The Kinetics of Anti-SARS-CoV-2 Antibodies in Pediatric Patients and the Characterization of Post-COVID-19 Condition at 6 Months After Infection: Protocol for a Longitudinal Observational Study.

BACKGROUND: Data regarding the kinetics of anti-SARS-CoV-2 antibodies and information about post-COVID-19 condition (colloquially known as "long COVID") in children are scarce, especially in low-income countries. Even though cases of COVID-19 in children are less prevalent than adults, post-COVID-19 condition cases in children are high and have a burden that may impact their growth and development. There are other features of antibody kinetics in connection with SARS-CoV-2 infection that are yet unknown as of this writing, especially in children following infection. Furthermore, the long-term results, risk factors, and underlying pathophysiology are still uncertain. To better understand post-COVID-19 condition in children, it is necessary to further investigate the impact of clinically significant factors such multisystem inflammatory syndrome and disease severity among hospitalized survivors through their SARS-CoV-2 antibody response. OBJECTIVE: We aim to analyze anti-receptor-binding domain SARS-CoV-2 immunoglobulin G antibodies over time and characterize the signs and symptoms of post-COVID-19 condition in pediatric patients at the time of diagnosis and at 2 weeks and 1, 3, and 6 months following infection. METHODS: This is a longitudinal observational study in Indonesia. Pediatric patients diagnosed with COVID-19 by positive molecular assay using nasopharyngeal swab will be tested for anti-SARS-CoV-2 antibodies using the Roche Elecsys Anti-SARS-CoV-2 S assay at the time of diagnosis and at 2 weeks and 1, 3, and 6 months following infection. Antibody titer data will be reported as means and SDs. The respondents' signs and symptoms will be observed up to 6 months after the onset of infection, including the vaccination event, reinfection, rehospitalization, and mortality. The clinical features will be reported as frequencies and percentages. RESULTS: Participant enrollment began in February 2022. As of September 30, 2022, a total of 58 patients were enrolled. After data collection, results are expected to be analyzed in August 2023. CONCLUSIONS: This study will allow us to know the kinetics of anti-receptor-binding domain SARS-CoV-2 immunoglobulin G antibodies and data regarding post-COVID-19 condition up to 6 months following infection in the Indonesian pediatric population. Furthermore, this study has the potential to serve as a foundation for government decisions about vaccination programs and prevention measures. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43344.

Pediatric Invasive Pneumococcal Disease (IPD) in Yogyakarta, Indonesia: A Case Series.

Given the fact that invasive pneumococcal disease (IPD) has a high clinical burden, particularly among children in developing countries, data on its occurrence and clinical profile in Indonesia is still insufficient. We presented 3 cases of IPD in children who were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia between 2016 and 2019. While our first 2 patients had milder course of disease, our third patient who presented with meningoencephalitis had poor outcome. Risk factors shown in our cases were young age and malignancy history. Multiple antibiotic resistance was observed in our isolates. The fact that none of our patients have received pneumococcal vaccination marks the necessity of this vaccine especially for at-risk children.

Intermittent screening and treatment for malaria complementary to routine immunisation in the first year of life in Papua, Indonesia: a cluster randomised superiority trial.

BACKGROUND: In Papua (Indonesia), infants with P. falciparum and/or P. vivax malaria are at risk of severe anaemia and death. We hypothesized that in an area of high malaria transmission, intermittent screening and treatment of infants with malaria (ISTi) will reduce morbidity compared to passive case detection (PCDi). METHODS: We conducted a cluster randomised, open label, superiority trial. A total of 21 clusters of village health posts (VHP) were randomised 1:1 to either IST for infants coinciding with 4 routine immunisation visits or PCDi. Healthy term infants born to consenting mothers enrolled into a maternal malaria cluster randomised trial were included in the study and followed for 12 months. Point of care malaria rapid diagnostic tests were used to detect peripheral parasitaemia at 2, 3, 4 and 9 months old in all infants in ISTi clusters and when symptomatic in PCDi clusters. Infants with detected peripheral parasitaemia were treated with dihydroartemisinin-piperaquine. The co-primary outcomes were the incidence rate of clinical malaria in the first year of life and the prevalence of parasitaemia at age 12 months. The incidence rate ratio and prevalence ratio between ISTi and PCDi were estimated using mixed-effects Poisson and log-binomial regression modelling (accounting for clustering at VHP level). RESULTS: Between May 2014 and February 2017, 757 infants were enrolled into the study, 313 into 10 ISTi clusters, and 444 into 11 PCDi clusters. Overall, 132 episodes of parasitaemia were detected, of whom 17 (12.9%) were in symptomatic infants. Over 12 months, the incidence rate (IR) of clinical malaria was 24 [95% CI, 10-50] per 1000 children-years at risk in the ISTi arm and 19 [95% CI, 8,38] per 1000 children-years in the PCDi arm (adjusted incidence rate ratio [aIRR] 1.77 [95% CI, 0.62-5.01]; p = 0.280). The prevalence of parasitaemia at 12 months was 13% (33/254) in the IST clusters and 15% (57/379) in the PCD clusters (adjusted prevalence ratio (aPR) = 0.92 (95% CI, 0.70-1.21), p = 0.55). There was no difference in the risk of anaemia between treatment arms. CONCLUSIONS: In high malaria transmission area outside of Africa, our study suggests that compared to PCDi, ISTi offers no significant benefit in reducing the risk of clinical malaria in infants born to women receiving effective protection from malaria during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02001428 , registered on 20 Nov 2013.

Supervised versus unsupervised primaquine radical cure for the treatment of falciparum and vivax malaria in Papua, Indonesia: a cluster-randomised, controlled, open-label superiority trial.

BACKGROUND: There is a high risk of Plasmodium vivax recurrence in patients treated for Plasmodium falciparum malaria in co-endemic areas. Primaquine radical cure has the potential to reduce P vivax recurrences in patients presenting with P falciparum as well as P vivax malaria but is undermined by poor adherence to the currently recommended 14-day regimen. We aimed to assess the efficacy and safety of supervised versus unsupervised primaquine radical cure in patients presenting with uncomplicated malaria. METHODS: We did a cluster-randomised, controlled, open-label superiority trial in Papua, Indonesia. 21 clusters of village health posts, matched by annual parasite index, were randomly assigned (1:1) to treat patients (age >12 months and body weight >5 kg) presenting with confirmed uncomplicated P falciparum or P vivax malaria with oral dihydroartemisinin-piperaquine plus either a supervised or unsupervised 14-day course of oral primaquine (0·5 mg/kg per day). Patients in the supervised group were supervised taking their primaquine dose on alternate days. Patients were followed-up for 6 months and those who presented again with malaria were retreated with the same drug regimen. Masking was not possible due to the nature of the study. The primary outcome was the incidence risk of P vivax malaria over 6 months, assessed in the modified intention-to-treat population (all patients who were assigned to a treatment group, excluding patients who were lost to follow-up after their first visit). This trial is now complete, and is registered with ClinicalTrials.gov, NCT02787070. FINDINGS: Between Sept 14, 2016, and July 31, 2018, 436 patients were screened for eligibility and 419 were enrolled; 223 (53%) patients in 11 clusters were assigned to supervised primaquine treatment and 196 (47%) in ten clusters to unsupervised primaquine treatment. 161 (72%) of 223 patients in the supervised group and 151 (77%) of 196 in the unsupervised group completed 6 months of follow-up. At 6 months, the incidence risk of P vivax recurrence in the supervised group was 29·7% (95% CI 16·4-49·9) versus 55·8% (32·3-81·8) in the unsupervised group (hazard ratio 0·23 [95% CI 0·07-0·76]; p=0·016). The incidence rate for P vivax recurrence was 539 (95% CI 390-747) infections per 1000 person-years in the supervised group versus 859 (673-1096) in the unsupervised group (incidence rate ratio 0·63 [95% CI 0·42-0·94]; p=0·025). The corresponding rates in the 224 patients who presented with P falciparum malaria were 346 (95% CI 213-563) and 660 (446-977; incidence rate ratio 0·52 [95% CI 0·28-0·98]; p=0·043). Seven serious adverse events were reported (three in the supervised group, four in the unsupervised group), none of which were deemed treatment-related, and there were no deaths. INTERPRETATION: In this area of moderate malaria transmission, supervision of primaquine radical cure treatment reduced the risk of P vivax recurrence. This finding was apparent for patients presenting with either P falciparum or P vivax malaria. Further studies are warranted to investigate the safety and efficacy of radical cure for patients presenting with uncomplicated falciparum malaria in other co-endemic areas. FUNDING: The Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Foreign Affairs and Trade of the Australian Government. TRANSLATION: For the Indonesian translation of the abstract see Supplementary Materials section.

Asymptomatic Vivax and Falciparum Parasitaemia with Helminth Co-Infection: Major Risk Factors for Anaemia in Early Life.

BACKGROUND: Anaemia in children under five years old is associated with poor health, growth and developmental outcomes. In Papua, Indonesia, where the burden of anaemia in infants is high, we conducted a community survey to assess the association between Plasmodium infection, helminth carriage and the risk of anaemia. METHODS: A cross sectional household survey was carried out between April and July 2013 in 16 villages in the District of Mimika using a multistage sampling procedure. A total of 629 children aged 1-59 months from 800 households were included in the study. Demographic, symptom and anthropometry data were recorded using a standardized questionnaire. Blood and stool samples were collected for examination. RESULTS: Of the 533 children with blood film examination, 8.8% (47) had P. vivax parasitaemia and 3.9% (21) had P. falciparum; the majority of children with malaria were asymptomatic (94.4%, 68/72). Soil transmitted helminth (STH) infection was present in 43% (105/269) of children assessed; those with STH were at significantly greater risk of P. vivax parasitaemia compared to those without STH (OR = 3.7 [95%CI 1.5-9.2], p = 0.004). Anaemia (Hb<10 g/dl) was present in 24.5% (122/497) of children and associated with P. vivax parasitaemia (OR = 2.9 [95%CI, 1.7-4.9], p = 0.001), P. falciparum parasitaemia (OR = 4.3 [95%CI, 2.0-9.4], p<0.001), hookworm carriage (OR = 2.6 [95%CI, 1.2-5.8], p = 0.026), Plasmodium-helminth coinfection (OR 4.0 [95%CI, 1.4-11.3], p = 0.008) and severe stunting (OR = 1.9 ([95%CI, 1.1-3.3], p = 0.012). CONCLUSIONS: Asymptomatic P. vivax and P. falciparum infections and hookworm all contribute to risk of paediatric anaemia in coendemic areas and should be targeted with prevention and treatment programs. The relationship between helminth infections and the increased risk of P. vivax parasitaemia should be explored prospectively.