MicrobiologyBytes

According to official estimates, rabies kills 55,000 people each year, primarily in India, Southeast Asia and Africa. However, the death toll is probably much higher; one report estimates that the number of deaths in some areas is possibly 100 times that reported. As rabies cases do not need to be reported to the authorities in many countries, and many people do not seek treatment or are misdiagnosed, obtaining an accurate estimate of the overall prevalence is difficult. Even the official death toll is higher than that for diseases such as human African trypanosomiasis, leishmaniasis and Chagas disease.

As with other diseases that are preventable and treatable, such as pneumonia, it seems unthinkable that rabies still claims so many lives. Successful control of rabies in the United Kingdom and the Americas shows that rabies can be controlled and possibly eliminated. Further research will bring us closer to this goal, but it will require funding agencies and governments to better understand the scope of the problem. Until then, important events like World Rabies Day will remain vital to shed light on this neglected problem.

Biting back against rabies. Nature Reviews Microbiology 8: 676 (October 2010) doi:10.1038/nrmicro2451

Related:

• Transmission and elimination of rabies
• Simplified rabies vaccination
• Pre-exposure and Post-exposure Prevention of rabies

A new DNA test for Human Papillomavirus (HPV) which causes cervical cancer is so much better than current methods that some gynecologists hope it will eventually replace the Pap smear in wealthy countries and other tests in poor ones. Not only could the new test for HPV save lives, scientists say that women over 30 could drop annual Pap smears and instead have the DNA test just once every 3, 5 or even 10 years, depending on which expert is asked. This optimism is based on an eight-year study of 130,000 women in India financed by the Bill and Melinda Gates Foundation and published recently in the New England Journal of Medicine:

HPV Screening for Cervical Cancer in Rural India. 2009 New Engl J. Med. 360: 1385-1394
In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

Related:

• From India to the World – A Better Way to Prevent Cervical Cancer. 2009 New Engl J. Med. 360: 1453-1455
• Should we cure cancer?
• HPV vaccines: prospects for eliminating ano-genital cancer
• Dumb and Dumber

Human disease attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for more than 2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because it has a large, slowly evolving DNA genome, researchers were able to construct a phylogeny of VARV by analyzing single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. The results reveal two primary VARV clades, which are likely to have diverged from an ancestral African rodent-borne variola-like virus either 16,000 or 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. The other primary clade included both alastrim minor, a phenotypically mild smallpox described from the Americas, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP.
Observations of smallpox-typical skin rashes on Egyptian mummies dating from 1100 to 1580 B.C. gave credibility to theories that ancient Egypt was an early (and perhaps the earliest) smallpox endemic region. However, smallpox researchers noted that “The most striking thing about smallpox is its absence from the books of the Old and New Testaments, and also from the literature of the Greeks and Romans. Such a serious disease as variola major is very unlikely to have escaped a description by Hippocrates if it existed.” Historical records from Asia describe evidence of smallpox-like disease in medical writings from ancient China (1122 B.C.) and India (as early as 1500 B.C.). The earliest unmistakable description of smallpox first appears in the 4th century A.D. in China, the 7th century A.D. in India and the Mediterranean, and the 10th century A.D. in southwestern Asia. These early Asian descriptions could indicate that pandemic smallpox originated in East Asia. Sequence analysis indicates that divergence between VARV and rodent poxviruses occurred from 16,000 YBP to 68,000 YBP, and that VARV seems to have evolved from a pathogen of African rodents and subsequently spread out of Africa.
On the origin of smallpox: Correlating variola phylogenics with historical smallpox records
PNAS USA 2007 104:15787-15792

What does this all mean?

• In spite of concerns about bioterrorism, smallpox is no longer a major human pathogen, but understanding the origin of this disease, which has been of major importance for most of human history, offers glimpses into how we might rapidly understand new emerging diseases as they appear.
• For a long time it has been generally believed the the most probable origin for smallpox virus was in Asia, but as with yellow fever and HIV, this new research seems to show that smallpox originally came out of Africa.