387treatment, experience adverse side effects from antibiotics or fail to respond rapidly
and recover. These factors have resulted in the worrying emergence of drug resis-
tance, leading to multi-drug resistant (MDR) and extensively drug resistant (XDR)
strains of TB becoming prevalent. This is a particular problem in the developing
world, where the majority of patients with TB also have HIV, making effective
eradication extremely diffi cult.
Isoniazid, one of the most important fi rst-line tuberculosis drugs, is acetylated in
the liver to a variable degree in different individuals giving rise to fast, intermediate
and slow acetylator phenotypes. Different genetic mutations may play a role in
determining how a patient will respond to the commonly used TB medication iso-
niazid (Werely et al. 2007 ). Acetylation status of individuals plays an important
contributory role in the tuberculosis pandemic. It is important to study the acetyla-
tion alleles, and to understand isoniazid metabolism and the manner in which it
could affect patient compliance, isoniazid-toxicity and the emergence of drug-
resistant strains of mycobacteria. These phenotypes have been linked to different
genetic variants, primarily present in the NAT2 gene (see Chap. 3 ). The standard
drug dose currently administered to patients, regardless of their acetylator status,
may not be appropriate for certain people. Individualization of isoniazid therapy
may help to prevent adverse drug reactions experienced by a small percentage of
patients thought to be ‘slow-acetylators’ of the drug. Conversely fast-acetylators
may not be receiving suffi cient amounts of the drug to combat TB successfully,
therefore increasing the likelihood of a relapse and development of drug resistance.
Confi rmation of the genetics of isoniazid metabolism by a simple test to determine
acetylator status would be desirable and this should be available at the same labora-
tories that currently perform diagnostics for TB.
Personalized Management of Viral Infections
Antiviral therapeutics is dealt with in detail in a special report on this topic
(Jain 2015a ). A schematic approach to integration of antiviral strategies is shown
in Fig. 11.1.
Currently used therapies for viral infections such as HIV/AIDS and infl uenza
target certain receptors or enzymes. Most of these are specifi c for each infection
whereas others such as protease inhibitors can be used in more than one type of
infection. None of these approaches cover multiple receptors. Effi cacy is limited
and there are problems with development of resistance, particularly in case of HIV.
Ligand-binding epitopes of proteins can mutate rapidly, as shown by viral muta-
tions that lead to escape from neutralizing antibodies. An approach, dubbed “check-
mate analysis,” may predict which antibodies or small molecule therapeutics will
best neutralize these viral mutations before they can develop into global epidemics
(Dickerson et al. 2007 ). This is phage-based method that allows rapid analysis
of molecules that perturb the binding of proteins to their ligands. Because the
system can amplify by replication, single-molecule sensitivity can be achieved.
Personalized Management of Viral Infections