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Thursday, 1 October 2015

Can we protect the population from Dengue diseases by a recombinant live attenuated tetravalent dengue vaccine?

Rapid Responses Published in BMJ on 29 September 2015as Letter to Editor

Research News

Trial results raise hope for dengue fever vaccine

BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h141 (Published 09 January 2015) Cite this as: BMJ 2015;350:h141
Authors

Professor Pranab Kumar Bhattacharya MD (Calcutta Univ) FIC Path(India)  now Professor of Pathology at   Murshidabad District Medical College, West Bengal Behrampore Station Road ; Behrampore Court Murshidabad District West Bengal India          
       


Dengue is a mosquito (Ades aegypti) borne viral illness in the tropics and subtropics including in India. Approximately 350 million infections occur annually, of which 96 millions have clinical manifestations on infection with one of four serotypes (DENV 1,2,3.4) of the dengue virus. These may result in asymptomatic infections, mild non-specific viral flu-like illness, classic dengue (DHF), and severe dengue-manifested by plasma leakage, hemorrhage, hepatitis, renal failure, multi-organ failure and finally death. Severe dengue may also manifest with variant types of atypical signs [3] and symptoms, and when a second infection with different serotypes occurs, people are at increased risk of severe dengue.
The incidence of dengue is increasing globally and becoming endemic. Dengue is almost endemic throughout India. The incidence of Dengue in 2014 was 47,000 cases in China as of May 2015; Malaysia reported more cases compared with 2014, and as of June 2015 Brazil reported over a million suspected cases of Dengue. Resource poor health care systems as in India depend on simple to perform and easy to interpret laboratory tests for diagnosis. It is known that early diagnosis of DHF and DSS followed by supportive therapy reduces morbidity and mortality from Dengue. Thrombocytopenia, NS1 antigen IgM & IgG by immunochromatographic tests are the mainstay of diagnosis of Dengue infections in peripheral areas; most tertiary care laboratories have Mac Enzyme Linked immunosorbant Assay for qualitative and quantitative detection, and PCR based diagnostic modality are found in research laboratories and medical colleges of Kolkata metro cities. Ns1 has 30% positivity, becoming more positive when there is more viral load.
There is yet no available medicine or vaccine for treatment and protection against dengue fever. Prevention is protection from mosquito bites and vector control--ie, reducing A. aegypti larvae and pupae.
There is a tetravalent recombinant live attenuated Dengue vaccine (CYT-TDV) having CYD-1 through CYD-4 which requires 3 injections at 0, 6, and 12 months. The efficacy rate was 60.8 (95% CI) and in children 64.7% (95%CI 58.7-69.8). For serotype DNV-1 the efficacy rate was 50.3%, for serotype 2, 42.3%, serotype 3, 74% and serotype-4, 77.4%. This vaccine was tested in 20,869 children in Latin America, where dengue infection is epidemic in age group 9-16 years, during June 2011-March 2012. [1] During follow up for 2 years a total of 10,053 febrile episodes were reported, 8965 (89.2%) blood samples were collected within 5 days of fever and VCD was diagnosed only in 668 cases by Mac ELISA and RTPCR; efficacy was highest for DNEV-4 and lowest for DNV-2 and varied between countries tested in a phase 3 clinical trial. [1]
Adverse effects of CYT-TDV occurred in 121 children, including moderate asthma attacks, allergic urticaria after the 2nd injection, acute peripheral neuropathy after the 1st injection, viral meningitis, unspecified seizure. Efficacy of this vaccine in reducing hospitalization is 80.3% against severe dengue.
The dengue vaccine is facing numerous challenges, according to the authors.[1] Viable dengue vaccine must be capable of protecting against disease caused by any of the 4 serotypes. [2] Problems include the lack of a validated animal model of human dengue disease, [3] incomplete understanding of immunopathology, [4], the release of neutralizing antibodies assays, and cross reactivity among serotypes.
Now the questions remain can we protect our population fom Dengue diseases and can we reduce the population of patients with severe dengue with this CYT-TDV vaccine? Why the disparity in efficacy in antibody response and against the 4 serotypes?
References
1] Luis Villov, Gustavo Horacid. Dayan ; Jose Arrendondo Gurcia; Doris Maribel Revera etal “ Efficacy of a tetravalent Dengue vaccine in Children in Latim Ameria” N engl.j. med 2015; 372; 113-23
2] Professor Pranab Kumar Bhattacharya, Ritwik Bhattacharya, Rupak Bhattacharya Dahlia Mukherjee, UpasanaBhattacharya etal Plaque reduction neutralization test for dengue virus is more sensitive test but expensive Rapid Response Published BMJ 13 December 2009 of article Clinical Review Diagnosis and management of dengue http://www.bmj.com/content/339/bmj.b4338/rapid-responses
3] Professor DR. Pranab Kumar Bhattacharya, Dengue fever in Kolkata, West Bengal India with atypical presentations and its prevention Blogs of Professor(Dr.) Pranab Kumar Bhattacharyya MD(cal.Univ) Pathology; http://totallydrugresistanttbemergesinindia.blogspot.in/2013/04/dengue-f...
Competing interests: No competing interests

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