The biochemistry of rapid replication
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48. Genome Replikin Count™ Predicts Increased Lethality of Resistant Tuberculosis April 3, 2012
(From Nature Precedings: doi:10.1038/npre.2012.7141.1 April 2012)


Samuel Bogoch and Elenore S. Bogoch, Foundation for Research on the Nervous System, Boston University School of Medicine, Bioradar UK Ltd, and Replikins Ltd. 36 The Fenway, Boston, MA 02215

Figure - Increase in Percent of Genome Sequences having Replikin Counts Greater than 4.0 with Increasing Drug Resistance and Lethality of Strains of Tuberculosis

This communication is one of four submitted together:
Genome Replikin Count™ Predicts Increased Lethality of Resistant Tuberculosis
Genome Replikin Count™ Predicts Increased Lethality of Malaria
Genome Replikin Count™ Predicts Increased Lethality of Cancer
Genome Replikin Count™ Predicts Increased Infectivity/Lethality of Viruses

Introduction

Tuberculosis remains a major infectious disease which accounts for approximately 3 million deaths per year worldwide. A series of effective drugs have been developed over several decades which have been recently challenged by two new circumstances: the first is the mutation of the tuberculosis genome to more lethal drug resistant forms, and the second is the association of tuberculosis with AIDS, both resulting in high mortality cases in such areas as KwaZulu-Natal in South Africa and in Europe and Asia.

No structures of infectious organisms have been described to date which correlate quantitatively and temporally with epidemic outbreaks, course, and lethality, and permit early or advance warning of such outbreaks. Replikins, first discovered in glioblastoma multiforme brain cancer cells rapidly replicating in tissue culture, are genomic structures related to rapid replication defined by the authors' algorithm: peptides 7 to 50 amino acids long, containing two or more lysines, six to ten amino acids apart, at least one histidine, and a lysine concentration of 6% or more (1,7). Replikins are the first reported conserved virus structures whose increasing concentration correlates quantitatively with, and predict, strain-specific virus outbreaks as well as their initial geographic location.

As observed in the 2009 H1N1 pandemic, advanced Replikins warning was published one year in advance, in April 2008 (3-5). The outbreak occurred in April 2009. Because of the time taken to produce vaccine, vaccine was not available when the brunt of the pandemic struck in April 2009. Only 20% of the world's population at risk had vaccine available, and that was eight months after the outbreak, when the virus Replikin Count had already indicated that the lethal aspects of the pandemic would soon be over except for a brief recurrence in December 2010, also predicted. Fortunately, so far, the H1N1 pandemic has been less severe than the three pandemics in the last century. The 2011 outbreaks have begun for both H1N1 and H5N1. Initial 'scout' virus outbreaks of H1N1 have occurred, again in Mexico, with Replikin Counts of the Infectivity Gene up to a record 16.7 and a human mortality rate of 10.7%; and outbreaks of H5N1 in Egypt, better established, have begun with a current cumulative mortality rate of from 34.7% to 37.8% (WHO). It is generally agreed that new approaches are required for the control of acute emergent diseases.

The benefits of having more time to prepare for and to respond to acute lethal environmental events has been demonstrated in satellite warnings for hurricanes. The consequences of having little or no advance warning have been recently demonstrated in earthquake-tsunamis and in the 2009 H1N1 influenza pandemic. While mutations can be detected, to date there have been no reliable technologies to predict emergence of specific virus or bacterial strains. The only global surveillance available is post outbreak and based solely on epidemiological data. Acute emergent infectious diseases coupled with current global travel pose challenges to timely implementation of public health measures such as tracking and isolation of cases, and the design, testing and distribution of specific effective vaccines and therapeutics to the world's population.

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