Pub Date : 2025-12-01Epub Date: 2025-10-06DOI: 10.1007/s12639-025-01863-7
Saumya Srivastava, Anil Kumar Gupta, Amit Singh, Sudip Kumar Datta, Sarman Singh
Toxoplasma gondii is a widespread protozoan parasite that poses significant health risks globally. Current serological tests for diagnosing T. gondii infections are hindered by high costs, cumbersomeness, and the necessity for skills and expertise. This study aimed to identify promising antigens for the development of an immunochromatographic rapid diagnostic test (RDT). Whole-cell antigens were isolated from the virulent RH strain of T. gondii maintained in Swiss albino male mice. After infection, peritoneal fluid was harvested, and tachyzoites were processed to obtain whole cell lysates, which were subjected to SDS-PAGE and Western blot analysis. Five novel antigenic protein bands reactive to anti-Toxoplasma IgG and IgM antibodies were identified on western blot. Subsequent LC-MS/MS analysis revealed 158 proteins. However, only 18 proteins were selected on the basis of high mascot score (> 40) and were investigated further. On BLAST search 10 of these proteins exhibited significant homology (> 90%) with closely related microorganisms hence these were excluded. Out of remaining 8, T. gondii specific glyceraldehyde-3-phosphate dehydrogenase (GAPDH1) and lactate dehydrogenase (LDH1) were found to be reactive to both IgG and IgM on western blot, indicating their potential as reliable biomarkers for T. gondii infection.
{"title":"Harnessing antigenic proteins of <i>Toxoplasma gondii</i> for efficient diagnosis: a study of promising candidates.","authors":"Saumya Srivastava, Anil Kumar Gupta, Amit Singh, Sudip Kumar Datta, Sarman Singh","doi":"10.1007/s12639-025-01863-7","DOIUrl":"https://doi.org/10.1007/s12639-025-01863-7","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> is a widespread protozoan parasite that poses significant health risks globally. Current serological tests for diagnosing <i>T. gondii</i> infections are hindered by high costs, cumbersomeness, and the necessity for skills and expertise. This study aimed to identify promising antigens for the development of an immunochromatographic rapid diagnostic test (RDT). Whole-cell antigens were isolated from the virulent RH strain of <i>T. gondii</i> maintained in Swiss albino male mice. After infection, peritoneal fluid was harvested, and tachyzoites were processed to obtain whole cell lysates, which were subjected to SDS-PAGE and Western blot analysis. Five novel antigenic protein bands reactive to anti-Toxoplasma IgG and IgM antibodies were identified on western blot. Subsequent LC-MS/MS analysis revealed 158 proteins. However, only 18 proteins were selected on the basis of high mascot score (> 40) and were investigated further. On BLAST search 10 of these proteins exhibited significant homology (> 90%) with closely related microorganisms hence these were excluded. Out of remaining 8, <i>T. gondii</i> specific glyceraldehyde-3-phosphate dehydrogenase (GAPDH1) and lactate dehydrogenase (LDH1) were found to be reactive to both IgG and IgM on western blot, indicating their potential as reliable biomarkers for <i>T. gondii</i> infection.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"897-907"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cystic echinococcosis is an important zoonotic disease and pose a significant health threat worldwide. Echinococcus granulosus (E. granulosus) has ten strains and exhibits many characteristics. Hence, the current study aims to identify the hydatid cysts genotype isolated from sheep and goats in Rasht County through morphological and molecular analyses. During 6 months (winter 2018 to summer 2019), 50 samples, including liver and lung tissues, were collected at Rasht County slaughterhouse (30 goats and 20 sheep). Hydatid cyst fluid (HCF) was extracted, and protocoleces were collected and rostellar hooks' morphological parameters were examined. DNA was extracted, polymerase chain reaction (PCR) was performed using primers on the ITS 1 gene using EgF and EgR, and the enzyme Bsh1236 I was used for digestion. The morphological and molecular analysis identified sheep and goat hydatid cyst isolated as strain G1-G3. This study highlights the importance of carefully monitoring the prevalence of hydatid disease in Rasht, Iran, especially in small ruminants. It is especially important for future studies in strain identification and awareness-raising about methods for preventing and controlling zoonotic diseases caused by E. granulosus. This research can be considered important for epidemiological studies and examining how the parasite spreads in other regions of the country and even globally in the face of drug resistance and common diseases between humans and livestock.
{"title":"Morphological and molecular investigation of hydatid cyst isolated from small ruminants in Rasht, Iran.","authors":"Saeed Farokhpey, Soheil Sadr, Saeed Yaghfoori, Hassan Borji","doi":"10.1007/s12639-025-01808-0","DOIUrl":"https://doi.org/10.1007/s12639-025-01808-0","url":null,"abstract":"<p><p>Cystic echinococcosis is an important zoonotic disease and pose a significant health threat worldwide. <i>Echinococcus granulosus</i> (<i>E. granulosus</i>) has ten strains and exhibits many characteristics. Hence, the current study aims to identify the hydatid cysts genotype isolated from sheep and goats in Rasht County through morphological and molecular analyses. During 6 months (winter 2018 to summer 2019), 50 samples, including liver and lung tissues, were collected at Rasht County slaughterhouse (30 goats and 20 sheep). Hydatid cyst fluid (HCF) was extracted, and protocoleces were collected and rostellar hooks' morphological parameters were examined. DNA was extracted, polymerase chain reaction (PCR) was performed using primers on the ITS 1 gene using EgF and EgR, and the enzyme Bsh1236 I was used for digestion. The morphological and molecular analysis identified sheep and goat hydatid cyst isolated as strain G1-G3. This study highlights the importance of carefully monitoring the prevalence of hydatid disease in Rasht, Iran, especially in small ruminants. It is especially important for future studies in strain identification and awareness-raising about methods for preventing and controlling zoonotic diseases caused by <i>E. granulosus</i>. This research can be considered important for epidemiological studies and examining how the parasite spreads in other regions of the country and even globally in the face of drug resistance and common diseases between humans and livestock.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"944-950"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-16DOI: 10.1007/s12639-025-01834-y
Tayebe Roostaei, Seyed Ali Hosseini, Faeze Foroughi-Parvar, Mousa Motavalli Haghi, Mehrdad Hajilooi, Mohammad Matini
Toxoplasma gondii causes common parasitic infection, and congenital toxoplasmosis is considered a serious public health concern. This study aimed to evaluate the utility of maternal blood PCR in distinguishing acute from chronic toxoplasmosis during pregnancy. From January to June 2023, 291 pregnant women in Malayer, western Iran, were screened for T. gondii IgG antibodies via ELISA. Seropositive samples underwent further testing for IgG avidity and IgM antibodies. Peripheral blood samples from IgG-positive women were then analyzed for T. gondii DNA by targeting the B1 gene through nested PCR. Among the 291 pregnant women, 77 (26.46%; 95% CI: 21.39-31.53) tested positive for anti-Toxoplasma IgG. Seropositivity rates were significantly higher in women aged 39 years or older. Anti-Toxoplasma IgM was detected in two of the IgG-positive samples. IgG avidity results showed low levels in four asymptomatic women, borderline levels in four women, and high levels in 69 women. The Toxoplasma B1 gene was detected in four out of the 77 seropositive samples. Based on the combination of serological and PCR results, primary infection was diagnosed in three PCR-positive women with low and borderline IgG avidity. Finally, acute toxoplasmosis was diagnosed in three pregnant women (1%), indicating that the risk of congenital toxoplasmosis remains a serious issue. Furthermore, these findings suggest that serology results should be interpreted in conjunction with additional confirmatory tests.
{"title":"The role of blood nested B1-gene in differentiation of acute toxoplasmosis from chronic infection during pregnancy.","authors":"Tayebe Roostaei, Seyed Ali Hosseini, Faeze Foroughi-Parvar, Mousa Motavalli Haghi, Mehrdad Hajilooi, Mohammad Matini","doi":"10.1007/s12639-025-01834-y","DOIUrl":"https://doi.org/10.1007/s12639-025-01834-y","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> causes common parasitic infection, and congenital toxoplasmosis is considered a serious public health concern. This study aimed to evaluate the utility of maternal blood PCR in distinguishing acute from chronic toxoplasmosis during pregnancy. From January to June 2023, 291 pregnant women in Malayer, western Iran, were screened for <i>T. gondii</i> IgG antibodies via ELISA. Seropositive samples underwent further testing for IgG avidity and IgM antibodies. Peripheral blood samples from IgG-positive women were then analyzed for <i>T. gondii</i> DNA by targeting the B1 gene through nested PCR. Among the 291 pregnant women, 77 (26.46%; 95% CI: 21.39-31.53) tested positive for anti-<i>Toxoplasma</i> IgG. Seropositivity rates were significantly higher in women aged 39 years or older. Anti-<i>Toxoplasma</i> IgM was detected in two of the IgG-positive samples. IgG avidity results showed low levels in four asymptomatic women, borderline levels in four women, and high levels in 69 women. The <i>Toxoplasma</i> B1 gene was detected in four out of the 77 seropositive samples. Based on the combination of serological and PCR results, primary infection was diagnosed in three PCR-positive women with low and borderline IgG avidity. Finally, acute toxoplasmosis was diagnosed in three pregnant women (1%), indicating that the risk of congenital toxoplasmosis remains a serious issue. Furthermore, these findings suggest that serology results should be interpreted in conjunction with additional confirmatory tests.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"889-896"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-04DOI: 10.1007/s12639-025-01840-0
Wagaw Abebe, Dagmawi Woldesenbet
Malaria is an infectious disease caused by parasitic protozoans of the genus Plasmodium. Malaria control efforts on a global scale are in danger due to the emergence and spread of drug-resistant malaria. Despite stakeholders' dedication to the prevention and treatment of malaria, the current state of global health does not offer an effective answer to the issue of drug resistance. Furthermore, there is an information gap about the molecular mechanisms of Plasmodium falciparum's drug resistance, which makes it difficult to develop monitoring systems. Most countries lack adequate and comprehensive information on antimalarial drug efficacy. Plasmodium falciparum has developed resistance to almost all anti-malarial drugs, which poses a significant danger to malaria control worldwide. The fundamental mechanism of artemisinin resistance is due to point mutations in the beta-propeller domain of the gene encoding Kelch protein 13. Atovaquone resistance can be caused by a variety of mutations in the cytochrome b gene, with the majority of mutations affecting the protein's ubiquinol binding site. Similarly, mutations in the Plasmodium falciparum chloroquine resistance transporter, Plasmodium falciparum multi-drug resistance 1, and an increase in Plasmodium falciparum Plasmepsin II and III copy numbers all lead to 4-aminoquinoline drug resistance. Also, the number of amino acid substitutions in dihydrofolate reductase and dihydropteroate synthase is correlated with the degree of antifolate drug resistance. Moreover, amino alcohol drug resistance is caused by Plasmodium falciparum multidrug resistance protein 1 and Plasmodium falciparum Na+/H + exchanger 1 mutations. In general, Plasmodium falciparum chloroquine resistance transporter, Plasmodium falciparum multidrug resistance protein 1, Plasmodium falciparum Na+/H + exchanger 1, plasmepsin II & III, cytochrome b gene, dihydrofolate reductase, Plasmodium falciparum ATPases 6, Plasmodium falciparum Kelch protein 13, and dihydropteroate synthase were just the molecular markers of drug resistance of Plasmodium falciparum. Future research on the molecular mechanisms of drug resistance in P. falciparum should focus on significant area including using transcriptomic and genomic technologies to identify genetic variations associated with resistance. Finding the protein interactions that underlie these resistance mechanisms requires proteomic research. Additionally, the possibility of resistance development may be decreased by investigating combination therapies that target several phases of the P. falciparum lifecycle. In order to successfully address drug resistance in malaria, it will be essential to strengthen worldwide monitoring systems and promote interdisciplinary collaboration among researchers and healthcare professionals. Furthermore, regular monitoring, identification, and limiting of dr
{"title":"A review on molecular markers of <i>Plasmodium falciparum</i>.","authors":"Wagaw Abebe, Dagmawi Woldesenbet","doi":"10.1007/s12639-025-01840-0","DOIUrl":"10.1007/s12639-025-01840-0","url":null,"abstract":"<p><p>Malaria is an infectious disease caused by parasitic protozoans of the genus <i>Plasmodium.</i> Malaria control efforts on a global scale are in danger due to the emergence and spread of drug-resistant malaria. Despite stakeholders' dedication to the prevention and treatment of malaria, the current state of global health does not offer an effective answer to the issue of drug resistance. Furthermore, there is an information gap about the molecular mechanisms of <i>Plasmodium falciparum</i>'s drug resistance, which makes it difficult to develop monitoring systems. Most countries lack adequate and comprehensive information on antimalarial drug efficacy. <i>Plasmodium falciparum</i> has developed resistance to almost all anti-malarial drugs, which poses a significant danger to malaria control worldwide. The fundamental mechanism of artemisinin resistance is due to point mutations in the beta-propeller domain of the gene encoding Kelch protein 13. Atovaquone resistance can be caused by a variety of mutations in the cytochrome b gene, with the majority of mutations affecting the protein's ubiquinol binding site. Similarly, mutations in the <i>Plasmodium falciparum</i> chloroquine resistance transporter, <i>Plasmodium falciparum</i> multi-drug resistance 1, and an increase in <i>Plasmodium</i> falciparum Plasmepsin II and III copy numbers all lead to 4-aminoquinoline drug resistance. Also, the number of amino acid substitutions in dihydrofolate reductase and dihydropteroate synthase is correlated with the degree of antifolate drug resistance. Moreover, amino alcohol drug resistance is caused by <i>Plasmodium falciparum</i> multidrug resistance protein 1 and <i>Plasmodium falciparum</i> Na+/H + exchanger 1 mutations. In general, <i>Plasmodium falciparum</i> chloroquine resistance transporter, <i>Plasmodium falciparum</i> multidrug resistance protein 1, <i>Plasmodium falciparum</i> Na+/H + exchanger 1, plasmepsin II & III, cytochrome b gene, dihydrofolate reductase, <i>Plasmodium falciparum</i> ATPases 6, <i>Plasmodium falciparum</i> Kelch protein 13, and dihydropteroate synthase were just the molecular markers of drug resistance of <i>Plasmodium falciparum</i>. Future research on the molecular mechanisms of drug resistance in <i>P. falciparum</i> should focus on significant area including using transcriptomic and genomic technologies to identify genetic variations associated with resistance. Finding the protein interactions that underlie these resistance mechanisms requires proteomic research. Additionally, the possibility of resistance development may be decreased by investigating combination therapies that target several phases of the <i>P. falciparum</i> lifecycle. In order to successfully address drug resistance in malaria, it will be essential to strengthen worldwide monitoring systems and promote interdisciplinary collaboration among researchers and healthcare professionals. Furthermore, regular monitoring, identification, and limiting of dr","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"821-833"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-14DOI: 10.1007/s12639-025-01832-0
Naglaa Fathi Abd El-Latif, Mona Hassan Elsayad, Dekam Eisay Abdulsalam, Wessam El-Hadidy, Gehan A M Khodear, Amani Kazem, Heba El-Hadad
Cystic echinococcosis is a neglected helminthic zoonosis caused by Echinococcus spp., mostly E. granulosus. Current chemotherapeutic treatment options are based on benzimidazoles; mainly albendazole (ABZ) which are of limited effectiveness. Therefore, new anti-echinococcosis treatment agents are needed. Nitazoxanide (NTZ) is a broad-spectrum drug against a wide variety of intestinal parasites. The current work aimed to evaluate the efficacy of ABZ, ABZ chitosan nanoparticles (ABZ/Cs NPs), NTZ and NTZ/Cs NPs in mice experimentally infected with E. granulosus. Swiss albino mice were inoculated intra-peritoneally with ~ 1000 protoscoleces harvested from hydatid cysts from slaughtered camels. Drugs were administered orally daily to mice subgroups as follows: ABZ (50 mg/kg/4 weeks), blank Cs NPs (30 mg/Kg/4 weeks), ABZ/Cs NPs (50 mg/kg/4 weeks), NTZ (200 mg /kg/ 14 days) NTZ/Cs NPs (200 mg/ kg /14 days) 16 weeks after infection. Drug efficacy was assessed by parasitological, morphological and histopathological studies on hydatid cysts collected from the studied groups. Results revealed that the studied treatments had variable efficacy. ABZ/Cs NPs showed higher anti-cystic activity relative to ABZ, NTZ, NTZ/ CSNPs. Survival time increased in subgroups treated with ABZ/Cs NPs and Cs NPs followed by NTZ/Cs NPs. Mice received ABZ and ABZ/Cs NPs showed the highest reduction of hydatid cysts in different organs. SEM revealed severe morphological changes mainly in subgroups receiving ABZ and ABZ/Cs NPs. It was concluded that chitosan nanoparticles could enhance the therapeutic efficacy of ABZ and NTZ in the treatment of cystic echinococcosis.
{"title":"Evaluation of the therapeutic efficacy of albendazole and nitazoxanide loaded chitosan nanoparticles against experimental echinococcosis.","authors":"Naglaa Fathi Abd El-Latif, Mona Hassan Elsayad, Dekam Eisay Abdulsalam, Wessam El-Hadidy, Gehan A M Khodear, Amani Kazem, Heba El-Hadad","doi":"10.1007/s12639-025-01832-0","DOIUrl":"https://doi.org/10.1007/s12639-025-01832-0","url":null,"abstract":"<p><p>Cystic echinococcosis is a neglected helminthic zoonosis caused by <i>Echinococcus</i> spp., mostly <i>E. granulosus</i>. Current chemotherapeutic treatment options are based on benzimidazoles; mainly albendazole (ABZ) which are of limited effectiveness. Therefore, new anti-echinococcosis treatment agents are needed. Nitazoxanide (NTZ) is a broad-spectrum drug against a wide variety of intestinal parasites. The current work aimed to evaluate the efficacy of ABZ, ABZ chitosan nanoparticles (ABZ/Cs NPs), NTZ and NTZ/Cs NPs in mice experimentally infected with <i>E. granulosus</i>. Swiss albino mice were inoculated intra-peritoneally with ~ 1000 protoscoleces harvested from hydatid cysts from slaughtered camels. Drugs were administered orally daily to mice subgroups as follows: ABZ (50 mg/kg/4 weeks), blank Cs NPs (30 mg/Kg/4 weeks), ABZ/Cs NPs (50 mg/kg/4 weeks), NTZ (200 mg /kg/ 14 days) NTZ/Cs NPs (200 mg/ kg /14 days) 16 weeks after infection. Drug efficacy was assessed by parasitological, morphological and histopathological studies on hydatid cysts collected from the studied groups. Results revealed that the studied treatments had variable efficacy. ABZ/Cs NPs showed higher anti-cystic activity relative to ABZ, NTZ, NTZ/ CSNPs. Survival time increased in subgroups treated with ABZ/Cs NPs and Cs NPs followed by NTZ/Cs NPs. Mice received ABZ and ABZ/Cs NPs showed the highest reduction of hydatid cysts in different organs. SEM revealed severe morphological changes mainly in subgroups receiving ABZ and ABZ/Cs NPs. It was concluded that chitosan nanoparticles could enhance the therapeutic efficacy of ABZ and NTZ in the treatment of cystic echinococcosis.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1055-1067"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-06-30DOI: 10.1007/s12639-025-01826-y
Emmanuel Okoro Enyi, Joy Chimuanya Nnanna
Malaria is a major public health concern responsible for significant mortality and morbidity, especially in sub-Saharan Africa. Accurate diagnosis is crucial for effective malaria control and elimination strategies. Recent studies have confirmed the existence of Plasmodium falciparum histidine-rich protein 2 and 3 (Pfhrp2/3) deficient malaria parasites, which pose significant challenges to malaria diagnosis and control. This review provides a comprehensive overview of the existing literature on Pfhrp2/3 deletions and their implications on malaria diagnosis and control. A literature search was conducted using a combination of keywords (Pfhrp2/3 deletions, malaria diagnosis, malaria control, rapid diagnostic tests) and medical subject headings (MeSH) terms (Malaria/diagnosis, Malaria/parasitology, Plasmodium falciparum/genetics) in ScienceDirect, Springer, Google Scholar, and PubMed. Studies published in English between 2018 and 2024 were included, and a total of 83 studies were selected for inclusion in the review based on predefined inclusion and exclusion criteria. This review highlights the significant challenges posed by Pfhrp2/3 deletions to malaria diagnosis and control and identifies potential solutions, including alternative diagnostic approaches and novel RDTs targeting multiple antigens.
{"title":"Overcoming the challenges of <i>Plasmodium falciparum</i> histidine-rich protein 2 and 3 deletions in malaria diagnosis and control.","authors":"Emmanuel Okoro Enyi, Joy Chimuanya Nnanna","doi":"10.1007/s12639-025-01826-y","DOIUrl":"https://doi.org/10.1007/s12639-025-01826-y","url":null,"abstract":"<p><p>Malaria is a major public health concern responsible for significant mortality and morbidity, especially in sub-Saharan Africa. Accurate diagnosis is crucial for effective malaria control and elimination strategies. Recent studies have confirmed the existence of <i>Plasmodium falciparum</i> histidine-rich protein 2 and 3 (<i>Pfhrp2/3</i>) deficient malaria parasites, which pose significant challenges to malaria diagnosis and control. This review provides a comprehensive overview of the existing literature on <i>Pfhrp2/3</i> deletions and their implications on malaria diagnosis and control. A literature search was conducted using a combination of keywords (<i>Pfhrp2/3</i> deletions, malaria diagnosis, malaria control, rapid diagnostic tests) and medical subject headings (MeSH) terms (Malaria/diagnosis, Malaria/parasitology, <i>Plasmodium falciparum</i>/genetics) in ScienceDirect, Springer, Google Scholar, and PubMed. Studies published in English between 2018 and 2024 were included, and a total of 83 studies were selected for inclusion in the review based on predefined inclusion and exclusion criteria. This review highlights the significant challenges posed by <i>Pfhrp2/3</i> deletions to malaria diagnosis and control and identifies potential solutions, including alternative diagnostic approaches and novel RDTs targeting multiple antigens.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"834-840"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-05-17DOI: 10.1007/s12639-025-01817-z
Zeinab R Hassan, Yasmeen M Shaaban, Eman M Mahmoud, Amany Mesbah Mohammed Ali, Fatma Al-Zahraa Nabil Al-Shahed, Doaa E A Salama, Amira Nasr Ismail Elsokary, Ranya M Abdelgalil, Marwa A Alanany, Mona T Koullah, Nora Seliem, Doaa Refaat Amin, Shimaa A Mohamed, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Mona M Amin, Maryam Mohammed Mohammed Hamouda, Shimaa Attia Atta, Reham Abdelmonem Gadallah, Sami Mohamed Nasr
Toxoplasmosis is a common protozoal disease that can cause serious complications. Hence the available drug therapies possess limited activity against chronic forms of the disease; thus, it is urgent to find more effective agents. The current study highlighted the therapeutic activity of bone marrow mesenchymal stem cells (BMSCs) and ginger combined with spiramycin against chronic experimental toxoplasmosis. A total of 48 male Swiss albino mice were distributed into 8 groups: non-infected non-treated, infected non-treated, infected treated by spiramycin, infected treated by BMSCs, infected treated by ginger, infected treated by combined BMSCs and spiramycin, infected treated by combined BMSCs and ginger, and infected treated by combined BMSCs, ginger, and spiramycin. The evaluation was performed through parasitological counting of brain cyst burden, histopathological examination, immunohistochemical cyclooxygenase-2 (COX-2) staining assessment, serum IL-10 measurement, and apoptotic gene markers assay. The results revealed that combined BMSCs, ginger, and spiramycin displayed significantly reduced parasitic cyst burden, restored histopathological changes, decreased COX2 expression, and downregulated caspases gene expression. It can be concluded that adding BMSCs and ginger to spiramycin provides a potent therapeutic agent against chronic toxoplasmosis.
{"title":"Therapeutic outcome of bone marrow stem cells and ginger in chronic murine toxoplasmosis.","authors":"Zeinab R Hassan, Yasmeen M Shaaban, Eman M Mahmoud, Amany Mesbah Mohammed Ali, Fatma Al-Zahraa Nabil Al-Shahed, Doaa E A Salama, Amira Nasr Ismail Elsokary, Ranya M Abdelgalil, Marwa A Alanany, Mona T Koullah, Nora Seliem, Doaa Refaat Amin, Shimaa A Mohamed, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Mona M Amin, Maryam Mohammed Mohammed Hamouda, Shimaa Attia Atta, Reham Abdelmonem Gadallah, Sami Mohamed Nasr","doi":"10.1007/s12639-025-01817-z","DOIUrl":"https://doi.org/10.1007/s12639-025-01817-z","url":null,"abstract":"<p><p>Toxoplasmosis is a common protozoal disease that can cause serious complications. Hence the available drug therapies possess limited activity against chronic forms of the disease; thus, it is urgent to find more effective agents. The current study highlighted the therapeutic activity of bone marrow mesenchymal stem cells (BMSCs) and ginger combined with spiramycin against chronic experimental toxoplasmosis. A total of 48 male <i>Swiss albino</i> mice were distributed into 8 groups: non-infected non-treated, infected non-treated, infected treated by spiramycin, infected treated by BMSCs, infected treated by ginger, infected treated by combined BMSCs and spiramycin, infected treated by combined BMSCs and ginger, and infected treated by combined BMSCs, ginger, and spiramycin. The evaluation was performed through parasitological counting of brain cyst burden, histopathological examination, immunohistochemical cyclooxygenase-2 (COX-2) staining assessment, serum IL-10 measurement, and apoptotic gene markers assay. The results revealed that combined BMSCs, ginger, and spiramycin displayed significantly reduced parasitic cyst burden, restored histopathological changes, decreased COX2 expression, and downregulated caspases gene expression. It can be concluded that adding BMSCs and ginger to spiramycin provides a potent therapeutic agent against chronic toxoplasmosis.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1012-1021"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-30DOI: 10.1007/s12639-025-01849-5
Patrick O Sakyi, Samuel K Kwofie, Theresa Manful Gwira, Christine Moore, Cynthia Amisigo, Emmanuel Broni, Whelton A Miller, Michael D Wilson, Richard K Amewu
The current therapeutic agents for the treatments of visceral leishmaniasis are ineffective, and cytotoxic. Therefore, there is the urgent need for new chemotypes for the treatment of the disease with novel mechanisms of action. In our previous investigation, we identified the triazolopyridazine, STOCK6S-84928 as a potential inhibitor of Leishmania donovani sterol methyltransferase (LdSMT) with IC50 value of 118.3 µM. To improve the biological activity of the initial hit compound, we hereby describe the results of structural-activity relationship studies on STOCK6S-84928 via chemical modifications on the scaffold and virtually screening of 250 compounds obtained against the Modeller generated LdSMT structure. A total of 21 compounds were found to have binding energies ranging from - 7.0 to - 9.2 kcal/mol lower or comparable to the 22,26-azasterol (- 7.6 kcal/mol), the known inhibitor of the target. Molecular docking and molecular dynamics simulations revealed Ile272 and Tyr275 to be pivotal for ligand binding. The compounds were predicted to possess leishmanicidal activities with good drug-like properties. Significantly, the compounds 8, 9, 21, and 23 were predicted to possess antineoplastic, anti-inflammatory, analgesics, protein and MAP kinase inhibitory activities with probability of activity (Pa) > 0.2 and probability of inactivity (Pi) < 0.16. Through the applications of cyclization, amination, Williamson's ether synthesis, and Suzuki cross-coupling reactions, the selected analogues of STOCK6S-84928 were synthesised in moderate to high yields and characterized by FTIR, LC-MS, and NMR spectroscopy methods. In vitro antileishmanial evaluation of the synthesized compounds identified 23 as the most potent, exhibiting L. donovani promastigotes inhibitory activities with IC50 value of (1.9 ± 0.1) µM. The ortho-difluoropheneyl group as well as the triazolopyridine moieties were suspected to be responsible for the observed activity. Similarly, the compounds 10 and 16 required (0.8 ± 0.1) µM and (0.6 ± 0.0) µM, respectively to eliminate 50% of Trypanosoma brucei.
Graphical abstract:
Supplementary information: The online version contains supplementary material available at 10.1007/s12639-025-01849-5.
{"title":"Molecular docking, design, synthesis and in vitro analysis identify [1,2,4]triazolo[4,3-b]pyridazine derivatives as inhibitors of <i>Leishmania donovani</i> sterol methyltransferase.","authors":"Patrick O Sakyi, Samuel K Kwofie, Theresa Manful Gwira, Christine Moore, Cynthia Amisigo, Emmanuel Broni, Whelton A Miller, Michael D Wilson, Richard K Amewu","doi":"10.1007/s12639-025-01849-5","DOIUrl":"https://doi.org/10.1007/s12639-025-01849-5","url":null,"abstract":"<p><p>The current therapeutic agents for the treatments of visceral leishmaniasis are ineffective, and cytotoxic. Therefore, there is the urgent need for new chemotypes for the treatment of the disease with novel mechanisms of action. In our previous investigation, we identified the triazolopyridazine, STOCK6S-84928 as a potential inhibitor of <i>Leishmania donovani</i> sterol methyltransferase (<i>Ld</i>SMT) with IC<sub>50</sub> value of 118.3 µM. To improve the biological activity of the initial hit compound, we hereby describe the results of structural-activity relationship studies on STOCK6S-84928 via chemical modifications on the scaffold and virtually screening of 250 compounds obtained against the Modeller generated <i>Ld</i>SMT structure. A total of 21 compounds were found to have binding energies ranging from - 7.0 to - 9.2 kcal/mol lower or comparable to the 22,26-azasterol (- 7.6 kcal/mol), the known inhibitor of the target. Molecular docking and molecular dynamics simulations revealed Ile272 and Tyr275 to be pivotal for ligand binding. The compounds were predicted to possess leishmanicidal activities with good drug-like properties. Significantly, the compounds <b>8</b>, <b>9</b>, <b>21</b>, and <b>23</b> were predicted to possess antineoplastic, anti-inflammatory, analgesics, protein and MAP kinase inhibitory activities with probability of activity (Pa) > 0.2 and probability of inactivity (Pi) < 0.16. Through the applications of cyclization, amination, Williamson's ether synthesis, and Suzuki cross-coupling reactions, the selected analogues of STOCK6S-84928 were synthesised in moderate to high yields and characterized by FTIR, LC-MS, and NMR spectroscopy methods. In vitro antileishmanial evaluation of the synthesized compounds identified <b>23</b> as the most potent, exhibiting <i>L. donovani</i> promastigotes inhibitory activities with IC<sub>50</sub> value of (1.9 ± 0.1) µM. The <i>ortho</i>-difluoropheneyl group as well as the triazolopyridine moieties were suspected to be responsible for the observed activity. Similarly, the compounds <b>10</b> and <b>16</b> required (0.8 ± 0.1) µM and (0.6 ± 0.0) µM, respectively to eliminate 50% of <i>Trypanosoma brucei.</i></p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12639-025-01849-5.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"987-1011"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-24DOI: 10.1007/s12639-025-01874-4
M I Okpala, C F Obi, G E Aneru, O O Uzondu, C N Iheagwam, C T Oyiga, I O Ezeh, R C Ezeokonkwo, D N Onah
African animal trypanosomosis is a major constraint to livestock production in sub-Saharan Africa. Chemotherapy remains the primary control strategy, but the efficacy of various trypanocide brands in circulation in Africa, especially in Nigeria, remains uncertain. This study aimed to evaluate and compare the efficacy of selected, commonly used commercial brands of diminazene aceturate and isometamidium chloride against experimental Trypanosoma brucei brucei infection in mice. A total of 35 adult male mice were randomly assigned to seven groups of five mice each. Group 1 served as the uninfected control, while groups 2-7 were intraperitoneally (i.p.) infected with 10⁶ trypanosomes. Group 2 was left untreated, while groups 3-5 were treated with diminazene aceturate brands (TrypanocideDA 1-3) respectively at a dose of 7.0 mg/kg on day 13 post-infection (p.i). Groups 6 and 7 received isometamidium chloride brands (TrypanocideISM 1 and 2) respectively at a dose of 0.5 mg/kg on day 13 p.i. Efficacy was assessed through clinical signs, parasitaemia, haematological parameters (PCV, Hb concentration, erythrocyte count, leucocyte counts), parasite clearance time, body weight, rectal temperature, and survival. Parasite clearance was fastest in group 3 (2.4 days post-treatment) compared to other treated groups (3 days post-treatment). Diminazene aceturate-treated groups exhibited shorter relapse times than isometamidium chloride-treated groups. Treatment reversed the reduction in haematological indices across all groups. The study concluded that isometamidium chloride brands demonstrated superior efficacy compared to diminazene aceturate brands in treating T. brucei brucei infections.
{"title":"Comparative efficacy of trypanocide brands against experimental <i>Trypanosoma brucei brucei</i> infections in mice.","authors":"M I Okpala, C F Obi, G E Aneru, O O Uzondu, C N Iheagwam, C T Oyiga, I O Ezeh, R C Ezeokonkwo, D N Onah","doi":"10.1007/s12639-025-01874-4","DOIUrl":"https://doi.org/10.1007/s12639-025-01874-4","url":null,"abstract":"<p><p>African animal trypanosomosis is a major constraint to livestock production in sub-Saharan Africa. Chemotherapy remains the primary control strategy, but the efficacy of various trypanocide brands in circulation in Africa, especially in Nigeria, remains uncertain. This study aimed to evaluate and compare the efficacy of selected, commonly used commercial brands of diminazene aceturate and isometamidium chloride against experimental <i>Trypanosoma brucei brucei</i> infection in mice. A total of 35 adult male mice were randomly assigned to seven groups of five mice each. Group 1 served as the uninfected control, while groups 2-7 were intraperitoneally (i.p.) infected with 10⁶ trypanosomes. Group 2 was left untreated, while groups 3-5 were treated with diminazene aceturate brands (TrypanocideDA 1-3) respectively at a dose of 7.0 mg/kg on day 13 post-infection (p.i). Groups 6 and 7 received isometamidium chloride brands (TrypanocideISM 1 and 2) respectively at a dose of 0.5 mg/kg on day 13 p.i. Efficacy was assessed through clinical signs, parasitaemia, haematological parameters (PCV, Hb concentration, erythrocyte count, leucocyte counts), parasite clearance time, body weight, rectal temperature, and survival. Parasite clearance was fastest in group 3 (2.4 days post-treatment) compared to other treated groups (3 days post-treatment). Diminazene aceturate-treated groups exhibited shorter relapse times than isometamidium chloride-treated groups. Treatment reversed the reduction in haematological indices across all groups. The study concluded that isometamidium chloride brands demonstrated superior efficacy compared to diminazene aceturate brands in treating <i>T. brucei brucei</i> infections.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1086-1099"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-19DOI: 10.1007/s12639-025-01846-8
Eman S El-Wakil, Mohamed Farid, Walaa A El Kholy
There are few treatment options available to treat toxoplasmosis. So, investigating possible antiparasitic agents from plants and nanoparticles that are widely available and reasonably priced might be a good substitute. This study aimed to examine the effect of Portulaca oleracea (P. oleracea) aqueous and methanolic extracts as a sole agent or loaded on iron oxide nanoparticles (FeONPs) compared to spiramycin on a murine model of Toxoplasma gondii (T. gondii) ME49 strain. Forty-eight Swiss albino mice were put into eight groups: GI: uninfected negative control; GII: infected, untreated positive control; GIII, GIV, GV, GVI, GVII, and GVIII: infected, treated with spiramycin (200 mg/kg), FeONPs (2.5 mg/kg), P. oleracea aqueous extract (2.5 mg/kg), P. oleracea methanolic extractt (2.5 mg/kg), P. oleracea aqueous extract loaded on FeONPs (2.5 mg/kg) and P. oleracea methanolic extract loaded on FeONPs (2.5 mg/kg) respectively. To evaluate the treatment effectiveness, parasitological counting for T. gondii cysts and histopathological assessment for brain sections using H&E were used. Also, the immunohistochemical expression of the ionized calcium-binding adapter molecule 1 (Iba-1) was investigated. T. gondii cysts number in the infected treated mice brains was significantly reduced, with GVIII having the best therapeutic efficacy with an efficiency percentage of 84% (P > 0.000). Also, this group had a remarkable improvement in the pathological changes induced by T. gondii and the highest reduction of Iba-1 expression (P > 0.000). According to this study, P. oleracea loaded on FeONPs could be a potential therapeutic candidate for treating toxoplasmosis, and administering the medications as nanoparticles enhances their therapeutic effect.
{"title":"Promising therapeutic effects of <i>Portulaca Oleracea</i> loaded iron oxide nanoparticles in <i>Toxoplasma gondii</i> infection in mice.","authors":"Eman S El-Wakil, Mohamed Farid, Walaa A El Kholy","doi":"10.1007/s12639-025-01846-8","DOIUrl":"https://doi.org/10.1007/s12639-025-01846-8","url":null,"abstract":"<p><p>There are few treatment options available to treat toxoplasmosis. So, investigating possible antiparasitic agents from plants and nanoparticles that are widely available and reasonably priced might be a good substitute. This study aimed to examine the effect of <i>Portulaca oleracea</i> (<i>P. oleracea</i>) aqueous and methanolic extracts as a sole agent or loaded on iron oxide nanoparticles (FeONPs) compared to spiramycin on a murine model of <i>Toxoplasma gondii</i> (<i>T. gondii</i>) ME49 strain. Forty-eight Swiss albino mice were put into eight groups: GI: uninfected negative control; GII: infected, untreated positive control; GIII, GIV, GV, GVI, GVII, and GVIII: infected, treated with spiramycin (200 mg/kg), FeONPs (2.5 mg/kg), <i>P. oleracea</i> aqueous extract (2.5 mg/kg), <i>P</i>. <i>oleracea</i> methanolic extractt (2.5 mg/kg), <i>P. oleracea</i> aqueous extract loaded on FeONPs (2.5 mg/kg) and <i>P. oleracea</i> methanolic extract loaded on FeONPs (2.5 mg/kg) respectively. To evaluate the treatment effectiveness, parasitological counting for <i>T. gondii</i> cysts and histopathological assessment for brain sections using H&E were used. Also, the immunohistochemical expression of the ionized calcium-binding adapter molecule 1 (Iba-1) was investigated. <i>T. gondii</i> cysts number in the infected treated mice brains was significantly reduced, with GVIII having the best therapeutic efficacy with an efficiency percentage of 84% (<i>P</i> > 0.000). Also, this group had a remarkable improvement in the pathological changes induced by <i>T. gondii</i> and the highest reduction of Iba-1 expression (<i>P</i> > 0.000). According to this study, <i>P. oleracea</i> loaded on FeONPs could be a potential therapeutic candidate for treating toxoplasmosis, and administering the medications as nanoparticles enhances their therapeutic effect.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1022-1031"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}