Guerrant International Symposium (2nd Intl Symp. on COVID-19/Infectious Diseases & their implications on Sustainable Development)

TB is set to regain its position as the leading infectious killer worldwide. The World Health Organization’s (WHO’s) End-TB Strategy aims to end the global TB pandemic by 2035. Since its launch in 2015, the strategy has marshalled unprecedented political will, international collaboration, and funding to develop better diagnostic tests, new drugs, and a new vaccine. However, we have not even reached the halfway mark in our  TB elimination goals. In this presentation, I shall argue that the reason for this disappointing progress might be underinvestment in a therapy we already have: food.

Undernutrition blunts the function of the immune system and increases the risk for TB so much so that it is likened to HIV/AIDS and called “nutritionally acquired immunodeficiency syndrome” or N-AIDS. Undernourished patients with TB get sicker, have more extensive lung damage, and are more likely to die from TB. It would be unimaginable to leave HIV/AIDS untreated so why do we tolerate neglect of N-AIDS?

Based on modeling studies, feeding an undernourished individual and increasing their body mass index (BMI) from 16 to 20 would decrease their risk for TB disease by about 50 percent. This would be as beneficial as the new TB vaccine, which is generating great enthusiasm. Of course, feeding people has benefits beyond mitigating TB risk: prevention of complications from vitamin and mineral deficiencies, protection against other infectious diseases, increased economic productivity, and decreased human suffering due to hunger. Thus, reducing undernutrition on a population-level may represent a sustainable approach to eliminating TB and preserving human capital which draws on lessons Dr. Guerrant has taught us all. 

To meet the goals of the End-TB Strategy, we must take immediate and radical action. Continued investment in diagnostics, drugs, and vaccines is critical, but we must also invest in meals as we do in medicines. The only way to make rapid progress toward TB elimination is extend our work upstream and focus on prevention by addressing socioeconomic factors such as undernutrition.

HVAC systems and air purifiers in classrooms, offices, and most other indoor spaces have an inherent design flaw when tackling the challenge of capturing airborne pathogens, such as COVID, Influenza, RSV, common cold and others, that can spread airborne-transmitted diseases [1,2]. Both technologies pull the air from one location to another within the indoor space: depending on whether it is an HVAC system or an air purifier, the air is pulled to either an HVAC air return or that of an air intake of an air purifier, thus potentially infecting others [3]. This study presents a proprietary, multiple patent-protected Air-Clenz™ technology platform that efficiently and quickly captures and purifies the exhaled air from each indoor occupant (in the form of a breath, cough, sneeze), before it disperses in the room atmosphere, and releases the purified air back into the venue, all within 5 seconds. Air-Clenz™ technology can be either built into a computer monitor or laptop, or can be attached as a retrofit, aftermarket peripheral, to existing monitors and laptops. Moreover, Air-Clenz™ system for classroom desks has been developed, which permits seated students to easily see and correspond with their teachers, while the system quickly captures and cleans air exhaled by the students and the surrounding general room air and releases it back as clean air as 99%+ free of pathogens, dust, smoke and other pollutants. The Clean Air Changes per Hour (ACH) is increased over 300 % depending on the number of Air-Clenz™ units utilized in the indoor venue. For a classroom of 20 students and a teacher, for instance, the ACH increases from 3 (assumed this is provided with the existing classroom HVAC) to ACH ~ 10, which is well-above than the recommended ideal ACH ~ 6 by Harvard T.H. Chan Public School of Health. A Computational Fluid Dynamics (CFD) model study proved that more than 95% of aerosols and droplets exhaled by the indoor occupants are being captured by the Air-Clenz™-enabled computer monitors, laptops or desks while the room noise level is below 35 dB. Air-Clenz™ technology is a versatile cost-effective platform that can lead to a significant reduction of the cross-infection risk in the current COVID-19 pandemic, but also a solution for minimizing any future airborne-transmitted diseases in confined multi-occupant indoor venues. Moreover, the exhaled-air-capturing-and-purification system enables better indoor air quality, which will result in better cognitive functions, performance, productivity, and happiness of the indoor occupants [4].

The first one thousand days in a person’s life set the stage for the rest of development, learning, and participation in community.  The brain is developing at a very rapid rate, and neurons undergo proliferation, growth, migration, differentiation, synapse formation, and myelination in this critical time period.  Many life influences contribute to early neurodevelopment, including caregiver stimulation, security and attachment, nutrition, safety and health. 

Infants who experience higher burdens of poverty, illness or malnutrition are more likely to experience challenges in growth and development.  Enteric infections are common in children growing up in low- and middle-income countries.  Enteric infections may cause diarrheal illness, and may also contribute to environmental enteropathy, malnutrition, challenges with linear growth, and school days lost due to poor health.  Children growing in families who experience high rates of illness may not be able to participate in play, learning experiences and exploration as often as healthier peers.  Enteric disease may lead to malnutrition and lack of nutrients needed for healthy brain growth and child development. 

In seeking to reduce educational disparities, interventions that target early life influences may help provide children with the best opportunities for health and thriving. 

In this session, we will explore the available data on early life infections and academic outcomes, as well as discuss opportunities for intervention. 

Objectives: Unlike most of the world’s nations, the Russian Federation has a growing incidence of people living with human immunodeficiency virus (HIV). Tuberculosis (TB) is the leading killer of people with HIV, and certain regions in Russia and countries of the former Soviet Union suffer endemic TB compounded by multidrug-resistant strains. In partnership with an academic university in the U.S. and regional academic and public health institutions in Irkutsk, Siberia in the Russian Federation, and supported by joint Russian Foundation for Basic Research and U.S. National Institutes of Health grants, we sought to understand the HIV/TB co-epidemic in Irkutsk, define the intersection of microbe, host and social factors that drive transmission and outcomes, and develop a person-centered mobile health-based programme to enhance integration of HIV and TB care in the region.

Results: We initially determined phenotypic and genotypic relationships within antibiotic resistance determining regions of regionally diverse circulating Mycobacterium tuberculosis strains including the identification of novel strains with enhanced intracellular survival. We then enrolled a prospective cohort of people with drug-resistant TB, the majority with HIV co-infection, and found distinct patterns of individual pharmacodynamic variability of key anti-TB drugs that determined treatment outcome when controlling for other co-variates. As injection drug use was treated with forms of incarceration and removal from larger society without access to opioid replacement therapy, injection drug use and other stigmatized behaviors were found to contribute to the social drivers of disease acquisition and treatment outcome. Thus, we next evaluated outcomes for a cohort of people with HIV, TB, and substance use in Irkutsk after participation in a multi-feature mHealth intervention called MOCT. Sixty patients were enrolled during hospitalization for TB. The majority linked to HIV care by 6 months (83%). Self-scoring of confidence in ability to communicate with HIV providers improved from baseline (median score 8, scale 1-10) to 6 months (10, p = 0.004). A higher proportion of the MOCT subset refilled antiretroviral therapy for HIV (69% vs. 43% in pre-intervention cohort, p = 0.01), with fewer deaths in the MOCT subset at 6 months (1 death vs. 10 deaths in pre-intervention cohort, p = 0.02) and a decreased likelihood of developing the composite outcome of death/failure to achieve viral suppression at 6 months (adjusted odds ratio = 0.33, p = 0.029). At the height of programmatic integration prior to Russia’s invasion of Ukraine, 4,640 people had attended mobile screening events for HIV testing in the Irkutsk region, 338 (7.5%) were HIV infected and linked to care; of those in care throughout the region, 2,005 were using the MOCT app. 

Conclusions: Our experience demonstrated that microbe, host and importantly sociobehavioral drivers of a considerable TB and HIV co-epidemic can served by using multimodal mobile health-based program to overcome stigma and social isolation, and enhance communication and streamline workflow between providers across multiple collaborating institutions. Social marginalization, such as policies of incarceration for addiction or exclusion of minority populations of sexual orientation or gender identity, were commonalities consistently shared in the HIV epidemic in Siberia/Russian Federation and the U.S. Gains toward inclusion and beneficial health outcomes that were observed prior to the abrupt end of the partnership following Russia’s invasion of Ukraine, are notably tenuous, and expected to erode as the war persists.

The post-COVID transformation of healthcare education is required to be aligned with the societal needs and with the evolving healthcare delivery systems. In the past few years, the world experienced unprecedented devastation, disruption, and death due to the COVID-19 global Pandemic. At the same time, the Pandemic acts as a transformation catalyst that accelerated the implementation and adoption of long overdue changes in healthcare education and practice, including telehealth and virtual learning. Interprofessional collaboration during the pandemic was able to foster healthcare transformation in several ways at the policy and legislative level, such as the fast-tracking of internationally trained professions. The role and use of digital technologies, specifically with the emergence of artificial intelligence (AI) and metaverse, in healthcare education and practice are being extended and solidified by the pandemic. Macro-level policies acknowledging the importance of population health are key for future interprofessional collaboration of stakeholders to address inequalities. Similarly, interprofessional collaboration is key to addressing the proliferation of misinformation. Interprofessional education and collaborative practice (IPECP) can be effectively utilized to combat misinformation by increasing health literacy amongst health professions and the communities they serve. 

Going forward, the integration and sustainability of digital technologies, AI, metaverse and IPECP in healthcare education and practice are crucial and the experience of utilizing these new approaches within the context of the COVID-19 pandemic should be reflected on, researched, and evaluated to inform future global healthcare systems and the workforce to provide and achieve the Quintuple Aim (better health, better care, better value, better work experience, and better health equity). As we are emerging out of the Pandemic, we have a unique opportunity to leverage on the lessons learned from the pandemic in fostering the healthcare transformation through innovation, digital technologies, and collaboration. 

The post-COVID transformation of healthcare education is required to be aligned with the societal needs and with the evolving healthcare delivery systems. In the past few years, the world experienced unprecedented devastation, disruption, and death due to the COVID-19 global Pandemic. At the same time, the Pandemic acts as a transformation catalyst that accelerated the implementation and adoption of long overdue changes in healthcare education and practice, including telehealth and virtual learning. Interprofessional collaboration during the pandemic was able to foster healthcare transformation in several ways at the policy and legislative level, such as the fast-tracking of internationally trained professions. The role and use of digital technologies, specifically with the emergence of artificial intelligence (AI) and metaverse, in healthcare education and practice are being extended and solidified by the pandemic. Macro-level policies acknowledging the importance of population health are key for future interprofessional collaboration of stakeholders to address inequalities. Similarly, interprofessional collaboration is key to addressing the proliferation of misinformation. Interprofessional education and collaborative practice (IPECP) can be effectively utilized to combat misinformation by increasing health literacy amongst health professions and the communities they serve. 

Going forward, the integration and sustainability of digital technologies, AI, metaverse and IPECP in healthcare education and practice are crucial and the experience of utilizing these new approaches within the context of the COVID-19 pandemic should be reflected on, researched, and evaluated to inform future global healthcare systems and the workforce to provide and achieve the Quintuple Aim (better health, better care, better value, better work experience, and better health equity). As we are emerging out of the Pandemic, we have a unique opportunity to leverage on the lessons learned from the pandemic in fostering the healthcare transformation through innovation, digital technologies, and collaboration. 

Society has hugely benefitted from recent advances in biological sciences through numerous applications in medicine, agriculture and industry. Current trends in society, governance structures and communications are however beginning to constrain potential benefits in some ways. Limitations are illustrated with examples selected from our own findings on the impacts of global climate change on mosquito borne diseases [1] involving the adaptation of fresh water mosquito vectors to salinity in coastal areas [1,2], the decrease in dengue transmission during COVID-19 lockdown [3], the recent spread of the malaria vector Anopheles stephensi in South Asia and Africa [4], as well as the use of molecular diagnostic techniques for differentiating tick-borne Lyme Disease and Relapsing Fever Borreliosis [5]. 

The contribution made by the recently developed vaccines in saving lives and preventing severe illness due to the COVID-19 throughout the world is widely recognised. However, some avoidable hindrances in the global implementation of the COVID-19 vaccination program that could have further reduced morbidity and mortality from COVID-19, are highlighted as another example.  


 

COVID-19 pandemic cause several impacts worldwide. All countries are affected and there are millions of death during the crisis. The lesson learnt from the crisis can be useful knowledge for our future. It is no doubt that the collaboration among mankind is the core concept for fighting for any global castastrophie. Although the problem is already not serious, it still requires further research and development toward the problem and other new problem emering problems. At present, post COVID-19 pandemic stage,  several problems still remain and there are possibilities of new emerging problems. To achieve a sustainable development in the post-COVID-19  world, the multidisciplinary and interdisciplianry collaboration is proven useful and effective approach.  In this talk, the importance of consillence of science, art and humanistic in corresponding to global criss is highlighted. The implication for future sutainable development is concluded.

Treatment options for mild to moderate COVID-19 is limited. N-acetylcysteine and bromhexine have antiviral activity and show potential as treatment options against SARS-CoV-2 infections. This study evaluates the in vitro antiviral effect of bromhexine (BMX) for SARS-CoV-2 and determines the efficacy of treatment with BMX in combination with N-acetylcysteine (NAC) to reduce clinical scores in patients with mild to moderate COVID-19. Upon evidence from pre-clinical studies, a single center randomized trial of BMX + NAC (ClinicalTrials.gov Identifier: NCT04928495) with420 participants in total took place in Fortaleza, CE, Brazil. Out of the 420 participants 140 received placebo, 140 received NAC alone, and 140 received NAC + BMX. Patients were monitored for 10-14 days, where physicians recorded all signs and symptoms reported. Nasopharyngeal swabs and blood samples were collected for SARS-CoV-2 RNA testing during the first visit, as well as 3 and 10 days after.  Blood samples were collected at first visit and 10 days after for immuno-inflammatory biomarkers measurements. Treatment with NAC+BMX reduced clinical scores and symptoms when compared to placebo group (2/26; 8% vs 7/18; 39%; p < 0.05). Fever (≥37.8°C) was reduced by NAC + BMX treatment when compared to treatment with NAC alone and placebo. This study was limited by a largely vaccinated population. Our analysis showed that BMX reduces SARS-CoV-2 infection in vitro. Clinical trial results suggested that combinatory treatment with NAC + BMX is beneficial in mild to moderate COVID-19.

Background
As the reduced eradication rate of Helicobacter pylori (H. pylori), we introduced string-test and quantitative PCR (qPCR) for susceptibility-guided therapy innovatively. The practicality of the string test was evaluated.
Methods
It was an open-label, non-randomized, parallel, single-center study, in which subjects tested by 13C- urea breath test (UBT) and string-qPCR were enrolled. Based on the results of string-qPCR, we calculated clarithromycin and levofloxacin resistance rates and gave 13C-UBT positive patients 14 days susceptibility-guided bismuth quadruple therapy. In the empirical therapy group, we retrospectively analyzed the treatment results of 13C-UBT positive patients also treated with bismuth quadruple at Shenzhen Luohu People's Hospital from January 2021 to May 2022. The eradication rate was compared between susceptibility-guided therapy and empirical therapy groups.
Results
The diagnosis of H. pylori infection using the string-qPCR had an overall concordance rate of 95.9% with the 13C-UBT results. Based on the results of string-qPCR, the clarithromycin and levofloxacin resistance rates were 26.1% and 31.8%, respectively. The patients who were given 14 days susceptibility-guided bismuth-based quadruple therapy achieved a high H. pylori eradication rate of 91.8%. Retrospective analysis of patient treatment data from January 2021 to May 2022 available in the hospital database revealed an overall success rate of 82.3% for those who received empirical bismuth-based quadruple therapies, which is marginally significantly lower than that of the string-qPCR susceptibility-guided group (p = 0.084).
Conclusion
The high treatment success rate of 91.8% indicates that the string-qPCR test is a valuable and feasible approach for clinical practice to help improve H. pylori treatment success rate.

Introduction: We discovered that IL-13 is elevated in patients with COVID-19, promoted disease in a mouse model, and in a RCT showed that IL-13/IL-4 blockade with dupilumab (anti-IL4Ra mAb) reduced mortality in patients with COVID-19. IL-13 induces the deposition of the polysaccharide hyaluronan (HA) in the lungs, and inhibition of the HA receptor CD44 protects from SARS-CoV-2 disease. We are determining the mechanisms by which alarmins such as IL-33 initiate a type 2 immune response, how IL-13 is induced, and its impact on HA matrices and CD44-mediated inflammation and disease.

Hypothesis: We hypothesize that IL-13 produced by ILC2s in the lung during COVID-19 induces a hyaluronan (HA) matrix that via HA receptors (including CD44⁺) recruits inflammatory cells, resulting in respiratory failure.

Significance: Uncovering the mechanisms of IL-13-induced hyaluronan matrices and signaling in driving COVID-19 severity has the promise of novel therapeutic approaches directed at the IL-13 - hyaluronan pathway, as well as being of importance for other pulmonary diseases where hyaluronan is known to contribute.

My career in science separates into two distinct halves:  The first half was focused on basic mechanisms by which bacterial toxins cause diarrhea and whether those mechanisms could be used in better diagnosis and treatment.  Realizing that simple salt, sugar and water ORT would be hard to beat, the second half became focused on the potentially life-long developmental and cognitive consequences of enteric infections (EE) that were not solved by simple ORT.  [This was for 2 reasons: it was not caused by just acute dehydration and it was associated with gut barrier disruption and inflammation that occurred even more frequently without overt diarrhea but with widespread, previously unrecognized ‘silent’ infections with multiple pathogens (predominantly bacterial and parasitic).]

I shall review first the basic science lessons I have learned from Mother Nature and second, the profound importance of understanding the threats to us all of not understanding the human ravages of disparity and inequity.  These are linked in lessons for the survival of our Homo sapiens species as we know it. 

 [They also reflect how my research career evolved from its first to its second half]

Cholera & Turista re cAMP/cGMP taught Nobel laureates Gilman and Murad very different lessons; and also a potential explanation for why we have the dreaded Alzheimer’s Disease ApoE4 risk allele.  Vicious cycles of poverty include three ‘new’ diseases: stunted growth, impaired cognitive development and later life metabolic diseases (HAZdrop, COGhit and METsyn).

The second half moved from understanding the molecular mechanisms of cholera and E. coli toxins’ opposite effects on adenylate and guanylate cyclase respectively to both surprisingly cause severe secretory diarrhea (as with epidemic cholera and ‘Turista’), hoping to improve on ORT, to realizing the greater, lasting importance of the “environmental enteropathy” (EE) that many enteric pathogens cause with potential long-term impairment of children’s growth and even cognitive development.

 I will note the impact, biomarkers, mechanisms and remediation of EE.

This work led to my writing about the “Evolution of Evolution: The Survival Value of Caring,” in which we can learn that evolution itself may be changing the fastest, traits that were once advantageous evolve to become disadvantageous and even threaten our survival.  The imperative of bridging our science with our humanity requires nothing less than a broadening of our concept of “self,” and a “Declaration of Interdependence.”   How the poorest on our planet fare is what will determine the fate of us all.

Thankfully, we have experts who can address sustainability lessons from COVID-19, TB and other pandemics (with Drs. Petri and Sinha) as well as threats to us all from troubling global disparities (with Drs. Scharf and Heysell) here with us today.