Development of highly efficient methods for comprehensive pathogen detection using next generation sequencing

概要

Challenges in diagnosing febrile illness
In the low resources area of the tropics, one of the most common symptoms reported by
a person seeking medical care is fever (1). Fever can be accompanied by other signs and
symptoms which can highlight the localization of the inflammation/infection, or it can
occur in isolation. Though these signs and symptoms can aid in diagnosis, the causal
pathogen remains difficult to be differentiated without further testing. On the other hand,
a fever without any localization features (referred to as undifferentiated fever) is
challenging for a health care worker to diagnose, mainly due to combination of nonspecific symptoms during acute phase and the wide range of the aetiologies, that span
across both infectious and non-infectious aetiology (1).
In the places where malaria is endemic, occurrence of fever is highly associated
with malaria. However, development and deployment of rapid diagnostic tests (RDTs) to
detect antigen originating from Plasmodium spp., the cause of malaria, has improved the
diagnosis and therapy for malaria (2). Decreased incidence of malarial fever has given
more space in the spotlight for other infectious aetiologies. In the past years, less common
aetiologies of fever, including Leptospira spp., Rickettsia spp., hepatitis B virus,
enterovirus, and cytomegalovirus have been reported (3,4). In the context of therapeutic
management, deployment of malaria RDT has led to a more rational usage of antimalarial
drugs in sub-Saharan Africa, but unsurprisingly it has also led to excessive prescription
of antibacterial drugs (2). Unfortunately, self-limited viral infections (particularly
respiratory viruses) were reported to have a high prevalence in primary care, suggesting
that the antibacterial drugs might be inappropriately prescribed (2). Tests such as RDT
(antigen or serology) are only currently available for several pathogens (Plasmodium spp.
and dengue virus, among others) and sophisticated tests, such as culture and polymerase
chain reaction (PCR), have limited availability. In addition, serology based RDTs have
several limitations such as risk of cross-reactivity in closely-related pathogens (i.e. crossreactivity between flaviviruses (5,6)), requiring extensive effort in development, and low
levels of immunoglobulin during the early course of an infectious disease. ...

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