Top Infectious Disease News of the Week— February 10, 2019

#5: CDC Issues Alert for Drug-Resistant Brucellosis Linked to Raw Milk Consumption

The US Centers for Disease Control and Prevention (CDC) has announced an investigation of exposure to Brucella strain RB51 following consumption of unpasteurized milk from Miller’s Biodiversity Farm in Quarryville, Pennsylvania.

Health officials in 19 states are advised to be aware that individuals who present to their health care provider with fever, sweats, loss of appetite, headache, fatigue, muscle and joint pain, and report having consumed unpasteurized milk may have been exposed to RB51.

RB51 is resistant to rifampin, a first-line antibiotic that would be used to prevent or treat brucellosis. The CDC recommends that anyone who may have been exposed to RB51 go to visit their health care provider to be evaluated in order to prevent infection and symptoms from developing.

Read about the CDC's warning.

#4: Inappropriate Antimicrobial Use in the Emergency Department for Skin and Soft Tissue Infections

Acute bacterial skin and skin structure infections (ABSSSIs) remain among the leading reasons patients visit the emergency department (ED). A retrospective study performed between 1997 and 2005 estimated 14.2 million ambulatory visits for skin and soft tissue infections (SSTIs), and the proportion of ED visits increased nearly 4-fold over the duration of the study.1 Skin and soft tissue infections lead to ABSSSIs, which are characterized by the US Food and Drug Administration as involving lesions with a size area of at least 75 cm.2 These lesions can include non-purulent cellulitis, purulent cellulitis, abscesses, and wound infections,3 some of which occur concurrently making it difficult when choosing antimicrobial therapy based on visual assessment alone. Studies have also shown high rates of inappropriate antibiotic prescribing and opportunity for improvement when it comes to ABSSSIs.2

Read about inappropriate antibicrobial use for SSIs.

#3: Zika Virus IgM Detected 12 to 19 Months Following Infection Onset, Study Finds

Since the introduction of Zika virus to the Americas in 2015 research has been key to understanding Zika transmission and infection and establishing clinical guidance. Now a new study by investigators at the Florida Department of Health and the US Centers for Disease Control and Prevention (CDC) is adding to the limited data on the duration of detectable Zika virus-specific immunoglobulin M (IgM) in infected persons.

Florida saw more than 350 laboratory-confirmed locally-acquired cases of the virus in 2016. The CDC’s current Zika testing guidance recommends Zika virus and/or dengue virus IgM testing of serum in certain situations and notes that while IgM levels vary in Zika cases, they are generally positive beginning 4 days after onset of symptoms and continuing for up to 12 weeks, though may persist for months to years.

In the new study published in the CDC journal Emerging Infectious Diseases, investigators have found that most study participants with prior Zika infection continued to have detectable Zika virus IgM a year or more beyond onset of illness.

Read about Zika virus IgM.

#2: FDA Issues Complete Response Letter for Iclaprim

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Motif Bio for iclaprim. The FDA's decision to not approve iclaprim for the treatment of acute bacterial skin and skin structure infections (ABSSI) was based on the need for additional data, according to the letter.

Iclaprim has a targeted Gram-positive spectrum of activity, which can decrease the use of broad-spectrum antibiotics to avoid resistance build-up, and reduce the impact on the microbiome. According to the FDA, more data is needed to evaluate the risk for liver toxicity before the approval of the New Drug Application.

According to an announcement by Motif Bio, the company will request a meeting with the FDA to determine a possible course of action to address the FDA's concerns.

Read about the FDA's CRL for Iclaprim.

#1: Presence of A3A Affects Latent HIV's Ability to Reactivate

Scientists have already had success in suppressing HIV-1, but what they don’t yet understand is how the virus becomes latent in infected cells, or how it becomes reactivated after latency.

Now, though, scientists have uncovered a major clue. Investigators at Yale University have demonstrated that the protein Apobec3A (A3A) has the power to promote latency or induce reactivation. The findings, published in the Proceedings of the National Academy of Sciences, could have implications for future HIV therapies.

A3A was already known to help the body suppress HIV during the time frame just after infection. However, Akiko Iwasaki, PhD, of the Yale University School of Medicine, and colleagues wondered what role A3A might play once the virus had entered the latent state.

To study the question, they took T cells lines infected with latent HIV and experimented by modifying genes to either overexpress A3A, or to knock down or knock out the protein.

When A3A was overexpressed, investigators observed lower levels of HIV reactivation. When A3A was decreased, HIV reactivation increased.

“Collectively, we provide evidence and a mechanism by which A3A reinforces HIV-1 latency in infected CD4 T cells,” Dr. Iwasaki and colleagues wrote.

A3A accomplishes the task of controlling HIV latency by binding to a particular part of DNA, Dr. Iwasaki and colleagues reported. The results were later replicated in human T cells.

Read about A3A's effect on latent HIV.