***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: INTRODUCTION Dengue is a rapidly exp and ing global health problem . Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide . The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk . The management of dengue virus infection is essentially supportive and symptomatic and no specific treatment is available for increasing the fallen platelets , which have a significant role in causing the mortality of dengue patient . This study was conducted to evaluate the platelet increasing efficacy of Carica papaya leaf extract ( CPLE ) in patients with dengue fever ( DF ) . AIM The administration of Carica papaya leaf extract should significantly increase the platelet count in cases of thrombocytopenia associated with dengue , preventing the patient to go in DHF or DSS conditions . MATERIAL AND METHODS A Multi-centric , Double blind , Placebo controlled , R and omized , prospect i ve study was conducted in 300 patients across 5 centres ' , to evaluate the Efficacy and Safety of Carica Papaya Leaf Extract , as empirical therapy for thrombocytopenia associated with dengue fever . The subjects were r and omized into two groups , as control and intervention group . Both the groups were managed by the st and ard management guidelines for dengue except steroid administration . In addition to this , the intervention group received CPLE tablet three times daily for five days . All of them were followed daily with platelet monitoring . This study has been registered in the clinical trial registry-India ( CTRI Registration number : CTRI/2015/05/005806 ) . RESULTS The results indicate that CPLE had significant increase(p < 0.01 ) in the platelet count over the therapy duration , in dengue fever patients , confirming CPLE accelerates the increase in platelet count compared to the control group . There were few adverse events related to GI disturbance like nausea and vomiting which were similar in both groups . CONCLUSIONS Thus this study concluded that Carica papaya leaf extract ( CPLE ) does significantly increase the platelet count in patients with thrombocytopenia associated with dengue with fewer side effects and good tolerability Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The study was conducted to investigate the platelet increasing property of Carica papaya leaves juice ( CPLJ ) in patients with dengue fever ( DF ) . An open labeled r and omized controlled trial was carried out on 228 patients with DF and dengue haemorrhagic fever ( DHF ) . Approximately half the patients received the juice , for 3 consecutive days while the others remained as controls and received the st and ard management . Their full blood count was monitored 8 hours for 48 hours . Gene expression studies were conducted on the ALOX 12 and PTAFR genes . The mean increase in platelet counts were compared in both groups using repeated measure ANCOVA . There was a significant increase in mean platelet count observed in the intervention group ( P < 0.001 ) but not in the control group 40 hours since the first dose of CPLJ . Comparison of mean platelet count between intervention and control group showed that mean platelet count in intervention group was significantly higher than control group after 40 and 48 hours of admission ( P < 0.01 ) . The ALOX 12 ( FC = 15.00 ) and PTAFR ( FC = 13.42 ) genes were highly expressed among those on the juice . It was concluded that CPLJ does significantly increase the platelet count in patients with DF and DHF OBJECTIVE Thrombocytopenia in dengue fever is a common and serious complication . However , no specific treatment is available for dengue fever induced thrombocytopenia . In few countries ( Pakistan , Malaysia , Sri Lanka and other Asian countries ) the leaf extract of Carica papaya has been effectively used for thrombocytopenia . So , the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients . METHODS All participants were r and omised into two groups , study group and control group ; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days . The controls were given only routine supportive treatment .  Daily complete blood counts , platelet counts and haematocrit level , liver function test , renal function test of both groups were observed . RESULTS On the first day platelet count of study group and control group was ( 59.82±18.63 , 61.06±20.03 thous and s , p value 0.36 ) . On the 2nd day platelet count of both study and control groups was not significantly different ( 61.67±19.46 and 59.93±19.52 thous and s , p value 0.20 ) but on 3rd day platelet count of study group was significantly higher than control group ( 82.96±16.72 , 66.45±17.36 thous and s , p value < 0.01 ) . On 4th and 5th day platelet count of study group ( 122.43±19.36 and 112.47±17.49 thous and s respectively ) was also significantly higher than the control group ( 88.75±21.65 and 102.59±19.35 thous and s ) ( p value < 0.01 ) . On 7th day platelet count of study group and control group were not significantly different ( 124.47±12.35 and 122.46±19.76 thous and s respectively , p value 0.08 ) . Average hospitalization period of study group v/s control group was 3.65±0.97 v/s 5.42±0.98 days ( p value < 0.01 ) . Average platelet transfusion requirement in study group was significantly less than control group ( 0.685 units per patient v/s 1.19 units per patient ) ( p value < 0.01 ) . CONCLUSIONS It is concluded that Carica papaya leaf extract increases the platelet count in dengue fever without any side effect and prevents the complication of thrombocytopenia . So , it can be used in dengue fever with thrombocytopenia patients BACKGROUND A c and i date tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries . We report the results of long-term follow-up interim analyses and integrated efficacy analyses . METHODS We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials , CYD14 and CYD15 , and a phase 2b trial , CYD23/57 . We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15 . RESULTS Follow-up data were available for 10,165 of 10,275 participants ( 99 % ) in CYD14  and 19,898 of 20,869 participants ( 95 % ) in CYD15 . Data were available for 3203 of the 4002 participants ( 80 % ) in the CYD23 trial included in CYD57 . During year 3 in the CYD14 , CYD15 , and CYD57 trials combined , hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group . Pooled relative risks of hospitalization for dengue were 0.84 ( 95 % confidence interval [ CI ] , 0.56 to 1.24 ) among all participants , 1.58 ( 95 % CI , 0.83 to 3.02 ) among those under the age of 9 years , and 0.50 ( 95 % CI , 0.29 to 0.86 ) among those 9 years of age or older . During year 3 , hospitalization for severe dengue , as defined by the independent data monitoring committee criteria , occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group . Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3 % ( 95 % CI , 55.7 to 64.5 ) for all participants , 65.6 % ( 95 % CI , 60.7 to 69.9 ) for those 9 years of age or older , and 44.6 % ( 95 % CI , 31.6 to 55.0 ) for those younger than 9 years of age . CONCLUSIONS Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up , the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group . ( Funded by Sanofi Pasteur ; Clinical Trials.gov numbers , NCT00842530 , NCT01983553 , NCT01373281 , and NCT01374516 . ) Objective Thrombocytopenia in dengue fever ( DF ) is a well-known complication in both adults and pediatric subjects . Management of DF primarily includes symptomatic and intensive supportive care . There are studies available on the efficacy and safety of Carica papaya leaf extract ( CPLE ) in adult patients with DF . However , there are no published studies available on the efficacy and safety of CPLE in the pediatric age group . Hence , this study was conducted . Methodology A prospect i ve , open-label , r and omized controlled study was conducted in subjects aged between 1 and 12 years having thrombocytopenia associated with DF ( NS-1 antigen positive ) or dengue hemorrhagic fever ( DHF ) grade s I and II . All participants were r and omized into the intervention group ( n = 147 , CPLE syrup + st and ard therapy ) and the control group ( n=147 , received only st and ard therapy ) . All subjects were followed up daily for 5 days with monitoring of blood counts . Results A total of 285 subjects were finally evaluated for efficacy , and nine dropped out ( seven in the control group and two in the intervention group ) . However , all 294 subjects were evaluated for safety . CPLE ( Caripill ) syrup increased the platelet count significantly compared to the control group ( P<0.05 ) . In the intervention group , the platelet count increased from day 3 onward : platelet count on day 3 ( mean platelet count = 89,739.31 , P=0.030 ) , day 4 ( mean platelet count = 120,788.96 , P=0.019 ) , and day 5 ( mean platelet count = 168,922.75 P=0.023 ) . Two children complained of nausea in the intervention group . Overall , Caripill syrup was well tolerated . Conclusion CPLE syrup significantly increases the  platelet count in pediatric DF patients and is well tolerated 
    Output:
    
Conclusions The clinical value of improvement in platelet count or early discharge is unclear in the absence of more robust indicators of favourable clinical outcome .
Current evidence is insufficient to comment on the role of CP extract in dengue .