Ebola virus disease: Recent advancs in diagnostics and therapeutics Supriya Jagga, Ashish Ranjan Sharma, Chiranjib Chakraborty, Sang-Soo Lee Asian Pacific Journal of Tropical Medicine 2019 12(9):385-395 Ebola virus disease (EVD) is associated with haemorrhagic fever in humans and nonhuman primates, with a high rate of fatality (up to 90%). Some outbreaks in human history have proven the lethality of EVD. The recent epidemic of 2014 and 2015 in West Africa was the deadliest of all time (11 284 deaths). To understand the transmission dynamics, we have reviewed the epidemiology of EVD to date. The absence of any licensed vaccines or approved drugs against Ebola virus (EBOV) further highlights the severity and crisis level of EVD. Some organizations (public and private) are making considerable efforts to develop novel therapeutic approaches or vaccines to contain the outbreak of EBOV shortly. Here, we summarized the various potential drugs and vaccines (undergoing multiple phases of clinical trials) that have arisen as an alternative against EBOV, and we highlighted the numerous issues and limitations hindering this process. Alternatively, an increasing focus on strengthening the medical and civic health structure could provide speedy benefits in containing the spread of EVD, as well as offer a resilient foundation for the deployment of novel drugs and vaccines to the affected countries, once such drugs and vaccines become available.

Long-term safety follow-up of children from a randomized—controlled phase II b proof—of—concept efficacy study of the live, attenuated, tetravalent dengue vaccine (CYD—TDV) in Thailand Kriengsak Limkittikul, Weerawan Hattasingh, Danaya Chansinghakul, Arunee Sabchareon, Wut Dulyachai, Carina Frago, T Anh Wartel, Edith Langevin, Sophia Gailhardou, Alain Bouckenooghe Asian Pacific Journal of Tropical Medicine 2019 12(9):396-403 Objective: To investigate the long-term safety of a tetravalent dengue vaccine (CYD-TDV) in children in a phase Π b follow-up study in Thailand. Methods: In the phase Π b study, children aged 4-11 years were randomized (2:1) to receive three injections of CYD-TDV or serve as control at 6-month intervals, with 25 months’ active follow-up (active phase). This study was an additional four-year passive surveillance for hospitalized virologically-confirmed dengue (VCD; hospital phase). Cases of hospitalized VCD, severe hospitalized VCD, vaccine-related serious adverse events, and deaths were reported for the total population, with post-hoc analyses by enrollment age (<9 and years). Results: Of 3 997 participants receiving injection, 80.1% were recruited to the hospital phase [2 131 (CYD-TDV); 1 072 (control)]. Eighty-five hospitalized VCD cases were reported in the CYD-TDV group and 46 in the control group during the four-year hospital phase [relative risk (RR): 0.93, 95% confidence interval (CI): 0.64-1.36]. The RR over six years of follow-up was 0.77 (95% CI: 0.57-1.05). In those aged ≥9 years, the cumulative RRs in the active phase, hospital phase, and entire six years were 0.28 (95% CI: 0.08-0.81), 0.51 (95% CI: 0.25-1.05), and 0.42 (95% CI: 0.24-0.75), respectively. In the overall population, there were ten severe hospitalized VCD cases in the CYD-TDV group and five in the control group over six years (RR: 1.00, 95% CI: 0.31-3.75). Conclusions: Over six years of follow-up, in children aged ≥9 years, CYD-TDV administration is associated with a reduced risk of hospitalized VCD.

Association between measles antibodies in vaccinated and naturally infected mothers with protective antibodies and the occurrence of measles in their children: A cross-sectional study in the Bavi district of Hanoi Cam Nhat Nguyen, Quynh Ngoc Nguyen, Than Huu Dao, Le Thi Quynh Mai Asian Pacific Journal of Tropical Medicine 2019 12(9):404-408 Objective: To determine the concentration and rate of decay of maternal IgG antibodies against measles prevalence in infants of vaccinated or naturally infected mothers and study initial measles immunization occurs in nine-month-old children. Methods: In total, 401 pregnant women and the same number of their subsequent newborns were recruited in the Bavi district of Hanoi in 2016-2017; they were divided into two groups: Older women (born before 1985, n=201) and younger women (born after 1990, n=200). Samples were collected at five time-points; week 36 of pregnancy, birth (cord), and 3, 6, and 9 months after birth. Measles-specific IgG antibody levels were recorded. Results: In total, 77.06% of the 401 pregnant women were seropositive for measles-specific IgG antibodies. A significantly greater proportion of mothers aged 30 and older (88.06%) and their newborn (93.53%) were seropositive compared to the mothers aged 25 and younger (66.00%), and their newborn (72.00%) (P<0.001). The infants of older mothers had significantly higher geometric mean titres (GMT) of measles IgG antibodies than the infants of younger mothers (P<0.001) at all time-points of the study period. The proportion of measles IgG antibodies together with GMT decreased from 82.97% (506.96) at the age of three months to 23.19% (45.22) at the age of nine months. Conclusions: This study provides a profile of maternal antibodies against measles in Vietnamese infants and investigates the early susceptibility to measles in both the infants of vaccinated mothers and mothers with naturally acquired immunity. These data suggest that determining the appropriate age for measles vaccination is paramount for the elimination of measles in Vietnam.

Chemoprotective activity of aqueous leaf extract of Acalypha wilkesiana against cyclophosphamide-induced toxicity in rats Chinedu P Anokwuru, God’swill N Anyasor, Olutayo S Shokunbi, Babajide Sopekan, Oyindamola K Osinuga, Olusola E Afolabi, Olamide B Arojojoye, Chibundu N Ezekiel, Isaiah DI. Ramaite Asian Pacific Journal of Tropical Medicine 2019 12(9):409-415 Objective: To investigate the protective effect of aqueous leaf extract of Acalypha (A.) wilkesiana Muell. Arg (Euphorbiaceae) against cyclophosphamide-induced toxicity in albino rats. Methods: Twenty male albino rats were randomly divided into five groups of four animals each. The control group (I) was fed with pellets and distilled water, while group II was orally administered with only 20 mg/kg cyclophosphamide. Groups III, IV and V were co- administered with 20 mg/kg body weight cyclophosphamide and 110, 220 and 440 mg/kg body weight A. wilkesiana leaf extract, respectively, for 7 d. After treatment, liver and kidney function biomarkers, haematological parameters, liver antioxidants, and mitochondrial membrane permeability transition pore opening were investigated. Results: A. wilkesiana leaf extract significantly reduced (P<0.05) cyclophosphamide-induced increase in plasma aspartate aminotransferase, alanine aminotransferase, creatinine, uric acid and urea. It increased superoxide dismutase, catalase, glutathione-S-transferase activities and reduced glutathione levels. It also increased packed cell volume count, hemoglobin concentration and white blood cell count while inhibiting the induction of mitochondrial swelling. Conclusions: This study demonstrates that aqueous extract of A. wilkesiana leaf protected tissues against cyclophosphamide-induced oxidative damage.

Curcuma angustifolia ameliorates carbon tetrachloride-induced hepatotoxicity in HepG2 cells and Swiss albino rats Sudipta Jena, Asit Ray, Diptirani Rath, Ambika Sahoo, Subhashree Singh, Noohi Nasim, Durga Madhab Kar, Sanghamitra Nayak Asian Pacific Journal of Tropical Medicine 2019 12(9):416-424 Objective: To determine the antioxidant and hepatoprotective potential of methanol extract of rhizome of Curcuma angustifolia (MECA) against carbon tetrachloride (CCl4)-induced hepatic damage in vitro and in vivo. Methods: DPPH, ABTS and reducing power assays were performed to estimate the antioxidant effect of MECA. In vitro cytotoxicity of MECA against HepG2 cells was evaluated, whereas serum biochemical parameters and levels of antioxidative enzymes were measured in vivo and in vitro. Additionally, histopathological studies were estimated in order to investigate the hepatoprotective efficacy of MECA. Furthermore, GC-MS analysis of the extract was performed to identify the chemical components. Results: MECA exhibited strong antioxidant activity and attenuated CCl4-induced decrease in the viability of HepG2 cells. Additionally, MECA significantly restored the ALT, AST, ALP, TP and albumin level in comparison with the CCl4 group. After pre-treatment with MECA, effects of SOD, CAT and GSH were increased as well as lipid peroxidation amount decreased on CCl4-induced hepatotoxicity in in vitro and in vivo model. Furthermore, histopathological observation confirmed that MECA reduced liver injury induced by CCl4 in rats. GC-MS analysis confirmed the presence of bioactive constituents such as α-tocopherol (12.27%), phytol (7.61%), squalene (3.71%), β-sitosterol (2.19%), eugenol (2.59%), curcumenol (1.20%), β-elemene (1.00%) and eucalyptol (0.89%). Conclusions: MECA contains antioxidant and hepatoprotective constituents such asa-tocopherol, phytol, squalene and eugenol and exerts hepatoprotective effect both in vitro and in vivo.

Inhibitory effects of methanolic Olea europaea and acetonic Acacia laeta on growth of Babesia and Theileria Amany Magdy Beshbishy, Gaber El-Saber Batiha, Oluyomi Stephen Adeyemi, Naoaki Yokoyama, Ikuo Igarashi Asian Pacific Journal of Tropical Medicine 2019 12(9):425-434 Objective: To evaluate the antipiroplasmic activities of methanolic extract of Olea europaea (MOE) and acetonic extract of Acacia laeta (AAL) against Babesia and Theileria parasites in vitro and evaluate the chemotherapeutic effects of these extracts against Babesia (B.) microti in vivo. Methods: Fluorescence assay using SYBR Green 1 nucleic acid stain was used to detect inhibitory effects of the two extracts as well as the combination effects of the two extracts with diminazene aceturate and atovaquone on four Babesia species and Theileria equi in vitro while for in vivo experiments, 8-weekold female BALB/c mice were injected intraperitoneally with 1 × 107B. microti-iRBCs and treated orally at a dose of 150 mg/kg of both extracts. Results: The half maximal inhibitory concentration (IC50) values of AAL against B. bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi were lower than those of MOE extracts. Toxicity assay on Madin–Darby bovine kidney, mouse embryonic fibroblast (MH/3T3), and human foreskin fibroblast cell lines showed that MOE and AAL affected only the viability of Madin–Darby bovine kidney cell line with half maximal effective concentrations (EC50) of (794.7±41.9) and (873.9±17.5) μg/mL, respectively. The oral treatments of MOE and AAL at 150 mg/kg inhibited the growth of B. microti in mice by 80.4% and 64.4%, respectively. The MOE and diminazene aceturate combination showed a higher chemotherapeutic effect than that of monotherapy. Conclusions: MOE and AAL have the potential to be an alternative remedy for treating piroplasmosis. Furthermore, the combination therapy of MOE + DA was more potent against B. microti infection in mice than their monotherapies.