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African meningitis belt: 2006
Newsdesk
producing cells were beginning to die. 2 weeks later, expression of an insulin receptor gene (insulin growth factor 2) had also dropped and cell death was evident. Brains injected with streptozotocin were around half the size of control brains injected with saline. “It’s really dramatic”, says de la Monte. But neurodegeneration was not the only hallmark of Alzheimer’s disease seen. Increased concentrations of GSK3 (the enzyme that triggers tau phosphorylation) and phosphorylated tau protein were evident. Increased concentrations of amyloid precursor protein mRNA and amyloid were also reported, and scattered extracellular plaque-like deposits were seen in the cerebral cortex and hypothalamus. Additionally, the researchers report high concentrations of acetylcholinesterase and low concentrations
of choline acetyltransferase. This indicates reduced concentrations of acetylcholine, a feature consistent with Alzheimer’s disease pathology. There was also evidence of neuroinflammation, and at age 4 weeks the animals displayed cognitive impairments in the Morris water maze (J Alzheimers Dis 2006; 9: 13–33). The results suggest that insulin deficiency in the brain may trigger Alzheimer’s disease, so therapies that boost insulin or the responsiveness to it might prove useful, says de la Monte. The study also raises the possibility that Alzheimer’s disease is a brainspecific neuroendocrine disorder. So de la Monte has coined an alternative moniker for the disorder—type 3 diabetes. Type 1 and 2 diabetes occur when the body is unable to produce or use pancreatic insulin. Type 3 diabetes,
she says, is a brain specific form displaying similar features—insulinproducing neurons die and surviving neurons become insulin resistant. To some this idea is controversial. “But if we start thinking differently about Alzheimer’s disease, we may be able to move forwards”, she says. “It’s an excellent model highlighting a primary metabolic abnormality in Alzheimer’s disease”, says George Perry (University of Texas, USA). Although it may seem counterintuitive, de la Monte thinks that the use of pups rather than adult rats is crucial to her model’s success. The brain regions hit hardest by Alzheimer’s disease are those where synaptic turnover is high. Developing brains have a high synaptic turnover in the same areas, so pups provide an ideal model.
Helen Pilcher
African meningitis belt: 2006 Halfway through the disease season in the African meningitis belt, and the number of cases and deaths among the seven countries affected in 2006 seem to be comparable to 2004 and 2005, both thought of as mild years. However, a severe outbreak of Neisseria meningitidis serogroup-A disease in Burkina Faso has reached epidemic proportions in 12 districts. Figures released by WHO on March 21 (http://www.who.int/csr/don/2006_ 03_21/en/print.html) show that there have been 5719 cases and 580 deaths in the region. Seven countries are affected: Burkina Faso, Côte d’Ivoire, Mali, and Niger in the west and Kenya, Sudan, and Uganda in the east. Around two-thirds of cases and deaths have been recorded in Burkina Faso. In west Africa, outbreaks have resulted from infection with serogroup A N meningitidis, whereas in east Africa, there have been outbreaks of serogroups A and W135. Vaccination programmes with bivalent AC vaccine have been launched in Burkina Faso http://neurology.thelancet.com Vol 5 May 2006
and Sudan and with trivalent ACW vaccine in Uganda. “The fact that we still experience yearly epidemics of group A N meningitidis in Africa is a bitter indictment of the lack of international commitment to the real public health challenges of developing countries”, says Josef Decosas (Plan West Africa, Accra, Ghana). Conjugate vaccines specific to both serogroups A and W135 could substantially lessen the yearly outbreaks. A conjugate group A vaccine developed by the Meningitis Vaccine Project recently passed phase I tests, and further testing of the vaccine will begin in Gambia and Mali later this year, with the hope that the low-cost vaccine will be available by 2009. Decosas believes that a group A vaccine could have been made available a decade ago had development efforts not been diverted to a group C vaccine for use in the more profitable European market. In Sudan, epidemic disease thresholds have been passed in four
states. 28 cases of W135 meningococcal disease and one death have been reported from the Hamadyia IDP (internally displaced people) camp in the West Darfur region of Sudan. A vaccine for group A seems now to be within sight; but according to Decosas, since an epidemic outbreak in Burkina Faso in 2002, “talk about a conjugate vaccine for W135 has all but died down”.
Peter Hayward
Mali Burkina Faso
Niger Sudan
CÔte d‘Ivoire
Uganda Kenya
Burkina Faso is the worst hit of the seven countries affected so far this season
389
producing cells were beginning to die. 2 weeks later, expression of an insulin receptor gene (insulin growth factor 2) had also dropped and cell death was evident. Brains injected with streptozotocin were around half the size of control brains injected with saline. “It’s really dramatic”, says de la Monte. But neurodegeneration was not the only hallmark of Alzheimer’s disease seen. Increased concentrations of GSK3 (the enzyme that triggers tau phosphorylation) and phosphorylated tau protein were evident. Increased concentrations of amyloid precursor protein mRNA and amyloid were also reported, and scattered extracellular plaque-like deposits were seen in the cerebral cortex and hypothalamus. Additionally, the researchers report high concentrations of acetylcholinesterase and low concentrations
of choline acetyltransferase. This indicates reduced concentrations of acetylcholine, a feature consistent with Alzheimer’s disease pathology. There was also evidence of neuroinflammation, and at age 4 weeks the animals displayed cognitive impairments in the Morris water maze (J Alzheimers Dis 2006; 9: 13–33). The results suggest that insulin deficiency in the brain may trigger Alzheimer’s disease, so therapies that boost insulin or the responsiveness to it might prove useful, says de la Monte. The study also raises the possibility that Alzheimer’s disease is a brainspecific neuroendocrine disorder. So de la Monte has coined an alternative moniker for the disorder—type 3 diabetes. Type 1 and 2 diabetes occur when the body is unable to produce or use pancreatic insulin. Type 3 diabetes,
she says, is a brain specific form displaying similar features—insulinproducing neurons die and surviving neurons become insulin resistant. To some this idea is controversial. “But if we start thinking differently about Alzheimer’s disease, we may be able to move forwards”, she says. “It’s an excellent model highlighting a primary metabolic abnormality in Alzheimer’s disease”, says George Perry (University of Texas, USA). Although it may seem counterintuitive, de la Monte thinks that the use of pups rather than adult rats is crucial to her model’s success. The brain regions hit hardest by Alzheimer’s disease are those where synaptic turnover is high. Developing brains have a high synaptic turnover in the same areas, so pups provide an ideal model.
Helen Pilcher
African meningitis belt: 2006 Halfway through the disease season in the African meningitis belt, and the number of cases and deaths among the seven countries affected in 2006 seem to be comparable to 2004 and 2005, both thought of as mild years. However, a severe outbreak of Neisseria meningitidis serogroup-A disease in Burkina Faso has reached epidemic proportions in 12 districts. Figures released by WHO on March 21 (http://www.who.int/csr/don/2006_ 03_21/en/print.html) show that there have been 5719 cases and 580 deaths in the region. Seven countries are affected: Burkina Faso, Côte d’Ivoire, Mali, and Niger in the west and Kenya, Sudan, and Uganda in the east. Around two-thirds of cases and deaths have been recorded in Burkina Faso. In west Africa, outbreaks have resulted from infection with serogroup A N meningitidis, whereas in east Africa, there have been outbreaks of serogroups A and W135. Vaccination programmes with bivalent AC vaccine have been launched in Burkina Faso http://neurology.thelancet.com Vol 5 May 2006
and Sudan and with trivalent ACW vaccine in Uganda. “The fact that we still experience yearly epidemics of group A N meningitidis in Africa is a bitter indictment of the lack of international commitment to the real public health challenges of developing countries”, says Josef Decosas (Plan West Africa, Accra, Ghana). Conjugate vaccines specific to both serogroups A and W135 could substantially lessen the yearly outbreaks. A conjugate group A vaccine developed by the Meningitis Vaccine Project recently passed phase I tests, and further testing of the vaccine will begin in Gambia and Mali later this year, with the hope that the low-cost vaccine will be available by 2009. Decosas believes that a group A vaccine could have been made available a decade ago had development efforts not been diverted to a group C vaccine for use in the more profitable European market. In Sudan, epidemic disease thresholds have been passed in four
states. 28 cases of W135 meningococcal disease and one death have been reported from the Hamadyia IDP (internally displaced people) camp in the West Darfur region of Sudan. A vaccine for group A seems now to be within sight; but according to Decosas, since an epidemic outbreak in Burkina Faso in 2002, “talk about a conjugate vaccine for W135 has all but died down”.
Peter Hayward
Mali Burkina Faso
Niger Sudan
CÔte d‘Ivoire
Uganda Kenya
Burkina Faso is the worst hit of the seven countries affected so far this season
389