There’s a great collection of freely available resources On the Nature website under Nature Collections – Malaria (maybe NPG is finally getting the message about open access – hey Nature, it’s good to share :-)
The world is on the verge of making major inroads against malaria – a deadly disease that still claims the lives of more than 1 million people annually, mostly children less than 5 years of age. Over the past decade, scientists, large pharmaceutical companies and small biotechnology firms, governments and philanthropic organizations have come together to mount a full frontal attack on malaria, and there is now even talk of the ‘E word’ – that is, eradication. This collection highlights advances in the deployment of existing tools, and in the basic science of malaria – particularly those flowing from sequencing of the malaria parasite genomes – that will underpin the next generation of malaria-control tools, which will be needed if the scourge of malaria is to be eradicated.
Contents:
Malaria: The end of the beginning – After decades of work, a pioneering malaria vaccine may soon reach the final phase of clinical trials. A vaccine that is far from perfect – but which may provide new direction and save thousands of lives.
Malaria vaccine gets shot in the arm from tests – Promising results pave the way for a vaccine candidate to undergo full-blown trials across Africa.
Malaria: The big push – Zambia, with help from partners around the world, is stepping up its battle against malaria.
The billion-dollar malaria moment – For years the global malaria effort has been asking for more resources. Now the field needs to figure out a systematic strategy for spending the money effectively.
Review: Malaria research in the post-genomic era
Articles:
Comparative genomics of the neglected human malaria parasite Plasmodium vivax
Genome sequence of the human malaria parasite Plasmodium falciparum
Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii
The genome of the simian and human malaria parasite Plasmodium knowlesi
The press was buzzing with speculation about the chances of a vaccine to prevent diabates. Very good news for diabetics? Well not so fast. Before we look at the science, let me tell you two things about myself. First, I have two close relatives who are affected by diabetes, so this is a disease I care a lot about. Second, I’ve been in the virology business a long time – and we’ve been here before.
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The new paper claimed to have detected “enterovirus capsid protein vp1″ in 44 out of 72 pancreases from children who had died of type-1 diabetes shortly after becoming ill, but in only three out of 50 neonatal and paediatric normal control specimens. Statistically there is a strong correlation in this study between diabetes and the presence of the virus protein, but a correlation does not indicate a cause. Are diabetics more susceptible to enterovirus infection? We don’t know. While it’s not ethically possible to satisfy Koch’s postulates in humans, we need to be very careful in inferring from small scale studies such as this one:
The microorganism must be found in abundance in all organisms suffering from the disease.
The microorganism must be isolated from a diseased organism and grown in pure culture.
The cultured microorganism should cause disease when introduced into a healthy organism.
The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.
There are over a hundred different enteroviruses and the antibody used for detection of virus protein in this study (yes, that’s right, just one non-specific antibody) does not identify the virus involved. Vaccine against diabetes? I don’t think so.
But as I said, we’ve been here before. There are reports of viruses associated with diabetes dating from the 1960s, and a very well known model of Coxsackie virus B4 causing diabetes in mice dating from the 1970s (Coxsackie Viruses and Diabetes Mellitus. BMJ 1973 November 3; 4(5887): 260–262). So does the latest work add anything new, and is a vaccine against diabetes just around the corner? No. I wish it was.
Cholera is an infectious form of gastroenteritis caused by the enterotoxin-producing strains of the curved Gram-negative bacillus Vibrio cholerae. Transmission to humans occurs through ingesting food or water that is contaminated with faecal matter from infected people. Classically the disease occurs where there is a lack or failure of sanitation, e.g. in crowded urban conditions in developing countries or following natural disasters. In its most severe forms, cholera is one of the most rapidly fatal illnesses known – in some circumstances infected patients may die within hours if medical treatment is not provided. Usually the disease progresses from the first liquid stool to shock (due to dehydration) in 4 to 12 hours, with death following in 18 hours to several days, unless oral rehydration therapy is provided.
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How does a tiny bacterium cause such rapid deaths? Cholera is a toxin-mediated disease. Vibrio cholerae produces cholera toxin, an enterotoxin which acts on the mucosal epithelium lining the small intestine, causing cell death and massive loss of body fluids into the gut, resulting in the the characteristic massive diarrhoea associated with the disease. Death is caused by hypovolemic shock due to the loss of body fluids, so first aid for cholera involves oral rehydration with isotonic liquids to combat these symptoms. Antibiotics are then given to speed up resolution of the infection.
Cholera seems to have originated in the Indian subcontinent and the disease spread by trade routes to Russia, then to Western Europe, and from Europe to North America during the nineteenth century. The history of cholera has been marked by a series of pandemics:
1816-1826 – First cholera pandemic
1829-1851 – Second cholera pandemic
1852-1860 – Third cholera pandemic. During this pandemic in 1854 John Snow identified contaminated water as the source of the disease by removal of the handle of the Broad Street pump in London.
1863-1875 – Fourth cholera pandemic
1881-1896 – Fifth cholera pandemic
1899-1923 – Sixth cholera pandemic
1961-1970s – Seventh cholera pandemic
Currently the disease is following a more endemic pattern, cropping up in poor countries and after natural disasters.
Vaccines against cholera are available but are not currently recommended for routine use. New oral vaccines against cholera are being developed, including a live-attenuated vaccine containing genetically manipulated V. cholerae, and an alternative vaccine containing killed whole-cell V. cholerae in combination with purified recombinant B subunit of the cholera toxin. Although the ultimate answer to cholera lies in public health and sanitation, at present the only feasible answer to cholera in poor countries is in vaccine development.
The Final Inch is a collaborative effort between Google.org and Vermilion Films to document the final stages of the historic global effort to eradicate polio. The story told is as much about the messengers as the message. You’ll meet Munzareen Fatima, one of the thousands of community workers across India working to persuade reluctant families to vaccinate their children, and Dr. Ashfaq Bhat, who travels into the backwaters of India’s Ganges Basin by boat and foot to detect emerging cases of polio. Martha Mason and Mikail Davenport describe the paralyzing challenges of childhood polio, reminding us that polio was once endemic in the United States and Europe:
The Final Inch will air in the USA on HBO in 2009.
Every day 2000 children die from malaria in Africa alone. The infection is transmitted from human to human by biting mosquitoes. Despite many years of effort, a vaccine is still not available to fight the deadly disease. Once injected by a mosquito, parasites migrate to the liver where they mature and then their sporozoites (infective cells) are released into the blood, causing disease and fatal complications. Human malaria is caused by Plasmodium falciparum, a unicellular protozoan parasite that is transmitted by Anopheles mosquitoes. An infectious mosquito injects saliva containing sporozoite forms of the parasite and these then migrate from the skin to the liver, where they establish an infection. Many intervention strategies are currently focused on preventing the establishment of infection by sporozoites. Clearly, an understanding of the biology of the sporozoite is essential for developing new intervention strategies. Sporozoites are produced within the oocyst, located on the outside wall of the mosquito midgut, and migrate after release from the oocysts to the salivary glands where they are stored as mature infectious forms. Comparison of the proteomes of sporozoites derived from either the oocyst or from the salivary gland reveals remarkable differences in the protein content of these stages despite their similar morphology. The changes in protein content reflect the very specific preparations the sporozoites make in order to establish an infection of the liver. Analysis of the function of several previously uncharacterized, conserved proteins revealed proteins essential for sporozoite development at distinct points of their maturation.
Researchers characterized a large number of parasite proteins that may prove useful in the development of a human malaria vaccine. A promising method for vaccination is to sufficiently weaken these parasites such that they invade liver cells and stimulate an immune response, but don’t develop further. This can be achieved by genetically inactivating individual parasite genes that are active during the parasite’s growth in the liver. The researchers achieved this by modifying the proteins essential for sporozoite development, which their study identified. Collaborators had previously shown how to successfully vaccinate mice using a rodent malaria which had one of these liver stage genes removed, specifically p36p.
A related article shows the first transition of such a vaccination from the rodent system to humans, by inactivating the equivalent gene (p52) in the major human malaria parasite, P. falciparum. Similar to the results with the rodent parasite, these human parasites are unable to develop in liver cells. This is the first time that genetic modification of a human parasite results in its growth arrest in a liver cell, opening up promising possibilities for its use as a human vaccine. These studies show how results obtained in rodent models of malaria can be pipelined to form the basis for clinical development of anti-malaria vaccines in humans.
Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity. PLoS Pathog 4(10): e1000195 Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito – early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. Despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocyte infectivity. The different sporozoite proteomes contain a large number of stage specific proteins whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may be essential for sporozoite infectivity to humans.
As this year’s flu season gets underway in the northern hemisphere, new research finds that when it comes to flu vaccination, more appears to be better. Two new studies published in the open access journal PLoS Medicine show that increasing the number of people vaccinated against influenza can decrease the burden of the disease, and not just in the individuals receiving the vaccine.
Targeted vaccination programs, in which flu vaccine is recommended for particular groups at high risk of spreading or experiencing complications of influenza, are commonly implemented. In contrast, the Canadian province of Ontario initiated a universal immunization program in 2000, in which flu vaccination is promoted and provided free of charge to everyone over the age of 6 months. The first study evaluated the effect of this universal immunization program on influenza-associated health outcomes. The researchers analyzed national and provincial data from 1997 to 2004, to compare changes in Ontario’s flu outcomes before and after introduction of universal vaccination with outcomes in other provinces, which continued targeted vaccination programs. They found that, compared with other Canadian provinces, Ontario’s universal vaccination program was associated with reductions in influenza outcomes including flu-related deaths, hospitalizations, and visits to emergency departments and doctors’ offices. The results did suggest, however, that increasing immunization rates may not be as effective in reducing mortality and health care use in older people, particularly those over 75 years of age, compared to younger people. However, even with enhanced access to free flu vaccines in Ontario, only an estimated average of 38% of the overall household population reported receiving them, suggesting that protection of older people by higher immunization rates of younger contacts who might expose them to influenza may still be of benefit.
The second study further investigated the concept of herd immunity, by which immunization of some individuals protects the overall population by reducing exposure of those who are not immunized. Using a mathematical model to simulate spread of influenza in nursing homes, researchers found that increasing the number of health care staff who are vaccinated can protect additional patients from influenza. They calculated that increasing the proportion of vaccinated health care workers from zero to 100% in a 30-bed nursing home department would reduce patient infections by about 60%, and that vaccinating seven health care workers would on average prevent one patient from getting influenza. They also found that no level of health care worker vaccination guarantees complete herd immunity, suggesting that even at high levels of immunization, increasing the number of nursing home staff who are vaccinated against flu each year will further reduce risk to patients. The authors also note that random variation, which occasionally leads to large outbreaks, limits the ability of small vaccination trials to assess the actual relationship between health-care worker vaccination and patient risk of influenza.
HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. The virus is carried in blood and in other body fluids including saliva, tears, semen and vaginal secretions and can be transmitted from person to person by a variety of means depending on the epidemiologic pattern within a geographic area.
Following acute infection with HBV, between 1 and 10% of healthy adults and 30–90% of infected babies become chronic virus carriers, some of whom are at risk of life-threatening diseases such as cirrhosis and primary hepatocellular carcinoma (HCC). Globally, at least 2 billion people or one third of the world population have been infected with HBV, over 378 million people (or 6% of the world population) are chronic carriers, and approximately 620,000 people die each year from acute and chronic HBV infection. In addition, approximately 4.5 million new HBV infections occur worldwide each year, of which a quarter progress to liver disease and cirrhosis.
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Vaccination is the most effective measure to control and prevent hepatitis B and its long-term serious consequences on global scale, both in terms of cost-effectiveness and benefit-cost ratios. The first available HBV vaccines were produced by harvesting the hepatitis B surface antigen (HBsAg) from plasma of chronic HBsAg carriers and became commercially available between 1981. Concern about the safety of these vaccines regarding transmission of blood-borne pathogens has proved to be largely unfounded. This led to the development of recombinant DNA hepatitis B vaccines, the second generation hepatitis B vaccines. The small envelope S protein is produced in yeast and the expressed HBsAg polypeptides then self-assemble into immunogenic spherical particles almost identical to the 22-nm particles found in serum of hepatitis B carriers. This new technology allowed the hepatitis B vaccine to become one of the most widely used vaccines in the world, in particular as part of the routine vaccination schedules for many of the world’s infants and children. During the 1990s, third-generation hepatitis B vaccines were developed in HBV transfected mammalian cells. These new HBV vaccines as well as novel new adjuvants have been shown to enhance the immunogenicity of such vaccines in immunocompromised hosts and non-responders to conventional vaccines.
Several hundred million doses of hepatitis B vaccine have been administered worldwide with an excellent record of safety and efficacy. Following a full course of vaccination (3 doses of vaccine given at 0, 1 and 6 months), seroprotection rates are close to 100% in children and almost 95% in healthy young adults. The results of effective implementation of universal hepatitis B vaccine programs are apparent in terms of reduction not only in incidence of acute hepatitis B infections, but also in the carrier rate in immunized cohorts, and in hepatitis-B-related mortality.
In accord with the WHO recommendations, universal HBV vaccination has been currently implemented in 168 countries world wide with an outstanding record of safety and efficacy. The effective implementation of such programmes of vaccination has resulted in a substantial decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. A future challenge is to overcome the social and economic hurdles which still hamper the introduction of HBV vaccination on a global scale.
There’s a great collection of freely available resources On the Nature website under Nature Collections – Malaria (maybe NPG is finally getting the message about open access – hey Nature, it’s good to share :-)
