Editorial
Advanced Molecular Techniques and Diagnosis of Febrile Illness
The application of
multiplex real-time (Reverse Transcriptase - RT) polymerase chain reaction
(PCR) in routine diagnosis of infectious diseases is unavoidable. In addition,
the technique urgently might be an alternative tool in the diagnosis of febrile
illnesses caused by many different kinds of etiologies including bacteria,
viruses, and parasites. In Nepal, arboviral infections mainly dengue and
chikungunya, scrub typhus, and leptospirosis are considered as major emerging
infections in the last two decades. In addition, these infections are the most
predominant neglected tropical diseases in tropical and subtropical regions
where more than 51% of the total population in Nepal is living. A few of these
infections are responsible for chronic infection causing a high morbidity rate.
A study reported up to 40% of acute chikungunya infections may lead to chronic
infections. Similarly, secondary infections can be more severe among flaviviruses
such as Dengue and Zika due to antibody-dependent enhancement. Unlike the diagnosis of other neglected
tropical diseases, the differential diagnosis of arboviral infections is quite
difficult as they all present similar clinical features, especially in Dengue Chikungunya
and Zika viral infections. However, few
studies showed a significant difference in clinical manifestations in specific
viral infections as well. Some clinical features are significantly associated
with bacterial and viral infections. High-grade fevers with longer mean duration of fever, severe musculoskeletal pain, central
nervous system (CNS) related symptoms (such as altered mentation, confusion, and
loss of consciousness), and elevated liver enzymes such as aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) are highly associated with viral
infections as compared to bacterial infections Finding such clinical
manifestations may be helpful in the differential diagnosis of febrile
illnesses as the point of care for future aspects. The other means of diagnosis
commonly used in hospital settings of Nepal are serological methods including
routinely used rapid diagnostic tests (RDTs) and Enzyme-Linked Immunosorbent
Assay (ELISA). However, these methods have a few drawbacks including
cross-reactivity, low sensitivity, and specificity making misdiagnosis of
infections. Moreover, these methods are not applicable to early diagnosis of
infections. An alternative to serological methods is molecular methods which
are currently not available for diagnostic purposes in most hospitals and health
care centers. Although the conventional PCR method has high sensitivity and
specificity, it may take a longer time and detect only a particular pathogen at a
time. The molecular method mainly real-time (RT) PCR has many advantages over
other conventional methods because of which the applications of this technique
for the diagnosis of infections or illnesses can’t be avoided. The techniques have
already been introduced in the diagnosis of respiratory viral pathogens to diagnose flu-like syndromes in very few hospital settings. However, many tertiary care
hospitals in Nepal have not been facilitated to use this technique in routine
diagnosis. In addition, febrile illnesses in tropical and subtropical regions
are the most undiagnosed illnesses. As a consequence, a number of patients have
been suffering from chronic bacterial and viral infections. Real-time (RT) PCR
is the only ultimate tool in the diagnosis of such illnesses. The method
has not only higher sensitivity (> 95%) and specificity (100%) but also
detects the possible pathogens as early as the first day of onset of illness.
Because of good reproducibility, sensitivity, and specificity, this method is
considered a gold standard method for the detection of RNA viruses in
clinical specimens. In addition, the multiplex real-time (RT) PCR detects
multiple pathogens in a single run making it more economical and less time-consuming in the hospital settings of low and middle-income countries. It seems
to be affordable to common people as well. While talking about the current situation in
Nepal, several tertiary care hospitals have upgraded to real-time PCR for
diagnosis of COVID-19 during the pandemic. Hence, a similar facility can be
extended to detect other pathogens in neglected tropical diseases and
febrile illnesses in routine diagnosis.
Komal Raj
Rijal, Editor in Chief
Upendra Thapa
Shrestha, Associate Editor
DOI: https://doi.org/10.3126/tujm.v10i1.60644
