Bisher AKIL, MD

Archive for the ‘Immune System’ Category


Coronoviruses in the news

In Immune System, Infections worthy of news on January 23, 2020 at 5:51 pm

An outbreak of respiratory illness caused by a novel (new) coronavirus (termed “2019-nCoV”) that was first detected in Wuhan City, Hubei Province, China and which continues to expand. Chinese health officials have reported hundreds of infections with 2019-nCoV in China, including outside of Hubei Province. A number of countries, including the United States, have been actively screening incoming travelers from Wuhan and human infections with 2019-nCoV have been confirmed in Taiwan, Thailand,  Japan and South Korea. The United States announced their first infection with 2019-nCoV detected in a traveler returning from Wuhan on January 21, 2020.

Coronaviruses are a large family of viruses, some causing illness in people and others that circulate among animals, including camels, cats and bats. Rarely, animal coronaviruses can evolve and infect people and then spread between people such as has been seen with MERS [ Middle East Respiratory Syndrome is viral respiratory illness that is new to humans. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries, including the United States. Most people infected with MERS-CoV developed severe respiratory illness, including fever, cough, and shortness of breath. Many of them have died] and SARS [Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus called SARS-associated coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003. The illness spread to more than two dozen countries in North America, South America, Europe, and Asia before the SARS global outbreak of 2003 was contained. Since 2004, there have not been any known cases of SARS reported anywhere in the world]. When person-to-person spread has occurred with SARS and MERS, it is thought to have happened via respiratory droplets produced when an infected person coughs or sneezes, similar to how influenza and other respiratory pathogens spread. Spread of SARS and MERS between people has generally occurred between close contacts. Past MERS and SARS outbreaks have been complex, requiring comprehensive public health responses.

Early on, many of the patients in the outbreak in Wuhan, China reportedly had some link to a large seafood and animal market, suggesting animal-to-person spread. However, a growing number of patients reportedly have not had exposure to animal markets, suggesting person-to-person spread is occurring. At this time, it’s unclear how easily or sustainably this virus is spreading between people.

Both MERS and SARS have been known to cause severe illness in people. The situation with regard to 2019-nCoV is still unclear. While severe illness, including illness resulting in a number of deaths has been reported in China, other patients have had milder illness and been discharged.

It’s not clear yet how easily 2019-nCoV spreads from person-to-person. It’s important to know this in order to better assess the risk posed by this virus. While CDC considers this is a serious public health concern, based on current information, the immediate health risk from 2019-nCoV to the general American public is considered low at this time.

More cases are likely to be identified in the coming days, including possibly more cases in the United States. Given what has occurred previously with MERS and SARS, it’s likely that some person-to-person spread will continue to occur.

Notes: the above information was compiled on 23 of January 2020, from various sources, and primarily from the CDC; although I usually report scientific data from peer-reviewed papers, I felt this need be reported given a lot of my patients travel to China for business. Bisher Akil, MD

 

Get Measles, Lose Immunity

In Immune System on November 5, 2019 at 11:42 pm

Measles infection appears to deplete a significant proportion of a person’s antibodies, thereby increasing susceptibility to other infections, according to a study in Science.

During a measles outbreak in the Netherlands, researchers measured antibodies against common viruses among 77 un-vaccinated children both before and 2 months after they were infected with measles. After severe cases of measles, patients lost a median of 40% of their preexisting pathogen-specific antibody repertoires. Children with mild cases lost 33%.

Controls who didn’t develop measles retained about 90% of their repertoires. In addition, children who had been vaccinated against measles-mumps-rubella actually saw increases in their antibody diversity.

The authors say that the antibodies begin to rebuild soon after measles infection. In experiments in monkeys, the depletion lasted for at least 5 months, and the authors say some of the loss may be permanent.

The authors conclude: “These findings underscore the crucial need for continued widespread vaccination.”

Source: Science article (free)

Background: NEJM Journal Watch Infectious Diseases coverage of measles infection despite evidence of immunity – Friday 11/1/2-019

Comments: A strong argument for vaccination, in case another one is needed-BA

Virus load is undetectable, but active virus still?

In HIV, Immune System on August 23, 2016 at 4:16 pm

HIV-infected patients taking antiretroviral medications with undetectable viral loads continue to have detectable HIV DNA in CD 4+ cells despite many years of therapy. Previous studies have found that most of that HIV DNA is defective and unable to replicate, a veritable “defective” of proviruses (the genetic material of a virus as incorporated into, and able to replicate with, the genome of a host cell). The current consensus view of the “defective” proviruses is that these are dead-end products that do not give rise to progeny (offspring) virus and thus collectively represent a “graveyard” of viruses.Now, a careful analysis reveals that these defective proviruses may not quite be as “dead” as we thought.

Investigators have now studied HIV DNA proviruses from four patients with undetectable plasma viral loads. As expected, the patients had defective proviruses with deletions or lethal mutations. Surprisingly, when cytoplasmic RNA from these patients was sequenced, the investigators found novel RNA transcripts matching the defective proviruses. These transcripts appeared to be capable of producing viral proteins. Investigators  propose that the proviruses persistently present in combination antiretroviral therapy-treated patients are not defective in a conventional sense, but rather represent incomplete forms of proviruses encoding translationally competent HIV-RNA transcripts. Strategies directed toward curing HIV-1 infection and eliminating the state of persistent immune activation need to include approaches designed to eliminate cells harboring such proviruses.

 

Appeared in JWatch August 5, 2016

Citation(s):Imamichi H et al. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc Natl Acad Sci U S A 2016 Aug 2; 113:8783. (http://dx.doi.org/10.1073/pnas.1609057113)

 

Comments: this could explain the presence of viral activation ( seen by careful analysis of T-cell panel, mediators, ..etc) in those with undetectable plasma virus load. The question remains, should this be controlled, can it lead to an increase in CD4+ counts in those with undetectable virus load? This is probably one of the biggest clinical hurdles left_BA

 

MERSA

In General Health, HIV, Immune System on February 28, 2013 at 6:55 pm

Earlier studies have suggested that HIV-infected individuals have an increased prevalence of nasal colonization with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and a greatly increased risk for CA-MRSA skin and soft-tissue infections. To explore the prevalence and colonization burden of CA-MRSA in HIV-infected and HIV-uninfected individuals, researchers studied patients admitted to a general medicine or HIV ward service at a Chicago hospital between March 2011 and April 2012.Patients were enrolled within 72 hours after admission and were swabbed for CA-MRSA at sites typical for colonization. Risk factors for CA-MRSA colonization were determined using a targeted questionnaire and review of medical records. Of the 745 participants (64% men; 63% black; mean age, 48), 374 were HIV infected. The overall prevalence of CA-MRSA colonization was 10% at the nares and 15% at extranasal sites. HIV-infected patients had a higher prevalence of colonization at any site than did HIV-uninfected patients (20% vs. 11%; P=0.002). Extranasal colonization was most frequent in perirectal and inguinal sites for HIV-infected patients, and in perirectal, inguinal, and throat sites for HIV-uninfected patients. In HIV-infected patients, mean CD4-cell count and median viral load did not differ between those who were and were not colonized with CA-MRSA. In multivariate analysis, factors associated with an increased colonization burden (number of sites colonized per patient) in HIV-infected patients were current or recent incarceration, male sex, and younger age; Hispanic ethnicity was associated with a decreased colonization burden. In HIV-uninfected patients, temporary housing was the only factor associated with a higher CA-MRSA colonization burden. Most of the CA-MRSA isolates (74%) were USA300. Predictors of this strain included HIV infection, male sex, younger age, and current or former illicit drug use.

Published in Journal Watch HIV/AIDS Clinical Care

Citation: Popovich KJ et al. Community-associated methicillin-resistant Staphylococcus aureus colonization burden in HIV-infected patients. Clin Infect Dis 2013 Feb 12;

Comments: The data is not new, but still important to emphasize: one out five HIV infected individuals carry MRSA and not in the usual places (so cultured the nasal area may not be revealing). This has diagnostic and treatment implication as well as public health change in policies_ BA

 

How effective is HPV vaccination?

In General Health, Immune System on February 25, 2013 at 12:18 am

The quadrivalent human papillomavirus (HPV) vaccine prevented genital wart acquisition among women in clinical trials , but its effect at the population level is just beginning to be evaluated. In Denmark, routine free HPV vaccination of 12-year-old girls was introduced in 2009, and the current estimated coverage is 80% for all three doses. Now, investigators have assessed the incidence of genital warts in 55% of the Danish population from 1996 to 2011. Annual incidence of genital warts rose in both women and men from 1996 to 2008, when a downward turn was noted among women but not men. This reduction was especially pronounced among 16- to 17-year-old women, in whom incidence fell 10-fold (from 382 per 100,000 to 40 per 100,000). During this period, prevalence of chlamydia and syphilis continued to rise.

Comment: The drop in prevalence of genital warts but not other sexually transmitted diseases suggests that the human papillomavirus vaccine — and not a behavioral change in the target population — was primarily responsible for this beneficial outcome. It also indicates the need to vaccinate both men and women. Such studies also demonstrate how countries with healthcare systems that allow for efficient delivery of preventive care as well as rapid assessment of the benefits at the national level. The U.S. would do well to learn from such successes.

CITATION: Baandrup L et al. Significant decrease in the incidence of genital warts in young Danish women after implementation of a national human papillomavirus vaccination program. Sex Transm Dis 2013 Feb; 40:130.

Published in Journal Watch Women’s Health


Enhance the Immune Response to HIV

In Immune System on April 1, 2009 at 12:53 am

When a viral infection cannot be eradicated and becomes chronic, the immune system gets exhausted. Human studies have shown that lymphocytes that are exhausted by chronic HIV infection display greater numbers of a receptor called programmed death 1 (PD-1). In an in vitro study, researchers found that an antibody that blocked the ability of PD-1 to activate its suicidal signals allowed lymphocytes to fight HIV more effectively (JW Gen Med Oct 10 2006).
Nine monkeys were treated with partially humanized PD-1 antibodies at 10 weeks or at 90 weeks after they were infected with simian immunodeficiency virus (SIV; a cousin of HIV). Five SIV-infected control monkeys were treated with an antibody against another receptor. The active treatment greatly increased the numbers and the function of both virus-specific CD8+ T cells and memory B cells. Treatment also greatly reduced viral load and led to a remarkable difference in mortality: 150 days after treatment, no treated monkeys, but four controls (80%), had died. Safety studies revealed no abnormalities in liver, kidney, or marrow in treated animals.


IL-2 increases CD4+ count but no clinical improvement

In Immune System on March 22, 2009 at 11:35 pm

Previous studies have suggested that adding Interleukin (IL)-2 will increase CD4+ cell count. The clinical benefit for such increase was inferred but not proven. In February 2009, during the 16th Conference on Retroviruses and Opportunistic Infections (CROI), two studies attempted to show the clinical benefit.
In the SILCAAT trial [Abstract 90bLB], 1695 patients who had CD4 counts <300 cells/mm3 while receiving antiretroviral therapy (ART) were randomized either to continue ART alone or to also receive IL-2 (4.5 million IU, delivered subcutaneously twice daily in at least 6 cycles of 5 days each, separated by 8-week intervals). The median nadir CD4 count was 60 cells/mm3, and the median entry CD4 count was 202 cells/mm3; 81% of patients had viral loads 500 copies/mL. The two treatment groups were well matched at baseline. During follow-up (median, 7.6 years), the IL-2 group averaged 57 more CD4 cells/mm3 than did the ART-alone group, but the rate of opportunistic disease or death was similar between the groups. Adverse event rates were also similar, except in the first year, when the IL-2 group had a higher rate of grade 4 events (mostly psychiatric and gastrointestinal).
The second study, ESPRIT trial, [Abstract 90aLB], had the same study design as SILCAAT, but the 4111 patients had baseline CD4 counts 300 cells/mm3, and the IL-2 was dosed differently (7.5 million IU, delivered subcutaneously twice daily in at least 3 cycles of 5 days each, separated by 8-week intervals). The overall median nadir CD4 count was 197 cells/mm3, and the mean enrollment CD4 count was 457 cells/mm3; 80% of patients had viral loads 500 copies/mL. Results were similar to those of the SILCAAT study: The IL-2 group gained more CD4 cells than did the ART-alone group (average difference, 153 cells/mm3) but did not have a lower rate of opportunistic disease or death. Again, the IL-2 group had an excess of grade 4 adverse events (this time, mostly vascular complications).
Comments: Why? usually more CD4+ cell count means better immune system and less infections, less death…etc. There is no clear answer, but there is no shortage of possibilities: maybe the cells generated are not as good as the cells one gets from ART; maybe IL-2 does something bad, maybe…etc. In the meantime, these were unexpected results _ BA