High Prevalence of Asymptomatic Malarial Anemia and Association with Early Conversion from Asymptomatic to Symptomatic Infection in a Plasmodium falciparum Hyperendemic Setting in Cameroon

Asymptomatic malarial parasitemia is highly prevalent in Plasmodium falciparum endemic areas and often associated with increased prevalence of mild to moderate anemia. The aim of this study was to assess the prevalence of anemia during asymptomatic malaria parasitemia and its interplay with persistent infection in highly exposed individuals. A household-based longitudinal survey was undertaken in a malaria hyperendemic area in Cameroon using multiplex nested polymerase chain reaction to detect plasmodial infections. Residents with P. falciparum asymptomatic parasitemia were monitored over a 3-week period with the aid of structured questionnaires and weekly measurements of axillary temperatures. Of the 353 individuals included (median age: 26 years, range 2–86 years, male/female sex ratio 0.9), 328 (92.9%) were positive for malaria parasitemia of whom 266 (81.1%) were asymptomatic carriers. The prevalence of anemia in the study population was 38.6%, of which 69.2% were asymptomatic. Multivariate analyses identified high parasitemia (> 327 parasites/µL) and female gender as associated risk factors of asymptomatic malarial anemia in the population. Furthermore, risk analyses revealed female gender and anemia at the time of enrolment as key predictors of early development of febrile illness (< 3 weeks post enrolment) among the asymptomatic individuals. Together, the data reveal an extremely high prevalence of asymptomatic malaria parasitemia and anemia in the study area, unveiling for the first time the association of asymptomatic malarial anemia with early clinical conversion from asymptomatic to symptomatic infection. Furthermore, these findings underscore the negative impact of asymptomatic malaria parasitemia on individual health, necessitating the development of appropriate control and preventive measures.

Sida acuta Burm.f. leaves ethanol extract ameliorates haematological and biochemical alterations induced by Plasmodium berghei ANKA-65 in mice

Background Malaria has continued to be a threat to man and his wellbeing, especially Africans and Asians. New antimalarial drugs are urgently needed to mitigate malaria treatment failure due to resistant Plasmodium species. Medicinal plants used by indigenous Nigerians for treating fever and malaria such as Sida acuta Burm.f. (Malvaceae) could be a promising source of lead compounds for developing new generations of antimalarial drugs. The effects of ethanol extract of S. acuta leaves (EESAL) on malaria parasitemia, haematological and biochemical status of P. berghei-infected mice were investigated, using the 4-day curative test. Methodology EESAL was prepared by maceration method. The phyto-constituents and acute toxicity profile of the extract were evaluated using standard protocols. In addition, malaria parasitemia and chemo-suppression, and indicators of haematological and biochemical status of P. berghei-infected mice treated with EESAL were assessed. Results At 200, 400 and 600 mg/kg/d b.w., p.o doses for 4 consecutive days, EESAL significantly (p < 0.05) decreased parasitaemia and suppressed malaria parasite by 89.64%, 95.95% and 97.38%, respectively comparable to negative control. The reduction in percentage malaria parasitemia by EESAL is comparable to Artemether (140 mg/kg/d b.w., p.o) used as standard antimalarial drug in this study. The packed cell volume (PCV), haemoglobin (Hb) concentration, and red blood cell (RBC) and white blood cell (WBC) counts of negative control are significantly (p < 0.05) higher than normal control. However, parasitized-EESAL-treated mice have significantly (p < 0.05) higher PCV value, Hb concentration and RBC and WBC counts than negative control. Similarly, treatment of parasitized mice with EESAL restored some indicators of the antioxidant, lipid peroxidation, lipid profile and liver status altered by malaria. In addition, EESAL was tolerable up to 5000 mg/kg b.w., p.o. Conclusion These results indicate that the EESAL possesses antimalarial activity and normalizes alterations in haematological and biochemical status of malaria-infected mice.

Epidemiological and clinical implications of asymptomatic malaria and schistosomiasis co-infections in a rural community in western Kenya

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.

Evaluation of Pilot Implementation of Seasonal Malaria Chemoprevention on Morbidity in youngChildren In Northern Sahelian Ghana

Background In Sahelian Africa, the risk of malaria increases with the arrival of the rains, during which most clinical malaria occur particularly in young children. Following successful trials in 2012, the World Health Organization (WHO) recommended the use of seasonal malaria chemoprevention (SMC) in areas where there is a seasonal peak in malaria. This study evaluated the pilot implementation of SMC in Northern Ghana. Methods Fourteen communities each serving as clusters were selected randomly from Lawra District of Upper West Region as intervention area and West Mamprusi District in the Northern Region as the control area all in Ghana. The intervention was undertaken by the National Malaria Control Program using Sulphadoxine Pyrimethamine plus Amodiaquine and standard WHO protocols. Before and after intervention surveys for malaria parasitemia and hemoglobin levels were assessed as well as monitoring of malaria morbidity. Results Incidence rates of severe malaria were 10 and 20 per 1000 person-years follow up in the intervention and comparison areas respectively with P.E of 45% (p = 0.62). For mild malaria, it was 220 and 170 per 1000 person-years in intervention and comparison area respectively with PE of − 25% (p = 0.31). Differences in anemia (Hb < 11.0g/dl) from baseline to end-line was a reduction of 0.16g/dl (p = 0.000) in intervention and an increase of 0.12g/dl (p = 0.002) in the control area. Mean Hb difference between baseline and end-line was a reduction of 0. 24g/dl (p = 0.000) in control and an increase of 0.39g/dl (p = 000) in the intervention area. At the end of the intervention, the proportion of children with asexual parasites reduced by 19% (p = 0.000) in the intervention and increased by 12%(p = 0.000) in the control area. Conclusion The feasibility of SMC in Northern Ghana was demonstrated as evidenced by high study retention, reduction in malaria parasitemia and anemia during the wet season.

Haemoglobin phenotypes and the risk of asymptomatic malaria parasitemia among blood donors in northwest Nigeria: clinical implications in the practice of tropical transfusion medicine

Background: In malaria-endemic populations, sickle cell trait (SCT) protects against both severe and non-severe malaria, but inconsistencies exist about protective effect of SCT on asymptomatic malarial parasitemia (AMP). Surprisingly, the effect of Hb-phenotypes on AMP has not been explored among blood donors in Nigeria or other malaria-endemic countries, where risks of AMP and transfusion transmitted malaria (TTM) are high. The objective of this study is to determine risk of AMP with respect to donor Hb-phenotypes (SCT versus HbAA), and elucidate clinical implications of AMP with respect to risk of TTM vis-à-vis the practice of transfusion medicine in Nigeria, and by implication other malaria-endemic tropical countries.Methodology: Analysis of 100 blood donors with AMP (cases) and 100 donors without AMP (controls) was performed. Frequencies of SCT and HbAA (determined by Hb electrophoresis) among cases and controls were compared by X2 -test. Risks of AMP (detected by microscopy) with respect to Hb-phenotypes were expressed as Odds ratios (OR) by case-control logistic regression.Results: In comparison with blood donor without AMP (controls), donors with AMP had lower frequencies of SCT (12% vs 28%, p<0.05) with corresponding higher frequencies of HbAA (88% vs 72%, p<0.05). HbAA is associated with high risk of AMP (OR=2.91, 95%CI: 2.10-3.48, p=0.021), while SCT is associated low risk of AMP (OR=0.49, 95%CI: 0.27-0.73, p=0.032).Conclusion: This finding shows that donor SCT is a surreptitious mitigator of the risk of AMP and TTM in the tropics. Therefore, patients who are selectively transfused with HbAA blood (e. g. neonates and sickle cell disease patients) could be at greater risks of TTM, and such patients need closer post transfusion monitoring. The risk of TTM calls for diligent post transfusion haemovigilance in Nigeria and other malaria endemic tropical countries in Africa Keywords: blood donors, sickle cell trait, asymptomatic malaria parasitemia, transfusion transmitted malaria

Mobile-Aware Deep Learning Algorithms for Malaria Parasites and White Blood Cells Localization in Thick Blood Smears

Effective determination of malaria parasitemia is paramount in aiding clinicians to accurately estimate the severity of malaria and guide the response for quality treatment. Microscopy by thick smear blood films is the conventional method for malaria parasitemia determination. Despite its edge over other existing methods of malaria parasitemia determination, it has been critiqued for being laborious, time consuming and equally requires expert knowledge for an efficient manual quantification of the parasitemia. This pauses a big challenge to most low developing countries as they are not only highly endemic but equally low resourced in terms of technical personnel in medical laboratories This study presents an end-to-end deep learning approach to automate the localization and count of P.falciparum parasites and White Blood Cells (WBCs) for effective parasitemia determination. The method involved building computer vision models on a dataset of annotated thick blood smear images. These computer vision models were built based on pre-trained deep learning models including Faster Regional Convolutional Neural Network (Faster R-CNN) and Single Shot Multibox Detector (SSD) models that help process the obtained digital images. To improve model performance due to a limited dataset, data augmentation was applied. Results from the evaluation of our approach showed that it reliably detected and returned a count of parasites and WBCs with good precision and recall. A strong correlation was observed between our model-generated counts and the manual counts done by microscopy experts (posting a spear man correlation of ρ = 0.998 for parasites and ρ = 0.987 for WBCs). Additionally, our proposed SSD model was quantized and deployed on a mobile smartphone-based inference app to detect malaria parasites and WBCs in situ. Our proposed method can be applied to support malaria diagnostics in settings with few trained Microscopy Experts yet constrained with large volume of patients to diagnose.