The Observatory and Fast Facts

March 25, 2020
Preventive Services Task Force updates recommendation for hepatitis C screening

The U.S. Preventive Services Task Force said recently that clinicians should screen all adults for the hepatitis C infection, updating its 2013 recommendation.

The earlier recommendation called for screening people at high risk for infection or one-time testing of adults born between 1945 and 1965. The new recommendation expands screening to all adults ages 18 to 79.

The task force said it updated its recommendation for these reasons:

• Treatment continues to evolve, and the duration of direct-acting antiviral regimens has been getting shorter with higher rates of sustained virologic response and less serious harm than earlier treatment regimens.

• Since 2013, the prevalence of HCV infection in adults ages 20 to 39 who inject drugs has increased.

• HCV infection rates for adults born between 1945 and 1965 remain relatively high.

Citing studies, the task force estimated that 4.1 million people have tested positive for the anti-HCV antibody, and 2.4 million have current infections.

The task force recommends screening with anti-HCV antibody testing followed by polymerase chain reaction testing for HCV RNA to identify chronic HCV infection.

HHS awards $117 million to end HIV epidemic in the U.S.

The U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), awarded approximately $117 million to expand access to HIV care, treatment, medication and prevention services. The investment is a component of the department’s initiative to reduce the number of new HIV infections in the United States by 90 percent by 2030.

The initiative and the awards focus on 48 counties, Washington, D.C., and San Juan, Puerto Rico, geographic areas where more than 50 percent of new HIV diagnoses occurred in 2016 and 2017, as well as the seven states with a substantial rural HIV burden.

HRSA’s Health Center Program awards will be used to identify at-risk individuals and engage in preventive services, test for HIV and prescribe pre-exposure prophylaxis (PrEP) when appropriate. Awards made to HRSA’s Ryan White HIV/AIDS Program recipients will be used to link people who are either newly diagnosed with HIV, or diagnosed but currently not in care, to essential HIV care, treatment and support services, helping them reach viral suppression and reduce HIV transmission.

HRSA awarded nearly $54 million to 195 health centers with service delivery sites in geographic locations identified by the EHE initiative. This first-of-its-kind program emphasizes outreach, HIV testing, partnerships and workforce expansion to increase access to and use of PrEP, as well as linking individuals who test positive for HIV to treatment.

RSA awarded approximately $63 million to 60 Ryan White HIV/AIDS Program recipients to link people with HIV to essential HIV care and treatment and support services, as well as to provide workforce training and technical assistance. This includes more than $55 million to 39 metropolitan areas and eight states, which are Ryan White HIV/AIDS Program Parts A and B jurisdictions, to enable recipients to implement strategies, interventions, approaches and core medical and support services to reduce new HIV infections in the U.S.

In addition, HRSA awarded approximately $3 million to 11 Ryan White HIV/AIDS Program Part F AIDS Education and Training Centers Program recipients to provide workforce capacity development and technical assistance to the identified jurisdictions.

HRSA also awarded $5 million to two organizations to provide technical assistance and systems coordination services to the 47 Parts A and B jurisdictions which received funding.

Researchers identify new target for antiviral treatment

As the coronavirus outbreak shows, viruses are a constant threat to humanity. Vaccines are regularly developed and deployed against specific viruses, but that process takes a lot of time, doesn’t help everyone who needs protection, and still leaves people exposed to new outbreaks and new viruses.

Now, researchers at Massachusetts General Hospital (MGH) have uncovered a novel potential antiviral drug target that could lead to treatments protecting against a host of infectious diseases – creating a pan, or universal, treatment. Their work suggests that the protein Argonaute 4 (AGO4) is an “Achilles heel” for viruses.

AGO4 is one of a family of AGO proteins. Until now, there has been little evidence of whether they have individual roles. The researchers, led by Kate L. Jeffrey, PhD, and her collaborators found that AGO4 plays a key role protecting cells against viral infections.

Specifically, this protein is uniquely antiviral in mammalian immune cells. The group studied the anti-viral effects of several Argonaute proteins and found that only cells that were deficient in AGO4 were “hyper-susceptible” to viral infection. In other words, low levels of AGO4 make mammalian cells more likely to become infected. This study was published by Cell Reports.

The MGH researchers suggest that boosting levels of AGO4 could shore up the immune system to protect against multiple viruses.

Study raises questions about antibiotics for pneumonia

A large study of patients hospitalized for pneumonia suggests that a treatment strategy designed to account for patients with antibiotic-resistant infections should be reconsidered.

The study, published in JAMA Internal Medicine, found that pneumonia patients who received empirical broad-spectrum antibiotics had a higher risk of death compared with those who received standard antibiotic therapy. They also had a higher risk of kidney injury, along with C. diff and other secondary infections.

The authors of the study say the findings are a good example of how efforts to improve clinical outcomes for patients can sometimes lead clinicians to adopt practices that aren’t backed by solid evidence. In the case of pneumonia, concerns about possible infection with resistant organisms like methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa has led to a strategy of early broad-spectrum antibiotics for certain patients.

The strategy goes back to the 2005 guidelines from the American Thoracic Society and the IDSA for treatment of adults who have community-acquired pneumonia (CAP). Those guidelines recommended that pneumonia patients who lived in nursing homes or had been in the hospital in the previous 90 days should be labeled as having healthcare-associated pneumonia (HCAP) and treated empirically with broad-spectrum antibiotics like vancomycin or piperacillin-tazobactam to cover for the possibility that the pneumonia was caused by MRSA or Pseudomonas.

Subsequently, a 2015 study of patients in the Department of Veterans Affairs (VA) healthcare system found that, after those guidelines were published, a substantial shift in treatment of CAP patients occurred, with the proportion of vancomycin prescribing rising from 16 percent in 2006 to 31 percent in 2010 and piperacillin-tazobactam prescribing jumping from 16 percent to 27 percent. This shift occurred even though less than 5 percent of patients in the study had resistant bacteria detected.

To get a better sense of how empiric broad-spectrum therapy is affecting clinical outcomes in CAP patients, a team led by investigators from the VA Salt Lake City Health Care System and the University of Utah conducted a retrospective cohort study of all CAP hospitalizations in the VA health care system from 2008 through 2013.

They specifically looked at the 30-day mortality rate associated with three empirical treatment regimens: standard antibiotics alone, standard antibiotics plus anti-MRSA therapy, and anti-MRSA therapy without standard antibiotics. Secondary outcomes included development of kidney injury and secondary infections with C. difficile, vancomycin-resistant Enterococcus species, or gram-negative bacteria.

Of the 88,605 CAP patients analyzed in the study, empirical anti-MRSA antibiotics were administered to 33,632 (38 percent), with 13,528 receiving empirical anti-MRSA therapy with standard antibiotics and 20,104 receiving anti-MRSA therapy without standard antibiotics. The 30-day all-cause mortality rate was 10 percent (8,929 patients). Only 2 percent of the patients (2,154) had MRSA detected by clinical culture.

After adjusting for comorbidities and other patient characteristics that might affect treatment regimens and risk of 30-day mortality, the analysis found that empirical anti-MRSA treatment plus standard therapy was significantly associated with greater 30-day mortality compared with standard therapy alone, as was anti-MRSA treatment with non-standard therapy.

Targeting immune cells to treat cerebral malaria

Researchers at the National Institutes of Health (NIH) found evidence that specific immune cells may play a key role in the devastating effects of cerebral malaria, a severe form of malaria that mainly affects young children.

The results, published in the Journal of Clinical Investigation, suggest that drugs targeting T cells may be effective in treating the disease.

More than 200 million people worldwide are infected annually with mosquito-borne parasites that cause malaria. In a subset of those patients, mainly young children, the parasites accumulate in brain blood vessels causing cerebral malaria, which leads to increased brain pressure from swelling. Even with available treatment, cerebral malaria still kills up to 25 percent of those affected resulting in nearly 400,000 deaths annually. Children who survive the infection will often have long-lasting neurological problems such as cognitive impairment.

The researchers examined brain tissue from 23 children who died of cerebral malaria and 11 children who died from other causes. The scientists used state-of-the-art microscopy to explore the presence of cytotoxic lymphocytes (CTLs) in the brain tissue samples. CTLs are a type of T cell in our immune system that is responsible for controlling infections throughout the body.

Current treatment strategies for cerebral malaria focus on red blood cells, which are thought to clog blood vessels and create potentially fatal blockages leading to extreme pressure in the brain. However, findings in the mouse model demonstrated that CTLs damage blood vessels, leading to brain swelling and death. The role of CTLs in cerebral malaria in children hasn’t been thoroughly investigated prior to this study.

The results of the current study demonstrate an increased accumulation of CTLs along the walls of brain blood vessel in the cerebral malaria tissue samples compared to non-cerebral malaria cases. The CTLs were also shown to contain and release effector molecules, which damage cells, suggesting that CTLs play a critical role in cerebral malaria by damaging the walls of brain blood vessels.

The NIH researchers compared CTL patterns in the cerebral malaria cases that were co-infected with HIV and those that were HIV negative. In the HIV-negative cases, the CTLs were seen lining up against the inside wall of the brain blood vessels. In the HIV-positive cases, the CTLs had migrated across the surface to the outside of the vessels.

Additional research is needed to uncover the role of T cells in human cerebral malaria. Future studies will also investigate how targeting T cells may help treat the disease. Plans for a clinical trial are underway to test the effects of a specific T cell blocker in cerebral malaria patients in Malawi