Challenges in diagnosis of clinical and subclinical Plasmodium falciparum infections in Ghana and feasibility of reactive interventions to shrink the subclinical reservoir.

Background: Reactive case detection (RCD) aims to reduce malaria transmission stemming from asymptomatic carriers. Symptomatic individuals diagnosed with malaria at a health centre are followed to their households, where members of the index case and neighbouring households are tested and treated for malaria. An RCD programme was tested in the Ashanti region of Ghana in order to study diagnostic accuracy in the hospital and household settings, assess the prevalence of subclinical infections and possible clustering in index case households, and identify operational challenges for future RCD programmes. Currently, transmission in this region is high, but reactive interventions might become an option once transmission is reduced. Methods: 264 febrile individuals were enrolled at the Mankranso Government Hospital and tested for malaria using rapid diagnostic tests (RDT). From the pool of RDT-positive febrile index cases, 14 successful RCD follow-ups were conducted, and 233 individuals were enrolled from the index case, neighbour, and control households. The sensitivity of diagnostic tools for clinical and subclinical cases was compared, including RDT, expert microscopy by World Health Organization-certified microscopists, field microscopy, and qPCR. Results: Poor diagnosis and low receptivity to RCD-style follow-ups were major limitations to a successful and effective RCD programme. Field microscopy detected only 49% of clinical infections compared to RDT. 54% of individuals did not agree to a follow-up, and 66% of attempted follow-ups failed. The system effectiveness of RCD, calculated as the product of correctly diagnosed index cases, successful follow-ups, and proportion of asymptomatic infections detected by RDT, was very low at 4.0%. Conclusions: Due to low system effectiveness and the endemic nature of the disease setting in which asymptomatic prevalence is high and infections are not clustered around index case households, RCD is currently not a feasible option for malaria control in this region. The operational challenges identified through this study may help inform future reactive intervention programme designs once transmission is reduced. [ABSTRACT FROM AUTHOR]