Dihydroartemisinin-piperaquine chemoprevention and malaria incidence after severe flooding: evaluation of a pragmatic intervention in rural Uganda

Background Malaria epidemics are a well-described phenomenon after extreme precipitation and flooding, which account for nearly half of global disasters over the past two decades. Yet few studies have examined mitigation measures to prevent post-flood malaria epidemics. Methods We conducted an evaluation of a malaria chemoprevention program implemented in response to severe flooding in western Uganda. Children ≤12 years of age from one village were eligible to receive 3 monthly rounds of dihydroartemisinin-piperaquine (DP). Two neighboring villages served as controls. Malaria cases were defined as individuals with a positive rapid diagnostic test result as recorded in health center registers. We performed a difference-in-differences analysis to estimate changes in the incidence and test positivity of malaria between intervention and control villages. Results A total of 554 children received at least one round of chemoprevention with 75% participating in at least two rounds. Compared to control villages, we estimated a 53.4% reduction (aRR 0.47, 95% CI 0.34 – 0.62, p<.01) in malaria incidence and a 30% decrease in the test positivity rate (aRR=0.70, CI 0.50 - 0.97, p=0.03) in the intervention village in the six months post-intervention. The impact was greatest among children receiving the intervention, but decreased incidence was also observed in older children and adults (aRR=0.57, CI 0.38-0.84, p<.01). Conclusions Three rounds of chemoprevention with DP delivered under pragmatic conditions reduced the incidence of malaria after severe flooding in western Uganda. These findings provide a proof-of-concept for the use of malaria chemoprevention to reduce excess disease burden associated with severe flooding.

Stepwise Development and Yearlong Assessment of a Pharmacist-Driven Molecular Rapid Diagnostic Test Result Service for Bloodstream Infections

Purpose: Provide a stepwise approach to the design and implementation of a service that integrates all staff pharmacists into the communication and interpretation of molecular rapid diagnostic tests (mRDT) for bloodstream infections and summarize outcomes from a 12-month post-implementation assessment. Physician and pharmacist impressions of the service are also described. Summary: mRDT have proven clinical benefit in the treatment of bacteremia. Pharmacy leadership can collaborate with other health system leaders to develop policies and a workflow that route result calls to pharmacists to maximize the impact of this technology. Pharmacist education, development of clinical resources and documentation templates allow all pharmacists to perform this antimicrobial stewardship service consistently and confidently. Physicians overwhelmingly recognize the value of this service and often accept the pharmacist’s recommendations. Antibiotic de-escalation was the most frequent outcome when changes to the antibiotic regimen were made. Conclusion: Pharmacists are well positioned to utilize results from mRDT to improve antibiotic selection. Through the use of competencies and internally-derived resources, all pharmacists, rather than just infectious diseases pharmacy specialists, can perform this important antibiotic stewardship activity and positively influence patient outcomes.

Using artificial intelligence to improve COVID-19 rapid diagnostic test result interpretation

Serological rapid diagnostic tests (RDTs) are widely used across pathologies, often providing users a simple, binary result (positive or negative) in as little as 5 to 20 min. Since the beginning of the COVID-19 pandemic, new RDTs for identifying SARS-CoV-2 have rapidly proliferated. However, these seemingly easy-to-read tests can be highly subjective, and interpretations of the visible “bands” of color that appear (or not) in a test window may vary between users, test models, and brands. We developed and evaluated the accuracy/performance of a smartphone application (xRCovid) that uses machine learning to classify SARS-CoV-2 serological RDT results and reduce reading ambiguities. Across 11 COVID-19 RDT models, the app yielded 99.3% precision compared to reading by eye. Using the app replaces the uncertainty from visual RDT interpretation with a smaller uncertainty of the image classifier, thereby increasing confidence of clinicians and laboratory staff when using RDTs, and creating opportunities for patient self-testing.

Clinical Characteristics and Outcome of Children Hospitalized With Scrub Typhus in an Area of Endemicity

Background Scrub typhus, caused by Orientia tsutsugamushi, is a major cause of acute febrile illness in children in the rural tropics. Methods We recruited 60 febrile pediatric patients with a positive scrub typhus rapid diagnostic test result and 40 healthy controls from Chiang Rai Province in northern Thailand. Diagnosis was confirmed by the detection of (1) O. tsutsugamushi–specific DNA in blood or eschar samples with a polymerase chain reaction assay, (2) a fourfold rise in immunoglobulin M (IgM) titer to ≥1:3200 in paired plasma samples with an indirect immunofluorescence assay (IFA), or (3) a single IgM titer of ≥1:3200 in an acute plasma sample with an IFA. Demographic, clinical, and laboratory data were collected, and patients were followed up for 1 year. Results Diagnosis was confirmed in 35 (58%) of 60 patients, and all controls tested negative for scrub typhus. Patients with confirmed scrub typhus had clinical symptoms, including fever (35 of 35 [100%]), eschar (21 of 35 [60%]), cough (21 of 35 [60%]), tachypnea (16 of 35 [46%]), lymphadenopathy (15 of 35 [43%]), and headache (14 of 35 [40%]). Only 4 (11%) of 35 patients received appropriate antibiotic treatment for scrub typhus before admission. The median fever-clearance time was 36 hours (interquartile range, 24–53 hours). Complications observed include hepatitis (9 of 35 [26%]), severe thrombocytopenia (7 of 35 [20%]), pneumonitis (5 of 35 [14%]), circulatory shock (4 of 35 [11%]), and acute respiratory distress syndrome (3 of 35 [9%]). Treatment failure, defined by failure to defervesce within 72 hours of antibiotic treatment initiation, was noted in 8 (23%) of 35 patients, and 1 (3%) of the 35 patients died. No evidence of relapse or reinfection was found. Conclusion Pediatric scrub typhus in northern Thailand is often severe and potentially fatal with delays in treatment a likely contributing factor. Additional studies to investigate the bacterial, pharmacologic, and immunologic factors related to treatment outcome along with measures to improve public awareness should be prioritized.