Development of New Strategies for Malaria Chemoprophylaxis: From Monoclonal Antibodies to Long-Acting Injectable Drugs.

Drug discovery for malaria has traditionally focused on orally available drugs that kill the abundant, parasitic blood stage. Recently, there has also been an interest in injectable medicines, in the form of monoclonal antibodies (mAbs) with long-lasting plasma half-lives or long-lasting depot formulations of small molecules. These could act as prophylactic drugs, targeting the sporozoites and other earlier parasitic stages in the liver, when the parasites are less numerous, or as another intervention strategy targeting the formation of infectious gametocytes. Generally speaking, the development of mAbs is less risky (costly) than small-molecule drugs, and they have an excellent safety profile with few or no off-target effects. Therefore, populations who are the most vulnerable to malaria, i.e., pregnant women and young children would have access to such new treatments much faster than is presently the case for new antimalarials. An analysis of mAbs that were successfully developed for oncology illustrates some of the feasibility aspects, and their potential as affordable drugs in low- and middle-income countries.

Delivery of seasonal malaria chemoprevention with enhanced infection prevention and control measures during the COVID-19 pandemic in Nigeria, Burkina Faso and Chad: a cross-sectional study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a WHO-recommended intervention for children aged 3-59 months living in areas of high malaria transmission to provide protection against malaria during the rainy season. Operational guidelines were developed, based on WHO guidance, to support countries to mitigate the risk of coronavirus disease 2019 (COVID-19) transmission within communities and among community distributors when delivering SMC. METHODS: A cross-sectional study to determine adherence to infection prevention and control (IPC) measures during two distribution cycles of SMC in Nigeria, Chad and Burkina Faso. Community distributors were observed receiving equipment and delivering SMC. Adherence across six domains was calculated as the proportion of indications in which the community distributor performed the correct action. Focus group discussions were conducted with community distributors to understand their perceptions of the IPC measures and barriers and facilitators to adherence. RESULTS: Data collectors observed community distributors in Nigeria (n = 259), Burkina Faso (n = 252) and Chad (n = 266) receiving IPC equipment and delivering SMC. Adherence to IPC indications varied. In all three countries, adherence to mask use was the highest (ranging from 73.3% in Nigeria to 86.9% in Burkina Faso). Adherence to hand hygiene for at least 30 s was low (ranging from 3.6% in Nigeria to 10.3% in Burkina Faso) but increased substantially when excluding the length of time spent hand washing (ranging from 36.7% in Nigeria to 61.4% in Burkina Faso). Adherence to safe distancing in the compound ranged from 5.4% in Chad to 16.4% in Nigeria. In Burkina Faso and Chad, where disinfection wipes widely available compliance with disinfection of blister packs for SMC was low (17.4% in Burkina Faso and 16.9% in Chad). Community distributors generally found the IPC measures acceptable, however there were barriers to optimal hand hygiene practices, cultural norms made social distancing difficult to adhere to and caregivers needed assistance to administer the first dose of SMC. CONCLUSION: Adherence to IPC measures for SMC delivery during the COVID-19 pandemic varied across domains of IPC, but was largely insufficient, particularly for hand hygiene and safe distancing. Improvements in provision of protective equipment, early community engagement and adaptations to make IPC measures more feasible to implement could increase adherence.

Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study.

BACKGROUND: Hydroxychloroquine had attracted significant attention in the initial phases of the COVID-19 pandemic but current recommendations do not support its use. However, the evidence against its use as pre-exposure prophylaxis have been of low to moderate quality and have been limited by high risk of bias. METHODS: Following institutional ethics committee approval, healthcare workers (n = 1294) completing their first week-long COVID in-patient duty, subsequent institutional quarantine and RT-PCR testing for COVID-19 infection were included for this prospective cohort study. Demographic data, hydroxychloroquine usage and related adverse effects were captured through a 'Caring for the Caregivers' surveillance system. A chi-Square test of independence was used to determine the effect of hydroxychloroquine prophylaxis. RESULTS: Among the 1294 participants (age: 31 ± 7 years, 61% women), 273 (21.1%) healthcare workers used hydroxychloroquine prophylaxis as per Indian Council of Medical Research recommendations and 83/1294 (6.4%) tested positive after their duty. There was no significant difference in COVID-19 incidence between those on hydroxychloroquine prophylaxis and those not on it (5.9% vs 6.6%, χ2 = 0.177, p = 0.675; RR = 0.89, 95% CI - 0.53 to 1.52). There were no significant adverse effects to hydroxychloroquine usage. CONCLUSION: This study demonstrated no benefit of hydroxychloroquine prophylaxis and provides quality evidence against its use in COVID-19 prevention.

Redox modulation of vitagenes via plant polyphenols and vitamin D: Novel insights for chemoprevention and therapeutic interventions based on organoid technology.

Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Here, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed. We also discuss the possible relationship between SARS-CoV-2, inflammation and cancer, exploiting innovative therapeutic approaches with HT-rich aqueous olive pulp extract (Hidrox®), a natural polyphenolic formulation, as well as the rationale of Vitamin D supplementation. Finally, we describe innovative approaches with organoids technology to study human carcinogenesis in preclinical models from basic cancer research to clinical practice, suggesting patient-derived organoids as an innovative tool to test drug toxicity and drive personalized therapy.

Dudrick Research Symposium: Expanding the boundaries of cancer care through nutrition support.

The 2020 Dudrick Research Symposium, entitled "Expanding the Boundaries of Cancer Care Through Nutritional Support," was held on March 30, at the American Society for Parenteral and Enteral Nutrition (ASPEN), Nutrition Science & Practice Conference. It was scheduled to take place in Tampa, Florida, but had to be held virtually. The Dudrick Symposium honors the many pivotal and innovative contributions made by the late Dr Stanley J. Dudrick, physician scientist, academic leader, and a founding member of ASPEN. This year, in addition to honoring his legacy, we honored his life. As the 2019 recipient of the Dudrick Research Scholar Award, Dr Pimiento chaired the symposium. The presentations focused on discussing the history, the present and future frontiers in the overlapping fields of nutrition support and cancer care. The late Dr John Daly opened the presentation with a moving tribute to Dr Dudrick's life and then spoke about the impact of nutrition support on surgical care and outcomes for cancer patients. Dr Pimiento discussed the role of nutraceuticals for cancer chemoprevention, and the level 1 clinical evidence surrounding this topic. Dr Kraemer explored the role of exercise physiology for optimal nutrient utilization and the overlap between targeted physical activity and nutrition support to obtain better outcomes on the cancer population. The symposium was closed by Dr Stephen Hursting, who discussed the impact of obesity in the soaring cancer rates and its relationship with clinical outcomes. In this article, we cover the presentations by Drs Pimiento and Kraemer.

Selenium as a Bioactive Micronutrient in the Human Diet and Its Cancer Chemopreventive Activity.

This review answers the question of why selenium is such an important trace element in the human diet. Daily dietary intake of selenium and its content in various food products is discussed in this paper, as well as the effects of its deficiency and excess in the body. Moreover, the biological activity of selenium, which it performs mainly through selenoproteins, is discussed. These specific proteins are responsible for thyroid hormone management, fertility, the aging process, and immunity, but their key role is to maintain a redox balance in cells. Furthermore, taking into account world news and the current SARS-CoV-2 virus pandemic, the impact of selenium on the course of COVID-19 is also discussed. Another worldwide problem is the number of new cancer cases and cancer-related mortality. Thus, the last part of the article discusses the impact of selenium on cancer risk based on clinical trials (including NPC and SELECT), systematic reviews, and meta-analyses. Additionally, this review discusses the possible mechanisms of selenium action that prevent cancer development.

Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine.

Severe durable changes may occur to the DNA structure caused by exogenous and endogenous risk factors initiating the process of carcinogenesis. By evidence, a large portion of malignancies have been demonstrated as being preventable. Moreover, the targeted prevention of cancer onset is possible, due to unique properties of plant bioactive compounds. Although genoprotective effects of phytochemicals have been well documented, there is an evident lack of articles which would systematically present the spectrum of anticancer effects by phytochemicals, plant extracts, and plant-derived diet applicable to stratified patient groups at the level of targeted primary (cancer development) and secondary (cancer progression and metastatic disease) prevention. Consequently, clinical implementation of knowledge accumulated in the area is still highly restricted. To stimulate coherent co-development of the dedicated plant bioactive compound investigation on one hand and comprehensive cancer preventive strategies on the other hand, the current paper highlights and deeply analyses relevant evidence available in the area. Key molecular mechanisms are presented to detail genoprotective and anticancer activities of plants and phytochemicals. Clinical implementation is discussed. Based on the presented evidence, advanced chemopreventive strategies in the context of 3P medicine are considered.

COVID-19 knowledge, beliefs, prevention behaviours and misinformation in the context of an adapted seasonal malaria chemoprevention campaign in six northern Nigerian States.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine and amodiaquine is an efficacious intervention for protection of children against Plasmodium falciparum malaria during the rainy season. In response to the global COVID-19 pandemic, Malaria Consortium adapted its SMC delivery model to ensure safety of distributors, data collectors and beneficiaries. We conducted a SMC monitoring survey in July 2020 in the states of Bauchi, Jigawa, Kano, Katsina, Sokoto and Yobe, with questions on COVID-19 prevention behaviours and symptoms, and belief in misinformation. We investigated the associations between receipt of information on COVID-19 by different sources, including from SMC distributors, and these three outcomes using logistic generalised estimating equations. We also considered moderation of effectiveness of message delivery by SMC distributors and adherence to use of face coverings. RESULTS: We obtained a representative sample of 40,157 caregivers of eligible children aged 3-59 months, of which 36,914 (91.92%) reported knowledge of COVID-19. The weighted proportions of respondents who correctly identified COVID-19 prevention behaviours and symptoms, and who reported belief in COVID-19 misinformation, were 80.52% (95% confidence interval [95% CI] 80.02-81.00), 81.72% (95% CI 81.23-82.20) and 22.90% (95% CI 22.24-23.57). Receipt of information on COVID-19 from SMC distributors during the campaign was significantly associated with higher odds of caregiver knowledge of COVID-19 prevention behaviours (odds ratio [OR] 1.78, 95% CI 1.64-1.94, p < 0.001) and symptoms (OR 1.74, 95% CI 1.59-1.90, p < 0.001) and lower odds of belief in COVID-19 misinformation (OR 0.92, 95% CI 0.85-1.00, p = 0.038). The associations between message delivery by SMC distributors and the three outcomes were moderated by their adherence to face covering use. Receipt of information by other sources used to deliver government public health messages, including radio and health facility workers, was also associated with knowledge of COVID-19. CONCLUSIONS: Malaria Consortium's SMC programme was successfully adapted in the context of COVID-19 and was a conduit for high-quality public health messages. Standard SMC monitoring and evaluation activities can be adapted to gather evidence on emerging public health issues such as the global COVID-19 pandemic.