Microscopic and Submicroscopic Asymptomatic Plasmodium falciparum Infections in Ghanaian Children and Protection against Febrile Malaria

Abstract

Naturally acquired immunity to Plasmodium falciparum malaria is thought to be non-sterile and sustained by persistence of low level parasitaemia. This study assessed the association between baseline microscopic and submicroscopic asymptomatic P. falciparum infections and anti-malarial antibody levels and whether these parasitaemia modify protective associations between antibody levels and malaria in Ghanaian children. Healthy children (N=973, aged 0.5-12 years) were recruited into a 50-week longitudinal malaria cohort study from January 2016 to January 2017. Baseline asymptomatic parasitaemia were determined by microscopy (microscopic parasitaemia) and polymerase chain reaction (submicroscopic parasitaemia) and antibody levels against crude schizont antigens measured by ELISA. Antibody levels, parasite diversity and risk of malaria in the ensuing transmission season were compared among children who had baseline asymptomatic microscopic or submicroscopic or no P. falciparum infections. Of the 99 asymptomatic baseline infections, 46 (46.5%) were microscopic and 53 (53.5%), submicroscopic. Cox regression analysis adjusting for age group, sex and community found a strong association between both baseline microscopic [Hazard ratio (HR)=0.36, 95%CI=(0.21, 0.63), p<0.001] and submicroscopic [HR=0.22, 95%CI=(0.11, 0.44), p<0.001] asymptomatic parasitaemia and a reduced risk of febrile malaria compared to those who were uninfected at baseline. Baseline asymptomatic submicroscopic parasitaemia had a significant effect on associations between anti-schizont antibodies and protection against febrile malaria (likelihood ratio test p<0.001). The study found both baseline P. falciparum asymptomatic microscopic and more strongly submicroscopic infections to be associated with protection against febrile malaria in the ensuing transmission season. This could have important implications for malaria sero-epidemiological studies and vaccine trials.

Hyper-prevalence of submicroscopic Plasmodium falciparum infections in a rural area of western Kenya with declining malaria cases

“…Additionally, these low transmission zones have been reported to be prone to submicroscopic P. falciparum infections [ 8 ]. The reduced microscopic infections rates and increased levels of submicroscopic infections within this study site may indicate declining parasite genetics [ 9 ], host exposure to fewer bites by infected Anophelines [ 10 , 11 ], and a faster rate of acquired immunity acquisition due to fewer parasite clones [ 15 , 43 ]. These three underlining factors have been previously linked to increased levels of submicroscopic P. falciparum infections.…”

“…Submicroscopic infections have been observed not only in high transmission settings but also in malaria endemic areas with seasonal or low transmission [ 7 , 8 ]. These infections also show reduced parasite genetic diversity [ 9 ], fewer infective Anopheles [ 10 , 11 ], lower adherence to anti-malarials drug regimens [ 12 – 14 ], and increased asexual parasite clearance rates [ 9 , 15 ]. Previous studies of submicroscopic parasitaemia have primarily been concerned with its occurrence in pregnant women [ 16 – 20 ] and cross-sectional community surveys of asymptomatic individuals [ 3 , 21 – 24 ].…”

Evidence for an Adult-Like Type 1-Immunity Phenotype of Vδ1, Vδ2 and Vδ3 T Cells in Ghanaian Children With Repeated Exposure to Malaria

“…Asymptomatic parasitemia was defined as children who had no clinical manifestations of malaria despite being microscopy positive at least once during the 42-week follow up period. In addition to not having fever, malaria free status was confirmed as being negative for any parasitemia by both microscopy and polymerase chain reaction (PCR) with specific primers targeting a 276-bp fragment of the 18S rRNA gene of P. falciparum as previously described ( 33 ). Children under 1 year or over 13 years old or having fever without any detectable P. falciparum parasitemia by microscopy at the time of sampling were excluded.…”

Plasmodium falciparumserology: A comparison of two protein production methods for analysis of antibody responses by protein microarray

“…Advances in technology have led to the development of new assay platforms that allow proteome scale investigation of antibody responses, such as the protein microarray [11,12] boasting significantly greater experimental throughput than more classical monoplex methods (e.g. ELISA) [13,14]. The ability to simultaneously interrogate large numbers of putative targets, using low volumes of sample, significantly increases the rate at which antibody responses to antigens can be characterised.…”

“…ELISA). [16,17] The ability to simultaneously interrogate large numbers of putative targets, using low volumes of sample, significantly increases the rate at which an individual’s antibody responses to antigens can be characterised. As such, protein microarray based approaches to biomarker identification and humoral response profiling in malaria, and other infectious diseases, have been increasingly adopted.…”