Olajumoke A. Morenikeji

A cross-sectional study on urogenital schistosomiasis in children; haematuria and proteinuria as diagnostic indicators in an endemic rural area of Nigeria

BACKGROUND Rapid and accurate diagnosis is necessary for the management of schistosomiasis in endemic areas. OBJECTIVE To assess the burden of urogenital schistosomiasis and the diagnostic efficiency of morbidity indicators of the disease in an endemic rural community of Nigeria. METHODS A cross-sectional school-based study was conducted. Urine samples of 487 pupils were screened microscopically for S. haematobium and tested for haematuria and proteinuria using chemical reagent strips. RESULTS The prevalence and intensity of infection were 57.1% and 45.0 eggs/10 mL urine respectively. Prevalence of infection in male (54.1%) and female (60.3%) individuals showed no significant variation (P>0.05). However, prevalence of infection was age dependent with those in age groups 3-5 and 12-14 years having the least and highest prevalence of infection respectively (P<0.05). Microhaematuria and proteinuria varied significantly with ages of the pupils with least (14.0, 40.0%) and highest (60.0, 80.0%) prevalence recorded in age groups 3-5 and 15-19 years respectively (P<0.05). Proteinuria showed higher sensitivity (80.3%) compared to microhaematuria (73.3%). CONCLUSION Schistosomiasis is highly endemic in the study area and the use of microhaematuria and proteinuria for mapping the infected population prior treatment could be adopted.

Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum Merozoite Surface Protein 1 types in individuals in Nigeria with sub-microscopic infection

BackgroundThe absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study.MethodsPlasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured.ResultsPlasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04).ConclusionsIn the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.

Poly( D,L -lactic- co -glycolic acid)-based artesunate nanoparticles: formulation, antimalarial and toxicity assessments

ObjectiveThe aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment.MethodsArtesunate was loaded with poly(D,L-lactic-co-glycolic acid) (PLGA) by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calorimetry analyses. In vivo antimalarial studies at 4 mg/kg were performed on Swiss male albino mice infected with Plasmodium berghei. Hematological and hepatic toxicity assays were performed. In vitro cytotoxicity of free and encapsulated artesunate (Art-PLGA) to cell line RAW 264.7 was determined at concentrations of 7.8–1000 μg/ml.ResultsThe particle size of the formulated drug was (329.3±21.7) nm and the entrapment efficiency was (38.4±10.1)%. Art-PLGA nanoparticles showed higher parasite suppression (62.6%) compared to free artesunate (58.2%, P<0.05). Platelet counts were significantly higher in controls (305 000.00±148 492.40) than in mice treated with free artesunate (139 500.00±20 506.10) or Art-PLGA (163 500.00±3535.53) (P<0.05). There was no sign of hepatic toxicity following use of the tested drugs. The half maximal inhibitory concentration (IC50) of Art-PLGA (468.0 μg/ml) was significantly higher (P<0.05) than that of free artesunate (7.3 μg/ml) in the in vitro cytotoxicity assay.ConclusionsA simple treatment of PLGA-entrapped artesunate nanoparticles with dual advantages of low toxicity and better antiplasmodial efficacy has been developed.概要目 的为疟疾治疗制定基于聚合物的青蒿琥酯纳米粒。创新点以聚乳酸羟乙酸共聚物 (PLGA) 为载体, 制备青蒿琥酯纳米颗粒。 并以小鼠为模型, 评估其抗 疟疗效和安全性。方 法以 PLGA 为载体, 采用从单一的水包油乳剂中进行溶剂蒸发的方法制备青蒿琥酯纳米颗粒。 借助 X 射线衍射和差示扫描量热分析对纳米颗粒进行表征。 以 4 mg/kg 的剂量对感染疟原虫的雄性瑞士白化小鼠进行体内抗疟活性的研究, 测定血液和肝毒性的相关指标。 体外实验以小鼠腹腔巨噬细胞细胞系 RAW 264.7 为模型, 在 7.8∼1000 μg/ml 浓度范围内, 测定游离型和包裹型青蒿琥酯的细胞毒性。结 论实验结果表明, 纳米颗粒的粒径为 (329.3± 21.7) nm, 包封率为(38.4±10.1)%。 与游离青蒿琥酯 (58.2%) 相比, 基于 PLGA 的青蒿琥酯纳米颗粒 (Art-PLGA) 具有较高的抑虫率 (62.6%), P<0.05 。 就血小板计数结果而言, 对照组 (305 000.00±148 492.40) 明显地高于游离青蒿琥酯组 (139 500.00±20 506.10) 和 Art-PLGA 组 (163 500.00±3535.53), P<0.05。 因此, 药物的使用没有导致肝毒性的产生。 体外细胞毒性试验结果表明, Art-PLGA 的半数抑制浓度 (IC50, 468.0 μg/ml) 显著高于游离青蒿琥酯 (7.3 μg/ml), P<0.05。 基于 PLGA 的青蒿琥酯纳米颗粒是一种有效安全的抗疟治疗方法。

Renal related disorders in concomitant Schistosoma haematobium-Plasmodium falciparum infection among children in a rural community of Nigeria.

Schistosomiasis and malaria are two common parasitic diseases that are co-endemic in resource-poor communities of sub-Saharan Africa. This study aims to assess the effects of single and concomitant Plasmodium falciparum and Schistosoma haematobium infections on two indicators of renal injury in school children in a rural community of Nigeria. A cross-sectional epidemiological survey was carried out on a total of 173 schoolchildren between ages 6 and 18 years (mean age 11.4±2.6 years). Urine and blood samples were collected by standard methods for concurrent microscopic diagnosis of S. haematobium and P. falciparum infections. Urinary blood (hematuria) and protein were determined using a urinalysis dipstick. The prevalence of single infections was 75.1% and 78.2% for S. haematobium and P. falciparum, respectively. A total of 57.1% individuals were infected with the two parasites. The prevalence of hematuria was significantly higher in the co-infection status (63.8%) than in single S. haematobium (52.2%) and P. falciparum (43.7%) infection statuses (p=0.04), while no significant variation was recorded in proteinuria in the three infection statuses (p=0.53). The proportion of children with renal injury associated with the co-infection of these parasites is very high, particularly in young children, who seem to have a higher prevalence of hematuria.

Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA) to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL). The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8%) at 5 mg/kg was significantly higher than in free drug (40.5%) of similar concentration (p < 0.05) but not at 10 mg/kg (49.5%) at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05). There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped nanoparticle showed higher toxicity compared with the free drug (p < 0.05) in exposed RAW 264.7 cell line. The cell viability was, however, higher in Cur-PLGA nanoparticles than in free curcumin at lower concentrations (p > 0.05). The antiplasmodial activity and safety of Cur-PLGA was better at lower concentration.

Pattern and associated risk factors of caprine pneumonia complex in Nigeria

Abstract Objective To investigate the pattern of lung consolidation in natural infections and identify the risk factors associated with caprine pneumonia in Nigeria so as to elucidate and aid the understanding of caprine respiratory disease complex in Nigeria. Methods A total of 700 goats were examined before slaughtering between March 2014 and July 2015. Ante mortem evaluation for physical characteristics, body condition, breed and sex, gross morphometry for estimation of the percentage of lung consolidation and histopathology was performed according to standard techniques. Data were presented in percentages, mean ± SEM and subjected to non-parametric analysis. Results The results showed that 30.3% of goats belonged to the breed of West African Dwarf, 55.4% Red Sokoto (RS) and 14.3% Sahelan. As for the age distribution, 3.7% of them were one year old, 30.7% were two years old and 65.6% were above two years old. The overall prevalence of pneumonia was 59.7%. The mean lung consolidation score was 8.1 ± 0.5, consolidation for male was 7.8 ± 0.5 and 21.4 ± 7.7 for female ( P P Conclusions Sex, breed and body scores were observed to be risk factors associated with caprine pneumonia in Nigerian goats. In this study, transport stress may be responsible for the high consolidation in RS. This information will help to increase the knowledge on the pathogenesis and the risk factors that often aggravate the prevalence of pneumonia in goats.

Serum Micronutrients in Helminth-infected Pregnant Women and Children: Suggestions for Differential Supplementation During Anti-helminthic Treatment

BACKGROUND The prevalence of helminth infection, which is known to affect nutritional status of the host, varies with age. The complex interplay between ages, nutrient requirements, and infection necessitated the need to recommend micronutrient supplementation during helminth infection among different age groups. OBJECTIVE The aim of this study was to determine the pattern of alteration in selected micronutrients in pregnant women and preschool- and school-aged children with helminth infection. METHODS We screened 245 pregnant women and 349 children for helminth infection. Of these, 17 (6.9%) pregnant women and 102 (29.2%) children (42 preschool- and 60 school-aged) had helminth infection. Only Ascaris lumbricoides was found in pregnant women, whereas the children had A lumbricoides, hookworm, Fasciola hepatica, and Trichuris trichiura infections. The helminth-infected (HI) pregnant women, preschool-aged children, and school-aged children were matched with helminth-negative (HN) pregnant women (n = 21), preschool-aged children (n = 42), and school-aged children (n = 50) who served as controls. Venous blood samples were obtained and analyzed for iron (Fe), zinc (Zn), selenium (Se), and vitamins A and C. Statistical analysis was done using Students t test, and P < 0.05 was considered statistically significant. FINDINGS Serum levels of Fe, Zn, and Se were significantly lower in HI pregnant women than HN pregnant women. In preschool-aged children, serum levels of Fe, Zn, and vitamin A were significantly lower in the HI than in the HN group. Similarly, serum levels of Zn and vitamin A were significantly lower in HI school-aged children than in the HN group. However, serum levels of Se were significantly higher in HI children (both age groups) than in the corresponding HN group. CONCLUSION Helminth infection alters different types of micronutrients in children and pregnant women. Results from the present study therefore suggest monitoring Fe, Zn, or vitamin A supplementation with an anti-helminthic regimen.

Serum Levels of Cytokines and IgE in Helminth-Infected Nigerian Pregnant Women and Children

BACKGROUND Helminth infection is an important health challenge. Because of modulation of the immune response toward T-helper 2 (Th2) cells, the immunologic interplay that manifest during the coexistence of helminth infection with other conditions is still poorly understood. OBJECTIVE This study determined the pattern of alteration in selected cytokines and immunoglobulin E (IgE) in pregnant women, preschool aged children, and school-aged children with helminth infection compared with uninfected groups. METHODS Seventeen pregnant women, 42 preschool-aged children, and 60 school-aged children with helminth infection (HI) were recruited into this study. They were matched with 21 pregnant women, 42 preschool-aged children, and 50 school-aged children without helminth infection (HN) who served as controls. Venous blood samples were collected from each participant and analyzed for serum levels of tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6), and IgE. Statistical analysis was done using the Student t test, and P < .05 was considered as statistically significant. FINDINGS Only serum level of IgE was significantly elevated in HI pregnant women compared with HN pregnant women. In HI preschool- and school-aged children, serum levels of IL-8, IL-6, and IgE were significantly elevated compared with HN children. However, preschool- and school-aged children with HI had similar levels of serum TNF-α and IL-10 compared with their corresponding HN groups. CONCLUSIONS It could be concluded that altered cytokines expression in children and pregnant women with helminth infection might have some implications on need for deworming programs to improve pregnancy outcomes and vaccine responses.

Acquisition, maintenance and adaptation of invasion inhibitory antibodies against Plasmodium falciparum invasion ligands involved in immune evasion

Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most individuals, independent of age. Antibodies levels measured by ELISA also varied within and between individuals over time and the antibodies against EBA181, PfRh2 and MSP2 declined more rapidly in younger individuals (≤15 years) compared with older (>15). The breadth of high antibody responses over time was more influenced by age than by the frequency of infection. High antibody levels were associated with a more stable invasion inhibitory response, which could indicate that during the long process of formation of immunity, many changes not only in levels but also in functional responses are needed. This is an important finding in understanding natural immunity against malaria, which is essential for making an efficacious vaccine.

Molluscicidal activities of curcumin-nisin polylactic acid nanoparticle on Biomphalaria pfeifferi

Background Snail intermediate host control is a widely canvassed strategy for schistosomiasis control in endemic countries. While there have been increasing studies on the search for potent molluscicides in the past years, the use of nanoparticulate agents as molluscicides is yet to gain wide attention. The aim of this study was to assess the molluscicidal potential of curcumin-nisin poly lactic acid (PLA) entrapped nanoparticle (CurNisNp) against Biomphalaria pfeifferi, a snail intermediate host for Schistosoma mansoni. Methodology/Principal findings CurNisNp formulated by double emulsion method was tested against the young adults, < 1 week, 1-2-week old juveniles, 1 day (blastula) and 7 day-old (hippo-stage) egg masses of B. pfeifferi. Mortality in the different stages was determined after 96-h of exposure at varying concentrations (350, 175, 87.5, 43.75 and 21.88 ppm). The sub-lethal effects of CurNisNp on the hatchability of the 7-day-old egg masses and egg laying capacity of the young adult snails were determined. The CurNisNp diameter, polydispersity index (PDI), zeta potential and drug entrapment efficiency were 284.0 ± 17.9 nm, 0.166 ± 0.03, -16.6 ± 2.45 mV and 35.0% respectively. The < 1 week old juveniles and the 1-day-old egg stage (blastula) of B. pfeifferi with LC50 277.9 ppm and 4279.5 ppm were the most susceptible and resistant stages to the drug respectively. CurNisNp was also observed to cause significant reductions (P<0.05) in egg hatchability and egg laying capacity with strong negative correlation between egg laying capacity and concentration (r = -0.928; P<0.05). Conclusion/Significance This study showed that CurNisNp has molluscicidal activities on different developmental stages of B. pfeifferi. It is therefore recommended that the formulation be more optimised to give a nanoparticle with a narrow range monodispersed PDI for better drug distribution and eventual greater molluscicidal activities.