Low clinical impact of HIV drug resistance mutations in oral pre-exposure prophylaxis: a systematic review and meta-analysis.

INTRODUCTION: Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM. METHODS: We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061. RESULTS: A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65-9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23-3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55-9.40) and 7.47% (95% CI 3.80-12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI -0.20 to 2.18, I2 = 0%; p = 0.10). DISCUSSION: Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21). CONCLUSIONS: Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use. PROSPERO Number: CRD42022356061.

Association between chest X-ray score and clinical outcome in COVID-19 patients: A study on modified radiographic assessment of lung edema score (mRALE) in Indonesia.

Radiological examinations such as chest X-rays (CXR) play a crucial role in the early diagnosis and determining disease severity in coronavirus disease 2019 (COVID-19). Various CXR scoring systems have been developed to quantitively assess lung abnormalities in COVID-19 patients, including CXR modified radiographic assessment of lung edema (mRALE). The aim of this study was to determine the relationship between mRALE scores and clinical outcome (mortality), as well as to identify the correlation between mRALE score and the severity of hypoxia (PaO2/FiO2 ratio). A retrospective cohort study was conducted among hospitalized COVID-19 patients at Dr. Soetomo General Academic Hospital Surabaya, Indonesia, from February to April 2022. All CXR data at initial admission were scored using the mRALE scoring system, and the clinical outcomes at the end of hospitalization were recorded. Of the total 178 COVID-19 patients, 62.9% survived after completing the treatment. Patients within non-survived had significantly higher quick sequential organ failure assessment (qSOFA) score (p<0.001), lower PaO2/FiO2 ratio (p=0.004), and higher blood urea nitrogen (p<0.001), serum creatinine (p<0.008) and serum glutamic oxaloacetic transaminase (p=0.001) levels. There was a significant relationship between mRALE score and clinical outcome (survived vs deceased) (p=0.024; contingency coefficient of 0.184); and mRALE score of ≥2.5 served as a risk factor for mortality among COVID-19 patients (relative risk of 1.624). There was a significant negative correlation between the mRALE score and PaO2/FiO2 ratio based on the Spearman correlation test (r=-0.346; p<0.001). The findings highlight that the initial mRALE score may serve as an independent predictor of mortality among hospitalized COVID-19 patients as well as proves its potential prognostic role in the management of COVID-19.

Puzzling Clinical Appearance of a Pancreatic Tuberculosis Case.

Tuberculosis (TB) is generally known as an infectious disease caused by Mycobacterium tuberculosis. Not only the lungs, TB can also infect various other organs. Pancreatic TB is a rare manifestation of extrapulmonary TB infection accounting for only 0-4.7% of the total TB cases worldwide. It's still intricating for clinicians to diagnose pancreatic TB due to the extremely rare prevalence and non-specific clinical signs and symptoms. Herein we report a 71-year-old male patient complaining of jaundice and weight loss. Clinical condition, laboratory and tumor markers, also MRI imaging showed no abnormality. We made the diagnosis through histopathological examination of tissues extracted from bypass biliodigestive procedure, showing granulomas, along with confirmed bacteriological analysis with Ziehl Nelsen staining. This patient received Fixed Drug Combination (FDC) of anti-tuberculosis therapy for 6 months. The patient gained weight, had an improvement of serum bilirubin level and had no remaining lesion in abdominal CT scan.

Development of a multiassay algorithm (MAA) to identify recent HIV infection in newly diagnosed individuals in Indonesia.

Ongoing HIV transmission is a public health priority in Indonesia. We developed a new multiassay algorithm (MAA) to identify recent HIV infection. The MAA is a sequential decision tree based on multiple biomarkers, starting with CD4+ T cells >200/µL, followed by plasma viral load (pVL) > 1,000 copies/ml, avidity index (AI) < 0 · 7, and pol ambiguity <0 · 47%. Plasma from 140 HIV-infected adults from 19 hospitals across Indonesia (January 2018 - June 2020) was studied, consisting of a training set (N = 60) of longstanding infection (>12-month) and a test set (N = 80) of newly diagnosed (≤1-month) antiretroviral (ARV) drug naive individuals. Ten of eighty (12 · 5%) newly diagnosed individuals were classified as recent infections. Drug resistance mutations (DRMs) against reverse transcriptase inhibitors were identified in two individuals: one infected with HIV subtype C (K219Q, V179T) and the other with CRF01_AE (V179D). Ongoing HIV transmission, including infections with DRMs, is substantial in Indonesia.

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.

Duration of SARS-CoV-2 RNA Shedding Is Significantly Influenced by Disease Severity, Bilateral Pulmonary Infiltrates, Antibiotic Treatment, and Diabetic Status: Consideration for Isolation Period.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; p = 0.001 and p = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (p = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36-6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14-6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02-4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74-7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding.

A rare case of Weil's disease with acute pancreatitis and acute kidney injury: focus on management - a case report.

The clinical spectrum of leptospirosis ranges from subclinical infection and anicteric fever to Weil's disease, a severely fatal infection. Acute inflammation of the pancreas is a rare manifestation of Weil's disease, and renal involvement is a hallmark in severe forms, leading to acute kidney injury (AKI) and representing a major risk factor for death. The aim of the case report was to present the clinical manifestations of Weil's disease with acute pancreatitis and AKI and to highlight the management of its complications. Case presentation: A 22-year-old male patient presented to the hospital with a chief complaint of a persisting fever, abdominal pain, nausea and vomiting, decreased appetite, malaise, and urine and feces discoloration. The patient's residence had flooded 2 weeks ago. Laboratory tests were performed and the patient was diagnosed with Weil's disease with the complication of acute pancreatitis, AKI, hyperkalemia, hyponatremia, hypotonic hypovolemic, metabolic acidosis, and hypoalbuminemia. Clinical discussion: The patient was treated with intravenous (i.v.) ceftriaxone at a dose of 2×1 g, i.v. metoclopramide at a dose of 3×10 mg, i.v. calcium gluconate at a dose of 1 g followed by dextrose (D) 40% with insulin 2 IU for six times, avoided nephrotoxic drugs, and fluid balance was maintained at I=O+500 ml. The patient received hemodialysis due to refractory hyperkalemia. Posttreatment follow-up presented improvements in complaints and laboratory parameters. Conclusion: Management of severe leptospirosis or Weil's disease with the complication of acute pancreatitis and AKI requires antibiotics and supportive therapy including adequate fluid resuscitation, proper and adequate nutrition, as well as the initiation of hemodialysis.

An Indonesian male with HIV/AIDS, pulmonary tuberculosis, and deep vein thrombosis: a case report and literature review.

HIV/AIDS and pulmonary tuberculosis (TB) are risk factors for deep vein thrombosis (DVT). However, the simultaneous occurrence of HIV/AIDS, pulmonary TB, and DVT is rare. Case Presentation: An Indonesian male, 30 years old, complained of pain, erythema, tenderness, and swelling in the left leg for 1 month, weight loss, and night sweats. The patient had been diagnosed with AIDS, a new case of pulmonary TB and TB lymphadenitis on therapy. Left inferior extremity vascular Doppler ultrasound showed partial DVT in the common femoral vein, superficial femoral to left popliteal vein. He received fondaparinux and warfarin therapy, and swelling and leg pain improved. Clinical Discussion: Although patients with HIV have a risk for venous thromboembolism, the occurrence mechanism of this phenomenon is still uncertain. Some factors affecting venous thromboembolism in HIV are low CD4 and Mycobacterium tuberculosis, which can induce anticardiolipin antibodies and hypercoagulation conditions. Conclusion: The patient diagnosed with DVT, a rare complication in HIV and pulmonary TB, is reported. This patient is getting better after using fondaparinux and Warfarin.

National early warning score (NEWS) 2 predicts hospital mortality from COVID-19 patients.

Background: COVID-19 has a high risk of mortality, especially in patients with comorbid diseases such as cardiac disease, type 2 diabetes mellitus, chronic kidney disease, and hypertension. The National Early Warning Score (NEWS) is a tool that helps in identifying changes in patient conditions that require intensive treatment. Objective: Analyzing NEWS-2 to identify the risk of death in COVID-19 patients. Methods: This research was conducted from June to July 2020 by using quota sampling. The number of participants in this study was 112 participants (case group = 56 participants and control group = 56 participants). Participants were assessed for NEWS-2 and evaluated for their treatment outcomes. The analysis used in this study was the Chi-squared test and logistic regression with p < 0.05. Results: 45 participants died of having NEWS-2 score >5, and as many as 50 participants showed an improvement in their condition by having NEWS-2 score 5 (OR = 34.091; p < 0.001). The accuracy of NEWS-2's assessment of mortality of COVID-19 patients had a sensitivity of 80.4% and a specificity of 89.3%. There were several comorbid diseases that had a significant relationship on mortality of COVID-19 patients such as cardiac disease (ß = 5.907; 1.107-31.527 95% CI; p = 0.038), T2DM (ß = 3.143; 1.269-7.783 95% CI; p = 0.013), CKD (ß = 3.851; 1.195-12.416 95% CI; p = 0.024), and hypertension (ß = 2.820; 1.075-7.399 95% CI; p = 0.035). Conclusion: The NEWS-2 can be used to identify the risk of death of COVID-19 patients.

The clinical impact of bacterial co-infection among moderate, severe and critically ill COVID-19 patients in the second referral hospital in Surabaya.

Background: Data on the prevalence of bacterial co-infections among COVID-19 patients are limited, especially in our country, Indonesia. We aimed to assess the rate of bacterial co-infections in hospitalized COVID-19 patients and report the most common microorganisms involved and the antibiotic use in these patients. Methods: This study is a retrospective cohort study, among COVID-19 adult patients admitted to Universitas Airlangga Hospital Surabaya from 14 March-30 September 2020. The bacterial infection is defined based on clinical assessment, laboratory parameters, and microbiology results. Results: A total of 218 patients with moderate to critical illness and confirmed COVID-19 were included in this study. Bacterial infection was confirmed in 43 patients (19.7%). COVID-19 patients with bacterial infections had longer hospital length of stay (17.6 ± 6.62 vs 13.31±7.12), a higher proportion of respiratory failure, intensive care treatment, and ventilator use. COVID-19 patients with bacterial infection had a worse prognosis than those without bacterial infection (p<0.04). The empirical antibiotic was given to 75.2% of the patients. Gram-negative bacteria were commonly found as causative agents in this study (n = 39; 70.37%). Conclusion: COVID-19 patients with bacterial infection have a longer length of stay and worse outcomes. Healthcare-associated infections during intensive care treatment for COVID-19 patients must be carefully prevented.

Point-of-care thrombocyte function testing using multiple-electrode aggregometry in dengue patients: an explorative study.

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.

Underdiagnoses of Rickettsia in patients hospitalized with acute fever in Indonesia: observational study results.

BACKGROUND: Reports of human rickettsial infection in Indonesia are limited. This study sought to characterize the epidemiology of human rickettsioses amongst patients hospitalized with fever at 8 tertiary hospitals in Indonesia. METHODS: Acute and convalescent blood from 975 hospitalized non-dengue patients was tested for Rickettsia IgM and IgG by ELISA. Specimens from cases with seroconversion or increasing IgM and/or IgG titers were tested for Rickettsia IgM and IgG by IFA and Rickettsia genomes using primers for Rickettsia (R.) sp, R. typhi, and Orientia tsutsugamushi. Testing was performed retrospectively on stored specimens; results did not inform patient management. RESULTS: R. typhi, R. rickettsii, and O. tsutsugamushi IgG antibodies were identified in 269/872 (30.8%), 36/634 (5.7%), and 19/504 (3.8%) of samples, respectively. For the 103/975 (10.6%) non-dengue patients diagnosed with acute rickettsial infection, presenting symptoms included nausea (72%), headache (69%), vomiting (43%), lethargy (33%), anorexia (32%), arthralgia (30%), myalgia (28%), chills (28%), epigastric pain (28%), and rash (17%). No acute rickettsioses cases were suspected during hospitalization. Discharge diagnoses included typhoid fever (44), dengue fever (20), respiratory infections (7), leptospirosis (6), unknown fever (6), sepsis (5), hepatobiliary infections (3), UTI (3), and others (9). Fatalities occurred in 7 (6.8%) patients, mostly with co-morbidities. CONCLUSIONS: Rickettsial infections are consistently misdiagnosed, often as leptospirosis, dengue, or Salmonella typhi infection. Clinicians should include rickettsioses in their differential diagnosis of fever to guide empiric management; laboratories should support evaluation for rickettsial etiologies; and public policy should be implemented to reduce burden of disease.

Endemic and emerging acute virus infections in Indonesia: an overview of the past decade and implications for the future.

Being the largest archipelago country in the world, with a tropical climate and a unique flora and fauna, Indonesia habitats one of the most diverse biome in the world. These characteristics make Indonesia a popular travel destination, with tourism numbers increasing yearly. These characteristics also facilitate the transmission of zoonosis and provide ideal living and breading circumstances for arthropods, known vectors for viral diseases. A review of the past 10 years of literature, reports of the Ministry of Health, Republic of Indonesia and ProMED-mail shows a significant increase in dengue infection incidence. Furthermore, chikungunya, Japanese encephalitis and rabies are proven to be endemic in Indonesia. The combination of cohort studies, governmental data and ProMED-mail reveals an integrated overview for those working in travel medicine and public health, focusing on both endemic and emerging acute virus infections. This review summarizes the epidemiology of acute virus infections in Indonesia, including outbreak reports, as well as public health response measurements and their potential or efficacy. Knowledge about human behaviour, animal reservoirs, climate factors, environment and their role in emerging virus infection are discussed. We aim to support public health authorities and health care policy makers in a One Health approach.

PREVALENCE OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS FROM NOSE AND THROAT OF PATIENTS ON ADMISSION TO MEDICAL WARDS OF DR SOETOMO HOSPITAL, SURABAYA, INDONESIA.

Epidemiological data of methicillin resistant Staphylococcus aureus (MRSA) carriage in Indonesian hospitals are still scarce. These data are required for health management of infectious diseases in order to control hospital MRSA. The carriage rate of MRSA in nose and throat of patients on admission to Dr Soetomo Hospital Surabaya, Indonesia was 8.1% of 643 patients, 5.4% from throat, 3.9% from nose and 1.2% from both sites. Prevalence of MRSA among patients admitted to surgical and non-surgical ward was not different (8.2% and 8.0%, respectively). Although MRSA prevalence in Indonesian hospitals is low compared to many other countries worldwide, appropriate health strategies will be needed to be implemented if this infection is to be controlled.

Detection of drug resistance-associated mutations in human immunodeficiency virus type 1 integrase derived from drug-naive individuals in Surabaya, Indonesia.

Although human immunodeficiency virus type 1 (HIV-1) infection causes serious health problems in Indonesia, information in regard to drug resistance is limited. We performed a genotypic study on HIV-1 integrase derived from drug-naive individuals in Surabaya, Indonesia. Sequencing analysis revealed that no primary mutations associated with drug resistance to integrase inhibitors were detected; however, secondary mutations, V72I, L74I/M, V165I, V201I, I203M, and S230N, were detected in more than 5% of samples. In addition, V201I was conserved among all samples. Most integrase genes were classified into CRF01_AE genes. Interestingly, 40% of the CRF01_AE genes had an unusual insertion in the C-terminus of integrase. These mutations and insertions were considered natural polymorphisms since these mutations coincided with previous reports, and integrase inhibitors have not been used in Indonesia. Our results indicated that further studies may be required to assess the impact of these mutations on integrase inhibitors prior to their introduction into Indonesia.

High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

BACKGROUND: Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs), we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1) and the prevalence of other blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus C (GBV-C), were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. CONCLUSIONS/SIGNIFICANCE: The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%). In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.