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Background  In the past two decades, there has been a reported decline in malaria in Ghana and the rest of the world; yet it remains the number one cause of mortality and morbidity. Human immuno-deficiency virus (HIV) and sickle cell disease (SCD) share a common geographical space with malaria in sub-Saharan Africa and an interaction between these three conditions has been suggested. This study determined the  Plasmodium falciparum  and non- P. falciparum  status of symptomatic and non-symptomatic residents of Mpraeso in the highlands of Kwahu-South district of Ghana based on evidence of current national decline. The influence of HIV and SCD on malaria was also determined.    Methods  Participants were 354 symptomatic patients visiting the Kwahu Government Hospital and 360 asymptomatic residents of the district capital. This cross-sectional study was conducted during the minor rainy season (October–December 2014). Rapid diagnostic tests (RDT), blood film microscopy and real-time polymerase chain reaction assessment of blood were done. Participants who tested positive with RDT were treated with artemisinin-based combination therapy; and assessment of venous blood was repeated 7 days after treatment. HIV screening and haemoglobin genotyping was done. Univariate and multivariate regression analysis was used to determine the influence of SCD and HIV.    Results    Plasmodium falciparum  was prevalent at 124/142 (87.3%).  Plasmodium malariae  was the only non-falciparum species detected at 18/142 (12.7%). HIV and SCD did not significantly increase odds of malaria infection. However, the use of ITN and recent anti-malarial intake significantly decreased the odds of being malaria infected by 0.45-fold and 0.46-fold respectively.    Conclusion    Plasmodium falciparum  and  P. malariae  infection are the prevailing species in the study area; albeit varying from the national average. HIV and SCD were not associated with the risk of having malaria.    Electronic supplementary material  The online version of this article (doi:10.1186/s12936-017-1823-y) contains supplementary material, which is available to authorized users.

Prevalence of Plasmodium falciparum and non-P. falciparum infections in a highland district in Ghana, and the influence of HIV and sickle cell disease