High prevalence of asymptomatic and sub-patent Plasmodium falciparum infections in Urban Bouaké, Côte d’Ivoire, but no hrp2 deletions: Implications for Malaria Control

Asymptomatic Plasmodium falciparum infections are common in endemic settings, yet diagnosing these infections remains challenging because they are often below the limit of detection of conventional light microscopy (LM) or rapid diagnostic tests (RDTs). Deletions of the hrp2/3 gene, encoding the protein detected by the most sensitive class of RDTs, present a further threat. In this study, the prevalence of asymptomatic and sub-patent P. falciparum infections was characterized in the rainy season in the city of Bouaké, Central Côte d’Ivoire. A cross-sectional survey was conducted in nine neighborhoods of Bouaké, Côte d’Ivoire, in 2016. Matched LM, RDTs, and varATS qPCR, were used to determine the prevalence of P. falciparum infections and to compare the performance of the different diagnostic methods. P. falciparum hrp2/3 deletions were typed by digital PCR. Among 2313 individuals, malaria prevalence was 10.8% by microscopy, 13.0% by RDT, 35.1% by qPCR, and 37.3% (863/2313) when all three methods were combined. 96.4% (832/863) of individuals with P. falciparum infections did not report a recent fever. 57.1% (493/863) of infections were sub-patent. The prevalence was highly heterogeneous across the neighborhoods, ranging from 15% to 55.2%, and differed among age groups (<5 years: 17.7%, 5-14 years: 42.7%, ≥15 years: 35.9%). Compared to varATS qPCR, LM and RDT had a low sensitivity of 24.3% and 34.2%, respectively, although both methods were highly specific (>96%). Sub-microscopic malaria infections were more prevalent in ≥15-year-olds (69.9%, 349/499) and in the neighborhood of Dar es Salam (75.9%, 44/58). No hrp2 deletions were observed, and two samples carried hrp3 deletion/wild-type mixed infections. The high prevalence of asymptomatic and sub-patent infections prompts the implementation of strategies targeting these parasite reservoirs to achieve reductions in malaria burden in this high-transmission city of Côte d’Ivoire. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The French Initiative 5% and Expertise France provided funding through Grant N°12INI210. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This research was approved by the Ethics Committee of the Ministry of Health of Côte d’Ivoire (June 2015 No. 029/MSLS/CNER-dkn) and the University of Notre Dame Institutional Review Board (18-08-4803). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data can be obtained from the corresponding authors.