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Trends in Parasitology Jun 2024Small-Saunders et al. uncovered a new facet of artemisinin resistance in Plasmodium in which parasites use a previously underexplored arm of stress response mechanisms....
Small-Saunders et al. uncovered a new facet of artemisinin resistance in Plasmodium in which parasites use a previously underexplored arm of stress response mechanisms. Through altered epitranscriptomic modifications on tRNA, changed translation patterns adapt resistant cells to facilitate entry into a quiescent-like state which provides the parasite an escape from many drugs.
PubMed: 38910099
DOI: 10.1016/j.pt.2024.06.004 -
Trends in Parasitology Jun 2024The protozoan parasite Plasmodium falciparum, responsible for the deadliest form of human malaria, employs antigenic variation via monoallelic expression as a key... (Review)
Review
The protozoan parasite Plasmodium falciparum, responsible for the deadliest form of human malaria, employs antigenic variation via monoallelic expression as a key survival strategy. The selective activation of one out of the 60-member var gene family is key to understanding the parasite's ability to cause severe disease and evade the host immune response. var gene activation is initiated by its relocation to a specialized expression site. While the perinuclear expression site (PES) plays a crucial role in enabling the expression of a single allele, the characteristics of this PES remain largely obscure. Recent breakthroughs in genome editing tools and the discovery of regulatory noncoding RNAs have shed light on this intriguing biological feature, offering significant insights into the mechanisms of pathogen virulence.
PubMed: 38910098
DOI: 10.1016/j.pt.2024.06.002 -
European Journal of Medicinal Chemistry Jun 2024The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput...
The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates.
PubMed: 38909569
DOI: 10.1016/j.ejmech.2024.116599 -
Diagnostic Microbiology and Infectious... Jun 2024Drug resistance surveillance is a major integral part of malaria control programs. Molecular methods play a pivotal role in drug resistance detection and related...
Drug resistance surveillance is a major integral part of malaria control programs. Molecular methods play a pivotal role in drug resistance detection and related molecular research. This study aimed to develop a rapid and accurate detection method for drug resistance of Plasmodium falciparum (P. falciparum). A quantitative real-time PCR (qPCR) assay has been developed that identifies the mutation at locus A256T in the P.falciparum multi-drug resistance(pfmdr1) gene producing amino acid change at position 86. The results of 198 samples detected by qPCR were consistent with nested PCR and sequencing, giving an accuracy of 94.3%. The sensitivity, specificity, positive and negative predictive value of qPCR were 85.7%, 97.6%, 90.0% and 96.4%, respectively. The results of qPCR are basically consistent with the nested PCR, which is expected to replace the nested PCR as a new molecular biological method for drug resistance detection, providing reliable technical support for global malaria prevention and control.
PubMed: 38909426
DOI: 10.1016/j.diagmicrobio.2024.116400 -
The National Medical Journal of India 2023Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal...
Burden of malaria during pregnancy in perennial transmission settings of two densely forested and remote blocks (Baihar and Birsa) of district Balaghat, Madhya Pradesh, central India.
Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal outcomes in endemic areas. Methods We did a field-based study to assess the burden of MIP (prevalence at the time of enrolment and follow-up) and to identify risk factors for MIP in the Birsa and Baihar blocks of district Balaghat in Madhya Pradesh, which have perennial malaria transmission. Malaria screening (during 2015-2017) was done by microscopy and bivalent rapid diagnostic test (SD Bioline RDT, malaria antigen Plasmodium falciparum/Plasmodium vivax Pf/Pv). Dried blood spots were used for haemoglobin estimation. Sociodemographic details with past and present pregnancy status were obtained. A subset of pregnant women were followed up for malaria during pregnancy. Women were also screened for malaria post delivery. Malaria treatment was given as per the National Guidelines of 2013. Multivariate analysis was done to assess independent risk factors for malaria. Results A total of 1728 pregnant women were screened, of which 1651 were included in the final analysis. Malaria prevalence at first screening was 23.4% (Pf 88%). Prevalence and Pf parasitaemia both were significantly higher among primigravid (G1) compared to multigravid (G>2; p value 0.012 and 0.019, respectively). Pregnant women of the Baiga ethnic group were more likely to have malaria compared to those belonging to the Gond group (OR [95% CI]; 2.4 [1.7-3.4]; p<0.00001) and non-indigenous group (OR [95% CI]; 8.3 [3.9-19.7]; p<0.00001). Primigravid status of women, first and second trimester of pregnancy, women belonging to indigenous ethnic tribal group and cash crop insufficiency for whole year (a socioeconomic indicator) in the family were the independent risk factors for malaria. Conclusion MIP is a major public health problem in forested tribal settlements of Birsa and Baihar blocks of Balaghat district in Madhya Pradesh and requires immediate intervention.
Topics: Humans; Female; Pregnancy; India; Adult; Pregnancy Complications, Parasitic; Prevalence; Risk Factors; Malaria, Falciparum; Young Adult; Malaria, Vivax; Forests; Adolescent; Antimalarials; Plasmodium falciparum
PubMed: 38909309
DOI: 10.25259/NMJI_535_21 -
Malaria Journal Jun 2024Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria.
BACKGROUND
Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria.
METHODS
Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients' general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented.
RESULTS
532 imported malaria cases were diagnosed over 11 years (2013-2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26-60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died.
CONCLUSIONS
The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.
Topics: Sri Lanka; Humans; Male; Adult; Middle Aged; Female; Young Adult; Communicable Diseases, Imported; Malaria, Falciparum; Malaria, Vivax; Aged; Adolescent; Malaria; Disease Eradication
PubMed: 38909255
DOI: 10.1186/s12936-024-05014-w -
Current Opinion in Insect Science Jun 2024Mosquito-borne diseases have a major impact on global human health. Biological agents that colonize the mosquito vector are increasingly explored as an intervention... (Review)
Review
Mosquito-borne diseases have a major impact on global human health. Biological agents that colonize the mosquito vector are increasingly explored as an intervention strategy to prevent vector-borne disease transmission. For instance, the release of mosquitoes carrying the endosymbiotic bacterium Wolbachia effectively reduced dengue virus incidence and disease. Insect-specific viruses are likewise considered as biocontrol agents against vector-borne diseases. While most studies focused on insect-specific viruses as an intervention against arthropod-borne viruses, we here consider whether mosquito-specific viruses may affect transmission of the malaria causing Plasmodium parasite by Anopheles mosquitoes. Although there is no direct experimental evidence addressing this question, we found that viral infections in dipteran insects activate some of the immune pathways that are antiparasitic in Anopheles. These findings suggest that indirect virus-parasite interactions could occur and that insect-specific viruses may modulate malaria transmission. Tripartite interactions between viruses, parasites, and Anopheles mosquitoes thus merit further investigation.
PubMed: 38908822
DOI: 10.1016/j.cois.2024.101222 -
Acta Tropica Jun 2024Malaria continues to be a global public health problem although it has been eliminated from many countries. Sri Lanka and China are two countries that recently achieved... (Review)
Review
Malaria continues to be a global public health problem although it has been eliminated from many countries. Sri Lanka and China are two countries that recently achieved malaria elimination status, and many countries in Southeast Asia are currently in the pipeline for achieving the same goal by 2030. However, Plasmodium knowlesi, a non-human primate malaria parasite continues to pose a threat to public health in this region, infecting many humans in all countries in Southeast Asia except for Timor-Leste. Besides, other non-human primate malaria parasite such as Plasmodium cynomolgi and Plasmodium inui are infecting humans in the region. The non-human primates, the long-tailed and pig-tailed macaques which harbour these parasites are now increasingly prevalent in farms and forest fringes close by to the villages. Additionally, the Anopheles mosquitoes belonging to the Lecuosphyrus Group are also present in these areas which makes them ideal for transmitting the non-human primate malaria parasites. With changing landscape and deforestation, non-human primate malaria parasites will affect more humans in the coming years with the elimination of human malaria. Perhaps due to loss of immunity, more humans will be infected as currently being demonstrated in Malaysia. Thus, control measures need to be instituted rapidly to achieve the malaria elimination status by 2030. However, the zoonotic origin of the parasite and the changes of the vectors behaviour to early biting seems to be the stumbling block to the malaria elimination efforts in this region. In this review, we discuss the challenges faced in malaria elimination due to deforestation and the serious threat posed by non-human primate malaria parasites.
PubMed: 38908421
DOI: 10.1016/j.actatropica.2024.107280 -
Scientific Reports Jun 2024The applicability of the specific human IgG antibody response to Anopheles gambiae salivary Gland Protein-6 peptide 1 (gSG6-P1 salivary peptide) as a biomarker able to...
The applicability of the specific human IgG antibody response to Anopheles gambiae salivary Gland Protein-6 peptide 1 (gSG6-P1 salivary peptide) as a biomarker able to distinguish the level of exposure to mosquito bites according to seasonal variations has not yet been evaluated in Central African regions. The study aimed to provide the first reliable data on the IgG anti-gSG6-P1 response in rural area in Cameroon according to the dry- and rainy-season. Between May and December 2020, dry blood samples were collected from people living in the Bankeng village in the forest area of the Centre region of Cameroon. Malaria infection was determined by thick-blood smear microscopy and multiplex PCR. The level of IgG anti-gSG6-P1 response, was assessed by enzyme-linked immunosorbent assay. Anopheles density and aggressiveness were assessed using human landing catches. The prevalence of malaria infection remains significantly higher in the rainy season than in the dry season (77.57% vs 61.44%; p = 0.0001). The specific anti-gSG6-P1 IgG response could be detected in individuals exposed to few mosquito bites and showed inter-individual heterogeneity even when living in the same exposure area. In both seasons, the level of anti-gSG6-P1 IgG response was not significantly different between Plasmodium infected and non-infected individuals. Mosquito bites were more aggressive in the rainy season compared to the dry season (human biting rate-HBR of 15.05 b/p/n vs 1.5 b/p/n) where mosquito density was very low. Infected mosquitoes were found only during the rainy season (sporozoite rate = 10.63% and entomological inoculation rate-EIR = 1.42 ib/p/n). The level of IgG anti-gSG6-P1 response was significantly higher in the rainy season and correlated with HBR (p ˂ 0.0001). This study highlights the high heterogeneity of individual's exposure to the Anopheles gambiae s.l vector bites depending on the transmission season in the same area. These findings reinforce the usefulness of the anti-gSG6-P1 IgG response as an accurate immunological biomarker for detecting individual exposure to Anopheles gambiae s.l. bites during the low risk period of malaria transmission in rural areas and for the differentiating the level of exposure to mosquitoes.
Topics: Animals; Anopheles; Humans; Cameroon; Immunoglobulin G; Insect Bites and Stings; Female; Adult; Male; Salivary Proteins and Peptides; Rural Population; Seasons; Adolescent; Young Adult; Malaria; Middle Aged; Child; Mosquito Vectors; Child, Preschool; Insect Proteins
PubMed: 38906949
DOI: 10.1038/s41598-024-58337-8 -
Scientific Reports Jun 2024Hemozoin is a natural biomarker formed during the hemoglobin metabolism of Plasmodium parasites, the causative agents of malaria. The rotating-crystal magneto-optical...
Hemozoin is a natural biomarker formed during the hemoglobin metabolism of Plasmodium parasites, the causative agents of malaria. The rotating-crystal magneto-optical detection (RMOD) has been developed for its rapid and sensitive detection both in cell cultures and patient samples. In the current article we demonstrate that, besides quantifying the overall concentration of hemozoin produced by the parasites, RMOD can also track the size distribution of the hemozoin crystals. We establish the relations between the magneto-optical signal, the mean parasite age and the median crystal size throughout one erythrocytic cycle of Plasmodium falciparum parasites, where the latter two are determined by optical and scanning electron microscopy, respectively. The significant correlation between the magneto-optical signal and the stage distribution of the parasites indicates that the RMOD method can be utilized for species-specific malaria diagnosis and for the quick assessment of drug efficacy.
Topics: Hemeproteins; Plasmodium falciparum; Humans; Erythrocytes; Malaria, Falciparum; Microscopy, Electron, Scanning
PubMed: 38906910
DOI: 10.1038/s41598-024-60988-6