MPox Skin Lesions.

Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.

Association of G6PD status and haemolytic anaemia in patients receiving anti-malarial agents: a systematic review and meta-analysis.

BACKGROUND: Some anti-malarial drugs often cause haemolytic anaemia in glucose-6-phosphate-dehydrogenase deficiency (G6PDd) patients. This study aims to analyse the association of G6PDd and anaemia in malaria patients receiving anti-malarial drugs. METHODS: A literature search was performed in major database portals. All studies searched using keywords with Medical Subject Headings (MeSH) were included, without date or language restriction. Pooled mean difference of haemoglobin and risk ratio of anaemia were analysed using RevMan. RESULTS: Sixteen studies comprising 3474 malaria patients that included 398 (11.5%) with G6PDd were found. Mean difference of haemoglobin in G6PDd/G6PD normal (G6PDn) patients was - 0.16 g/dL (95% CI - 0.48, 0.15; I2 5%, p = 0.39), regardless of the type of malaria and dose of drugs. In particular with primaquine (PQ), mean difference of haemoglobin in G6PDd/G6PDn patients with dose < 0.5 mg/kg/day was - 0.04 (95% CI - 0.35, 0.27; I2 0%, p = 0.69). The risk ratio of developing anaemia in G6PDd patients was 1.02 (95% CI 0.75, 1.38; I2 0%, p = 0.79). CONCLUSION: Single or daily standard doses of PQ (0.25 mg/kg/day) and weekly PQ (0.75 mg/kg/week) did not increase the risk of anaemia in G6PDd patients.

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.

Parenteral and Oral Anticoagulant Treatment for Hospitalized and Post-Discharge COVID-19 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of anticoagulants has been endorsed by different hematological societies as coagulation abnormalities are key features of COVID-19 patients. This systematic review and meta-analysis aims to provide the most recent update on available evidence on the clinical benefits and risk of oral and parenteral anticoagulants, as well agents with anticoagulant properties, in hospitalized and post-discharge COVID-19 patients. METHODS: This systematic review synthesizes data on the outcome of anticoagulation in hospitalized and post-discharge COVID-19 patients. Dichotomous variables from individual studies were pooled by risk ratio (RR) and their 95% confidence interval (95% CI) using the random-effects model. Meta-analyses were performed when feasible. RESULTS: We included 32 studies from 2.815 unique citations, including 7 randomized clinical trials. A total of 33.494 patients were included. Outcomes measured include mortality and survival rates, the requirement for ICU care and mechanical ventilation. A pooled meta-analysis favors anticoagulant compared to no anticoagulant with reduced mortality in hospitalized patients (RR 0,55; 95%CI 0,43-0,66; p<0,001). Higher dose of anticoagulant also showed treatment benefit compared to standard prophylactic dose in selected populations (RR 0,68; 95%CI 0,40-0,96; p<0,001). Regular, pre-hospital anticoagulation prior to hospitalization yielded mixed result. There are currently no data on the benefit of anticoagulation on post-discharge COVID-19 patients. CONCLUSION: Determination of the presence of thrombosis in COVID-19 is important, as therapeutic dosage of anticoagulants, rather than prophylatic dose, would be indicated in such clinical situation. Anticoagulants were found to decrease the mortality of hospitalized COVID-19. The results from this study are important in the tailored treatment of COVID-19 patients. Further studies on the need for oral anticoagulation for outpatients or post-discharge is warranted. This study has been registered in PROSPERO database (CRD42020201418).

Black Fungus Complicated with COVID-19 in a Man with Underlying Non-Hodgkin's Lymphoma.

COVID-19 is a disease reported to suppress cellular immunity. This may lead to the development of opportunistic infections, among others black fungus, or mucormycosis. On the other hand, pre-existing defect in immunity may render patients susceptible to both mucormycosis and COVID-19. Mucormycosis is a relatively rare fungal infection with rapid progression unless diagnosed promptly and treated adequately, and urgent surgical and medical intervention is lifesaving. The manifestation of mucormycosis largely depends on the presence of exposure to the pathogen and the existing risk factor of the host. As black fungus is locally invasive, the majority of cases will involve tissue damage with local destruction and contiguous spread to nearby structure. We here with present a case of black fungus complicated with COVID-19 in a man with underlying non-Hodgkin's lymphoma.

The Validation of Drug Resistance in Pneumonia (DRIP) Score in Predicting Infections due to Drug-Resistant Pathogens in Community-acquired Pneumonia at Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

BACKGROUND: The emergence of drug-resistant pathogens (DRP) in recent years possibly contributes to the common problems associated with community-acquired pneumonia. However, to predict the risk of the ailment, the DRIP score is mainly applied, although no validation study has been reported in Indonesia. Therefore, the score prediction accuracy in the population, patient characteristics and germ patterns appears indefinite, particularly for Cipto Mangunkusumo Hospital, Jakarta. The purpose of this study is to determine the DRIP performance as an instrument in predicting infections due to drug-resistant pathogens (DRP) in community-acquired pneumonia at Cipto Mangunkusumo Hospital. METHODS: This research employed a cross-sectional design, where the subjects were community-acquired pneumonia patients treated between January 2019 and June 2020. In addition, adequate medical records of the participants were obtained. The condition is defined as DRP when the sputum culture results show resistance to non-pseudomonal ß-lactam antibiotics, macrolides, and respiratory fluoroquinolones. Furthermore, the score performance was analyzed by determining the calibration and discrimination values, using the Hosmer-Lemeshow test and AUROC, respectively. RESULTS: A total of 254 subjects were known to have satisfied the selection criteria. These participants were categorized into DRP and non-DRP groups, with 103 (40.6%) and 151 (59.4%) patients, correspondingly. The DRIP calibration analysis using the Hosmer-Lemeshow test obtained p-value = 0.001 (p <0.05), while an AUC value of 0.759 (CI 95%, 0.702-0.810) was derived from the ROC curve. However, at a score of ≥ 4, the DRIP showed sensitivity, specificity, positive and negative predictive values of 70.9, 92.7, 86.9, and 82.3%, respectively. CONCLUSION: The DRIP score demonstrated a significant performance in predicting infections due to DRP in community-acquired pneumonia.

The Comparison of Point Prevalence Survey (PPS) and Gyssens Flowchart Approach on Antimicrobial Use Surveillance in Indonesian National Referral Hospital.

The antimicrobial resistance (AMR) rate in Indonesia is steadily rising, despite the existing national action plan in 2014. In line with the Global Action Plan on AMR, proper surveillance on antimicrobial usage and resistance are needed. At present, antimicrobial surveillance (AMS) data in Indonesia is heterogeneous, fragmented, and localized. The common method of antimicrobial surveillance (AMS) in referral hospitals is by implementing Gyssens flowchart during Antimicrobial Resistance Control Program Committee clinical rounds. However, the recent method of AMS with Point Prevalence Survey (PPS) offers many advantages include its concise and simple protocol, large data collection, shorter required time, comprehensive data outcomes, real-time data, and standardized parameters. In low-middle income countries such as Indonesia with its restricted resources in AMS, PPS is superior compared to the 'traditional' hospital clinical round in generating representative and homogenous outcomes that can be compared to data from other centers worldwide.

Clinical Evaluation of HIV/AIDS Patients on Antiretroviral Therapy using HIV Symptoms Index: A reliability and Applicability Evaluation using Indonesian Language.

BACKGROUND: HIV/AIDS is a chronic, lifelong disease with a wide clinical spectrum which could decrease the quality of life. Objective symptoms measurement is important because it is correlated to treatment adherence and progressivity of the disease. Currently, there is no clinical tool available to evaluate symptoms of HIV infection and the treatment's side effect for the outpatient setting. This study aimed is to assess the reliability of the Indonesian version of HIV Symptom Index for measuring symptoms of HIV/AIDS patients, and use it for assessment of their symptom profile. METHODS: this is a cross sectional study in outpatient HIV/AIDS subjects (n=87) recruited in Cipto Mangunkusumo Hospital's HIV clinic from September-November 2018. The HIV Symptom Index consisted of 20 items evaluating somatic, psychologic, and the combination of both symptoms, and its' language adaptation to Indonesian was done with Beaton and Guillemin method. Reliability of the Indonesian version of HIV Symptom Index was tested by alpha cronbach's a coefficient analysis, and the internal validity was tested with multitrait scaling analysis before being used to profile the symptom pattern of HIV/AIDS patients. RESULTS: Indonesian version of HIV Symptom Index is reliable (cronbach alpha 0.76) and valid (multitrait correlation >0.4) for measuring symptoms of HIV/AIDS patients. The most common symptom is fatigue (55.7%), followed by insomnia (43.3%), dizziness and lightheadedness (42.3%), skin problems (42.3%), and pain, numbness, or tingling in the hands or feet (39.2%). CONCLUSION: Indonesian version of HIV symptom Index is reliable and valid to measure symptoms of HIV/AIDS patiens objectively.

Early Detection of Plasma Leakage in Dengue Hemorrhagic Fever.

Dengue viral infection remains a major public health problem. As many as 400 million people are infected yearly. Even though the vaccine is available, the use of dengue vaccine is still limited due to some concerns. Among patient infected with dengue viral infection, early recognition of the virus and prompt supportive treatment are important to avoid complication and mortality.The clinical spectrum of dengue viral infection is diverse ranging from undifferentiated fever to dengue shock syndrome characterized by plasma leak and hemoconcentration. No specific antiviral therapy is available. Therefore, anticipation of complication should be performed adequately.The most dangerous complication of dengue infection is shock syndrome. Hypothetically the occurrence of shock is a result of secondary viral infection. The manifestation of increased vascular permeability and low intravascular volume lead to the development of shock. In addition to that, another complex mechanism underlies the occurrence of shock such as endothelial dysfunction that could happened abruptly. No specific method exists to identify this condition as early as possible.During dengue infection, fever can be last between 2 and 7 days. The localized plasma leakage could happen and manifested as a pleural effusion fluid accumulation in abdominal cavity or hemoconcentration. This will only last for 48 hours and will be resolved later spontaneously. Severity of leakage varies among patients and the unanticipated of leakage due to failure to recognize and treat this manifestation related to mortality.Most of the fatal cases of dengue are related to late detection of the illness as shown by massive hemorrhage and severe intravascular volume depletion. The role of dendritic cells is as the initiator of immune response that facilitate virus uptake. On the other hand, the non-neutralize cross reactive antibodies will increase virus uptake and resulted in more viral replication. Some studies showed higher NS1 protein were found in patients with more severe disease. In addition to that antibody to NS1 could bind to the endothelial cells and lead to apoptosis of these cells. Both host and viral factors contribute to the severity of the illness.One of the important factors for dengue viral infection is the capacity of clinicians to identify the risk factors for shock. Studies reported that female, infants, elderly, patients with concomitant diseases are prone to have more severe infection. Virus serotype and genetic susceptibility may also contribute but the evidence is still limited. So, those are not sensitive enough be used in clinical setting.Besides those, after the diagnosis of with dengue infection based on WHO criteria and confirmation by serology detection or viral material in the blood, no specific sign and symptoms are available to determine any potential severity. There were studies performed to monitor the plasma leakage using mean arterial blood pressure (MAP) instead of hematocrit values. Rapid intervention can be administered by monitoring MAP to avoid deleterious consequences.The classification of WHO 1997 or 2009 were not able to detect the plasma leakage earlier. Nainggolan et al presented the resulted of their observation among early dengue infection which was the occurrence of gallbladder wall thickening as a manifestation of plasma leakage. Ultrasonographic measurement is valuable and applicable to detect plasma leakage in earlier phase with positive likelihood ratio 2.14 (95% CI 1.12 - 4.12). Similar report from Indonesia also showed the role of ultrasonography in dengue.

Antifungal Susceptibility Testing in HIV/AIDS Patients: a Comparison Between Automated Machine and Manual Method.

AIM: to evaluate the performance of Vitek2 compact machine (Biomerieux Inc. ver 04.02, France) in reference to manual methods for susceptibility test for Candida resistance among HIV/AIDS patients. METHODS: a comparison study to evaluate Vitek2 compact machine (Biomerieux Inc. ver 04.02, France) in reference to manual methods for susceptibility test for Candida resistance among HIV/AIDS patient was done. Categorical agreement between manual disc diffusion and Vitek2 machine was calculated using predefined criteria. Time to susceptibility result for automated and manual methods were measured. RESULTS: there were 137 Candida isolates comprising eight Candida species with C.albicans and C. glabrata as the first (56.2%) and second (15.3%) most common species, respectively. For fluconazole drug, among the C. albicans, 2.6% was found resistant on manual disc diffusion methods and no resistant was determined by Vitek2 machine; whereas 100% C. krusei was identified as resistant on both methods. Resistant patterns for C. glabrata to fluconazole, voriconazole and amphotericin B were 52.4%, 23.8%, 23.8% vs. 9.5%, 9.5%, 4.8% respectively between manual diffusion disc methods and Vitek2 machine. Time to susceptibility result for automated methods compared to Vitex2 machine was shorter for all Candida species. CONCLUSION: there is a good categorical agreement between manual disc diffusion and Vitek2 machine, except for C. glabrata for measuring the antifungal resistant. Time to susceptibility result for automated methods is shorter for all Candida species.

Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia.

BACKGROUND: Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy. A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide. METHODS: During March to July 2013, an open-label, randomized trial enrolled Indonesian soldiers with vivax malaria at Sragen, Central Java, after six months duty in malarious Papua, Indonesia. No malaria transmission occurred at the study site and P. vivax recurrences in the 12 months following therapy were classified as relapses. A historic relapse control derived from a cohort of soldiers who served in the same area of Papua was applied to estimate risk of relapse among randomized treatment groups. Those were: 1) AS followed 2d later by PQ (0.5 mg/kg daily for 14d); 2) co-formulated AS-PYR concurrent with the same regimen of PQ; or 3) co-formulated DHA-PP concurrent with the same regimen of PQ. RESULTS: Among 532 soldiers, 219 had vivax malaria during the four months following repatriation to Java; 180 of these were otherwise healthy and G6PD-normal and enrolled in the trial. Subjects in all treatment groups tolerated the therapies well without untoward events and cleared parasitemia within three days. First relapse appeared at day 39 post-enrollment, and the last at day 270. Therapeutic efficacy of PQ against relapse by incidence density analysis was 92 % (95 %CI = 83-97 %), 94 %(95 %CI = 86-97 %), and 95 %(95 %CI = 88-98 %) when combined with AS, AS-PYR, or DHA-PP, respectively. CONCLUSIONS: This trial offers evidence of good tolerability and efficacy of PQ against P. vivax relapse when administered concurrently with DHA-PP or AS-PYR. These offer alternative partner drugs for radical cure with primaquine. The AS arm demonstrated efficacy with a total dose of 7 mg/kg PQ without concurrently administered blood schizontocide, another option when primaquine therapy is removed in time from the treatment of the acute malaria or applied presumptively without an attack. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82366390, assigned 20 March 2013.

EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

Snakebite in Indonesia.

Indonesia as one of the largest tropical and agricultural countries in the world shared the particularly high burden cases of snakebite. In the last decade, World Health Organization (WHO) has listed snakebite as one of the neglected tropical disease. The clinical manifestations of snakebite could vary according to the type of venoms ranging from mild to life threatening condition. Appropriate first aid treatment and comprehensive management of snakebite cases are warranted to reduce mortality and morbidity rates.

Diagnostic and antibiotic use practices among COVID-19 and non-COVID-19 patients in the Indonesian National Referral Hospital.

BACKGROUND: Little is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities. METHODS: We linked and analyzed routine databases of hospital admission, microbiology laboratory and drug dispensing of Indonesian National Referral Hospital from 2019 to 2020. Patients were classified as COVID-19 cases if their SARS-CoV-2 RT-PCR result were positive. Blood culture (BC) practices and time to discontinuation of parenteral antibiotics among inpatients who received a parenteral antibiotic for at least four consecutive days were used to assess diagnostic and antibiotic use practices, respectively. Fine and Grey subdistribution hazard model was used. RESULTS: Of 1,311 COVID-19 and 58,917 non-COVID-19 inpatients, 333 (25.4%) and 18,837 (32.0%) received a parenteral antibiotic for at least four consecutive days. Proportion of patients having BC taken within ±1 calendar day of parenteral antibiotics being started was higher in COVID-19 than in non-COVID-19 patients (21.0% [70/333] vs. 18.7% [3,529/18,837]; p<0.001). Cumulative incidence of having a BC taken within 28 days was higher in COVID-19 than in non-COVID-19 patients (44.7% [149/333] vs. 33.2% [6,254/18,837]; adjusted subdistribution-hazard ratio [aSHR] 1.71, 95% confidence interval [CI] 1.47-1.99, p<0.001). The median time to discontinuation of parenteral antibiotics was longer in COVID-19 than in non-COVID-19 patients (13 days vs. 8 days; aSHR 0.73, 95%Cl 0.65-0.83, p<0.001). CONCLUSIONS: Routine electronic data could be used to inform diagnostic and antibiotic use practices in LMICs. In Indonesia, the proportion of timely blood culture is low in both COVID-19 and non-COVID-19 patients, and duration of parenteral antibiotics is longer in COVID-19 patients. Improving diagnostic and antimicrobial stewardship is critically needed.

Antimicrobial resistance among common bacterial pathogens in Indonesia: a systematic review.

Background: The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia. Methods: We systematically searched Embase, PubMed and Global Health Database and three Indonesian databases for original peer-reviewed articles in English and Indonesian, published between January 1, 2000 and May 25, 2023, that reported antimicrobial susceptibility for the 12 GLASS target pathogens from human samples. Pooled AMR prevalence estimates were calculated for relevant pathogen-antimicrobial combinations accounting for the sampling weights of the studies (PROSPERO: CRD42019155379). Findings: Of 2182 search hits, we included 102 papers, comprising 19,517 bacterial isolates from hospitals (13,647) and communities (5870). In hospital settings, 21.6% of Klebsiella pneumoniae isolates, 18.3% of Escherichia coli isolates, 35.8% of Pseudomonas aeruginosa isolates and 70.7% of Acinetobacter baumannii isolates were carbapenem-resistant; 29.9% of Streptococcus pneumoniae isolates were penicillin-resistant; and 22.2% of Staphylococcus aureus isolates were methicillin-resistant. Hospital prevalence of carbapenem-resistant K. pneumoniae and E. coli, and penicillin-resistant S. pneumoniae increased over time. In communities, 28.3% of K. pneumoniae isolates and 15.7% of E. coli isolates were carbapenem-resistant, 23.9% of S. pneumoniae isolates were penicillin-resistant, and 11.1% of S. aureus isolates were methicillin-resistant. Data were limited for the other pathogens. Interpretation: AMR prevalence estimates were high for critical gram-negative bacteria. However, data were insufficient to draw robust conclusions about the full contemporary AMR situation in Indonesia. Implementation of national AMR surveillance is a priority to address these gaps and inform context-specific interventions. Funding: Wellcome Africa Asia Programme Vietnam.

Barriers and enablers to blood culture sampling in Indonesia, Thailand and Viet Nam: a Theoretical Domains Framework-based survey.

OBJECTIVE: Blood culture (BC) sampling is recommended for all suspected sepsis patients prior to antibiotic administration. We examine barriers and enablers to BC sampling in three Southeast Asian countries. DESIGN: A Theoretical Domains Framework (TDF)-based survey, comprising a case scenario of a patient presenting with community-acquired sepsis and all 14 TDF domains of barriers/enablers to BC sampling. SETTING: Hospitals in Indonesia, Thailand and Viet Nam, December 2021 to 30 April 2022. PARTICIPANTS: 1070 medical doctors and 238 final-year medical students were participated in this study. Half of the respondents were women (n=680, 52%) and most worked in governmental hospitals (n=980, 75.4%). OUTCOME MEASURES: Barriers and enablers to BC sampling. RESULTS: The proportion of respondents who answered that they would definitely take BC in the case scenario was highest at 89.8% (273/304) in Thailand, followed by 50.5% (252/499) in Viet Nam and 31.3% (157/501) in Indonesia (p<0.001). Barriers/enablers in nine TDF domains were considered key in influencing BC sampling, including 'priority of BC (TDF-goals)', 'perception about their role to order or initiate an order for BC (TDF-social professional role and identity)', 'perception that BC is helpful (TDF-beliefs about consequences)', 'intention to follow guidelines (TDF-intention)', 'awareness of guidelines (TDF-knowledge)', 'norms of BC sampling (TDF-social influence)', 'consequences that discourage BC sampling (TDF-reinforcement)', 'perceived cost-effectiveness of BC (TDF-environmental context and resources)' and 'regulation on cost reimbursement (TDF-behavioural regulation)'. There was substantial heterogeneity between the countries. In most domains, the lower (higher) proportion of Thai respondents experienced the barriers (enablers) compared with that of Indonesian and Vietnamese respondents. A range of suggested intervention types and policy options was identified. CONCLUSIONS: Barriers and enablers to BC sampling are varied and heterogenous. Cost-related barriers are more common in more resource-limited countries, while many barriers are not directly related to cost. Context-specific multifaceted interventions at both hospital and policy levels are required to improve diagnostic stewardship practices.

Implementation of a Randomized, Placebo-Controlled Trial of Live Attenuated Malaria Sporozoite Vaccines in an Indonesian Military Study Population.

Malaria eradication efforts prioritize safe and efficient vaccination strategies, although none with high-level efficacy against malaria infection are yet available. Among several vaccine candidates, Sanaria® PfSPZ Vaccine and Sanaria PfSPZ-CVac are, respectively, live radiation- and chemo-attenuated sporozoite vaccines designed to prevent infection with Plasmodium falciparum, the leading cause of malaria-related morbidity and mortality. We are conducting a randomized normal saline placebo-controlled trial called IDSPZV1 that will analyze the safety, tolerability, immunogenicity, and efficacy of PfSPZ Vaccine and PfSPZ-CVac administered pre-deployment to malaria-naive Indonesian soldiers assigned to temporary duties in a high malaria transmission area. We describe the manifold challenges of enrolling and immunizing 345 soldier participants at their home base in western Indonesia before their nearly 6,000-km voyage to eastern Indonesia, where they are being monitored for incident P. falciparum and Plasmodium vivax malaria cases during 9 months of exposure. The unique regulatory, ethical, and operational complexities of this trial demonstrate the importance of thorough planning, frequent communication, and close follow-up with stakeholders. Effective engagement with the military community and the ability to adapt to unanticipated events have proven key to the success of this trial.

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.

Antibody Responses and Reactogenicity of a Heterologous, Full-Dose Messenger RNA-1273 Booster in Heavily SARS-CoV-2-Exposed CoronaVac-Vaccinated Health-Care Workers in Indonesia: A Real-World Observational Study.

Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2-exposed Indonesian health-care workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG binding antibody (Bab) titers in all 304 participants, and neutralizing antibody titers in a random subset of 71 participants, on stored paired serum samples taken before and 28 days after a full-dose (100-µg) mRNA-1273 booster. At the time of the mRNA-1273 boost, 107 participants (35.2%) were not previously infected (naive vaccinated), 42 (13.8%) were infected before CoronaVac (infected vaccinated), and 155 (51.0%) were infected after CoronaVac (mostly during the Delta wave; vaccinated infected). At time of the mRNA-1273 boost, neutralizing antibodies could still be detected in 83% of participants (59 of 71) overall, 60% of naive-vaccinated participants (15 of 25), 95.7% of vaccinated-infected participants (22 of 23), and 95.7% of infected vaccinated participants (22 of 23). After the mRNA-1273 boost, 100% of participants (71 of 71) had neutralizing antibody activity, with increases in median Bab and neutralizing antibody serum titers of 9.3- and 27.0-fold overall, 89.1- and 2,803.4-fold in naive-vaccinated participants, 15.9- and 19.9-fold in infected-vaccinated participants, and 2.2- and 18.4-fold in vaccinated-infected participants. In the multivariable analysis, Bab titers after the mRNA-1273 boost were greatest in individuals who had a previous virus breakthrough post-CoronaVac, and when a longer time period (> 4 months) had elapsed since the most recent prior "spike antigen exposure" (either second CoronaVac or virus breakthrough). Overall, adverse reactions were mild and short-lived. In conclusion, a full-dose mRNA-1273 booster after CoronaVac was well tolerated and immunogenic after 28 days, including in those with very low antibody levels.

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.