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Scientific Reports Jun 2024Among the factors affecting the effectiveness of malaria control is poor knowledge of the entomologic drivers of the disease. We investigated anopheline populations as...
Among the factors affecting the effectiveness of malaria control is poor knowledge of the entomologic drivers of the disease. We investigated anopheline populations as part of a baseline study to implement house screening of windows and doors as a supplementary malaria control tool towards elimination in Jabi Tehnan district, Amhara Regional State of Ethiopia. The samples were surveyed monthly using CDC light traps between June 2020 and May 2021. Mosquito trap density (< 3 mosquitoes/trap) was low, however, with a high overall Plasmodium sporozoite rate (9%; indoor = 4.3%, outdoor = 13.1%) comprising P. falciparum (88.9%) and P. vivax (11.1%). Anopheles gambiae s.l., mostly An. arabiensis, comprised > 80% of total anopheline captures and contributed ~ 42% of Plasmodium-infected mosquitoes. On the other hand, morphologically scored Anopheles funestus s.l., constituting about 6% of anopheline collections, accounted for 50% of sporozoite-infected mosquitoes. Most of the infected An. funestus s.l. specimens (86.7%) were grouped with previously unknown or undescribed Anopheles species previously implicated as a cryptic malaria vector in the western Kenyan highlands, confirming its wider geographic distribution in eastern Africa. Other species with Plasmodium infection included An. longipalpis C, An. theileri, An. demillioni, and An. nili. Cumulatively, 77.8% of the infected mosquitoes occurred outdoors. These results suggest efficient malaria parasite transmission despite the low vector densities, which has implications for effective endpoint indicators to monitor malaria control progress. Additionally, the largely outdoor infection and discovery of previously unknown and cryptic vectors suggest an increased risk of residual malaria transmission and, thus, a constraint on effective malaria prevention and control.
Topics: Ethiopia; Animals; Anopheles; Mosquito Vectors; Humans; Malaria; Plasmodium falciparum; Plasmodium vivax; Sporozoites; Mosquito Control; Malaria, Vivax; Malaria, Falciparum; Female
PubMed: 38871839
DOI: 10.1038/s41598-024-64436-3 -
Scientific Reports Jun 2024Intestinal parasitic infections (IPIs) can lead to significant morbidity and mortality in cancer patients. While they are unlikely to cause severe disease and are...
Intestinal parasitic infections (IPIs) can lead to significant morbidity and mortality in cancer patients. While they are unlikely to cause severe disease and are self-limiting in healthy individuals, cancer patients are especially susceptible to opportunistic parasitic infections. The gut microbiota plays a crucial role in various aspects of health, including immune regulation and metabolic processes. Parasites occupy the same environment as bacteria in the gut. Recent research suggests intestinal parasites can disrupt the normal balance of the gut microbiota. However, there is limited understanding of this co-infection dynamic among cancer patients in Malaysia. A study was conducted to determine the prevalence and relationship between intestinal parasites and gut microbiota composition in cancer patients. Stool samples from 134 cancer patients undergoing active treatment or newly diagnosed were collected and examined for the presence of intestinal parasites and gut microbiota composition. The study also involved 17 healthy individuals for comparison and control. Sequencing with 16S RNA at the V3-V4 region was used to determine the gut microbial composition between infected and non-infected cancer patients and healthy control subjects. The overall prevalence of IPIs among cancer patients was found to be 32.8%. Microsporidia spp. Accounted for the highest percentage at 20.1%, followed by Entamoeba spp. (3.7%), Cryptosporidium spp. (3.0%), Cyclospora spp. (2.2%), and Ascaris lumbricoides (0.8%). None of the health control subjects tested positive for intestinal parasites. The sequencing data analysis revealed that the gut microbiota diversity and composition were significantly different in cancer patients than in healthy controls (p < 0.001). A significant dissimilarity was observed in the bacterial composition between parasite-infected and non-infected patients based on Bray-Curtis (p = 0.041) and Jaccard (p = 0.021) measurements. Bacteria from the genus Enterococcus were enriched in the parasite-infected groups, while Faecalibacterium prausnitzii reduced compared to non-infected and control groups. Further analysis between different IPIs and non-infected individuals demonstrated a noteworthy variation in Entamoeba-infected (unweighted UniFrac: p = 0.008), Cryptosporidium-infected (Bray-Curtis: p = 0.034) and microsporidia-infected (unweighted: p = 0.026; weighted: p = 0.019; Jaccard: p = 0.031) samples. No significant dissimilarity was observed between Cyclospora-infected groups and non-infected groups. Specifically, patients infected with Cryptosporidium and Entamoeba showed increased obligate anaerobic bacteria. Clostridiales were enriched with Entamoeba infections, whereas those from Coriobacteriales decreased. Bacteroidales and Clostridium were found in higher abundance in the gut microbiota with Cryptosporidium infection, while Bacillales decreased. Additionally, bacteria from the genus Enterococcus were enriched in microsporidia-infected patients. In contrast, bacteria from the Clostridiales order, Faecalibacterium, Parabacteroides, Collinsella, Ruminococcus, and Sporosarcina decreased compared to the non-infected groups. These findings underscore the importance of understanding and managing the interactions between intestinal parasites and gut microbiota for improved outcomes in cancer patients.
Topics: Humans; Malaysia; Gastrointestinal Microbiome; Male; Female; Middle Aged; Intestinal Diseases, Parasitic; Adult; Neoplasms; Aged; Feces; Tertiary Care Centers; Hospitals, Teaching; Prevalence; Cryptosporidium; Entamoeba; Microsporidia; Coinfection; RNA, Ribosomal, 16S
PubMed: 38871760
DOI: 10.1038/s41598-024-59969-6 -
PLoS Pathogens Jun 2024Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. In low transmission...
Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. In low transmission settings, parasites recombine with themselves, and the clonal lineage is propagated rather than broken up by outcrossing. We investigated whether stochastic/neutral factors drive the persistence and abundance of Plasmodium falciparum clonal lineages in Guyana, a country with relatively low malaria transmission, but the only setting in the Americas in which an important artemisinin resistance mutation (pfk13 C580Y) has been observed. We performed whole genome sequencing on 1,727 Plasmodium falciparum samples collected from infected patients across a five-year period (2016-2021). We characterized the relatedness between each pair of monoclonal infections (n = 1,409) through estimation of identity-by-descent (IBD) and also typed each sample for known or candidate drug resistance mutations. A total of 160 multi-isolate clones (mean IBD ≥ 0.90) were circulating in Guyana during the study period, comprising 13 highly related clusters (mean IBD ≥ 0.40). In the five-year study period, we observed a decrease in frequency of a mutation associated with artemisinin partner drug (piperaquine) resistance (pfcrt C350R) and limited co-occurence of pfcrt C350R with duplications of plasmepsin 2/3, an epistatic interaction associated with piperaquine resistance. We additionally observed 61 nonsynonymous substitutions that increased markedly in frequency over the study period as well as a novel pfk13 mutation (G718S). However, P. falciparum clonal dynamics in Guyana appear to be largely driven by stochastic factors, in contrast to other geographic regions, given that clones carrying drug resistance polymorphisms do not demonstrate enhanced persistence or higher abundance than clones carrying polymorphisms of comparable frequency that are unrelated to resistance. The use of multiple artemisinin combination therapies in Guyana may have contributed to the disappearance of the pfk13 C580Y mutation.
Topics: Plasmodium falciparum; Guyana; Malaria, Falciparum; Humans; Antimalarials; Drug Resistance; Artemisinins; Mutation; Protozoan Proteins
PubMed: 38870266
DOI: 10.1371/journal.ppat.1012013 -
BMC Public Health Jun 2024. Splash pads for recreational purposes are widespread. Using these pads can pose a health risk if they lack installation regulation and water quality supervision. Our...
BACKGROUND
. Splash pads for recreational purposes are widespread. Using these pads can pose a health risk if they lack installation regulation and water quality supervision. Our aim was to describe a waterborne disease outbreak caused by Clostridium perfringens and Cryptosporidium spp. in a Barcelona district and the measures taken for its control.
METHODS
. On August 2018, 71 cases of acute gastroenteritis were detected, affecting people who used a splash pad or were in contact with a user. Microbiological and environmental investigations were carried out. A descriptive analysis of the sample and Poisson regression models adjusted for age and sex were performed, obtaining frequencies, median values, and adjusted prevalence ratios with their 95% confidence intervals.
RESULTS
The median age of the cases was 6.7 years, 27 (38%) required medical care, and three (4.2%) were hospitalized. The greater the number of times a person entered the area, the greater the number of symptoms and their severity. Nineteen (76%) of the 25 stool samples collected from cases showed the presence of one or both pathogens. Environmental investigations showed deficiencies in the facilities and identified the presence of both species in the splash pad. Health education and hygiene measures were carried out, and 14 days after the closure of the facilities, no more cases related to the pad were recorded.
CONCLUSIONS
. Specific regulations are needed on the use of splash pads for recreational purposes. Until these regulations are in place, these types of facility should comply with the regulations that apply to swimming pools and spas, including those related to the design of the tanks, water recirculation systems, and adequate disinfection systems.
Topics: Humans; Disease Outbreaks; Male; Female; Spain; Cryptosporidium; Clostridium Infections; Cryptosporidiosis; Adult; Child; Adolescent; Child, Preschool; Middle Aged; Young Adult; Clostridium perfringens; Gastroenteritis; Waterborne Diseases; Infant; Water Microbiology
PubMed: 38867266
DOI: 10.1186/s12889-024-18870-7 -
Malaria Journal Jun 2024Malaria remains a major global health problem although there was a remarkable achievement between 2000 and 2015. Malaria drug resistance, along with several other...
BACKGROUND
Malaria remains a major global health problem although there was a remarkable achievement between 2000 and 2015. Malaria drug resistance, along with several other factors, presents a significant challenge to malaria control and elimination efforts. Numerous countries in sub-Saharan Africa have documented the presence of confirmed or potential markers of partial resistance against artemisinin, the drug of choice for the treatment of uncomplicated Plasmodium falciparum malaria. The World Health Organization (WHO) recommends regular surveillance of artemisinin therapeutic efficacy to inform policy decisions.
METHODS
This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated P. falciparum malaria in Ethiopia since 2004. Using a single-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria in Metehara Health Centre, central-east Ethiopia. Out of 2332 malaria suspects (1187 males, 1145 females) screened, 80 (50 males, 30 females) were enrolled, followed up for 28 days, and 73 (44 males, 29 females) completed the follow up. The study was conducted and data was analysed by employing the per-protocol and Kaplan-Meier analyses following the WHO Malaria Therapeutic Efficacy Evaluation Guidelines 2009.
RESULTS
The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitaemia and fever by day (D) 3. The prevalence of gametocytes decreased from 6.3% on D0 to 2.5% on D2, D3, D7, and ultimately achieving complete clearance afterward.
CONCLUSION
The overall cure rate for AL treatment was 100%, demonstrating its high efficacy in effectively eliminating malaria parasites in patients. No serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that AL remains a highly efficacious treatment for uncomplicated P. falciparum malaria in the study site after 20 years of its introduction in Ethiopia.
Topics: Humans; Ethiopia; Malaria, Falciparum; Artemether, Lumefantrine Drug Combination; Male; Female; Antimalarials; Adult; Adolescent; Young Adult; Child, Preschool; Child; Prospective Studies; Middle Aged; Infant; Artemisinins; Fluorenes; Treatment Outcome; Ethanolamines; Aged; Drug Combinations; Plasmodium falciparum
PubMed: 38867217
DOI: 10.1186/s12936-024-04991-2 -
Scientific Reports Jun 2024We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was...
We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was conducted in Alexandria University hospitals' outpatient clinics. 192 participants were enrolled from September 2022 to November 2023. Anti-Toxoplasma IgG and IgM were determined in serum and saliva by ELISA. An in-Silico study examined TgERP's protein-protein interactions (PPIs) with pro-inflammatory cytokine receptors, anti-inflammatory cytokine, cell cycle progression regulatory proteins, a proliferation marker, and nuclear envelope integrity-related protein Lamin B1. Our findings revealed that anti-T. gondii IgG were detected in serum (66.1%) and saliva (54.7%), with 2.1% of both samples were positive for IgM. Salivary IgG had 75.59% sensitivity, 86.15% specificity, 91.40% PPV, 64.40% NPP, 79.17% accuracy and fair agreement with serum IgG. On the other hand, the sensitivity, specificity, PPV, NPV, and accuracy in detecting salivary IgM were 75.0%, 99.47%, 75.0%, 99.47%, and 98.96%. AUC 0.859 indicates good discriminatory power. Examined synthetic drugs and natural products can target specific amino acids residues of TgERP that lie at the same binding interface with LB1 and Ki67, subsequently, hindering their interaction. Hence, salivary samples can be a promising diagnostic approach. The studied drugs can counteract the pro-inflammatory action of TgERP.
Topics: Humans; Male; Saliva; Toxoplasma; Female; Adult; Toxoplasmosis; Immunoglobulin G; Cross-Sectional Studies; Inflammation; Immunoglobulin M; Middle Aged; Young Adult; Antibodies, Protozoan; Computer Simulation; Seroepidemiologic Studies; Adolescent; Molecular Docking Simulation
PubMed: 38866852
DOI: 10.1038/s41598-024-63735-z -
Toxoplasma gondii infection and high levels of IgE are associated to erythema nodosum leprosy (ENL).PloS One 2024Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and...
Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), the major cause of irreversible neuropathy in leprosy, which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. Leprosy remains persistently endemic in our region where it predominantly affects lowest socioeconomic conditions people, as Toxoplasma gondii infection in the municipality studied. Previously, we have shown T. gondii coinfection as a risk marker for leprosy, mainly in its severe form. This present study assessed whether T. gondii infection is also a risk factor for leprosy reactions and the predictive value of immunoglobulin production prior to development of leprosy reactions. Patients with leprosy (n = 180), co-infected or not with T. gondii, had their serum investigated for levels of IgA, IgE, IgG1, IgG2, IgG3 and IgG4 anti-PGL-1 by ELISA prior to development of leprosy reactions. The serologic prevalence for T. gondii infection was 87.7% in leprosy reaction patients reaching 90.9% in those with ENL. The leprosy reaction risk increased in T. gondii seropositive individuals was two-fold ([OR] = 2.366; 95% confidence interval [CI 95%]: 1.024-5.469) higher than those seronegative, and considering the risk of ENL, this increase was even more evident (OR = 6.753; 95% CI: 1.050-72.85) in coinfected individuals. When evaluated the prediction of anti-PGL-1 immunoglobulin levels for development of leprosy reactions in patients coinfected or not with T. gondii, only the increase IgE levels were associated to occurrence of reactional episodes of leprosy, specifically ENL type, in patients coinfected with T. gondii, compared to those not coinfected or no reaction. Thus, the immunomodulation in co-parasitism T. gondii-M. leprae suggest increased levels of IgE as a biomarker for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.
Topics: Humans; Toxoplasmosis; Erythema Nodosum; Female; Male; Adult; Immunoglobulin E; Middle Aged; Toxoplasma; Coinfection; Mycobacterium leprae; Young Adult; Adolescent; Risk Factors; Aged; Leprosy, Lepromatous
PubMed: 38865430
DOI: 10.1371/journal.pone.0300704 -
PLoS Neglected Tropical Diseases Jun 2024Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The...
BACKGROUND
Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates.
METHODS AND FINDINGS
A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence.
CONCLUSIONS
This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.
Topics: Animals; Mice; Plasmodium vivax; Malaria Vaccines; Plasmodium berghei; Protozoan Proteins; Humans; Malaria, Vivax; Female; Antigens, Protozoan; Antibodies, Protozoan; Malaria; Mice, Inbred BALB C
PubMed: 38865344
DOI: 10.1371/journal.pntd.0012231 -
Frontiers in Immunology 2024Despite decades of effort, malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both...
BACKGROUND
Despite decades of effort, malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both diagnosis as well as treatment hamper effective public health interventions.
METHODS AND RESULTS
To discover new vaccine candidates, we used our whole proteome differential screening method and identified PfGBP130 as a parasite protein uniquely recognized by antibodies from children who had developed resistance to infection but not from those who remained susceptible. We formulated PfGBP130 as lipid encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens and evaluated the efficacy of murine polyclonal anti-PfGBP130 antisera to inhibit parasite growth in vitro. Immunization of mice with PfGBP130-A (aa 111-374), the region identified in our differential screen, formulated as a DNA plasmid or lipid encapsulated mRNA, but not as a recombinant protein, induced antibodies that inhibited RBC invasion . mRNA encoding the full ectodomain of PfGBP130 (aa 89-824) also generated parasite growth-inhibitory antibodies.
CONCLUSION
We are currently advancing PfGBP130-A formulated as a lipid-encapsulated mRNA for efficacy evaluation in non-human primates.
Topics: Animals; Plasmodium falciparum; Antibodies, Protozoan; Mice; Erythrocytes; Malaria, Falciparum; Humans; Malaria Vaccines; Protozoan Proteins; Antigens, Protozoan; Immunization; Female
PubMed: 38863702
DOI: 10.3389/fimmu.2024.1350560 -
Open Biology Jun 2024species encode a unique set of six modular proteins named LCCL lectin domain adhesive-like proteins (LAPs) that operate as a complex and that are essential for malaria...
species encode a unique set of six modular proteins named LCCL lectin domain adhesive-like proteins (LAPs) that operate as a complex and that are essential for malaria parasite transmission from mosquito to vertebrate. LAPs possess complex architectures obtained through unique assemblies of conserved domains associated with lipid, protein and carbohydrate interactions, including the name-defining LCCL domain. Here, we assessed the prevalence of LAP orthologues across eukaryotic life. Our findings show orthologous conservation in all apicomplexans, with lineage-specific repertoires acquired through differential gene loss and duplication. Besides Apicomplexa, LAPs are found in their closest relatives: the photosynthetic chromerids, which encode the broadest repertoire including a novel membrane-bound LCCL protein. LAPs are notably absent from other alveolate lineages (dinoflagellates, perkinsids and ciliates), but are encoded by predatory colponemids, a sister group to the alveolates. These results reveal that the LAPs are much older than previously thought and pre-date not only the Apicomplexa but the Alveolata altogether.
Topics: Protozoan Proteins; Phylogeny; Evolution, Molecular; Plasmodium; Alveolata; Protein Domains; Apicomplexa; Lectins
PubMed: 38862023
DOI: 10.1098/rsob.230451