Studies on the Development of Scarring Trachoma in Tanzania

Trachoma is an ancient blinding disease which remains a public health and socio-economic threat to many communities, mainly in sub-Saharan Africa. Repeated conjunctival infection with Chlamydia trachomatis is thought to cause prolonged inflammation which leads to scarring and blindness, however, the disease is often found to progress in the absence of detected infection. Furthermore, despite apparently similar infection exposure, only some individuals progress to scarring. The relationship between infection and scarring progression and the immunopathological mechanisms underlying it are not clearly understood. A four-year longitudinal study was conducted in northern Tanzania in order to identify associations between C. trachomatis infection, conjunctival inflammation and immuno-fibrogenic gene expression with disease and scarring progression. Children aged 6-10 years at baseline were eligible for inclusion and 666 children were enrolled in the study. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection and immuno-fibrogenic gene expression by qPCR were collected at each time-point. Conjunctival photographs from baseline and final timepoints were graded and compared side-by-side to determine scarring incidence and progression. All community members were offered mass drug administration (MDA) with azithromycin for trachoma control annually for three years during the study. Host immuno-fibrogenic gene expression was profiled at the first five time-points. At baseline, host immune responses were analysed in relation to C. trachomatis infection, trachomatous inflammation – follicular (TF), papillary inflammation (TP) and scarring. Th1 and NK cell associated pathways were strongly associated with infection, suggesting their importance in the clearance of infection. Growth and matrix factors (MMPs) were strongly associated with the inflammation that persisted after infection was cleared (TF/TP), suggesting they might contribute to scarring development. Th17 pathway-associated cytokines were associated with infection and inflammation, therefore their contribution to protection versus pathology is unclear. The effect of azithromycin on inflammatory gene expression was investigated due to the reported immunomodulatory role of this antibiotic. Azithromycin treatment was found to have an anti-inflammatory effect on conjunctival gene expression, detectable three months posttreatment, suggesting that it may protect against pathological inflammation and therefore scarring development. The effect was gone by 6 months post treatment. Of the 448 children with outcome data, 103 (23.0%) had trachomatous scarring progression over the four-year study period. In 48 (10.7%) children this was incident scarring, whereas 55 (12.3%) had progression of pre-existing scarring. Scarring progression was strongly associated with papillary inflammation. Weaker associations between TF and C. trachomatis infection with scarring in univariate models were absent in a multivariable model adjusting for TP. These data suggest that the effect of infection and TF is mediated through TP, and that other factors contributing to the development of TP are important in driving scarring progression. Female sex was also associated with scarring progression. These findings suggest that the use of TP by trachoma control programs might be a more discriminating clinical marker to predict future scarring disease and requirements for trichiasis surgery than TF. In addition to clearing C. trachomatis infection, MDA might have an additional independent mechanism for reducing conjunctival inflammation, which may reduce subsequent risk of scarring progression

Hubungan Faktor Individu terhadap Keluhan Computer Vision Syndrome pada Karyawan Perusahaan Jasa Tenaga Kerja

Karyawan perusahaan jasa tenaga kerja memiliki poyensi terkena Computer Vision Syndrome (CVS) dikarenakan hampir semua aktivitas pekerjaan menggunakan Visual Display Terminal (VDT) berupa komputer atau laptop. Hasil dari survei kuesioner pada karyawan perusahaan jasa tenaga kerja dengan menggunakan kuesioner identifikasi gejala CVS, didapatkan karyawan yang mengalami keluhan CVS sebesar 97% dari 36 responden. Penelitian ini bertujuan untuk mengidentifikasi keluhan CVS pada perusahaan jasa tenaga kerja yang berhubungan dengan faktor individu. Faktor individu berupa durasi penggunaan VDT, durasi penggunaan smartphone dan durasi istirahat. Pengambilan data pada penelitian ini dilakukan dengan melakukan penyebaran kuesioner. Keluhan CVS diidentifikasi dengan menggunakan kuesioner Computer Vision Syndrome Quetionnaire (CVS-Q). Metode yang digunakan untuk mengetahui uji hubungan antar variabel menggunakan uji chi square. Untuk faktor yang berhubungan dengan keluhan CVS adalah durasi penggunaan VDT (p-value = 0,028) dan durasi istirahat (p-value = 0,012). Sedangkan untuk faktor yang tidak berhubungan adalah durasi istirahat (p-value = 0,592). Rekomendasi yang dapat diberikan antara lainmelakukan sosialisasi pencegahan keluhan CVS, pembuatan poster pencegahan keluhan CVS, dan penggunaan kacamata anti radiasi saat melakukan pekerjaan

Perancangan Sistem Diagnosis Kesehatan Manusia Melalui Screening Digital Berbasis Desktop Application Menggunakan Metode Forward Chaining dan Neural Network

Masalah pelayanan rumah sakit salah satunya antrian merupakan hal yang penting karena mempengaruhi produktivitas rumah sakit. Atrian rumah sakit dapat disebabkan karena banyaknya pasien serta lamanya penanganan pasien. Menurut Peraturan Menteri Kesehatan Republik Indonesia Nomor  30 Tahun 2022, standar kepuasan pasien terhadap pelayanan kesehatan harus mencapai ≥ 90 % dimana salah satu indikatornya yaitu lama waktu tunggu. Lamanya waktu tunggu atau antrian dapat menyebabkan pelayanan medis menjadi kurang maksimal terutama pada pasien yang memiki keluhan darurat (Prabowo, 2019). Oleh karena itu, untuk meningkatkan produktivitas pelayanan rumah sakit dilakukan perancangan sistem diagnosis kesehatan manusia melalui screening digital berbasis desktop application menggunakan metode forward chaining dan neural network untuk memudahkan dokter dalam mendiagnosa penyakit pasien. Pada inovasi ini juga dilengkapi dengan deteksi tingkat keparahan dan rekomendasi pengobatan kepada pasien. Tujuan dari penelitian ini yaitu menciptakan model pengetahuan yang dapat memprediksi penyakit pasien. Hasil dari penelitian ini yaitu didapatkan tingkat akurasi pengujian diagnosis penyakit pasien mencapai 86,6% dengan kemampuan fungsional aplikasi diagnosis yang dirancang dapat berfungsi 100%. Dengan adanya inovasi ini, diagnosis gejala penyakit manusia dapat dilakukan secara tepat dan tepat sehingga produktivitas rumah sakit dan derajat kesehatan pada setiap masyarakat di Indonesia meningkat

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania.

\ud \ud Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa

Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level

HDAC 阻害剤は Diethylstilbestrol による性腺刺激ホルモン細胞からのプロラクチン細胞への分化転換を抑制する

Diethylstilbestrol (DES), an estrogen agonist, increases prolactin (PRL) cells through transdifferentiation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells to PRL cells as well as proliferation of PRL cells in adult male mouse pituitary. Since hyperacetylation of histone H3 is implicated in the regulation of activation of various genes, we examined the effect of DES on the state of histone H3 acetylation. DES significantly reduced the immunohistochemical signal for acetylated histone H3 at lysine 9 (H3K9ac) in PRL, LH and FSH cells, but not for H3K18ac or H3K23ac. DES-treated mice were injected intraperitoneally with HDAC inhibitors (HDACi), sodium phenylbutyrate (NaPB) or valproic acid (VPA), to mimic the acetylation level of histone H3. As expected, HDACi treatment restored the level of H3K9ac expression in these cells, and also inhibited DES-induced increase in PRL cells. Furthermore, NaPB and VPA also abrogated the effects of DES on the population density of both LH and FSH cells. Similarly, the numbers of proliferating and apoptotic cells in the pituitary in NaPB- or VPA-treated mice were comparable to those of the control mice. Considered together, these results indicated that the acetylation level of histone H3 plays an important role in DES-induced transdifferentiation of LH to PRL cells as well as proliferation of PRL cells.長崎大学学位論文 学位記番号:博(医歯薬)甲第1128号 学位授与年月日:平成31年3月20日Author: Nandar Tun, Yasuaki Shibata, Myat Thu Soe, Myo Win Htun, Takehiko KojiCitation: Histochemistry and Cell Biology, 151(4), pp.291-303; 2018Nagasaki University (長崎大学)課程博