted time series or cross-sectional without temporal or geographical controls. Papers describing qualitative studies, case studies, process evaluations and cost-effectiveness studies linked to an eligible paper were also included. Study quality was assessed using the Cochrane risk of bias checklist and GRADE criteria. Important influences on scaling up were identified and assessed across delivery strategies.
FINDINGS
A total of 32 papers describing 20 African studies were reviewed. Many delivery strategies involved health sectors and retail outlets (partial subsidy), antenatal care clinics (full subsidy) and campaigns (full subsidy). Strategies achieving high ownership among households and use among children < 5 delivered ITNs free through campaigns. Costs were largely comparable across strategies; ITNs were the main cost. Cost-effectiveness estimates were most sensitive to the assumed net lifespan and leakage. Common barriers to delivery included cost, stock-outs and poor logistics. Common facilitators were staff training and supervision, cooperation across departments or ministries and stakeholder involvement.
CONCLUSION
There is a broad taxonomy of strategies for delivering ITNs at scale.
Topics: Animals; Global Health; Humans; Insecticide-Treated Bednets; Insecticides; Malaria; Plasmodium malariae; Plasmodium vivax; Public Health; Social Marketing
PubMed: 22984312
DOI: 10.2471/BLT.11.094771 -
Acta Tropica Oct 2012Plasmodium malariae is a protozoan parasite that causes malaria in humans and is genetically indistinguishable from Plasmodium brasilianum, a parasite infecting New...
Plasmodium malariae is a protozoan parasite that causes malaria in humans and is genetically indistinguishable from Plasmodium brasilianum, a parasite infecting New World monkeys in Central and South America. P. malariae has a wide and patchy global distribution in tropical and subtropical regions, being found in South America, Asia, and Africa. However, little is known regarding the genetics of these parasites and the similarity between them could be because until now there are only a very few genomic sequences available from simian Plasmodium species. This study presents the first molecular epidemiological data for P. malariae and P. brasilianum from Brazil obtained from different hosts and uses them to explore the genetic diversity in relation to geographical origin and hosts. By using microsatellite genotyping, we discovered that of the 14 human samples obtained from areas of the Atlantic forest, 5 different multilocus genotypes were recorded, while in a sample from an infected mosquito from the same region a different haplotype was found. We also analyzed the longitudinal change of circulating plasmodial genetic profile in two untreated non-symptomatic patients during a 12-months interval. The circulating genotypes in the two samples from the same patient presented nearly identical multilocus haplotypes (differing by a single locus). The more frequent haplotype persisted for almost 3 years in the human population. The allele Pm09-299 described previously as a genetic marker for South American P. malariae was not found in our samples. Of the 3 non-human primate samples from the Amazon Region, 3 different multilocus genotypes were recorded indicating a greater diversity among isolates of P. brasilianum compared to P. malariae and thus, P. malariae might in fact derive from P. brasilianum as has been proposed in recent studies. Taken together, our data show that based on the microsatellite data there is a relatively restricted polymorphism of P. malariae parasites as opposed to other geographic locations.
Topics: Alleles; Animals; Brazil; Culicidae; Genetic Variation; Genotype; Haplorhini; Humans; Malaria; Microsatellite Repeats; Molecular Epidemiology; Molecular Sequence Data; Multilocus Sequence Typing; Plasmodium; Primate Diseases
PubMed: 22705349
DOI: 10.1016/j.actatropica.2012.05.016 -
Emerging Infectious Diseases Jun 2023Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4...
Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4 Plasmodium spp. by performing PCR on dried blood spots collected within 8 regions of Tanzania during 2017. Among 3,456 schoolchildren, 22% had P. falciparum, 24% had P. ovale spp., 4% had P. malariae, and 0.3% had P. vivax infections. Most (91%) schoolchildren with P. ovale infections had low parasite densities; 64% of P. ovale infections were single-species infections, and 35% of those were detected in low malaria endemic regions. P. malariae infections were predominantly (73%) co-infections with P. falciparum. P. vivax was detected mostly in northern and eastern regions. Co-infections with >1 non-P. falciparum species occurred in 43% of P. falciparum infections. A high prevalence of P. ovale infections exists among schoolchildren in Tanzania, underscoring the need for detection and treatment strategies that target non-P. falciparum species.
Topics: Humans; Child; Plasmodium falciparum; Prevalence; Tanzania; Coinfection; Plasmodium malariae; Malaria; Malaria, Falciparum; Malaria, Vivax
PubMed: 37209670
DOI: 10.3201/eid2906.221016 -
Malaria Journal Sep 2013In Ethiopia Plasmodium falciparum and Plasmodium vivax are the dominant species accounting for roughly 60 and 40% of malaria cases, respectively. Recently a major shift...
BACKGROUND
In Ethiopia Plasmodium falciparum and Plasmodium vivax are the dominant species accounting for roughly 60 and 40% of malaria cases, respectively. Recently a major shift from P. falciparum to P. vivax has been observed in various parts of the country but the epidemiology of the other human malaria species, Plasmodium ovale spp. and Plasmodium malariae remains poorly understood. The aim of this study was to assess P. ovale curtisi and wallikeri infection in north-west Ethiopia by using microscopy and nested PCR.
METHODS
A health institution-based survey using non-probability sampling techniques was conducted at Maksegnet, Enfranze and Kola Diba health centres and Metema hospital in North Gondar. Three-hundred patients with signs and symptoms consistent with malaria were included in this study and capillary blood was collected for microscopic examination and molecular analysis of Plasmodium species. Samples were collected on Whatman 903 filter papers, stored in small plastic bags with desiccant and transported to Vienna (Austria) for molecular analysis. Data from study participants were entered and analysed by SPSS 20 software.
RESULTS
Out of 300 study participants (167 males and 133 females), 184 samples were classified positive for malaria (133 P. falciparum and 51 P. vivax) by microscopy. By species-specific PCR 233 Plasmodium spp (95% CI: 72.6-82) were detected and the majority 155 (66.5%, 95% CI: 60.2-72.3) were P. falciparum followed by P. vivax 69 (29.6%, 95% CI; 24.1-35.8) and 9 (3.9%, 95% CI: 2-7.2) samples were positive for P. ovale. Seven of P. ovale parasites were confirmed as P. ovale wallikeri and two were confirmed as P. ovale curtisi. None of the samples tested positive for P. malariae. During microscopic examination there were high (16.3%) false negative reports and all mixed infections and P. ovale cases were missed or misclassified.
CONCLUSION
This study indicates that P. ovale malaria is under-reported in Ethiopia and provides the first known evidence of the sympatric distribution of indigenous P. ovale wallikeri and P. ovale curtisi in Ethiopia. Therefore, further studies assessing the prevalence of the rare species P. ovale and P. malariae are urgently needed to better understand the species distribution and to adapt malaria control strategies.
Topics: Adolescent; Adult; DNA, Protozoan; Ethiopia; Female; Humans; Malaria; Male; Microscopy; Molecular Sequence Data; Plasmodium ovale; Polymerase Chain Reaction; Prevalence; Sequence Analysis, DNA; Young Adult
PubMed: 24073668
DOI: 10.1186/1475-2875-12-346