Researchers from Rigshospitalet – Copenhagen University Hospital – and the University of Copenhagen have discovered why malaria parasites are able to hide from the immune defences of expectant mothers, allowing the parasite to attack the placenta. The discovery is an important part of the efforts researchers are making to understand this frequently fatal disease and to develop a vaccine. Staff member at CMP. Photo: Lars Hviid"We have found one likely explanation for the length of time it takes for the expectant mother's immune defences to discover the infection in the placenta," says Lea Barfod, MSc, who is working with Professor Lars Hviid at the Centre for Medical Parasitology, University of Copenhagen.
"The parasites are able to assume a camouflage that prevents their recognition by the immune system antibodies which would otherwise combat them. So although the immune system has all the weapons it needs to fight the infection of the placenta, these weapons are ineffectual simply because the enemy is hard to spot. Ironically the camouflage also consists of antibodies, but of a type that does not help to fight infection."
The malaria parasite at war with the immune system
One human being in twelve is infected with malaria. That means 500 million people are carrying the tiny parasite, and it kills a million of them a year. The disease costs so many lives because the parasite constantly outmanoeuvres the human immune system. It starts by hiding in the red blood cells. The immune system does not bother with these as the spleen usually filters defective blood cells.
To avoid this filter, the parasite ejects a protein hook which attaches to the inner wall of the blood vessel, and even if the immune system antibodies destroy one such hook, the parasite has more than sixty in its arsenal. One of them has evolved specially to attach to the placenta. While the war is being waged the parasite propagates and infects more and more red blood cells, which are normally used for transporting nutrients and oxygen around the body.
Fighting from house to house
"In an advanced version of hide-and-seek the parasites keep looking for new ways of preventing the antibodies from recognising them. It is a kind of urban guerrilla war in which the fighting is conducted from house to house," says Lars Hviid.
"One example is the ability of the parasites to hide in the placenta. The first time an African woman conceives her placenta provides a new opportunity for the parasite to hide: a new house, so to speak, and in a way that prevents discovery by the immune system. It takes time for the immune defences to react to the new threat, and meanwhile the camouflaged parasite harms the woman and her unborn child."
The researchers are now going to study whether the malaria parasite also uses its camouflage at other stages of an infection.
"Perhaps it is not only the parasites in the placenta that are capable of hiding like this," Lars Hviid says.
"It takes the body a surprisingly long time to develop protection from Malaria, and perhaps the trick we have just discovered is part of the explanation. It is important for us to find out if this is the case in order to help us to understand malaria in general, but also to help us in our efforts to develop a vaccination. We have plenty of work to be going on with," Lars Hviid concludes.
###
Lea Barfod and Lars Hviid's discovery has just been published in the Proceedings of the National Academy of Sciences of the United States of America.
Contact: Professor Lars Hviid : lhviid@sund.ku.dk 452-274-7426 University of Copenhagen
Showing posts with label Denmark. Show all posts
Showing posts with label Denmark. Show all posts
Thursday, 14 July 2011
Monday, 30 May 2011
TUBERCULOSIS: Denmark: Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007.
Gry Assam Taarnhoj et al. : Source: BMC Pulmonary Medicine 2011, 11:26
Human Immunodeficiency Virus (HIV) infection predisposes to tuberculosis (TB). We described incidence, risk factors and prognosis of TB in HIV-1 infected patients during pre (1995-1996), early (1997-1999), and late Highly Active Antiretroviral Therapy (HAART) (2000-2007) periods.
Methods:
We included patients from a population-based, multicenter, nationwide cohort.
We calculated incidence rates (IRs) and mortality rates (MRs). Cox's regression analysis was used to estimate risk factors for TB infection with HAART initiation included as time updated variable.
Kaplan-Meier was used to estimate mortality after TB.
Results:
Among 2,668 patients identified, 120 patients developed TB during the follow-up period. The overall IR was 8.2 cases of TB/1,000 person-years of follow-up (PYR).
IRs decreased during the pre-, early and late-HAART periods (37.1/1000 PYR, 12.9/1000 PYR and 6.5/1000 PYR respectively). African and Asian origin, low CD4 cell count and heterosexual and injection drug user route of HIV transmission were risk factors for TB and start of HAART reduced the risk substantially.
The overall MR in TB patients was 34.4 deaths per 1,000 PYR (95% Confidence Interval: 22.0-54.0) and was highest in the first two years after the diagnosis of TB.
Conclusions:
Incidence of TB still associated with conventional risk factors as country of birth, low CD4 count and route of HIV infection while HAART reduces the risk substantially. The mortality in this patient population is high in the first two years after TB diagnosis.
http://7thspace.com/headlines/383507/incidence_risk_factors_and_mortality_of_tuberculosis_in_danish_hiv_patients_1995_2007.html
Human Immunodeficiency Virus (HIV) infection predisposes to tuberculosis (TB). We described incidence, risk factors and prognosis of TB in HIV-1 infected patients during pre (1995-1996), early (1997-1999), and late Highly Active Antiretroviral Therapy (HAART) (2000-2007) periods.
Methods:
We included patients from a population-based, multicenter, nationwide cohort.
We calculated incidence rates (IRs) and mortality rates (MRs). Cox's regression analysis was used to estimate risk factors for TB infection with HAART initiation included as time updated variable.
Kaplan-Meier was used to estimate mortality after TB.
Results:
Among 2,668 patients identified, 120 patients developed TB during the follow-up period. The overall IR was 8.2 cases of TB/1,000 person-years of follow-up (PYR).
IRs decreased during the pre-, early and late-HAART periods (37.1/1000 PYR, 12.9/1000 PYR and 6.5/1000 PYR respectively). African and Asian origin, low CD4 cell count and heterosexual and injection drug user route of HIV transmission were risk factors for TB and start of HAART reduced the risk substantially.
The overall MR in TB patients was 34.4 deaths per 1,000 PYR (95% Confidence Interval: 22.0-54.0) and was highest in the first two years after the diagnosis of TB.
Conclusions:
Incidence of TB still associated with conventional risk factors as country of birth, low CD4 count and route of HIV infection while HAART reduces the risk substantially. The mortality in this patient population is high in the first two years after TB diagnosis.
http://7thspace.com/headlines/383507/incidence_risk_factors_and_mortality_of_tuberculosis_in_danish_hiv_patients_1995_2007.html
Sunday, 6 March 2011
TUBERCULOSIS: Tuberculous meningitis in Denmark: a review of 50 cases
Author: Anne-Sophie ChristensenAse AndersenVibeke ThomsenPeter AndersenIsik Johansen
Credits/Source: BMC Infectious Diseases 2011, 11:47
Tuberculous meningitis is the most severe manifestation of extrapulmonary tuberculosis with a high mortality rate and a high rate of sequelae among survivors. The aim of this study is to assess the current epidemiology, clinical features, diagnostic procedures, treatment and outcome in patients with tuberculous meningitis in Denmark, a country with a low tuberculosis incidence.
Methods: A nationwide retrospective study was conducted, comprising all patients notified with tuberculous meningitis (TBM) in Denmark from 2000-2008.Medical records were reviewed using a standardised protocol.
Results: Fifty patients, including 12 paediatric patients, were identified. 78% of the patients were immigrants from countriesof high tuberculosis endemicity.64% of all patients had a pre-existing immunosuppressive condition; 10% were HIV positive, 48% were HIV seronegative and 42% had an unknown HIV status. Median symptom duration before admission was 14 days in the Danish patient population and 20 days in the immigrant group.Biochemical analysis of cerebrospinal fluid (CSF) samples revealed pleocytosis in 90% with lymphocyte predominance in 66%. Protein levels were elevated in 86%.The most common findings on neuro-radiological imaging were basal meningeal enhancement, tuberculomas and hydrocephalus. Lumbar puncture was performed on 42 patients; 31 of these specimens (74%) had a positive CSF culture for mycobacteria and 9.5% were smear positive for acid-fast bacilli.The overall mortality rate was 19% and 48% of the remaining patients had neurological sequelae of varying degree.
Conclusion: TBM is a rare but severe manifestation of extrapulmonary TB in Denmark. The clinician must be prepared to treat empirically if the suspicion of TBM has arisen to improve treatment outcome.
http://7thspace.com/headlines/373610/tuberculous_meningitis_in_denmark_a_review_of_50_cases.html
Credits/Source: BMC Infectious Diseases 2011, 11:47
Tuberculous meningitis is the most severe manifestation of extrapulmonary tuberculosis with a high mortality rate and a high rate of sequelae among survivors. The aim of this study is to assess the current epidemiology, clinical features, diagnostic procedures, treatment and outcome in patients with tuberculous meningitis in Denmark, a country with a low tuberculosis incidence.
Methods: A nationwide retrospective study was conducted, comprising all patients notified with tuberculous meningitis (TBM) in Denmark from 2000-2008.Medical records were reviewed using a standardised protocol.
Results: Fifty patients, including 12 paediatric patients, were identified. 78% of the patients were immigrants from countriesof high tuberculosis endemicity.64% of all patients had a pre-existing immunosuppressive condition; 10% were HIV positive, 48% were HIV seronegative and 42% had an unknown HIV status. Median symptom duration before admission was 14 days in the Danish patient population and 20 days in the immigrant group.Biochemical analysis of cerebrospinal fluid (CSF) samples revealed pleocytosis in 90% with lymphocyte predominance in 66%. Protein levels were elevated in 86%.The most common findings on neuro-radiological imaging were basal meningeal enhancement, tuberculomas and hydrocephalus. Lumbar puncture was performed on 42 patients; 31 of these specimens (74%) had a positive CSF culture for mycobacteria and 9.5% were smear positive for acid-fast bacilli.The overall mortality rate was 19% and 48% of the remaining patients had neurological sequelae of varying degree.
Conclusion: TBM is a rare but severe manifestation of extrapulmonary TB in Denmark. The clinician must be prepared to treat empirically if the suspicion of TBM has arisen to improve treatment outcome.
http://7thspace.com/headlines/373610/tuberculous_meningitis_in_denmark_a_review_of_50_cases.html
Monday, 21 February 2011
MALARIA: Malarone in pregnancy
Amy Norton : Feb 16, 2011
NEW YORK (Reuters Health) - Pregnant women who take the anti-malarial drug Malarone during their first trimester might not be increasing their baby's risk of birth defects, a new study suggests.
Most anti-malaria drugs -- including this one -- are not approved for use in pregnancy. So when pregnant women want to travel to malaria-ridden regions, they face a huge problem: should they take preventive medicines that haven't been proven safe for the fetus?
In general, experts advise all pregnant women to avoid traveling to countries where malaria is common, since the infection itself may be dangerous to the mother and fetus.
The new study, published in the Archives of Internal Medicine, is the first to look at pregnant women's use of Malarone -- known generically as atovaquone-proguanil -- and the risk of birth defects.
So the researchers say it is too soon to declare the drug safe for the small number of pregnant women who might need to take it.
The cheapest and mostly widely used anti-malaria drug, called chloroquine, is considered safe during pregnancy. But resistance to that drug has become common worldwide.
Another anti-malaria drug, the antibiotic doxycycline, is known to have adverse effects on the fetus.
In the new study, researchers looked at data on nearly 571,000 births in Denmark between 2000 and 2008. Overall, 2 to 3 out of every 100 newborns had a birth defect.
Among the 149 women who used Malarone at some point during the first trimester, roughly one of every hundred had a baby with a birth defect.
The findings offer some reassurance that the drug is not linked to any large risk of birth defects, said lead researcher Dr. Bjorn Pasternak, of Statens Serum Institute in Copenhagen.
Still, since only a small number of women in the study took Malarone during early pregnancy, the findings cannot rule out the possibility of some risk, Pasternak said.
"We believe it is far too soon to declare this drug to be safe for use in pregnancy," he told Reuters Health in an email.
Malarone is not inexpensive -- it costs close to $200 for 24 pills. The number of pills a woman would have to take depends on how long she stays in the malaria region.
Caused by a mosquito-borne parasite, malaria is widespread (the technical term is "endemic") in large areas of Africa, Asia and South and Central America, where it kills about 1 million people a year.
An estimated 10,000 to 30,000 travelers develop malaria every year, and about 150 die.
http://www.reuters.com/article/2011/02/16/us-malaria-drug-idUSTRE71F66K20110216?feedType=RSS&feedName=healthNews
NEW YORK (Reuters Health) - Pregnant women who take the anti-malarial drug Malarone during their first trimester might not be increasing their baby's risk of birth defects, a new study suggests.
Most anti-malaria drugs -- including this one -- are not approved for use in pregnancy. So when pregnant women want to travel to malaria-ridden regions, they face a huge problem: should they take preventive medicines that haven't been proven safe for the fetus?
In general, experts advise all pregnant women to avoid traveling to countries where malaria is common, since the infection itself may be dangerous to the mother and fetus.
The new study, published in the Archives of Internal Medicine, is the first to look at pregnant women's use of Malarone -- known generically as atovaquone-proguanil -- and the risk of birth defects.
So the researchers say it is too soon to declare the drug safe for the small number of pregnant women who might need to take it.
The cheapest and mostly widely used anti-malaria drug, called chloroquine, is considered safe during pregnancy. But resistance to that drug has become common worldwide.
Another anti-malaria drug, the antibiotic doxycycline, is known to have adverse effects on the fetus.
In the new study, researchers looked at data on nearly 571,000 births in Denmark between 2000 and 2008. Overall, 2 to 3 out of every 100 newborns had a birth defect.
Among the 149 women who used Malarone at some point during the first trimester, roughly one of every hundred had a baby with a birth defect.
The findings offer some reassurance that the drug is not linked to any large risk of birth defects, said lead researcher Dr. Bjorn Pasternak, of Statens Serum Institute in Copenhagen.
Still, since only a small number of women in the study took Malarone during early pregnancy, the findings cannot rule out the possibility of some risk, Pasternak said.
"We believe it is far too soon to declare this drug to be safe for use in pregnancy," he told Reuters Health in an email.
Malarone is not inexpensive -- it costs close to $200 for 24 pills. The number of pills a woman would have to take depends on how long she stays in the malaria region.
Caused by a mosquito-borne parasite, malaria is widespread (the technical term is "endemic") in large areas of Africa, Asia and South and Central America, where it kills about 1 million people a year.
An estimated 10,000 to 30,000 travelers develop malaria every year, and about 150 die.
http://www.reuters.com/article/2011/02/16/us-malaria-drug-idUSTRE71F66K20110216?feedType=RSS&feedName=healthNews
Wednesday, 2 February 2011
TUBERCULOSIS: Promising New Approach to a TB Vaccine (H56)
Jan. 25, 2011
C Aagaard et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nature Medicine. DOI: 10.1038/nm.2285 (2011).
A team of European and U.S. researchers have found that a new vaccine strategy tested in mice provides improved protection from tuberculosis (TB) infection than the vaccine currently used in humans, known as BCG. Their findings were published online on January 23rd in the journal Nature Medicine.
Led by scientists at the Statens Serum Institut (SSI) in Denmark, the study was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the Bill & Melinda Gates Foundation. The NIAID support was through the TB Vaccine Testing and Research Materials program at Colorado State University, an initiative to speed the development of new TB vaccines and treatments.
Caused by the bacterium Mycobacterium tuberculosis (Mtb), TB remains one of the major causes of disability and death worldwide, with an estimated 1.7 million deaths in 2009 and increasing rates of drug-resistant disease. The BCG vaccine, the only one approved for human use, provides limited protection against immediate TB illness but does not prevent reactivation of latent infection, in which Mtb persists in human cells for years and may later develop into active disease.
In this study, researchers at SSI combined two proteins that had previously been tested with a new component, a stress response protein that Mtb produces during latent infection. This three-component vaccine, known as H56, was administered to uninfected mice before and after Mtb infection. The multistage vaccine not only protected against initial illness, but controlled reactivation of latent infection and reduced Mtb levels in the lungs more effectively than BCG alone. Because of the success of this study, the vaccine candidate is now entering clinical development.
Christine Sizemore, Ph.D., chief of the Tuberculosis, Leprosy and other Mycobacterial Diseases Section at NIAID, is available to comment on this article. To schedule interviews, please contact Nalini Padmanabhan, 301-402-1663, niaidnews@niaid.nih.gov.
http://www.niaid.nih.gov/news/newsreleases/2011/Pages/TBvaccineCollaboration.aspx
C Aagaard et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nature Medicine. DOI: 10.1038/nm.2285 (2011).
A team of European and U.S. researchers have found that a new vaccine strategy tested in mice provides improved protection from tuberculosis (TB) infection than the vaccine currently used in humans, known as BCG. Their findings were published online on January 23rd in the journal Nature Medicine.
Led by scientists at the Statens Serum Institut (SSI) in Denmark, the study was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the Bill & Melinda Gates Foundation. The NIAID support was through the TB Vaccine Testing and Research Materials program at Colorado State University, an initiative to speed the development of new TB vaccines and treatments.
Caused by the bacterium Mycobacterium tuberculosis (Mtb), TB remains one of the major causes of disability and death worldwide, with an estimated 1.7 million deaths in 2009 and increasing rates of drug-resistant disease. The BCG vaccine, the only one approved for human use, provides limited protection against immediate TB illness but does not prevent reactivation of latent infection, in which Mtb persists in human cells for years and may later develop into active disease.
In this study, researchers at SSI combined two proteins that had previously been tested with a new component, a stress response protein that Mtb produces during latent infection. This three-component vaccine, known as H56, was administered to uninfected mice before and after Mtb infection. The multistage vaccine not only protected against initial illness, but controlled reactivation of latent infection and reduced Mtb levels in the lungs more effectively than BCG alone. Because of the success of this study, the vaccine candidate is now entering clinical development.
Christine Sizemore, Ph.D., chief of the Tuberculosis, Leprosy and other Mycobacterial Diseases Section at NIAID, is available to comment on this article. To schedule interviews, please contact Nalini Padmanabhan, 301-402-1663, niaidnews@niaid.nih.gov.
http://www.niaid.nih.gov/news/newsreleases/2011/Pages/TBvaccineCollaboration.aspx
Tuesday, 21 December 2010
TUBERCULOSIS: Recurrent tuberculosis in Denmark: relapse vs. re-infection.
Int J Tuberc Lung Dis. 2010 Apr;14(4):447-53.
Bang D, et al. International Reference Laboratory of Mycobacteriology, National Centre for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
Abstract
SETTING: Denmark, a country with a low-incidence of tuberculosis (TB).
OBJECTIVE: To analyse the proportion of relapse vs. re-infection and to compare selected characteristics between the two subgroups.
DESIGN: A population-based cohort study. All 4154 Mycobacterium tuberculosis isolates from patients in Denmark genotyped by insertion sequence 6110 restriction fragment length polymorphism were followed for recurrent TB over 13.5 years. Recurrent cases were classified as relapse or re-infection by genotype patterns in initial and serial disease episodes.
RESULTS: Recurrent TB was found in 73 (1.8%) cases. Identical M. tuberculosis genotypes in initial and serial episodes were found in 54 (1.3%), indicating relapse, whereas different genotypes, representing re-infection, were found in 19 (0.5%) cases. Cavitary TB in the initial episode was significantly associated with relapse (OR 4.6, 95%CI 1.1-26.9) compared to re-infection.
CONCLUSION: The rate of recurrent TB is low in Denmark. Comparing selected characteristics between the relapse and re-infection subgroups revealed that only the presence of cavitary disease was associated with relapse. Although recurrent TB was rarely due to re-infection, the risk of re-infection increased with time.
http://www.ncbi.nlm.nih.gov/pubmed/20202303
Bang D, et al. International Reference Laboratory of Mycobacteriology, National Centre for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
Abstract
SETTING: Denmark, a country with a low-incidence of tuberculosis (TB).
OBJECTIVE: To analyse the proportion of relapse vs. re-infection and to compare selected characteristics between the two subgroups.
DESIGN: A population-based cohort study. All 4154 Mycobacterium tuberculosis isolates from patients in Denmark genotyped by insertion sequence 6110 restriction fragment length polymorphism were followed for recurrent TB over 13.5 years. Recurrent cases were classified as relapse or re-infection by genotype patterns in initial and serial disease episodes.
RESULTS: Recurrent TB was found in 73 (1.8%) cases. Identical M. tuberculosis genotypes in initial and serial episodes were found in 54 (1.3%), indicating relapse, whereas different genotypes, representing re-infection, were found in 19 (0.5%) cases. Cavitary TB in the initial episode was significantly associated with relapse (OR 4.6, 95%CI 1.1-26.9) compared to re-infection.
CONCLUSION: The rate of recurrent TB is low in Denmark. Comparing selected characteristics between the relapse and re-infection subgroups revealed that only the presence of cavitary disease was associated with relapse. Although recurrent TB was rarely due to re-infection, the risk of re-infection increased with time.
http://www.ncbi.nlm.nih.gov/pubmed/20202303
TUBERCULOSIS: TB high in Greenland
A survey shows that 43 per cent of people in Kuummiut, Greenland are infected with tuberculosis bacteria.
Kuummiut (founded 1915) is a settlement in the Sermersooq municipality and has a population of about 400.
Tasiilaq's hospital is now examining all those infected with TB. How many of those infected who developed TB disease is not yet known, Sermitsiaq.AG reports.
Tuberculosis has been a problem for centuries in Greenland, but by a great effort from 1955 on managed to reduce the incidence by 90 per cent, and brought Greenland's TB incidence in line with Denmark.
But since 1990 there has again been a rise in tuberculosis cases.
The last five years have seen an average 73 cases per year, equivalent to a frequency of about 130:100,000 inhabitants. This places Greenland on a par with several African and Asian countries.
http://www.sikunews.com/News/Denmark-Greenland/TB-high-in-Greenland-7621
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