Epidemiological and clinical implications of asymptomatic malaria and schistosomiasis co-infections in a rural community in western Kenya
Authors: Kamau Edwin , Yates Adam , Maisiba Risper , Singoei Valentine , Opot Benjamin , Adeny Rose , Arima Cornel O. , Otieno Victor , Sumbi Catherine S. , Okoth Raphael O. , Abdi Farid , Mwalo Maurine , Ochola Jew , Otieno June , Ake Julie , Imbach Michelle , Turley Hannah A. , Juma Dennis , Akala Hoseah M. , Owuoth John , Andagalu Ben , Crowell Trevor A. , Nwoga Chiaka , Cowden Jessica , Polyak Christina S. ,   for the RV393 Study Group, Adongo Rachel , Aguttu Rachel , Bondo Michael , Broach Erica , Busisa Christine , Copeland Nate , de Souza Mark , Eller Leigh Anne , Gogo Milicent , Hassen Zebiba , Hu Dale , Juma Anne , Kasera Oscar , Li Qun , Mbuchi Margaret , Milazzo Mark , Modjarrad Kayvon , Ngonda Eric , Nyariro Jacob , Ohore Roseline , Okumu Thomas , Omondi Mary , Oyieke Cephas A. , Omondi Everlyne E. , Akolo Vincent L. , Ogolo Agneta A. , Ayaya Michael O. , Omondi Timothy , Ooro Linnah , Orando Beatrice , Owira Victorine , Oyugi Roselyn , Robb Merlin , Rono Eric , Tran Chi 
Published: September 2021

Abstract
Background
Malaria and schistosomiasis present considerable disease burden in tropical and sub-tropical areas and severity is worsened by co-infections in areas where both diseases are endemic. Although pathogenesis of these infections separately is well studied, there is limited information on the pathogenic disease mechanisms and clinical disease outcomes in co-infections. In this study, we investigated the prevalence of malaria and schistosomiasis co-infections, and the hematologic and blood chemistry abnormalities in asymptomatic adults in a rural fishing community in western Kenya.

Methods
This sub-study used samples and data collected at enrollment from a prospective observational cohort study (RV393) conducted in Kisumu County, Kenya. The presence of malaria parasites was determined using microscopy and real-time-PCR, and schistosomiasis infection by urine antigen analysis (CCA). Hematological analysis and blood chemistries were performed using standard methods. Statistical analyses were performed to compare demographic and infection data distribution, and hematologic and blood chemistry parameters based on different groups of infection categories. Clinically relevant hematologic conditions were analyzed using general linear and multivariable Poisson regression models.

Results
From February 2017 to May 2018, we enrolled 671 participants. The prevalence of asymptomatic Plasmodium falciparum was 28.2% (157/556) and schistosomiasis 41.2% (229/562), with 18.0% (100/556) of participants co-infected. When we analyzed hematological parameters using Wilcoxon rank sum test to evaluate median (IQR) distribution based on malarial parasites and/or schistosomiasis infection status, there were significant differences in platelet counts (p = 0.0002), percent neutrophils, monocytes, eosinophils, and basophils (p < 0.0001 each). Amongst clinically relevant hematological abnormalities, eosinophilia was the most prevalent at 20.6% (116/562), whereas thrombocytopenia was the least prevalent at 4.3% (24/562). In univariate model, Chi-Square test performed for independence between participant distribution in different malaria parasitemia/schistosomiasis infection categories within each clinical hematological condition revealed significant differences for thrombocytopenia and eosinophilia (p = 0.006 and p < 0.0001, respectively), which was confirmed in multivariable models. Analysis of the pairwise mean differences of liver enzyme (ALT) and kidney function (Creatinine Clearance) indicated the presence of significant differences in ALT across the infection groups (parasite + /CCA + vs all other groups p < .003), but no differences in mean Creatinine Clearance across the infection groups.

Conclusions
Our study demonstrates the high burden of asymptomatic malaria parasitemia and schistosomiasis infection in this rural population in Western Kenya. Asymptomatic infection with malaria or schistosomiasis was associated with laboratory abnormalities including neutropenia, leukopenia and thrombocytopenia. These abnormalities could be erroneously attributed to other diseases processes during evaluation of diseases processes. Therefore, evaluating for co-infections is key when assessing individuals with laboratory abnormalities. Additionally, asymptomatic infection needs to be considered in control and elimination programs given high prevalence documented here.