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

MRSA Infection in Patients Hospitalized at Sanglah Hospital: A Case Series

This is the first report of MRSA infection in Sanglah Hospital. We reviewed eight patients with MRSA infection from microbiologi laboratory records between January and May 2011, than followed by tracing medical records to obtained data of the patients. Five of cases with sepsis, 1 case with osteomyelitis, and the two others with mediastinitis and pneumonia. The patients were kept in private isolated room and barrier-nursing technique was strictly followed. Further action was culturing specimen taken from the patients nose, throat, axilla, and samples taken from the health care workers, with no MRSA colonization were found. Five patients demonstrated good respond to intravenous administration of either vancomycin or linezolide. Three were died due to septic shock before the laboratory culture and antimicrobial susceptibility availabled. All of the strains isolated more than 48 hours after admission and also demonstrated clinical risk factors for hospitalized acquired MRSA (HAMRSA). These strains had  resistance to ß-lactams but remain susceptible to many non ß-lactam antibiotics, as reported in some community acquired MRSA (CA-MRSA) isolates. Future study using molecular typing required to fully understand the magnitude and ongoing evolution of MRSA infections.Key words: MRSA, Antimicrobial susceptibility, treatmen

Predictors to Achieve Normal Nutrition Status: Longitudinal Study Among HIV Children on Antiretroviral Treatment in Bali

Background and purpose: Malnutrition is common in children with HIV/AIDS. Antiretroviral therapy (ART) improves the nutritional status; however, information about predictors affecting the changes of nutritional status is limited and inconsistent.Methods: The retrospective survival study analyzed secondary data of 84 undernourished children receiving ART in Sanglah Central Hospital in 2010 to 2015. Demographic, clinical and socio-economic characteristics at ART initiation were linked to the achievement of normal nutritional status (z-score ? -2 SD). Kaplan Meier analysis was used to obtain the incidence rate and median time and cox proportional hazards models to identify its predictors.Results: Of the 73.81% of children achieved a normal nutrition status with the incidence of children achieving normal nutritional was 19 per 100 child months, and a median time of 4 months 10 days. Children with birth weight ?2500 gr (AHR=5.41; 95%CI: 1.76-16.61), without candidiasis (AHR=3.72; 95%CI: 1.27-10.93), Clinical WHO Stage III (AHR=1.6; (95%CI: 1.08-4.24), Clinical WHO Stage II (AHR=4.49; 95%CI: 1.95-10.79) and early ART intiation (AHR=0.91; 95%CI: 0.83-0.98) were predictors to achieve normal nutritional status.Conclusion: Clinical characteristics of children are predictors of achieving a normal nutritional status

Predictors of Loss to Follow Up and Mortality Among Children ?12 Years Receiving Anti Retroviral Therapy During the First Year at a Referral Hospital in Bali

Background and purpose: Many HIV-infected children in Bali have started antiretroviral therapy (ART), but loss to follow up (LTFU) is a continuing concern, and the issue of childhood adherence is more complex compared to adults.Methods: This was a retrospective study among cohort of 138 HIV+ children on ART in Sanglah General Hospital, Denpasar, Bali from January 2010 to December 2015. Kaplan-Meier analysis was used to describe incidence and median time to LTFU/mortality and Cox Proportional Hazard Model was used to identify predictors. Variables which were analysed were socio-demographic characteristics, birth history, care giver and clinical condition of the children.Results: Mean age when starting ARV therapy was 3.21 years. About 25% experienced LTFU/death by 9.1 month resulting in an incidence rate of 3.28 per 100 child month. The higher the WHO stage, the higher the risk for LTFU/mortality along with low body weight (AHR=0.90; 95%CI: 0.82-0.99).Conclusion: Clinical characteristics were found as predictors for LTFU/mortality among children on ART

Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol) according to exposure to different combination antiretroviral regimens in Asian (n = 2051) and Australian (predominantly Caucasian, n = 794) cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs) and either of at least one protease inhibitor (PI) or non-nucleoside-reverse transcriptases (NNRTIs). We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both); and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: <0.001) but not in case of other lipids (P for interaction: >0.05). The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations

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