53 research outputs found
Slow Release Ivermectin Formulation for Malaria Control: a Pilot Study in 80-kg Pigs
Vector control with long-lasting insecticidal nets (LLINs) and
indoor residual spraying are responsible for more than two
thirds of the reduction seen in malaria prevalence in Africa
over the last 15 years (1)....
Screening for an ivermectin slow-release formulation suitable for malaria vector control
BACKGROUND: The prospect of eliminating malaria is challenged by
emerging insecticide resistance and vectors with outdoor and/or
crepuscular activity. Ivermectin can simultaneously tackle these
issues by killing mosquitoes feeding on treated animals and
humans. A single oral dose, however, confers only short-lived
mosquitocidal plasma levels. METHODS: Three different
slow-release formulations of ivermectin were screened for their
capacity to sustain mosquito-killing levels of ivermectin for
months. Thirty rabbits received a dose of one, two or three
silicone implants containing different proportions of
ivermectin, deoxycholate and sucrose. Animals were checked for
toxicity and ivermectin was quantified periodically in blood.
Potential impact of corresponding long-lasting formulation was
mathematically modelled. RESULTS: All combinations of
formulation and dose released ivermectin for more than 12 weeks;
four combinations sustained plasma levels capable of killing 50%
of Anopheles gambiae feeding on a treated subject for up to 24
weeks. No major adverse effects attributable to the drug were
found. Modelling predicts a 98% reduction in infectious vector
density by using an ivermectin formulation with a 12-week
duration. CONCLUSIONS: These results indicate that relatively
stable mosquitocidal plasma levels of ivermectin can be safely
sustained in rabbits for up to six months using a silicone-based
subcutaneous formulation. Modifying the formulation of
ivermectin promises to be a suitable strategy for malaria vector
control
Antiviral activity of Ageratina havanensis and major chemical compounds from the most active fraction
Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation
BACKGROUND: Mosquitoes that feed on animals can survive and
mediate residual transmission of malaria even after most humans
have been protected with insecticidal bednets or indoor residual
sprays. Ivermectin is a widely-used drug for treating parasites
of humans and animals that is also insecticidal, killing
mosquitoes that feed on treated subjects. Mass administration of
ivermectin to livestock could be particularly useful for
tackling residual malaria transmission by zoophagic vectors that
evade human-centred approaches. Ivermectin comes from a
different chemical class to active ingredients currently used to
treat bednets or spray houses, so it also has potential for
mitigating against emergence of insecticide resistance. However,
the duration of insecticidal activity obtained with ivermectin
is critical to its effectiveness and affordability. RESULTS: A
slow-release formulation for ivermectin was implanted into
cattle, causing 40 weeks of increased mortality among Anopheles
arabiensis that fed on them. For this zoophagic vector of
residual malaria transmission across much of Africa, the
proportion surviving three days after feeding (typical mean
duration of a gonotrophic cycle in field populations) was
approximately halved for 25 weeks. CONCLUSIONS: This implantable
ivermectin formulation delivers stable and sustained
insecticidal activity for approximately 6 months. Residual
malaria transmission by zoophagic vectors could be suppressed by
targeting livestock with this long-lasting formulation, which
would be impractical or unacceptable for mass treatment of human
populations
Structural and functional analysis of virus factories purified from Rabbit vesivirus-infected Vero cells
Rabbit vesivirus infection induces membrane modifications and accumulation of vesicular structures in
the cytoplasm of infected Vero cells. Crude RaV replication complexes (RCs) have been purified and their
structural and functional properties have been characterized.We show that calnexin, an ER-resident protein,
RaV non-structural proteins 2AB-, 2C-, 3A-, 3B- and 3CD-like as well as viral RNAs co-localize within
membranous structures which are able to replicate the endogenous RNA templates. The purified virus
factories protected their viral RNA contents from microccocal nuclease degradation and were inaccessible
to exogenously added synthetic transcripts. In addition, we have shown that RCs can be used to
investigate uridylylation of native endogenous VPg. In contrast to the observation that the virus factories
were inaccessible to RNAs, RCs were accessible to added recombinant VPg which was subsequently
nucleotidylylated. Nevertheless no elongation of an RNA chain attached to native or recombinant VPg
could be demonstrated
Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae
Mass administration of endectocides, drugs that kill
blood-feeding arthropods, has been proposed as a complementary
strategy to reduce malaria transmission. Ivermectin is one of
the leading candidates given its excellent safety profile. Here
we provide proof that the effect of ivermectin can be boosted at
two different levels by drugs inhibiting the cytochrome or ABC
transporter in the mammal host and the target mosquitoes. Using
a mini-pig model, we show that drug-mediated cytochrome P450/ABC
transporter inhibition results in a 3-fold increase in the time
ivermectin remains above mosquito-killing concentrations. In
contrast, P450/ABC transporter induction with rifampicin
markedly impaired ivermectin absorption. The same
ketoconazole-mediated cytochrome/ABC transporter inhibition also
occurs outside the mammal host and enhances the mortality of
Anopheles gambiae. This was proven by using the samples from the
mini-pig experiments to conduct an ex-vivo synergistic bioassay
by membrane-feeding Anopheles mosquitoes. Inhibiting the same
cytochrome/xenobiotic pump complex in two different organisms to
simultaneously boost the pharmacokinetic and pharmacodynamic
activity of a drug is a novel concept that could be applied to
other systems. Although the lack of a dose-response effect in
the synergistic bioassay warrants further exploration, our study
may have broad implications for the control of parasitic and
vector-borne diseases
High Pressure Sputtering of materials for selective contacts in emerging photovoltaic cells
In this work we have explored the growth by high pressure sputtering (HPS) of materials intended for novel selective contacts for photovoltaic cells. This technique shows promise for the low-damage low-temperature deposition of PV materials. We studied the deposition of ITO, MoOx and TiOx using pure Ar and mixed Ar/O2 atmospheres as well as ceramic or metallic targets. We show that HPS deposition of these materials is feasible. The growth rate is greatly reduced when oxygen is added to the argon sputtering atmosphere. The best sputtering RF power was 20-45 W for the pressure range studied. Finally, as-deposited films present high surface recombination, but a mild hot plate anneal at 200ºC recovers long effective lifetimes
Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters
This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe
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