Optimalisasi Produksi Enzim Kitinase Pada Isolat Jamur Kitinolitik Dari Sampel Tanah Rizosfer

The rhizosphere is the zone of soil surrounding a plant root where plant roots, soil and the soil biota interact with each other. Chitinolytic fungi has been effectively used in biological control agens. The chitinase activity causes lysis of the fungi cell wall pathogen. The aim of the research was to find optimization of activity chitinase enzyme from rhizosphere soil was conducted in vitro. Optimal growth chitinase production for TKR3 fungi isolate were concentration of chitin 0,2% (b/v), pH 5,5, temperature 30ºC, agitation 150 rpm and incubation time at four days. The optimum yield of chitinase production is influenced by fungal species and environmental conditions

Epidemiology and clinical presentation of community-acquired Staphylococcus aureus bacteraemia in children under 5 years of age admitted to the Manhica District Hospital, Mozambique, 2001-2019

Staphylococcus aureus bacteraemia (SAB) is one of the most common bloodstream infections globally. Data on the burden and epidemiology of community-acquired SAB in low-income countries are scarce but needed to defne preventive and management strategies. Blood samples were collected from children<5 years of age with fever or severe disease admitted to the Manhiça District Hospital for bacterial isolation, including S. aureus. Between 2001 and 2019, 7.6% (3,197/41,891) of children had bacteraemia, of which 12.3% corresponded to SAB. The overall incidence of SAB was 56.1 episodes/100,000 children-years at risk (CYAR), being highest among neonates (589.8 episodes/100,000 CYAR). SAB declined signifcantly between 2001 and 2019 (322.1 to 12.5 episodes/100,000 CYAR). In-hospital mortality by SAB was 9.3% (31/332), and signifcantly associated with infections by multidrugresistant (MDR) strains (14.7%, 11/75 vs. 6.9%, 14/204 among non-MDR, p=0.043) and methicillin-resistant S. aureus (33.3%, 5/15 vs. 7.6%, 20/264 among methicillin-susceptible S. aureus, p=0.006). Despite the declining rates of SAB, this disease remains an important cause of death among children admitted to MDH, possibly in relation to the resistance to the frst line of empirical treatment in use in our setting, suggesting an urgent need to review current policy recommendationspublishersversionpublishe

Different pattern of stool and plasma gastrointestinal damage biomarkers during primary and chronic HIV infection

Introduction: Primary HIV infection (PHI) is the initial phase after HIV acquisition characterized by high viral replication, massive inflammatory response and irreversible immune-damage, particularly at the gastrointestinal level. In this study we aimed to characterize the dynamics of gastrointestinal damage biomarkers during the different phases of HIV infection and assess their association with HIV-disease markers and their accuracy to differentiate PHI from chronic HIV infection (CHI). Methods: PHI-individuals (n = 57) were identified as HIV-seronegative/HIV-RNA positive and were followed up for one year at the Manhiça District Hospital in Mozambique. Ten plasma and 12 stool biomarkers were quantified by Luminex or ELISA and levels were compared to CHI-naive (n = 26), CHI on antiretroviral-treatment (ART; n = 30) and HIV-uninfected individuals (n = 58). Regression models adjusted by time point were used to estimate the association of the biomarkers with HIV-disease markers. Receiver operating curves were compared for the best accuracy to distinguish PHI from CHI. Results: Soluble (s)CD14 was significantly associated with the CD4/CD8 ratio (P < 0.05) and viremia levels (P < 0.0001) during PHI. Plasma zonulin and stool lactoferrin were significantly higher in PHI as compared to CHI-individuals (P < 0.05). Plasma zonulin demonstrated the best accuracy to identify PHI among HIV-infected individuals (AUC = 0.85 [95% CI 0.75–0.94]). Using a cutoff value of plasma zonulin ≥ 8.75 ng/mL the model identified PHI with 87.7% sensitivity (95% CI 76.3–94.9) and 69.2% specificity (95% CI 48.2–85.7). An adjusted multivariate model including age, plasma zonulin and sCD14 further increased the classification performance (AUC = 0.92 [95% CI 0.86–0.99]). Conclusions: While the stool biomarkers did not provide any predictive ability to distinguish PHI from CHI-individuals, plasma sCD14 and zonulin were significantly associated with HIV-disease markers and PHI identification, respectively. These inflammatory biomarkers may be useful to monitor changes in gastrointestinal integrity during HIV infection

Studi Awal Estimasi Dosis Internal 177lu-dota Trastuzumab pada Manusia Berbasis Uji Biodistribusi pada Mencit

STUDI AWAL ESTIMASI DOSIS INTERNAL 177Lu-DOTA TRASTUZUMAB PADA MANUSIA BERBASIS UJI BIODISTRIBUSI PADA MENCIT. Radiofarmaka baru untuk pengobatan penyakit kanker payudara tipe HER-2, 177Lu-DOTA Trastuzumab, telah berhasil diproduksi oleh Pusat Teknologi Radioisotop dan Radiofarmaka (PTRR) BATAN. Demi keamanan produk dan keselamatan pasien, radiofarmaka baru tersebut perlu dilengkapi dengan data studi dosis internal yang dilakukan setelah uji praklinis pada hewan coba selesai. Oleh karena itu, studi ini bertujuan untuk melakukan estimasi dosis pada pasien yang dihitung berdasarkan data uji biodistribusi pada mencit. Studi Uji biodistribusi dilakukan pada 25 ekor mencit dan diamati biodistribusinya pada organ-organ, diantaranya otak, Perut, usus, jantung , ginjal, hati, paru-paru, otot, tulang, limpa dan kandung kemih. Pengamatan cacahan organ dilakukan pada jam ke 1, 2, 3, 4, 24, 48 pasca injeksi radiofarmaka 177Lu DOTA-Trastuzumab sebesar 100mCi. Hasil yang diperoleh dari uji biodistribusi adalah % ID/gram organ tikus, kemudian dilakukan konversi perhitungan ke % ID/gram organ manusia. Untuk mengestimasi dosis ke manusia, hasil %ID/gram organ tersebut dipakai sebagai input pada software dosimetri internal OLINDA/EXM, dengan cara melakukan plotting %ID/gram versus waktu, yang akan menghasilkan residence time di masing-masing organ. Setelah residence time diperoleh, dosis internal radiasi pada masing-masing organ dan seluruh tubuh dapat diketahui. Hasil studi menunjukkan bahwa tiga organ yang memiliki dosis internal tertinggi 177Lu DOTA Trastuzumab adalah : paru-paru, hati dan ovarium dengan dosis masing-masing 0,063; 0,046 dan 0,025 mSv/MBq. Disimpulkan bahwa hasil estimasi dosis internal radiasi total yang diperoleh manusia pada penyuntikan radiofarmaka 177Lu-DOTA Trastuzumab adalah 0.21 mSv/MBq

Perancangan Hewan Coba Model untuk Karsinoma Payudara HER-2 Positif Menggunakan Agen Imunosupresan

The development of therapeutic drug for malignancy in Indonesia is often constrained because of the inability to provide animal models for preclinical study. These animal models are an animal model with a malignancy mass which have special characteristics, not just the tumor mass. Animal models that are usually used for this purpose is immunodeficient animals. This animal must be kept in sterile animal care, but the facility is not readily available in Indonesia. The purpose of this study was to develop a method for providing an animal model of nude mice replacement that has fairly low immunity but are still able to live in non-sterile animal care facilities. The study was conducted at the Laboratory Animal and Cytogenetics, Center for Radioisotope and Radiopharmaceuticals Technology, Batan, Serpong in the period of July to November 2014. SKBR-3 cell lines were inoculated on two groups of immunocompetent mice (Mus musculus) strain Balb/c, namely the treatment group (n=8) and controls (n=8). Cyclosporine A as an immunosupressan agent was given only to the treatment group before and after SKBR 3 inoculation. No macroscopically visible tumor growth at the site of inoculation in both of groups. There was a significant difference between the treatment group and the control group in leukocyte levels (p: 0.01), lymphocytes (p: 0.01), monocytes (p: 0.01), and neutrophil segments (p: 0.01). Two treatment groups of mice obtained cloudy degeneration in the liver. This method has significantly reduced the immunity of mice (Mus musclus) strain Balb/c but still cannot grow malignancies in experimental animals

Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial

BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. Herein, we report the final results from the same trial, including the efficacy of a booster dose. METHODS: From March 27, 2009, until Jan 31, 2011, children (age 5-17 months) and young infants (age 6-12 weeks) were enrolled at 11 centres in seven countries in sub-Saharan Africa. Participants were randomly assigned (1:1:1) at first vaccination by block randomisation with minimisation by centre to receive three doses of RTS,S/AS01 at months 0, 1, and 2 and a booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and a dose of comparator vaccine at month 20 (R3C group); or a comparator vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were followed up until Jan 31, 2014. Cases of clinical and severe malaria were captured through passive case detection. Serious adverse events (SAEs) were recorded. Analyses were by modified intention to treat and per protocol. The coprimary endpoints were the occurrence of malaria over 12 months after dose 3 in each age category. In this final analysis, we present data for the efficacy of the booster on the occurrence of malaria. Vaccine efficacy (VE) against clinical malaria was analysed by negative binomial regression and against severe malaria by relative risk reduction. This trial is registered with ClinicalTrials.gov, number NCT00866619. FINDINGS: 8922 children and 6537 young infants were included in the modified intention-to-treat analyses. Children were followed up for a median of 48 months (IQR 39-50) and young infants for 38 months (34-41) after dose 1. From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the C3C group, 6616 episodes occurred in the R3R group (VE 36.3%, 95% CI 31.8-40.5) and 7396 occurred in the R3C group (28.3%, 23.3-32.9); compared with 171 children who experienced at least one episode of severe malaria in the C3C group, 116 children experienced at least one episode of severe malaria in the R3R group (32.2%, 13.7 to 46.9) and 169 in the R3C group (1.1%, -23.0 to 20.5). In young infants, compared with 6170 episodes of clinical malaria that met the primary case definition in the C3C group, 4993 episodes occurred in the R3R group (VE 25.9%, 95% CI 19.9-31.5) and 5444 occurred in the R3C group (18.3%, 11.7-24.4); and compared with 116 infants who experienced at least one episode of severe malaria in the C3C group, 96 infants experienced at least one episode of severe malaria in the R3R group (17.3%, 95% CI -9.4 to 37.5) and 104 in the R3C group (10.3%, -17.9 to 31.8). In children, 1774 cases of clinical malaria were averted per 1000 children (95% CI 1387-2186) in the R3R group and 1363 per 1000 children (995-1797) in the R3C group. The numbers of cases averted per 1000 young infants were 983 (95% CI 592-1337) in the R3R group and 558 (158-926) in the R3C group. The frequency of SAEs overall was balanced between groups. However, meningitis was reported as a SAE in 22 children: 11 in the R3R group, ten in the R3C group, and one in the C3C group. The incidence of generalised convulsive seizures within 7 days of RTS,S/AS01 booster was 2.2 per 1000 doses in young infants and 2.5 per 1000 doses in children. INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. Efficacy was enhanced by the administration of a booster dose in both age categories. Thus, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission. FUNDING: GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative

Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial

BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. Herein, we report the final results from the same trial, including the efficacy of a booster dose. METHODS: From March 27, 2009, until Jan 31, 2011, children (age 5-17 months) and young infants (age 6-12 weeks) were enrolled at 11 centres in seven countries in sub-Saharan Africa. Participants were randomly assigned (1:1:1) at first vaccination by block randomisation with minimisation by centre to receive three doses of RTS,S/AS01 at months 0, 1, and 2 and a booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and a dose of comparator vaccine at month 20 (R3C group); or a comparator vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were followed up until Jan 31, 2014. Cases of clinical and severe malaria were captured through passive case detection. Serious adverse events (SAEs) were recorded. Analyses were by modified intention to treat and per protocol. The coprimary endpoints were the occurrence of malaria over 12 months after dose 3 in each age category. In this final analysis, we present data for the efficacy of the booster on the occurrence of malaria. Vaccine efficacy (VE) against clinical malaria was analysed by negative binomial regression and against severe malaria by relative risk reduction. This trial is registered with ClinicalTrials.gov, number NCT00866619. FINDINGS: 8922 children and 6537 young infants were included in the modified intention-to-treat analyses. Children were followed up for a median of 48 months (IQR 39-50) and young infants for 38 months (34-41) after dose 1. From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the C3C group, 6616 episodes occurred in the R3R group (VE 36.3%, 95% CI 31.8-40.5) and 7396 occurred in the R3C group (28.3%, 23.3-32.9); compared with 171 children who experienced at least one episode of severe malaria in the C3C group, 116 children experienced at least one episode of severe malaria in the R3R group (32.2%, 13.7 to 46.9) and 169 in the R3C group (1.1%, -23.0 to 20.5). In young infants, compared with 6170 episodes of clinical malaria that met the primary case definition in the C3C group, 4993 episodes occurred in the R3R group (VE 25.9%, 95% CI 19.9-31.5) and 5444 occurred in the R3C group (18.3%, 11.7-24.4); and compared with 116 infants who experienced at least one episode of severe malaria in the C3C group, 96 infants experienced at least one episode of severe malaria in the R3R group (17.3%, 95% CI -9.4 to 37.5) and 104 in the R3C group (10.3%, -17.9 to 31.8). In children, 1774 cases of clinical malaria were averted per 1000 children (95% CI 1387-2186) in the R3R group and 1363 per 1000 children (995-1797) in the R3C group. The numbers of cases averted per 1000 young infants were 983 (95% CI 592-1337) in the R3R group and 558 (158-926) in the R3C group. The frequency of SAEs overall was balanced between groups. However, meningitis was reported as a SAE in 22 children: 11 in the R3R group, ten in the R3C group, and one in the C3C group. The incidence of generalised convulsive seizures within 7 days of RTS,S/AS01 booster was 2.2 per 1000 doses in young infants and 2.5 per 1000 doses in children. INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. Efficacy was enhanced by the administration of a booster dose in both age categories. Thus, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission. FUNDING: GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative