-
Malaria Journal Nov 2022Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive...
BACKGROUND
Indonesia is progressing towards malaria elimination. To achieve this goal, intervention measures must be addressed to cover all Plasmodium species. Comprehensive control measures and surveillance programmes must be intensified. This study aims to determine the prevalence of microscopic and submicroscopic malaria in Langkat district, North Sumatera Province, Indonesia.
METHODS
A cross-sectional survey was conducted in six villages in Langkat district, North Sumatera Province in June 2019. Data were recorded using a standardized questionnaire. Finger pricked blood samples were obtained for malaria examination using rapid diagnostic test, thick and thin blood smears, and polymerase chain reaction.
RESULTS
A total of 342 individuals were included in the study. Of them, one (0.3%) had a microscopic Plasmodium malariae infection, no positive RDT examination, and three (0.9%) were positive for P. malariae (n = 1) and Plasmodium knowlesi (n = 2). The distribution of bed net ownership was owned by 40% of the study participants. The participants had a house within a radius of 100-500 m from the forest (86.3%) and had the housing material of cement floor (56.1%), a tin roof (82.2%), wooden wall (35.7%), bamboo wall (28.1%), and brick wall (21.6%).
CONCLUSION
Malaria incidence has substantially decreased in Langkat, North Sumatera, Indonesia. However, submicroscopic infection remains in the population and may contribute to further transmission. Surveillance should include the detection of microscopic undetected parasites, to enable the achievement of malaria elimination.
Topics: Humans; Plasmodium knowlesi; Plasmodium malariae; Cross-Sectional Studies; Indonesia; Malaria; Plasmodium falciparum
PubMed: 36333701
DOI: 10.1186/s12936-022-04335-y -
Scientific Reports Nov 2022The simian parasite Plasmodium knowlesi is the predominant species causing human malaria infection, including hospitalisations for severe disease and death, in Malaysian...
The simian parasite Plasmodium knowlesi is the predominant species causing human malaria infection, including hospitalisations for severe disease and death, in Malaysian Borneo. By contrast, there have been only a few case reports of knowlesi malaria from Indonesian Borneo. This situation seems paradoxical since both regions share the same natural macaque hosts and Anopheles mosquito vectors, and therefore have a similar epidemiologically estimated risk of infection. To determine whether there is a true cross-border disparity in P. knowlesi prevalence, we conducted a community-based malaria screening study using PCR in Kapuas Hulu District, West Kalimantan. Blood samples were taken between April and September 2019 from 1000 people aged 6 months to 85 years attending health care facilities at 27 study sites within or close to jungle areas. There were 16 Plasmodium positive samples by PCR, five human malarias (two Plasmodium vivax, two Plasmodium ovale and one Plasmodium malariae) and 11 in which no species could be definitively identified. These data suggest that, if present, simian malarias including P. knowlesi are rare in the Kapuas Hulu District of West Kalimantan, Indonesian Borneo compared to geographically adjacent areas of Malaysian Borneo. The reason for this discrepancy, if confirmed in other epidemiologically similar regions of Indonesian Borneo, warrants further studies targeting possible cross-border differences in human activities in forested areas, together with more detailed surveys to complement the limited data relating to monkey hosts and Anopheles mosquito vectors in Indonesian Borneo.
Topics: Animals; Humans; Indonesia; Plasmodium knowlesi; Malaria; Anopheles; Mosquito Vectors; Haplorhini; Malaysia
PubMed: 36329096
DOI: 10.1038/s41598-022-21570-0 -
Pathogens (Basel, Switzerland) Sep 2022is a neglected human malaria parasite with low parasitemia that often results in the misdiagnosis and underestimation of the actual disease burden of this pathogen....
is a neglected human malaria parasite with low parasitemia that often results in the misdiagnosis and underestimation of the actual disease burden of this pathogen. Microscopy is the best diagnostic tool, despite the fact that rapid diagnostic tests (RDTs) are the best surveillance tool for malaria diagnosis in many rural areas for their ease of use in elimination settings. For parasite antigen detection other than , RDTs depend on essential glycolytic proteins, i.e., lactate dehydrogenase (pLDH) and aldolase (pAldo) antigens. There is a lack of species-specific test kits for , and overall, its rapid antigenic test accuracy is questionable. False negative results can accelerate the burden of asymptomatic malaria infection and transmission. Here, we report a case of a malaria patient in Bangladesh infected with who tested negative on pLDH and pAldo based RDTs. This case provides useful information for health providers to be aware of possible RDT failure and also for the future development of analytically sensitive test kits for
PubMed: 36297130
DOI: 10.3390/pathogens11101072 -
International Journal of Molecular... Sep 2022Molecular diagnostic approaches are increasingly included in the diagnostic workup and even in the primary diagnosis of malaria in non-endemic settings, where it is...
Molecular diagnostic approaches are increasingly included in the diagnostic workup and even in the primary diagnosis of malaria in non-endemic settings, where it is difficult to maintain skillful microscopic malaria detection due to the rarity of the disease. Pathogen-specific nucleic acid amplification, however, bears the risk of overlooking other pathogens associated with febrile illness in returnees from the tropics. Here, we assessed the discriminatory potential of metagenomic sequencing for the identification of different species with various parasitemia in EDTA blood of malaria patients. Overall, the proportion of spp.-specific sequence reads in the assessed samples showed a robust positive correlation with parasitemia (Spearman r = 0.7307, = 0.0001) and a robust negative correlation with cycle threshold (Ct) values of genus-specific real-time PCR (Spearman r = -0.8626, ≤ 0.0001). Depending on the applied bioinformatic algorithm, discrimination on species level was successful in 50% (11/22) to 63.6% (14/22) instances. Limiting factors for the discrimination on species level were very low parasitemia, species-depending lacking availability of reliable reference genomes, and mixed infections with high variance of the proportion of the infecting species. In summary, metagenomic sequencing as performed in this study is suitable for the detection of malaria in human blood samples, but the diagnostic detection limit for a reliable discrimination on species level remains higher than for competing diagnostic approaches like microscopy and PCR.
Topics: Edetic Acid; Humans; Malaria; Nucleic Acids; Parasitemia; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Real-Time Polymerase Chain Reaction
PubMed: 36232449
DOI: 10.3390/ijms231911150 -
Electrochimica Acta Oct 2022The absence of reliable species-specific diagnostic tools for malaria at point-of-care (POC) remains a major setback towards effective disease management. This is partly...
The absence of reliable species-specific diagnostic tools for malaria at point-of-care (POC) remains a major setback towards effective disease management. This is partly due to the limited sensitivity and specificity of the current malaria POC diagnostic kits especially in cases of low-density parasitaemia and mixed species infections. In this study, we describe the first label-free DNA-based genosensors based on electrochemical impedance spectroscopy (EIS) for species-specific detection of and . The limits of detection (LOD) for the three species-specific genosensors were down in attomolar concentrations ranging from 18.7 aM to 43.6 aM, which is below the detection limits of previously reported malaria genosensors. More importantly, the diagnostic performance of the three genosensors were compared to quantitative real-time polymerase chain reaction (qPCR) assays using purified genomic DNA and the paired whole blood lysates from clinical samples. Remarkably, all the qPCR-positive purified genomic DNA samples were correctly identified by the genosensors indicating 100% sensitivity for each of the three malaria species. The specificities of the three genosensors ranged from 66.7% to 100.0% with a Therapeutic Turnaround Time (TTAT) within 30 min, which is comparable to the TTAT of current POC diagnostic tools for malaria. This work represents a significant step towards the development of accurate and rapid species-specific nucleic acid-based toolkits for the diagnosis of malaria at the POC.
PubMed: 36225971
DOI: 10.1016/j.electacta.2022.140988 -
MBio Oct 2022Several unrelated classes of antimalarial compounds developed against Plasmodium falciparum target a parasite-specific P-type ATP-dependent Na pump, PfATP4. We have...
Several unrelated classes of antimalarial compounds developed against Plasmodium falciparum target a parasite-specific P-type ATP-dependent Na pump, PfATP4. We have previously shown that other malaria parasite species infecting humans are less susceptible to these compounds. Here, we generated a series of transgenic Plasmodium knowlesi orthologue replacement (OR) lines in which the endogenous locus was replaced by a recodonized atp4 () coding region or the orthologous coding region from P. falciparum, Plasmodium malariae, Plasmodium ovale subsp. , or Plasmodium vivax. Each OR transgenic line displayed a similar growth pattern to the parental P. knowlesi line. We found significant orthologue-specific differences in parasite susceptibility to three chemically unrelated ATP4 inhibitors, but not to comparator drugs, among the P. knowlesi OR lines. The PfATP4 transgenic line of P. knowlesi was significantly more susceptible than our control PkATP4 line to three ATP4 inhibitors: cipargamin, PA21A092, and SJ733. The PvATP4 and PmATP4 lines were similarly susceptible to the control PkATP4 line, but the PocATP4 line was significantly less susceptible to all ATP4 inhibitors than the PkATP4 line. Cipargamin-induced inhibition of Na efflux was also significantly greater with the P. falciparum orthologue of ATP4. This confirms that species-specific susceptibility differences previously observed in studies of human isolates are partly or wholly enshrined in the primary amino acid sequences of the respective ATP4 orthologues and highlights the need to monitor efficacy of investigational malaria drugs against multiple species. P. knowlesi is now established as an important model for studying drug susceptibility in non-falciparum malaria parasites. Effective drugs are vital to minimize the illness and death caused by malaria. Development of new drugs becomes ever more urgent as drug resistance emerges. Among promising compounds now being developed to treat malaria are several unrelated molecules that each inhibit the same protein in the malaria parasite-ATP4. Here, we exploited the genetic tractability of P. knowlesi to replace its own ATP4 genes with orthologues from five human-infective species to understand the drug susceptibility differences among these parasites. We previously estimated the susceptibility to ATP4-targeting drugs of each species using clinical samples from malaria patients. These estimates closely matched those of the corresponding "hybrid" P. knowlesi parasites carrying introduced ATP4 genes. Thus, species-specific ATP4 inhibitor efficacy is directly determined by the sequence of the gene. Our novel approach to understanding cross-species susceptibility/resistance can strongly support the effort to develop antimalarials that effectively target all human malaria parasite species.
Topics: Animals; Humans; Plasmodium knowlesi; Antimalarials; Parasites; Adenosine Triphosphatases; Plasmodium falciparum; Malaria, Falciparum; Malaria; Cations; Adenosine Triphosphate
PubMed: 36190127
DOI: 10.1128/mbio.01178-22 -
Frontiers in Microbiology 2022Malaria elimination includes neglected human malaria parasites spp., and . Biological features such as association with low-density infection and the formation of... (Review)
Review
Malaria elimination includes neglected human malaria parasites spp., and . Biological features such as association with low-density infection and the formation of hypnozoites responsible for relapse make their elimination challenging. Studies on these parasites rely primarily on clinical samples due to the lack of long-term culture techniques. With improved methods to enrich parasite DNA from clinical samples, whole-genome sequencing of the neglected malaria parasites has gained increasing popularity. Population genomics of more than 2200 global isolates has improved our knowledge of parasite biology and host-parasite interactions, identified vaccine targets and potential drug resistance markers, and provided a new way to track parasite migration and introduction and monitor the evolutionary response of local populations to elimination efforts. Here, we review advances in population genomics for neglected malaria parasites, discuss how the rich genomic information is being used to understand parasite biology and epidemiology, and explore opportunities for the applications of malaria genomic data in malaria elimination practice.
PubMed: 36160257
DOI: 10.3389/fmicb.2022.984394 -
Diagnostics (Basel, Switzerland) Sep 2022Malaria is one of the most common tropical diseases encountered by members of the French military who are deployed in operations under constrained conditions in...
Malaria is one of the most common tropical diseases encountered by members of the French military who are deployed in operations under constrained conditions in malaria-endemic areas. Blood smear microscopy-the gold standard for malaria diagnosis-is often not available in such settings, where the detection of malaria relies on rapid diagnostic tests (RDTs). Ten RDTs (from Biosynex, Carestart, Humasis, SD Bioline, and CTK Biotech), based on the detection of the histidine-rich protein 2 (HRP2) or lactate dehydrogenase (pLDH, PfLDH, or PvLDH), were assessed against 159 samples collected from imported malaria cases, including 79 , 37 , 22 , and 21 parasites. Samples had been previously characterised using microscopy and real-time PCR. The overall sensitivities for the test ranged from 69.8% (111/159) to 95% (151/159). There was no significant difference for the specific detection of (96.2% to 98.7%, = 0.845). No significant difference was found between sensitivities to by pan LDH or pvLDH (81.1% (30/37) to 94.6% (35/37) ( = 0.845)). Some of the RDTs missed most of and , with sensitivities for all RDTs ranging respectively from 4.5% (1/22) to 81.8% (18/22) and 14.3% (3/21) to 95.2% (20/21). Carestart Malaria Pf/Pan (pLDH) Ag G0121, a pLDH-based RDT (PfLDH and pLDH), showed the highest sensitivities to (98.7%, 78/79), (94.6%, 35/37), (81.8%, 18/22), and (95.2%, 20/21) and meets the requirements for military deployments in malaria-endemic areas.
PubMed: 36140641
DOI: 10.3390/diagnostics12092240 -
Malaria Journal Sep 2022In sub-Saharan Africa, malaria is the common diagnosis for febrile illness and related clinical features, resulting in the under-diagnosis of other aetiologies, such as...
BACKGROUND
In sub-Saharan Africa, malaria is the common diagnosis for febrile illness and related clinical features, resulting in the under-diagnosis of other aetiologies, such as arboviruses and Rickettsia. While these may not be significant causes of mortality in malaria-endemic areas, they affect the daily life and performance of affected individuals. It is, therefore, important to have a clear picture of these other aetiologies to institute correct diagnoses at hospitals and improve patient outcomes.
METHODS
Blood samples were collected from patients with fever and other clinical features associated with febrile illness at selected hospitals in the malaria-endemic counties of Busia, Bungoma, and Kakamega, and screened for Crimean-Congo haemorrhagic fever, Sindbis, dengue and chikungunya viruses, Rickettsia africae, and Plasmodium spp. using high-throughput real-time PCR techniques. A logistic regression was performed on the results to explore the effect of demographic and socio-economic independent variables on malaria infection.
RESULTS
A total of 336 blood samples collected from hospital patients between January 2018 and February 2019 were screened, of which 17.6% (59/336) were positive for Plasmodium falciparum and 1.5% (5/336) for Plasmodium malariae. Two patients had dual P. falciparum/P. malariae infections. The most common clinical features reported by the patients who tested positive for malaria were fever and headache. None of the patients were positive for the arboviruses of interest or R. africae. Patients living in Busia (OR 5.2; 95% CI 2.46-11.79; p < 0.001) and Bungoma counties (OR 2.7; 95% CI 1.27-6.16; p = 0.013) had higher odds of being infected with malaria, compared to those living in Kakamega County.
CONCLUSIONS
The reported malaria prevalence is in line with previous studies. The absence of arboviral and R. africae cases in this study may have been due to the limited number of samples screened, low-level circulation of arboviruses during inter-epidemic periods, and/or the use of PCR alone as a detection method. Other sero-surveys confirming their circulation in the area indicate that further investigations are warranted.
Topics: Arboviruses; Fever; Hospitals; Humans; Kenya; Malaria; Plasmodium malariae; Real-Time Polymerase Chain Reaction; Rickettsia
PubMed: 36115978
DOI: 10.1186/s12936-022-04287-3 -
Scientific Reports Sep 2022The merozoite surface protein-1 (MSP1) is a prime candidate for an asexual blood stage vaccine against malaria. However, polymorphism in this antigen could compromise...
The merozoite surface protein-1 (MSP1) is a prime candidate for an asexual blood stage vaccine against malaria. However, polymorphism in this antigen could compromise the vaccine's efficacy. Although the extent of sequence variation in MSP1 has been analyzed from various Plasmodium species, little is known about structural organization and diversity of this locus in Plasmodium malariae (PmMSP1). Herein, we have shown that PmMSP1 contained five conserved and four variable blocks based on analysis of the complete coding sequences. Variable blocks were characterized by short insertion and deletion variants (block II), polymorphic nonrepeat sequences (block IV), complex repeat structure with size variation (block VI) and degenerate octapeptide repeats (block VIII). Like other malarial MSP1s, evidences of intragenic recombination have been found in PmMSP1. The rate of nonsynonymous nucleotide substitutions significantly exceeded that of synonymous nucleotide substitutions in block IV, suggesting positive selection in this region. Codon-based analysis of deviation from neutrality has identified a codon under purifying selection located in close proximity to the homologous region of the 38 kDa/42 kDa cleavage site of P. falciparum MSP1. A number of predicted linear B-cell epitopes were identified across both conserved and variable blocks of the protein. However, polymorphism in repeat-containing blocks resulted in alteration of the predicted linear B-cell epitope scores across variants. Although a number of predicted HLA-class II-binding peptides were identified in PmMSP1, all variants of block IV seemed not to be recognized by common HLA-class II alleles among Thai population, suggesting that diversity in this positive selection region could probably affect host immune recognition. The data on structural diversity in PmMSP1 could be useful for further studies such as vaccine development and strain characterization of this neglected malaria parasite.
Topics: Base Sequence; Epitopes, B-Lymphocyte; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Merozoite Surface Protein 1; Nucleotides; Plasmodium malariae
PubMed: 36114242
DOI: 10.1038/s41598-022-19049-z