Thrombocytopenia and platelet dysfunction are commonly observed in patients with dengue virus (DENV) infection and may contribute to complications such as bleeding and plasma leakage. The etiology of dengue-associated thrombocytopenia is multifactorial and includes increased platelet clearance. The binding of the coagulation protein von Willebrand factor (VWF) to the platelet membrane and removal of sialic acid (desialylation) are two well-known mechanisms of platelet clearance, but whether these conditions also contribute to thrombocytopenia in dengue infection is unknown. In two observational cohort studies in Bandung and Jepara, Indonesia, we show that adult patients with dengue not only had higher plasma concentrations of plasma VWF antigen and active VWF, but that circulating platelets had also bound more VWF to their membrane. The amount of platelet-VWF binding correlated well with platelet count. Furthermore, sialic acid levels in dengue patients were significantly reduced as assessed by the binding of Sambucus nigra lectin (SNA) and Maackia amurensis lectin II (MAL-II) to platelets. Sialic acid on the platelet membrane is neuraminidase-labile, but dengue virus has no known neuraminidase activity. Indeed, no detectable activity of neuraminidase was present in plasma of dengue patients and no desialylation was found of plasma transferrin. Platelet sialylation was also not altered by in vitro exposure of platelets to DENV nonstructural protein 1 or cultured DENV. In contrast, induction of binding of VWF to glycoprotein 1b on platelets using the VWF-activating protein ristocetin resulted in the removal of platelet sialic acid by translocation of platelet neuraminidase to the platelet surface. The neuraminidase inhibitor oseltamivir reduced VWF-induced platelet desialylation. Our data demonstrate that excessive binding of VWF to platelets in dengue results in neuraminidase-mediated platelet desialylation and platelet clearance. Oseltamivir might be a novel treatment option for severe thrombocytopenia in dengue infection.
Background: Morbidity and mortality of HIV/AIDS infections is still high and as a global health problem particularly in Low-Middle Income Countries (LMICs). Indonesia ranks third in Asia Pacific in increasing HIV infection. A Study on risk factors for mortality in HIV/AIDS patients in Dr. Kariadi General Hospital has never been conducted. This study analyzed the risk factors for mortality among HIV/AIDS patients.Methods: Case control study, data from medical records of inpatients and outpatients in Dr. Kariadi General Hospital from January 2015 to December 2017.Results: Study subject: Two hundred and ten HIV/AIDS patients, were included; 105 (56.75%) as cases and 105 (9.65%) control patients. The significant risk factors for mortality were as follow: male sex (p = 0.030); age ≥ 45 years (p = 0.035); non compliance to treatment (p = 0,000); WHO clinical stage III and IV (p = 0,000); co-infection of pulmonary tuberculosis (p = 0,000); CD4 cell count < 200 cells/mm3 (p = 0,000); eGFR < 60 mL/minute/1.72 m2 (p = 0.001) and Haemoglobin level < 10 g/dL (p = 0.008). The non-significant risk factors for mortality were as follow: level of education (p = 0.650); Hepatitis B co-infection (p = 0.153) and Hepatitis C co-infection (p = 0.506). The most important risk factors for mortality in this study in were non compliance to treatment (p = 0.003; OR = 3.285) and CD4 count < 200 cells/mm3 (p = 0.014; OR = 5.480).Conclusion: In this study, the risk factors for mortality in HIV/AIDS patients were male sex; age ≥ 45 years; non compliance to treatment; WHO clinical stage III and IV; co-infection of pulmonary tuberculosis, CD4 count < 200 cells/mm3; eGFR < 60 mL/minute/1.72 m2 and Hb level < 10 g/dL. The most important risk factors for mortality were non compliance to treatment and CD4 count < 200 cells / mm3.
Purpose Indonesia, a high populous and the second-highest country in epidemicity of hepatitis B in South-East Asia require maintaining its capacity of monovalent hepatitis B production to keep up with both the national immunization program and global needs. To keep the sustainability of the vaccine, a new bulk is needed to be made available. This study aims to evaluate the immunogenicity and safety of Bio Farma newly formulated recombinant hepatitis B vaccines, which came from different sources of bulk, compared to the already registered hepatitis B vaccine. Materials and Methods An experimental, randomized, double-blind, cohort intervention phase II clinical trial was conducted on three recombinant hepatitis B vaccines from different bulk sources, with Bio Farma registered hepatitis B vaccine as the control group. A total of 536 participants around age 10 to 40 years old were thricely vaccinated with twice serological assessments. The subject’s safety was monitored for 28 days after each vaccination. Results Of 536 enrolled participants, 521 finished the vaccination and serology assessments. The investigational products were proven not to be inferior to the control. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the investigational products and control. No serious adverse event was found to be related to the investigational vaccines. Conclusion Investigational vaccines are shown to be equally immunogenic and safe as the control vaccine.
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