Introduction:Renal damage is a consequence of severe malaria, and is generally caused by sequestration of Plasmodium falciparum-infected erythrocytes in the renal microcirculation, which leads to obstruction, hypoxia, and ischemia. This triggers high mobility group box 1 (HMGB1) to send a danger signal through toll-like receptors 2 and 4. This signal up-regulates inducible nitric oxide (iNOS) and nitrotyrosine to re-perfuse the tissue, and also increases heat shock protein 70 (HSP70) expression. As no study has examined the involvement of intracellular secondary molecules in this setting, the present study compared the renal expressions of HSP70, HMGB1, iNOS, and nitrotyrosine between mice suffered from severe malaria and normal mice. Methods: C57BL/6 mice were divided into an infected group (intraperitoneal injection of 10 6 P. berghei ANKA) and a noninfected group. Renal damage was evaluated using hematoxylin eosin staining, and immunohistochemistry was used to evaluate the expressions of HSP70, HMGB1, iNOS, and nitrotyrosine. Results: Significant inter-group differences were observed in the renal expressions of HSP70, HMGB1, and iNOS (p=0.000, Mann-Whitney test), as well as nitrotyrosine (p=0.000, independent t test). The expressions of HSP70 and HMGB1 were strongly correlated (p=0.000, R=1.000). No correlations were observed between iNOS and HMGB, HMGB1 and nitrotyrosine, HSP70 and nitrotyrosine, or iNOS and nitrotyrosine. Conclusions: It appears that HMGB1, HSP70, iNOS, and nitrotyrosine play roles in the renal damage that is observed in mice with severe malaria. Only HSP70 expression is strongly correlated with the expression of HMGB1.

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Dengue viral infection is a global disease with a spectrum of clinical manifestations mild fever to severe disease both dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF is severe form of dengue fever (DF), which can be life-threatening. Climate changes is not the only factor that affects dengue transmission, but also globalization changes includes travel and trade. The pathogenesis of dengue infection is complex. The mechanism involved antibody-dependent enhancement, NS1 and its antibodies, T cells, and DENV genomics. There are several novel methods to detect the presence of dengue virus in the body of infected patients. These include ELISA-specific IgM and IgG detection, detection of monoclonal antibodies and mosquito cell strains, and PCR reverse transcriptase detection. Several trials found novel methods to predict the severity of dengue hemorrhagic fever earlier. These include platelet count, Aspartate aminotransferase / platelet count index (APRI) Index, serum chymase level, serum cytokine/chemokine profile, Tropomyosin-alpha 1 (TPM 1), Reticulocyte Production Index (RPI), and Immature Platelet Fraction (IPF). Several pharmacological therapies are known to have potential antidengue effect. Some of these are corticosteroids, antimalarial drugs, doxycycline and tetracycline, anticholesterol drugs, IVIG, celgosivir, balapiravir, pentoxifylline and calcium supplementation. Some natural products are known to have activity against Aedes aegypti through antiviral mechanisms, larvacidal activity, mosquitocidal, and mosquito repellants. It can be developed as the latest therapy of dengue hemorrhagic fever on the future. The objective of this paper is to provide new insight about the development of dengue hemorrhagic fever related to the history of its distribution, pathogenesis, and the latest developments related to detection methods, severity prediction methods, and the management of dengue hemorrhagic fever on the future. Keywords: globalization changes, novel detection methods, severity prediction methods, latest development in DHF therapy

Brotowali (BR) extract (Tinospora crispa) can be used as an antimalarial. Aim: to determine the effect of BR extract in histopathological and expression of NFκB in mice tubules infected by Plasmodium berghei treated by artesunate (AR). Method: we used 42 C57BL / 6J strain mice as experimental animals, which were randomly divided into 7 groups : negative control (NC), positive control (PC), treatment group consist of AR 32 mg/kb (group 1); BR 70 mg/kg (group 2), combination of AR+BR 50 mg/kg (group 3), AR+BR 60 mg/kg (group 4), and AR+BR 70 mg/kg (group 5). Histological examination (hematoxylin-eosin (HE) staining) and expression of NFKB (immunohistochemical staining) in the kidneys were performed on 7th and 14th. Result: compared to PC group, BR with doses of 70 mg until 14th day, improved the degree of tubular necrosis, interstitial fibrosis, tubular degeneration, and inflammatory cell infiltration (p <0.001) but did not reach NC group (p <0.05). The combination of AR+BR until the 14th day with dose of 50, 60, 70 mg all of dose improves significantly in-term of degree of tubular cell necrosis and inflammatory cell infiltration. The degree of interstitial fibrosis on 14th day only improved in group 4 and 5 (p<0.001 and p=0.003). The level of NF-kB expression on day 7 and day 14 was reduced in group 2, group 4, and group 5 compared to PC group. There was positive correlation on 7th and 14th between NF-kβ expression and tubular degeneration, tubular cell necrosis, inflammatory cell infiltration, and interstitial fibrosis. Conclusion: the combination of AR+BR extract can improve histopathological features and reduce NF-kβ expression in mice tubules infected by Plasmodium berghei with an optimal dose was 60 mg/day for 7-14 days or 70 mg for 7 days.

Penemuan kombinasi terapi baru untuk malaria dianggap penting karena kemampuan resistensi dari Plasmodium terhadap pengobatan terdahulu. Sebanyak 18 mencit dibagi ke dalam kelompok kontrol negatif, kontrol positif, kelompok artesunat, serta kelompok kombinasi artesunat dengan brotowali (dosis 50 mg, 60 mg dan 70 mg). Selain kontrol negatif, semua mencit diinfeksi Plasmodium berghei. Selanjutnya diamati derajat parasitemianya sampai hari ke-7, kemudian dilakukan pemeriksaaan imunohistokimia guna mengetahui ekspresi HSP70 dan endoglin pada otak mencit. Kombinasi artesunat injeksi dan ekstrak brotowali terbukti dapat menurunkan derajat parasitemia lebih baik dari pemberian terapi tunggal artesunat dan meningkatkan ekspresi HSP70 dan endoglin. Kesimpulannya, kombinasi terapi malaria menggunakan artesunat dan brotowali terbukti berpotensi sebagai terapi kombinasi yang efektif terhadap malaria karena mampu menurunkan derajat parasitemia sampai 0% dan meningkatkan ekspresi HSP70 dan endoglin pada otak mencit C57BL/6J secara signifikan.