Challenges of diagnosing severe malaria with complications in adult patients: a case report.

BACKGROUND: Malaria is known to be the main cause of death in malaria-endemic areas. The authors report a case of severe malaria in an adult with no history of travel from an endemic area with good outcomes after hospitalization. CASE PRESENTATION: A 46-year-old man was brought to the Emergency Room (ER) because of fever and chills for 6 days. Complaints were accompanied by nausea and vomiting three times a day. The patient also experienced headaches, weakness, coughing, and a runny nose after two days of admission. The patient had no history of traveling from a malaria-endemic area. The patient was transferred from the Emergency Department (ED) to the High Care Unit (HCU), and during 1 day of intensive care at the HCU, there was a clinical deterioration characterized by dyspnea, icteric sclerae, acral edema, tenderness in both calves, and rash in the abdominal area. Due to worsening respiratory function, the patient was placed on a ventilator. During intensive treatment, the patient continued to show deterioration. The clinical findings suggested a possible feature of Weil's disease or fulminant hepatitis, and although the patient was in intensive care, there was no clinically significant improvement. Furthermore, microscopic blood smear examination and rapid diagnostic tests (RDTs) for malaria were carried out on the 4th day of treatment with negative results. As there was no clinically significant improvement, it was decided to take a blood smear and repeat RDT on the twelfth day, which showed a positive result for falciparum malaria. Subsequently, artesunate was administered intravenously, and the patient's condition began to improve with a negative parasite count the following day. The patient was discharged in good clinical condition on day 25 of treatment. CONCLUSION: Good quality malaria diagnostic techniques are essential to diagnose malaria. A timely diagnosis of malaria has the potential to save the patient. Because Jakarta is not a malaria endemic area, it was concluded that this case was an introduced malaria case.

Validation of Drug Resistance in Pneumonia (DRIP) Score as Empirical Antibiotic Failure Predictor in Community-Acquired Pneumonia Patients in Cipto Mangunkusumo Hospital.

BACKGROUND: The incidence of CAP due to Drug-Resistant Pathogen (DRP) requires broad-spectrum antibiotic therapy, Drugs Resistance in Pneumonia (DRIP) score can predict these cases. The use of the DRIP score can prevent antibiotic failure and long hospitalization, but validation is needed so that the DRIP score can be used according to the local community at Cipto Mangunkusumo National Central Public Hospital. METHODS: This research is a retrospective cohort study in CAP patients who were hospitalized during the period January 2019 to June 2020. Data were taken from medical records. Failure of empiric antibiotics occurs when one of these criteria is found: patient mortality, ICU transfer, and escalation of antibiotics as well as length of stay. RESULTS: 480 patients met the criteria. There were 331 patients (69%) with a DRIP score of <4 and 149 patients (31%) with a DRIP score of≥4. A total of 283 patients (59%) of antibiotic failures were detailed in 174 patients with a DRIP score <4 and 109 patients DRIP score ≥4. DRIP calibration using the Hosmer-Lemeshow test obtained p-value= 0.667 (p>0.05). AUC observations on the ROC curve obtained 0.651 (95% CI; 0.601-0.700). CONCLUSION: The DRIP score has low accuracy performance and calibration value in predicting empirical antibiotic failure and poor discriminatory value.

Identifying Predictors of Mortality in Sepsis Patients with Malignancy: A Retrospective Cohort Study.

BACKGROUND: Sepsis is a major problem that contributes to a high mortality rate. Its mortality is especially high in patients with malignancy. One study reported that sepsis patients with malignancy have a 2.32 times higher risk of mortality compared to patients without malignancy. For this reason, factors that influence mortality in sepsis patients with malignancy become especially important to provide effective and efficient therapy. This study aims to identify factors that influence mortality in sepsis patients with malignancy. METHODS: This study is a retrospective cohort study using medical records of sepsis patients with malignancy who were treated at Cipto Mangunkusumo Hospital from 2020 to 2022. A bivariate analysis was carried out and followed by a logistic regression analysis on variables with p-value<0.25 on the bivariate analysis. RESULTS: Among the 350 eligible sepsis subjects with malignancy, there was an 82% mortality rate (287 subjects). Bivariate and multivariate analyses revealed significant associations between mortality and both SOFA score (adjusted Odds Ratio of 5.833, 95%CI 3.214-10.587) and ECOG performance status (adjusted Odds Ratio of 3.490, 95%CI 1.690-7.208). CONCLUSION: SOFA score and ECOG performance status are significantly associated with sepsis patient mortality in malignancy cases.

Expanded dengue syndrome in diabetic patient with history of COVID-19 infection: a case report.

Introduction: Overlapping symptoms between dengue and coronavirus disease 2019 (COVID-19) may become a diagnostic challenge; moreover, social stigma and fear of being diagnosed with COVID-19 may lead the patients to delayed medical visit. Delayed medical management of dengue may lead to expanded dengue syndrome and a fatal outcome. Case presentation: A 35-year-old female patient with uncontrolled diabetes mellitus and a recent COVID-19 infection presented with a continuous fever for 4 days. She delayed seeking medical advice due to traumatized being infected by COVID-19, the self-isolation protocol, and the COVID-19 protocol in every hospital for every febrile patient. She developed multiorgan failure during her hospitalization and was diagnosed with expanded dengue syndrome. Clinical discussion: Diagnosing the etiology of acute febrile illness in the COVID-19 pandemic era is problematic. Most of healthcare facilities warranted COVID-19 evaluation in every acute febrile patient. This protocol may lead to a potential delayed diagnosis and serve as a barrier to accessing healthcare facility. False perception, fear and anxiety of being isolated, discrimination in society, and others may lead to stigmatization of COVID-19 and affect the individual decision for COVID-19 testing and seeking medical advices. Our patient had a fatal outcome due to delayed detection and treatment of dengue hemorrhagic fever. Conclusion: Delayed management of expanded dengue syndrome leads to a fatal outcome. Stigma may play a role as the barrier for seeking medical advice. Having a broad differential diagnosis in COVID-19 pandemic era is essential.

COVID-19 Screening Score for Patients without Acute Respiratory Symptoms Undergoing Emergency Medical Procedures in Indonesia.

To rule out coronavirus disease-2019 (COVID-19) in patients scheduled to undergo emergency medical procedures, SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) must be performed. In developing countries, the use of SARS-CoV-2 RT-PCR has been limited by its unavailability and long processing time. Hence, a quick screening score to predict COVID-19 may help healthcare practitioners determine which patients without acute respiratory symptoms can safely undergo an emergency medical procedure. We conducted a cross-sectional study of adult patients without acute respiratory symptoms who were admitted to the emergency department and underwent an emergency medical procedure within 24 hours after admittance. We collected baseline demographic data, COVID-19 screening variables, and SARS-CoV-2 RT-PCR as the gold standard for COVID-19 diagnosis. Bivariate and multivariate analyses were performed, and a scoring system was developed using statistically significant variables from the multivariate analysis. With data from 357 patients, multivariate backward stepwise logistic regression analysis resulted in two significant COVID-19 predictors: the presence of SARS-CoV-2-IgM antibody (adjusted odds ratio [aOR]: 7.02 [95% CI: 1.49-32.96]) and typical chest x-ray (aOR: 23.21 [95% CI: 10.01-53.78]). A scoring system was developed using these predictors with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.64-0.78). For a cutoff point of ≥ 2, the scoring system showed 42.5% sensitivity and 97.1% specificity but had poor calibration (Hosmer-Lemeshow test P value < 0.001). We believe that the development of this COVID-19 quick screening score may be helpful in a resource-limited clinical setting, but its moderate discrimination and poor calibration hinder its use as a replacement for the SARS-CoV-2 RT-PCR test for COVID-19 screening.

Association of viral kinetics, infection history, NS1 protein with plasma leakage among Indonesian dengue infected patients.

OBJECTIVES: Plasma leakage, a hallmark of disease in Dengue virus (DENV) infection, is an important clinical manifestation and is often associated with numerous factors such as viral factors. The aim of this study is to investigate the association of virus serotype, viral load kinetics, history of infection, and NS1 protein with plasma leakage. METHODS: Subjects with fever ≤ 48 hours and positive DENV infection were included. Serial laboratory tests, viral load measurements, and ultrasonography examination to assess plasma leakage were performed. RESULTS: DENV-3 was the most common serotype found in the plasma leakage group (35%). Patients with plasma leakage demonstrated a trend of higher viral load and a longer duration of viremia compared to those without. This was significantly observed on the fourth day of fever (p = 0.037). We found higher viral loads on specific days in patients with plasma leakage in both primary and secondary infections compared to those without. In addition, we also observed more rapid viral clearance in patients with secondary infection. NS1 protein, especially after 4 days of fever, was associated with higher peak viral load level, even though it was not statistically significant (p = 0.470). However, pairwise comparison demonstrated that peak viral load level in the group of patients with circulating NS1 detected for 7 days was significantly higher than the 5-day group (p = 0.037). CONCLUSION: DENV-3 was the most common serotype to cause plasma leakage. Patients with plasma leakage showed a trend of higher viral load and a longer duration of viremia. Higher level of viral load was observed significantly on day 5 in patients with primary infection and more rapid viral clearance was observed in patients with secondary infection. Longer duration of circulating NS1 protein was also seen to be positively correlated with higher peak viral load level although not statistically significant.

Depression as a Consequence of Elder Mistreatment: A Case Report.

A 61-year-old elderly woman came to the emergency room in tertiary hospital in Jakarta, Indonesia due to epigastric pain for the past 7 months which was worsened in the past 4 days. Due to her illness, her daughters prevent her to do daily chores and her hobbies, such as singing and gardening. On admission, she had hypertension with moderate dependency, frail, cognitive impairment, malnutrition, risk of sarcopenia, and risk of depression. She was later diagnosed with poorly differentiated colon adenocarcinoma and adjustment disorders with anxiety and depressive reaction due to emotional elder mistreatment. There are a variety of forms of elder abuse, not only physical, but also emotional, sexual, financial, and neglect. The prevalence of elder mistreatment is projected between 5% and 10% all over the world and it is thought to be underdiagnosed. Among the consequences of mistreatment or abuse include social alongside, economic, physical, and mental (e.g., isolation, constrained relationships, and broken social networks). This is a case report of depression because of elder mistreatment.

Risk Factors for Temporary Vascular Access Infection in Patients with End-Stage Renal Disease Undergoing Hemodialysis in Cipto Mangunkusumo Hospital.

BACKGROUND: Temporary vascular access is used to provide adequate hemodialysis for patients who are initiating dialysis or are awaiting maturation of a more permanent vascular access. However, infection is one of the most frequent complications of using temporary vascular access and is the second leading cause of death in patients undergoing hemodialysis after cardiovascular events. There has been no research on the risk factors for the incidence of infection in patients using temporary vascular access in Indonesia. METHODS: This is a retrospective cohort study utilizing secondary data from medical records of 318 subjects aged 18 years and older with end-stage renal disease and undergoing hemodialysis using temporary vascular access at Cipto Mangunkusumo Hospital. RESULTS: Temporary vascular access infection was found in 125 of 318 subjects (39.3%). The risk factors of temporary vascular catheter infection in the multivariate analysis were females (OR 1.731; 95% CI 1.050-2.854; p=0.032), low hemoglobin levels (OR 2.293; 95% CI 1.353-3.885; p=0.002), presence of diabetes mellitus (OR 2.962; 95% CI 1.704-5.149; p<0.001) and duration of catheter insertion (OR 5.322; 95% CI 1.871-15-135; p=0.002). The association between ferritin and catheter insertion site was not analyzed as a risk factor because it was not performed in all subjects. CONCLUSION: The incidence of infection in patients with end -stage renal disease undergoing hemodialysis using temporary vascular access at Cipto Mangunkusumo Hospital was 39.3%. Female gender, low hemoglobin level, diabetes mellitus, and duration of catheter insertion were risk factors for temporary vascular access infection.

Observational Study on Secondary Bacterial Infection and the Use of Antibiotics in COVID-19 Patients Treated in a Tertiary Referral Hospital.

BACKGROUND: Data on secondary bacterial infection in patients with COVID-19 in Indonesia are still limited, while the use of empirical antibiotics continues to increase. This study aims to determine the secondary bacterial infection rate in hospitalized COVID-19 patients and factors related to secondary bacterial infection. METHODS: This is a retrospective cohort study on hospitalized COVID-19 patients undergoing treatment at Cipto Mangunkusumo Hospital from March 2020 to September 2020. Secondary bacterial infection is defined as the identification of a bacterial pathogen from a microbiological examination. RESULTS: From a total of 255 subjects, secondary infection was identified in 14.5%. Predictors of secondary infection were early symptoms of shortness of breath (OR 5.31, 95% CI 1.3 - 21.5), decreased consciousness (OR 4.81, 95% CI 1.77 - 13.0), length of stay > 12 days (OR 8.2, 95% CI 2.9 - 23.3), and central venous catheter placement (OR 3.0, 95% CI 1.1 - 8.0) The most common pathogen of secondary bacterial infection is Acinetobacter sp. (n=9; 28%). Empirical antibiotics were administered to 82.4% of subjects with predominant use of macrolides (n=141; 32.4%). CONCLUSION: The secondary bacterial infection rate in COVID-19 was 14.5% and is associated with dyspnea, decreased consciousness, length of stay >12 days, and central venous catheter placement. The use of antibiotics in COVID-19 reaches 82.4% and requires special attention to prevent the occurrence of antibiotic resistance.

Extrapulmonary Manifestations COVID-19.

After being declared as a pandemic on March 11, 2020 by the World Health Organization, COVID-19 has affected 497 million people worldwide as of 9 April 2022. COVID-19 is a disease with a plethora of clinical manifestations, which extends to those beyond pulmonary signs and symptoms. Studies that report on the clinical presentation of COVID-19 rarely report specifically on cases with only extrapulmonary manifestations of COVID-19. Extrapulmonary clinical presentations of COVID-19 without pulmonary signs and symptoms is rare, and in such cases, COVID-19 is rarely suspected.We herewith describe four patients with extrapulmonary manifestations of COVID-19, with positive SARS-COV-2 PCR when the test was performed for initial patient screening. The first patient is a 44-year-old female who developed painful ulcer with burning sensation at the lateral side of the tongue along with low grade fever. This symptom appeared after the initial complaints of coughing and nasal congestion subsided.  The second patient is a 37-year-old male, who complained of red eyes  with itchiness and increased tear production for 3 days before seeing an ophthalmologist. The third patient is a 44-year-old female who developed burning sensation and soreness on her throat upon swallowing with fever and chills. These symptoms appear consecutively without any respiratory complaint. The fourth patient is a previously healthy, 30-year-old female, with a normal weight and BMI, and without any comorbidity, cardiovascular risk and neither personal nor family history of cardiovascular disease. In these 4 patients, COVID-19 stomatitis, conjunctivitis, pharyngitis and COVID-19-associated atrial fibrillation was subsequently diagnosed, respectively.In the pandemic stage of COVID-19, COVID-19 screening has often been routinely performed due to the high risk of transmission. However, the decrease in the number of COVID-19 cases may prompt physicians to perform SARS-COV-2 testing based on clinical suspicion. It is imperative to consider the likelihood of COVID-19 and perform SARS-COV-2 PCR in patients with extrapulmonary complaints that have persisting complaints despite treatment.

The role of IL-6, ferritin, and coagulopathy in Covid-19 clinical progression.

Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular coagulation. However, the relationship between IL-6 and coagulopathy remains unclear in COVID-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analyzed the effect of those parameters on the worsening of COVID-19 patients. Methods A prospective cohort study was conducted in moderate and severe COVID-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate COVID-19) were included in this study. A total of 35 out of 61 severe and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 ( p=0.5), -0.13 ( p=0.27), 0.01 ( p=0.91), and 0.03 ( p=0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (>60%). Conclusions In COVID-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with disease deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. Therefore, changes in IL-6 and D-dimer can predict worsening in moderate and severe COVID-19 patients.

Revisiting the Overlooked Infection: Rickettsioses.

The prevalence of human Rickettsioses cases in Indonesia is unknown and could probably be underestimated. The high prevalence of seropositive Rickettsia sp. was reported in small mammals (as vectors) and humans. In Indonesia, a recent study in patients with acute fever revealed that the prevalence of Rickettsioses is 10%. Many cases of Rickettsioses were often misdiagnosed with dengue fever, enteric fever, or leptospirosis due to their overlapping clinical manifestation. The limitation of point of care testing in Indonesia hindered the adequacy of diagnosis confirmation. Appropriate empirical or definitive treatment with macrolide, mainly doxycycline, is preferable compared to other broad-spectrum antibiotics, such as cephalosporin or quinolones. Moreover, when left untreated, Rickettsioses may deteriorate progressively to fatal outcomes, such as meningitis, sepsis, and even death. The awareness of health care practitioners, the availability of confirmatory rapid diagnostic tests and adequate treatment choices are important in eradicating this disease.

Circulation of Various Dengue Serotypes in a Community-Based Study in Jakarta, Indonesia.

Dengue virus (DENV) infection remains to be a serious health problem in Indonesia. Community-based dengue studies to determine circulating DENV serotypes based on the geography and season are limited owing to the expensive cost and significant effort required. Many patients with DENV infection are not hospitalized and many visit the hospital in the later phase of the disease. In this study, we performed active DENV surveillance in a community in Jakarta to study the circulating dengue serotypes; adult febrile patients with fever less than 48 hours were recruited. Disease severity was defined using the World Health Organization (WHO) 1997 guidelines. Rapid NS1 dengue antigen detection was used to screen patients with DENV in the community. Viral culture using the C6/36 cell line, an increased antibody titer on hemagglutination inhibition test and enzyme linked immunosorbent assay, or detection of the viral genome on reverse transcription-polymerase chain reaction was used to confirm DENV infection. Of the 102 patients, 68 (66.7%) were confirmed to have DENV infection, with DENV-2 being the most dominant serotype, followed by DENV-3, DENV-1, and DENV-4, in concordance with several reports of mixed DENV infection. Interestingly, in terms of disease severity, although DENV-3 infection was not the predominant circulating serotype, infection with it tended to cause a more severe disease than infection with DENV-2.

Gallbladder Wall Thickening for Early Detection of Plasma Leakage in Dengue Infected Adult Patients.

BACKGROUND: plasma leakage is defined as ≥20% elevation of hematocrit from baseline or decrease in convalescence or evidence of plasma leakage such as pleural effusion, ascites or hypoproteinaemia/hypoalbuminaemia. These signs of plasma leakage, in the early phase, are usually difficult to ascertain by physical examination and laboratory tests where the patient is only reflecting a mild degree of plasma leakage. This study aimed to investigate whether gallbladder wall thickening (GBWT) in the early phase of the disease can be used to detect the occurrence of plasma leakage in dengue patients. METHODS: a diagnostic study was conducted among dengue patients. Patients with fever less than 3 days, positive results of non-structural protein 1 antigen dengue and RT-PCR examination were included consecutively. Laboratory tests and chest and abdominal ultrasonography examination were also performed daily from day-3 to day-7 of fever to confirm the occurrence of plasma leakage using WHO 1997 criteria during treatment. RESULTS: there were 69 patients included in this study. Male patients were found more frequently (52.2%), average age was 24.2 years, and 46 patients (66.7%) presented with secondary dengue infection. On the third day of fever, 37 patients presented with GBWT, 30 of which showed plasma leakage during treatment. Out of 46 patients found to have plasma leakage during treatment, 12 patients had presented with plasma leakage on the third day of fever. Sensitivity and specificity of GBWT on the third day of fever were 65% (95% CI: 0,51-0,79) and 70% (95% CI: 0.51-0.88); PPV and NPV were 81% (95% CI: 0.68-0.94) and 50% (95% CI: 0.33-0.67); LR (+) and LR (-) were 2.14 (95% CI: 1.12-4.12) and 0.5 (95% CI: 0.31-0.81), respectively. CONCLUSION: gallbladder wall thickening in the early phase of the disease can be used to detect the occurrence of plasma leakage in adult dengue infected patients.

The Tolerability and Efficacy of Oral Isotonic Solution versus Plain Water in Dengue Patients: A Randomized Clinical Trial.

BACKGROUND: Plasma leakage plays an important role in dengue infection, and this condition can lead to hemoconcentration, hypovolemia, and shock. Fluid replacement is the main treatment for dengue. There is a lack of evidence to support certain oral fluid therapy as a treatment for dengue patients. OBJECTIVES: The objective of this study is to evaluate tolerability and efficacy of oral isotonic solution (OIS) compared to plain water as a fluid replacement in dengue patients. MATERIALS AND METHODS: A randomized, clinical trial with single-blinded groups was conducted to compare tolerability and efficacy of OIS and plain water in dengue patients. We evaluated gastrointestinal disturbances (nausea, vomiting, and bloating), body temperature, mean arterial pressure (MAP), fluid balance, hematocrit, Na+, and K+ levels. Data were analyzed with SPSS 20.0, and figures were made with GraphPad Prism version 5.01. RESULTS: Twenty four subjects were included and divided equally into two groups. Our results showed that there are no significant differences but indicate several noteworthy trends. The intervention group (OIS) experienced less nausea, less vomiting, had positive fluid balance and higher MAP, and became afebrile faster compared to the control group (plain water). CONCLUSION: Although not statistically significant, this study shows the trend that OIS is well-tolerated and effective for dengue patients compared to plain water.

Laboratory parameters for predicting Salmonella bacteraemia: a prospective cohort study.

Blood cultures for a definitive diagnosis of typhoid fever takes time and are not routinely available. We thus investigated laboratory parameters to predict Salmonella bacteraemia. We conducted a prospective cohort study in Jakarta, Indonesia. Patients with suspected typhoid fever admitted to hospital from October 2014 to December 2016 were included. Out of 187 individuals, 27 had Salmonella typhi and 12 had S. paratyphi in blood cultures. Absolute eosinopenia, elevated aspartate aminotransferase and elevated C-reactive protein > 40 mg/L were positive predictors.

Dengue score: a proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection.

BACKGROUND: There are several limitations in diagnosing plasma leakage using the World Health Organization (WHO) guidelines of dengue hemorrhagic fever. We conducted a study to develop a dengue scoring system to predict pleural effusion and/or ascites using routine laboratory parameters. METHODS: A prospective observational study was carried out at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Dengue-infected adults admitted on the third febrile day from March, 2010 through August, 2015 were included in the study. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites and to convert the prediction model into a scoring system. RESULTS: A total of 172 dengue-infected adults were enrolled in the study. Of the 172 patients, 101 (58.7 %) developed pleural effusion and/or ascites. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites in dengue-infected adults. The predictors were scored based on the following calculations: hemoconcentration ≥15.1 % had a score of 1 (OR, 3.11; 95 % CI, 1.41-6.88), lowest albumin concentration at critical phase ≤3.49 mg/dL had a score of 1 (OR, 4.48; 95 % CI, 1.87-10.77), lowest platelet count ≤49,500/µL had a score of 1 (OR, 3.62; 95 % CI, 1.55-8.49), and elevated ratio of AST ≥2.51 had a score of 1 (OR 2.67; 95 % CI, 1.19-5.97). At a cut off of ≥ 2, the Dengue Score predicted pleural effusion and/or ascites diagnosis with positive predictive value of 79.21 % and negative predictive value of 74.63 %. This prediction model is suitable for calibration and good discrimination. CONCLUSIONS: We have developed a Dengue Score that could be used to identify pleural effusion and/or ascites and might be useful to stratify dengue-infected patients at risk for developing severe dengue.

The Differences Between Interleukin-6 and C-reactive Protein Levels Among Adult Patients of Dengue Infection with and without Plasma Leakage.

AIM: to determine the differences in IL-6 and CRP levels among groups of dengue infection patients with and without plasma leakage. METHODS: a cross-sectional study was conducted in adult patients with dengue infection who were treated at Cipto Mangunkusumo and Persahabatan Hospital between 1 March 2014 and 1 April 2015. The study analyzed differences in IL-6 and CRP levels on the 3rd and 5th day of fever in both groups, as well as differences in each group. Interleukin-6 and CRP levels in both groups, was analyzed using unpaired t-test or Mann-Whitney and in each group, the data was subsequently analyzed using paired t-test or Wilcoxon test. RESULTS: the samples of study consisted of 24 subjects with plasma leakage and 20 subjects without plasma leakage. The level of IL-6 for groups with and without plasma leakage for the 3rd and the 5th day of fever were 8.56 (1.85-96.15) vs. 3.80 (1.94-81.93) pg/mL (p=0.069) and 4.30 (1.60-70.28) vs. 2.76 (1.26-11.67) pg/mL (p=0.025), respectively; while for CRP level, there were 10.1 (4.3-36.5) vs 6.8 (3.0-21.6) mg/L (p=0.014) and 5.0 (2.0-20.1) vs 2.9 (0.1-9.9) mg/L (p=0.048). The level of IL-6 on the 3rd and the 5th day of fever in the group with and without plasma leakage were 8.56 (1.85-96.15) vs. 4.30 (1.60-70.28) pg/mL (p=0.037) and 3.80 (1.94-81.93) vs. 2.76 (1.26-11.67) pg/mL (p=0.005). The level of CRP on the 3rd and 5th day of fever in the group with and without plasma leakage were 10.1 (4.3-36.5) vs. 5.0 (2.0-20.1) mg/L (p=0.0001) and 6.8 (0.3-21.6) vs. 2.9 (0.1-9.9) mg/L (p=0.0001). CONCLUSION: there was no difference in IL-6 level on the 3rd day of fever between the two groups; while on the 5th day of fever, the IL-6 level was higher in the group with plasma leakage. The level of CRP on the 3rd and the 5th day of fever were higher in the group with plasma leakage. The levels of IL-6 and CRP on the 3rd day of fever were higher than the levels on the 5th day of fever in both groups.

Concurrent infections of dengue viruses serotype 2 and 3 in patient with severe dengue from Jakarta, Indonesia.

OBJECTIVE: To describe the clinical manifestation of patient with severe dengue, to identify the serotypes and genotypes of dengue viruses (DENV) which concurrently infecting the patient, and to explore the possible relationship of severe dengue with the concurrent infection of DENV. METHODS: Dengue diagnosis was performed using NS1 antigen detection and IgG/IgM ELISA. Standard clinical and laboratory examinations were performed to obtain the clinical and hematological data. DENV concurrent infections were detected and confirmed using RT-PCR and DENV Envelope gene sequencing. Phylogenetic analyses were performed to determine the genotypes of the viruses. RESULTS: The patient was classified as having severe dengue characterized by severe plasma leakage, hemorrhage, and organ damage involving lung, liver, and kidney. Concurrent infection of DENV serotype 2 and 3 was observed. The infecting DENV-2 virus was grouped into Cosmopolitan genotype while DENV-3 virus was classified into Genotype I. Both viruses were closely related to isolates that were endemic in Jakarta. Viremia measurement was conducted and revealed a significantly higher virus titer of DENV-3 compared to DENV-2. CONCLUSIONS: The occurrence of multi-serotype DENV infections was presented in a patient with severe clinical manifestation in Indonesia. The hyperendemicity of dengue in Indonesia may contribute to the DENV concurrent infections cases and may underlie the severity of the disease.

Time since onset of disease and individual clinical markers associate with transcriptional changes in uncomplicated dengue.

BACKGROUND: Dengue virus (DENV) infection causes viral haemorrhagic fever that is characterized by extensive activation of the immune system. The aim of this study is to investigate the kinetics of the transcriptome signature changes during the course of disease and the association of genes in these signatures with clinical parameters. METHODOLOGY/PRINCIPLE FINDINGS: Sequential whole blood samples from DENV infected patients in Jakarta were profiled using affymetrix microarrays, which were analysed using principal component analysis, limma, gene set analysis, and weighted gene co-expression network analysis. We show that time since onset of disease, but not diagnosis, has a large impact on the blood transcriptome of patients with non-severe dengue. Clinical diagnosis (according to the WHO classification) does not associate with differential gene expression. Network analysis however, indicated that the clinical markers platelet count, fibrinogen, albumin, IV fluid distributed per day and liver enzymes SGOT and SGPT strongly correlate with gene modules that are enriched for genes involved in the immune response. Overall, we see a shift in the transcriptome from immunity and inflammation to repair and recovery during the course of a DENV infection. CONCLUSIONS/SIGNIFICANCE: Time since onset of disease associates with the shift in transcriptome signatures from immunity and inflammation to cell cycle and repair mechanisms in patients with non-severe dengue. The strong association of time with blood transcriptome changes hampers both the discovery as well as the potential application of biomarkers in dengue. However, we identified gene expression modules that associate with key clinical parameters of dengue that reflect the systemic activity of disease during the course of infection. The expression level of these gene modules may support earlier detection of disease progression as well as clinical management of dengue.