-
Malaria Journal Apr 2019Malaria is endemic in Tanzania with majority of clinical cases caused by Plasmodium falciparum. Additionally, Plasmodium malariae and Plasmodium ovale spp. are also...
BACKGROUND
Malaria is endemic in Tanzania with majority of clinical cases caused by Plasmodium falciparum. Additionally, Plasmodium malariae and Plasmodium ovale spp. are also present and clinical manifestations caused by these infections are not well described. Clinical episodes caused by P. malariae infections are often characterized by a relatively mild illness with a low number of parasites, which can persist for long periods. In this report, two cases of P. malariae infections that were identified during a clinical trial evaluating the P. falciparum malaria vaccine candidate, PfSPZ Vaccine are described. The two participants were followed up and monitored for clinical and laboratory parameters to assess vaccine safety providing the opportunity to study clinical manifestations of P. malariae over 4 months.
CASE PRESENTATION
Two young, healthy Tanzanian men infected with low density asexual blood stage P. malariae diagnosed by quantitative polymerase chain reaction (qPCR) are described. Retrospective analysis of collected and stored blood samples revealed that the two volunteers had constant asexual blood stage parasitaemia for more than 4 months. During the 132 days of infection, the volunteers' vital signs, body temperature and serum biochemistry all remained within normal ranges. Haematological abnormalities, which were transiently outside normal ranges, were regarded as not clinically significant. During this time period, four consecutive evaluations of blood samples by thick blood smear microscopy conducted by an experienced microscopist were all negative, indicating the presence of low-density sub-microscopic infections.
CONCLUSIONS
The two cases of P. malariae infections presented here confirm the ability of this Plasmodium species to persist at low density in the human host for extended time periods without causing clinical symptoms. The presented data also demonstrate that clinical study sites in malaria endemic regions need to have a strong malaria diagnostic infrastructure, including the ability of capturing sub-microscopic parasitaemia and differentiation of Plasmodium species. Trial registration ClinicalTrials.gov: NCT02613520, https://clinicaltrials.gov/ct2/show/NCT02613520 , Registered: November 24th 2015, Enrolment of the first participant to the trial: December 15th 2015, Trial was registered before the first participant was enrolled.
Topics: Asymptomatic Infections; Humans; Malaria; Malaria Vaccines; Male; Microscopy; Parasitemia; Plasmodium malariae; Randomized Controlled Trials as Topic; Real-Time Polymerase Chain Reaction; Retrospective Studies; Tanzania; Vaccination; Young Adult
PubMed: 31036014
DOI: 10.1186/s12936-019-2787-x -
Journal of Postgraduate Medicine 2018
Topics: Adult; Amodiaquine; Antimalarials; Artemisinins; Drug Combinations; Fever; Humans; India; Kenya; Malaria; Male; Plasmodium malariae; Primaquine; Travel; Treatment Outcome
PubMed: 29692404
DOI: 10.4103/jpgm.JPGM_358_17 -
Clinical Laboratory Oct 2021The imported cases of Plasmodium malariae (P. malariae) and Plasmodium ovale (P. ovale) malaria are increasing annually, especially in central China. Here, we report a...
BACKGROUND
The imported cases of Plasmodium malariae (P. malariae) and Plasmodium ovale (P. ovale) malaria are increasing annually, especially in central China. Here, we report a case of serological rapid diagnostic test (RDT)-negative P. malariae malaria imported from West Africa.
METHODS
The case patient was exclusively diagnosed with P. malariae through microscopy, Plasmodium genus-specific nested polymerase chain reaction (PCR), and sequencing of targeted P. malariae circumsporozoite (pmcsp) gene, except for serological RDT.
RESULTS
The patient was discharged in stable condition after 5 days of hospitalization, with no overt malaria parasites or associated symptoms.
CONCLUSIONS
This case reveals that asymptomatic P. malariae infections can occur among exported laborers back from malaria-endemic areas, some of whom may escape serological screening test or RDT, posing a continuing potential threat to malaria control. Therefore, PCR-based molecular techniques are more effective and necessary than serological RDT for malaria surveillance nationwide.
Topics: Africa, Western; Diagnostic Tests, Routine; Humans; Malaria; Plasmodium malariae; Plasmodium ovale
PubMed: 34655199
DOI: 10.7754/Clin.Lab.2021.210208 -
Malaria Journal May 2023Malaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned...
BACKGROUND
Malaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned travellers has become important. The accurate and timely diagnosis of malaria is the key in preventing re-establishment, and malaria rapid diagnostic tests (RDTs) are frequently used due to their convenience. However, the RDT performance in Plasmodium malariae (P. malariae) infection diagnosis remains unknown.
METHODS
This study analysed epidemiological features and diagnosis patterns of imported P. malariae cases from 2013 to 2020 in Jiangsu Province and evaluated the sensitivity of four parasite enzyme lactate dehydrogenase (pLDH)-targeting RDTs (Wondfo, SD BIONLINE, CareStart and BioPerfectus) and one aldolase-targeting RDT(BinaxNOW) for P. malariae detection. Furthermore, influential factors were investigated, including parasitaemia load, pLDH concentration and target gene polymorphisms.
RESULTS
The median duration from symptom onset to diagnosis among patients with P. malariae infection was 3 days, which was longer than that with Plasmodium falciparum (P. falciparum) infection. The RDTs had a low detection rate (39/69, 56.5%) among P. malariae cases. All tested RDT brands had poor performance in P. malariae detection. All the brands except the worst-performing SD BIOLINE, achieved 75% sensitivity only when the parasite density was higher than 5000 parasites/μL. Both pLDH and aldolase showed relatively conserved and low gene polymorphism rates.
CONCLUSIONS
The diagnosis of imported P. malariae cases was delayed. The RDTs had poor performance in P. malariae diagnosis and may threaten the prevention of malaria re-establishment from returned travellers. The improved RDTs or nucleic acid tests for P. malariae cases are urgently needed for the detection of imported cases in the future.
Topics: Humans; Plasmodium malariae; Rapid Diagnostic Tests; Malaria; Malaria, Falciparum; China; Fructose-Bisphosphate Aldolase; Aldehyde-Lyases; L-Lactate Dehydrogenase
PubMed: 37226272
DOI: 10.1186/s12936-023-04596-1 -
PLoS Neglected Tropical Diseases May 2019A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination. Despite the need to target all Plasmodium...
A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination. Despite the need to target all Plasmodium species, current focus is mainly directed towards Plasmodium falciparum, and to a lesser extent P. vivax. There is a substantial lack of data on both global and local transmission patterns of the neglected malaria parasites P. malariae and P. ovale spp. We used a species-specific real-time PCR assay targeting the Plasmodium 18s rRNA gene to evaluate temporal trends in the prevalence of all human malaria parasites over a 22-year period in a rural village in Tanzania.We tested 2897 blood samples collected in five cross-sectional surveys conducted between 1994 and 2016. Infections with P. falciparum, P. malariae, and P. ovale spp. were detected throughout the study period, while P. vivax was not detected. Between 1994 and 2010, we found a more than 90% reduction in the odds of infection with all detected species. The odds of P. falciparum infection was further reduced in 2016, while the odds of P. malariae and P. ovale spp. infection increased 2- and 6-fold, respectively, compared to 2010. In 2016, non-falciparum species occurred more often as mono-infections. The results demonstrate the persistent transmission of P. ovale spp., and to a lesser extent P. malariae despite a continued decline in P. falciparum transmission. This illustrates that the transmission patterns of the non-falciparum species do not necessarily follow those of P. falciparum, stressing the need for attention towards non-falciparum malaria in Africa. Malaria elimination will require a better understanding of the epidemiology of P. malariae and P. ovale spp. and improved tools for monitoring the transmission of all Plasmodium species, with a particular focus towards identifying asymptomatic carriers of infection and designing appropriate interventions to enhance malaria control.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; DNA, Protozoan; Female; Humans; Infant; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Prevalence; RNA, Ribosomal, 18S; Real-Time Polymerase Chain Reaction; Tanzania; Young Adult
PubMed: 31136585
DOI: 10.1371/journal.pntd.0007414 -
Scientific Reports Jul 2020The genomic diversity of Plasmodium malariae malaria parasites is understudied, partly because infected individuals tend to present with low parasite densities, leading...
The genomic diversity of Plasmodium malariae malaria parasites is understudied, partly because infected individuals tend to present with low parasite densities, leading to difficulties in obtaining sufficient parasite DNA for genome analysis. Selective whole genome amplification (SWGA) increases the relative levels of pathogen DNA in a clinical sample, but has not been adapted for P. malariae parasites. Here we design customized SWGA primers which successfully amplify P. malariae DNA extracted directly from unprocessed clinical blood samples obtained from patients with P. malariae-mono-infections from six countries, and further test the efficacy of SWGA on mixed infections with other Plasmodium spp. SWGA enables the successful whole genome sequencing of samples with low parasite density (i.e. one sample with a parasitaemia of 0.0064% resulted in 44% of the genome covered by ≥ 5 reads), leading to an average 14-fold increase in genome coverage when compared to unamplified samples. We identify a total of 868,476 genome-wide SNPs, of which 194,709 are unique across 18 high-quality isolates. After exclusion of the hypervariable subtelomeric regions, a high-quality core subset of 29,899 unique SNPs is defined. Population genetic analysis suggests that P. malariae parasites display clear geographical separation by continent. Further, SWGA successfully amplifies genetic regions of interest such as orthologs of P. falciparum drug resistance-associated loci (Pfdhfr, Pfdhps, Pfcrt, Pfk13 and Pfmdr1), and several non-synonymous SNPs were detected in these genes. In conclusion, we have established a robust SWGA approach that can assist whole genome sequencing of P. malariae, and thereby facilitate the implementation of much-needed large-scale multi-population genomic studies of this neglected malaria parasite. As demonstrated in other Plasmodia, such genetic diversity studies can provide insights into the biology underlying the disease and inform malaria surveillance and control measures.
Topics: Animals; DNA, Protozoan; Drug Resistance; Genetics, Population; Humans; Malaria; Nucleic Acid Amplification Techniques; Plasmodium malariae; Polymorphism, Single Nucleotide; Whole Genome Sequencing
PubMed: 32616738
DOI: 10.1038/s41598-020-67568-4 -
Emerging Infectious Diseases Jun 2007Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by...
Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by microscopic examination, identified P. falciparum, P. vivax, and P. malariae. PCR confirmed the P. malariae and P. falciparum but not P. vivax infections. DNA sequencing and rRNA gene sequences showed transmission of P. malariae. This report confirms that P. malariae is still being transmitted in Haiti.
Topics: Animals; Base Sequence; Haiti; Humans; Jamaica; Malaria; Molecular Sequence Data; Plasmodium malariae; Prevalence; Refugees
PubMed: 17553241
DOI: 10.3201/eid1306.061227 -
The Journal of Parasitology Apr 2002During malaria surveys in Myanmar, 2 peculiar forms of Plasmodium malariae-like parasites were found. The morphologies of their early trophozoite stages were distinct...
During malaria surveys in Myanmar, 2 peculiar forms of Plasmodium malariae-like parasites were found. The morphologies of their early trophozoite stages were distinct from that of the typical P. malariae, resembling instead that of Plasmodium vivax, var. minuta, reported by Emin, and Plasmodium tenue, reported by Stephens, both in 1914. Two polymerase chain reaction (PCR)-based diagnoses, which target the same regions in the small subunit ribosomal RNA (SSUrRNA) genes, indicated that these parasites were new variant forms of P. malariae and that they could be separated into 2 genetic types that correlated with the 2 morphological types. Sequence analysis of the SSUrRNA and the circumsporozoite protein genes revealed that they were distinct both from each other and from other known P. malariae isolates and that the P. tenue-like type was closer to a monkey quartan malaria parasite, Plasmodium brasilianum. These results illustrate that the microscopic appearance of human P. malariae parasites may be more varied than previously assumed and suggest the value of molecular tools in the evaluation of malaria morphological variants.
Topics: Animals; Base Sequence; DNA, Protozoan; Humans; Malaria; Molecular Sequence Data; Myanmar; Nucleic Acid Hybridization; Plasmodium malariae; Polymerase Chain Reaction; Protozoan Proteins; RNA, Ribosomal; Rural Population; Sequence Homology, Nucleic Acid
PubMed: 12054010
DOI: 10.1645/0022-3395(2002)088[0350:UPMLPI]2.0.CO;2 -
Malaria Journal Feb 2011Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P.... (Comparative Study)
Comparative Study
BACKGROUND
Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns--one seasonal, one perennial--to explore the effects of transmission on population structures.
METHODS
Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters.
RESULTS
Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting.
CONCLUSIONS
The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cluster Analysis; DNA Fingerprinting; DNA, Protozoan; Female; Genotype; Haplotypes; Humans; Infant; Linkage Disequilibrium; Malaria; Malawi; Male; Microsatellite Repeats; Middle Aged; Plasmodium falciparum; Plasmodium malariae; Young Adult
PubMed: 21314950
DOI: 10.1186/1475-2875-10-38 -
International Journal For Parasitology Oct 2016Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P.... (Comparative Study)
Comparative Study
Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status.
Topics: Adult; Africa, Western; Animals; Antigens, Protozoan; Antigens, Surface; China; Chromobox Protein Homolog 5; Genetic Variation; Genome, Protozoan; Humans; Interspersed Repetitive Sequences; Male; Membrane Proteins; Multigene Family; Phylogeny; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Young Adult
PubMed: 27392654
DOI: 10.1016/j.ijpara.2016.05.009