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Frontiers in Immunology 2024Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against...
Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.
Topics: Animals; Malaria Vaccines; Protozoan Proteins; Mice; Plasmodium vivax; Antibodies, Protozoan; Poly I-C; Malaria, Vivax; Aluminum Hydroxide; Immunoglobulin G; Female; Adjuvants, Immunologic; Immunity, Humoral; Immunity, Cellular; Mice, Inbred BALB C
PubMed: 38650939
DOI: 10.3389/fimmu.2024.1331474 -
PeerJ 2024COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to...
BACKGROUND
COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to synthesize literature on the clinical outcomes of COVID-19 and malaria co-infection to develop effective prevention and treatment strategies.
METHODS
A comprehensive literature search was conducted using MeSH terms and keywords from the start of the COVID-19 pandemic to January 2023. The review included original articles on COVID-19 and malaria co-infection, evaluating their methodological quality and certainty of evidence. It was registered in PROSPERO (CRD42023393562).
RESULTS
Out of 1,596 screened articles, 19 met the inclusion criteria. These studies involved 2,810 patients, 618 of whom had COVID-19 and malaria co-infection. Plasmodium falciparum and vivax were identified as causative organisms in six studies. Hospital admission ranged from three to 18 days. Nine studies associated co-infection with severe disease, ICU admission, assisted ventilation, and related complications. One study reported 6% ICU admission, and mortality rates of 3%, 9.4%, and 40.4% were observed in four studies. Estimated crude mortality rates were 10.71 and 5.87 per 1,000 person-days for patients with and without concurrent malaria, respectively. Common co-morbidities included Diabetes mellitus, hypertension, cardiovascular diseases, and respiratory disorders.
CONCLUSION
Most patients with COVID-19 and malaria co-infection experienced short-term hospitalization and mild to moderate disease severity. However, at presentation, co-morbidities and severe malaria were significantly associated with higher mortality or worse clinical outcomes. These findings emphasize the importance of early detection, prompt treatment, and close monitoring of patients with COVID-19 and malaria co-infection.
Topics: Humans; COVID-19; Coinfection; Malaria; SARS-CoV-2; Hospitalization; Comorbidity; Malaria, Falciparum
PubMed: 38646476
DOI: 10.7717/peerj.17160 -
Acta Tropica Jul 2024Malaria remains a highly prevalent infectious disease worldwide, particularly in tropical and subtropical regions. Effectively controlling of mosquitoes transmitting of...
Effect of nanoformulation Azadirachta indica on some factors associated with the vectorial capacity and competence of Anopheles aquasalis experimentally infected with Plasmodium vivax.
Malaria remains a highly prevalent infectious disease worldwide, particularly in tropical and subtropical regions. Effectively controlling of mosquitoes transmitting of Plasmodium spp. is crucial in to control this disease. A promising strategy involves utilizing plant-derived products, such as the Neem tree (Azadirachta indica), known for its secondary metabolites with biological activity against various insect groups of agricultural and public health importance. This study investigated the effects of a nanoformulation prototype Neem on factors linked to the vector competence of Anopheles aquasalis, a malaria vector in Latin America. Different concentrations of the nanoformulation were supplied through sugar solution and blood feeding, assessing impacts on longevity, fecundity, fertility, and transgenerational survival from larvae to adults. Additionally, the effects of the Neem nanoformulation and NeemAZAL® formulation on the sporogonic cycle of P. vivax were evaluated. Overall, significant impacts were observed at 100 ppm and 1,000 ppm concentrations on adult survival patterns and on survival of the F1 generation. A trend of reduced oviposition and hatching rates was also noted in nanoformulation-consuming groups, with fertility and fecundity declining proportionally to the concentration. Additionally, a significant decrease in the infection rate and intensity of P. vivax was observed in the 1,000 ppm group, with a mean of 3 oocysts per female compared to the control's 27 oocysts per female. In the commercial formulation, the highest tested concentration of 3 ppm yielded 5.36 oocysts per female. Concerning sporozoite numbers, there was a reduction of 52 % and 87 % at the highest concentrations compared to the control group. In conclusion, these findings suggest that the A. indica nanoformulation is a potential as a tool for malaria control through reduction in the vector longevity and reproductive capacity, possibly leading to decreased vector population densities. Moreover, the nanoformulation interfered with the sporogonic development of P. vivax. However, further basic research on Neem formulations, their effects, and mechanisms of action is imperative to gain a more specific perspective for safe field implementation.
Topics: Animals; Anopheles; Azadirachta; Female; Mosquito Vectors; Plasmodium vivax; Fertility; Plant Extracts; Larva; Longevity; Mosquito Control
PubMed: 38642694
DOI: 10.1016/j.actatropica.2024.107223 -
Malaria Journal Apr 2024In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and...
BACKGROUND
In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and human malaria cases, leading to temporal heterogeneity. The main variables influencing spatial transmission include location of communities, mosquito behaviour, land use/land cover, and human ecology/behaviour. The main objective was to evaluate seasonal and microgeographic biting behaviour of the malaria vector Nyssorhynchus (or Anopheles) darlingi in Amazonian Peru and to investigate effects of seasonality on malaria transmission.
METHODS
We captured mosquitoes from 18:00 to 06:00 h using Human Landing Catch in two riverine (Lupuna, Santa Emilia) and two highway (El Triunfo, Nuevo Horizonte) communities indoors and outdoors from 8 houses per community, during the dry and rainy seasons from February 2016 to January 2017. We then estimated parity rate, daily survival and age of a portion of each collection of Ny. darlingi. All collected specimens of Ny. darlingi were tested for the presence of Plasmodium vivax or Plasmodium falciparum sporozoites using real-time PCR targeting the small subunit of the 18S rRNA.
RESULTS
Abundance of Ny. darlingi varied across village, season, and biting behaviour (indoor vs outdoor), and was highly significant between rainy and dry seasons (p < 0.0001). Biting patterns differed, although not significantly, and persisted regardless of season, with peaks in highway communities at ~ 20:00 h in contrast to biting throughout the night (i.e., 18:00-06:00) in riverine communities. Of 3721 Ny. darlingi tested for Plasmodium, 23 (0.62%) were infected. We detected Plasmodium-infected Ny. darlingi in both community types and most (20/23) were captured outdoors during the rainy season; 17/23 before midnight. Seventeen Ny. darlingi were infected with P. vivax, and 6 with P. falciparum. No infected Ny. darlingi were captured during the dry season. Significantly higher rates of parity were detected in Ny. darlingi during the rainy season (average 64.69%) versus the dry season (average 36.91%) and by community, Lupuna, a riverine village, had the highest proportion of parous to nulliparous females during the rainy season.
CONCLUSIONS
These data add a seasonal dimension to malaria transmission in peri-Iquitos, providing more evidence that, at least locally, the greatest risk of malaria transmission is outdoors during the rainy season mainly before midnight, irrespective of whether the community was located adjacent to the highway or along the river.
Topics: Animals; Female; Humans; Anopheles; Malaria; Peru; Mosquito Vectors; Malaria, Vivax; Bites and Stings; Seasons; Malaria, Falciparum; Plasmodium
PubMed: 38641572
DOI: 10.1186/s12936-024-04940-z -
Science Advances Apr 2024Approximately 3.3 billion people live with the threat of malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria....
Approximately 3.3 billion people live with the threat of malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria. This work demonstrates that an enzyme-cleavable polymeric prodrug of tafenoquine addresses key requirements for a mass administration, eradication campaign: excellent subcutaneous bioavailability, complete parasite control after a single dose, improved therapeutic window compared to the parent oral drug, and low cost of goods sold (COGS) at less than $1.50 per dose. Liver targeting and subcutaneous dosing resulted in improved liver:plasma exposure profiles, with increased efficacy and reduced glucose 6-phosphate dehydrogenase-dependent hemotoxicity in validated preclinical models. A COGS and manufacturability analysis demonstrated global scalability, affordability, and the ability to redesign this fully synthetic polymeric prodrug specifically to increase global equity and access. Together, this polymer prodrug platform is a candidate for evaluation in human patients and shows potential for eradication campaigns.
Topics: Humans; Antimalarials; Aminoquinolines; Malaria; Malaria, Vivax; Liver
PubMed: 38640243
DOI: 10.1126/sciadv.adk4492 -
Antimicrobial Agents and Chemotherapy Apr 2024The development of novel antiplasmodial compounds with broad-spectrum activity against different stages of parasites is crucial to prevent malaria disease and parasite...
The development of novel antiplasmodial compounds with broad-spectrum activity against different stages of parasites is crucial to prevent malaria disease and parasite transmission. This study evaluated the antiplasmodial activity of seven novel hydrazone compounds (referred to as CB compounds: CB-27, CB-41, CB-50, CB-53, CB-58, CB-59, and CB-61) against multiple stages of parasites. All CB compounds inhibited blood stage proliferation of drug-resistant or sensitive strains of in the low micromolar to nanomolar range. Interestingly, CB-41 exhibited prophylactic activity against hypnozoites and liver schizonts in , a primate model for . Four CB compounds (CB-27, CB-41, CB-53, and CB-61) inhibited oocyst formation in mosquitoes and five CB compounds (CB-27, CB-41, CB-53, CB-58, and CB-61) hindered the development of ookinetes. The CB compounds did not inhibit the activation of female and male gametocytes . Isobologram assays demonstrated synergistic interactions between CB-61 and the FDA-approved antimalarial drugs, clindamycin and halofantrine. Testing of six CB compounds showed no inhibition of glutathione S-transferase as a putative target and no cytotoxicity in HepG2 liver cells. CB compounds are promising candidates for further development as antimalarial drugs against multidrug-resistant parasites, which could also prevent malaria transmission.
PubMed: 38639491
DOI: 10.1128/aac.01643-23 -
The Journal of Biological Chemistry May 2024The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region...
The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.
Topics: Plasmodium vivax; Reticulocytes; Humans; Protozoan Proteins; Antigens, CD; Receptors, Transferrin; Anion Exchange Protein 1, Erythrocyte; Protein Binding; Merozoite Surface Protein 1; Malaria, Vivax; Animals
PubMed: 38636656
DOI: 10.1016/j.jbc.2024.107285 -
Journal of Vector Borne Diseases Apr 2024Anopheles stephensi is responsible for the transmission of malaria in urban areas. Vector competence of An. stephensi from a non-malarious (Coimbatore) and highly...
BACKGROUND OBJECTIVES
Anopheles stephensi is responsible for the transmission of malaria in urban areas. Vector competence of An. stephensi from a non-malarious (Coimbatore) and highly malarious (Chennai) urban areas in Tamil Nadu state of India, was investigated to find the reason for non-transmission of malaria in Coimbatore.
METHODS
Vector competence (susceptibility/refractoriness) of An. stephensi mosquitoes from Chennai (malarious) and Coimbatore (non-malarious) to Plasmodium vivax (Chennai) was investigated. Bioassays were carried out concurrently in both these strains by artificial membrane feeding technique using the same malaria-infected blood. An. stephensi were dissected to observe infection in midgut and salivary gland. The parasite infection, oocyst and sporozoite positivity rate, the oocyst load, correlation between male-female gametocyte ratio and infection, and Survival Analysis of parasitic stages during sporogony were analyzed and compared.
RESULTS
The overall infection rate was 45.8 and 41.2 percent in Chennai and Coimbatore, respectively. Oocyst count ranged from 1-80 and 1-208 respectively and not statistically significant. Oocyst positivity was high from Day 8-21 in both strains. The Mean Survival Day (MSD) for oocyst was Day 14 in both strains. Sporozoite was observed in four experiments in each of the strains and the MSD for sporozoites was Day 20 in Chennai and Day 17 in Coimbatore.
INTERPRETATION CONCLUSION
An. stephensi of Chennai and Coimbatore are equally susceptible to P. vivax infection and non-transmission of malaria in Coimbatore can be attributed to external factors such as the presence of preferential breeding habitat, vector density, vector survival, and weather. The only difference observed was the comparatively shortened oocyst maturation time in the Coimbatore strain which requires further investigation.
PubMed: 38634456
DOI: 10.4103/JVBD.JVBD_7_24 -
MedRxiv : the Preprint Server For... Apr 2024Zoonotic and symptomatic and asymptomatic infections occur across endemic areas of Southeast Asia. Most infections are low-parasitemia, with an unknown proportion...
BACKGROUND
Zoonotic and symptomatic and asymptomatic infections occur across endemic areas of Southeast Asia. Most infections are low-parasitemia, with an unknown proportion below routine microscopy detection thresholds. Molecular surveillance tools optimizing the limit of detection (LOD) would allow more accurate estimates of zoonotic malaria prevalence.
METHODS
An established ultra-sensitive genus quantitative-PCR (qPCR) assay targeting the 18S rRNA gene underwent LOD evaluation with and without reverse transcription (RT) for , and using total nucleic acid preserved (DNA/RNA Shield) isolates and archived dried blood spots (DBS). LODs for selected specific assays, and reference and -specific assays were determined with RT. Assay specificities were assessed using clinical malaria samples and malaria-negative controls.
RESULTS
The use of reverse transcription improved species detection by up to 10,000-fold ( genus), 2759-fold (), 1000-fold () and 10-fold (). The median LOD with RT for the Kamau et al. genus RT-qPCR assay was ≤0.0002 parasites/μL for and 0.002 parasites/μL for both and . The LODs with RT for -specific PCRs were: Imwong et al. 18S rRNA (0.0007 parasites/μL); Divis et al. real-time 18S rRNA (0.0002 parasites/μL); Lubis et al. hemi-nested (1.1 parasites/μL) and Lee et al. nested 18S rRNA (11 parasites/μL). The LOD for and specific assays with RT were 0.02 and 0.20 parasites/μL respectively. For DBS samples the median LOD for the genus qPCR with RT was 0.08, and without RT was 19.89 parasites/uL (249-fold change); no LOD improvement was demonstrated in DBS archived beyond 6 years. The genus and -assays were 100% specific for species and detection, respectively, from 190 clinical infections and 48 healthy controls. Reference specific primers demonstrated known cross-reactivity with .
CONCLUSION
Our findings support the use of an 18S rRNA genus qPCR and species-specific nested PCR protocol with RT for highly-sensitive surveillance of zoonotic and human species infections.
PubMed: 38633782
DOI: 10.1101/2024.04.04.24305339 -
Malaria Journal Apr 2024Achieving effective control and elimination of malaria in endemic regions necessitates a comprehensive understanding of local mosquito species responsible for malaria...
BACKGROUND
Achieving effective control and elimination of malaria in endemic regions necessitates a comprehensive understanding of local mosquito species responsible for malaria transmission and their susceptibility to insecticides.
METHODS
The study was conducted in the highly malaria prone Ujina Primary Health Center of Nuh (Mewat) district of Haryana state of India. Monthly entomological surveys were carried out for adult mosquito collections via indoor resting collections, light trap collections, and pyrethrum spray collections. Larvae were also collected from different breeding sites prevalent in the region. Insecticide resistance bioassay, vector incrimination, blood meal analysis was done with the collected vector mosquitoes.
RESULTS
A total of 34,974 adult Anopheles mosquitoes were caught during the survey period, out of which Anopheles subpictus was predominant (54.7%). Among vectors, Anopheles stephensi was predominant (15.5%) followed by Anopheles culicifacies (10.1%). The Human Blood Index (HBI) in the case of An. culicifacies and An. stephensi was 6.66 and 9.09, respectively. Vector incrimination results revealed Plasmodium vivax positivity rate of 1.6% for An. culicifacies. Both the vector species were found resistant to DDT, malathion and deltamethrin.
CONCLUSION
The emergence of insecticide resistance in both vector species, compromises the effectiveness of commonly used public health insecticides. Consequently, the implementation of robust insecticide resistance management strategies becomes imperative. To effectively tackle the malaria transmission, a significant shift in vector control strategies is warranted, with careful consideration and adaptation to address specific challenges encountered in malaria elimination efforts.
Topics: Animals; Humans; Insecticides; Insecticide Resistance; Anopheles; Malaria; DDT; Mosquito Control; Mosquito Vectors; Nitriles; Pyrethrins; India
PubMed: 38632650
DOI: 10.1186/s12936-023-04797-8