prophylactic drugs
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The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

Acneiform eruption is a devastating cutaneous side effect of cetuximab, a monoclonal antibody used to treat a variety of cancers. Despite its effectiveness, many patients avoid or discontinue it after experiencing its dermatological side effects as it negatively impacts their quality of life (QoL). This displays the immense need for multidisciplinary collaboration to prevent and treat cetuximab-induced acneiform eruption (CIAE). Prevention methods include, but are not limited to, education, skin care routines, and prophylactic drugs. The following measures reduce the likelihood of developing CIAE and decrease its severity, making it easier to treat if it were to occur. Ongoing research on the treatment of CIAE continues. Of these treatments, oral tetracyclines and systemic corticosteroids have been shown to be the most effective by far. This commentary aims to evaluate the study by Park et al. [Dermatology. 2021;237(3):457–63], further elaborate on prevention and treatment measures of CIAE, and highlight the implications of CIAE on a patient’s QoL.

Background Targeting interventions to areas that have recently experienced cases of disease is one strategy to contain outbreaks of infectious disease. Such case-area targeted interventions (CATI) have become an increasingly popular approach for dengue control but there is little evidence to suggest how precisely targeted or how recent cases need to be, to mount an effective response. The growing interest in the development of prophylactic and therapeutic drugs for dengue has also given new relevance for CATI strategies to interrupt transmission or deliver early treatment. Methods/Principal findings Here we develop a patch-based mathematical model of spatial dengue spread and fit it to spatiotemporal datasets from Singapore. Simulations from this model suggest CATI strategies could be effective, particularly if used in lower density areas. To maximise effectiveness, increasing the size of the radius around an index case should be prioritised even if it results in delays in the intervention being applied. This is partially because large intervention radii ensure individuals receive multiple and regular rounds of drug dosing or vector control, and thus boost overall coverage. Given equivalent efficacy, CATIs using prophylactic drugs are predicted to be more effective than adult mosquito-killing vector control methods and may even offer the possibility of interrupting individual chains of transmission if rapidly deployed. CATI strategies quickly lose their effectiveness if baseline transmission increases or case detection rates fall. Conclusions/Significance These results suggest CATI strategies can play an important role in dengue control but are likely to be most relevant for low transmission areas where high coverage of other non-reactive interventions already exists. Controlled field trials are needed to assess the field efficacy and practical constraints of large operational CATI strategies.

The dissociation phenomenon of epizootic cultures of Moraxella was studied. The study was conducted in economic entities of Almaty region of the Republic of Kazakhstan for 233 heads of cattle with clinical signs of keratoconjunctivitis. Isolation of the causative agent of Moraxella was performed by bacteriological washes from the conjunctival sacs of the eyes of animals. The laboratory study was carried out according to the approved methodological guidelines. It was found that bacteria of the genus Moraxella dissociate when grown on a solid nutrient medium for more than 6 hours in a thermostat at 37 °C. The bacteria were studied by the following methods: staining according to White-Wilson, thermoagglutination and acriflavine assay. When evaluating the grown colonies according to White-Wilson, the optimal dilution for crystal violet was found to be 1 : 2000, and for gentian violet stain 1 : 1000. In this case, the colonies in the S-form have a dark purple color with a metallic tint, and the dissociated colonies in the R-form do not stain. In the presence of dissociated cells, precipitation (thermoagglutination), sediment formation and clearing of the supernatant fluid at 90 °C for 30 minutes were noted. The suspension of undissociated colonies remained cloudy. When weighing microbial cells isolated by a bacterial loop from individual grown colonies in a solution of acriflavine, dissociated bacteria stick together to form conglomerates. When studying the antigenic activity of the S-, R- forms of Moraxella, it was revealed that the activity of the S-antigen significantly exceeded that of the R-forms. Data on the dissociation of Moraxella cultures can be used for the development of diagnostic and prophylactic drugs against moraxellosis in cattle.

COVID-19 pandemic effected more than 180 million people around the globe causing more than four million deaths as of July 2021. Sars-CoV-2, the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing however prophylactic drugs are highly demanded to ensure a secure social contact. There have been a number of drug molecules repurposed to fight against Sars-CoV-2, however the proofs for the effectiveness of these drug candidates is limited. Here we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of the Sars-CoV2 into the Vero6 cell lines and IFNAR-/- mouse models by attaching to spike protein of the Sars-CoV-2. Given the current mutation frequency of the Sars-CoV-2 we believe that GRFT protein-based drugs will have a high impact in preventing the transmission both on Wuhan strain as well as any other emerging variants including delta variant causing high speed spread of COVID-19.

Background. Currently, the researches focused on the design of new diagnostic and preventive preparations based on bacteriophages are underway, so it is importatnt to study the biological properties of cholera phages along with their genetic structure. This information is necessary to predict the phage life cycle and assess the prospects of its practical use in experiments, phagodiagnostics and phagoprophylaxis.Materials and methods. The presence or absence of genes characteristic of temperate bacteriophages was tested using a database created by the authors and developed software "PhageAnalyzer", which allows for rapid analysis of bacteriophage genome-wide sequencing data and prediction of their life cycle.Results and discussion. The morphological structure of experimental diagnostic cholera phages is represented by head bacteriophages of various morphogroups. Negative colonies phage differed in diameter, shape and degree of transparency. No genetic determinants of resistance factors and toxins have been found in the genomes of bacteriophages Rostov-1, Rostov-6, Rostov 7, and Rostov M3. Results of phylogenetic analysis demonstrated that the studied experimental cholera bacteriophages resemble headphages from the genus Vibrio, but are unique, since they lie outside “cluster groups”. Vibrio phages Rostov-1 and Rostov M3 are appeared to be lytic. Genes characteristic of moderate bacteriophages were found in cholera phages Rostov-6 and Rostov 7.Conclusion. The experimental cholera bacteriophage Rostov-1 can be used to differentiate cholera vibrion O1 the serogroup of the El Tor biovar, and Vibrio phage Rostov M3 can be used to differentiate the Classical biovar. Both bacteriophages are lytic and promising components for creating prophylactic drugs against cholera. Vibrio phages Rostov-6 and Rostov 7 can be successfully used only in experimental activities, as well as for monitoring cholera vibrions in the environment. Complete genomic sequences are deposited and available in the international database Genbank (NCBI).

Abstract Introduction Current prophylactic drugs for cluster headache are associated with limited efficacy, serious side effects and poor tolerability. Greater occipital nerve injection (GON-injection) has been proven effective and safe as a single, one-time injection in episodic (ECH), and to a lesser extent, chronic cluster headache (CCH). We aim to analyse the effectiveness and safety of repeated GON-injections in medically intractable chronic cluster headache (MICCH). Methods Clinical data of all cluster headache patients who had received at least one GON-injection between 2014 and 2018 in our tertiary headache centre were retrieved from patients’ medical records. Clinical history was taken as part of routine care shortly before and 6 weeks after GON-injection. Results We identified 47 MICCH patients (79 injections), and compared results with 22 non-MI CCH patients (30 injections) and 50 ECH patients (63 injections). Nineteen MICCH patients received repeated injections (32 in total, range 2–8). Rates of clinical relevant improvement to a first injection were similar in all groups (MICCH: 60%, non-MICCH 73%, ECH 76%; attack freedom: MICCH: 30%, non-MICCH 32%, ECH 43%). Furthermore, no difference in response to the first and second injection was shown between groups (all p > 0.29). Median effect duration in MICCH was 6 weeks (IQR 2.8–12 weeks). Side effects were only mild and local. Conclusion In this retrospective analysis, first and repeated GON-injections were well-tolerated and equally effective in MICCH as in non-MICCH, and ECH.

Background: Multiple studies are evaluating how to prevent SARS-CoV-2 infection. Interventions are wide ranging and include vaccines, prophylactic drugs, public health safety measures, and behavioural interventions. Heterogeneity in the outcomes measured and reported is leading to research waste and inefficiency, slowing worldwide identification and implementation of effective methods to prevent infection. A core outcome set (COS) for studies of interventions to prevent SARS-CoV-2 infection has recently been developed, identifying infection as a critical outcome to measure. This paper examines how SARS-CoV-2 infection outcomes are measured in registered COVID-19 prevention trials and considers how this can be improved. Methods: We searched the Cochrane COVID-19 Study Register to identify and review SARS-CoV-2 infection outcomes in prevention trials, including the rationale for choice of outcome measurement. We included phase 3 and 4 trials of COVID-19 prevention interventions. Early phase trials and studies relating to the transmission, treatment or management of COVID-19 were excluded. Results: We identified 430 entries in the register, of which 199 unique prevention trials were included across eight settings and 12 intervention types. Fifteen (8%) trials did not include any SARS-CoV-2 infection outcomes. The remaining 184 (92%) studies included a total of 268 SARS-CoV-2 infection outcomes, of which 32 (17%) did not specify how infection would be measured. Testing (i.e. formal diagnostic test) as a standalone method for determining infection was used in 57 (31%) trials, whereas defining infection by symptoms alone was used in 16 (9%) trials. All other trials (n=79, 43%) included multiple infection outcomes, defined in different ways. Discussion: There is considerable variation in how SARS-CoV-2 infection is measured within and across different interventions and settings. Furthermore, few studies report the rationale for outcome selection and measurement. Better transparency and standardisation of SARS-CoV-2 infection measurement is needed for the findings from prevention trials to inform decision-making.

At present, in order to expand the raw material base, modern phyto-production is most interested in the use of medicinal plants' organs that were not previously used, but containing flavonoids. The Grossularia reclinata leaves, which are a cheap and affordable plant material, can become a promising source for the creation of phytopreparations containing flavonoid compounds. The aim of the study was to identify and quantify the sum of flavonoids' substances in terms of rutin in the Grossularia reclinata leaves. Material and methods. Qualitative reactions were selected to confirm the presence of flavonoids' substances; differential spectrophotometry was used for their quantitative assessment. Results. It was found that the total content of flavonoids in terms of rutin in alcohol extract from these leaves is on average 0.557 ± 0.0061%, which exceeds their content fruits that were used in medicine by 1.86 times. Comparative analysis of the flavonoids' sum of in the medicinal plants' leaves made it possible to determine that this group of biologically active substances in the Grossularia reclinata leaves is represented in greater quantities than in the motherwort herb (0.2%), wormwood (0.3%) and the tripartite series (0 ,five%). Conclusions: The results of the study allow us to consider this plant raw material promising for the production of new therapeutic and prophylactic drugs.

We conducted a survey of canine microfilaraemia in 768 dogs in Chanthaburi, Samut Sakhon, and Narathiwat provinces of Thailand using a novel semi-automated, microfluidic device that is easy and rapid to perform. Microfilariae species were identified using High Resolution Melting real-time PCR (HRM real-time PCR). The prevalence of canine microfilaremia was 16.2% (45/278) in Chanthaburi and 5.5% (12/217) in Samut Sakhon. The prevalence of canine microfilaremia in Narathiwat was 22.7% (67/273). Brugia pahangi and Dirofilaria immitis were the predominant species of filariae found in the infected dogs from Chanthaburi and Narathiwat, respectively. The low prevalence of canine microfilaremia of Samut Sakhon may reflect the success of the Soi Dog foundation’s efforts and the establishment of veterinary control programs. An effective disease control and prevention strategies is needed in Chanthaburi and Narathiwat to reduce the risks of zoonotic transmission of the parasites. An appropriate drug treatment should be given to infected dogs and prophylactic drugs are suggested to be given to dogs age ≤1-year-old to prevent filarial infection. The novel microfluidic device could be implemented for surveillance of filariae infection in other animals.