Ebola Will Spread if Resources Are Not Brought to Bear

 Acting swiftly and decisively to extinguish the Ebola outbreak in Uganda is an important priority not just for Uganda, but for Africa and the world. The current outbreak has, thus far, been confirmed to have killed 10 -- including 4 healthcare workers -- and while over 40 cases have been confirmed, none have been outside of Uganda where several districts are reporting cases. However, there is a strong possibility that it will spread to other countries. If resources are not brought to bear, that spread is likely to be an eventuality.

The Outbreak's Origin

Uganda is a nation that has faced a half dozen prior outbreaks of Ebola. Accordingly, the virus is not an unknown entity there. This current outbreak was declared in September 2022 with the confirmation of a fatal case in a 24-year-old male. This was unlikely to be the first case as unexplained deaths had been reported in the first weeks of September. It is unknown precisely how this outbreak started and exactly when it began, though it is likely to have been a few weeks prior to the first confirmed case, as clinical misdiagnosis of Ebola as typhoid, meningitis, malaria, and other infectious diseases can occur.

The Sudan Strain

Complicating this outbreak is the fact that of the six species of Ebola that have been described, the Ugandan outbreak is caused by the Sudan strain. This strain, which is highly lethal, is one which has not been involved in human outbreaks since 2012 and is often overshadowed by the more prolific Zaire strain. The Zaire strain was responsible for the massive 2013-2014 West African outbreak and, not coincidentally, is the strain for which vaccines and monoclonal antibodies are available. Unfortunately, countermeasures for one Ebola strain do not have an impact on others. The exact animal reservoir of the Sudan strain and why and how it emerges have not yet been established. It is assumed to be harbored by bats, like other strains of Ebola.

On-the-Ground Needs

Despite Uganda's past Ebola experiences, it is clear from the pleas of health leaders in the country that they are unable to effectively combat the virus. Coupled with this are concerns about testing capacity, personal protective equipment, economic concerns of physicians, and the need for investigational vaccine trials to commence. This last point is an important lesson to carry forward from 2013-2014: successful vaccine trials that demonstrate efficacy of candidate vaccines in development can be conducted in the midst of an outbreak. There are currently two Sudan Ebola vaccine candidates poised to be tested. The leading candidate, developed by The Sabin Institute, exists in a small ready-to-use supply (though more is available in bulk form). Monoclonal antibody development is also being funded. It is important to emphasize that simple measures, such as intravenous fluid and electrolyte replacement, can have considerable impacts on mortality rates, if these minimal resources needed to provide such supportive care are in place.

A ministerial level meeting is being convened next week by the World Health Organization and the Africa Centers for Disease Control and Prevention. In addition to providing material resources, it will be critical for the health authorities to gain the trust of the population they're advising, as mistrust of simple health messages -- such as safe burial practices -- can foster the spread of the virus (as occurred in West Africa in 2014). Battling misinformation such as allegations of witchcraft are, unfortunately, necessary.

Meeting the Challenge

It is critical for the world to recognize that, just as in 2013-2014, the longer an Ebola outbreak is left to fester in one geographic region the more likely an imported case becomes. As the U.S. painfully learned from the panic and chaos that ensued in Dallas with the initial misdiagnosis and death of Thomas Eric Duncan and the transmission of the virus to two healthcare workers, it is much better to fight and contain Ebola at its source than deal with imported cases and the cascading melee they prompt in various countries around the world. Travel screening of those traveling from Uganda has already been initiated in the U.S., but a much more impactful action would be augmenting testing, contact tracing, public health messaging, and treatment capacity in those regions of Uganda with cases.

Ebola is a deadly, scary disease but one that is not very contagious. It does not possess pandemic potential as it is spread through blood and body fluids, delimiting the efficiency of its transmission. Nevertheless, as was seen in 2013-2014, chains of transmission can be very long and the death and destruction it can cause sizable. It can be stopped in its tracks if resources are brought to bear.

In the wake of COVID-19, it takes a high degree of evasion to not recognize the need for competent and well-resourced responses to infectious disease threats as they appear.

Amesh Adalja, MD, is a senior scholar at the Johns Hopkins Center for Health Security, and a practicing infectious disease, critical care, and emergency physician in Pittsburgh.

https://www.medpagetoday.com/opinion/second-opinions/101118

Seneca Therapeutics Receives FDA Clearance to Begin SVV-001 Phase I/II

 Seneca Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to the development of novel immunotherapies for difficult to treat solid cancers announced today it had received FDA clearance to begin a Phase I/II clinical study utilizing Seneca Valley Virus (“SVV-001”) in combination with a checkpoint inhibitor. This Phase I/II study with SVV-001 is in patients that are TEM8 positive and SVV-001 permissive with neuroendocrine tumors or neuroendocrine carcinomas. The study should begin enrollment early in 2023.

https://www.biospace.com/article/releases/seneca-therapeutics-receives-fda-clearance-to-begin-svv-001-phase-i-ii-clinical-study

Kira Receives FDA Clearance of IND Application for Phase 2 Evaluation in Systemic Lupus

 

Phase 1 supporting data indicated an encouraging profile and confirmed the dual mechanism of action achieved through targeting both the alternative and terminal complement pathways  Kira Pharmaceuticals, a global biotechnology company pioneering transformational complement therapies to treat immune-mediated diseases, announced today that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for KP104, a first-in-class bifunctional biologic that selectively and synergistically targets the alternative and terminal complement pathways. The Phase 2 trial will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KP104 in participants with systemic lupus erythematosus associated thrombotic microangiopathy (SLE-TMA) in the US, China, and Australia. The IND was supported by Phase 1 data (SYNERGY-1 Study), which demonstrated proof-of-mechanism for KP104 on both the terminal and alternative complement pathways and showed an encouraging profile for the Phase 2 study in SLE-TMA. https://www.biospace.com/article/releases/kira-pharmaceuticals-receives-fda-clearance-of-ind-application-for-phase-2-evaluation-of-kp104-in-systemic-lupus-erythematosus-associated-thrombotic-microangiopathy-sle-tma-/?keywords=kira

Needs More Salt

 One year ago, the Food and Drug Administration issued Guidance for Industry, a document setting out goals to reduce sodium content—generally found as sodium chloride (salt)—in commercially processed, packaged, and prepared foods. Shortly afterward, the Competitive Enterprise Institute submitted a request for correction (RFC) of the guidance under the Information Quality Act (IQA). Defying a requirement to respond within 60 days, the FDA has not replied.

The Competitive Enterprise Institute (where I am a senior fellow) filed the RFC—an administrative mechanism to seek correction of inaccurate agency information—because the FDA failed to conduct a peer review of its scientific findings before issuing guidance that may harm more people than it helps. This is an important safeguard under the IQA, which Congress enacted to ensure the “quality, objectivity, utility, and integrity of information (including statistical information) disseminated by Federal agencies.”

Agencies issuing “influential” scientific information—defined as having a “substantial impact on important public policies or important private sector decisions”—must conduct a pre-dissemination peer review utilizing qualified and independent specialists in the relevant field who were not involved in producing the agency’s draft. Guidelines setting sodium-concentration targets for all “Commercially Processed, Packaged, and Prepared Foods” in the more than $2 trillion food service and retailing industry are clearly “influential.” And while the guidance is technically voluntary, the FDA has indicated that it will “specifically encourage attention by” food manufacturers with large market share, as well as national restaurant and retail food chains.

Yet the FDA failed to conduct a peer review. Further, the agency’s own scientific review, while quite detailed, failed to acknowledge considerable uncertainty in the field.

The guidance is based on the premise that lowering sodium intake, regardless of individuals’ current intake levels and health status, will lower blood pressure and, in turn, reduce the incidence of cardiovascular disease and death. Sodium consumption is linked to the development of hypertension, a leading cause of heart disease and stroke, but the connections are not straightforward.

A 2020 review of randomized controlled trials—the gold standard for scientific studies—assessing the effect on blood pressure and potential side effects of reducing salt intake by the highly respected Cochrane Library found a minuscule (0.3 percent) decrease in blood pressure in white people with normal blood pressure and a small decrease (about 3.5 percent) in people with elevated blood pressure. A few trials suggested these effects may be somewhat greater in black and Asian people. But these minimal benefits carried health costs. Sodium reduction resulted in significant increases in cholesterol and triglycerides—both associated with cardiovascular disease—which were more consistent than the blood pressure declines, especially in non-hypertensive people.

Instead of targeting sodium reduction at the hypertensive population most likely to benefit, the FDA guidance prescribes it for everyone. And the guidance fails to distinguish between people with high sodium intakes and those with normal or low sodium intakes.

Multiple studies suggest that low sodium intake can be just as detrimental as high sodium intake, leading to increased risk of cardiovascular disease and death in “those with or without hypertension.” A prospective trial in the prestigious New England Journal of Medicine found that daily sodium intake between three and six grams (g) per day—a range consumed by most of the world’s population, including in the U.S., where the average is 3.4 g—was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake.

In fact, sodium intake has been remarkably uniform worldwide over time. An analysis of 190 peer-reviewed studies found a narrow range of 2.6 g to 4.8 g per day that was reproducible over five decades and 45 countries with diverse populations, eating habits, and food industries. The average daily intake of 3.7 g was higher than the U.S. average.

Last year, researchers concluded that the available evidence shows the optimal level of sodium intake is between three grams and five grams per day. Since 80 percent of Americans have daily intake below five grams, the authors argued that “efforts to reduce sodium intake in entire populations cannot be justified.”

Sodium reduction should be targeted at hypertensive people with high-sodium diets. The FDA’s indiscriminate guidance may actually increase cardiovascular disease and death for many Americans.

The point of the pre-dissemination peer-review requirement is to resolve scientific uncertainties before agencies issue guidance that will have enormous health and economic consequences. But despite learning of its procedural lapse and the outstanding scientific issues a year ago, the FDA has yet to act.

The FDA should withdraw its sodium guidance and start the peer-review process. Doing so would take one step toward restoring the public confidence that government health authorities lost during the pandemic.

Joel Zinberg, M.D., J.D., is a senior fellow at the Competitive Enterprise Institute, an associate clinical professor of surgery at the Icahn Mount Sinai School of Medicine in New York, and the director of Paragon Health Institute’s Public Health and American Well-being Initiative. He was general counsel and senior economist in 2017–19 at the Council of Economic Advisers, where he specialized in health policy.

https://www.city-journal.org/fda-sodium-folly

CDC: Record Number Of Children Hospitalized With Weakened Immune Systems

 Official data suggests that more children and young adults than ever have been hospitalized with colds and respiratory issues, according to the Daily Mail, which notes that "experts have repeatedly warned lockdowns and measures used to contain Covid like face masks also suppressed the spread of germs which are crucial for building a strong immune system in children."

According to a retrospective report by the Centers for Disease Control (CDC), levels of common cold viruses hit their highest level among non-adults in August 2021 - when levels had been much lower in previous years during the same month.

According to the data which sampled nearly 700 children, nearly 55% tested positive for RSV in August 2021. Of that, 450 were moved to emergency departments where nearly 35% had RSV - which is comparable to the winter months when over 30% of patients regularly have the virus, according to the report.

The CDC samples random pediatric hospitals across the US and makes national estimates to gauge how prevalent viruses are. 

There were nearly 700 children in hospital sick with a respiratory virus across the seven wards studied in August last year, of which just over half had tested positive for respiratory syncytial virus (RSV) - which is normally benign.

This was the highest levels ever recorded in summer, and came off the back of a year and a half of brutal pandemic restrictions forcing many to stay indoors.

The record all-time high is in December, when 60 per cent of children on wards with respiratory illnesses were infected with RSV. -Daily Mail

What's more, separate data from the CDC indicates that hospital visits for those under four years old may be getting worse. For the week ending Sept. 18 of this year, 4.7% of ER visits in the US for toddlers were for breathing difficulties.

Yale medical director Dr. Scott Roberts told the Mail that lockdowns robbed children of the ability to build up immunity to common illnesses.

"There are two implications to this," he said. "First, the gap gives time for the viruses to mutate even further to cause more severe disease. And second, whatever immunity was built up to those viruses' it will have waned making the immune response now much less potent."

Roberts added that his son, who just turned two-years-old, was coming down with repeated infections after starting daycare.

"We were pretty sheltered during the pandemic," he said, adding "But now my son has just started daycare and he is getting constant infections."

The rise in hospitalizations among children was noted in the CDC's Morbidity and Mortality Weekly Report (MMWR), after scientists monitored seven hospitals in seven states for the number of children admitted for respiratory issues. Each child was then tested to determine what disease they had - which doesn't necessarily mean that was the reason for hospitalization.

https://www.zerohedge.com/medical/cdc-record-number-children-hospitalized-weakened-immune-systems

Perturbed network in ALS, frontotemporal neurodegeneration

 JEAN-MARC GALLO AND DIETER EDBAUER

DOI: 10.1126/science.ade4210

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that share clinical, pathological, and genetic features. A pathological hallmark of ALS-FTD is the presence of ubiquitin-positive protein aggregates (or inclusions) in the cytoplasm of affected neurons. The main component of inclusions in most ALS cases and half of FTD cases is the mostly nuclear RNA binding protein, TDP-43 (TAR DNA binding protein 43) (1). The existence of rare ALS-causing mutations in TARDBP, which encodes TDP-43, suggests a causal role of TDP-43 dysfunction in the pathogenesis of ALS-FTD (2, 3). Pathogenic mutations in several other genes are more common in ALS and FTD, but how they trigger cytoplasmic aggregation of TDP-43 remains unknown. On page 94 of this issue, Shao et al. (4) partly address this by showing that two ALS-FTD–associated genes cooperate to cause TDP-43 cytoplasmic aggregation by impairing endosome maturation.

https://www.science.org/doi/10.1126/science.ade4210

HC Wainwright Initiates Aptorum On Upcoming 'Innovative Pipeline'

 

• HC Wainwright initiated coverage on Aptorum Group Limited 
  APM+2.58%+ Free Alerts
   with a Buy rating and a price target of $8.
• The analyst is bullish on Aptorum based on three points: 
  • Promising preclinical efficacy of lead product candidate ALS-4, both on a standalone basis and in combination with standard of care vancomycin, against Staphylococcus aureus (SA) infection.
  • Blockbuster potential of SACT-1’s in vivo neuroblastoma tumor reduction effects in combination with SOC chemotherapy
  • The significant potential of the company’s nascent programs and ongoing collaborations to generate future value and importantly, near-term revenues. 
• With Aptorum’s market cap of $39 million, the analyst believes revenues from Aptorum’s recent launch of NativusWell in Hong Kong de-risk concerns related to near-term financing needs. 
• HC Wainwright thinks the shares are an attractive value proposition ahead of initiation of a Phase 2a trial of ALS-4 in patients with SA infections, Phase 1b/2a study with SACT-1 in neuroblastoma, and expansion of NativusWell commercialization viewed as positive catalysts by year-end 2022 or early 1Q23.

https://www.benzinga.com/general/biotech/22/10/29188574/hc-wainwright-initiates-aptorum-on-upcoming-innovative-pipeline