In this week’s press release:
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Rapid test would save babies from syphilis
Screening pregnant women with newer, rapid syphilis tests would improve the survival and health of babies, according to research from Haiti.
About half of pregnancies in women with untreated syphilis end in death of the baby before or shortly after birth, and surviving infants may suffer lifelong effects such as mental disability, deafness, or blindness. Testing for syphilis infection during pregnancy can prevent these outcomes, but only if the mothers receive prompt treatment. Syphilis tests currently in use require a woman to make a second trip to the clinic to receive her test results. In practice, this means that many mothers in poor countries, especially in rural areas, don’t find out they are infected in time to receive treatment to save their babies.
In a study published in the open-access journal PLoS Medicine (www.plosmedicine.org), Bruce Schackman and colleagues from Weill Medical College of Cornell University and the GHESKIO Center in Port-au-Prince, Haiti calculated the cost-effectiveness of newer syphilis tests that provide rapid results, allowing women to receive treatment (usually the antibiotic penicillin) immediately. Even though the cost of rapid test kits is higher than for older tests, the researchers found that better outcomes in fetal health and survival would make rapid testing more cost-effective, especially in areas where it is difficult for women to return to the clinic. Rapid testing was also more effective than treating women based on signs of infection on physical exam.
The infrastructure that poor countries are already establishing to screen expectant mothers for HIV would permit adding a rapid syphilis test at minimal incremental cost. The researchers estimate that integrating rapid syphilis testing into scaled-up prenatal health programs in Haiti would prevent 1,125 cases of congenital syphilis as well as 1,223 stillbirths or neonatal deaths each year at a cost of $525,000.
According to this study, which was sponsored by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases and by the US National Institutes of Health, prenatal care that integrates HIV and syphilis screening will have a powerful effect on improving child survival and health in Haiti, and can be a model for similar programs throughout the world.
Citation: Schackman BR, Neukermans CP, Fontain SNN, Nolte C, Joseph P, et al. (2007) Cost-effectiveness of rapid syphilis screening in prenatal HIV testing programs in Haiti. PLoS Med 4(5): e183.
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Lithium shows promise in mouse model of devastating neurodegenerative disorder
Lithium is one of the oldest psychiatric drugs and still used routinely to ameliorate the symptoms of mood disorders. New results by Huda Zoghbi (Baylor College of Medicine and Howard Hughes Medical Institute), Harry Orr (University of Minnesota) and colleagues now suggest that lithium also holds promise in treating a group of devastating neurodegenerative disorders for which no other treatments exist at present. As the researchers report in the international open-access medical journal PLoS Medicine, dietary lithium markedly improved the symptoms in a mouse model of spinocerebellar ataxia.
Spinocerebellar ataxia type 1 (SCA1) is part of a group of inherited, incurable neurodegenerative disease called “triplet repeat diseases”. These diseases kill patients (who are typically diagnosed in their thirties and forties) within a few years of disease onset. The name refers to the underlying genetic abnormality: Information for making proteins is stored in DNA as groups of three nucleotides (codons), each specifying a different amino acid (the building blocks of proteins). In triplet repeat diseases, patients inherit a mutant gene containing abnormally long stretches of repeated codons. In SCA1, the repeated codon is CAG, which specifies glutamine, and patients have an abnormal glutamine stretch in the Ataxin1 protein. This stretch causes Ataxin1 to accumulate and to have altered protein interactions that are toxic to a group of cerebellar neurons called Purkinje cells (which normally coordinate movement) and hippoca mpal neurons (which are important for memory). Patients gradually lose movement control, have impaired cognitive function, and eventually die from the disease because other neurons in the brain stem also degenerate.
The researchers bred mice carrying a mutant gene for Ataxin1 containing a very long CAG repeat (Sca1154Q/2Q mice) which resemble human patients in symptoms and disease progression. After weaning, the mice were fed normal food or food supplemented with lithium for several weeks before assessing their ability to coordinate their movements and testing their cognitive skills. Dietary lithium (given before or after symptoms appeared) improved both coordination and learning and memory in the mutantmice. Lithium did not change the overall appearance of the brain in the Sca1154Q/2Q mice, but it did partly reverse hippocampal neuron degeneration in these animals.
Lithium did not improve the lifespan of the Sac1154Q/2Q mice either (although this could be because the mutant SCA1 protein has some deleterious effects outside the brain). Lithium alone is thus unlikely to be a miracle cure for spinocerebellar ataxia, but the research suggests that is might be of some help to patients who currently have no other treatments available, even if (as is usual), their condition is not diagnosed until the disease is quite advanced.
Given that lithium is in clinical use, the work by Zoghbi and colleagues is expected to quickly lead to clinical trials which will examine whether lithium does indeed have beneficial effects in human patients with spinocerebellar ataxia and related diseases.
Citation: Watase K, Gatchel JR, Sun Y, Emamian E, Atkinson R, et al. (2007) Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med 4(5): e182.
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Monoclonal neutralizing antibodies show promise against avian flu
Starting with blood of patients who survived a bout of avian flu (infection with the H5N1 strain), Cameron Simmons (of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam) and colleagues generated neutralizing human monoclonal antibodies and show that they can halt viral growth in mice deliberately infected with H5N1 virus.
The researchers isolated and immortalized antibody-producing immune cells from the patients’ blood and purified the antibody made by individual cells. These monoclonal antibodies were then tested for their ability to neutralize H5N1 and other flu viruses in laboratory assays. The researchers identified several antibodies that neutralized the H5N1 strain with which the patients were originally infected and chose four for further study. In the laboratory, all four antibodies neutralized closely related H5N1 viruses and two antibodies also neutralized an H5N1 virus from a different lineage (clade) that has also caused human disease.
The researchers then tested the four antibodies in mice infected with an H5N1 virus from VietNam. The antibodies protected mice when given prior to infection, and up to 72 hours after the infection. The researchers showed that the antibodies protected mice by limiting viral replication, by lessening the deleterious effects of the virus in the lungs, and by stopping viral spread out of the lungs. Three of the four antibodies studied also protected mice infected with a H5N1 virus from a different clade.
These results indicate that passive immunotherapy with human monoclonal antibodies could help to combat avian H5N1 if (or when) it starts a human pandemic. Passive immunotherapy is already used to prevent infections with several viruses. In addition, a crude form of the approach—early treatment of patients with plasma (the liquid portion of blood) from convalescent patients—halved the death rate during the Spanish flu pandemic.
Large amounts of pure monoclonal antibodies can be readily made for clinical use and, importantly, this study indicates that some monoclonal antibodies neutralize H5N1 viruses from different clades.
The researchers sound a note of caution, however. They suggest that before passive immunotherapy can help to halt an H5N1 pandemic, additional monoclonal antibodies should be made to provide doctors with a battery of neutralizing antibodies that can neutralize not only all the currently circulating H5N1 viruses but hopefully also any newly emerging pandemic versions.
Citation: Simmons CP, Bernasconi NL, Suguitan AL, Mills K, Ward JM, et al. (2007) Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.PLoS Med 4(5): e178.
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Human Herpes Virus 6B is associated with mesial temporal lobe epilepsy
There is strong evidence that one particular type of epilepsy is associated with a viral infection, report researchers in PLoS Medicine this week. The international group of researchers, led by Steve Jacobson from National Institute of Neurological Disorders and Stroke, USA, found DNA from the virus, Human Herpes Virus 6B (HHV-6B) in specific regions of the brains in 11 of 16 patients with mesial temporal lobe epilepsy (MTLE) referred for investigation compared with zero of seven (0%) patients without MTLE.
MTLE is a common, severe, type of epilepsy that usually begins in childhood. Mesial temporal sclerosis is a change often seen in the brains of patients with this form of epilepsy. Temporal lobectomy is often used to control MTLE. HHV6 is usually acquired in early childhood - more than 90% of the general population can be shown to have been infected with the virus. After primary infection, HHV-6 can persist lifelong in some white blood cells, salivary glands, and in the central nervous system. Two HHV-6 variants are known, HHV-6A and HHV-6B. Active infection or reactivation of HHV-6 in the brain has been previously shown to be associated with neurological disorders, including epilepsy and encephalitis.
As well as showing the presence of viral DNA in patients with MTLE, in additional studies in one patient who had surgery over many months because of recurrent epilepsy, the researchers were able to detect an antigen (HHV-6 gp116/54/64), which is specific for HHV-6B, in astrocytes (primary brain cells). Finally, the authors showed that infection of cell cultures of astrocyes infected with HHV-6 showed a marked decrease in the expression of one protein, EAAT, which is known to be involved in transmitting glutamate across cell membranes; glutamate is a substance that acts to carry signals within the brain.
Overall, the researchers have now have detected HHV-6B in 15 of 24 patients with mesial temporal sclerosis or MTLE, in contrast to zero of 14 with other syndromes. If these findings are confirmed in other groups of patients with this form of epilepsy, it may open up new avenues of therapy.
Citation: Fotheringham J, Donati D, Akhyani N, Fogdell-Hahn A, Vortmeyer A, et al. (2007) Association of human herpesvirus- 6B with mesial temporal lobe epilepsy. PLoS Med 4(5): e180.
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HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites
Based on a comparison of HIV-negative or HIV-infected primigravid and multigravid women, Kevin Kain and colleagues suggest that opsonic phagocytosis might protect against pregnancy-associated malaria, and that HIV infection might impair this parasite clearance mechanism.
Citation: Keen J, Serghides L, Ayi K, Patel SN, Ayisi J, et al. (2007) HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites. PLoS Med 4(5): e181.
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