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Wellcome Open Research 2023Falciparum malaria remains a global health problem. Two vaccines, based on the circumsporozoite antigen, are available. RTS, S/AS01 was recommended for use in 2021...
Safety and immunogenicity of varied doses of R21/Matrix-M™ vaccine at three years follow-up: A phase 1b age de-escalation, dose-escalation trial in adults, children, and infants in Kilifi-Kenya.
BACKGROUND
Falciparum malaria remains a global health problem. Two vaccines, based on the circumsporozoite antigen, are available. RTS, S/AS01 was recommended for use in 2021 following the advice of the World Health Organisation (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization and WHO Malaria Policy Advisory Group (MPAG). It has since been pre-qualified in 2022 by the WHO. R21 is similar to RTS, S/AS01, and recently licensed in Nigeria, Ghana and Burkina Faso following Phase 3 trial results.
METHODS
We conducted a Phase 1b age de-escalation, dose escalation bridging study after a change in the manufacturing process for R21. We recruited healthy adults and children and used a three dose primary vaccination series with a booster dose at 1-2 years. Variable doses of R21 and adjuvant (Matrix-M ™) were administered at 10µgR21/50 µg Matrix-M™, 5µgR21/25µg Matrix-M™ and 5µgR21/50µg Matrix-M™ to 20 adults, 20 children, and 51 infants.
RESULTS
Self-limiting adverse events were reported relating to the injection site and mild systemic symptoms. Two serious adverse events were reported, neither linked to vaccination. High levels of IgG antibodies to the circumsporozoite antigen were induced, and geometric mean titres in infants, the target group, were 1.1 (0.9 to 1.3) EU/mL at day 0, 10175 (7724 to 13404) EU/mL at day 84 and (following a booster dose at day 421) 6792 (5310 to 8687) EU/mL at day 456.
CONCLUSION
R21/Matrix-M™ is safe, and immunogenic when given at varied doses with the peak immune response seen in infants 28 days after a three dose primary vaccination series given four weeks apart. Antibody responses were restored 28 days after a 4 dose given one year post a three dose primary series in the young children and infants.
REGISTRATION
Clinicaltrials.gov (NCT03580824; 9 of July 2018; Pan African Clinical Trials Registry (PACTR202105682956280; 17 May 2021).
PubMed: 38813551
DOI: 10.12688/wellcomeopenres.19795.1 -
Turkish Journal of Medical Sciences 2023It was aimed to evaluate the positive effects of health behaviors (general hygiene, wearing face masks, physical distancing, and travel restrictions) acquired during the...
BACKGROUND/AIM
It was aimed to evaluate the positive effects of health behaviors (general hygiene, wearing face masks, physical distancing, and travel restrictions) acquired during the coronavirus disease 2019 (COVID-19) pandemic on the prevention of other infectious diseases in Ankara Province, Türkiye.
MATERIALS AND METHODS
This study was designed retrospectively. Among the notifiable group A infectious diseases, acute intestinal infections (AIIs) with International Classification of Diseases, Tenth Revision diagnosis codes A09 (diarrhea and gastroenteritis presumed to be of infectious origin), R11 (nausea and vomiting), and K52 (other noninfectious gastroenteritis and colitis), as well as influenza, tuberculosis, measles, varicella, malaria, and meningococcal meningitis were included in the scope of this study.The data of the selected infectious diseases in Ankara Province for the last 2 years before the pandemic (January 2018-December 2019) and for the 2-year period of the pandemic (January 2020-December 2021) were analyzed after checking the data. The number of cases were presented as frequencies, the 1-sample chi-squared test was used in the statistical analysis and the statistical significance level (α) was taken as 0.05.
RESULTS
The findings for each disease/disease group were discussed under separate headings. Comparing the prepandemic period (2018-2019) with the pandemic period (2020-2021), the decreases in the number of cases of selected infectious diseases, except influenza, were statistically significant.
CONCLUSION
Undoubtedly, the experience gained from the pandemic struggle will guide us in shaping our future lives. From this point forward, we should be aware that living in crowded environments and as a highly mobile population, that unhygienic habits are unfavorable for the spread of all infectious diseases, and we should take care to continuously apply the precautions for healthy living in our new lifestyle.
Topics: Humans; COVID-19; Retrospective Studies; Health Behavior; Turkey; Communicable Diseases; SARS-CoV-2; Hygiene; Masks; Physical Distancing; Pandemics; Communicable Disease Control; Travel
PubMed: 38813503
DOI: 10.55730/1300-0144.5745 -
Infectious Disease Modelling Sep 2024We propose a malaria model involving the sensitive and resistant strains, which is described by reaction-diffusion equations. The model reflects the scenario that the...
We propose a malaria model involving the sensitive and resistant strains, which is described by reaction-diffusion equations. The model reflects the scenario that the vector and host populations disperse with distinct diffusion rates, susceptible individuals or vectors cannot be infected by both strains simultaneously, and the vector population satisfies the logistic growth. Our main purpose is to get a threshold type result on the model, especially the interaction effect of the two strains in the presence of spatial structure. To solve this issue, the basic reproduction number (BRN) and invasion reproduction number (IRN) of each strain ( = 1 and 2 are for the sensitive and resistant strains, respectively) are defined. Furthermore, we investigate the influence of the diffusion rates of populations and vectors on BRNs and IRNs.
PubMed: 38813135
DOI: 10.1016/j.idm.2024.05.001 -
Health Science Reports Jun 2024Severe acute malnutrition remains a significant health challenge, particularly in low- and middle-income countries. The aim of this study was to determine the survival...
BACKGROUND AND AIMS
Severe acute malnutrition remains a significant health challenge, particularly in low- and middle-income countries. The aim of this study was to determine the survival time of under-five children with severe acute malnutrition.
METHODS
A retrospective cohort study was conducted at a hospital, focusing on under-five children with severe acute malnutrition. The study included 322 inpatients admitted to the Chiro hospital in Chiro, Ethiopia, between September 2019 and August 2020, whose data was obtained from medical records. Survival functions were analysed using Kaplan‒Meier plots and log-rank tests. The survival time of severe acute malnutrition was further analysed using the Cox proportional hazards model and Bayesian parametric survival models, employing integrated nested Laplace approximation methods.
RESULTS
Among the 322 patients, 118 (36.6%) died as a result of severe acute malnutrition. The estimated median survival time for inpatients was found to be 2 weeks. Model selection criteria favored the Bayesian Weibull accelerated failure time model, which demonstrated that age, body temperature, pulse rate, nasogastric (NG) tube usage, hypoglycemia, anemia, diarrhea, dehydration, malaria, and pneumonia significantly influenced the survival time of severe acute malnutrition.
CONCLUSIONS
This study revealed that children below 24 months, those with altered body temperature and pulse rate, NG tube usage, hypoglycemia, and comorbidities such as anemia, diarrhea, dehydration, malaria, and pneumonia had a shorter survival time when affected by severe acute malnutrition under the age of five. To reduce the death rate of children under 5 years of age, it is necessary to design community management for acute malnutrition to ensure early detection and improve access to and coverage for children who are malnourished.
PubMed: 38812715
DOI: 10.1002/hsr2.2135 -
Targeting Prohibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development.IScience Jun 2024Malaria parasite invasion to host erythrocytes is mediated by multiple interactions between merozoite ligands and erythrocyte receptors that contribute toward the...
Malaria parasite invasion to host erythrocytes is mediated by multiple interactions between merozoite ligands and erythrocyte receptors that contribute toward the development of disease pathology. Here, we report a novel antigen prohibitin "PHB2" and identify its cognate partner "Hsp70A1A" in host erythrocyte that plays a crucial role in mediating host-parasite interaction during merozoite invasion. Using small interfering RNA (siRNA)- and glucosamine-6-phosphate riboswitch (glmS) ribozyme-mediated approach, we show that loss of Hsp70A1A in red blood cells (RBCs) or PHB2 in infected red blood cells (iRBCs), respectively, inhibit PHB2-Hsp70A1A interaction leading to invasion inhibition. Antibodies targeting PHB2 and monoclonal antibody therapeutics against Hsp70A1A efficiently block parasite invasion. Recombinant PHB2 binds to RBCs which is inhibited by anti-PHB2 antibody and monoclonal antibody against Hsp70A1A. The validation of PHB2 to serve as antigen is further supported by detection of anti-PHB2 antibody in patient sera. Overall, this study proposes PHB2 as vaccine candidate and highlights the use of monoclonal antibody therapeutics for future malaria treatment.
PubMed: 38812541
DOI: 10.1016/j.isci.2024.109918 -
Malaria Journal May 2024The recent reduction in malaria burden in Côte d'Ivoire is largely attributable to the use of long-lasting insecticidal nets (LLINs). However, this progress is...
Combined use of long-lasting insecticidal nets and Bacillus thuringiensis israelensis larviciding, a promising integrated approach against malaria transmission in northern Côte d'Ivoire.
BACKGROUND
The recent reduction in malaria burden in Côte d'Ivoire is largely attributable to the use of long-lasting insecticidal nets (LLINs). However, this progress is threatened by insecticide resistance and behavioral changes in Anopheles gambiae sensu lato (s.l.) populations and residual malaria transmission, and complementary tools are required. Thus, this study aimed to assess the efficacy of the combined use of LLINs and Bacillus thuringiensis israelensis (Bti), in comparison with LLINs.
METHODS
This study was conducted in the health district of Korhogo, northern Côte d'Ivoire, within two study arms (LLIN + Bti arm and LLIN-only arm) from March 2019 to February 2020. In the LLIN + Bti arm, Anopheles larval habitats were treated every fortnight with Bti in addition to the use of LLINs. Mosquito larvae and adults were sampled and identified morphologically to genus and species using standard methods. The members of the An. gambiae complex were determined using a polymerase chain reaction technique. Plasmodium infection in An. gambiae s.l. and malaria incidence in local people was also assessed.
RESULTS
Overall, Anopheles spp. larval density was lower in the LLIN + Bti arm 0.61 [95% CI 0.41-0.81] larva/dip (l/dip) compared with the LLIN-only arm 3.97 [95% CI 3.56-4.38] l/dip (RR = 6.50; 95% CI 5.81-7.29; P < 0.001). The overall biting rate of An. gambiae s.l. was 0.59 [95% CI 0.43-0.75] biting/person/night in the LLIN + Bti arm against 2.97 [95% CI 2.02-3.93] biting/person/night in LLIN-only arm (P < 0.001). Anopheles gambiae s.l. was predominantly identified as An. gambiae sensu stricto (s.s.) (95.1%, n = 293), followed by Anopheles coluzzii (4.9%; n = 15). The human-blood index was 80.5% (n = 389) in study area. EIR was 1.36 infected bites/person/year (ib/p/y) in the LLIN + Bti arm against 47.71 ib/p/y in the LLIN-only arm. Malaria incidence dramatically declined from 291.8‰ (n = 765) to 111.4‰ (n = 292) in LLIN + Bti arm (P < 0.001).
CONCLUSIONS
The combined use of LLINs with Bti significantly reduced the incidence of malaria. The LLINs and Bti duo could be a promising integrated approach for effective vector control of An. gambiae for elimination of malaria.
Topics: Cote d'Ivoire; Bacillus thuringiensis; Animals; Anopheles; Larva; Malaria; Mosquito Control; Insecticide-Treated Bednets; Female; Mosquito Vectors; Humans; Male; Adolescent; Child, Preschool; Young Adult; Child; Adult
PubMed: 38812003
DOI: 10.1186/s12936-024-04953-8 -
Malaria Journal May 2024The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include...
BACKGROUND
The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055).
METHODS
This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony.
RESULTS
A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field.
CONCLUSION
While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.
Topics: Zambia; Animals; Mosquito Control; Anopheles; Mosquito Vectors; Female; Male; Cross-Sectional Studies; Malaria; Seasons; Insecticides; Sugars; Humans; Feeding Behavior
PubMed: 38811947
DOI: 10.1186/s12936-024-04990-3 -
International Journal For Parasitology.... Apr 2024Target-based approaches have traditionally been used in the search for new anti-infective molecules. Target selection process, a critical step in Drug Discovery,...
Target-based approaches have traditionally been used in the search for new anti-infective molecules. Target selection process, a critical step in Drug Discovery, identifies targets that are essential to establish or maintain the infection, tractable to be susceptible for inhibition, selective towards their human ortholog and amenable for large scale purification and high throughput screening. The work presented herein validates the Plasmodium falciparum mRNA 5' triphosphatase (PfPRT1), the first enzymatic step to cap parasite nuclear mRNAs, as a candidate target for the development of new antimalarial compounds. mRNA capping is essential to maintain the integrity and stability of the messengers, allowing their translation. PfPRT1 has been identified as a member of the tunnel, metal dependent mRNA 5' triphosphatase family which differs structurally and mechanistically from human metal independent mRNA 5' triphosphatase. In the present study the essentiality of PfPRT1 was confirmed and molecular biology tools and methods for target purification, enzymatic assessment and target engagement were developed, with the goal of running a future high throughput screening to discover PfPRT1 inhibitors.
PubMed: 38810336
DOI: 10.1016/j.ijpddr.2024.100537 -
PloS One 2024A low technology emanator device for slowly releasing vapour of the volatile pyrethroid transfluthrin was recently developed in Tanzania that provides robust protection...
BACKGROUND
A low technology emanator device for slowly releasing vapour of the volatile pyrethroid transfluthrin was recently developed in Tanzania that provides robust protection against night biting Anopheles and Culex vectors of malaria and filariasis for several months. Here these same emanator devices were assessed in Dar es Salaam city, as a means of protection against outdoor-biting Aedes (Stegomia) aegypti, the most important vector of human arboviruses worldwide, in parallel with similar studies in Haiti and Brazil.
METHODS
A series of entomological experiments were conducted under field and semi-field conditions, to evaluate whether transfluthrin emanators protect against wild Ae. aegypti, and also compare the transfluthrin responsiveness of Ae. aegypti originating from wild-caught eggs to established pyrethroid-susceptible Ae. aegypti and Anopheles gambiae colonies. Preliminary measurements of transfluthrin vapour concentration in air samples collected near treated emanators were conducted by gas chromatography-mass spectrometry.
RESULTS
Two full field experiments with four different emanator designs and three different transfluthrin formulations consistently indicated negligible reduction of human landing rates by wild Ae. aegypti. Under semi-field conditions in large cages, 50 to 60% reductions of landing rates were observed, regardless of which transfluthrin dose, capture method, emanator placement position, or source of mosquitoes (mildly pyrethroid resistant wild caught Ae. aegypti or pyrethroid-susceptible colonies of Ae. aegypti and An. gambiae) was used. Air samples collected immediately downwind from an emanator treated with the highest transfluthrin dose (15g), contained 12 to 19 μg/m3 transfluthrin vapour.
CONCLUSIONS
It appears unlikely that the moderate levels of pyrethroid resistance observed in wild Ae. aegypti can explain the modest-to-undetectable levels of protection exhibited. While potential inhalation exposure could be of concern for the highest (15g) dose evaluated, 3g of transfluthrin appears sufficient to achieve the modest levels of protection that were demonstrated entomologically. While the generally low levels of protection against Aedes reported here from Tanzania, and from similar entomological studies in Haiti and Brazil, are discouraging, complementary social science studies in Haiti and Brazil suggest end-users perceive valuable levels of protection against mosquitoes. It therefore remains unclear whether transfluthrin emanators have potential for protecting against Aedes vectors of important human arboviruses.
Topics: Animals; Fluorobenzenes; Tanzania; Aedes; Cyclopropanes; Mosquito Control; Insecticides; Mosquito Vectors; Humans; Anopheles; Insect Bites and Stings; Pyrethrins
PubMed: 38809841
DOI: 10.1371/journal.pone.0299722 -
PloS One 2024[This corrects the article DOI: 10.1371/journal.pone.0244457.].
Correction: Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.
[This corrects the article DOI: 10.1371/journal.pone.0244457.].
PubMed: 38809835
DOI: 10.1371/journal.pone.0304728