A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

Family Characteristics and Structure as Determinants of Sexual Abuse Among Female Secondary School Students in Nigeria: A Brief Report.

Child sexual abuse is associated with factors that enhance the vulnerability of the child, raising physical and mental health complications in adulthood. Three hundred and fifty students participated in this cross-sectional study. Important determinants of sexual abuse were parents not living together, not living with parents, family type, and current parents' marital status (p < 0.05). Respondents living with both parents were two times less likely to experience sexual abuse (OR = 0.5, CI: 0.3, 0.9) than respondents living with their guardians. Respondents whose parents were living together were about two times less likely to experience sexual abuse (OR = 0.6, CI: 0.3-0.9) than respondents whose parents were not living together. Respondents whose parents were either divorced or separated were about six times more likely to experience sexual abuse (OR = 5.6, CI: 1.1-27.2) than respondents with widowed parents. The study showed that parental togetherness protected against child vulnerability and risk of being sexually abused.

The feasibility of epidemiological research on prostate cancer in African men in Ibadan, Nigeria.

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/m(2)). 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.

International note: awareness and context of cyber-harassment among secondary school students in Oyo state, Nigeria.

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.

Solving teenage and young mothers' childhood immunization hesitance and non-compliance through mobile immunization friendly service for working mothers in Ibadan, Nigeria- A research note.

Mobile Immunization for working mothers (SheVaccs) is an intervention targeted at working mothers in the informal markets of Ibadan to address problem of vaccine hesitance and drop-out among different categories of mother. These mothers have great responsibilities-keeping their homes stable and their children healthy. But these mothers have challenges of different magnitudes that prevented them from immunizing their children, and for teenage mothers they are faced with socio-cultural and socio-economic obstacles and have not responded positively to childhood immunization. In relation to these challenges, SheVaccs intervention study provided friendly immunization, counselling services, and information around vaccination schedules to working mothers in Ibadan, Nigeria. The intervention covered adolescent and young mothers' population in the selected markets. Mobile clinic was set up in 3 different purposively selected markets in Ibadan. Data were collected through qualitative methods of observation and 21 in-depth interviews with teenage mothers, and 6 key informant interviews with their significant others. All data were subjected to content analysis. The age range of mothers involved in the study was between 17-23 years, almost all participants had no post- secondary school education. All mothers in this study find it difficult to attend conventional immunization centers, due to stigmatization, subtle hostility and embarrassment they experienced during pregnancy and after in some of these centers. Many of them were ignorant and have also been mis-socialized into motherhood and childcare. They preferred an immunization service that is mobile, with "strangers" who are friendly, understanding and will not judge them for ''being anti-social". Friendly Mobile immunization services targeted at teenage and young mothers will remove clog of stigmatization and hostility and minimize incidence of childhood Immunization Hesitance and non-compliance to schedule.

Is TNF alpha a mediator in the co-existence of malaria and type 2 diabetes in a malaria endemic population?

Malaria remains a disease of public health importance globally, especially in sub-Saharan Africa. Malaria deaths reduced globally steadily between 2000-2019, however there was a 10% increase in 2020 due to disruptions in medical service during the COVID-19 pandemic. Globally, about 96% of malaria deaths occurred in 29 countries; out of which, four countries (Nigeria, the Democratic Republic of the Congo, the Niger, and the United Republic of Tanzania) accounted for just over half of the malaria deaths. Nigeria leads the four countries with the highest malaria deaths (accounting for 31% globally). Parallelly, sub-Saharan Africa is faced with a rise in the incidence of Type 2 diabetes (T2D). Until recently, T2D was a disease of adulthood and old age. However, this is changing as T2D in children and adolescents is becoming an increasingly important public health problem. Nigeria has been reported to have the highest burden of diabetes in Africa with a prevalence of 5.77% in the country. Several studies conducted in the last decade investigating the interaction between malaria and T2D in developing countries have led to the emergence of the intra-uterine hypothesis. The hypothesis has arisen as a possible explanation for the rise of T2D in malaria endemic areas; malaria in pregnancy could lead to intra-uterine stress which could contribute to low birth weight and may be a potential cause of T2D later in life. Hence, previous, and continuous exposure to malaria infection leads to a higher risk of T2D. Current and emerging evidence suggests that an inflammation-mediated link exists between malaria and eventual T2D emergence. The inflammatory process thus, is an important link for the co-existence of malaria and T2D because these two diseases are inflammatory-related. A key feature of T2D is systemic inflammation, characterized by the upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) which leads to impaired insulin signaling. Malaria infection is an inflammatory disease in which TNF-α also plays a major role. TNF-α plays an important role in the pathogenesis and development of malaria and T2D. We therefore hypothesize that TNF-α is an important link in the increasing co-existence of T2D.

Drug Use Practices and Self-Treatment for Suspected Malaria in Ibadan, Nigeria.

Antimalarial drug failures have been reported anecdotally in Nigeria, and malarial self-treatment practices could be a contributing factor. This study was designed to assess the pattern of drug use practices and self-treatment options among caregivers in Ibadan, Nigeria. We carried out a descriptive cross-sectional study among 283 study participant pairs (children under 5 years of age with suspected malaria and their caregivers). Structured questionnaires were used as research instruments. The results indicated that most caregivers were mothers (88.8%), 69% of caregivers self-prescribed and self-managed malaria for children under 5 years old without immediate hospital visits, and 76.4% of the caregivers believed most recommended and available antimalarial drugs were ineffective. Generally, 44.2% of respondents preferred and used antibiotics as a treatment strategy for malaria, 13.2% used agbo (a locally made liquid extract of plants and roots), 12.5% used prayers, and 19.6% used antimalarial drugs. Overall, only 57.1% of respondents stated that they always complete the standard antimalarial dosage regimen. The choice of malaria self-treatment options was significantly linked to the level of education. The findings identified antibiotics, agbo, and prayers as the immediate choices for self-treating malaria disease in Ibadan. Furthermore, incomplete adherence to antimalarial drugs is a general practice in Ibadan. Malaria self-treatment policy and continuous education on antimalarial drug use tailored to the different literacy and education levels of the general public is hereby recommended to reduce the risk of development of parasite resistance to effective anti-malarial drugs.

Fibroblast Growth Factor 23 (FGF 23) and intact parathyroid hormone (iPTH) as markers of mineral bone disease among Nigerians with non-diabetic kidney disease.

Background: Excess cardiovascular burden in patients with chronic kidney disease (CKD) has been attributed to the occurrence of CKD-Mineral Bone Disease (CKD - MBD). This study aimed to determine the spectrum of CKD-MBD among Nigerians with CKD using Fibroblast Growth Factor 23 (FGF 23) and intact Parathyroid Hormone (iPTH). Methods: Cross sectional survey of 105 patients with non-diabetic CKD and 104 controls. Information obtained were demographics, aetiology of CKD, features of CKD-MBD. Serum iPTH and FGF 23 were assayed. Results: The mean ages were 48.7±15.3 vs 48.6±17.4 years while 54.7% and 45.2% were males for cases and controls, respectively. The mean plasma FGF 23 (392.8±35.3 vs 133.8±22.7 RU/mL and plasma iPTH (289±25.6 vs 118±10.8 ng/L, respectively. The frequency of elevated FGF 23 (45.7% vs 24.0%, p<0.01) and abnormal iPTH (53.3% vs 14.1%, p- 0.01) were higher in cases. The prevalence of MBD were (59.0% vs 14.4%, p<0.01) in cases and controls while dialysis status OR 2.94, 95% CI (1.2803-5.3645), and elevated FGF 23 OR, 1.87, 95% CI (1.1782-5.4291) were associated with CKD-MBD. Conclusion: The study demonstrated high prevalence of CKD-MBD among patients with non-diabetic CKD while FGF23 and iPTH were useful assays in the diagnosis of CKD-MBD among Nigerians with CKD.

Patterns of polymorphism in genomic regions flanking three highly polymorphic surface antigens in Plasmodium falciparum.

Many surface antigens of the human malaria parasite Plasmodium falciparum show extraordinary diversity, with different alleles being so divergent as to be unalignable in some coding regions. To better understand the population history and modes of selection on such loci, we sequenced genomic regions flanking the highly polymorphic genes merozoite surface protein-1, merozoite surface protein-2, and circumsporozoite protein, from reference isolates of P. falciparum. Diversity was much lower in genomic flanking regions than in the coding sequences. Average pairwise nucleotide diversity for these regions was 0.00088, similar to other genomic regions not thought to be evolving under balancing selection, suggesting against balancing selection acting on promoter regions of these genes. Most observed polymorphisms were singletons. A higher ratio of SNPs to indels than previously reported for P. falciparum was observed. An 11 bp repeat upstream of msp2 showed an intriguing pattern of polymorphism possibly suggestive of purifying selection on total allele length.

Early home treatment of childhood fevers with ineffective antimalarials is deleterious in the outcome of severe malaria.

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.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Complementary feeding practices among mothers and nutritional status of infants in Akpabuyo Area, Cross River State Nigeria.

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.

Prevalence and correlates of the perpetration of cyberbullying among in-school adolescents in Oyo State, 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 <5% accessed it about once every 2 weeks. One hundred and fifty-six (23.9%) had harassed someone electronically, 260 (39.8%) had been victimized, and 137 (21.0%) were both victims and perpetrators. Common modes of harassment were via phone calls 99 (63.5%), chat rooms 70 (44.9%), and text messages 60 (38.5%). Students who had been victims of cyberbullying (OR=21.76, 95% CI=12.64-37.47) and those with daily Internet access (OR=2.32, 95% CI=1.28-4.19) had significantly higher Oods of being perpetrators. 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.

Tumour necrosis factor alpha promoter polymorphism, TNF-238 is associated with severe clinical outcome of falciparum malaria in Ibadan southwest Nigeria.

Tumour necrosis factor (TNF) - α has been shown to play an important role in the pathogenesis of falciparum malaria. Two TNF promoter polymorphisms, TNF-308 and TNF-238 have been associated with differential activity and production of TNF. In order to investigate the association between TNF-308 and TNF-238 and the clinical outcome of malaria in a Nigerian population, the two TNF polymorphisms were analysed using Sequenom iPLEX Platform. A total of 782 children; 283 children with uncomplicated malaria, 255 children with severe malaria and 244 children with asymptomatic infection (controls) were studied. The distribution of TNF-308 and TNF-238 genotypes were consistent with the Hardy-Weinberg equilibrium. Distribution of both TNF polymorphisms differed significantly across all clinical groups (TNF-308: p=0.007; TNF-238: p=0.001). Further tests for association with severe malaria using genotype models controlling for age, parasitaemia and HbAS showed a significant association of the TNF-238 polymorphism with susceptibility to severe malaria (95% CI=1.43-6.02, OR=2.94, p=0.003237) The GG genotype of TNF-238 significantly increased the risk of developing cerebral malaria from asymptomatic malaria and uncomplicated malaria (95% CI=1.99-18.17, OR=6.02, p<0.001 and 95% CI=1.78-8.23, OR=3.84, p<0.001 respectively). No significant association was found between TNF-308 and malaria outcome. These results show thegenetic association of TNF-238 in the clinical outcome of malaria in Ibadan, southwest Nigeria. These findings add support to the role of TNF in the outcome of malaria infection. Further large scale studies across multiple malaria endemic populations will be required to determine the specific roles of TNF-308 and TNF-238 in the outcome of falciparum malaria infection.

Differences in the malariometric indices of asymptomatic carriers in three communities in ibadan, Nigeria.

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.

Killer-cell immunoglobulin-like receptors and falciparum malaria in southwest Nigeria.

Killer-cell immunoglobulin-like receptors (KIRs) are a group of natural killer cell receptors (NKRs) that regulate NK-cell-mediated production of interferon gamma (IFN-γ) in response to infection. These receptors have recently been suggested to influence the severity of clinical Plasmodium falciparum malaria infection. We examined the KIR locus in relation to malaria in children from southwest Nigeria. Sequence specific priming (SSP)-PCR was used to detect the KIR genes. The presence or absence of fifteen different KIR genes was determined in each individual and the proportions compared across 3 clinical groups; asymptomatic malaria, uncomplicated clinical malaria and severe clinical malaria. The genes KIR2DL5, KIR2DS3 and KIR2DS5 were present in a significantly higher proportion of individuals in the asymptomatic control group than in the malaria cases. Furthermore, KIR2DS3 and KIR2DS5 were present in a higher proportion of uncomplicated malaria cases than severe malaria cases. Carriage c-AB2 genotype (which comprises all centromeric KIR genes including KIR2DL5, KIR2DS3 and KIR2DS5) decreases with severity of the disease suggesting that the KIR AB profile might be associated with protection from severe malaria infection in this population in Nigeria.

Genome-wide and fine-resolution association analysis of malaria in West Africa.

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.