Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13 : 01 , a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13 : 01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10 −9 , confirming the strong association of HLA-B*13 : 01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13 : 01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.

Background Tuberculosis is one of the deadliest disease caused by Mycobacterium tuberculosis. Its treatment still becomes a burden for many countries including Indonesia. Drug resistance is one of the problems in TB treatment. However, a development in the molecular field through Whole-genome sequencing (WGS) can be used as a solution in detecting mutations associated with TB- drugs. This investigation intended to implement this data for supporting the scientific community in deeply understanding any TB epidemiology and evolution in Papua along with detecting any mutations in genes associated with TB-Drugs. Result A whole-genome sequencing was performed on the random samples from TB Referral Laboratory in Papua utilizing MiSeq 600 cycle Reagent Kit (V3). Furthermore, TBProfiler was used for genome analysis, RAST Server was employed for annotation, while Gview server was applied for BLAST genome mapping and a Microscope server was implemented for Regions of Genomic Plasticity (RGP). The largest genome of M. tuberculosis obtained was at the size of 4,396,040 bp with subsystems number at 309 and the number of coding sequences at 4326. One sample (TB751) contained one RGP. The drug resistance analysis revealed that several mutations associated with TB-drug resistance existed. In details, mutations of rpoB gene which were identified as S450L, D435Y, H445Y, L430P, and Q432K had caused the reduced effectiveness of rifampicin; while the mutases in katG (S315T), kasA (312S), inhA (I21V), and Rv1482c-fabG1 (C-15 T) genes had contributed to the resistance in isoniazid. In streptomycin, the resistance was triggered by the mutations in rpsL (K43R) and rrs (A514C, A514T) genes, and, in Amikacin, its resistance was led by mutations in rrs (A514C) gene. Additionally, in Ethambutol and Pyrazinamide, their reduced effectiveness was provoked by embB gene mutases (M306L, M306V, D1024N) and pncA (W119R). Conclusions The results from whole-genome sequencing of TB clinical sample in Papua, Indonesia could contribute to the surveillance of TB-drug resistance. In the drug resistance profile, there were 15 Multi Drugs Resistance (MDR) samples. However, Extensively Drug-resistant (XDR) samples have not been found, but samples were resistant to only Amikacin, a second-line drug.

Importance: Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy (MDT) which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, leprosy is still a problem. Furthermore, there had been reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. HLA-B*13:01 has been found to be associated with DHS and prospective screening has proven its ability to prevent DHS in the Chinese population, but has not been validated in Indonesians. Objective: To validate HLA-B*13:01 as a biomarker for DHS in the Indonesian population. Design: This is a case-control study. Setting: Population-based, multi-district recruitment from primary care centers in two of the top 3 most prevalent provinces in Indonesia, Papua and West Papua. Participants: Leprosy patients who presented themselves with DHS were recruited as case subjects (34 cases) and leprosy patients without DHS were recruited as control subjects (52 controls). Exposure: Leprosy patients who had undergone multi-drug treatment for leprosy under the standard WHO guideline, consisting of rifampicin, dapsone and clofazamine. Main Outcome and Measures: The association of HLA-B*13:01 to DHS based on difference in allele frequencies between cases and controls. HLA-B alleles were typed using the gold-standard Sequence Based Typing method. Results were analyzed using logistic regression and risk assessment was carried out. Results: The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio=247.6 and P-value=4.81E-9, confirming the strong association of HLA-B*13:01 to DHS in the Indonesian population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. Conclusions and Relevance: HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future. Keywords: HLA-B*13:01, dapsone hypersensitivity syndrome, leprosy, dapsone, adverse drug reaction, Papua, Indonesia

Abstrak Latar belakang: Lepra masih menjadi masalah kesehatan di Papua terutama di Kota Jayapura.Banyaknya kasus relaps dan default juga menjadi tantangan dalam eliminasi lepra di Jayapura. Kasusrelaps dan riwayat default pada beberapa penelitian berkaitan dengan resistensi terhadap multi drugtreatment (MDT). Tujuan penelitian ini adalah mendeteksi keberadaan mutasi gen rpoB M. leprae padapasien relaps, default dan pasein yang kurang peka terhadap terapi MDT di Kota Jayapura. Metode: Sampel diperoleh dari pasien yang terdiagnosis lepra dengan kriteria pasien relaps, default danpasien yang terus bergejala setelah terapi MDT sebanyak 34 sampel. Sampel diambil dalam bentuk insisikulit (skin silt) daun telinga. DNA diekstraksi dengan menggunakan kit Qiagen. Gen rpoB diamplifikasimelalui teknik PCR dan analisis nukleotida dilakukan melalui sekuensing. Analisis mutasi dilakukanmelalui BLAST dengan basis data GenBank. Hasil: Sebanyak 34 sampel yang diperiksa, 9 diantaranya positif BTA sedangkan 25 yang lainnya negatifBTA. Pada hasil PCR, sampel yang berhasil teramplifikasi sebanyak 31 sampel, dan 3 sampel tidakteramplifikasi. Hasil BLAST menunjukkan bahwa tidak ditemukan adanya mutasi pada gen rpoB yangdapat menyebabkan resistensi terhadap rifampisin. Kesimpulan: Kesimpulan dari penelitian ini adalah gen rpoB Mycobacterium leprae asal Jayapuratidak mengandung mutasi yang dapat menyebabkan terjadinya resistensi terhadap rifampisin. Dengandemikian rifampisin masih sensitif untuk pengobatan lepra di Kota Jayapura. Kata kunci: Lepra, gen rpoB, rifampisin, Mycobacterium leprae. AbstractBackground: Leprosy remains a prominent health problem in Papua especially in Jayapura City. Numerouscases of relapse and default are also challenges in leprosy elimination in Jayapura. Studies in Relapsecases and history of defaults revealed some resistance related to multi-drug treatment (MDT). The purposeof this study was to detect the presence of mutation in rpoB M. leprae gene in patient relapse, default andpatients who are less sensitive to MDT therapy in Jayapura City. Method: Samples were obtained from patients diagnosed with leprosy with criteria of relapse, defaultand symptomatic patients after receiving MDT therapy. A total of 34 samples were taken in the form ofskin incision (skin silt) of the earlobe. DNA was extracted using Qiagen kit. rpoB gene from extractedDNA was amplified through PCR method followed by nucleotide sequences. Analysis of mutation waselaborated using BLAST according to GenBank database. Result: 34 samples were examined, and 9 were positive for Ziehl-Neelsen (ZN)staining, while the 25 werenegative. In the PCR results, the samples that successfully amplified were 31 samples, and 3 samples werenot amplified. The results of BLAST indicated that no mutations in the rpoB gene found in which able toinitiate resistance to rifampicin. Conclusion: The conclusion of this study is the rpoB Mycobacterium leprae gene from Jayapura did notcontain any mutations that could trigger resistance to rifampicin. Thus rifampicin is still sensitive forleprosy treatment in Jayapura City. Keywords: Leprosy, rpoB gene, rifampicin, Mycobacterium leprae

Yaws is still unfinished  health  problem  in Jayapura City, there is still have enclave yaw’s disease. This study aimed to know clinical and result of Rapid Test Diagnostic of yaws  after mass therapy used azitromisin and to know about sanitation according to yaws. These was descriptive and cross sectional study design. Method of this study are interview, clinical examination, RDT and lesion sampel using Darkfield microscope and microscope. From 229 respondences after mass therapy of azitromisin in Jayapura City consist of 113 boys and 116 girls. The youngest about 3 years old and the oldest about 15 years old. Most of them have already have good personal hygiene from the highest presentance of taking bath, bathing used soap and changing clothes after bathing. Prevalence of yaws are tend to decreased, we found only 5 RDT (+). Frambusia masih menjadi masalah kesehatan yang belum terselesaikan, masih terdapat daerah kantong frambusia di Kota Jayapura. Penelitian ini bertujuan untuk mendapatkan gambaran secara klinis maupun pemeriksaan RDT frambusia setelah pengobatan massal dan mengetahui data sanitasi terkait frambusia ini. Jenis penelitian yang digunakan yaitu observasional     dengan desain potong lintang (cross sectional). Metode yang digunakan terdiri dari wawancara dengan kuesioner, pemeriksaan klinis,  pemeriksaan RDT dan pemeriksaan sampel berupa apusan lesi dengan menggunakan mikroskop lapangan gelap dan mikroskop cahaya biasa (pewarnaan gram). Hasil yang didapat berupa data dari 229 responden yang telah mendapatkan pengobatan Azitromisin di Kota Jayapura  yang terdiri dari responden laki – laki berjumlah 113 orang dan responden perempuan berjumlah 116 orang. Umur termuda ditemukan berumur 3 tahun dan umur tertinggi 15 tahun. Sebagian besar responden sudah memiliki personal hygiene  yang cukup baik dilihat dari tingginya persentase frekuensi mandi, pelaksanaan mandi memakai sabun dan mengganti baju setelah mandi. Angka kasus frambusia di Kota Jayapura cenderung turun dimana ditemukan hanya 5 responden dengan RDT (+).