Changes in exhaled 13CO2/12CO2 breath delta value as an early indicator of infection in intensive care unit patients


BACKGROUND We have developed a new, noninvasive predictive marker for onset of infection in surgical intensive care unit (ICU) patients. The exhaled 13CO2/12CO2 ratio, or breath delta value (BDV), has been shown to be an early marker for infection in a proof of concept human study and in animal models of bacterial peritonitis. In these studies, the BDV changes during onset and progression of infection, and these changes precede physiological changes associated with infection. Earlier diagnosis and treatment will significantly reduce morbidity, mortality, hospitalization costs, and length of stay. The objective of this prospective, observational, multicenter study was to determine the predictive value of the BDV as an early diagnostic marker of infection.

METHODS Critically ill adults after trauma or acute care surgery with an expected length of stay longer than 5 days were enrolled. The BDV was obtained every 4 hours for 7 days and correlated to clinical infection diagnosis, serum C-reactive protein, and procalcitonin levels. Clinical infection diagnosis was made by an independent endpoint committee. This trial was registered at the US National Institutes of Health (ClinicalTrials.gov) NCT02327130.

RESULTS Groups were demographically similar (n = 20). Clinical infection diagnosis was confirmed on day 3.9 ± 0.63. Clinical suspicion of infection (defined by SIRS criteria and/or new antibiotic therapy) was on day 2.1 ± 0.5 in all infected patients. However, 5 (56%) of 9 noninfected subjects also met clinical suspicion criteria. The BDV significantly increased by 1‰ to 1.7‰ on day 2.1 after enrollment (p < 0.05) in subjects who developed infections, while it remained at baseline (± 0.5‰) for subjects without infections.

CONCLUSION A BDV greater than 1.4‰ accurately differentiates subjects who develop infections from those who do not and predicts the presence of infection up to 48 hours before clinical confirmation. The BDV may predict the onset of infection and aid in distinguishing SIRS from infection, which could prompt earlier diagnosis, earlier appropriate treatment, and improve outcomes.

LEVEL OF EVIDENCE Diagnostic test, level III.

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Infected EBOLA carriers escape quarantine hospital in the Democratic Republic of Congo


Image: Infected EBOLA carriers escape quarantine hospital in the Democratic Republic of Congo

A new and growing Ebola outbreak is hitting the Democratic Republic of Congo, and additional concerns have been raised as three infected people escaped their quarantine hospital, potentially infecting countless others.

The three patients had been quarantined in the northwestern city of Mbandaka, a port city with a population of nearly 1.2 million. Two of the patients have passed away, while a third has been found alive and brought back to the hospital for observation. Medecins Sans Frontieres said that two of the escapees had been brought by their families to a church to pray.

World Health Organization Spokesman Tarik Jasarevic told ABC News that while the incident was very concerning, it isn’t unusual for people to wish to spend their final moments in their homes with loved ones. WHO staff is now redoubling its efforts to track down everyone who might have come into contact with these patients.

The problem is compounded by the fact that Ebola is so easily spread. Exposure to the body, fluids, or even personal items of someone who has died from the disease can spread it easily, something that not everyone there is aware of. The WHO is working with community and religious leaders to get the word out in hopes of keeping infections to a minimum.

Another challenge is the fact that traditional practices in the area don’t match up with health recommendations, particularly when it comes to funeral practices. In addition, some of the rural population does not believe in Ebola in the first place and has no faith in the ability of Western medicine to help.

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Workers from the WHO and Oxfam are going door to door to let everyone know what hygienic precautions they can take to lower their chances of contracting the deadly disease. They’re also letting them know about symptoms to look out for, which include headache, muscle pain, fatigue, fever, diarrhea, vomiting, rash, and bleeding or bruising.

How far will the current outbreak spread?

Until recently, the current Ebola outbreak had been confined to the country’s rural areas, but it has now made its way to bigger cities like Mbandaka, where it has the potential to spread to many more people. The city’s location along the Congo River and its use as a transit hub is raising fears about just how far the outbreak could spread. The city of Kinshasa, which has a population of 10 million, is just downstream, and across the river is the Republic of the Congo’s capital, Brazzaville.

So far, 58 people have reported hemorrhagic fever symptoms in the country, although it’s likely that there are many more cases going unreported given the general mistrust of doctors in the country. Thirty cases have tested positive for Ebola, 14 are suspected, and 14 are considered probable. Some of the infected include health care workers. Twenty-two people have died so far in what is the country’s ninth outbreak since the deadly virus was first identified in 1976, and the outbreak only started earlier this month.

Experts have said that the outbreak has now reached a critical point, with the next few weeks indicating whether they’ll be able to keep the outbreak under control or if it will hit urban areas in full force. Health workers have a list of more than 600 people who are known to have come into contact with confirmed cases, and they are working hard to keep it from becoming a repeat of past outbreaks. One of the biggest Ebola outbreaks struck Guinea, Sierra Leone, and Liberia between 2013 and 2016, killing more than 11,300 people.

Sources for this article include:

DailyStar.co.uk

ABCNews.go.com

CBC.ca

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Infection and OR staff hair


We had an independent nurse evaluate us for upcoming JCAHO inspection. We ‘failed’ due to not covering facial hair and chest hair with scrub attire and in addition were told folks with hairy arms needed long-sleeve scrub tops. Of course this comes from the all powerful AORN. Being an evidence-based person at heart, I began to look for some evidence regarding covering up (that is how I stumbled onto your blog). Do you have any knowledge of evidence based practice regarding hair covering and infection rates?

Great question. Where do they come up with these things? Chest hair? Arm hair? Long-sleeve scrub tops?

For the record, I am against wound infections. I would do any reasonable thing to try to prevent them.

I suspect your independent nurse evaluator may have over-interpreted the rules. My distaste for the Joint Commission (by the way, don’t ever say “JCAHO” again) runs deep, but I don’t think even they have thought of those wrinkles to the hair issue.

It is possible though as the JC and the AORN seemed to be obsessed with hair.

I assume long sleeve scrub tops would be for the circulating nurse only. If the surgeon and the scrub tech wore long sleeves, they wouldn’t be able to properly wash their hands and arms.

Regarding the chest hair, are we talking male or female staff? (Just kidding.)

As far as I know, there is not one shred of evidence linking hair on the head, face, chest or arms of OR staff to patient infections. This is after an exhaustive search of PubMed, CDC, and holding nothing back, I even crowd-sourced the question on Twitter.

In case some readers missed my post on the ritual of clipping the hair of patients before surgery, the link is here. The post was about rules that people make up without any justification to drive us all crazy.

I have collected several such rules from other frustrated readers. Here they are.

  • No forced-air warming until patient is draped.
  • No briefcases in the OR.
  • No one may enter the room without the circulator’s permission.
  • No room warming as it may cause condensation on surgical instruments. (Condensation causes infections? And children and burn victims who may become hypothermic in a cold room be damned!)
  • Remove masks every time you leave the OR. And no letting them hang down with just the lower tie done.
  • Masks must be worn by anyone in the scrub sink area even if that person is not scrubbing but just walking by.
  • All OR personnel must wear long sleeves because of the potential for “shedding skin.”
  • Patient hair on the operative site must be clipped in an area other than the operating room.

But the independent nurse reviewer has spoken. I’m betting that long sleeve scrub tops and chest hair police will soon appear in your OR.

Mounting data suggest antibacterial soaps do more harm than good.


Few pros, but cons include upped risk of infection, microbiome changes, drug resistance.

Whether you’re coming home from an airport fluttering with international germs, a daycare full of sticky-fingered toddlers, or just a grimy office building, scrubbing your hands with bacteria-busting soap seems like a great idea. But the data that have washed up on the cleansers in recent years suggest that they actually do more harm than good—for you, those around you, and the environment.

Scientists report that common antibacterial compounds found in those soaps, namely triclosan and triclocarban, may increase the risk of infections, alter the gut microbiome, and spur bacteria to become resistant to prescription antibiotics. Meanwhile, proof of the soaps’ benefits is slim.

There are specific circumstances in which those antimicrobials can be useful, civil engineer Patrick McNamara of Marquette University in Milwaukee told Ars. Triclosan, for instance, may be useful to doctors scrubbing for minutes at a time before a surgery or for hospital patients who can’t necessarily scrub with soap but could soak in a chemical bath. Triclosan and triclocarban do kill off bacteria during long washes. But most people only clean their hands for a few seconds. “There’s evidence that there is no improvement with using soaps that have these chemicals relative to washing your hands under warm water for 30 seconds with soaps without these chemicals,” he said.

And the point hasn’t been lost on the US Food and Drug Administration. Though the agency ruled years ago that triclosan and other antimicrobials are safe, it’s now revisiting claims that the chemicals make soaps and other personal care products better. The FDA has asked antibacterial soap makers to send in data showing that their soaps beat out regular soaps at keeping people germ-free and healthy. The agency expects to announce this September whether the submitted data pass muster. If they don’t, the companies that make up the $5.5 billion soap market may be forced to ditch the chemicals entirely.

Sullied Soaps

In the meantime, however, researchers seem to be digging up more and more dirt on the chemicals, particularly triclosan. This antimicrobial is widely used in not just hand soaps, but body washes, shampoos, toothpastes, cosmetics, household cleaners, medical equipment, and more. And it’s just as pervasive in people as it is in homes and clinics. Triclosan easily enters bodies by ingestion (think toothpaste) or skin absorption. It’s commonly found in people’s urine, blood, breast milk, and even their snot.

A 2014 study led by microbiologist Blaise Boles of the University of Michigan in Ann Arbor tested 90 adults and found that 41 percent (37 people) had triclosan-laced boogers. Antimicrobial-snot paradoxically doubles your odds of having the potentially-infectious Staphylococcus aureusbacteria up your nose.

In rats exposed to triclosan, Dr. Boles and his colleagues found that triclosan exposure made it more difficult, not less, for the rodents to fend off Staph invasions. Triclosan seems to make the bacteria “stickier”—better able to adhere to proteins and surfaces. That stickiness could be whyStaph is so good at hunkering down in the schnoz, setting the stage for future infections.

Other researchers have been looking at how triclosan and other antimicrobials may alter microbial communities further down from the nose—in the gut.

Microbiologist Thomas Sharpton of Oregon State University and his colleagues are currently studying triclosan’s effect on the gut microbiomes of zebrafish, a model organism for vertebrate development. Their preliminary data suggest that the antimicrobial causes swift, sweeping changes in the zebrafish gut microbiome, altering both diversity and community structure.

In another study, presented April 1 at the Endocrine Society‘s 98th annual meeting in Boston, researchers report that mother rats exposed to triclocarban—an antimicrobial used most frequently in bar soaps—passed on the chemical to their pups. The study, led by public health researcher Rebekah Kennedy of the University of Tennessee, Knoxville, also found that the chemical altered the microbiomes of both the mothers and the babies.

“Our research adds to the growing body of scientific literature suggesting unintended health consequences related to non-prescription antimicrobial use and will allow pregnant and nursing mothers to make informed decisions regarding use of these antimicrobial products,” said Dr. Kennedy.

But, Dr. Sharpton cautions, we don’t know yet if such microbiome changes are lasting or if they spark health effects. “We’re really are in the beginning days of understanding how to interpret changes in the microbiome,” he said to Ars.

Still, previous studies have linked dampened diversity and rapid microbial changes from prescription antibiotics to health effects, such as a greater risk of intestinal infections. The results certainly warrant follow-up research, both Sharpton and Kennedy said.

Flush with chemicals

While researchers continue to work out what antimicrobials do while they’re in people’s bodies, Dr. McNamara of Marquette University focuses on what the chemicals do once people pee them out or wash them down the drain. McNamara and his colleagues have been tracking both triclosan and triclocarban in wastewater treatment plants, where both chemicals can accumulate.

In a 2014 study, McNamara’s research team found that triclosan messed with the microbial communities that break down sewage, in some cases sabotaging their ability to digest the sludge. The chemical also caused a spike in the presence of a gene called mexB in the sewage microbes. This gene codes for a pump that allows bacteria to simply kick out triclosan before it can kill them off. This pump, McNamara hypothesizes, also spits out common prescription antibiotics, such as ciprofloxacin. In experiments, bacteria with mexB were resistant to antibiotics, too.

In a January study, McNamara, his graduate student Daniel Carey, and colleagues found that triclocarban had the same effect as triclosan—it also disrupts the microbial communities that digest sewage and spurs bacteria to become resistant to drugs.

From wastewater treatment plants, these superbugs can leak out into waterways, wildlife, and potentially back to people, McNamara told Ars.

While some experts are hopeful that actions by the FDA and state regulators may nix the use of these chemicals in commercial products, McNamara thinks consumer choices may be the most powerful way to reduce use of the chemicals. People could use regular soap or ethanol-based sanitizers and have effective, less risky cleansers, he said. “There’s a way that we can still keep our hygiene without having these extra chemicals.”

UNICEF study reveals two-thirds of rural Indian children who die below the age of five are lost to treatable conditions like premature birth, infection, and diarrhoea


Despite the government’s efforts to curb child mortality, children under the age of five continue to die due to medical negligence and lack of timely medical aid.

A study, funded by the Ministry of Health and Family Welfare, USAID and UNICEF, conducted in rural areas of 16 districts from eight states across India, revealed that even today newborns suffer from infections, acute respiratory infection (ARI) and diarrhoea, which accounts for approximately 63 per cent of deaths in children under the age of five.

The study conducted by the Department of Biostatistics, All India Institutes of Medical Sciences (AIIMS), along with the INCLEN Trust International, was published in the latest issue of Indian Journal of Community Medicine.

Children under the age of five continue to die of diseases such as acute respiratory infection and diarrhoea

Children under the age of five continue to die of diseases such as acute respiratory infection and diarrhoea

The survey conducted in around 216,794 households revealed that more than 1,656 children under the age of five die due to various reasons.

The autopsies were analysed to learn the specific causes of deaths. In newborns, these were shown to be birth asphyxia, premature birth, and infection.

All this contributed to more than 67.5 per cent of the neonatal deaths, while in children aged 29 days to 59 months, ARI and diarrhea accounted for 54.3 per cent of deaths.

Shockingly, the families of 52.6 per cent of newborns and 21.7 per cent of infants and children under the age of five, did not seek any medical care.

The study said that substantial delays in seeking medical attention led to deaths either at home or during transit.

Little girls continue to be ignored in the Indian households, as the study revealed that baby girls born at home, or born in a health center run by unskilled health workers and caregivers with less than primary education were at a higher risk.

States such as Bihar, Madhya Pradesh, Rajasthan, Uttar Pradesh and Andhra Pradesh have recorded high mortality rates in children below five, and these were dubbed high-burden states in India.

Low birth weight and premature birth were the leading causes of neonatal mortality in Karnataka, Maharashtra, and Odisha. In Uttar Pradesh and Haryana, children largely died in the post-neonatal period due to diarrhoea.

“The majority of these deaths could have been prevented with the interventions offered in primary and secondary care,” the study revealed.

The study has indicated that arranging for transportation and social support for accompanying and deciding health care needs are interlinked and these were reported to be the major difficulties faced by families living in remote villages.

A contrary report was released by the National Family Health Survey (NFHS).

This survey was conducted in four of the 15 states and union territories, and it concluded that fewer children were dying in infancy and early childhood.

The Health Ministry recently said after the last round of NFHS in 2005-06, the infant mortality has declined in all the states/union territories.

The Ministry also said that all the 15 states/union territories have low death which is 51 deaths per 1,000 children born each day. It also added that there is a considerable variation among the states and the union territories.

 

The Sooner, The Better .


New approaches to diagnosing bacterial infections may one day allow the identification of pathogens and their antibiotic susceptibility in a matter of hours or minutes.

Depending on the microbe’s propensity to grow in culture and the amount of it present in the sample, it can take a day or longer for the lab to identify the pathogen, and an additional one to two days to get the antibiotic susceptibility results. But in many cases it can be impractical or risky for a clinician to wait for those results before initiating treatment. Therefore, he or she will make an educated guess as to the cause of the infection and might send the patient home with a prescription for a broad-spectrum antibiotic capable of ridding the body of a number of bacterial pathogens.

This practice means that doctors sometimes prescribe antibiotics when they are not necessary, potentially leading to harmful side effects and contributing to the emergence of antibiotic resistance. In other instances, when a bacterial infection is resistant to the empiric antibiotic therapy, delays in treatment with an appropriate antibiotic may increase the risk that the infection will worsen or spread to others. “If there were rapid diagnostics available, we could provide more-targeted treatments sooner, rather than later,” says Joseph Liao, associate professor of urology at Stanford University’s medical school and the chief of urology at the VA Palo Alto Health Care System in California.

To speed the diagnosis of infections, Liao and others are developing simple and inexpensive tests based on biosensors that convert the molecular recognition of a target molecule into signals that can be measured optically, electrically, mechanically, or magnetically. Well-known examples of commonly used biosensor-based assays include home pregnancy tests and handheld glucose monitors. Biosensor technologies for infectious diseases still need to clear significant regulatory hurdles before they can be used clinically, but they already show promise as portable and easy-to-use tools to rapidly identify a variety of pathogenic bacteria and to inform effective treatments. Here, The Scientistlooks at three such technologies under development.

Magnetic DNA Sandwich

Researchers: Hakho Lee, assistant professor, and Ralph Weissleder, director, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School

Technology: Using a miniaturized nuclear magnetic resonance (NMR) device created by Weissleder’s lab, Lee and Weissleder’s team developed an assay that can determine whether or not a sample contains virtually any species of bacteria or specifically identify 13 different bacterial pathogens in about two hours’ time (Nat Nanotechnol, 8:369-75, 2013). The researchers first isolate RNA from bacteria and use PCR to amplify a 50-70–nucleotide region of the 16S ribosomal RNA—either a region that is highly conserved among most bacterial species (for universal detection of bacteria), or a sequence that is unique to a particular pathogen of interest (for species-specific detection). Then they mix a sample of the PCR reaction with microbeads covalently coated with DNA probes 18–22 nucleotides in length that are designed to bind to one end of the PCR product. After washing away unbound DNA and beads, they add magnetic nanoparticles conjugated with DNA strands that bind to the opposite end of the PCR amplicon, forming a so-called magnetic sandwich complex with the bacteria-derived DNA in the center. “Eventually what we have are microbeads coated with these magnetic nanoparticles,” Lee says.

After further washing to rid the beads of unbound nanoparticles, the researchers place the sample inside their miniaturized NMR device. The NMR signal in samples that contain magnetic nanoparticles decays faster than in those that do not, Lee says, thus enabling detection of samples that contain bacteria.

Application: The assay was able to detect as few as one or two bacteria added to a 10-mL sample of whole blood and also provided an estimate of the number of bacteria present in a sample. It also accurately diagnosed a variety of patient specimens—including lung fluid, pelvic abscess contents, urine, and bile—as either positive or negative for bacteria. In samples positive for bacteria, the assay correctly identified all of the bacterial species that could be detected by standard culture, as well as two additional species not detected by culture.

Pros:

  • The assay can be performed using as little as 10 μL of a patient sample.
  • The detection step has very low background, because the samples have no inherent magnetic signal.
  • The miniature NMR device is small, portable, and inexpensive. Lee says the device itself costs roughly $500 to build, and estimates that the cost of the magnetic nanoparticles and other reagents is about $10 per assay.

Cons:

  • The assay involves multiple, independent steps that can increase the risk of contamination and inaccurate results.
  • No multiplexing. The assay must be repeated for each bacterial species of interest.

Other applications: Using a similar strategy, the group developed an assay for the detection of PCR-amplified DNA from Mycobacterium tuberculosis. The assay is performed on a microfluidic chip that handles the PCR, bead capture and labeling, and NMR detection steps (Nat Commun, 4:1752, 2013). In addition, the team has varied the molecules used for capturing and labeling to detect other molecules of interest besides bacterial nucleic acids. For instance, Lee and Weissleder detected cancer cells in patient biopsies using magnetic nanoparticles that glom onto antibodies bound to particular cancer-related proteins present on the cell surface (Sci Transl Med, 3:71ra16, 2011).

Electric Nucleic Acid Test

CLOSING THE CIRCUIT: In the electronic chip (top), a pair of reference and counter electrodes runs along the bottom of each liquid channel, and working electrodes are situated perpendicular to and underneath the channels; gold microelectrodes (yellow) rise up from the working electrodes and into the channels. Nucleic acid probes (orange, shown in a cross-sectional view of a single microelectrode, middle) immobilized on the microelectrode capture the negatively charged target DNA (navy), attracting cations and triggering redox reactions that generate an electrical current.

Technology: Kelley’s group developed an electronic chip that can rapidly detect DNA from 20 different bacterial species that frequently cause urinary tract infections and 10 different genes that confer antibiotic resistance. The chip features a pair of counter and reference electrodes running along the inner surface of each of five liquid channels. Each channel is further subdivided into five separate wells containing an electrocatalytic solution, and an array of 20 so-called working electrodes runs perpendicular to and underneath the wells. Bushy, gold microelectrodes sprout from the working electrodes and into each well, but remain electrically isolated from the counter and reference electrode pair.

Each well’s microelectrodes are coated with a nucleic acid-based probe designed to bind only to nucleic acid from a specific target pathogen or antibiotic-resistance gene. When a probe binds its target DNA sequence, cations in the electrocatalytic solution are attracted to the negatively charged phosphate backbone of the nucleic acid. The ions in the solution then undergo a series of oxidation and reduction reactions, generating a current that flows between the working electrode and the pair of counter and reference electrodes in the well. The resulting electrical signal in each well can be measured using a simple device called a potentiostat.

Application: The chip was able to detect DNA from bacterial lysates containing as little as one bacterial cell per μL. What’s more, the electrical signal could be detected after only a two-minute hybridization between the sample and the probes (Nat Commun, 4:2001, 2013).

Pros:

  • Multiplexing. Depending on the probes present on the chip, the method can screen a sample for a variety of pathogens simultaneously, or a combination of pathogens and antibiotic-resistance genes.
  • Kelley says the reagents needed for the assay are inexpensive, and the chip itself costs only a few dollars to make.
  • Very fast.

Cons:

  • Not yet demonstrated to work with clinical samples
  • The detection limit of one cell per μL is not likely to be sensitive enough to detect bacteria in some types of patient samples, such as blood.

Vibe Monitors

MONITORING VIBRATIONS: A laser beam deflected off the surface of a cantilever can detect the nanoscale movements caused by viable bacteria.

Technology: Using a tiny diving board–like device called a cantilever that’s traditionally used in atomic force microscopy (AFM), Longo’s group devised a way to rapidly determine bacterial resistance to antibiotics. The researchers coat a chemically treated cantilever with living bacteria and immobilize one end of it inside a chamber filled with bacterial growth medium. The bacteria cause the free end of the cantilever to vibrate at a certain frequency as they move and carry out ordinary metabolic functions. Those nanoscale vibrations are monitored using a laser beam that reflects off the surface of the cantilever and into a detector.

Upon exposure to an antibiotic, the fluctuations caused by antibiotic-susceptible bacteria grind to a halt within a matter of minutes, and do not recover in the presence of fresh growth medium without the drug. By contrast, the fluctuations caused by bacteria resistant to the antibiotic initially stall in the presence of the drug, but gradually resume as the bugs ramp up the molecular pathways they need to survive the treatment.

Application: Longo’s team demonstrated that lab-grown cultures of antibiotic-sensitive Escherichia coli and Staphylococcus aureus—two of the most common human pathogens that are rapidly developing resistance to many available antibiotics—cease to produce fluctuations of the cantilever within five minutes or less after antibiotic treatment. By contrast, fluctuations caused by antibiotic-resistant strains of the same microbes resumed within 15 minutes of antibiotic exposure (Nat Nanotechnol, 8:522-26, 2013). Although the tests were performed on a traditional atomic force microscope, which can cost hundreds of thousands of dollars, Longo says his team has developed simplified prototype versions of the instrument for $5,000–$10,000 that are designed specifically for antibiotic susceptibility testing and that don’t require expertise in AFM to operate.

Pros:

  • Fast. The team obtained their results for E. coli and S. aureus in about 30 minutes each. Longo suggests the method may be particularly useful for assessing the antibiotic susceptibility of slow-growing organisms such as M. tuberculosis, which does not grow rapidly in culture. Traditional culture-based tests of antibiotic susceptibility for M. tuberculosis can require weeks, but using this method, Longo says his team has been able to cut that time down to under four hours.
  • AFM cantilevers are fairly inexpensive, selling for around $5–$10 each.

Cons:

  • Longo’s team has not yet tested the technique with clinical samples.
  • No multiplexing. Can only analyze one sample of bacteria at a time, though Longo says his group is working on a multicantilever system.
  • Cannot yet characterize a mixture that contains more than one bacterial species. “If an antibiotic affects one species but not the other, you wouldn’t know what’s going on,” Longo says, because the drop in movement of the susceptible species would be masked by the fluctuations of the resistant species.

Pregnancy and Infection .


Pregnant women have an increased severity of infections with some organisms, including influenza virus, hepatitis E virus, herpes simplex virus, and malaria parasites. A new review on this topic includes an update on immunologic alterations during pregnancy.

Pregnant women are more severely affected by infections with some organisms, including influenza virus, hepatitis E virus, and herpes simplex virus, and malaria parasites. The evidence is more limited for organisms that cause coccidioidomycosis, measles, smallpox, and varicella. The threshold for diagnostic evaluation, as well as hospitalization and treatment, may be lower for pregnant women than for other patients, and this factor may bias some of the reports of increased disease severity.

Clinical Pearls

  • How does pregnancy impact the severity of influenza infection?

Pregnant women are at increased risk for severe illness from influenza virus infection. Cardiopulmonary adaptive changes occurring during pregnancy, such as increased heart rate and stroke volume and reduced pulmonary residual capacity, may increase the risk of hypoxemia and contribute to the increased severity. During the pandemic of 1918, maternal mortality was 27% (50% when influenza was complicated by pneumonia), and during the pandemic of 1957, 50% of deaths among reproductive-age women occurred among those who were pregnant. During the 2009 H1N1 influenza A pandemic, pregnant women were generally at increased risk for severe disease, including disease leading to hospitalization, admission to an intensive care unit, or death, as compared with nonpregnant women and the general population. In the United States, 5% of all deaths from pandemic influenza were among pregnant women, although pregnant women represent only about 1% of the U.S. population.

  • What impacts the risk of malaria infection in pregnancy and what are the harmful effects?

In areas of high transmission, most women harboring parasites do not present with symptoms. Of pregnant women who are symptomatic, the majority are women having their first pregnancy; women who have been pregnant more than once and who live in areas where malaria is highly endemic are less likely to present with clinical signs or symptoms of malaria, even if they have high parasite loads. Pregnant women have a risk of severe malaria that is three times as high as that among nonpregnant women; a median maternal mortality of 39% has been reported in studies in the Asia-Pacific region. Maternal death also has been reported in association with P. vivax infection. The harmful effects of malaria (mainly due to P. falciparum) during pregnancy — maternal anemia, low birth weight, and preterm birth — have long been recognized. In areas of stable endemic transmission (e.g., sub-Saharan Africa), up to 25% of pregnant women have acute infection, leading to placental malaria. P. falciparum is the only species associated with placental sequestration, which is believed to be the cause of many of the manifestations of P. falciparum disease during pregnancy.

Morning Report Questions

Q: What is the impact of listeria infection during pregnancy?

A: Primarily a foodborne pathogen, listeria can contaminate a variety of raw foods, such as uncooked meats and vegetables, unpasteurized milk, and soft cheeses. Infection may be asymptomatic or may be manifested as an influenza-like illness; severe infection is rare during pregnancy, and no maternal deaths due to listeriosis have been reported among pregnant hospitalized women. L. monocytogenes infections most commonly occur during the third trimester and seem to be rare earlier in pregnancy. However, listeria has a predilection for the placenta and fetus, and, depending on the stage of pregnancy, listeriosis can lead to pregnancy loss, stillbirth, preterm birth, or serious neonatal disease.

Q: What changes in the immune system occur during pregnancy?   

A: There is evidence that aspects of innate immunity (phagocytic activity, (alpha)-defensin expression, and numbers of neutrophils, monocytes, and dendritic cells) are maintained or enhanced during pregnancy, particularly during the second and third trimesters. Conversely, the number of CD3+ T lymphocytes (both CD4+ and CD8+) decrease during pregnancy as do Th1 and Th2 responses to mitogenic or antigenic lymphocyte stimulation. However, there is limited information on the longitudinal trends of such alterations during pregnancy. Levels of several cytokines are altered: levels of interferon-(gamma), monocyte chemoattractant protein 1, and eotaxin are decreased in most pregnant women, whereas tumor necrosis factor (alpha), interleukin-10, and granulocyte colony-stimulating factor levels rise. Data indicating that fetus-specific cytotoxic T-cell responses can be generated during pregnancy without loss of the fetus, as well as data from studies of pregnant mice showing normal memory T-cell development after lymphocytic choriomeningitis virus infection, contradict the idea of systemic immunosuppression during pregnancy. A more recent theory proposed a shift from Th1 to Th2 immunity during pregnancy. Th2 cells stimulate B lymphocytes, increase antibody production, and suppress the cytotoxic T-lymphocyte response, decreasing the robustness of cell-mediated immunity.

Antibiotics are ‘not for snot’


Running noses and green phlegm do not mean patients need antibiotics, say doctors and public health experts.

It was described as a “prevailing myth” that the drugs were needed to treat such infections.

Snotty child

Public Health England and the Royal College of General Practitioners said the symptoms were often caused by viruses.

And the use of antibiotics was leading to resistance, they said.

Public Health England said its own research showed that 40% of people thought antibiotics would help a cough if the phlegm was green, while very few thought it would make a difference to clear-coloured phlegm.

Dr Cliodna McNulty, from the organisation, said: “It’s a prevailing myth that anyone with green phlegm or snot needs a course of antibiotics to get better.

“Most of the infections that generate lots of phlegm and snot are viral illnesses and will get better on their own although you can expect to feel pretty poorly for a few weeks.

“The problems of antibiotic resistance are growing. Everyone can help by not using antibiotics for the treatment of uncomplicated infections.”

Taking antibiotics affects the trillions of bacteria that naturally live in the human body and can lead to resistance.

Dr Maureen Baker, chairwoman of the Royal College of GPs, said: “Overuse of antibiotics is a serious public health concern.

“Infections adapt to antibiotics used to kill them and can ultimately make treatment ineffective so it’s crucial that antibiotics are used appropriately.”

The green colour in phlegm and snot is the result of a protein made by the immune system to fight infection.

The latest advice comes on European Antibiotics Awareness Day.

‘Unpredictable pandemics’ warning


The world needs to be prepared for “unpredictable pandemics” from viruses making the leap from animals to people, scientists in Taiwan say.

Their warning follows the first reported case of a common bird flu, H6N1, being detected in a woman, earlier this year.

The patient recovered and no other cases have been detected.

But the Lancet Respiratory Medicine report said “intensive” monitoring of bird flu was needed.

In May 2013, the first human case of an H6N1 bird flu was detected in a woman in Taiwan. One of her neighbours bred ducks, geese and chickens – although the precise source of the infection has not been detected.

Many sub-types of influenza, such as those that cause seasonal flu or the swine flu pandemic, are known to infect people, but H6N1 is not one of them.

The report, by the Centres for Disease Control in Taiwan, said: “The occurrence of a human case of H6N1 infection shows the unpredictability of influenza viruses.

Influenza

“Our report highlights the need for influenza pandemic preparedness , including intensive surveillance for ever evolving avian influenza viruses.”

Prof Wendy Barclay, from Imperial College London, said these infections may have happened in the past but improved technology had meant this one had been discovered.

She said: ” Is this a truly new thing or are we now just better at seeing it?”

She told the BBC she expected far more of these cases to be reported in the next few years as more hospitals were geared up to look for novel bird flus.

Prof Barclay added: “This is a single case with no evidence of human transmission, but as always we should keep an eye on it and do studies to see how close it is to being able to spread between humans.”

Nutritional interventions for reducing morbidity and mortality in people with HIV.


HIV/AIDS has long been synonymous with wasting and weight loss. For example, in South Africa, it was known as “slims” disease. Coupled with this, it’s known that adequate nutrition is important for optimal immune and metabolic function and, so, one might expect that dietary support would improve clinical outcomes in HIV-infected individuals by reducing HIV-related complications and attenuating progression of HIV disease. This should lead to better quality of life and, ultimately, less disease-related mortality. Therefore, this Cochrane Review from February 2013 examines the experimental evidence for the effects of nutritional interventions given orally on important clinical outcomes for adults and children with HIV infection and finds that there is relatively little research to help decision makers.

The authors searched many databases, trawled through references and contacted people working in the area. However, only 14 relatively small, randomized trials came to light, which met their inclusion criteria. Just three of these reported on mortality, two that had recruited adults and the other, from South Africa, had recruited children.

A wide range of macronutrient supplements were studied with just two of the trials (one in adults and one in children) studying the same one, a food supplement called Spirulina. There was also wide variation in other aspects of the trials, including the outcomes that were measured and reported and the types of people who took part, in relation to stage of HIV, HIV treatment status and general nutrient status. When the authors assessed the quality of the trials, none of the trials were graded as providing strong evidence. This was mostly because the trials were small and had a high risk of bias due to a lack of blinding and the large proportion of people who left the trials early.

The latest version of the review is an update of the earlier review from 2007, which had included 8 trials from high-income countries, with fewer than 500 HIV+ adults in total. Patients with confirmed secondary infections or other signs and symptoms of infection, such as fever, chills, or persistent diarrhea, were not eligible for any of those trials. This made it difficult to determine the applicability of the findings to the types of people who are most likely to need effective macronutrient supplementation. Six new studies have been added in the update, bringing the number of participants to more than 1700 adults and nearly 300 children. Four of the new trials are from Africa, and there is one from Brazil and one from India. The new trials also include two trials that had recruited participants with opportunistic infections (tuberculosis and persistent diarrhea).

Bringing the evidence together and, where possible, combining the findings of similar trials in meta-analyses identified no significant benefits for supplementary food, daily supplement of Spirulina or a nutritional supplement enhanced with protein with respect to death in HIV+ adults and children. In HIV+ adults with weight loss, nutritionally balanced macronutrient supplements aimed at improving energy intake by 600-960 kcal/day increased intakes of energy and protein compared with no supplement or nutrition counselling alone, but had no effect on other anthropometric or immunologic parameters. From the meta-analyses, supplementation with macronutrient formulas given to provide protein, energy or both and fortified with micronutrients, in conjunction with nutrition counselling, significantly improved energy intake (3 trials; n=131; MD 394 kcal/day; 95% CI: 225 to 562; p<0.00001) and protein intake (2 trials; n=81; MD 23.5 g/day; 95% CI: 12.7 to 34.0; p<0.00001) compared with no nutritional supplementation or nutrition counselling alone.

The authors conclude that supplementation with specific macronutrients such as amino acids, whey protein concentrate or Spirulina did not significantly alter clinical, anthropometric or immunological outcomes in HIV-infected adults and children. They call for future research that takes better account of the needs and resources of the HIV+ individual, the clinician treating them and the people caring for them. They highlight areas of ongoing uncertainty, including the choice between using resources for antiretroviral treatment for HIV+ people or nutritional interventions, the populations that might benefit most (e.g. malnourished HIV+ people, HIV+ people with uncontrolled weight loss, HIV+ people with opportunistic infections or HIV+ lactating mothers), the role of nutritional counseling compared to nutritional interventions in well-resourced settings, and how the use of anti-retroviral therapy might make it difficult to detect the effects of nutritional interventions.

Soure: Cochrane Library