BALB/c Mice as Animal Model in Dengue Infection Research: Role of Endothelial Activation

Introduction. There were various challenges in using experimental animals model for dengue infection studies aside from the fact that dengue infection only naturally affects humans and does not manifest clinical signs as in humans. Various experimental animals have been used in dengue research, but the mouse model is more widely used since it is easier to obtain although sometimes they do not show clinical symptoms but may still measure the immune response. BALB/c mice are immunocompetent mice that have the potential to be used in dengue infection research. Endothelial cell activation plays a role in the pathogenesis of dengue virus infection which contributes to plasma leakage. One of the biomarkers of endothelial cell activation is soluble intercellular adhesion molecule 1 (sICAM-1).Method. An analytic observational study was conducted using BALB/c mice aged 8 weeks and weighed 40 grams. Selected BALB/c mice were randomly assigned to serotype 2 dengue virus containing 2.1 x 106 pfu/ml intraperitoneally, given only once. A total of 11 mice were injected with dengue virus serotype 2 and 11 mice were not injected with dengue virus. On the second day of virus injection, non structural (NS) 1 antigen dengue examination was carried out to prove that the BALB/c mice were indeed infected with dengue virus. In BALB/c mice that were proven to be infected with dengue virus, sICAM-1 levels were examined in serum after 7 days of infection. Mice that were not injected with dengue virus also examined sICAM-1Results. All of BALB/c mice injected with dengue virus were proven to be infected, as indicated by the detection of NS1 antigen in their serum. The mean serum level of NS1 antigen was 88.35 ng/ml (mean 95.34 ng/ml and standard deviation 21.94). The level of sICAM-1 in BALB/c mice infected with dengue virus (mean = 1.34) was significantly higher than mice that were not infected (mean =  0.79), with a p-value 0.045Conclusions. BALB/c mice were proven to be infected with dengue virus by detecting ns1 dengue virus antigen in the serum. The sICAM-1 levels in the group of BALB/c mice infected with dengue serotype 2 were significantly higher than the BALB/c mice that were not infected with dengue virus

SUBTIPE HIV-1 DI BEBERAPA DAERAH DI INDONESIA DAN PERANNYA SEBAGAI PETUNJUK DINAMIKA EPIDEMI HIV

Subtipe HIV-1 dapat ditentukan dengan melakukan analisis sekuens nukleotida dari gen selubung luar HIV-1, dengan mengekstrak DNA proviral dari sampel pasien, dan memakainya dalam PCR khusus untuk envelope HIV-1. Kemudian ini di sekuens dan dianalisis dengan memakai rujukan sekuens dari bank gen LANL (Los Alamos National Library) untuk menentukan subtipe. Distribusi geografi subtipe HIV-1 bersifat dinamis. Sampai sekarang terdapat 9 subtipe HIV dan 34 circulating recombinant forms (CRFs). Penelitian terdahulu mendapatkan ada dua subtipe HIV-1 yang beredar di Indonesia, Subtipe B dan CRF01_AE. Dengan mengetahui subtipe HIV-1 dapat membantu penelusuran arah epidemi dan memberikan informasi untuk merencanakan pencegahan HIV demikian juga memberikan informasi yang diperlukan dalam pembuatan vaksin. Oleh karena itu sangat penting dilakukan penelitian mengenai subtipe HIV di Indonesia.Rancangan penelitian adalah cross-sectional analytic yang dilakukan di Klinik Pelayanan AIDS di Denpasar, Bali dan Panti Rehabilitasi Narkoba di Bogor, Jawa Barat. Responden adalah odha dewasa yang memenuhi kriteria inklusi (odha dewasa dan bersedia ikut dalam penelitian) dan responden dipilih secara non probability sampling sampai memenuhi jumlah sampel yang dibutuhkan. Dengan memakai rumus 16.4 Sastroasmoro S. and Ismael S. (2002), jumlah sampel minimal dihitung sebesar 65. Untuk hipotesis 1, melihat perbedaan Subtipe HIV-1 dengan cara transmisi virus, analisis data menggunakan uji statistik Chi-Square. Untuk hipotesis 2, membandingkan Subtipe HIV-1 dengan derajat penyakit, analisis data menggunakan uji statistik Fisher’s Exact test, sedangkan untuk analisis data epidemiologi kasus dikerjakan secara deskriptif. Hasil disajikan dalam bentuk tabel, gambar pohon phylogenetic dan narasi.Dari penelitian ini didapatkan empat jenis subtipe di Indonesia, yaitu Subtipe B, CRF01_AE, C dan G (A/G). Semua pengguna narkotika suntik (penasun) terinfeksi oleh Subtipe CRF01_AE, dan hubungan ini terbukti secara statistic bermakna (Chi-square test with continuity correction value 7,951 p = 0,005) (Tabel 5.3.1). Subtipe HIV-1 tidak berhubungan secara bermakna dengan derajat penyakit, akan tetapi terdapat kecenderungan CRF01_AE mempunyai lebih banyak kasus dengan derajat penyakit berat dibandingkan dengan NonCRF01_AE. Prevalensi kasus dengan performance yang terganggu pada CRF01_AE adalah 30,3% sedangkan pada Non CRF01_AE 14,3%. Perbedaan ini secara statistic tidak bermakna (Fisher’s-Exact test p = 0,3445 (Tabel 5.11). Dari analisis Phylogenetic didapatkan bahwa transmisi HIV pada populasi risiko tinggi di Indonesia bersifat dinamis, dan epidemi yang terjadi tidak terpisah diantara populasi dengan faktor risiko yang berbeda.Kesimpulan dari penelitian adalah: CRF01_AE merupakan subtipe yang paling banyak didapatkan dan tersebar disebagian besar wilayah. CRF01_AE didapatkan pada populasi penasun, heteroseksual, penjaja seks komersial dan pelanggannya. Karena prevalensi HIV pada penasun sangat tinggi, baik di Bali maupun daerah lainnya di Indonesia (50%), maka ada kemungkinan penasun merupakan episentrum epidemi HIV di Bali dan beberapa daerah di Indonesia, yang akan menyebar ke populasi umum melalui kelompok heteroseksual risiko tinggi yaitu PSK dan pelanggannya. Sedangkan Subtipe B, C dan G (AG) terdapat baik pada homoseks dan heteroseks, namun tidak ada penasun. Data tersebut didukung oleh gambaran pohon phylogenetic (Gambar 5.3). Pemakaian DBS dalam penelitian ini cukup praktis dan aman, walaupun keberhasilannya masih rendah (44,9%). Sekarang sudah ada kertas saring yang lebih baik dan sesuai untuk dipakai pada penelitian yang akan datang.Saran dari penelitian ini adalah, dalam program harm reduction bagi penasun hendaknya juga menekankan pemakaian kondom secara konsisten dengan pasangan seksualnya. Disamping itu disarankan perlunya melakukan pemeriksaan subtipe HIV secara periodik karena distribusi subtipe HIV bersifat dinamis.</p

A Peer-support Mini-counseling Model to Improve Treatment in HIV-positive Pregnant Women in Kupang City, East Nusa Tenggara, Indonesia

Objectives Low adherence to antiretroviral (ARV) therapy in pregnant women with human immunodeficiency virus (HIV) increases the risk of virus transmission from mother to newborn. Increasing mothers’ knowledge and motivation to access treatment has been identified as a critical factor in prevention. Therefore, this research aimed to explore barriers and enablers in accessing HIV care and treatment services. Methods This research was the first phase of a mixed-method analysis conducted in Kupang, a remote city in East Nusa Tenggara Province, Indonesia. Samples were taken by purposive sampling of 17 people interviewed, consisting of 6 mothers with HIV, 5 peer facilitators, and 6 health workers. Data were collected through semi-structured interviews, focus group discussions, observations, and document review. Inductive thematic analysis was also performed. The existing data were grouped into several themes, then relationships and linkages were drawn from each group of informants. Results Barriers to accessing care and treatment were lack of knowledge about the benefits of ARV; stigma from within and the surrounding environment; difficulty in accessing services due to distance, time, and cost; completeness of administration; drugs’ side effects; and the quality of health workers and HIV services. Conclusions There was a need for a structured and integrated model of peer support to improve ARV uptake and treatment in pregnant women with HIV. This research identified needs including mini-counseling sessions designed to address psychosocial barriers as an integrated approach to support antenatal care that can effectively assist HIV-positive pregnant women in improving treatment adherence

Clinical Features of COVID-19 Patients at Udayana University Hospital During First Three Months of the COVID-19 Pandemic

COVID-19 exhibits a wide variety of symptoms, ranging from mild, moderate, severe, and critical respiratory dysfunctions up to death. Therefore, this study aimed to examine the demographic, clinical, and laboratory profile of COVID-19 patients admitted to Udayana University Hospital, Bali, during the first three months of the pandemic. Data were collected from the electronic medical records of 236 patients hospitalized from April to June 2020. The samples had a mean age of 40 years old, and they consisted of 58.50% male. Based on the records, the common clinical characteristics included fever (52.5%) and cough (47.5%), followed by less common traits, such as sore throat (18.2%), dyspnea (10.2%), flu (8.9%), and headache (3.8%). Laboratory results during admission showed an average lymphocyte count of 2.16 ± 2.19 × 109 cells/L and a neutrophil- lymphocyte ratio of 3.02 ± 3.41. The majority of patients were private corporation employees (30.51%), followed by migrant workers (21.19%). Furthermore, a fatality rate of 1.69% was recorded in the study hospital. These results were expected to provide epidemiological knowledge of COVID-19 patients, which can help clinicians to anticipate possible outcomes during treatment

Diarrhea Among International Travelers in Bali-Indonesia: Clinical and Microbiological Finding

Introduction: Diarrhea is a common illness among travelers to developing countries. Located in a tropical region, Bali has a potentially high prevalence of travelers diarrhea. This hospital-based cross-sectional study was carried out to assess the clinical and microbiological profiles of diarrhea among travelers admitted to Kasih Ibu hospital, Denpasar-Bali. Methods: This study enrolled a total of 71 patients at Kasih Ibu hospital between April 2015 and August 2016. All patients completed an epidemiologic questionnaire; their clinical histories were taken, and physical examinations were performed. Stool samples were collected for bacterial and parasitologic studies and susceptibility testing. Results: Most patients were female (70.4%), and the nationality of most patients was Dutch (15.5%). Secretory diarrhea was the most frequently found diarrheal type (88.7%), with only 5.6% of cases having severe dehydration which developed into acute kidney injury. A high percentage of Entamoeba spp. was also seen in this study (54.9%). Of the 37 stool samples available for microbiological testing, 62.2% showed growth; Escherichia coli was the most commonly isolated bacteria (54.1%). Patients not infected by Entamoeba spp. were found more likely to experience nausea and vomiting (P Conclusion: Secretory diarrhea was the most prevalent type of diarrhea among travelers admitted to Kasih Ibu hospital, Bali. The most frequently found pathogens were Entamoeba spp. and E. coli. Although most patients had only mild dehydration as a complication, acute kidney injury did occur in some cases

Anal human papillomavirus genotype distribution and its associations with abnormal anal cytology among men who have sex with men

BACKGROUND Anal human papillomavirus (HPV) is associated with the severity of anal cytologic abnormalities that are precancerous lesions. Knowledge of HPV type distribution in populations at risk for anal cancer is needed. This study investigated anal HPV infections and cytological abnormalities among men who have sex with men (MSM). METHODS A cross-sectional study was conducted involving 90 men aged >30 years with a history of anal sexual intercourse with men. Demographic characteristics and sexual behaviors were collected by using a self-completed questionnaire. Anal cytological results were examined, and HPV genotyping was performed by the Linear Array HPV genotyping test. Descriptive analyses of subject characteristics, prevalence, and 95% confidence intervals (CI) were performed. A chi-square test was used to determine their associations with high-risk HPV infection and cytological abnormalities. RESULTS The overall prevalence of abnormal cytology was 32% (24/75), atypical squamous cells of undetermined significance (ASCUS) 17.33 % (13/75), 14.66% (11/75) were classified as low-grade SIL (LSIL) and no participant had high-grade SIL (HSIL). Prevalence of HPV infection with normal cytology was 86.27% (44/51), ASCUS 92.30% (12/13), and LSIL 100% (11/11). The most common types of anal HPV in participants with cytological abnormalities are HPV 16, HPV 18 for high-risk HPV, and HPV 11, HPV 6 for low-risk HPV. There were no associations between the predictor variables and the abnormal cytology (p>0.05). CONCLUSION There was a high prevalence of HPV infection in MSM with abnormal anal cytology. A routine anal Pap smear program and vaccination are needed to prevent HPV infection and anal dysplasia in MSM

Diarrhea Among International Travelers in BaliIndonesia: Clinical and Microbiological Finding

Introduction: Diarrhea is a common illness among travelers to developing countries. Located in a tropical region, Bali has a potentially high prevalence of travelers diarrhea. This hospital-based cross-sectional study was carried out to assess the clinical and microbiological profiles of diarrhea among travelers admitted to Kasih Ibu hospital, Denpasar-Bali. Methods: This study enrolled a total of 71 patients at Kasih Ibu hospital between April 2015 and August 2016. All patients completed an epidemiologic questionnaire; their clinical histories were taken, and physical examinations were performed. Stool samples were collected for bacterial and parasitologic studies and susceptibility testing. Results: Most patients were female (70.4%), and the nationality of most patients was Dutch (15.5%). Secretory diarrhea was the most frequently found diarrheal type (88.7%), with only 5.6% of cases having severe dehydration which developed into acute kidney injury. A high percentage of Entamoeba spp. was also seen in this study (54.9%). Of the 37 stool samples available for microbiological testing, 62.2% showed growth; Escherichia coli was the most commonly isolated bacteria (54.1%). Patients not infected by Entamoeba spp. were found more likely to experience nausea and vomiting (P < 0.005). Conclusion: Secretory diarrhea was the most prevalent type of diarrhea among travelers admitted to Kasih Ibu hospital, Bali. The most frequently found pathogens were Entamoeba spp. and E. coli. Although most patients had only mild dehydration as a complication, acute kidney injury did occur in some cases

Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from TAHOD

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P = 0.002), had HIV viral load ≥500 copies/mL or missing (P = 0.021), had shorter history of HIV infection (P = 0.048), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P < 0.001). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P < 0.001), missing recent HIV viral load (P < 0.001), negative hepatitis C test (P = 0.025), and previous temporary LTFU episodes (P < 0.001). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced

Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD).</p> <p>Methods</p> <p>Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models.</p> <p>Results</p> <p>A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation.</p> <p>Conclusions</p> <p>After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain.</p