Akeem A. Akindele

Ficolin-2 Levels and FCN2 Genetic Polymorphisms as a Susceptibility Factor in Schistosomiasis

BACKGROUND Human ficolin-2 (L-ficolins) encoded by the FCN2 gene are pattern-recognition proteins involved in innate immunity and are associated with several infectious diseases. METHODS A Nigerian cohort of 168 Schistosoma haematobium-infected individuals and 192 healthy controls were examined for functional single-nucleotide polymorphisms in the promoter region (-986G>A, -602G>A, -4A>G) and in exon 8 (+6424G>T) using real-time polymerase chain reaction. RESULTS The FCN2 -986A and -4G alleles were significantly associated with the occurrence of schistosomiasis (P = .0004 for -986G>A; P = .0001 for -4A>G). The heterozygous genotypes (P = .0006 for -986G>A; P = .0002 for -4A>G) were observed to be a risk factor for susceptibility to schistosomiasis, whereas the homozygous genotypes of major alleles (P = .0002 for -986G>A; P = .0001 for -4A>G) were observed to shield against schistosomiasis. The haplotype AGGG (P = .0002) was observed to be a risk factor for susceptibility to schistosomiasis compared with controls, and the haplotype GGAG (P = .04) was observed to confer protection compared with patients. Ficolin-2 serum level was significantly higher in controls (P < .005) and in controls with GGAG haplotypes (P < .0001). CONCLUSIONS Our findings demonstrate that FCN2 promoter variants (-986G>A and -4A>G) influence ficolin-2 serum levels and susceptibility to schistosomiasis.

Mannose binding lectin and susceptibility to Schistosomiasis

Abstract Background. Human ficolin 2 (encoded by FCN2) and mannose-binding lectin (encoded by MBL2) bind to specific pathogen-associated molecular patterns, activate the complement lectin cascade in a similar manner, and are associated with several infectious diseases. Our recently published study established certain FCN2 promoter variants and ficolin-2 serum levels as protective factors against schistosomiasis. Methods. We used the Nigerian cohort from our recently published study, which included 163 Schistosoma haematobium–infected individuals and 183 matched healthy subjects, and investigated whether MBL deficiency and MBL2 polymorphisms are associated with schistosomiasis. Results. MBL serum levels were significantly higher in controls and were associated with protection (P < .0001). The −550H minor allele was significantly associated with protection (P = .03), and the heterozygous genotypes −550HL were observed to confer protection (P = .03). The MBL2*HYPA haplotype was significantly associated with protection (P = .03), with significantly higher serum MBL levels in controls (P = .00073). The heterozygous 6-bp deletion in the promoter was observed to be a susceptibility factor in schistosomiasis (P = .03). Conclusions. In agreement with findings from our recently published study, the findings reported here support the observation that MBL is also associated with protection in schistosomiasis.

Malaria: Control, Elimination, and Eradication

Control, elimination, and eradication of malaria is one of the world’s greatest public health challenges, especially in Sub-Saharan Africa. While there has been an impressive gain in malaria control with decreased mortality rate over the years, eradication and elimination seem to be elusive in Sub-Saharan Africa. Control and elimination of malarial parasites was previously achieved in Europe and America using insecticides and manipulation of environmental and ecological characteristics. The emergence of drug-resistant parasites coupled with environments that support the breeding of mosquito vector and the need for caution with insecticides, such as dichlorodiphenyltrichloroethane, has slowed down control efforts, making elimination and eradication an uphill task in Sub-Saharan Africa. The expectation of producing an effective vaccine has been on for >40 years, but the recent breakthrough announcement of a malaria vaccine showing some level of protection among infants and children 3–4 years post vaccination seems like an excellent starting point. The globally accepted strategy for the control of malaria rely on chemotherapy, but unfortunately the overreliance on chemotherapy without proper control of drug usage and diagnosis has encouraged the selection of drug-resistant parasites, significantly contributing to the problem. Therefore, the prospects of malaria eradication rest heavily on integrated approaches that would include chemotherapy, vector control, manipulation of environmental and ecological characteristics, and vaccination. This article reviews the current state of malaria control and elimination and the need for an multistrategic integrated approach in order to achieve malaria eradication if the challenges faced by elimination are addressed.

Low MBL-associated serine protease 2 (MASP-2) levels correlate with urogenital schistosomiasis in Nigerian children

The human mannose‐binding lectin (MBL) and ficolins (FCN) are involved in pathogen recognition in the first line of defence. They support activation of the complement lectin cascade in the presence of MBL‐associated serine protease 2 (MASP‐2), a protein that cleaves the C4 and C2 complement components. Recent studies found that distinct MBL2 and FCN2 promoter variants and their corresponding serum levels are associated with relative protection from urogenital schistosomiasis.

Co-endemicity of Loiasis and Onchocerciasis in Rain Forest Communities in Southwestern Nigeria

Background Loiasis is currently receiving attention as a disease of public health importance because of the possibility of increased risk of developing neurologic serious adverse event following mass ivermectin treatment against onchocerciasis in individual co-infected with Onchocerca volvulus and Loa loa. Methodology/Principal Findings Rapid assessment procedure for loiasis (RAPLOA) was conducted in 12 communities covering the 3 senatorial districts of Osun State, Nigeria. A total of 960 people were interviewed for history of eye worm using the WHO guidelines for rapid assessment. The survey confirmed the presence of loiasis in all the 12 communities with 4 in Osun East/Ife south senatorial district being at high risk with a prevalence of over 40%. Based on the RAPLOA results, communities within Osun East/Ife south senatorial district were selected for microfilaraemic assessment of L. loa and O. volvulus. A total of 1115 and 1091 individuals were screened for L. loa and O. volvulus microfilaria worms respectively. 160 (14.3%) had L. loa microfilaria detected in their blood with 8 (5.0%) individuals having L. loa loads above 8000 mf/ml. 166 (15.2%) subjects had O. volvulus microfilaria (range 4-504 mf/ml) detected in their skin snip. 30 (2.69%) subjects were co-infected with both L. loa and O. volvulus. There was a significant variation in the prevalence (2.1% to 33.3%) of onchocerciasis in the communities studied (p = 0.001). Five (41.7%) of the studied communities had a prevalence that is equal to or greater than 20%. Conclusions/Significance Low prevalence of onchocerciasis and loiasis co-infection in this study suggests that loiasis may not pose a serious epidemiological threat to the continuous distribution and sustainability of ivermectin for the treatment of onchocerciasis. Evaluation of the interruption of onchocerciasis transmissions in this region using all the indicators set forth by WHO is therefore suggested.

Prevalence of enteric parasitic infections among people living with HIV in Abeokuta, Nigeria

Introduction Enteric parasitic infections have been increasingly recognized as etiology of life-threatening chronic diarrhea in PLWHA in sub-Saharan Africa. This study investigated the prevalence and burden of intestinal parasitic infection among PLWHA in Abeokuta, southwest Nigeria. Methods Freshly passed stool samples were collected from PLWHA. Detection of Cryptosporidium spp and Microsporidium spp was carried out with Kinyouns stain and Webers Chromotrope-based stain respectively. Investigation of other intestinal parasites was done using the direct saline preparation and formol-ether concentration methods. CD4+ T cell count was measured using Partec flow cytometry technique Results A total of 231 (males: females 96:135; mean age 31.81±11.40 years) PLWHA were recruited into the study, among whom 84 (36.4%) were infected with at least one intestinal parasites. Fifty two (22.5%) individuals were positive for Cryptosporidium spp and a significant association between Cryptosporidium sppand diarrhea was observed (p=0.006). Seven (3.0%) were positive for Microsporidium spp. Helminths recovered included Ascaris lumbricoides (20.8%), hookworm (6.5%), Strongyloides stercoralis (4.3%), Trichuris trichiura (5.6%) and Taenia spp. (5.6%). Cryptosporidium spp, Microsporidium spp and S. stercoralis were significantly associated with CD4+ count ≥ 200 cells/mm3 (p<0.05). Cryptosporidium sppand A. lumbricoides were significantly observed among patients that are anti-retroviral therapy (ART) naive. Conclusion High prevalence of opportunistic parasitic infection was significantly correlated with diarrhea, low CD4+ count and ART naïve individuals in the study. These findings re-emphasize the need for early diagnosis of opportunistic parasites and appropriate intervention among PLWHA.

Prevalence of asymptomatic malaria and anaemia among elderly population in Osun state Southwestern, Nigeria

Malaria remains a major global disease burden, with approximately 438,000 deaths annually. Malaria is ranked by World Health Organization as the largest single component of the disease burden in Africa, accounting for approximately 250 million clinical cases and approximately 1 million deaths each year. 1,2 In Africa, malaria is responsible for about 20-30% of hospital admissions and about 30-50% of outpatient consultations. Sub-Saharan African countries are disproportionately affected by malaria due to the presence of mosquito vectors, widespread poverty, limited infrastructure, and overburdened health systems. Those living in extreme poverty are most vulnerable to infectious diseases. In Nigeria, malaria is holoendemic with seasonal variations throughout the year which comprises of a distinctive rainy and dry season. It is a major cause of morbidity and mortality in Nigeria, and at least 100% of the population suffers from one episode of malaria each year. The malaria situation in Nigeria is very burdensome and it impedes human development. It is both a cause and consequence of underdevelopment. 3 ABSTRACT

Interleukin-4 and STAT6 promoter polymorphisms but not interleukin-10 or 13 are essential for schistosomiasis and associated disease burden among Nigerian children

Schistosomiasis is endemic in many parts of rural Africa, with previous reports showing interleukin-13 polymorphisms as drivers of infectivity and disease severity in West Africa while IL-13/IL-4 polymorphisms contributes to patterns of reinfection in East Africa. We have shown that there is a genetic delineation in susceptibility to and severity of infectious diseases in Africa, in addition to sub-continental differences in disease pattern. Therefore, which immunoregulatory biomarkers are essential in driving S. haematobium infection or regulate disease burden among Nigerian school children? One hundred and thirty one age and sex-matched schistosome-infected children and 275 uninfected controls, of same ethnicity, recruited from southwestern Nigeria, were screened for variability of cytokine genes, IL-10 (rs1800872), IL-13 (rs7719175), IL-4 (rs2243250) and STAT6 (rs3024974), utilizing a polymerase chain reaction-restriction fragment length polymorphism assay. We found no difference in genotypic or allelic frequencies of IL-10 and IL-13 promoter polymorphisms alone or in association with disease. Contrariwise, we report significant differences in the frequencies of IL-4 and STAT6 variants between groups. For IL-4, the rs2243250 T/T variant was significantly different for genotypes (71.6% versus 51.2%; p < .0004) and alleles (82.6% versus 71.1%; p < .001) between disease and control groups respectively. For STAT6 (rs3024974), the frequencies of genotypes C/C and C/T are 75.4% and 24.6%, both showing an association with disease; none of the infected subjects had the T/T variant. Despite minor differences in disease covariates, we found no association between IL-4 and STAT6 variants with age, gender or anemia. However, mean egg count (indicative of disease burden), was regulated based on IL-4 variants, with highest burden in infected subjects with rs2243250 T/T variant (mean egg count: 207.5 eggs/10 ml of urine) versus rs2243250 C/T heterozygotes (mean egg count: 84.3 eggs/10 ml of urine) versus rs2243250 C/C (mean egg count: 127.9 eggs/10 ml of urine). Comparing rs2243250 C/T versus rs2243250 T/T (p < .008) or rs2243250 C/C + C/T versus rs2243250 T/T (p < .016) reveals an association with disease burden. We conclude that the IL-4 promoter gene is a susceptibility factor for schistosomiasis, and essential to regulate disease burden, with worse disease among carriers of the rs2243250 T/T variant. The absence of the STAT6, rs3024974T/T variant among infected subjects reveal the necessity of the STAT6 promoter gene in driving susceptibility to schistosomiasis in Nigeria.