Agnes Rengga Indrati

Platelet function alterations in dengue are associated with plasma leakage

Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengue, we measured platelet activation status and the response to the platelet agonist TRAP using flow cytometer-based assays. Patients were monitored daily for plasma leakage by ultrasonography. Acute dengue was associated with platelet activation with an increased expression of the activated fibrinogen receptor (αIIbβ3), the lysosomal marker CD63 and the alpha-granule marker CD62P (P-selectin). Upon maximal platelet activation by TRAP, platelet function defects were observed with a significantly reduced maximal activated αIIbβ3 and CD63 expression and reduced platelet-monocyte and platelet-neutrophil complexes. Patients in the lowest tertile of activated αIIbβ3 and CD63 expression had an odds ratio for plasma leakage of 5.2 (95% confidence interval [CI] 1.3-22.7) and 3.9 (95% CI 1.1-13.7), respectively, compared to the highest tertile. Platelet-derived serotonin has previously been related to plasma leakage and we found increased intra-platelet serotonin concentrations in our patients. In conclusion, platelet activation with platelet function alterations can be found in patients with acute dengue and this may contribute to dengue-associated plasma leakage.

Inverse Relationship of Serum Hepcidin Levels with CD4 Cell Counts in HIV-Infected Patients Selected from an Indonesian Prospective Cohort Study

Background Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB. Methods Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm3 (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin. Results A total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection. Conclusion Iron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.

Anemia and iron homeostasis in a cohort of HIV-infected patients in Indonesia

BackgroundAnemia is a common clinical finding in HIV-infected patients and iron deficiency or redistribution may contribute to the development of low hemoglobin levels. Iron overload is associated with a poor prognosis in HIV and Hepatitis C virus infections. Iron redistribution may be caused by inflammation but possibly also by hepatitis C co-infection. We examined the prevalence of anemia and its relation to mortality in a cohort of HIV patients in a setting where injecting drug use (IDU) is a main mode of HIV transmission, and measured serum ferritin and sTfR, in relation to anemia, inflammation, stage of HIV disease, ART and HCV infection.MethodsPatient characteristics, ART history and iron parameters were recorded from adult HIV patients presenting between September 2007 and August 2009 in the referral hospital for West Java, Indonesia. Kaplan-Meier estimates and Coxs regression were used to assess factors affecting survival. Logistic regression was used to identity parameters associated with high ferritin concentrations.ResultsAnemia was found in 49.6% of 611 ART-naïve patients, with mild (Hb 10.5 - 12.99 g/dL for men; and 10.5 - 11.99 g/dL for women) anemia in 62.0%, and moderate to severe anemia (Hb < 10.5 g/dL) in 38.0%. Anemia remained an independent factor associated with death, also after adjustment for CD4 count and ART (p = 0.008). Seroprevalence of HCV did not differ in patients with (56.9%) or without anemia (59.6%). Serum ferritin concentrations were elevated, especially in patients with anemia (p = 0.07) and/or low CD4 counts (p < 0.001), and were not related to hsCRP or HCV infection. Soluble TfR concentrations were low and not related to Hb, CD4, hsCRP or ART.ConclusionHIV-associated anemia is common among HIV-infected patients in Indonesia and strongly related to mortality. High ferritin with low sTfR levels suggest that iron redistribution and low erythropoietic activity, rather than iron deficiency, contribute to anemia. Serum ferritin and sTfR should be used cautiously to assess iron status in patients with advanced HIV infection.

T-CD4+ DAN PROFIL LIPID DI HIV

Human Immunodeficiency Virus (HIV) infection patients are often reported to be associated with changes of lipid metabolism. A previous study suspected that there was a correlation between low CD4+ T-lymphocyte counts with the lipid profile in HIV-infected patients. The objective of this study was to know the assessment of the lipid profile (total cholesterol, HDL, LDL and triglyceride) in patients with HIV infection and their correlation with CD4+ T-Lymphocyte count. This study was conducted at the Hasan Sadikin Hospital, Bandung using retrospective data, and analysis method as the study design. The study was performed on 402 HIV-infected patients. A significant difference was found in all lipid parameters between patients with and without ART (p<0.05). Weak correlations were found between CD4+ T-Lymphocyte with total cholesterol and HDL levels (r<0.04), and a very weak correlation as well with the LDL level (r<0.2). There was no correlation with the triglyceride levels (p=0.751). The lipid profile showed a weak correlation with CD4+ T-Lymphocyte, therefore, it can not be used as a parameter to know the severity of disease relating to the HIV infection. However, it can be useful for monitoring the metabolic effect of the given therapy, because there was a significant difference between those patients with and without ART.

Association of Colecalciferol, Ferritin, and Anemia among Pregnant Women: Result from Cohort Study on Vitamin D Status and Its Impact during Pregnancy and Childhood in Indonesia

Studies had shown that iron-cycling was disturbed by inflammatory process through the role of hepcidin. Pregnancy is characterized by shifts of interleukin. Our objective was to determine if 25(OH) vitamin D (colecalciferol) status was associated with ferritin, anemia, and its changes during pregnancy. Method. A cohort study was done in 4 cities in West Java, Indonesia, beginning in July 2016. Subjects were followed up until third trimester. Examinations included were maternal ferritin, colecalciferol, and haemoglobin level. Result. 191 (95.5%) subjects had low colecalciferol, and 151 (75.5%) among them were at deficient state. Anemia is found in 15 (7.5%) subjects, much lower than previous report. Proportion of anemia increased by trimester among women with colecalciferol deficiency. Ferritin status and prepregnancy body mass index in the first trimester were correlated with anemia (r = 0.147, p = 0.038 and r = −0.56, p = 0.03). Anemia in the second trimester was strongly correlated with anemia in the third trimester (r = 0.676, p < 0.01). Conclusion. Our study showed that the state of colecalciferol was not associated with either ferritin state or anemia, but proportion of anemia tends to increase by trimester in the colecalciferol deficient subjects.

Uji Diagnostik Pemeriksaan Kadar Transforming Growth Factor Beta 1 Cairan Pleura pada Pleuritis Tuberkulosis

Sulitnya penegakan diagnosis pleuritis tuberkulosis (TB) disebabkan oleh gambaran klinis yang tidak spesifik dan rendahnya sensitivitas pemeriksaan bakteriologik, akibat cairan pleura yang bersifat pausibasiler. Transforming growth factor beta 1 (TGF-β1) mampu menekan respons imun seluler terhadap M. tuberculosis, berperan dalam aktivasi TB laten, kerusakan jaringan, dan fibrosis. Penelitian ini bertujuan mengetahui peranan pemeriksaankadarTGF-β1 cairan pleura dalam penegakan diagnosis pleuritis TB. Penelitian ini adalah uji diagnostik, pengambilan data secara potong lintang. Bahan pemeriksaan berupa cairan pleura yang disimpan dalam ultra low freezer dari pasien rawat inap di RSUP Dr. Hasan Sadikin (RSHS) Bandung dan Rumah Sakit Paru Dr. H.A Rotinsulu Bandung periode Oktober 2014 Maret 2015. Total subjek penelitian 68, terdiri dari 17 pleuritis TB confirmed , 22 pleuritis TB probable, dan 29 pleuritis non TB.Kadar TGF-β1 cairan pleura pleuritis TB: 41,4 (10,4 19.481) pg/mL. Pemeriksaan kadar TGF-β1 menunjukkan sensitivitas 66,7%, spesifisitas 65,5% pada nilai cut-off >37 pg/mL. Sensitivitas pemeriksaan kadar TGF-β1 lebih tinggi bila dibanding dengan pemeriksaan bakteriologik. Hasil negatif pada pemeriksaan bakteriologik dari subjek pleuritis TB probable , 77,3% di antaranya memberikan hasil positif pada pemeriksaan kadar TGF-β1. Pemeriksaan ini dapat digunakan sebagai tambahan modalitas pemeriksaan laboratorium untuk mendiagnosis pleuritis TB, terutama bila didapatkan hasil negatif pada pemeriksaan bakteriologik, namun kecurigaan pleuritis TB sangat kuat. Kata kunci: Kadar TGF-β1, pemeriksaan bakteriologik, pleuritis TB Diagnostic Value of Pleural Fluid Transforming Growth Factor Beta 1 Level in Tuberculous Pleurisy Tuberculous(TB) pleurisy was difficult to be diagnosed as it has nonspecific symptoms and low sensitivity in bacteriological tests which are caused by paucibacillary of pleural fluid. Transforming Growth Factor Beta 1 (TGF-β1) could suppress the immune response to M. tuberculosis infection, activating latent TB infection that involves tissue damages and fibrosis. This study aimed to determine the role of pleural fluid TGF-β1 level in diagnosing TB pleurisy. This was a cross-sectional specific descriptive observational study involving a total subjects of 68 that consisted of 17 confirmed TB pleurisy, 22 probable TB pleurisy, and 29 non-TB pleurisy. Pleural fluid collected in October 2014 March 2015 from the subjects was stored in an ultra low freezer. The which.level of TGF-β1 in pleural fluid in TB pleurisy was 41,4(10,4 19.481) pg/mL. Pleural fluid TGF-β1 level showed a sensitivity of 66,7%, specificity of 65,5% and a cut-off value >37pg/mL. The sensitivity level of pleural fluid TGF-β1 was higher than that of the bacteriological test. Pleural fluid TGF-β1 level can be used as an adjunct modality of laboratory test for diagnosing TB pleurisy, especially for patient with high suspiscion of TB pleurisy but yield negative result in the bacteriological test. Key words: Bacteriological tests, TB pleurisy, TGF-β1 levels

Validitas Pemeriksaan Antigen P24 HIV Metode Rapid Immunochromatography Terhadap Viral Load RNA HIV Metode PCR

Latar belakang. Bayi yang dilahirkan oleh ibu pengidap HIV/AIDS akan mengandung antibodi HIV ibu dalam darahnya, terdeteksi sampai usia 18 bulan. Pemeriksaan virologi (RNA/DNA HIV dan antigen p24 HIV) sesuai standar WHO adalah pemeriksaan HIV pada bayi dan anak <18 bulan terlahir dari ibu HIV/ AIDS. Tujuan. Mengetahui validitas pemeriksaan antigen p24 HIV metode rapid immunochromatogrpahy terhadap viral load RNA HIV metode PCR pada bayi dan anak <18 bulan dengan ibu HIV/AIDS. Metode. Penelitian dilakukan di RSUP dr. Hasan Sadikin Bandung dan RSK Dharmais Jakarta, periode April-September 2013. Subjek penelitian adalah 72 bayi dan anak berusia <18 bulan yang lahir dari ibu HIV/AIDS. Hasil . Sembilan (12,5%) dari 72 subjek penelitian terdeteksi HIV pada pemeriksaan viral load RNA HIV, 2 (22,2%) di antaranya positif pada pemeriksaan antigen p24 HIV. Didapatkan sensitivitas 22,2%, spesifisitas 100%, dan akurasi 90,3%. Kesimpulan. Pemeriksaan antigen p24 HIV metode rapid immunochromatography memiliki spesifisitas tinggi, sensitivitas rendah sehingga pemeriksaan antigen p24 HIV metode rapid immunohromatography ini dapat digunakan sebagai alat diagnostik.