Phases and Outcomes of Dengue Fever
Dengue fever is one of the most common mosquito-borne viral diseases, caused by dengue virus. It is the most rapidly spreading mosquito borne viral disease in the word. As the symptoms of the disease resemble the common flu symptoms, people often neglect the fever and others signs and symptoms, which may lead to serious health issues (Simmons et al., 2015). For identifying the disease, the laboratory tests of patient’s blood samples are mandatory, which are demonstrated in the following paragraphs.
The pre-pathogenesis is referred to the phase of the disease, which is also known as incubation period, the period between the exposure of the infection to the host body, i.e. the mosquito bite in case of dengue and the onset of disease symptoms like fever, rashes, headache, pain in joints etc. In case of dengue, the incubation period or pre-pathogenesis stage is 3 to 14 days. The disease is transmitted through the bite of infected Aedes aegypti mosquito (Martina, 2014). The infected mosquito, when bites a healthy human host, the virus are injected into the blood through the injury site and the viral replication starts in WBCs. The infection related symptoms are absent during this phase, until the viral production is enough to fully activate the host immune system.
During the pre-pathogenesis stage, the biological function of the immune system is changed. During this period, the viral replication takes place in the WBC, which, upon reaching a standard number, i.e. viral load, triggers the onset of the disease by activating the immune system (OhAinle & Harris, 2014). For instance, as the virus enters WBCs, they activate the signalling procedures by the WBCs, which in turn change the cytokines and interferon secretion patterns.
However, no significant symptoms or changes are detected, through which the pre-pathogenesis stage can be identified in a human host.
During the pre-pathogenesis phase, no significant symptoms arrive, in case of dengue. The pre-pathogenesis phase is the period between the mosquito bite and the arrival of symptoms (Hunsperger et al., 2014). Thus, during this phase, the individual experiences no such symptoms to detect the disease.
Dengue infection usually leads to fever, nausea, headache, joint pain, rash development in acute phase. However, in severe cases, it can lead to fatal consequences. The disease outcomes can be divided into three phases, i.e. the febrile phase, the critical phase and the recovery phase. During the febrile phase, the patient will suffer from high fever, headache, diarrhoea and muscle pain. However, if not left untreated, the critical phase begins with low blood pressure, pleural effusion ascites, gastrointestinal bleeding and haemorrhage. Haemorrhage is the outcomes of severe types of dengue, other than dengue fever, which are dengue haemorrhagic syndrome and dengue shock syndrome (Hunsperger et al., 2016). These are the outcomes of secondary infection or plasma leakage, leading to organ dysfunction. Without treatment for ceasing the fluid loss or haemorrhage and reduced pressure can lead to fatal consequences. However, with proper care and maintenance of fluid balance, the patient will progress towards recovery phase and will recover within 7-10 days.
Treatment and Management Options
There are no specific antiviral drugs for dengue infection; however, it is crucial to maintain the fluid balance, as there is rapid fluid loss during the disease period. The treatment and management types and time depends upon the patient’s status. For instance, whether the patient is able to intake adequate fluid and passing urine, if not, the oral rehydration therapy is administered, during the critical phase of pathogenesis. The patients with severe dengue type, like haemorrhage and extremely low blood pressure, are taken care into intensive care unit, which include nasogastric intubation, intramuscular injections (Ferraz et al., 2013). In patients, with significantly low level of platelets and hemocrit, blood transfusion is initiated, with packed red blood cells or whole blood or platelets. On the other hand, during the recovery phase, IV fluid is discontinued, as the patient becomes able to retain fluid. During the progression with stable vital signs, loop diuretics like furosemide can be administered for eliminating excess fluid build up in body.
There are several laboratory test developed for identifying the dengue infection in patient’s blood. There are mainly two key types of laboratory diagnosis methods for dengue infection.
Detection of Dengue virus (Direct method)
- Isolation of virus by culture
- Detection of viral nucleic acid by PCR
- Detection of viral antigen (NS1) by ELISA
The specificity and sensitivity is higher in direct methods, compared to the indirect methods. For instance, detection of viral antigen from the patient’s blood sample is more confident result than detecting antibody. However, in case of antigen detection, sometimes, during the first few days of pathogenesis phase, the antigen is not detected in blood, which in turn gives negative results. In this case, in order to confirm the infection, in later phase of pathogenesis, after viral clearance, serology testing gives the positive results, confirming the disease (Carter et al., 2015). However, detection of viral nucleic acid via PCR and virus isolation through culture gives more sensitive result than serology testing.
- Detection of viral antigen (NS1) by ELISA- In case of ELISA, an index value is calculated by dividing the sample absorbance by cut off value. The index value, if <9, it is negative; if >11, it is positive
- Detection of Anti-Dengue antibody IgM by ELISA- Similar to the previous one, the index value, if <1, it is positive and if >1, it is negative (Welch, Chang & Litwin, 2014)
- In case of virus isolation in culture, the number of plaques, for determining a positive result would depend upon the concentration of virus inoculum plated
- In case of nucleic acid identification by PCR, the similarity between the sample’s nucleic acid and the template dengue antigen’s nucleic acid will determine the presence of virus
For each laboratory tests of dengue, there is an optimum time, when the laboratory tests gives the valid and most appropriate results. For instance, it case of Dengue NS1 antigen detection, within 1 to 5 days of the disease onset, the test will give valid results, as the viral antigen remains viable till 5 days of disease onset and then removed by the immune cells, from the blood. On the other hand, when the patient’s blood sample is tested within 5-7 days of disease symptoms onset, the detection of IgM antibody by ELISA is recommended, as during this period of pathogenesis, immune system produces a large amount of IgM antibody against the dengue antigen (Carter et al., 2015). If the blood test is done after 7 days, in serology laboratory testing, IgG antibody detection is suggested along with the IgM, because, after 7-10 days, the amount of IgM antibody reduces significantly and replaced totally by IgG, which remains in the blood for months. In case of viral isolation from culture or nucleic acid identification via PCR, sample within 1 to 5 days of the onset of the disease symptoms are tested, it is because, after 5 days, the immune system clears the viral antigens from the blood.
Based on the analysis, it can be interpreted that the within all the laboratory diagnosis tests for identifying dengue pathogen, serology testing of antibody IgM and IgG are the best, as these are cheap and provides reliable results throughout the pathogenesis phase. Although, the best result is provided by PCR, i.e. nucleic acid identification, but the process is expensive (Hunsperger et al., 2016).
Conclusion
In conclusion, it can be said that Dengue one of the most common viral disease that needs special care during the pathogenesis. Here, the pre-pathogenesis stage has been demonstrated. Several specific tests are there for identifying the disease; however, the best test is recommended to the patient, based on the status of the patient and period of the onset of disease.
Reference List
Carter, M. J., Emary, K. R., Moore, C. E., Parry, C. M., Sona, S., Putchhat, H., … & Day, N. P. (2015). Rapid diagnostic tests for dengue virus infection in febrile Cambodian children: diagnostic accuracy and incorporation into diagnostic algorithms. PLoS neglected tropical diseases, 9(2), e0003424.
Ferraz, F. O., Bomfim, M. R. Q., Totola, A. H., Ávila, T. V., Cisalpino, D., Pessanha, J. E. M., … & Teixeira, M. M. (2013). Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil. Journal of Clinical Virology, 58(1), 41-46.
Hunsperger, E. A., Muñoz-Jordán, J., Beltran, M., Colón, C., Carrión, J., Vazquez, J., … & Margolis, H. S. (2016). Performance of dengue diagnostic tests in a single-specimen diagnostic algorithm. The Journal of infectious diseases, 214(6), 836-844.
Hunsperger, E. A., Yoksan, S., Buchy, P., Nguyen, V. C., Sekaran, S. D., Enria, D. A., … & Guzman, M. G. (2014). Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody. PLoS neglected tropical diseases, 8(10), e3171.
Martina, B. E. (2014). Dengue pathogenesis: a disease driven by the host response. Science progress, 97(3), 197-214.
OhAinle, M., & Harris, E. (2014). 12 Dengue Pathogenesis: Viral Factors. Dengue and dengue hemorrhagic fever, 229.
Simmons, C. P., McPherson, K., Chau, N. V. V., Tam, D. H., Young, P., Mackenzie, J., & Wills, B. (2015). Recent advances in dengue pathogenesis and clinical management. Vaccine, 33(50), 7061-7068.
Welch, R. J., Chang, G. J. J., & Litwin, C. M. (2014). Comparison of a commercial dengue IgM capture ELISA with dengue antigen focus reduction microneutralization test and the Centers for Disease Control dengue IgM capture-ELISA. Journal of virological methods, 195, 247-249.
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