90
cryptococcal meningitis; Candida infection or colonization of the respiratory or
urinary tract; febrile neutropenia in leukaemia; Aspergillus bronchitis in bronchiectasis; and allergic, chronic, and invasive fungal sinusitis and Pneumocystis pneumonia in HIV negative patients) and the accurate diagnosis is crucial to avoid antibiotics
and/or antifungals misuse (Denning et al. 2017).
4.5 Resistance in Virus
Viruses have an innate ability to evade antiviral drugs since its replication is prone to
a high error rate (Sanjuán et al. 2010). Thus, the gain of resistance, which normally
involves some type of interference in protein-protein interaction (PPI) or a mutation
in the drug binding site, entails an equilibrium between the ability to evade the selective pressure without affecting the pathogen fitness (Götte 2012; Wensing et al.
2017). Many factors contribute to the virus’s ability to overcome antiviral drugs, like
its replication and mutation rate, viral fitness, and load, being specific for each drug/
microorganism (Mason et al. 2018). A rapid replication/higher viral load lead to a
higher frequency of mutation whereas the viral fitness determines if the pathogen
can compete and survive in the environment (under antiviral pressure) after the
mutation. The viruses that denote main concerns to human health are the human
immunodeficiency virus (HIV), hepatitis B (HBV) and C (HCV), and Influenza.
HIV is a global problem that nowadays affects especially developing countries
and currently has a variety of treatment options (e.g. over 30 antivirals, nucleoside
reverse transcriptase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors) (Larder and Kemp 1989; De Clercq and Li 2016; Mason et al.
2018). The WHO recommendation is for all infected people to undertake antiretroviral treatment, which increases the probability to develop antiviral resistance and
this prospect demand constant monitoring to prevent HIV spread. Influenza virus
causes severe respiratory infections with annual epidemics, pandemics and endemic
infections due to its rapid and constant evolution (Lee and Ison 2012). Antiviruses
are associated with overall improvement and clearance of the disease; however,
resistance represents a significant health issue. Antiviral resistant strains are not
affected by drug therapy and retain replication and transmission fitness, being
responsible for severe outbreaks (Li et al. 2015).
4.6 Resistance in Parasites
Parasites cause numerous severe diseases that are normally entirely dependent on
antiparasitic drugs, due to the lack of economic incentives for research and development (Elsheikha et al. 2011; Secor et al. 2015). Antiparasitic resistance is linked
with biological characteristics of the pathogen that allows them to escape the drug
effect, which is a direct link with the pathogen host interactions. Furthermore,
M. Santana et al.
cryptococcal meningitis; Candida infection or colonization of the respiratory or
urinary tract; febrile neutropenia in leukaemia; Aspergillus bronchitis in bronchiectasis; and allergic, chronic, and invasive fungal sinusitis and Pneumocystis pneumonia in HIV negative patients) and the accurate diagnosis is crucial to avoid antibiotics
and/or antifungals misuse (Denning et al. 2017).
4.5 Resistance in Virus
Viruses have an innate ability to evade antiviral drugs since its replication is prone to
a high error rate (Sanjuán et al. 2010). Thus, the gain of resistance, which normally
involves some type of interference in protein-protein interaction (PPI) or a mutation
in the drug binding site, entails an equilibrium between the ability to evade the selective pressure without affecting the pathogen fitness (Götte 2012; Wensing et al.
2017). Many factors contribute to the virus’s ability to overcome antiviral drugs, like
its replication and mutation rate, viral fitness, and load, being specific for each drug/
microorganism (Mason et al. 2018). A rapid replication/higher viral load lead to a
higher frequency of mutation whereas the viral fitness determines if the pathogen
can compete and survive in the environment (under antiviral pressure) after the
mutation. The viruses that denote main concerns to human health are the human
immunodeficiency virus (HIV), hepatitis B (HBV) and C (HCV), and Influenza.
HIV is a global problem that nowadays affects especially developing countries
and currently has a variety of treatment options (e.g. over 30 antivirals, nucleoside
reverse transcriptase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors) (Larder and Kemp 1989; De Clercq and Li 2016; Mason et al.
2018). The WHO recommendation is for all infected people to undertake antiretroviral treatment, which increases the probability to develop antiviral resistance and
this prospect demand constant monitoring to prevent HIV spread. Influenza virus
causes severe respiratory infections with annual epidemics, pandemics and endemic
infections due to its rapid and constant evolution (Lee and Ison 2012). Antiviruses
are associated with overall improvement and clearance of the disease; however,
resistance represents a significant health issue. Antiviral resistant strains are not
affected by drug therapy and retain replication and transmission fitness, being
responsible for severe outbreaks (Li et al. 2015).
4.6 Resistance in Parasites
Parasites cause numerous severe diseases that are normally entirely dependent on
antiparasitic drugs, due to the lack of economic incentives for research and development (Elsheikha et al. 2011; Secor et al. 2015). Antiparasitic resistance is linked
with biological characteristics of the pathogen that allows them to escape the drug
effect, which is a direct link with the pathogen host interactions. Furthermore,
M. Santana et al.