Performance of Xpert® MTB/RIF in detecting Multidrug-Resistance Tuberculosis in West Java, Indonesia

Indonesia is the 2nd country with the highest tuberculosis (TB) caseload in the world. Inappropriate TB treatment may lead to multidrug-resistance tuberculosis (MDR-TB) development. TB rapid detection is important, and very much needed, to prevent transmission and deaths due to this disease. The Xpert® MTB/RIF is proposed to address this problem. This study aimed to assess the performance of the Xpert® MTB/RIF test in West Java, Indonesia. This was a cross-sectional study conducted on MDR-TB suspects referred to Dr. Hasan Sadikin General Hospital Bandung, West Java, Indonesia, using data from the eTB Manager. The performance of Xpert® MTB/RIF testing and its validity was tested against conventional drug susceptibility testing (DST). In total, data from 4,452 MDR-TB suspects were retrieved but only 578 data that had both DST and Xpert® MTB/RIF results were included in the study. The Xpert® MTB/RIF showed a sensitivity of 88% (95%CI: 85%-91%), specificity of 66% (95%CI: 60%-72%), positive predictive value of 79% (95%CI: 75%-83%), and negative predictive value of 80% (95%CI: 74%-85%), with a detection accuracy of 79%. Xpert® MTB/RIF test in this study shows a good performance for the diagnosis of MDR-TB when compared to the Mycobacterium tuberculosis culture as the gold standard. Therefore, rapid Xpert® MTB/RIF examination is recommended for MDR-TB screening for countries with a high TB burden as a complementary tool to the reference standard test. Performa Xpert® MTB/RIF Dalam Mendeteksi Tuberculosis Resisten Obat di Jawa Barat, IndonesiaIndonesia adalah negara ke-2 dengan jumlah kasus tuberkulosis (TB) tertinggi di dunia. Pengobatan TB yang tidak sesuai dapat mengakibatkan kuman TB menjadi resisten terhadap obat TB yang disebut TB multidrug-resistances (TB-MDR). Untuk itu diperlukan alat deteksi yang mumpuni sehingga kuman TB-DR dapat segera didiagnosis dan diberikan pengobatan yang tepat; dengan demikian pencegahan dan kematian akibat TB dapat ditekan. Penelitian ini bertujuan untuk mengukur performa mesin Xpert® MTB/RIF dalam mendeteksi kuman TB-MDR di Jawa Barat, Indonesia. Studi potong lintang dilakukan dengan mengambil data dari 4452 pasien terduga TB-MDR yang terregistrasi di eTB Manager selama tahun 2012-2016 yang dikirim ke Rumah Sakit Dr. Hasan Sadikin Bandung. Walaupun demikian, hanya 578 yang memiliki hasil test kultur untuk mengetahui sensitivitas obat TB. Dari kedua test tersebut, didapatkan Xpert® MTB/RIF memiliki sensitivitas 88% (95% IK: 85%-91%), spesifisitas 66% (95%CI: 60%-72%), positive predictive value 79% (95% IK: 75%-83%), dan negative predictive value 80% (95% IK: 74%-85%), dengan akurasi 79%. Test TB-MDR menggunakan Xpert® MTB/RIF pada penelitian ini menunjukkan performa yang baik, sehingga test ini sangat direkomendasikan untuk deteksi TB-MDR yang cepat, utamanya di daerah dengan prevalensi TB yang tinggi

Upper Lower Segment Ratio Comparison between Obese and Normal Children Aged 7 to 10 Years Old

Background: Upper lower segment ratio is an anthropometric measurement that often used to detect the presence of abnormal growth. Growth is affected by many factor, one of them is nutrional status. Obesity prevalence in Indonesian children increases annually. These children show an accelerated growth in pre-puberty compared to normal children in their age. This study aimed to analyze the difference in upper lower segment ratio between obese and normal children aged 7 to 10 years old.Methods: A cross sectional study was carried out in children aged 7 to 10 years old in three Elemantary School in Bandung during September–October 2013. Height and weight were measured to calculate body mass index (BMI) score and were grouped into obese (BMI >95th percentile) and normal (BMI 10th–85th percentile). The upper lower segment ratio was compared between obese and normal children and the level of the significant difference were analyzed by unpaired T-test.Results: From a total of 200 children recruited, 90 were obese and 110 were normal. There was no significant difference between upper lower segment ratio in obese and normal children (p=0.603) with mean ratio 1.137 and 1.142 respectively. The mean of upper lower segment ratio in obese boys was higher than normal boys (mean ratio 1.15 and 1.14 respectively), but obese girls had a lower ratio compared to normal girls (mean ratio 1.12 and 1.14 respectively).Conclusions: There is no difference between upper lower segment ratio in obese and normal children aged 7 to 10 years old. [AMJ.2016;3(1):147–51] DOI: 10.15850/amj.v3n1.72

Distribution of VDR Gene Polymorphisms Bsm-I rs1544410 and Apa-I rs7975232 among HIV/AIDS Patients from West Java

Vitamin D receptor, encoded by VDR gene, mediates vitamin D functions by not only regulating calcium metabolism and homeostasis but also in regulating immune response. Polymorphisms in VDR gene may increase the progression of human immunodeficiency virus (HIV) infection into acquired immunodeficiency syndrome (AIDS). This study aimed to explore the distribution of VDR polymorphisms among HIV sero-positive patients in West Java. A cross-sectional study was performed, recruiting 96 patients infected with HIV and VDR polymorphisms were analyzed. The genotype distributions of Bsm-I among HIV-infected patients were 2.2%, 18.5%, and 79.3% for BB, Bb, and bb, respectively whereas the distributions of Apa-I were 54.4%, 38.9%, and 6.7% for AA, Aa and aa, respectively. The frequency of VDR polymorphisms in Bsm-I among HIV-infected patients in West Java were considered high for b allele (88.6%), and in contrast for A allele in Apa-I that was 73.91%. Further studies involving healthy controls are needed to explore the VDR polymorphisms distribution in general population. Moreover, a cohort study, albeit challenging, is needed to further assess the association between VDR polymorphisms and the progression of HIV infection.Distribusi Polimorfisme gen VDR Bsm-I rs1544410 dan Apa-I rs7975232 pada Pasien HIV/AIDS di Jawa BaratReseptor vitamin D yang dikode oleh gen VDR mempunyai peranan penting terhadap fungsi vitamin D, tidak hanya dalam regulasi metabolisme dan keseimbangan kalsium namun juga berperan dalam meregulasi respon imun. Polimorfisme pada gen VDR ditengarai dapat meningkatkan progresivitas infeksi human immunodeficiency virus (HIV) menjadi acquired immunodeficiency syndrome (AIDS). Penelitian ini bertujuan mengetahui distribusi polimorfisme gen VDR pada pasien HIV di Jawa Barat. Penelitian ini melibatkan 96 pasien HIV dan dilakukan analisis polimorfisme gen VDR. Distribusi genotip Bsm-I pada pasien HIV di Jawa Barat adalah 2,2%, 18,5%, dan 79,3% untuk BB, Bb, dan bb, secara beurutan; sedangkan pada Apa-I adalah 54,4%, 38,9%, dan 6,7% untuk AA, Aa, dan aa. Frekuensi polimorfisme pada Bsm-I pada pasien HIV di Jawa Barat tergolong tinggi pada alel b (88,6%) dan berbanding terbalik pada dan Apa-I dengan alel A yaitu 73,91%. Penelitian lebih lanjut yang melibatkan individu kontrol diperlukan untuk mengetahui distribusi polimorfisme gen VDR pada populasi umum. Selain itu, studi kohort pada pasien HIV/AIDS diperlukan untuk menilai hubungan antara polimorfisme gen VDR terhadap progresivitas infeksi HIV

Moringa oleifera Lam. to accelerate wound healing: a review

An injury to the skin that disrupts the soft tissue may form a wound. The healing process in response to injury is a dynamic and well-regulated process of cellular, humoral, and molecular mechanisms that consists of four partly overlapping phases: hemostasis, inflammation, proliferation, and remodeling. An impaired wound-healing process may cause a formation of an abnormal scar and chronic wounds, leading to a reduced life quality. Therefore, it needs an optimal prevention strategy. Many modalities have been claimed to accelerate wound healing. The trend of using natural products is increasing in most Southeast Asian countries due to their biodiversity. Nowadays, studies on natural compounds are increasing to accelerate wound healing. Moringa oleifera Lam. is a high-value plant that each part of it has a high nutritional value as well as a great range of medicinal uses, including anti-inflammatory, antimicrobial, antioxidant, and wound healing properties. In this review, we have explored the M. oleifera that are very rich in vitamins, minerals, fatty acids, and phytochemical compounds like quercetin, kaempferol, and vicenin-2, that play a role in the wound healing process. Moreover, these compounds may enhance the healing of wounds with pathological conditions such as diabetes, immunocompromised and persistent infection

Upper Lower Segment Ratio Comparison between Obese and Normal Children Aged 7 to 10 Years Old

Background: Upper lower segment ratio is an anthropometric measurement that often used to detect the presence of abnormal growth. Growth is affected by many factor, one of them is nutrional status. Obesity prevalence in Indonesian children increases annually. These children show an accelerated growth in pre-puberty compared to normal children in their age. This study aimed to analyze the difference in upper lower segment ratio between obese and normal children aged 7 to 10 years old.Methods: A cross sectional study was carried out in children aged 7 to 10 years old in three Elemantary School in Bandung during September–October 2013. Height and weight were measured to calculate body mass index (BMI) score and were grouped into obese (BMI >95th percentile) and normal (BMI 10th–85th percentile). The upper lower segment ratio was compared between obese and normal children and the level of the significant difference were analyzed by unpaired T-test.Results: From a total of 200 children recruited, 90 were obese and 110 were normal. There was no significant difference between upper lower segment ratio in obese and normal children (p=0.603) with mean ratio 1.137 and 1.142 respectively. The mean of upper lower segment ratio in obese boys was higher than normal boys (mean ratio 1.15 and 1.14 respectively), but obese girls had a lower ratio compared to normal girls (mean ratio 1.12 and 1.14 respectively).Conclusions: There is no difference between upper lower segment ratio in obese and normal children aged 7 to 10 years old. [AMJ.2016;3(1):147–51] DOI: 10.15850/amj.v3n1.72

Effect of Moringa Leave Ethanol Extract on Accelerating Wound Healing Process

TGF-β and VEGF are vital in cell proliferation and regeneration, as evidenced in processes like wound healing. The leaves of Moringa oleifera Lam exhibit anti-inflammatory and cell regenerative properties that may facilitate the transition from the inflammatory to the proliferative phase, enhancing wound repair. This research sought to discern the potential of orally administered moringa leaf extract in augmenting systemic wound healing, focusing on TGF-β and VEGF serum as in vivo molecular markers. This research was conducted at the Animal Laboratory of the Faculty of Medicine, Universitas Padjadjaran, and the Laboratory of Molecular Genetics, Universitas Padjadjaran, from January to March 2022. We divided thirty Swiss Webster mice into two categories: healthy and wound-treated. Wounded mice received 100 mg/kgBW Na CMC as a negative control, 500 mg/kgBW zinc syrup as a positive control, and M. oleifera leaves ethanol extract (MOLE) in doses of 280 and 560 mg/kgBW orally from day 3 to day 6. Wound progression was documented and measured on days 0, -1, -3, and -6. Day-6 blood samples were obtained, and TGF-β and VEGF serum levels were gauged using ELISA. Results from day 6 revealed that wound coverage in the 280 and 560 mg/kgBW MOLE groups was 13.76±5% and 13.38±4%, respectively. These percentages notably surpassed that of the negative control group (p=0.005). However, the TGF-β and VEGF serum levels in the MOLE-treated groups did not differ significantly from the negative control (p=0.081 and p=0.149, respectively). Thus, the study concludes that while MOLE expedites wound closure, it does so without the systemic involvement of TGF-β and VEGF in vivo

N-Acetyltransferase 2 (NAT2) Acetylator Status among Systemic Lupus Erythematosus Patients from A Tuberculosis Endemic Area in Bandung, Indonesia

BACKGROUND: Systemic lupus erythematosus (SLE) patients living in Indonesia are prone to tuberculosis (TB) infection, since this country ranks second globally for TB prevalence. Isoniazid, an anti-tuberculosis (TB) drug, is metabolized by enzyme N-acetyltransferase 2 (NAT2) that is encoded by NAT2 gene. NAT2 haplotype, referring as acetylator status, may predispose as genetic factor in SLE development or complicate SLE therapy. This study explored the NAT2 haplotypes and acetylator status among SLE patients living in a TB endemic area.METHODS: Genomic DNA of 260 registered SLE patients at The Rheumatology Clinic of Dr. Hasan Sadikin General Hospital, Bandung, Indonesia were isolated. NAT2 gene was amplified and sequenced, then NAT2 haplotypes and the acetylator status among SLE patients with or without TB history were determined and presented.RESULTS: Most of SLE patients registered were female (n=250; 96.2%). The median age of patients when SLE was diagnosed for the first time was 27 years old (8-69 years), with organ involvement predominantly in musculoskeletal (80.8%) and mucocutaneous (73.1%). TB history, mostly pulmonary TB, was present in 23.1% of SLE patients of whom TB was diagnosed before SLE (10.4%) or after SLE (10.7%) or both before and after SLE (2%). The acetylator status was mostly intermediate (61.5%) with the NAT2*4/*6B was the most prevalent haplotype (25.8%).CONCLUSION: There is a high number of intermediate and low acetylator status among SLE patients. Since these SLE patients live in TB endemic area, the NAT2 acetylator status determination among SLE patients before starting TB therapy may have clinical benefit to decrease a possible drug induced liver injury, and this warrants further study.KEYWORDS: NAT2, acetylator, systemic lupus erythematosus, tuberculosi

Distribution of rs1801279 and rs1799930 Polymorphisms in NAT2 Gene among Population in Kupang, Nusa Tenggara Timur, Indonesia

BACKGROUND: N-acetyltransferase-2 (NAT2) enzyme, encoded by NAT2 gene, plays a key role in metabolism of anti-tuberculosis (TB) drug isoniazid. Polymorphisms in NAT2 gene may result in different responses to TB therapy. Since TB prevalence in the eastern part of Indonesia is high, the aim of this study is to explore the distribution of NAT2 gene polymorphisms among population from Kupang, Nusa Tenggara Timur.METHODS: A total of 234 respondents were included from Kupang in 2012. Polymorphisms of NAT2 gene were examined using mass screening platform and the genotypes distribution were presented in percentage. To confirm NAT2 gene polymorphisms, polymerase chain reaction (PCR)-sequencing was performed in a subset of population.RESULTS: The polymorphisms of NAT2 gene showed that the distribution of rs1801279 for GG genotype was 100%; whereas the genotype distribution of rs1799930 for GG, GA and AA was 57%, 35.1% and 7.9%, respectively. In a subset of individuals (n13), acetylator status was well determined by PCR-sequencing, resulting in individual with wild type fast acetylator (NAT2*4; n4), intermediate (NAT2*4/*5 or NAT2*4/*6 or NAT2*4/*7; n7) and poor acetylators (NAT2*6/*6 or NAT2*7/*7; n2).CONCLUSION: The amino acid change in rs1799930 result in intermediate and poor acetylator status in Kupang population. This may lead to suboptimal response of TB therapy. Assessing acetylator status before TB therapy is important and may serve as personalized INH therapy.KEYWORDS: NAT2 gene, polymorphism, acetylator status, Kupan

Phylogenetic Analysis of Human Papillomavirus 16 and 52 L1 Gene from Cervical Cancer in Bandung, Indonesia

BACKGROUND: Chronic infection with high-risk type of human papillomavirus (HPV) can cause cervical cancer. Previous studies showed that multiple infections of HPV are found in cervical cancer caused by multiple HPV infections and the most common are HPV-16 and HPV-52. The origin of HPV-16 circulating in Indonesia varies. The purpose of this study was to explore the origin of multiple infections of HPV-52 and HPV-16 in cervical cancer by using a phylogenetic tree.METHODS: During July-November 2010, 100 women were diagnosed with cervical cancer in the Department of Obstetrics and Gynecology, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Only 96 patients were involved in this study. Ninety-six samples of HPV deoxyribonucleic acid (DNA) were isolated from biopsied tissue of cervical cancer. Multiple infections of HPV genotypes HPV-16 and HPV-52 were confirmed by using the linear assay for HPV genotyping test. Afterward,HPV-52L1 gene was amplified by using self-designed primer. L1 gene was also sequenced and analyzed using phylogenetic program (MEGA6.06).RESULTS: The result of phylogenetic tree construction showed that isolated HPV-52 originated from multiple infections of HPV-16 and HPV-52 from cervical cancer patients in Bandung were in a subgroup with isolates originating from EU077219 Canada (America) and KT799980 southwest China (Asia). Isolate HPV-16 in one subgroup with isolates originating from KU951191.1 (Southwest China).CONCLUSION: L1 gene sequence from multiple infections isolated from HPV-16 and HPV-52 from cervical cancer patients in Bandung refers to the variation of L1 gene reported from Canada and southwest China. This proves that Indonesia’s HPV clusters are located in the strains found in America and Asia.KEYWORDS: multiple infections, HPV-16, HPV-52, L1 gene, phylogeneti

Natural resistance-associated macrophage protein 1 gene polymorphisms in thalassemia patients with tuberculosis infection

that needs regular blood transfusions leading to accumulation of iron in the cells. This iron overload level in macrophage might cause intracellular bacteria, particularly Mycobacterium tuberculosis (MTB) to multiply. Polymorphisms in natural resistance-associated macrophage protein 1 (NRAMP1), a metal transporter across the phagosome membrane, play important role in regulating iron, which is also needed by MTB. Increased iron in thalassemia patients may have an increased potential risk for TB. Objective To compare natural resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms (INT4, D543N, and 3’UTR) in thalassemia patients with and without tuberculosis (TB) infection. Methods A cross-sectional measurement of NRAMP1 genetic polymorphisms was performed in pediatric thalassemia patients with TB (n=40) and without TB (n=50). Iron status including serum iron, total iron-binding capacity (TIBC), and ferritin, was compared between the two groups. The NRAMP1 genetic polymorphisms were analysed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Allelic and genotypic distributions of each polymorphism were assessed for possible associations with TB infection. Results Mean serum iron and TIBC in thalassemia patients with TB were higher compared to thalassemia patients without TB (mean serum: 166.26 vs. 134.92 μmol/L, respectively; P=0.026) and (mean TIBC: 236.78 vs. 195.84 μmol/L, respectively; P=0.029). In thalassemia patients with TB, we observed significantly higher frequency of the C allele in INT4 (10% vs. 2%, respectively; OR=5.44; 95%CI 1.1 to 26.4; P=0.02) and the TGTG deletion allele (78.8% vs. 51%, respectively; OR=3.56; 95%CI 1.83 to 6.9; P=0.0002) in 3’UTR polymorphisms than in thalassemia patients without TB. There were no significant  differences in distributions of the A allele between TB and non-TB groups (16.3% vs. 15%, respectively; P=0.84) or the GA genotype (32.5% vs. 30%, respectively; P=0.79) in D543N. Conclusion The NRAMP1 polymorphisms are known to be associated with major gene susceptibility to TB, and in our thalassemia patients this association is even more pronounced