METHODS: Ten RDTs were evaluated: nine to detect clinical P. knowlesi infections from Malaysia, and nine assessing limit of detection (LoD) for P. knowlesi (PkA1-H.1) and P. falciparum (Pf3D7) cultures. Targets included Plasmodium-genus parasite lactate dehydrogenase (pan-pLDH) and P. vivax (Pv)-pLDH.
RESULTS: Samples were collected prior to antimalarial treatment from 127 patients with microscopy-positive PCR-confirmed P. knowlesi mono-infections. Median parasitaemia was 788/µL (IQR 247-5,565/µL). Pan-pLDH sensitivities ranged from 50.6% (95% CI 39.6-61.5) (SD BIOLINE) to 87.0% (95% CI 75.1-94.6) (First Response® and CareStart™ PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit™). For parasite counts ≥200/µL, pan-pLDH (Standard Q) and Pv-pLDH RDTs exceeded 95% sensitivity. Specificity of RDTs against 26 PCR-confirmed negative controls was 100%. Sensitivity of six highest performing RDTs were not significantly different when comparing samples taken before and after (median 3 hours) antimalarial treatment. Parasite ring stages were present in 30% of pre-treatment samples, with ring stage proportions (mean 1.9%) demonstrating inverse correlation with test positivity of Biocredit™ and two CareStart™ RDTs.For cultured P. knowlesi, CareStart™ PAN demonstrated the lowest LoD at 25 parasites/µL; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/µL. Pv-pLDH LoD for P. knowlesi was 49 parasites/µL. No false-positive results were observed in either P. falciparum-pLDH or histidine-rich-protein-2 channels.
CONCLUSION: Selected RDTs demonstrate sufficient performance for detection of major human malaria species including P. knowlesi in co-endemic areas where microscopy is not available, particularly for higher parasite counts, although cannot reliably differentiate among non-falciparum malaria.
METHODS: A parallel, cluster, randomized controlled, interventional trial is being conducted for 18 months in Damansara Damai, Selangor, Malaysia, to determine the efficacy of using gravid oviposition sticky (GOS) trap and dengue non-structural 1 (NS1) antigen test for early surveillance of dengue among Aedes mosquitoes to reduce dengue outbreaks. Eight residential apartments were randomly assigned into intervention and control arms. GOS traps are set at the apartments to collect Aedes weekly, following which dengue NS1 antigen is detected in these mosquitoes. When a dengue-positive mosquito is detected, the community will be advised to execute vector search-and-destroy and protective measures. The primary outcome concerns the the percentage change in the (i) number of dengue cases and (ii) durations of dengue outbreaks. Whereas other outcome measures include the change in density threshold of Aedes and changes in dengue-related knowledge, attitude and practice among cluster inhabitants.
DISCUSSION: This is a proactive and early dengue surveillance in the mosquito vector that does not rely on notification of dengue cases. Surveillance using the GOS traps should be able to efficiently provide sufficient coverage for multistorey dwellings where population per unit area is likely to be higher. Furthermore, trapping dengue-infected mosquitoes using the GOS trap, helps to halt the dengue transmission carried by the mosquito. It is envisaged that the results of this randomized controlled trial will provide a new proactive, cheap and targeted surveillance tool for the prevention and control of dengue outbreaks.
TRIAL REGISTRATION: This is a parallel-cluster, randomized controlled, interventional trial, registered at ClinicalTrials.gov (ID: NCT03799237), on 8th January 2019 (retrospectively registered).