Burden of HIV, HBV and syphilis among children in urban Ethiopia: Community-based cross-sectional study.

BACKGROUND: Children have largely been ignored in the fight against sexually transmitted infection (STI). Among children, STI is reported to be a globally emerging public health challenge. We evaluated the burden of HIV, hepatitis B virus (HBV) and syphilis among children (< 15 years old) and its determinants in urban Ethiopia. METHODS: For this study, we used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), collected through a nationally representative, community-based study conducted in Ethiopia from October 2017 to April 2018. We used plasma samples from 4729 children. Moreover, we linked the data and analysed them alongside their respective mothers. Child and maternal HIV status was determined using the national testing algorithm. Plasma samples from children were also tested for syphilis and HBV surface antigen. A descriptive analysis was done followed by bivariable analysis with 95% confidence interval (CI) at a significance level of p < 0.05. We finally evaluated predictors of STIs using regression analysis. RESULTS: HIV, HBV and syphilis prevalence rates among urban children in Ethiopia were 0.36%, 1.48% and 0.28%, respectively. Children living in Gambella and Addis Ababa had a 6.41-fold (95% CI: 3.20-9.88) and 4.20-fold (95% CI: 3.24-5.46) higher risk of HIV infection compared with those in Dire Dawa. Children of HIV-positive mothers had a 10.31-fold (95% CI: 3.20-18.19) higher risk of HIV infection, and if those mothers were not taking highly active antiretroviral therapy (HAART), the risk was 7.27 times higher (95% CI: 2.57-12.64). Those who were from HIV-positive mothers with viral load ≥ 1000 copies/mL had a 18.64-fold (95% CI: 6.36-31.24) higher risk of HIV infection and those with a history of breastfeeding had a 3.27-fold (95% CI: 1.11-5.67) higher risk. Children from Addis Ababa had a 3.26-fold (95% CI: 1.64-6.66) higher risk of HBV infection compared with those from Dire Dawa. Moreover, for those from HIV-positive mothers and whose mother was not taking HAART, the risk of HBV transmission was 6.37 (95% CI: 2.20-19.96) and 3.62 (95% CI: 1.27-11.29), respectively. Children living in Gambella, Somali, Afar and Tigray had a 7.21-fold (95% CI: 2.30-18.68), 3.10-fold (95% CI: 1.28-3.74) and 1.32-fold (95% CI: 1.11-3.38) higher risk of acquiring active syphilis compared with those living in Dire Dawa, respectively. Those from HIV-positive mothers also had a 4.22-fold (95% CI: 1.16-8.39) higher risk of acquiring active syphilis. CONCLUSION: The burden of HIV, HBV and syphilis was high among children in urban Ethiopia. The key determinants for the high burden of HIV, syphilis and HBV were maternal factors including maternal HIV status and breastfeeding. This might be due to the challenges associated with mother-to-child transmission. Hence, the programme shall focus on the elimination of the triple infections of HIV, syphilis and HBV.

Analysis of the upstream genetic structures of the ISEcp1-blaCTX-M transposition units in Escherichia coli isolates carrying blaCTX-M obtained from the Indonesian and Vietnamese communities.

Extended spectrum ß-lactamase (ESBL)-producing Escherichia coli have been found in healthy individuals in Indonesia and Vietnam. The ISEcp1-blaCTX-M transposition unit of ESBL-producing bacterial isolates has been considered responsible for the production of CTX-M type ESBL and it is important for the dissemination of blaCTX-M . This study aimed to characterize the upstream genetic structure (UGS) of E. coli isolates possessing blaCTX-M-1 group and/or blaCTX-M-9 group genes obtained from healthy individuals in Indonesia and Vietnam. A total of 501 CTX-M type ESBL-producing E. coli isolates possessing blaCTX-M-1 group and/or blaCTX-M-9 group genes were obtained from healthy individuals of the two countries in 2018. The UGSs of the ISEcp1-blaCTX-M transposition unit of the 501 ESBL-producing E. coli isolates were amplified by barcode-adaptor-ligation-mediated PCR and analyzed using the Nanopore sequencer. The obtained sequence information was used to classify the UGSs of the ISEcp1-blaCTX-M transposition unit. From the 501 ESBL-producing E. coli isolates, 502 UGSs were obtained, which were classified into 85 UGS types based on the sequence. ISEcp1 of 359 (71.5%) of the 502 UGSs was disrupted by gene insertion, and ISEcp1-blaCTX-M transposition unit of most (87.1%) of the determined UGSs was confirmed as plasmidic. Only 6 (7.1%) of the 85 UGS types were common to both countries. Our results indicated that many different UGSs of ISEcp1-blaCTX-M transposition units were detected in Indonesia and Vietnam; hence, we suggest that structurally different kinds of plasmids harboring blaCTX-M were separately distributed in the two countries.

Differential effects of chromosome and plasmid blaCTX-M-15 genes on antibiotic susceptibilities in extended-spectrum beta-lactamase-producing Escherichia coli isolates from patients with urinary tract infection.

OBJECTIVES: To compare antibiotic susceptibilities between chromosomal and plasmid blaCTX-M-15 locations in urinary tract infection-causing extended-spectrum ß-lactamases-producing Escherichia coli blaCTX-M-15 isolated in Indonesia. METHODS: A total of 84 strains identified as extended-spectrum ß-lactamases-producing E. coli were isolated from patients with urinary tract infection in Indonesia in 2015. Antimicrobial susceptibility tests were performed on these strains using 18 antibiotics, and extended-spectrum ß-lactamase bla genes were detected by polymerase chain reaction. Gene localization of blaCTX-M-15 -positive strains was confirmed by Southern blot hybridization, and epidemiological typing was conducted using multilocus sequence typing. RESULTS: Of 54 strains harboring the blaCTX-M-15 gene, 27 showed localization on chromosome, 20 on plasmid, and seven on chromosome and plasmid. Most multilocus sequence typing sequence types of the 27 strains with chromosomal blaCTX-M-15 were ST405 (25.9%) and ST131 (22.2%) strains, whereas the 20 strains with plasmid-blaCTX-M-15 were mostly ST410 (55.0%). CONCLUSIONS: Extended-spectrum ß-lactamases-producing E. coli blaCTX-M-15 with plasmid genes show significantly higher resistant rates against piperacillin-tazobactam but lower resistant rates against chloramphenicol compared to chromosomal strains in Indonesian patients with urinary tract infection. Mechanistic investigations will be necessary to advance our knowledge of antimicrobial resistance in urinary tract infection.

Characterization of CTX-M-type-extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolated from Indonesian undergraduate medical students of a university in Surabaya, Indonesia.

Enterobacteriaceae isolates producing CTX-M-type extended-spectrum ß-lactamase (ESBL) has been found in hospitalized patients and healthy individuals in communities of the Southeast Asian countries. Medical students might have more risk of ESBL-producing Enterobacteriaceae contagion, because medical students who belong to communities have direct and indirect contacts with workers and patients in healthcare facilities. The aim of this study was to collect information for evaluation of the potential risk of ESBL-producing Enterobacteriaceae contagion in Indonesian undergraduate medical students by characterizing genotypic properties of Escherichia coli isolates-producing CTX-M-type ESBL. A total 141 fecal samples collected from 207 medical students of a university in Surabaya, Indonesia were subjected to PCR, XbaI and S1 nuclease-pulsed-field gel electrophoresis (PFGE), Southern blotting, and sequencing analysis. Eighty-two ESBL-producing Enterobacteriaceae, including 75 E. coli and 7 Klebsiella pneumoniae were isolated from 79 (56.0%) students. Among 75 ESBL-producing E. coli, blaCTX-M-15 was the most prevalent type (44.0%). Although XbaI-PFGE results showed genetic background of the E. coli isolates producing CTX-M-type ESBL were diverse, five clonal spread cases of certain E. coli producing CTX-M-type ESBL isolates were observed among the medical students. Our results suggested that ESBL-producing Enterobacteriaceae might be circulating among the medical students through contaminated environment such as in a university or communities they belonged.

Prevalence and characterisation of Staphylococcus aureus causing community-acquired skin and soft tissue infections on Java and Bali, Indonesia.

OBJECTIVES: To define the role of Staphylococcus aureus in community settings among patients with skin and soft tissue infections (SSTI) in Indonesia. METHODS: Staphylococcus aureus were cultured from anterior nares, throat and wounds of 567 ambulatory patients presenting with SSTI. The mecA gene and genes encoding Panton-Valentine leukocidin (PVL; lukF-PV and lukS-PV) and exfoliative toxin (ET; eta and etb) were determined by PCR. Clonal relatedness among methicillin-resistant S. aureus (MRSA) and PVL-positive S. aureus was analysed using multilocus variable-number tandem-repeat analysis (MLVA) typing, and multilocus sequence typing (MLST) for a subset of isolates. Staphylococcal cassette chromosome mec (SCCmec) was determined for all MRSA isolates. Moreover, determinants for S. aureus SSTI, and PVL/ET-positive vs PVL/ET-negative S. aureus were assessed. RESULTS: Staphylococcus aureus were isolated from SSTI wounds of 257 (45.3%) patients, eight (3.1%) of these were MRSA. Genes encoding PVL and ETs were detected in 21.8% and 17.5% of methicillin-susceptible S. aureus (MSSA), respectively. PVL-positive MRSA was not detected. Nasopharyngeal S. aureus carriage was an independent determinant for S. aureus SSTI (odds ratio [OR] 1.8). Primary skin infection (OR 5.4) and previous antibiotic therapy (OR 3.5) were associated with PVL-positive MSSA. Primary skin infection (OR 2.2) was the only factor associated with ET-positive MSSA. MLVA typing revealed two more prevalent MSSA clusters. One ST1-MRSA-SCCmec type IV isolate and a cluster of ST239-MRSA-SCCmec type III were found. CONCLUSIONS: Community-acquired SSTI in Indonesia was frequently caused by PVL-positive MSSA, and the hospital-associated ST239-MRSA may have spread from the hospital into the community.

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health.

Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

Occurrence and characterization of carbapenem-resistant Gram-negative bacilli: A collaborative study of antibiotic-resistant bacteria between Indonesia and Japan.

OBJECTIVES: To explore the occurrence and characterization of carbapenemase-producing pathogens among carbapenem-resistant Gram-negative bacilli isolated from hospitalized patients with urinary tract infection in Indonesia. METHODS: This was a study promoted by the Japanese-Indonesian collaborative research program in the Japan Initiative for Global Research Network on Infectious Diseases. Bacterial pathogens were prospectively isolated from urine specimens of hospitalized urinary tract infection patients at Dr. Soetomo Hospital (Surabaya, Indonesia). All Gram-negative bacteria resistant to third-generation cephalosporin or carbapenem were included in this study. Carbapenemase genes were investigated for phenotype and genotype. RESULTS: In total, 1082 Gram-negative bacilli were isolated, of which 116 strains were resistant to imipenem or meropenem (carbapenem-resistant Gram-negative bacilli), and 22 strains were carbapenemase-producing Gram-negative bacilli. Carbapenemase-producing Gram-negative bacilli consisted of Acinetobacter baumannii (n = 4), Pseudomonas aeruginosa (n = 4), Klebsiella pneumoniae (n = 5), Providencia rettgeri (n = 4) and five others. The carbapenemase-producing Gram-negative bacilli included NDM-1 (n = 18, 81.8%, in Enterobacteriaceae and Acinetobacter spp.) and IMP-7 (n = 4, 18.2%, all in P. aeruginosa). Among carbapenem-resistant Gram-negative bacilli, all four P. aeruginosa were sensitive to colistin, and all six Acinetobacter spp. were sensitive to minocycline, colistin and tigecycline. Of those patients harboring carbapenemase-producing Gram-negative bacilli, 12 (54.5%) were seriously ill at the time of admission, with longer hospital stays and three deaths (13.6% mortality rate). CONCLUSIONS: Urinary tract infection-causing carbapenem-resistant Gram-negative bacilli are widely disseminated in Indonesia. The NDM-1 phenotype seems to be dominant, and it can be treated with colistin and tigecycline in most cases. Most patients harboring carbapenemase-producing Gram-negative bacilli are seriously ill, have a bad prognosis, with a longer hospital stay and a significant mortality rate.

Characterisation of clinical Staphylococcus aureus isolates harbouring mecA or Panton-Valentine leukocidin genes from four tertiary care hospitals in Indonesia.

OBJECTIVES: To determine the prevalence, antimicrobial susceptibility profiles and clonal distribution of either methicillin-resistant Staphylococcus aureus (MRSA) or Panton-Valentine leukocidin (PVL)-positive S. aureus obtained from clinical cultures in Indonesian hospitals. METHODS: S. aureus isolates from clinical cultures of patients in four tertiary care hospitals in Denpasar, Malang, Padang and Semarang were included. We assessed the antimicrobial susceptibility profiles using the Vitek2(®) system, determined the presence of the mecA gene and genes encoding PVL using PCR and analysed the clonal relatedness with Raman spectroscopy. SCCmec typing was performed for all MRSA isolates. Multilocus sequence typing (MLST) was performed for a subset of isolates. RESULTS: In total, 259 S. aureus strains were collected. Of these, 17/259 (6.6%) and 48/259 (18.5%) were MRSA and PVL-positive methicillin-susceptible S. aureus (MSSA), respectively. The prevalence of MRSA and PVL-positive MSSA ranged between 2.5-8.9% and 9.5-29.1%, respectively and depended on geographic origin. PVL-positive MRSA were not detected. Raman spectroscopy of the strains revealed multiple Raman types with two predominant clusters. We also showed possible transmission of a ST239-MRSA-SCCmec type III strain and a ST121 PVL-positive MSSA in one of the hospitals. CONCLUSIONS: We showed that MRSA and PVL-positive MSSA are of clinical importance in Indonesian hospitals. A national surveillance system should be set-up to further monitor this. To reduce the prevalence of MRSA in Indonesian hospitals, a bundle of intervention measures is highly recommended.

Spirituality, Religiosity, and Health: a Comparison of Physicians' Attitudes in Brazil, India, and Indonesia.

BACKGROUND: One of the biggest challenges in the spirituality, religiosity, and health field is to understand how patients and physicians from different cultures deal with spiritual and religious issues in clinical practice. PURPOSE: The present study aims to compare physicians' perspectives on the influence of spirituality and religion (S/R) on health between Brazil, India, and Indonesia. METHOD: This is a cross-sectional, cross-cultural, multi-center study carried out from 2010 to 2012, examining physicians' attitudes from two continents. Participants completed a self-rated questionnaire that collected information on sociodemographic characteristics, S/R involvement, and perspectives concerning religion, spirituality, and health. Differences between physicians' responses in each country were examined using chi-squared, ANOVA, and MANCOVA. RESULTS: A total of 611 physicians (194 from Brazil, 295 from India, and 122 from Indonesia) completed the survey. Indonesian physicians were more religious and more likely to address S/R when caring for patients. Brazilian physicians were more likely to believe that S/R influenced patients' health. Brazilian and Indonesians were as likely as to believe that it is appropriate to talk and discuss S/R with patients, and more likely than Indians. No differences were found concerning attitudes toward spiritual issues. CONCLUSION: Physicians from these different three countries had very different attitudes on spirituality, religiosity, and health. Ethnicity and culture can have an important influence on how spirituality is approached in medical practice. S/R curricula that train physicians how to address spirituality in clinical practice must take these differences into account.

Management of wounds in diabetes by administering allicin and quercetin in emulsion form as wound medicine in diabetic rat models.

Wounds in diabetes is a complex problem that requires effective treatment at a high cost. Adjuvant therapy from natural bioactive elements can be an alternative to overcome problems in diabetic wound healing disorders. Allicin and quercetin are natural bioactive substances contained in several fruit or vegetable plants that have various pharmacological effects. The purpose of this study was to determine the effect of allicin and quercetin in emulsion form as wound medicine in helping the wound healing process. Diabetic wistar rats with wounds on their backs measuring 1 × 1 cm were divided into four treatment groups which were given wound medicine once a day for seven days according to their distribution. The wound healing process was evaluated on the third and seventh day. Data were observed and analyzed using appropriate statistical tools. Measurement of wound healing indicators was carried out by examining wound contraction and histopathological examination showing that the treatment group given the allicin and quercetin formula experienced an improvement compared to the treatment group without allicin and quercetin. Allicin and quercetin increase the percentage of wound contraction, increase the density of blood vessels and the epithelialization process in the wound so that the wound healing process becomes faster. In conclusion, allicin and quercetin can be effective adjuvant therapies in helping wound healing in diabetes. Wound medication in the form of an emulsion is an effective choice, because it can maintain the stability of the allicin and quercetin content and can make the wound environment moist.

Metagenome and Resistome Analysis of Beta-Lactam-Resistant Bacteria Isolated from River Waters in Surabaya, Indonesia.

Antimicrobial agents are administered to humans and livestock, and bacterial antimicrobial resistance (AMR) and antimicrobial agents are released into the environment. In this study, to investigate the trend of AMR in humans, livestock, and the environment, we performed a metagenomic analysis of multidrug-resistant bacteria with CHROMagar ESBL in environmental river water samples, which were collected using syringe filter units from waters near hospitals, downtown areas, residential areas, and water treatment plants in Surabaya, Indonesia. Our results showed that Acinetobacter, Pseudomonas, Aeromonas, Enterobacter, Escherichia, and Klebsiella grew in CHROMagar ESBL; they were most frequently detected in water samples from rivers surrounding hospitals contaminated with various AMR genes (ARGs) in high levels. These results identified bacteria as ARG reservoirs and revealed that hospitals could be sources for various ARGs disseminated into the environment. In conclusion, this study details a novel metagenomic analysis of collected bacteria in environmental water samples using a syringe filter unit for an AMR epidemiological study based on the One Health approach.

Evidence of Placental Villous Inflammation and Apoptosis in Third-Trimester Symptomatic SARS-CoV-2 Maternal Infection.

PURPOSE: In view of conflicting reports on the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to infect placental tissue, this study aimed to further evaluate the impact of inflammation and placental damage from symptomatic third-trimester maternal COVID-19 infection. MATERIALS AND METHODS: This case-control study included 32 placenta samples each from symptomatic COVID-19 pregnancy and normal non-COVID-19 pregnancy. The villous placental area's inflammatory expression [angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine-2 (TMPRSS2), interferon-γ (IFN-γ), interleukin-6 (IL-6), and SARS-CoV-2 spike protein] and apoptotic rate were examined using immunohistochemistry and Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Comparison and correlation analysis were used based on COVID-19 infection, placental SARS-CoV-2 spike protein evidence, and maternal severity status. RESULTS: Higher expressions of TMPRSS2, IFN-γ, and trophoblast apoptotic rate were observed in the COVID-19 group (p<0.001), whereas ACE-2 and IL-6 expressions were not significantly different from the control group (p>0.05). Additionally, SARS-CoV-2 spike protein was detected in 8 (25%) placental samples of COVID-19 pregnancy. COVID-19 subgroup analysis revealed increased IFN-γ, trophoblast, and stromal apoptosis (p<0.01). Moreover, the results of the current study revealed no correlation between maternal COVID-19 severity and placental inflammation as well as the apoptotic process. CONCLUSION: The presence of SARS-CoV-2 spike protein as well as altered inflammatory and apoptotic processes may indicate the presence of placental disturbance in third-trimester maternal COVID-19 infection. The lack of correlation between placental disruption and maternal severity status suggests the need for more research to understand the infection process and any potential long-term impacts on all offsprings born to COVID-19-infected pregnant women.

Impact TB co-infections on immune tolerance among people living with HIV: a systematic review.

BACKGROUND: The high-burden regions of Sub-Saharan Africa, which accounted for greater than 70% of the HIV epidemic, are disproportionately affected by the high rates of TB coinfection. This might be explained by, the low immune tolerance of the population due to malnutrition and chronic infections aggravating immune suppression. In this review, we discuss the immunopathogenesis of this common co-infection that causes significant morbidity and mortality in people living with HIV globally. METHODS: We used published studies using a two-step search strategy. Initial search of Pub Med Central and Google Scholar was undertaken followed by an analysis of the keywords. A second search using all the reference list of all identified reports and articles was searched for additional studies. Literature published as of January 1, 1981, that meets the inclusion criteria were considered. Qualitative data was extracted from papers included in the review. RESULT: Mortality occurs at both ends of the immunological spectrum of TB at one end HIV uninfected patient dies from asphyxiation from acute massive hemoptysis due to cavitary TB; at the other end, and far more frequently HIV-infected patient with disseminated TB dies from overwhelming infection with less evidence of focal pathology. There is no clear sign that the HIV-TB epidemic is slowing, especially considering the emergence of increasingly drug-resistant strains of MTB. A major challenge for the future is to discover immune correlates of TB protection and TB disease risk. Failure to define this conclusively has hindered TB prevention strategies, including the design of new TB vaccines to replace BCG, which provides only shortlived efficacy, prevents severe forms of the extra-pulmonary disease and is contraindicated in PLHIV. CONCLUSION: Understanding TB and HIV infection through immunological advances needs to be combined to describe the complex interactions between TB and HIV and the effects of ART. The complex interactions between the individual components of innate and acquired immune responses to TB and HIV infection is also likely to be the next step forward.

HAART induced inflammation, toxicity and its determinants among HIV positive children in Addis Ababa, Ethiopia.

Background: Highly Active Antiretroviral therapy (HAART) plays significant role in reduction of mortality among children infected with HIV. Despite the inevitable impact of HAART on inflammation and toxicity, there is limited evidence on its impact among children in Ethiopia. Moreover, evidence on contributing factors to toxicity has been poorly described. Hence, we evaluated HAART induced inflammation and toxicity among children taking HAART in Ethiopia. Method: This cross-sectional study was conducted among children (<15 years old) taking HAART in Ethiopia. Stored plasma samples and secondary data from a previous study on HIV-1 treatment failure were used for this analysis. By 2018, a total of 554 children were recruited from randomly selected 43 health facilities in Ethiopia. The different levels of liver (SGPT), renal (Creatinine) and hematologic toxicity (Hemoglobin) toxicity were assessed using established cut-off value. Inflammatory biomarkers (CRP and vitamin-D) were also determined. Laboratory tests were done at the national clinical chemistry laboratory. Clinical and baseline laboratory data were retrieved from the participant's medical record. Questionnaire was also administered to study guardians to assess individual factors to inflammation and toxicity. Descriptive statistics was used to summarize the characteristics of the study participants. Multivariable analysis was conducted and considered significant at P < 0.05. Result: Overall 363 (65.6%) and 199 (36%) of children taking HAART in Ethiopia developed some level of inflammation and vitamin-D in-sufficiency, respectively. A quarter of the children 140 (25.3%) were at Grade-4 liver toxicity while renal toxicity were 16 (2.9%). A third 275 (29.6%) of the children also developed anemia. Children who were on TDF+3 TC + EFV, those who were not virally suppressed and children with liver toxicity were at 17.84 (95%CI = 16.98, 18.82), 2.2 (95%CI = 1.67, 2.88) and 1.20 (95%CI = 1.14, 1.93) times risk of inflammation, respectively. Children on TDF+3 TC + EFV, those with CD4 count of <200 cells/mm3 and with renal toxicity were at 4.10 (95%CI = 1.64, 6.89), 2.16(95%CI = 1.31, 4.26) and 5.94 (95%CI = 1.18, 29.89) times risk of vitamin-D in-sufficiency, respectively. Predictors of liver toxicity were history of HAART substitution (AOR = 4.66; 95%CI = 1.84, 6.04) and being bedridden (AOR = 3.56; 95%CI = 2.01, 4.71). Children from HIV positive mother were at 4.07 (95%CI = 2.30, 6.09) times risk of renal toxicity while the different type of HAARTs had different level of risk for renal toxicity AZT+3 TC + EFV (AOR = 17.63; 95%CI = 18.25, 27.54); AZT+3 TC + NVP (AOR = 22.48; 95%CI = 13.93, 29.31); d4t+3 TC + EFV (AOR = 4.34; 95%CI = 2.51, 6.80) and d4t+3 TC + NVP (AOR = 18.91; 95%CI = 4.87, 27.74) compared to those who were on TDF+3 TC + NVP. Similarly, children who were on AZT+3 TC + EFV were at 4.92 (95%CI = 1.86, 12.70) times risk of anemia compared to those who were on TDF+ 3 TC + EFZ. Conclusion: The high level of HAART induced inflammation and liver toxicity among children calls for the program to consider safer regimens for pediatric patients. Moreover, the high proportion of vitamin-D in-sufficiency requires program level supplement. The impact of TDF+3 TC + EFV on inflammation and vitamin-D deficiency calls for the program to revise this regimen.

The use of antibiotic prophylaxis in patients undergoing urologic procedures in an academic hospital Surabaya: A retrospective study.

INTRODUCTION: Prophylactic antibiotics in urological procedures are essential to prevent postoperative infections. A different approach in selecting antibiotic prophylaxis according to the type of procedure is needed. METHODOLOGY: A retrospective study was carried out at an academic hospital in Surabaya, Indonesia, by collecting medical records of patients who underwent urologic procedures within 2019- 2020, including microbiological data. RESULT: One hundred seventy-nine urological procedures were assessed. Antibiotic prophylaxis was administered in the clean-contaminated and clean procedures (93.2% and 6.8%, respectively). Ceftriaxone was commonly used (69.3%), single-dose, one day before the surgery. Gram-negative bacteria were widely found in the urinary culture of patients (75.2%). E. coli, K. pneumoniae, and P. aeruginosa were dominating with low susceptibility to cephalosporins. ESBL-producing bacteria were E. coli (64%) and K. pneumoniae (89%). CONCLUSIONS: The 3rd generation cephalosporins (ceftriaxone) are mostly used in urological procedures despite the low susceptibility against this antibiotic in cultured E coli, P. aeruginosa, and K. pneumonia. The aminoglycosides have relatively good activity and have been suggested in several guidelines for urologic procedures, such as prostate and urinary tract stone procedures. It is crucial to consider the incision site, type of procedure, and bacterial profile in the hospital to propose antibiotic prophylaxis guidelines.

The role of mediator suppressor of cytokine signaling (SOCS), toll-like receptor 3 (TLR-3) and nuclear factor kappa B (NFκB) on cytokine production during dengue virus infection.

Inability to understand the pathogenesis of severe dengue, in particular the control mechanism of immune responses, has led to high mortality rate for patients with dengue shock syndrome (DSS). The aim of this study was to determine the control mechanism of cytokine production by mediator suppressor of cytokine signaling (SOCS), toll-like receptor 3 (TLR-3) and nuclear factor kappa B (NFκB) during DENV infection. Peripheral blood mononuclear blood cells (PBMC), isolated from healthy individuals, were infected with dengue virus (DENV)-2 strain SJN-006 Cosmopolitan genotype (isolated from Bali, Indonesia). The relative gene expression of SOCS-3, TLR-3, NFκB, and the cytokine genes (interleukin (IL)-6, IL-8, interferon inducible protein 10 (IP-10), and macrophage inflammatory protein-1 beta (MIP-1ß)) were measured using qRT-PCR at 6, 12 and 24 hours post infection (hpi). Student t-test and Mann-Whitney test were used to compare the gene expressions while causal correlations were analyzed using regression test and path analyses. DENV-2 infection increased the gene expression of SOCS-3, TLR-3, and NFκB after 12 and 24 hpi. The expression of IL-6, IL-8, IP-10, and MIP-1ß genes was increased and peaked at different times post-infection. NFκB and SOCS-3 genes likely have role in the upregulation of IL-8 and IL-6 gene expression, respectively. MIP-1ß gene expression was significantly induced by both NFκB and SOCS-3. In conclusion, our study suggested that SOCS-3, TLR-3, and NFκB are important in regulating the production of IL-6, IL-8, IP-10, MIP-1ß during early phase of DENV-2 infection. This enriches our understanding on pathogenesis pathway of DENV-associated cytokine storm.

Rapid typing of extended-spectrum ß-lactamase- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolates by use of SpectraCell RA.

Enterobacteriaceae are important pathogens of both nosocomial and community-acquired infections. In particular, strains with broad-spectrum beta-lactamases increasingly cause problems in health care settings. Rapid and reliable typing systems are key tools to identify transmission, so that targeted infection control measures can be taken. In this study, we evaluated the performance of Raman spectroscopic analysis (RA) for the typing of multiresistant Escherichia coli and Klebsiella pneumoniae isolates using the SpectraCell RA bacterial strain analyzer (River Diagnostics). Analysis of 96 unrelated isolates revealed that RA generated highly reproducible spectra and exhibited a discriminatory power that is comparable to pulsed-field gel electrophoresis. Furthermore, adequate results were obtained for three collections of clinical isolates. RA was able to discriminate outbreak-related isolates from isolates that were not involved in an outbreak or transmission. Furthermore, it was found that the RA approach recognized clones, irrespective of the extended-spectrum ß-lactamase type. It can be concluded that RA is a suitable typing technique for E. coli and K. pneumoniae isolates. Combining high reproducibility, speed, and ease-of-use, this technique may play an important role in monitoring the epidemiology of these important nosocomial species.

Faecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae among humans in Java, Indonesia, in 2001-2002.

OBJECTIVE: To characterise commensal Escherichia coli and other Enterobacteriaceae with reduced susceptibility to cefotaxime that were collected in a large survey carried out among 3995 patients and healthy persons in two urban regions on Java, Indonesia, in 2001-2002. METHODS: The putative extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae were analysed using double-disk synergy tests, isoelectric focusing, PCR assays, DNA sequencing, and pulsed-field gel electrophoresis (PFGE). RESULTS: On the day of discharge after five or more days of hospitalisation, at least 95 of 999 (9.5%) patients carried ESBL-positive Enterobacteriaceae as dominant faecal flora. Six patients were simultaneously colonised with E. coli and Klebsiella pneumoniae isolates with ESBL activity. On admission, only 6 of 998 (0.6%) patients were colonised. Faecal carriage of ESBL-producing Enterobacteriaceae among healthy persons or persons visiting a public health centre was not detected. The 107 ESBL-positive strains included 68 E. coli, 35 K. pneumoniae, and four other Enterobacteriaceae. bla(CTX-M-15) was the most prevalent ESBL in both E. coli (47.1%) and K. pneumoniae (45.7%), but the E. coli O25b-ST131 clone was virtually absent. Other ESBL types found were: SHV-2, -2a, -5, -12, CTX-M-3, -9, -14, and TEM-19. PFGE revealed extensive genetic diversity among the isolates. CONCLUSIONS: In 2001-2002, faecal carriage of ESBL-producing Enterobacteriaceae as dominant flora in Indonesia was almost exclusively hospital-associated. The presence of various bla(ESBL) genes and the extensive genetic diversity among isolates argue against a single/dominant strain outbreak.

The susceptibility pattern and distribution of blaOXA-23 genes of clinical isolate Acinetobacter baumannii in a tertiary hospital, Indonesia.

INTRODUCTION: Acinetobacter baumannii, a pathogen of concern in hospitals worldwide, has diverse antimicrobial resistance mechanisms leading to limiting the antibiotic options and carbapenemase enzyme production is one of the common mechanisms in carbapenem resistance. The epidemiology and resistance pattern of clinical isolates are critical in developing a prevention and treatment strategy. The aim of this was to determine the prevalence and resistance pattern of carbapenem non-susceptible strains (CNS) A. baumannii at Arifin Achmad General Hospital, Pekanbaru, Indonesia. METHODOLOGY: Data were retrieved from the culture and susceptibility test results from various clinical specimens from January 2015 to December 2019. A susceptibility test was conducted using Vitek 2 Compact following the manufacturer's protocol. To explore the genetic profile of CNS A. baumannii, we amplified the blaOXA-23 and blaOXA-51 genes, carbapenemase producing genes, using a duplex polymerase chain reaction (PCR) among 24 isolates Chi-squared was used to assess the factors associated with the presence of CNS A. baumannii. RESULTS: Between 2015-2019, 1.263 A. baumannii isolates were tested and the prevalence of CNS A. baumannii was 50%. The trend decreased from 53% in 2016 to 45% in 2019. The proportion of CNS A. baumannii was higher among samples from patients treated in the Intensive Care Unit (ICU) compared to non-ICU (p < 0.001). The CNS A. baumannii was also more frequently detected from sputum than from non-sputum samples (p = 0.009). CNS A. baumannii were highly resistant to almost all antibiotics and the highest susceptibility was to amikacin, tigecycline, and trimethoprim/sulfamethoxazole with 64%, 53%, and 43%, respectively. The blaOXA-23 gene was detected in 92% of tested CNS A. baumannii isolates. CONCLUSIONS: The prevalence of CNS A. baumannii is high at Arifin Achmad Hospital Riau, Indonesia. This is also supported by the high prevalence of the blaOXA-23 gene among tested isolates. Based on the antibiotic susceptibility pattern there are limited antibiotic choices for CNS A. baummannii urging the strengthening of antimicrobial stewardship programs in the country.

Multicenter Study of the Risk Factors and Outcomes of Bloodstream Infections Caused by Carbapenem-Non-Susceptible Acinetobacter baumannii in Indonesia.

The prevalence of bacteremia caused by carbapenem-non-susceptible Acinetobacter baumannii (CNSAB) continues to increase, and it is associated with a high mortality rate. Early recognition of infection and mortality determinants risk factors is necessary for adequate antibiotic administration. We aimed to determine the risk factors and outcomes of CNSAB bacteremia in Indonesia. A multicenter case-control study was conducted in three referral hospitals in Indonesia. Data were collected retrospectively from January 2019 to December 2021. Cases were defined as patients with bacteremia where CNSAB was isolated from the blood, while the controls were patients with bacteremia caused by carbapenem-susceptible A. baumannii (CSAB). Risk factors for bacteremia and mortality associated with CNSAB bacteremia were determined using univariates analysis (chi-squared and Student's t-test or Mann-Whitney test) and multivariate logistic regression analysis. A total of 144 bacteremia patients were included, of whom 72 patients were for each case and control group. The final model of multivariate regression analysis revealed that bacteremia source from the lower respiratory tract (adjusted odds ratio (aOR): 3.24; 95% CI: 1.58-6.63, p = 0.001) and the use of central venous catheter (aOR: 2.56; 95% CI: 1.27-5.18; p = 0.009) were independent risk factors for CNSAB bacteremia. Charlson Comorbidity Index ≥ 4 (aOR: 28.56; 95% CI: 3.06-265.90, p = 0.003) and Pitt Bacteremia Score ≥ 4 (aOR: 6.44; 95% CI: 1.17-35.38; p = 0.032) were independent risk factors for mortality due to CNSAB bacteremia. Only high Pitt Bacteremia Score was an independent risk factor for mortality of CSAB bacteremia. In conclusion, we identified the risk factors for CNSAB-associated bacteremia and the risk factors for death, which are relevant for empiric therapy and infection control prevention, as well as prognosis evaluation of patients with bloodstream infections.