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.

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.

Molnupiravir and Nirmatrelvir/Ritonavir: The New Available Antiviral Options for COVID-19.

Coronavirus disease 2019 (COVID-19) is a respiratory tract disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the complexity of multimorbidity in Indonesia, it is crucial to find another line of antiviral for COVID-19. This article aims to review two antivirals, molnupiravir and nirmatrelvir/ritonavir, that have been studied extensively in treating COVID-19 with promising results, and their availability in Indonesia. Molnupiravir and nirmatrelvir/ritonavir are two of many repurposed drugs in clinical trials, which have been reported to have a mechanism in quick clearance of SARS-CoV-2, reduction in viral load, and fast symptoms recovery time in phase 1 and 2 clinical trials. Phase 2/3 clinical study in COVID-19 patients without any indication for hospitalization showed that molnupiravir and nirmatrelvir/ritonavir significantly reduced the risk of hospitalization and death.

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.

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.

Immunogenicity Assessment of the SARS-CoV-2 Protein Subunit Recombinant Vaccine (CoV2-IB 0322) in a Substudy of a Phase 3 Trial in Indonesia.

BACKGROUND: COVID-19 is one of the most devastating pandemics of the 21st century. Vaccination is one of the most effective prevention methods in combating COVID-19, and one type of vaccine being developed was the protein subunit recombinant vaccine. We evaluated the efficacy of the CoV2-IB 0322 vaccine in Depok, Indonesia. METHODS: This study aimed to assess the humoral and cellular immune response of the CoV2-IB 0322 vaccine compared to an active control vaccine (COVOVAX™ Vaccine). A total of 120 subjects were enrolled and randomized into two groups, with 60 subjects in each group. Participants received either two doses of the CoV2-IB 0322 vaccine or two doses of the control vaccine with a 28-day interval between doses. Safety assessments were conducted through onsite monitoring and participant-reported adverse events. Immunogenicity was evaluated by measuring IgG anti-RBD SARS-CoV-2 and IgG-neutralizing antibodies. Cellular immunity was assessed by specific T-cell responses. Whole blood samples were collected at baseline, 14 days, 6 months, and 12 months after the second dose for cellular immunity evaluation. RESULTS: Both vaccines showed high seropositive rates, with neutralizing antibody and IgG titers peaking 14 days after the second dose and declining by 12 months. The seroconversion rate of anti-S IgG was 100% in both groups, but the rate of neutralizing antibody seroconversion was lower in the CoV2-IB 0322 vaccine group at 14 days after the second dose (p = 0.004). The CoV2-IB 0322 vaccine showed higher IgG GMT levels 6 and 12 months after the second dose (p < 0.001 and p = 0.01). T-cell responses, evaluated by IFN-γ, IL-2, and IL-4 production by CD4+ and CD8+ T-cells, showed similar results without significant differences between both groups, except for %IL-2/CD4+ cells 6 months after the second dose (p = 0.038). CONCLUSION: Both vaccines showed comparable B- and T-cell immunological response that diminish over time.

Immunogenicity and safety of SARS-CoV-2 recombinant protein subunit vaccine (IndoVac) adjuvanted with alum and CpG 1018 in Indonesian adults: A phase 3, randomized, active-controlled, multicenter trial.

BACKGROUND: Bio Farma has developed a recombinant protein subunit vaccine (IndoVac) that is indicated for active immunization in population of all ages. This article reported the results of the phase 3 immunogenicity and safety study in Indonesian adults aged 18 years and above. METHODS: We conducted a randomized, active-controlled, multicenter, prospective intervention study to evaluate the immunogenicity and safety of IndoVac in adults aged 18 years and above. Participants who were SARS-CoV-2 vaccine-naïve received two doses of either IndoVac or control (Covovax) with 28 days interval between doses and were followed up until 12 months after complete vaccination. RESULTS: A total of 4050 participants were enrolled from June to August 2022 and received at least one dose of vaccine. The geometric mean ratio (GMR) of neutralizing antibody at 14 days after the second dose was 1.01 (95 % confidence interval (CI) 0.89-1.16), which met the WHO non-inferiority criteria for immunobridging (95 % CI lower bound > 0.67). The antibody levels were maintained through 12 months after the second dose. The incidence rate of adverse events (AEs) were 27.95 % in IndoVac group and 32.15 % in Covovax group with mostly mild intensity (27.70 %). The most reported solicited AEs were pain (14.69 %) followed by myalgia (7.48 %) and fatigue (6.77 %). Unsolicited AEs varied, with each of the incidence rate under 5 %. There were no serious AEs assessed as possibly, probably, or likely related to vaccine. CONCLUSIONS: IndoVac in adults showed favourable safety profile and elicited non-inferior immune response to Covovax. (ClinicalTrials.gov: NCT05433285, Indonesian Clinical Research Registry: INA-R5752S9).

Rare cardiac complication of toxoplasmosis in immunocompetent host.

Myocarditis is a rare complication of toxoplasmosis, especially in immunocompetent individuals. We present a case of a 28-year-old man with a history of fever and chest pain suggestive of myocarditis. Fever, along with lymphadenopathy, electrocardiography, imaging, and serologic testing, showed Toxoplasma gondii as the probable etiology. An excellent response to treatment confirmed the diagnosis.