The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial.

INTRODUCTION: Symptoms reported following the administration of investigational drugs play an important role in decisions for registration and treatment guidelines. However, symptoms are subjective, and interview methods to quantify them are difficult to standardise. We explored differences in symptom reporting across study sites of a multicentre antimalarial trial, with the aim of informing trial design and the interpretation of safety and tolerability data. METHODS: Data were derived from the IMPROV trial, a randomised, placebo-controlled double blinded trial of high dose primaquine to prevent Plasmodium vivax recurrence conducted in eight study sites in Afghanistan, Ethiopia, Indonesia and Vietnam. At each follow up visit a 13-point symptom questionnaire was completed. The number and percentage of patients with clinically relevant symptoms following the administration of primaquine or placebo, were reported by study site including vomiting, diarrhoea, anorexia, nausea, abdominal pain and dizziness. Multivariable logistic regression was used to estimate the confounder-adjusted site-specific proportion of each symptom. RESULTS: A total of 2,336 patients were included. The greatest variation between sites in the proportion of patients reporting symptoms was for anorexia between day 0 and day 13: 97.3% (361/371) of patients in Arba Minch, Ethiopia, reported the symptom compared with 4.7% (5/106) of patients in Krong Pa, Vietnam. Differences attenuated slightly after adjusting for treatment arm, age, sex, day 0 parasite density and fever; with the adjusted proportion for anorexia ranging from 4.8% to 97.0%. Differences between sites were greater for symptoms graded as mild or moderate compared to those rated as severe. Differences in symptom reporting were greater between study sites than between treatment arms within the same study site. CONCLUSION: Despite standardised training, there was large variation in symptom reporting across trial sites. The reporting of severe symptoms was less skewed compared to mild and moderate symptoms, which are likely to be more subjective. Trialists should clearly distinguish between safety and tolerability outcomes. Differences between trial arms were much less variable across sites, suggesting that the relative difference in reported symptoms between intervention and control group is more relevant than absolute numbers and should be reported when possible. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01814683; March 20th, 2013.

Adapting international clinical trials during COVID-19 and beyond.

BACKGROUND: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. THE NEW WORKING MODEL: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice-compliant antimalarial trials and foster cross-country and cross-study site collaboration. CONCLUSION: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research.

Spatial analysis to evaluate risk of malaria in Northern Sumatera, Indonesia.

BACKGROUND: As Indonesia aims for malaria elimination by 2030, provisional malaria epidemiology and risk factors evaluation are important in pursue of this national goal. Therefore, this study aimed to understand the risk factor of malaria in Northern Sumatera. METHODS: Malaria cases from 2019 to 2020 were obtained from the Indonesian Ministry of Health Electronic Database. Climatic variables were provided by the Center for Meteorology and Geophysics Medan branch office. Multivariable logistic regression was undertaken to understand the risk factors of imported malaria. A zero-inflated Poisson multivariable regression model was used to study the climatic drivers of indigenous malaria. RESULTS: A total of 2208 (indigenous: 76.0% [1679] and imported: 17.8% [392]) were reported during the study period. Risk factors of imported malaria were: ages 19-30 (adjusted odds ratio [AOR] = 3.31; 95% confidence interval [CI] 1.67, 2.56), 31-45 (AOR = 5.69; 95% CI 2.65, 12.20), and > 45 years (AOR = 5.11; 95% CI 2.41, 10.84). Military personnel and forest workers and miners were 1,154 times (AOR = 197.03; 95% CI 145.93, 9,131.56) and 44 times (AOR = 44.16; 95% CI 4.08, 477,93) more likely to be imported cases as compared to those working as employees and traders. Indigenous Plasmodium falciparum increased by 12.1% (95% CrI 5.1%, 20.1%) for 1% increase in relative humidity and by 21.0% (95% CrI 9.0%, 36.2%) for 1 °C increase in maximum temperature. Plasmodium vivax decreased by 0.8% (95% CrI 0.2%, 1.3%) and 16.7% (95% CrI 13.7%, 19.9%) for one meter and 1 °C increase of altitude and minimum temperature. Indigenous hotspot was reported by Kota Tanjung Balai city and Asahan regency, respectively. Imported malaria hotspots were reported in Batu Bara, Kota Tebing Tinggi, Serdang Bedagai and Simalungun. CONCLUSION: Both indigenous and imported malaria is limited to a few regencies and cities in Northern Sumatera. The control measures should focus on these risk factors to achieve elimination in Indonesia.

Comparison of the performance of the CareStart Malaria Pf/Pan Combo test and field microscopy in the diagnosis of Plasmodium vivax malaria in North Sumatera, Indonesia.

BACKGROUND: In areas where malaria is endemic and where trained microscopists are not available, rapid diagnostic tests (RDTs) are needed not only to allow prompt treatment without delay but also to prevent overdiagnosis and overtreatment based on clinical judgements that may lead to drug resistance. This study aimed to compare the performances of the CareStart Pf/Pan Combo test to field microscopy, which is considered to be the gold standard for malaria diagnosis. METHODS: Any person with a fever or a history of fever within 48 h who came to the health centre was recruited for the study and tested both by the CareStart Pf/Pan test and by field microscopy. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were analysed with both methods. RESULTS: Two-hundred study participants were enrolled: 96 (48%) were found to be positive through microscopy, while 100 (50%) participants were found to be positive through RDT. The RDT produced four false-positive results. High sensitivity and specificity were observed for the CareStart Pf/Pan test (100 and 96.15%, respectively). The CareStart Pf/Pan test also showed excellent agreement with the field microscopy results. CONCLUSION: The Carestart Pf/Pan could be used as an alternative diagnostic test in malaria-endemic areas where facility for performing microscopy is not available.

Haematological profile of children with malaria in Sorong, West Papua, Indonesia.

BACKGROUND: Malaria remains a major public health problem in Indonesian Papua, with children under five years of age being the most affected group. Haematological changes, such as cytopenia that occur during malaria infection have been suggested as potential predictors and can aid in the diagnosis of malaria. This study aimed to assess the haematological alterations associated with malaria infection in children presenting with signs and symptoms of malaria. METHODS: A retrospective study was performed by collecting data from the medical records of malaria patients at Sorong Regional General Hospital, Sorong, West Papua, Indonesia, both from outpatient and inpatient clinics, from January 2014 until December 2017. The laboratory profile of children suffering from malaria was evaluated. RESULTS: One hundred and eighty-two children aged 1 month to 18 years old were enrolled. The subjects were mostly male (112, 61.5%) with a mean age of 6.45 years (SD = 4.3 years). Children below 5 years of age suffered the most from malaria in this study (77, 42.3%). One hundred two subjects (56%) were infected with Plasmodium falciparum. Half of the enrolled subjects (50%) had haemoglobin level (Hb) between 5.1 and 10 gr/dL. A total of 41 children (53.2%) less than 5 years old suffered from P. falciparum infection. In the age group of 5-10 years, there were 34 children (57.6%) who suffered from P. falciparum, and in the age group > 10 years, 27 children (58.7%) suffered from P. falciparum infection. Only 4 subjects (5.2%) in the less than 5 years old age group had mixed malaria infection. Among eight predictors of the haematological profile, there were five predictors that were significantly associated with the diagnostic criteria, namely haemoglobin, haematocrit, leukocytes, platelets and monocytes (p < 0.05). Generally, clinical symptoms are not significantly associated with a malaria diagnosis, and only one variable showed a significant relationship, pale, with a P value of 0.001. CONCLUSIONS: Children with malaria had changes in some haematological markers, with anaemia, low platelet count, white blood count, and lymphocyte count being the most important predictors of malaria infection in the study area. These markers could be used to raise suspicion of malaria in children living in high endemic areas, such as West Papua.

Correction: Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003084.].

Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial.

BACKGROUND: Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria. METHODS: We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683). FINDINGS: Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (-0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group). INTERPRETATION: In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria. FUNDING: UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).

Prevalence and risk factors of soil-transmitted helminthiasis among school children living in an agricultural area of North Sumatera, Indonesia.

BACKGROUND: Soil-transmitted helminth infection (STH) is one of the neglected tropical disease that affects approximately 2 billion people globally. School children represent the age group that is most commonly infected with STHs, resulting in poor school performance, impaired cognitive function, and many other detrimental effects. The transmission of STH is determined by many factors, such as hygiene and sanitation. Understanding the factors that influence disease transmission in a particular area is key to effective STH control. The objective of this study was to determine the prevalence of STH in North Sumatera and to identify the associated risk factors among school children. METHODS: A cross-sectional study was carried out among primary school children in Suka village, Tigapanah subdistrict. Stool samples were processed using a single Kato-Katz method. The potential risk factors analyzed were parent education and occupation, hand washing habits, latrine usage, footwear usage and contact with soil. The Chi-square test was performed to identify an association between risk factors and parasitological results. Logistic regression analysis was used to measure the strength of association. RESULTS: We enrolled 468 school children between 6 and 12 years of age. Among those children, 268 children (57.24%) were positive for one or more STH infections. Approximately 62.39% of children played with soil/dirt every day, and only 50% regularly washed their hands after activities. Most of the children wore shoes/slippers when going outside (87.82%) and used a latrine for defecation (85.04%). Playing with soil/dirt have been shown to increase the risk of STH infections 7.53 times, while hand washing habits and latrine usage decreased the risk of STH infections 0.16 times each. CONCLUSION: The prevalence of STH infection in school children in Suka village, Tigapanah subdistrict is still high. Playing with soil/dirt increased the risk of infection, while hand washing habits and latrine usage decreased the risk of infection. The combined strategies of improving the personal hygiene of children and biannual deworming can reduce the risk of STH infection in school children in Suka village, Tigapanah subdistrict.

Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.

The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.

Antimicrobial resistance in uropathogens and appropriateness of empirical treatment: a population-based surveillance study in Indonesia.

Objectives: Urinary tract infections (UTIs) are a common reason for empirical treatment with broad-spectrum antibiotics worldwide. However, population-based antimicrobial resistance (AMR) prevalence data to inform empirical treatment choice are lacking in many regions, because of limited surveillance capacity. We aimed to assess the prevalence of AMR to commonly used antimicrobial drugs in Escherichia coli and Klebsiella pneumoniae isolated from patients with community- or healthcare-associated UTIs on two islands of Indonesia. Methods: We performed a cross-sectional patient-based study in public and private hospitals and clinics between April 2014 and May 2015. We screened patients for symptoms of UTIs and through urine dipstick analysis. Urine culture and susceptibility testing were supported by telemicrobiology and interactive virtual laboratory rounds. Surveillance data were entered in forms on mobile phones. Results: Of 3424 eligible patients, 3380 (98.7%) were included in the final analysis, and yielded 840 positive cultures and antimicrobial susceptibility data for 657 E. coli and K. pneumoniae isolates. Fosfomycin was the single oral treatment option with resistance prevalence <20% in both E. coli and K. pneumoniae in community settings. Tigecycline and fosfomycin were the only options for treatment of catheter-associated UTIs with resistance prevalence <20%, whilst the prevalence of resistance to meropenem was 21.3% in K. pneumoniae . Conclusions: Patient-based surveillance of AMR in E. coli and K. pneumoniae causing UTIs indicates that resistance to the commonly available empirical treatment options is high in Indonesia. Smart AMR surveillance strategies are needed to inform policy makers and to guide interventions.

A randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine combined with primaquine for radical treatment of vivax malaria in Sumatera, Indonesia.

BACKGROUND: A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established. METHODS: We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year. RESULTS: Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ. CONCLUSIONS: In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated. CLINICAL TRIALS REGISTRATION: NCT01288820.

Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020-2023): a multicentre prospective cohort study.

Background: Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods: A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The participant hospitals were conveniently sampled based on existing collaborations, site willingness and available study resources, and included six urban and two rural general hospitals from East Nusa Tenggara, Jakarta, and North Sumatra provinces. Factors associated with severe disease and day-28 mortality were examined using logistic and Cox regression. Findings: Among 822 participants, the age-adjusted percentage of severe disease was 26.8% (95% CI 22.7-30.9) for pre-delta, 50.1% (44.0-56.2) for delta, and 15.2% (9.7-20.7) for omicron. The odds of severe disease were 64% (18-84%) lower for omicron than delta (p < 0.001). One or more vaccine doses reduced the odds of severe disease by 89% (65-97%) for delta and 98% (91-100%) for omicron. Age-adjusted mortality was 11.9% (8.8-15.0) for pre-delta, 24.4% (18.8-29.9) for delta and 9.6% (5.2-14.0) for omicron. The day-28 cumulative incidence of death was lower for omicron (9.2% [5.6-13.9%]) than delta (28.6% [22.0-35.5%]) (p < 0.001). Severe disease on admission was the predominant prognostic factor for death (aHR34.0 [16.6-69.9] vs mild-or-moderate; p < 0.001). After controlling for disease severity on admission as an intermediate, the risk of death was 48% (32-60%) lower for omicron than delta (p < 0.001); and 51% (38-61%; p < 0.001) lower for vaccinated participants than unvaccinated participants overall, and 56% (37-69%; p < 0.001) for omicron, 46% (-5 to 73%; p = 0.070) for pre-delta (not estimable for delta). Interpretation: Infections by omicron variant resulted in less severe and fatal outcomes than delta in hospitalised patients in Indonesia. However, older, and unvaccinated individuals remained at greater risk of adverse outcomes. Funding: University of Oxford and Wellcome Trust.

Effectiveness of dihydroartemisinin-piperaquine after 10 years as treatment for vivax malaria in Indonesia.

INTRODUCTION: Dihydroartemisin-piperaquine (DHP) is a type of artemisinin-based combination therapy (ACT) that is extensively used in Indonesia as first-line malaria treatment over the past 10 years. Therefore, DHP has been known to have high efficacy, but re-evaluation of the efficacy was needed since the treatment was being used for a long time. METHODOLOGY: A cohort prospective study on pediatric and adult patients diagnosed with vivax malaria in Kualuh Leidong health centre was conducted from November 2019 - April 2020 to evaluate the efficacy of DHP for the treatment of malaria vivax. The efficacy of DHP was monitored by evaluating the clinical symptoms and serial peripheral blood smear at day 1,2,3,7,14,21 and 28. RESULTS: A total of 60 children and adults diagnosed with malaria vivax were enrolled for this study. Major symptoms such as fever, sweating and dizziness were found in all of subjects. The mean number of parasites on day 0 of observation in the child and adult groups was 313.33/µL and 328/µL respectively (p = 0.839). Meanwhile, the mean number of gametocytes on day 0 was 74109.33/µL in the child group and 61661.33/µL in the adult group. There was a reduction in the number of gametocytes on the 1st day of observation in the child and adult groups to 669.33/µL and 489.33/µL respectively (p = 0.512). No recrudescence occurred in either group within 28 days of observation. CONCLUSIONS: DHP is still efficacious and safe as a first-line treatment for vivax malaria in Indonesia, with 100% cure rate at 28 days of observation.

Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening.

Primaquine for radical cure of Plasmodium vivax malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine. Routine safety monitoring by physical examination, urine inspection, and blood haemoglobin (Hb) assessment were performed in all those trials. Early signs of acute haemolysis, i.e., dark urine and haemoglobin drop >20%, occurred only after day 3 and as late as day 8 of primaquine dosing. All patients were hospitalized and fully recovered, all but one following blood transfusion rescue. Hb nadir was 4.7 to 7.9 g/dL. Hospitalization was for 1 to 7 days. Hb levels returned to baseline values 3 to 10 days after transfusion. Failed G6PD screening procedures in these trials led G6PD-deficient patients to suffer harmful exposures to primaquine. The safe application of primaquine anti-relapse therapy requires G6PD screening and anticipation of its failure with a means of prompt detection and rescue from the typically abrupt haemolytic crisis.

Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency.

BACKGROUND: The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited. METHODS: Within the context of a multicentre, randomised clinical trial of two primaquine regimens in P. vivax malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study. They were treated with a weekly dose of 0.75 mg/kg primaquine for 8 weeks (PQ8W) plus dihydroartemisinin piperaquine (Indonesia) or chloroquine (Afghanistan, Ethiopia, Vietnam). G6PD status was diagnosed using the fluorescent spot test and confirmed by genotyping for locally prevalent G6PD variants. The risk of P. vivax recurrence following PQ8W and the consequent haematological recovery were characterized in all patients and in patients with genotypically confirmed G6PD variants, and compared with the patients enrolled in the main randomised control trial. RESULTS: Between July 2014 and November 2017, 42 male and 8 female patients were enrolled in Afghanistan (6), Ethiopia (5), Indonesia (19), and Vietnam (20). G6PD deficiency was confirmed by genotyping in 31 patients: Viangchan (14), Mediterranean (4), 357A-G (3), Canton (2), Kaiping (2), and one each for A-, Chatham, Gaohe, Ludhiana, Orissa, and Vanua Lava. Two patients had recurrent P. vivax parasitaemia (days 68 and 207). The overall 12-month cumulative risk of recurrent P. vivax malaria was 5.1% (95% CI: 1.3-18.9) and the incidence rate of recurrence was 46.8 per 1000 person-years (95% CI: 11.7-187.1). The risk of P. vivax recurrence was lower in G6PD deficient patients treated with PQ8W compared to G6PD normal patients in all treatment arms of the randomised controlled trial. Two of the 26 confirmed hemizygous males had a significant fall in haemoglobin (>5g/dl) after the first dose but were able to complete their 8 week regimen. CONCLUSIONS: PQ8W was highly effective in preventing P. vivax recurrences. Whilst PQ8W was well tolerated in most patients across a range of different G6PD variants, significant falls in haemoglobin may occur after the first dose and require clinical monitoring. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT01814683).

Transmission and Profile of COVID-19 in Children in North Sumatera, Indonesia.

BACKGROUND: In December 2019, a cluster of viral pneumonia cases, later identified as coronavirus disease 2019 (COVID-19), was first reported in Wuhan, China, and then continued to spread to other parts of the world. COVID-19 is thought to be more prevalent in adults than children; therefore, information about COVID-19 burden and characteristics in children is lacking. METHODS: We gathered data on the profile and transmission in children with COVID-19 from data collected by the North Sumatera Provincial Health Office team. Data were presented as mean±SD and percentage. Statistical analysis was performed using STATA version 15.0. RESULTS: From April to October 2020, there were 1125 confirmed COVID-19 cases in children in North Sumatera, representing approximately 8.9% of all cases. Death occurred in 0.62% of the patients, and the children who died had underlying diseases. Four major clusters of COVID-19 infection in children were found in three Islamic boarding schools and one refugee shelter. CONCLUSION: A high number of children in North Sumatera were affected by COVID-19, and mortality was found to be higher in children with underlying diseases. Major clusters were found in places with prolonged and repeated activities in close contact, such as boarding schools and a refugee shelter.

Spatio-Temporal Patterns of Dengue Incidence in Medan City, North Sumatera, Indonesia.

Dengue has been a perennial public health problem in Medan city, North Sumatera, despite the widespread implementation of dengue control. Understanding the spatial and temporal pattern of dengue is critical for effective implementation of dengue control strategies. This study aimed to characterize the epidemiology and spatio-temporal patterns of dengue in Medan City, Indonesia. Data on dengue incidence were obtained from January 2016 to December 2019. Kulldorff's space-time scan statistic was used to identify dengue clusters. The Getis-Ord Gi* and Anselin Local Moran's I statistics were used for further characterisation of dengue hotspots and cold spots. Results: A total of 5556 cases were reported from 151 villages across 21 districts in Medan City. Annual incidence in villages varied from zero to 439.32 per 100,000 inhabitants. According to Kulldorf's space-time scan statistic, the most likely cluster was located in 27 villages in the south-west of Medan between January 2016 and February 2017, with a relative risk (RR) of 2.47. Getis-Ord Gi* and LISA statistics also identified these villages as hotpot areas. Significant space-time dengue clusters were identified during the study period. These clusters could be prioritized for resource allocation for more efficient prevention and control of dengue.

Effectiveness Hand Washing and Hand Rub Method in Reducing Total Bacteria Colony from Nurses in Medan.

BACKGROUND: Hospital-acquired infection (HAI) is a major problem for the patient's health care and may impact the duration of treatment. Hand hygiene is a simple procedure but giving good prevention usually done among nurses at the hospital. AIM: Objective of the study is to determine the effectivity of handwashing method compared to hand rub to eliminate microorganisms on nurse's hands at Sumatera Utara University Hospital. This is an experimental analytic study using random sampling technique. METHODS: There were 16 nurses enrolled in this study. There were 2 groups involved; the first group using handwashing with soap and the other one using hand rub. The swabs were taken from each hand from both groups before and after washing their hands. Moreover, the swabs directly sent to Microbiology Laboratory of Sumatera Utara University to identify bacteria which colonise the hand. RESULTS: There were no significant differences between using handwashing method compared to hand rub in reducing total bacterial colony on hands (p = 0.088). The average of total colony decreased by using handwashing method is 59.5%, and by using a hand, rub is 47.2%. CONCLUSION: Hand hygiene method using alcohol-based hand rub liquid has been recommended by WHO and can replace hand washing method in a particular situation.

Risk Factors for Soil-Transmitted Helminthiasis in Preschool Children Living in Farmland, North Sumatera, Indonesia.

BACKGROUND: Disease burden from soil-transmitted helminthiasis (STH) is mainly attributed to its chronic and insidious impact on health and quality of life. Strategy recommended by World Health Organization (WHO) to control it was previously focused on school-aged children, but now preschool-aged children are involved. This study was intended to determine STH infection risk factors in preschool children. METHODS: A cross-sectional study was conducted in Suka Village, North Sumatera, Indonesia, from October to December 2016. Subjects were children aged 1 to 5 years without history of taking antihelminthic. Subjects were obtained by consecutive sampling. Demographic data and risk factors for helminthiasis were collected using questionnaire-based interview. Subjects were divided into two groups, positive and negative STH infection, based on Kato Katz method. Analysis was done using chi-square and logistic regression test. p value < 0.05 was considered significant. RESULTS: We enrolled 90 subjects in this study, with the mean age being 31.7 months. STH infection prevalence was 34.4%. Statistical analysis revealed that mother/caregiver hand washing habit (p = 0.007), mother/caregiver nail trimming habit (p = 0.018), and children nail trimming habit (p = 0.022) were significant risk factors for STH infection. CONCLUSION: Mother/caregiver hand washing habit is the most influential risk factor for STH infection in preschool children.