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Purpose Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Summary The controlled induction of haemoxygenase-1 (HO-1), an enzyme that catabolizes haem, has been shown to reduce haem, preventing pathologies associated with haem toxicity. The hemoglobin genotype HbAS confers reduced susceptibility to severe complications of malaria by a mechanism that is not well understood. Using a longitudinal approach, we investigated the effect of baseline concentrations of HO-1 on the accumulation of haem during acute Plasmodium falciparum malaria in HbAS and HbAA genotypes. Plasma concentrations of haem, HO-1 and cytokines were quantified in venous blood obtained from children (9 months–5 years of age) during malaria infection, and at convalescence (baseline levels). Parasitaemia was determined during malaria infection. In patients with the HbAA genotype, there was a significant elevation in the plasma concentration of haem (P = 0.002), and a consequent increased induction of HO-1 (P

Host genetic factors that influence the outcome of Plasmodium falciparum malaria infection are not fully understood. These include alpha-thalassemia, sickle cell disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency and cytochrome b5 reductase 3 (CYB5R3) T117S and ferroportin Q248H polymorphisms. G6PD, an X-linked gene, encodes the sole enzyme in red blood cells that produces NADPH for protection from reactive oxygen species. Hemi- or homozygosity for G6PD A+ (G6PD c. 376G) is an African specific polymorphism with reduced activity (PMID:26633385) but no apparent phenotype; hemi- or homozygosity for G6PD A- (G6PD c 202A/376G) is associated with both decreased activity and increased risk for oxidant-induced hemolysis (PMID:27040960). A Malaria Genomic Epidemiology Network (MalariaGEN) study with almost 30,000 participants reported that G6PD A- increases the risk for severe malarial anemia (PMID:25261933). CYB5R3 in red blood cells transfers electrons from NADH to cytochrome b5, which in turn converts methemoglobin to hemoglobin. The African-specific CYB5R3 T117S variant, is not associated with methemoglobinemia (PMID:9048929) but may afford some protection from malarial anemia in Zambian children. A prevalent African-specific Q248H mutation of the iron exporter, ferroportin, may protect from high malarial parasitemia (PMID: 29599243). We genotyped 212 Nigerian children (age 4 months - 16 years) for these genetic factors: 117 were asymptomatic children who were studied in the community and 95 were children who were studied at the time of admission to hospital with severe malaria (severe anemia and/or cerebral malaria). We isolated DNA from dried blood spots and crude DNA lysate was used for Taqman genotyping to screen for G6PD A+, G6PD A-, FPN Q248H, sickle cell disease and CYB5R3 T117S and multiplex PCR was used to identify the 3.7 kb and 4.2 kb α-globin gene deletions. The clinical characteristics of the two groups of children are shown in Table 1. Children with severe malaria were significantly younger than the children from the community. The gene frequency of CYB5R3 T117S was 0.303, of hemoglobin S was 0.094, and of FPN Q248H was 0.062. The prevalences of hemizygous and homozygous G6PD A+ and A- were 13.9% and 16.0%, respectively. In addition, the prevalences of single and double alpha globin gene deletions were 34.7 % and 11.7%, respectively. Table 2 compares the prevalence of these genotypes in asymptomatic children versus those admitted with severe malaria. Alpha-thalassemia tended to be more prevalent in the asymptomatic children while ferroportin Q248H and G6PD A- were more prevalent in the children with severe malaria. Some genes seemed to have heterogenous associations: sickle trait and homozygous CYB5R3 T117S tended to be more prevalent in the asymptomatic children while hemoglobin SS and heterozygous T117S tended to be more prevalent in the children with severe malaria. In a logistic regression model that adjusted for age, alpha thalassemia (odds ratio 0.6, P=0.038), hemoglobin S trait (odds ratio 0.5, P=0.203), and CYB5R3 T117S homozygous state (odds ratio 0.5, P=0.211) independently decreased the risk of severe malaria, while ferroportin Q248H (odds ratio 5.1, P=0.008) and G6PD deficiency (1.6, P=0.049) independently increased the risk of severe malaria. In conclusion, our results suggest that common genetic factors affect the risk of severe malaria in children. Research to illuminate the mechanisms of these effects may enhance our understanding of the pathogenesis of severe malaria and point to novel preventive and therapeutic measures. Disclosures Gordeuk: Global Blood Therapeutics: Consultancy, Honoraria, Research Funding; Emmaus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Modus Therapeutics: Consultancy, Honoraria; Pfizer: Research Funding; Inctye: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Ironwood: Research Funding; Imara: Research Funding.

We determined the awareness and context of cyber-harassment among secondary school students (653 survey respondents and 18 in-depth interviewees) in Oyo state, Nigeria. Respondents' mean age was 14.2 ± 2.2 years and 53.9% were aware of cyber-harassment occurring in their school or among their friends. Cyber-harassment was often perpetrated via phone calls (62.5%), text messaging (36.9%), chat rooms (28.7%), through pictures or video clips sent via mobile phones (11.9%), emails (6.8%) or websites (5.9%). Cyber-harassment behaviours mentioned were the use of abusive words (25.4%), saying mean things or making fun of the victim (13.9%), solicitations for relationships (7.9%) or sex (6.8%) and spreading rumours about the victim (6.8%). In-depth interviewees recounted experiences of cyber-harassment suffered by their friends. Many were relationship-related, sexual solicitations and threats and corroborated quantitative findings. Respondents are aware of cyber-harassment occurring among students in the study area. Comprehensive interventions to address the problem need to be instituted.

This study was conducted to determine the malariometric indices of children in three different settings in Ibadan, Nigeria. Children were recruited from an urban slum (Oloomi) and a periurban (Sasa) and a rural community (Igbanda) in Ibadan. Children aged between 2 and 10 years were randomly selected from primary schools in the urban and periurban areas. In the rural community, children were recruited from the centre of the village. A total of 670 (55.0%) out of 1218 children recruited were positive for malaria parasitaemia. The urban population had the highest proportion of children with malaria parasitaemia. Splenomegaly was present in 31.5%, hepatomegaly in 41.5%, hepatosplenomegaly in 27.5%, and anaemia in 25.2% of the children. The parasite density was not significantly different among children in the three communities. Children in the rural community had the highest mean PCV of 34.2% and the lowest rates of splenomegaly (6.1%), hepatomegaly (7.6%), and hepatosplenomegaly (4.6%). The spleen rates, liver rates, and presence of hepatosplenomegaly and anaemia were similar in the urban and periurban communities. The malariometric indices among the asymptomatic carriers were high, especially in the urban slum. This stresses the need for intensified efforts at controlling the disease in the study area.

Background Malnutrition in infants during weaning has been attributed to inappropriate complementary feeding practices and it underlies more than one-third of child mortality in Nigeria. Thus, addressing the influence of complementary feeding practice on nutritional status may be an important approach to reducing the burden of child malnutrition. This cross-sectional study investigated the association between complementary feeding practices among mothers and nutritional status of their infants in Akpabuyo Local Government Area, Nigeria. The study enrolled 330 mother–child pairs from 10 randomly selected out of 32 Health Facilities in Akpabuyo. Socio-demographic information, child and maternal characteristics were obtained using an interviewer-administered questionnaire. Complementary feeding practices were assessed with World Health Organization infant and young child feeding indicators. Nutritional indicators wasting, underweight and stunting were determined. Results Prevalence of timely introduction of complementary feeding among infants aged 6–8 months was 85.4%, minimum dietary diversity rate was 31.5%, and minimum meal frequency 36.7%, the rate of minimum acceptable diet was 7.3%. One-third (33.3%) of the infants were underweight, 26.4%, wasted and 24.6%, stunted. Children who did not receive timely complementary foods had higher odds for wasting (OR 5.15; 95% CI 1.50–17.73). Children who did not receive the minimum dietary diversity had higher odds for underweight than children who received the minimum dietary diversity (OR 2.07; 95% CI 1.17–3.70). Children who did not receive the minimum feeding frequency were more likely to be stunted than their peers who received the minimum feeding frequency (OR 1.57; 95% CI 1.53–4.03). Conclusion Sub-optimal complementary feeding predisposed to infant’s malnutrition.

Background Men of African descent have the highest incidence and mortality rates of prostate cancer (PrCa) worldwide. Notably, PrCa is increasing in Africa with Nigerian men being mostly affected. Thus, it is important to understand risk factors for PrCa in Nigeria and build capacity for cancer research. The goals of this study were to determine the feasibility of conducting an epidemiological study of PrCa and to obtain preliminary data on risk factors for PrCa in Nigeria. Methods A case–control study (50 cases/50 controls) was conducted at the University College Hospital (UCH) in Ibadan, Nigeria, between October 2011 and December 2012. Men aged 40 to 80 years were approached for the study and asked to provide informed consent and complete the research protocol. Logistic regression models were used to examine associations between demographic, social and lifestyle characteristics and risk of PrCa. Results The participation rate among cases and controls was 98% and 93%, respectively. All participants completed a questionnaire and 99% (50 cases/49 controls) provided blood samples. Cases had a median serum diagnostic PSA of 73 ng/ml, and 38% had a Gleason score 8–10 tumor. Family history of PrCa was associated with a 4.9-fold increased risk of PrCa (95% CI 1.0 - 24.8). There were statistically significant inverse associations between PrCa and height, weight and waist circumference, but there was no association with body mass index (kg/m2). There were no associations between other socio-demographic and lifestyle characteristics and PrCa risk. Conclusion This feasibility study demonstrated the ability to ascertain and recruit participants at UCH and collect epidemiological, clinical and biospecimen data. Our results highlighted the advanced clinical characteristics of PrCa in Nigerian men, and that family history of PrCa and some anthropometric factors were associated with PrCa risk in this population. However, larger studies are needed to better understand the epidemiological risk factors of PrCa in Nigeria.

Objective: Cyberharassment/cyberbullying is a global problem that has been inadequately investigated in developing countries. In this paper, we present findings on the prevalence and predictors of perpetration of cyberbullying among in-school adolescents in Oyo state, Nigeria. Methods: A total of 653 students were selected via multi-stage sampling. Information on history of perpetrating harassment via an electronic medium in the 3-month period preceding the survey was obtained. Results: Respondents’ mean age was 14.2±2.2 years and 51.3% were females. All respondents had personal mobile phones and about half had Internet access. About 40% accessed the Internet every day while about 48% accessed it at least once to several times a week and Conclusion: About a quarter of students were perpetrators of cyberbullying, and the correlates of perpetration were history of cyber victimization and daily Internet access. Intervention programs must be instituted for victims as well as frequent users of the Internet to curb the problem in the study area.

H3Africa is developing capacity for health-related genomics research in Africa

Background Child car-passenger safety practices remain low in Nigeria. We present findings from the formative phase of a project to deliver an m-health intervention on child-passenger safety to mothers/caregivers attending selected child-immunisation clinics in Ibadan. The aims were to describe: current legal provisions and awareness of child-passenger safety measures, acceptability of a mobile-phone intervention to improve child-passenger safety and availability and costs of standard age-appropriate child seats. Methods Twenty-three key-informant interviews [with enforcement officers (4), doctors (3), teachers (3) and mothers of infants and school-age children (11)] and a market survey were conducted. Data were analysed with ATLAS.ti. Results Current laws do not directly address child safety although the Highway Code stipulates that child-passengers should be restrained in age-appropriate seats and those ≤12years should sit at the back. Most interviewees were aware of the need to use infant seats but not of the need for child-and booster seats. Some barriers to the use of child carseats were lack of knowledge of its importance and cost. Interviewees felt enactment and enforcement of laws and enlightenment were necessary for compliance. Acceptance of a mobile-phone intervention, (although not necessarily a mobile application), was very high. Participants stated that it was cost-effective and convenient. Interviewees suggested the use of calls, bulk SMS, twitter® and facebook®. Twelve retail stores selling items for children were visited. Most stores had about two to three seats each because of low demand. Barely-used and brand new age-appropriate seats were available although infant seats were mostly seen. Most seats had appropriate standard labels. One barely-used booster seat (cost:$30) was seen. Costs of infant seats ranged from $25 – $180 and toddler seats, $30 – $405. Conclusions Findings indicate that an m-health intervention is acceptable and would be timely in improving car-passenger safety practices among the study participants.

Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries. © 2008 Macmillan Publishers Limited. All rights reserved.

Background Early diagnosis and prompt treatment including appropriate home-based treatment of malaria is a major strategy for malaria control. A major determinant of clinical outcome in case management is compliance and adherence to effective antimalarial regimen. Home-based malaria treatment with inappropriate medicines is ineffective and there is insufficient evidence on how this contributes to the outcome of severe malaria. This study evaluated the effects of pre-hospital antimalarial drugs use on the presentation and outcome of severe malaria in children in Ibadan, Nigeria. Methods Two hundred and sixty-eight children with a median age of 30 months comprising 114 children with cerebral malaria and 154 with severe malarial anaemia (as defined by WHO) were prospectively enrolled. Data on socio-demographic data, treatments given at home, clinical course and outcome of admission were collected and analysed. Results A total of 168 children had treatment with an antimalarial treatment at home before presenting at the hospital when there was no improvement. There were no significant differences in the haematocrit levels, parasite counts and nutritional status of the pre-hospital treated and untreated groups. The most commonly used antimalarial medicine was chloroquine. Treatment policy was revised to Artemesinin-based Combination Therapy (ACT) in 2005 as a response to unacceptable levels of therapeutic failures with chloroquine, however chloroquine use remains high. The risk of presenting as cerebral malaria was 1.63 times higher with pre-hospital use of chloroquine for treatment of malaria, with a four-fold increase in the risk of mortality. Controlling for other confounding factors including age and clinical severity, pre-hospital treatment with chloroquine was an independent predictor of mortality. Conclusion This study showed that, home treatment with chloroquine significantly impacts on the outcome of severe malaria. This finding underscores the need for wide-scale monitoring to withdraw chloroquine from circulation in Nigeria and efforts intensified at promoting prompt treatment with effective medicines in the community.

Falciparum malaria is a leading cause of morbidity and mortality in endemic regions of the world. In areas of intense transmission of P. falciparum children less than the age of 5 years are the most susceptible to severe malaria. The complex interactions between the parasite the human host the vector and environment or social factors may influence the outcome of a malaria infection (White & Ho 1992). Control measures have been based on wide-scale attempts at the reduction in transmission with anti-vector measures and therapeutic management of clinical disease. In sub-Saharan Africa however control is mainly focused on management of the clinical disease and more recently on the use of intermittent preventive treatment (IPT) in pregnant women. Individual preventive measures such as the use of mosquito repellants and the use of insecticide treated bed nets (ITNs) and curtains also influence the risk of host-vector contact host infection and consequently mortality especially in children susceptible to the severe forms of the disease. (excerpt)

Intraleucocytic malaria pigment has been suggested as a measure of disease severity in malaria. We have tested this hypothesis by studying 146 children aged 6 months to 14 years in 4 categories--cerebral malaria, mild malaria, asymptomatic malaria and 'no malaria'--in Ibadan, Nigeria, an area of intense malaria transmission in Africa. Children with cerebral malaria were studied at the university hospital, those with mild malaria at 2 primary health centres and the other 2 groups were studied in a primary school. The proportion of pigment-containing neutrophils showed a clear rise across the spectrum no malaria--asymptomatic malaria--mild malaria--cerebral malaria (median values 2.0%, 6.5%, 9.0% and 27.0%, respectively; P0.0001). The proportion of pigment-containing monocytes did not differ significantly between the mild malaria, asymptomatic malaria and no malaria groups but the cerebral malaria group had a higher median value than the other 3 groups. The ratio of pigment-containing neutrophils to pigment-containing monocytes showed the same trend across the groups of subjects as was observed with the number of pigment-containing neutrophils. It is concluded that the pigment-containing neutrophil count is a simple marker of disease severity in childhood malaria in addition to the parasite count.