medicine and health

ScienceDaily (Oct. 18, 2012) — Researchers at the Johns Hopkins Bloomberg School of Public Health have determined a new mechanism by which the mosquitoes' immune system can respond with specificity to infections with various pathogens, including the parasite that causes malaria in humans, using one single gene. Unlike humans and other animals, insects do not make antibodies to target specific infections. According to the Johns Hopkins researchers, mosquitoes use a mechanism known as alternative splicing to arrange different combinations of binding domains, encoded by the same AgDscam gene, into protein repertoires that are specific for different invading pathogens.

The researchers' findings were published October 18 in the journal Cell Host & Microbe and could lead to new ways to prevent the spread of a variety of mosquito born illnesses.

Mosquitoes and other insects use their primitive innate immune systems to successfully fight infections with a broad spectrum of viruses, bacteria, fungi and parasites, despite the lack of antibodies that are part of the more sophisticated human immune system. The effectiveness of the human immune system is to a large degree based on the ability to produce an enormous variety of antibodies containing different immunoglobulin domains that can specifically tag and label a pathogen for destruction. This great variety of pathogen-binding antibodies is achieved by combining different immunoglobulin gene segments and further mutate them through mechanisms called somatic recombination and hypermutation. While mosquitoes also have genes encoding immunoglobulin domains, they lack these specific mechanisms to achieve pathogen recognition diversity.

The Johns Hopkins researchers discovered a different way by which mosquitoes can combine immunoglobulin domains of a single gene called AgDscam (Anopheles gambiae Down Syndrome Cell Adhesion Molecule) to produce a variety of pathogen-binding proteins. The AgDscam gene is subjected to a mechanism called alternative splicing that combines different immunoglobulin domains into mature AgDscam proteins, depending on which pathogen has infected the mosquito. The researchers showed that this alternative splicing is guided by the immune signal transducing pathways (analogous to electrical circuits) that they previously demonstrated to activate defenses against different malaria parasites and other pathogens. While alternative splicing of the AgDscam gene does not nearly achieve the degree of pathogen recognition diversity of human antibodies, it does nevertheless vastly increase the variety of pathogen binding molecules.

"Using antibodies to fight infection is like fishing with a harpoon -- it's very targeted. The mosquito's innate immune system is more like fishing with a net -- it catches a bit of everything," explained George Dimopoulos, PhD, senior investigator of the study and professor with the Johns Hopkins Malaria Research Institute. "However, we discovered that immune pathway-guided alternative splicing of the AgDscam gene renders the mosquito's immune net, so to speak, more specific than previously suspected. The mosquito's immune system can come up with approximately 32,000 AgDscam protein combinations to target infections with greater specificity."

Dimopoulos and his group are developing a malaria control strategy based on mosquitoes that have been genetically modified to possess an enhanced immune defense against the malaria parasite Plasmodium. One obstacle to this approach is the great variety of Plasmodium strains that may interact somewhat differently with the mosquito's immune system.

"Some of these strains may not be detected by the engineered immune system proteins that mediate their killing. Our new discovery may provide the means to create genetically modified mosquitoes that can target a broader variety of parasite strains, like casting a net rather than shooting with a harpoon," said Dimopoulos.

Malaria kills more than 800,000 people worldwide each year. Many are children.

The research was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Disease, the Calvin A. and Helen H. Lang Fellowship, and the Johns Hopkins Malaria Research Institute.

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The above story is reprinted from materials provided by Johns Hopkins Bloomberg School of Public Health.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Yuemei Dong, Chris M. Cirimotich, Andrew Pike, Ramesh Chandra and George Dimopoulos. Anopheles NF-kB -Regulated Splicing Factors Direct Pathogen-Specific Repertoires of the Hypervariable Pattern Recognition Receptor AgDscam. Cell Host & Microbe, October 18, 2012

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Sharp rise in children admitted to hospital with throat infections since 1999

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ScienceDaily (Oct. 19, 2012) — The number of children admitted to hospital in England for acute throat infections increased by 76 per cent between 1999 and 2010, according to new research published October 19 in Archives of Disease in Childhood.

Acute throat infection (ATI), which includes acute tonsillitis and acute pharyngitis, is one of the most common reasons for consulting a GP. The majority of ATIs are self-limiting and can be managed at home or by the GP, but a small proportion may require hospital admission.

This study investigated admission rates for children up to age 17 with ATI alongside trends in tonsillectomy rates, between 1999 and 2010. The study was motivated by concerns that the decline in tonsillectomy rates in recent years has led to an increase in hospital admissions for tonsillitis of increased severity. It also investigated whether performing fewer tonsillectomies is associated with higher rates of complications such as quinsy, an abscess that can occur when an infection spreads from a tonsil to the surrounding area.

The research, which was funded by a fellowship from the National Institute for Health Research, showed that the number of children admitted to hospital with ATI increased from 12,283 in 1999 to 22,071 in 2010 -- a rise in admission rate of 76 per cent. Short hospital stays, lasting less than two days, increased by 115 per cent over the decade, and accounted for the majority of admissions. Stays of two or more days in hospital for ATI decreased slightly, while quinsy rates remained stable. The authors found no evidence of an association between tonsillectomy trends and admission rates or the severity of ATI or quinsy.

The authors suggest that the dramatic increase in ATI admissions is probably explained by a large number of children being admitted for ATIs who would have formerly been managed in the community. The reasons for this may include changes in the provision of out-of-hours care in general practice and an increase in workload in Accident in Emergency departments. The four hour maximum waiting time in A&E, introduced in 2002, might have meant that doctors, who are under greater pressures, are more inclined to admit children to hospital with an ATI, the authors suggest.

Dr Elizabeth Koshy, from the School of Public Health at Imperial College London, who led the study said: "It is very concerning that there has been a major increase in hospital admissions for children with acute throat infections, particularly among those aged under five. We think this is likely to be due to problems at the primary care and secondary care interface. Our findings relating to short hospital stays suggest that many of the children admitted with acute throat infections could have been effectively managed in the community. Our study highlights the need to urgently address the issue of healthcare access, with improved models of integrated care within primary and secondary care, to avoid potentially unnecessary hospital admissions for relatively minor infections in the future."

Although these findings suggest that declining tonsillectomy rates do not appear to be associated with an increase in more severe ATI or quinsy rates, further research is needed to confirm this. Dr Koshy adds: "Tonsillectomy is a major and costly operation with potentially serious complications. So it seems sensible for clinicians to maintain a high threshold for referring children with recurrent throat infections for tonsillectomy and restrict it to those children who are most severely affected by these infections."

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The above story is reprinted from materials provided by Imperial College London.
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Journal Reference:

E. Koshy, J. Murray, A. Bottle, P. Aylin, M. Sharland, A. Majeed, S. Saxena. Significantly increasing hospital admissions for acute throat infections among children in England: is this related to tonsillectomy rates? Archives of Disease in Childhood, 2012; DOI: 10.1136/archdischild-2012-301755

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Latest Meningitis Outbreak Toll: 20 Deaths and 257 Infections, CDC Says

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By Steven Reinberg and Margaret Steele
HealthDay Reporters

THURSDAY, Oct. 18 (HealthDay News) -- Another person has died and 10 more have been sickened in the nationwide meningitis outbreak believed to be tied to contaminated steroid injections, bringing the totals to 20 deaths and 257 infections, U.S. health officials reported Thursday.

It's suspected that the steroid, contaminated with a fungus, was manufactured by the New England Compounding Center of Framingham, Mass. Last month the company voluntarily recalled three lots of the steroid, methylprednisolone acetate, which is injected into patients for back and joint pain. The company has since shut down operations and stopped distributing its products, health officials said.

On Thursday, federal health officials said they'd confirmed the presence of a fungus known as Exserohilum rostratum in unopened vials of the steroid from one of the three lots. The laboratory confirmation further links the steroid from these lots and the subsequent infections to the Massachusetts specialty pharmacy, said officials from the U.S. Centers for Disease Control and Prevention and the U.S. Food and Drug Administration.

Tests on the other two lots and other injectable products from the company are continuing, officials said.

The CDC and state health departments estimate that roughly 14,000 patients may have gotten steroid injections from the three lots, and nearly 97 percent of them have been contacted for medical follow-up.

Meningitis is potentially fatal inflammation of the lining surrounding the brain and spinal cord.

All of the 254 fungal meningitis patients were thought to be injected with methylprednisolone acetate, according to the CDC.

There have been three cases of what the CDC calls "peripheral joint infection," meaning an infection in a knee, hip, shoulder or elbow. These joint infections aren't considered as dangerous as injections near the spine for back pain that have been linked to the potentially fatal meningitis infections.

The 14,000 people who may have gotten injections of the steroid include not only patients who got shots for back pain and are most at risk for meningitis, but also others who received shots for pain in their knees and shoulders.

All of the infected patients are thought to have received the medication from the Massachusetts pharmacy, according to the CDC.

The FDA said it was advising all health-care professionals to follow up with any patients who were given any injectable drug from or produced by the New England Compounding Center. These drugs include medications used in eye surgery, and a heart solution purchased from or produced by the company after May 21.

The New England Compounding Center is what's known as a compounding pharmacy. These pharmacies combine, mix or alter ingredients to create specific drugs to meet the specific needs of individual patients, according to the FDA. Such customized drugs are frequently required to fill special needs, such as a smaller dose, or the removal of an ingredient that might trigger an allergy in a patient.

The CDC on Thursday had the following state-by-state breakdown of cases: Florida: 13 cases, including 3 deaths; Idaho, 1 case; Illinois, 1 case; Indiana: 34 cases, including 2 deaths; Maryland: 16 cases, including 1 death; Michigan: 49 cases, including 4 deaths; Minnesota: 7 cases; New Hampshire: 8 cases; New Jersey: 13 cases; New York: 1 case; North Carolina: 2 cases; Ohio: 10 cases; Pennsylvania: 1 case; Tennessee: 63 cases, including 8 deaths; Texas: 1 case; Virginia: 37 cases, including 2 deaths.

Health officials said they expect to see more cases of the rare type of meningitis, which is not contagious, because symptoms can take a month or more to appear.

Infected patients have developed a range of symptoms approximately one to four weeks following their injection. People who have had a steroid injection since July, and have any of the following symptoms, should talk to their doctor as soon as possible: worsening headache, fever, sensitivity to light, stiff neck, new weakness or numbness in any part of your body, slurred speech, the CDC said.

Infected patients must receive intravenous drugs in a hospital.

Compounding pharmacies like the New England Compounding Center traditionally started out as community-based neighborhood druggists. But over time, the practices of some compounding pharmacies have expanded, sometimes beyond their intended limits, experts explained.

According to the Associated Press, this isn't the first time the New England Compounding Center has encountered problems with contaminated injections. In 2007, the company settled a lawsuit that claimed that an 83-year-old man died in 2004 after contracting fatal bacterial meningitis from a shot produced by the compounding center. The pharmacy reached a settlement with the man's widow before the case went to trial, the AP said.

Compounding pharmacies aren't subject to the same FDA oversight as regular drug manufacturers are, and some members of Congress now say the meningitis outbreak highlights the need for more regulatory control.

The CDC released a list of the approximately 75 health-care facilities that received contaminated product.

Copyright © 2012 HealthDay. All rights reserved. SOURCES: Oct. 18, 2012, news release, U.S. Centers for Disease Control and Prevention, and U.S. Food and Drug Administration; Oct. 18, 2012, updated statistics, U.S. Centers for Disease Control and Prevention; Associated Press

Friday, October 19, 2012

Meningitis Crisis Expands; More Infections, Deaths

10:39 PM

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By Brenda Goodman, MA
WebMD Health News

Reviewed by Louise Chang, MD

Oct. 11, 2012 -- The crisis surrounding the multistate outbreak of fungal meningitis linked to tainted steroid shots deepened Thursday, as federal officials reported that more people had received the shots than previously believed. Doctors also reported the first case of a joint infection outside the spine.

The CDC says close to 14,000 people may have gotten the shots, not 13,000 as was first estimated.

Fourteen people have died since the outbreak was first reported last month.

In all, 169 cases of the rare brain infection have been reported in 11 states. Tennessee, Michigan, Virginia, Indiana, and Maryland have been the hardest hit.

"These 14,000 patients received the medication as a steroid injection either in the spinal area or into a joint space, such as a knee, shoulder, or ankle," said J. Todd Weber, MD, chief of the Prevention and Response Branch, Division of Healthcare Quality Promotion at the CDC, in a press briefing.

Health officials have contacted about 90% of the affected patients to warn them about possible health risks related to the shots.

"We know we are not out of the woods yet," Weber said, noting that it can take weeks to months to develop symptoms of a fungal infection. Those include headache, fever, back pain, nausea, and redness or swelling at the injection site.

"Patients and their doctors will need to be vigilant for at least several months following injection," said Weber, who is leading the response to the outbreak for the CDC. He urged patients who were feeling unwell to seek immediate medical attention.

He also warned patients and doctors that it is difficult to test for the two fungi that have been causing the meningitis cases. The CDC confirmed the presence of the fungus exserohilum in 10 of the people with meningitis and the fungus aspergillus in one person with meningitis.

"Patients who received an injection with one of the three recalled lots of steroids may be diagnosed with meningitis, but their fungal testing may be negative. In these cases, patients should still be treated for meningitis," Weber said.

So far, 50 vials of methylprednisolone acetate from the New England Compounding Center, in Framingham, Mass., have tested positive for two species of fungus linked to the outbreak.

In addition, federal officials said on Thursday that one patient had an infected ankle after receiving one of the shots. Doctors are waiting on a lab test to determine whether that infection was caused by a fungus, as the meningitis cases were.

In rare cases, fungal infections in the joints can cause septic arthritis, says Luis Ostrosky-Zeichner, MD.

"Infections in the joint are generally very severe because they destroy a lot of the lining of the joint, and they're very disabling," says Ostrosky-Zeichner, director of the laboratory of mycology research at the University of Texas Health Science Center in Houston.

Ostrosky-Zeichner says fungal arthritis may require surgery and months of treatment with intravenous antifungal drugs, which are known to be toxic to the kidneys and other organs.

"We know how upsetting these recent events have been, and we send our deepest sympathies to all who are impacted by this tragic situation," said Deborah M. Autor, JD, deputy commissioner for Global Regulatory Operations and Policy at the FDA.

The FDA's role in regulating compounding pharmacies was limited in 2002. The agency is largely empowered to act only after a problem has already been identified.

"What this points out is that the practice of pharmacy has changed quite a bit. The world has changed a lot since the days of mortar and pestle. This is the time for pharmacists, for lawmakers, for regulators, for doctors, to sit down and grapple with this new model of pharmacy compounding and come up with a regulatory scheme that controls the risk," Autor said.

SOURCES: Joint press briefing, CDC, FDA, and the Massachusetts Department of Health. Luis Ostrosky-Zeichner, MD, director of the laboratory of mycology research, The University of Texas Health Science Center in Houston, Texas.Deborah M. Autor, JD, Deputy Commissioner for Global Regulatory Operations and Policy, FDA. J. Todd Weber, MD, Chief of Prevention and Response Branch, Division of Healthcare Quality Promotion, CDC.