-
Emerging Infectious Diseases Jun 2024During May-July 2023, a cluster of 7 patients at local hospitals in Florida, USA, received a diagnosis of Plasmodium vivax malaria. Whole-genome sequencing of the...
During May-July 2023, a cluster of 7 patients at local hospitals in Florida, USA, received a diagnosis of Plasmodium vivax malaria. Whole-genome sequencing of the organism from 4 patients and phylogenetic analysis with worldwide representative P. vivax genomes indicated probable single parasite introduction from Central/South America.
Topics: Humans; Malaria, Vivax; Florida; Plasmodium vivax; Phylogeny; Male; Whole Genome Sequencing; Female; Adult; Middle Aged
PubMed: 38662728
DOI: 10.3201/eid3006.240336 -
BioRxiv : the Preprint Server For... Apr 202448/45, a gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we...
BACKGROUND
48/45, a gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant 48/45 protein (r48/45) with sera from -exposed African donors.
METHODS
r48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria - In addition, BALB/c mice were immunized with the r48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of NF-54 gametocytes to evaluate the parasite-boosting effect on r48/45 antibody titers. Specific anti-48/45 IgG purified from African sera was used to evaluate the TB activity on using standard mosquito membrane feeding assays (SMFA).
RESULTS
r48/45 protein showed cross-reactivity with sera of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p<0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults (≥ 17 years) than young children (≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p<0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with gametocytes boosted anti-48/45 antibody responses, recognizing gametocytes in indirect immunofluorescence antibody test. Notably, r48/45 affinity-purified African IgG exhibited a TB activity of 61% against in SMFA.
CONCLUSION
African sera (exposed only to cross-recognized the r48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a and cross-protective TB vaccine.
PubMed: 38659832
DOI: 10.1101/2024.04.10.588966 -
Revista Do Instituto de Medicina... 2024Quilombo remnant communities are areas officially recognized by the Brazilian government as historical communities founded by formerly enslaved individuals. These...
Quilombo remnant communities are areas officially recognized by the Brazilian government as historical communities founded by formerly enslaved individuals. These communities are mostly located in the endemic areas of malaria in the Brazilian Amazon. We retrospectively described the prevalence of malaria among individuals living in 32 recognized quilombo remnant communities in the Baiao and Oriximina municipalities located in the Para State. The number of malaria cases and the Annual Parasitic Incidence (API) recorded by the Brazilian malaria surveillance system (SIVEP-Malaria) from January 2005 to December 2020 were analyzed. We found that all communities registered at least one case over the 16-year period, the most frequent parasitic species being Plasmodium vivax (76.1%). During this period, 0.44% (4,470/1,008,714) of the malaria cases registered in Para State were reported in these quilombo remnant communities, with frequencies of 10.9% (856/7,859) in Baiao municipality and 39.1% (3,614/9,238) in Oriximina municipality, showing that individuals living in these rural communities are exposed to malaria. These data indicate that effective surveillance requires improved measures to identify malaria transmission among vulnerable populations living in quilombo remnant communities in the Brazilian Amazon.
Topics: Humans; Brazil; Cross-Sectional Studies; Retrospective Studies; Prevalence; Vulnerable Populations; Malaria, Vivax; Incidence; Female; Male; Adult; Rural Population; Adolescent; Malaria; Young Adult; Child; Middle Aged; Malaria, Falciparum; Child, Preschool
PubMed: 38656041
DOI: 10.1590/S1678-9946202466025 -
Journal of Medicinal Chemistry May 2024Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA...
Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by and , , , and . Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have values ranging from 3 nM to >10 μM, depending on the structure of the inhibitor and the biological origin of the enzyme. X-ray crystal structures show that, on binding, these prolinol-containing inhibitors stimulated the movement of active site loops in the enzyme. Against in cell culture, a prodrug exhibited an EC of 10 μM. Thus, these compounds are excellent candidates for further development as drug leads against infectious diseases as well as being potential anticancer agents.
Topics: Drug Design; Pentosyltransferases; Enzyme Inhibitors; Structure-Activity Relationship; Crystallography, X-Ray; Humans; Models, Molecular; Trypanosoma brucei brucei; Molecular Structure; Catalytic Domain
PubMed: 38651522
DOI: 10.1021/acs.jmedchem.4c00021 -
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: Poly I-C; Plasmodium vivax; Immunity, Humoral; Immunity, Cellular; Protozoan Proteins; Malaria Vaccines; Aluminum Hydroxide; Immunoglobulin G; Male; Animals; Plasma Cells; Female; Mice, Inbred C57BL; Recombinant Proteins; Vaccination; Adjuvants, Vaccine; Immunogenicity, Vaccine; Malaria, Vivax
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