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A total of 182 human cases of avian influenza have been reported in Indonesia in the period 2004-2011, with a case fatality rate (CFR) among them of 86%. Various risk factors for avian influenza transmission have also been identified, including a high population, having many types of poultry (broiler, layer, village chickens, etc), traditional poultry systems that promote close human relationships, and the presence of several areas in Indonesia which are strategic locations as a place to rest and meet various wild birds. Vaccination is one of the efforts to prevent the re-emergence of H5N1 avian influenza transmission. However, the avian influenza vaccine for the public is not yet available in Indonesia. The purpose of this review article is to examine the avian influenza vaccine in humans as a preventive measure against the re-emergence of avian influenza in Indonesia, and to determine the progress of developing avian influenza vaccines. The results of the review show that several avian influenza vaccine candidates have been approved by WHO, one of which is a vaccine candidate using an isolated virus from Indonesia. This information on the development of avian influenza vaccines for humans is useful and can be used as an avian influenza pre-pandemic preparedness in Indonesia. Abstrak Sebanyak 182 kasus flu burung pada manusia telah dilaporkan di Indonesia pada periode tahun 2004-2011, dengan case fatality rate (CFR) sebesar 86%. Berbagai faktor risiko penularan flu burung juga telah diidentifikasi, antara lain jumlah penduduk yang tinggi, memiliki banyak jenis unggas (ayam broiler, layer, kampong, dsb), sistem perunggasan tradisional yang membuat kedekatan hubungan antara manusia, dan adanya beberpa wilayah di Indonesia yang menjadi lokasi strategis sebagai tempat istirahat dan bertemunya berbagai unggas liar. Vaksinasi merupakan salah satu upaya untuk mencegah munculnya kembali penularan flu burung H5N1. Namun demikian, vaksin flu burung untuk masyarakat belum tersedia hingga saat ini. Tujuan dari review artikel ini adalah untuk mengkaji vaksin flu burung pada manusia sebagai tindakan pencegahan terhadap kemunculan kembali flu burung di Indonesia, dan untuk mengetahui kemajuan pengembangan vaksin flu burung. Hasil review menunjukkan beberapa kandidat vaksin flu burung telah disetujui oleh WHO, salah satunya adalah kandidat vaksin menggunakan isolat virus asal Indonesia. Informasi perkembangan vaksin flu burung bagi manusia ini bermanfaat dan dapat digunakan sebagai kesiapsiagaan prepandemi flu burung di Indonesia.

Diphtheria is a vaccine-preventable disease. The clinical features and complications of diphtheria are associated with toxins produced by the causative bacteria. Diphtheria toxin synthesis is encoded by tox gene. This study aimed to provide an overview of the DNA sequences of the tox gene of Corynebacterium diphtheriae causing diphtheria in several region of Indonesia. A total of 65 Corynebacterium diphtheriae isolated from several provinces in Indonesia (2010-2017) were used as samples. Isolates recultured on blood agar medium (BA), incubated at 37 0 C overnight. DNA extraction conducted using the QiaAmp DNA Mini Kit. The DNA sequencing was carried out using the Whole Genome Sequencing (WGS) approach. The data conversion and analysis conducted using U-gene and BioEdit programs. Examination of 65 isolate C. diphtheriae with 1683 bp of tox gene sequences showed that there are 3 patterns of gene sequences with 3 mutation site. All mutations were silent mutation. The mutation sites were also not commonly used as 3’end binding site of the PCR primer. We concluded that tox gene of C. diphtheriae that causes diphtheria in some provinces in Indonesia have limited variations and these variations do not encode amino acid changes. This indicates that the vaccines used in Indonesia are still in accordance with the variations in circulating bacteria and PCR can be used for screening and predicting the toxigenicity of diphtheria-causing bacteria. Keywords: C. diphtheriae, gene tox, diphtheria, Indonesia Abstrak Difteri merupakan salah satu penyakit yang dapat dicegah dengan imunisasi (PD3I). Gambaran klinis dan komplikasi difteri dikaitkan dengan toksin yang diproduksi oleh bakteri penyebab. Sintesis toksin difteri dikode oleh gen tox. Penelitian ini bertujuan untuk memberikan gambaran sekuens DNA gen tox Corynebacterium diphtheriae penyebab difteri di beberapa wilayah Indonesia. Sebanyak 65 isolat C. diphtheriae tersimpan milik Badan Litbangkes yang diisolasi dari beberapa wilayah Indonesia tahun 2010- 2017 dijadikan sebagai sampel. Rekultur dilakukan pada medium agar darah (BA), diinkubasi pada suhu 37 o C selama sehari semalam. Ekstraksi DNA menggunakan kit QiaAmp DNA Minikit. Sekuensing DNA dilakukan dengan pendekatan Whole Genome Sequencing (WGS). Konversi dan analisis data menggunakan program U-gene dan BioEdit.Pemeriksaan 65 isolat C. diphtheriae dengan 1683 bp sekuens gen tox menunjukkan ada 3 pola sekuens gen dengan 3 lokasi mutasi. Seluruh mutasi bersifat silent mutation. Lokasi mutasi juga bukan merupakan tempat penempelan ujung 3’ primer PCR yang umum digunakan. Berdasarkan hasil penelitian dapat disimpulkan bahwa variasi gen tox yang ditemukan pada C. diphtheriae penyebab difteri di Indonesia memiliki variasi yang terbatas dan mutasi yang ada tidak mengkode perubahan asam amino. Hal ini mengindikasikan bahwa vaksin yang digunakan di Indonesia masih sesuai dengan variasi bakteri yang bersirkulasi. Hasil penelitian juga mengindikasikan bahwa PCR dapat digunakan untuk skrining dan memprediksi toksigenisitas bakteri penyebab difteri. Kata kunci : C. diphtheriae, gen tox, difteri, Indonesia

Identification of ESBL-E.coli from environment without selective medium will be challenging to do considering that E.coli mixes with various other microorganisms in the environment. This study aimed to determine the performance of TBX Agar supplemented with Cefotaxime as a selective medium for ESBL-E. coli screening from 138 water samples of environmental sampling obtained from rivers, open sewers in the market, poultry slaughterhouses and hospital waste water inlets and outlets around Jakarta. Laboratory examinations were carried out through the filtration stage, inoculation on the TBX Agar supplemented with Cefotaxime medium as well as species confirmation and ESBL with the indol test and double-disk test. The results showed that 87.08% (40-100%) of suspect colonies growing on TBX Agar supplemented with Cefotaxime medium were confirmed as E.coli and 82.51% (12-100%) were confirmed as ESBL-E.coli. However, there was no correlation between TBX Agar supplemented with Cefotaxime performance and sampling locations. Based on the results of the study, it can be concluded that the TBX supplemented with Cefotaxime medium can be used for ESBL-E.coli screening in the environment, but further confirmation is needed using the indole and double-disk tests. Keywords: Escherichia coli, ESBL, TBX Agar suplemented with Cefotaxime Abstrak Identifikasi ESBL-E.coli tanpa medium selektif akan sangat sulit dilakukan pada sampel lingkungan mengingat ESBL-E.coli bercampur dengan berbagai mikroorganisme lainnya. Tujuan penelitian ini yaitu untuk mengetahui performa TBX Agar yang disuplementasi Cefotaxime sebagai medium selektif untuk skrining ESBL-E.coli. Sampel penelitian sebanyak 138 sampel air lingkungan yang diambil dari sungai, saluran pembuangan terbuka di pasar, rumah pemotongan hewan unggas (RPHU) serta inlet dan outlet limbah rumah sakit di sekitar Jakarta. Pemeriksaan laboratorium melalui tahapan filtrasi, inokulasi pada medium TBX Agar dengan suplementasi Cefotaxime serta konfirmasi spesies dan ESBL dengan uji indol dan double-disk test. Hasil menunjukkan bahwa koloni tersangka yang tumbuh pada medium TBX Agar dengan suplementasi Cefotaxime sebanyak 87,08% (40-100%) terkonfirmasi sebagai E.coli dan 82,51% (12-100%) terkonfirmasi sebagai ESBL-E.coli. Namun, tidak ada hubungan antara performa TBX Agar dengan suplementasi Cefotaxime dengan lokasi pengambilan sampel. Berdasarkan hasil penelitian dapat disimpulkan bahwa medium TBX Agar dengan suplementasi Cefotaxime cocok digunakan untuk skrining ESBL-E.coli di lingkungan namun tetap diperlukan konfirmasi lanjut menggunakan uji indol dan double disk test. Kata kunci: Escherichia coli, ESBL, TBX Agar suplemented with Cefotaxime

Background: In Corynebacterium diphtheriae, the dtxR gene plays a role in regulating diphtheria toxin synthesis. The dtxR gene is often used as a marker for identifying C. diphtheriae by the polymerase chain reaction (PCR) method because it is present in all strains of this bacterium. Mutations in the dtxR gene can cause the over-synthesis of diphtheria toxin and reduce PCR assays' sensitivity. Objectives: This study aimed to describe the polymorphisms in the dtxR gene of C. diphtheriae isolated from a diphtheria outbreak in Indonesia. Methods: Forty-eight isolates of C. diphtheriae were obtained from clinical samples (throat/nasopharyngeal swabs) of diphtheria cases and close contacts. The isolates were revived on a blood agar plate (BAP), bacterial colonies were harvested, and deoxyribonucleic acid (DNA) was extracted. The DNA sequencing was carried out using a Whole-genome Sequencing (WGS) approach. The data were converted and analyzed with U-gene software. The dtxR gene analysis was performed with C. diphtheriae PW8 as references. Results: There were 59-point mutation locations in 48 isolates examined. None of these single nucleotide polymorphisms (SNPs) coded for amino acid changes. Based on the mutation pattern, seven clades/groups of the dtxR gene of 48 C. diphtheriae isolates were examined. Conclusions: At least seven types of DNA sequences and more than 50 SNPs of the dtxR gene were identified in 48 C. diphtheriae isolates from a diphtheria outbreak in Indonesia. Although all of them are silent mutations, they must be considered in the design of PCR examination in diphtheria laboratories.

Background: Corynebacterium diphtheriae, C. ulcerans, and C. pseudotuberculosis are known as diphtheria-causing bacteria. Although diphtheria therapy is administered based on the clinical manifestations, some cases are mild and atypical. The immediate and accurate identification of diphtheria-causing bacteria is of paramount importance to prevent the spread of the disease and provide case management as early as possible. Unfortunately, conventional methods as the gold standard are time-consuming. Objectives: This study aimed to develop and implement a multiplex real-time PCR with the dtxR and tox genes as the target to identify three species of diphtheria-causing bacteria and screen their toxigenicity quickly and accurately. Methods: The research sample encompassed seven reference strains, one synthetic DNA, 30 archived isolates, and 924 clinical specimens isolated from 311 diphtheria cases and 613 close contacts. The conventional methods as the gold standard and the established PCR assay were used to verify the results of multiplex real-time PCR developed in this study. Results: The multiplex real-time PCR could identify seven reference strains, one synthetic DNA, and 30 archived isolates as accurately as the conventional methods and the established PCR. Similar to established PCR, the multiplex real-time PCR identified diphtheria-causing bacteria in 120 (38.6%) out of 311 and 12 (2%) out of 613 clinical specimens from diphtheria cases and close contacts, respectively. Meanwhile, the conventional methods identified diphtheria-causing bacteria in 79 (25.4%) out of 311 and three (0.5%) out of 613 clinical specimens. Conclusions: The multiplex real-time PCR developed in this study can be used to identify three species of diphtheria-causing bacteria and screen their toxigenicity quickly and accurately. However, in this study, no diphtheria-causing bacteria other than C. diphtheriae was found in the clinical samples using the PCR or conventional methods. PCR is more sensitive than the conventional methods and can be used as an additional test in diphtheria laboratories.

Background: The World Health Organization reported Indonesia as one of the countries with the most prevalent cases of diphtheria worldwide. The microbiological aspects of diphtheria-inducing bacteria are of great significance in tracing disease transmission and case management. However, clinical aspects are critical for updating clinical features and case management in the field, which may sometimes differ from theoretical foundations. Objectives: This study aimed to identify the microbiological and clinical aspects, including molecular typing and case fatality rates, in diphtheria-confirmed cases from the capital city of Indonesia, Jakarta, and surrounding areas in 2017. Methods: The microbiological aspect of 40 diphtheria-confirmed cases were obtained by re-identify diphtheria-inducing bacteria isolated from the samples, while the clinical aspects of the cases were obtained from the medical records and epidemiological data. The chi-square test was used to examine the correlation between fatal cases and myocarditis and diphtheria antitoxin administration delay. In this study, P ≤ 0.05 was set as the significance level. Results: All 40 diphtheria confirmed cases were induced by toxigenic Corynebacterium diphtheriae with two biotypes, namely intermedius (60.0%) and mitis (40.0%). There are six sequence types of bacteria with two main sequence types, ie, ST534 (46.4%) and ST377 (35.7%). The proportions of cases that had a fever and sore throat were 72.5% and 77.5%, respectively; however, the prevalence rates of the cases with pseudomembrane and bull neck were 100% and 47%, respectively. Most cases were administered a combination of penicillin or erythromycin with other antibiotics (40%), and 22.5% of the cases only received penicillin. Myocarditis was noticed in three fatal cases, and their relationship was statistically significant (P = 0.000). All five fatal cases (12.5% of cases) received diphtheria antitoxin (DAT) lately or had not received it yet. Conclusions: Toxigenic C. diphtheriae with two biotypes (namely mitis and intermedius) and two main sequence types (ie, ST534 and ST377) was the causative agent of diphtheria-confirmed cases from Jakarta and surrounding areas in 2017. It was also concluded that those fatal cases were correlated with myocarditis complications.

Background: Indonesia is one of the five countries with the highest number of diphtheria cases worldwide. Diphtheria is caused by the toxigenic strains Corynebacterium diphtheriae, C. ulcerans, and C. pseudotuberculosis. The diphtheria-causing bacteria can be identified using conventional and molecular methods, including polymerase chain reaction (PCR) assay. We used the PCR assay as additional testing, because in island countries like Indonesia, specimen transport is a serious challenge to maintaining bacterial survival. Objectives: This study aimed to evaluate the PCR assay as additional testing to identify diphtheria-causing bacteria in the diphtheria laboratory. Methods: In this cross-sectional study, a total of 178 pairs of the throat and nasal swabs from diphtheria suspected cases and close contacts were collected from seven provinces in Indonesia in 2016. All samples were directly identified by the conventional method and multiplex PCR assay. Statistical analysis was conducted using the 2 × 2 tables to determine the sensitivity and specificity of both methods, while the χ2 test was used to examine the correlation between specimen examination delay and the differentiation of results. A P-value < 0.05 was considered as statistically significant. Results: Out of 178 examined samples, eight samples were identified as diphtheria-positive by both the conventional method and PCR assay, while nine samples were only detected by the PCR assay. All diphtheria-causing bacteria found in the positive samples were toxigenic C. diphtheriae. The diphtheria-causing bacteria were found in 27.6% of cases and 6.0% of close contacts using the PCR assay versus 13.8% of cases and 2.7% of close contacts using the conventional method. Statistical analysis showed that the PCR assay is about twice more sensitive than the conventional method. There was a significant correlation between the differentiation of results and > 72 hours’ specimen examination delay with a P-value of 0.04 (< 0.05). Conclusions: The PCR assay is more sensitive than the conventional method to identify diphtheria-causing bacteria and may be applied as additional testing to increase the positivity rate of diphtheria-confirmed cases in Indonesia as an archipelago country where geographical factors and specimen transport are real obstacles.

The World Health Organization (WHO) has been implementing antimicrobial surveillance with a “One Health” approach, known as the Global Surveillance ESBL E. coli Tricycle Project. We describe the implementation of the Tricycle Project (pilot) in Indonesia, focusing on its results, challenges and recommendations. The samples were 116 patients with bloodstream infections caused by ESBL E. coli, 100 rectal swabs collected from pregnant women, 240 cecums of broiler, and 119 environmental samples, using the standardized method according to the guidelines. ESBL-producing E. coli was found in 40 (40%) of the 100 pregnant women, while the proportion of ESBL-producing E. coli was 57.7% among the total E. coli-induced bloodstream infections. ESBL-producing E. coli was isolated from 161 (67.1%) out of 240 broilers. On the other hand, the average concentration of E. coli in the water samples was 2.0 × 108 CFU/100 mL, and the ratio of ESBL-producing E. coli was 12.8% of total E. coli. Unfortunately, 56.7% of questionnaires for patients were incomplete. The Tricycle Project (pilot) identified that the proportion of ESBL-producing E. coli was very high in all types of samples, and several challenges and obstacles were encountered during the implementation of the study in Indonesia. The finding of this study have implication to health/the antimicrobial resistance (AMR) surveillance. We recommend continuing this project and extending this study to other provinces to determine the AMR burden as the baseline in planning AMR control strategies in Indonesia. We also recommend improving the protocol of this study to minimize obstacles in the field., Highlights • Tricycle project is the first antimicrobial surveillance with one health approach in Indonesia. • The burden of ESBL E.coli in Environment in Jakarta. • The ESBL E.coli as indicator for antimicrobial surveillance in One Health approach.

In diphtheria laboratory examinations, the PCR test can be applied to isolates and clinical specimens. This study aimed to develop a PCR assay to identify the species and toxigenicity of diphtheria-causing bacteria, including the prediction of some NTTB types. Seven reference isolates, four synthetic DNA samples, 36 stored isolates, and 487 clinical samples used for PCR optimization. The PCR results was confirmed by DNA sequence analysis. The results of the PCR examination of the 7 reference isolates and 36 stored isolates were similar to the results obtained using conventional methods as gold standard, both for diphtheria-causing and non-diphtheria-causing bacteria. The validation of the PCR results using DNA sequence analysis showed that there was no mispriming or misamplification. The multiplex PCR assay developed in this study could correctly identify the species and toxigenicity of diphtheria-causing bacteria, including the prediction of some NTTB types not yet covered by established PCR methods.

Taman kota merupakan salah satu jenis ruang terbuka publik, yang terletak pada tempat yang strategis diwilayah kota. Fungsi utamanya adalah sebagai fasilitas bagi masyarakat untuk berkumpul, disamping fungsi lainnya, yaitu sebagai paru paru kota. Taman kota yang ada di kota Semarang, tersebar di wilayah kota Semarang, berupa taman kota bersifat aktif maupun pasif. Taman kota aktif, merupakan tempat berkumpulnya masyarakat untuk beraktifitas, berinteraksi dan bersosialisasi. Penelitian terhadap lima taman kota di kota Semarang ini bertujuan untuk mengetahui unsur keindahan dari masing-masing taman kota. Kajian estetika lingkungan ini berdasarkan teori Berlyne dengan metode deskriptif kualitatif. Hasil penelitian berupa perbandingan pengamatan taman kota berdasarkan faktor kompleksitas, keunikan, ketidaksenadaan, dan kejutan.

Atorvastatin is one of the statins which is used as the first line therapy for hyperlipidemia. The patent of atorvastatin innovator ended in 2011. Besides the innovator brand of atorvastatin, several brand and one generic atorvastatin tablet are currently marketed in Indonesia. In this research, dissolution profiles, assay and physical quality were investigated for three atorvastatin tablet samples consist of one innovator sample, two atorvastatin copy layer products (branded generic atorvastatin sample and atorvastatin generic sample). The dissolution testing were done using FDA (Food and Drug Administration) method. The result shows that the innovator and branded generic samples meet all the requirements for physical quality, meanwhile the generic sample failed to meet the disintegration test criteria. The branded generic sample has similar dissolution profile with the innovator, while the generic tablet was not similar. The assay were conducted using High Performance Liquid Chromatography (HPLC) method. The assay result of the innovator, branded generic, and generic samples respectively were 97,54%, 106,36% and 97,65% which means that all samples comply with general requirement of active pharmaceutical ingredient in tablet.

The limited availability of medicinal plants as well as their limitations in cultivation as a source of medicinal compounds can lead to excessive harvesting, habitat destruction and destructive exploration. This led to the extinction of rare plants and caused the condition of natural resources worse. The purpose of this study is to elucidate the potential of bioreactor in terms of its ability to increase the active compounds of plant obtained from C. roseus, ajmalicine. The data was obtained from various references. The main references discuss about ajmalicine and bioreactor.In general, the concentration of compounds produced by cell suspension is higher than its original concentration in the plants. In study cases of ajmalicine, the compounds were produced as much as seven times more than these compounds in native plants. Other studies show that the use of different plant organs, the addition of elicitor, the weight ofinitial cells as well as aeration rate can affect the concentration of ajmalicine obtained from medium in the bioreactor. Tissue cultured plants in bioreactor can produce se- condary metabolites in a short time with high yields. However, previous optima- zation should be carried out in terms of adding elicitor, aeration rate and pH condition of the bioreactor.

The fence of a dwelling house was originally as a barrier between the property area and the surrounding environment. In a residential house, the fence also acts as a boundary between one house and another. In development, the fence of a residential house becomes part of the design of a residential house. Fences become a very important element in a dwelling, so the fence design becomes an identity of the occupants of the dwelling. How the social strata of residents can affect the appearance and physical condition of a residential fence. The study was conducted in several residential houses with various types of residential classification in Pasadena Housing Semarang. The results showed that the material of a fence turned out to be influenced by the level of social strata of residential owners as seen from the classification of the type of residence. Abstrak Pagar sebuah rumah tinggal pada awalnya sebagai pembatas antara area properti dan lingkungan sekitar. Pada sebuah rumah tinggal, pagar juga berperan sebagai batas antara rumah tinggal satu dengan yang lain. Pada perkembangan, pagar sebuah rumah tinggal menjadi bagian dari desain sebuah rumah tinggal. Pagar menjadi elemen yang sangat penting pada sebuah rumah tinggal, sehingga desain pagar menjadi sebuah identitas dari penghuni rumah tinggal tersebut. Bagaimana strata sosial penghuni rumah tinggal dapat mempengaruhi tampilan dan kondisi fisik sebuah pagar rumah tinggal. Penelitian dilakukan pada beberapa rumah tinggal dengan berbagai klasifikasi tipe rumah tinggal di Perumahan Pasadena Semarang. Hasil penelitian didapatkan bahwa material sebuah pagar ternyata mendapat pengaruh dari tingkat strata sosial pemilik rumah tinggal yang dilihat dari klasifikasi tipe rumah tinggal tersebut.

Background/aim: The aim of this study was to find out characteristics and patterns of the spread of Corynebacterium diphtheriaeisolated from Jakarta and the surrounding areas, using the whole genome sequencing WGS technique and multilocus sequence typing MLST approach.Materials and methods: The study samples consisted of 86 C. diphtheriae isolates, which were isolated from diphtheria patients and close contacts of patients. The DNA sequencing was carried out using the WGS technique. Data conversion applied the U-gene software. Molecular typing was conducted through the MLST approach, then followed by online data analysis. Results: The results showed that as many as 43 50% of all samples examined were new types with the same allele profile, namely 9-1-13-4-3-3-4. New sequence type C. diphtheriae is registered in the MLST global database as ST534 based on the allele profile. The tox gene analysis in 43 isolates with ST534 indicated that there were three mutation positions, all of which were silent mutations.Conclusion: The main cause of diphtheria in Jakarta and the surrounding areas is a new sequence type of C. diphtheriae registered as ST534.