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Antimicrobial Agents and Chemotherapy Jul 2016Artemisinin resistance in Plasmodium falciparum, the agent of severe malaria, is currently a major obstacle to malaria control in Southeast Asia. A gene named "kelch13"...
Artemisinin resistance in Plasmodium falciparum, the agent of severe malaria, is currently a major obstacle to malaria control in Southeast Asia. A gene named "kelch13" has been associated with artemisinin resistance in P. falciparum The orthologue of the kelch gene in P. vivax was identified and a small number of mutations were found in previous studies. The kelch orthologues in the other two human malaria parasites, P. malariae and P. ovale, have not yet been studied. Therefore, in this study, the orthologous kelch genes of P. malariae, P. ovale wallikeri, and P. ovale curtisi were isolated and analyzed for the first time. The homologies of the kelch genes of P. malariae and P. ovale were 84.8% and 82.7%, respectively, compared to the gene in P. falciparum kelch polymorphisms were studied in 13 P. malariae and 5 P. ovale isolates from Thailand. There were 2 nonsynonymous mutations found in these samples. One mutation was P533L, which was found in 1 of 13 P. malariae isolates, and the other was K137R, found in 1 isolate of P. ovale wallikeri (n = 4). This result needs to be considered in the context of widespread artemisinin used within the region; their functional consequences for artemisinin sensitivity in P. malariae and P. ovale will need to be elucidated.
Topics: Antimalarials; Artemisinins; Humans; Malaria, Falciparum; Mutation; Plasmodium malariae; Plasmodium ovale; Polymorphism, Genetic; Thailand
PubMed: 27114275
DOI: 10.1128/AAC.00138-16 -
Frontiers in Immunology 2019IL-10 produced by CD4 T cells suppresses inflammation by inhibiting T cell functions and the upstream activities of antigen presenting cells (APCs). IL-10 was first... (Review)
Review
IL-10 produced by CD4 T cells suppresses inflammation by inhibiting T cell functions and the upstream activities of antigen presenting cells (APCs). IL-10 was first identified in Th2 cells, but has since been described in IFNγ-producing Tbet Th1, FoxP3 CD4 regulatory T (Treg) and IL-17-producing CD4 T (Th17) cells, as well as many innate and innate-like immune cell populations. IL-10 production by Th1 cells has emerged as an important mechanism to dampen inflammation in the face of intractable infection, including in African children with malaria. However, although these type I regulatory T (Tr1) cells protect tissue from inflammation, they may also promote disease by suppressing Th1 cell-mediated immunity, thereby allowing infection to persist. IL-10 produced by other immune cells during malaria can also influence disease outcome, but the full impact of this IL-10 production is still unclear. Together, the actions of this potent anti-inflammatory cytokine along with other immunoregulatory mechanisms that emerge following infection represent a potential hurdle for the development of immunity against malaria, whether naturally acquired or vaccine-induced. Recent advances in understanding how IL-10 production is initiated and regulated have revealed new opportunities for manipulating IL-10 for therapeutic advantage. In this review, we will summarize our current knowledge about IL-10 production during malaria and discuss its impact on disease outcome. We will highlight recent advances in our understanding about how IL-10 production by specific immune cell subsets is regulated and consider how this knowledge may be used in drug delivery and vaccination strategies to help eliminate malaria.
Topics: Animals; Humans; Interleukin-10; Malaria; Malaria Vaccines; Plasmodium malariae; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 30809232
DOI: 10.3389/fimmu.2019.00229 -
Malaria Journal Nov 2018Multiplex bead assays (MBA) that measure IgG antibodies to the carboxy-terminal 19-kDa sub-unit of the merozoite surface protein 1 (MSP1) are currently used to determine...
Specificity of the IgG antibody response to Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale MSP1 subunit proteins in multiplexed serologic assays.
BACKGROUND
Multiplex bead assays (MBA) that measure IgG antibodies to the carboxy-terminal 19-kDa sub-unit of the merozoite surface protein 1 (MSP1) are currently used to determine malaria seroprevalence in human populations living in areas with both stable and unstable transmission. However, the species specificities of the IgG antibody responses to the malaria MSP1 antigens have not been extensively characterized using MBA.
METHODS
Recombinant Plasmodium falciparum (3D7), Plasmodium malariae (China I), Plasmodium ovale (Nigeria I), and Plasmodium vivax (Belem) MSP1 proteins were covalently coupled to beads for MBA. Threshold cut-off values for the assays were estimated using sera from US citizens with no history of foreign travel and by receiver operator characteristic curve analysis using diagnostic samples. Banked sera from experimentally infected chimpanzees, sera from humans from low transmission regions of Haiti and Cambodia (N = 12), and elutions from blood spots from humans selected from a high transmission region of Mozambique (N = 20) were used to develop an antigen competition MBA for antibody cross-reactivity studies. A sub-set of samples was further characterized using antibody capture/elution MBA, IgG subclass determination, and antibody avidity measurement.
RESULTS
Total IgG antibody responses in experimentally infected chimpanzees were species specific and could be completely suppressed by homologous competitor protein at a concentration of 10 μg/ml. Eleven of 12 samples from the low transmission regions and 12 of 20 samples from the high transmission area had antibody responses that were completely species specific. For 7 additional samples, the P. falciparum MSP1 responses were species specific, but various levels of incomplete heterologous competition were observed for the non-P. falciparum assays. A pan-malaria MSP1 cross-reactive antibody response was observed in elutions of blood spots from two 20-30 years old Mozambique donors. The antibody response from one of these two donors had low avidity and skewed almost entirely to the IgG subclass.
CONCLUSIONS
Even when P. falciparum, P. malariae, P. ovale, and P. vivax are co-endemic in a high transmission setting, most antibody responses to MSP1 antigens are species-specific and are likely indicative of previous infection history. True pan-malaria cross-reactive responses were found to occur rarely.
Topics: Adolescent; Adult; Antibodies, Protozoan; Cambodia; Child; Humans; Immunoglobulin G; Malaria; Malaria, Falciparum; Malaria, Vivax; Middle Aged; Mozambique; Plasmodium; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Protozoan Proteins; Species Specificity; Young Adult
PubMed: 30413163
DOI: 10.1186/s12936-018-2566-0 -
Parasitology May 2007Plasmodium malariae, a protozoan parasite that causes malaria in humans, has a global distribution in tropical and subtropical regions and is commonly found in sympatry...
Plasmodium malariae, a protozoan parasite that causes malaria in humans, has a global distribution in tropical and subtropical regions and is commonly found in sympatry with other Plasmodium species of humans. Little is known about the genetics or population structure of P. malariae. In the present study, we describe polymorphic genetic markers for P. malariae and present the first molecular epidemiological data for this parasite. Six microsatellite or minisatellite markers were validated using 76 P. malariae samples from a diverse geographical range. The repeat unit length varied from 2 to 17 bp, and up to 10 different alleles per locus were detected. Multiple genotypes of P. malariae were detected in 33 of 70 samples from humans with naturally acquired infection. Heterozygosity was calculated to be between 0.236 and 0.811. Allelic diversity was reduced for samples from South America and, at some loci, in samples from Thailand compared with those from Malawi. The number of unique multilocus genotypes defined using the 6 markers was significantly greater in Malawi than in Thailand, even when data from single genotype infections were used. There was a significant reduction in the multiplicity of infection in symptomatic infections compared with asymptomatic ones, suggesting that clinical episodes are usually caused by the expansion of a single genotype.
Topics: Alleles; Animals; DNA, Protozoan; Genetic Markers; Genotype; Humans; Malaria; Microsatellite Repeats; Plasmodium malariae; Polymerase Chain Reaction; Polymorphism, Genetic
PubMed: 17140466
DOI: 10.1017/S0031182006001958 -
Malaria Journal May 2019Plasmodium malariae is the most neglected of the six human malaria species and it is still unknown which is the mechanism underlying the long latency of this Plasmodium. (Review)
Review
BACKGROUND
Plasmodium malariae is the most neglected of the six human malaria species and it is still unknown which is the mechanism underlying the long latency of this Plasmodium.
CASE PRESENTATION
A case of PCR-confirmed P. malariae recurrence in a 52-year old Italian man was observed 5 months after a primary attack. In the interval between the two observed episodes of malaria the patient denied any further stay in endemic areas except for a visit to Libya, a country considered malaria-free. Genomic DNA of the P. malariae strain using five microsatellites (PM2, PM9, PM11, PM25, PM34) and the antigen marker of circumsporozoite (csp) was amplified and sequenced. Analysis of polymorphisms of the P. malariae csp central repeat region showed differences between the strains responsible of the first and second episode of malaria. A difference in the allele size was also observed for the sequence analysis of PM2 microsatellites.
CONCLUSIONS
Plasmodium malariae is a challenging human malaria parasite and even with the use of molecular techniques the pathogenesis of recurrent episodes cannot be precisely explained.
Topics: Adult; Aged; Antimalarials; Female; Genome, Protozoan; Humans; Infant; Malaria; Male; Microsatellite Repeats; Middle Aged; Phylogeny; Plasmodium malariae; Polymerase Chain Reaction; Polymorphism, Genetic; Recurrence; Young Adult
PubMed: 31088460
DOI: 10.1186/s12936-019-2806-y -
PloS One 2019Plasmodium malariae is the third most prevalent human malaria-causing species and has a patchy, but ample distribution in the world. Humans can host the parasite for...
BACKGROUND
Plasmodium malariae is the third most prevalent human malaria-causing species and has a patchy, but ample distribution in the world. Humans can host the parasite for years without presenting significant symptoms, turning its diagnosis and control into a difficult task. Here, we investigated the immunogenicity of recombinant proteins of P. malariae MSP1.
METHODS
Five regions of PmMSP1 were expressed in Escherichia coli as GST-fusion proteins and immunized in BALB/c mice. The specificity, subtyping, and affinity of raised antibodies were evaluated by enzyme-linked immunosorbent assays. Cellular immune responses were analyzed by lymphoproliferation assays and cytokine levels produced by splenocytes were detected by cytometry.
RESULTS
We found that N-terminal, central regions, and PmMSP119 are strongly immunogenic in mice. After three doses, the induced immune responses remained high for 70 days. While antibodies induced after immunization with N-terminal and central regions showed similar affinities to the target antigens, affinities of IgG against PmMSP119 were higher. All proteins induced similar antibody subclass patterns (predominantly IgG1, IgG2a, and IgG2b), characterizing a mixed Th1/Th2 response. Further, autologous stimulation of splenocytes from immunized mice led to the secretion of IL2 and IL4, independently of the antigen used. Importantly, IgG from P. malariae-exposed individuals reacted against PmMSP1 recombinant proteins with a high specificity. On the other hand, sera from P. vivax or P. falciparum-infected individuals did not react at all against recombinant PmMSP1 proteins.
CONCLUSION
Recombinant PmMSP1 proteins are very useful diagnostic markers of P. malariae in epidemiological studies or in the differential diagnosis of malaria caused by this species. Immunization with recombinant PmMSP1 proteins resulted in a significant humoral immune response, which may turn them potential component candidates for a vaccine against P. malariae.
Topics: Amino Acid Sequence; Animals; Antibodies, Protozoan; Cell Proliferation; Cytokines; Humans; Immunization; Immunoglobulin G; Interleukin-4; Malaria; Merozoite Surface Protein 1; Mice, Inbred BALB C; Plasmodium malariae; Recombinant Proteins; Spleen
PubMed: 31344067
DOI: 10.1371/journal.pone.0219629 -
Diagnostics (Basel, Switzerland) Aug 2022Northeastern states of India share international borders with Myanmar, China, Bangladesh, and Bhutan, contributing 7.45% of the overall malaria cases in the country....
Northeastern states of India share international borders with Myanmar, China, Bangladesh, and Bhutan, contributing 7.45% of the overall malaria cases in the country. Mizoram accounts for the highest malaria burden in the northeastern states, with perennial transmission in the hilly and deep-forested areas. (93%) is the most prevalent human species, followed by ; however, information on and is negligible. Rapid diagnostic tests (RDTs) are the most preferred malaria diagnostic tool followed by microscopy in this high malaria-endemic region. The present epidemiological study was carried out in July and August 2019 to assess the malaria burden in and around the Chawngte primary health center, Lawngtlai District of Mizoram, using RDTs and microscopy as diagnostic tools. World Health Organization-certified level I microscopists examined the blood smears. Diagnosis using RDTs resulted in 151 malaria cases (: 136; : 15) out of 948 screened fever cases. However, blood smear examination detected 179 cases (: 154; : 17; mixed + infection: 3; : 5). Analysis revealed that the risk of malaria infection was higher in the ≥5-year-old subjects than in the under-5 age group. The mean parasite density of (1455.00/μL blood) was the lowest; cf. with : 12,275.08/μL blood. Surveillance at the point-of-care level using microscopy was able to detect all the four human species and their mixed infections, including , which were missed with RDTs. Thus, the quality of microscopy along with trained manpower should be strengthened to diagnose all human malaria parasite species (particularly and ) until the molecular tools are deployed at the field level to achieve malaria elimination by 2030.
PubMed: 36010365
DOI: 10.3390/diagnostics12082015 -
One Health (Amsterdam, Netherlands) Jun 2021Efforts for malaria elimination in India focus solely on the more prevalent human malaria parasites of and . The three non species - and are seldom studied though...
BACKGROUND
Efforts for malaria elimination in India focus solely on the more prevalent human malaria parasites of and . The three non species - and are seldom studied though they are often present as mixed infections with and thus may be misdiagnosed. This study provides a comprehensive landscape of , and infections from 1930 to 2020.
METHODOLOGY
We systematically searched for published literature on , and in India from PubMed database and collated data from 35 studies. The data, starting from 1930, were mapped decade-wise across India. The prevalence of the three neglected species and their proportional contribution to reported mixed-infection were also calculated and analysed.
PRINCIPAL FINDINGS
Amongst the three non species, infections have been reported in greater numbers across India and were mostly mono-infections till 1980. From 1983 onwards, reports of mixed infections with started to emerge. In contrast, reports on occurrence of are still rare barring few mixed infection studies. Further, mono- and mixed cases were first reported in 2004 in India and now has been found reported from four Indian states.
CONCLUSION
This is the first account of country-wide assimilation of reported malaria parasite species data that covers , and infection profiles from 1930 to 2020. This study illustrates the need to survey all 5 human malaria parasite species in India and to target them collectively during the malaria elimination phase.
PubMed: 33251321
DOI: 10.1016/j.onehlt.2020.100190 -
Parasites & Vectors Jan 2023Malaria control efforts are highly skewed towards Plasmodium falciparum while overlooking other Plasmodium species such as P. malariae. A better understanding of the...
BACKGROUND
Malaria control efforts are highly skewed towards Plasmodium falciparum while overlooking other Plasmodium species such as P. malariae. A better understanding of the role of Plasmodium species other than P. falciparum is needed to strengthen malaria elimination initiatives. The aim of the present study was to elucidate the contribution of P. malariae to malaria transmission in Cameroon.
METHODS
The study was conducted in the Ngatti Health District, a forest-savannah transition area in the Adamawa Region, Cameroon. A total of 497 individuals aged from 1 to 85 years were diagnosed with malaria in November 2020 using a rapid diagnostic test (RDT) and microscopy. Adult mosquitoes were collected between September 2019 and March 2020 by indoor aspiration and identified morphologically and molecularly. The infection status of Plasmodium spp. was also determined by quantitative PCR, and dried blood spots were collected from 156 participants with the aim to detect different Plasmodium species by nested PCR.
RESULTS
The overall Plasmodium prevalence was 50.3%, 51.8% and 64.7%, as detected by microscopy, the RDT and PCR, respectively. Based on the PCR results, P. falciparum was the most prevalent species (43%); followed by co-infections P. falciparum/P. malariae (17%), P. falciparum/P. ovale (1.3%), P. falciparum/P. ovale/P. malariae (1.3%); and then by P. malariae mono-infection (2.5%). The same trend was observed using microscopy, with 35% of participants infected with P. falciparum, 11% co-infected with P. falciparum/P. malariae and 4% infected with P. malariae. The prevalence and parasite density of malaria infection varied significantly with age group (P < 0.05), with the highest prevalence rate observed in children aged 6-10 years (P = 0.0001) while the density of Plasmodium infection increased significantly in children aged < 5 years compared to the other age groups (P = 10). Among the 757 Anopheles mosquitoes collected, 737 (97.35%) were An. funestus sensu stricto, 15 (1.9%) were An. gambiae and 5 (0.6%) were An. hancocki. The Plasmodium species recorded at the head/thorax level were P. falciparum and P. malariae, with a sporozoite infection rate of 8.4%; the highest sporozoite infection rate was recorded at Mibellon village (13.6%).
CONCLUSION
The results of this study reveal the significant contribution of P. malariae, in addition to P. falciparum, to the high malaria transmission rate in this region. These findings highlight the need to deploy initiatives to also tackle this Plasmodium species to eliminate malaria in the region.
Topics: Child; Adult; Animals; Humans; Infant; Child, Preschool; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Plasmodium malariae; Cameroon; Malaria; Malaria, Falciparum; Plasmodium falciparum; Anopheles; Prevalence; Forests
PubMed: 36698132
DOI: 10.1186/s13071-022-05635-7 -
Malaria Journal Dec 2021Information on the foci of Plasmodium species infections is essential for any country heading towards elimination. Odisha, one of the malaria-endemic states of India is...
BACKGROUND
Information on the foci of Plasmodium species infections is essential for any country heading towards elimination. Odisha, one of the malaria-endemic states of India is targeting elimination of malaria by 2030. To support decision-making regarding targeted intervention, the distribution of Plasmodium species infections was investigated in hard-to-reach areas where a special malaria elimination drive, namely Durgama Anchalare Malaria Nirakaran (DAMaN) began in 2017.
METHODS
A cross-sectional survey was conducted in 2228 households during July to November 2019 in six districts, to evaluate the occurrence of Plasmodium species. The species were identified by polymerase chain reaction (PCR) followed by sequencing, in case of Plasmodium ovale.
RESULTS
Of the 3557 blood specimens tested, malaria infection was detected in 282 (7.8%) specimens by PCR. Of the total positive samples, 14.1% were P. ovale spp. and 10.3% were Plasmodium malariae infections. The majority of P. ovale spp. (75.8%) infections were mixed with either Plasmodium falciparum and/or Plasmodium vivax and found to be distributed in three geophysical regions (Northern-plateau, Central Tableland and Eastern Ghat) of the State, while P. malariae has been found in Northern-plateau and Eastern Ghat regions. Speciation revealed occurrence of both Plasmodium ovale curtisi (classic type) and Plasmodium ovale wallikeri (variant type).
CONCLUSIONS
In the present study a considerable number of P. ovale spp. and P. malariae were detected in a wide geographical areas of Odisha State, which contributes around 40% of the country's total malaria burden. For successful elimination of malaria within the framework of national programme, P. ovale spp. along with P. malariae needs to be incorporated in surveillance system, especially when P. falciparum and P. vivax spp. are in rapid decline.
Topics: Disease Eradication; Humans; India; Malaria; Neglected Diseases; Plasmodium malariae; Plasmodium ovale; Prevalence
PubMed: 34949205
DOI: 10.1186/s12936-021-04010-8