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Summary: A study of 145 apparently healthy primary school children in Erunmu, a village in south-west Nigeria, has revealed the prevalence of asympto matic malaria parasitaemia to be 80 percent during the peak malaria transmission season. A prevalence of 15.2 percent hepatomegaly was the most common finding, followed by splenom egaly in 11.7 percent and hepatosplenomegaly in 6.2 percent of the subjects. The occurrence of hepatomegaly was significantly (P

Antibiotic-resistant bacteria (ARB) strains have become a global health threat. This study aimed to determine the antibiotic susceptibility pattern of Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from wells in Ondo town, Southwest Nigeria. Twenty-eight well water samples were analyzed for the presence of K. pneumoniae and P. aeruginosa by standard pour plate technique. The bacterial isolates were tested against eight commonly use antibiotics using Kirby Bauer disc diffusion method. The percentage occurrence of K. pneumoniae and P. aeruginosa in the well water samples were 17.86% and 21.43%, respectively. Two multi-drug resistant strains of K. pneumoniae were isolated, which were resistant to at least three classes of antibiotics. Fifty percent of the P. aeruginosa isolates were resistant to caftazidime, cefuroxime, nitrofurantoin, and ampicillin. None of the isolates was fully susceptible to cefuroxime, but have all showed resistance to β-lactam (ceftazidime, cefuroxime augmentin, and ampicillin) antibiotics. Cefuroxime may not be effective an effective drug in the treatment of K. pneumoniae and P. aeruginosa implicated infections in these communities in Ondo. Also, the over-use of antibiotics should be discouraged in order to curtail the menace of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A alleles have been suggested to play a role in the outcome of P. falciparum malaria infection in a Malian study. Herein, we investigated the association between HLA-A alleles and the outcome of malaria infection in children in Ibadan southwest Nigeria. HLA-A genotyping was performed on 393 children samples (DNA) using the sequence-based method. We compared genotype and allele frequencies data obtained from these Nigerian children; 176 with asymptomatic malaria infection (controls), 124 with uncomplicated malaria and 93 children with severe malaria (51 severe malarial anaemia and 42 cerebral malaria). We found a high frequency of HLA-A*36:01 (13.5%) in the entire studied population and also confirmed the high frequency of a previously reported allele of African origin (HLAA* 30:01). After adjusting for age and parasite density, we found a significant association between HLA-A*20:01:01 (OR = 3.19, p < 0.001) and susceptibility to severe malarial anaemia. We also found significant associations between HLA-A* 29:02:01 (OR = 7.26, p = 0.008) and A* 66:02 (Or = 4.19, p = 0.03) and susceptibility to cerebral malaria. Our findings suggest that HLA-A alleles play a role in the outcome of malaria in children in Ibadan. These findings may help elucidate the molecular background of malaria resistance in the study population. [ABSTRACT FROM AUTHOR]

As the genetic diversity of Plasmodium falciparum infections in humans is implicated in the pathogenesis of malaria, the association between P. falciparum diversity at the merozoite surface protein-2 (msp2) locus and the severity of childhood malaria was investigated in Ibadan, in south–western Nigeria. The 400 children enrolled had acute uncomplicated malaria (144), cerebral malaria (64), severe malarial anaemia (67) or asymptomatic infections with P. falciparum (125). Nested PCR was used to investigate the msp2 genotype(s) of the parasites infecting each child. In terms of the complexity of infection and frequency of polyinfection, the children with asymptomatic infection were significantly different from those with uncomplicated malaria or severe malaria. The median number of FC27 alleles detected was higher in the asymptomatic children than in the symptomatic. After controlling for age and level of parasitaemia (with 'asymptomatic infection' as the reference category), a child in whom no FC27 alleles were detected was found to be at five-fold greater risk of uncomplicated malaria, and a child without polyinfection was found to have a three-fold increased risk of severe malarial anaemia and a six-fold increased risk of cerebral malaria. It therefore appears that msp2 genotypes are associated with asymptomatic carriage and that children with mono-infections are more likely to develop severe malaria than children with polyinfections. [ABSTRACT FROM AUTHOR]

Abstract 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.

Background: Apolipoprotein L1 gene ( APOL1 ) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population., Methods: We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex., Results: Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis., Conclusions: In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)., (Copyright © 2024 Massachusetts Medical Society.)

The utilization of music intervention featuring auditory binaural beats (BBs) has garnered attention as a promising avenue for enhancing the health and well-being of younger, healthy individuals. This scoping review systematically examines the effects and correlates associated with BB stimulation in the context of older adults' health. Additionally, it briefly addresses how incorporating BBs as a therapeutic modality can facilitate medical treatment strategies and support the rehabilitation of aging populations. Employing scoping review methodology, and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension (PRISMA-ScR) for Scoping Review guidelines, a comprehensive literature search of seven databases was conducted. Twelve articles meeting the predefined inclusion criteria were identified and subsequently incorporated into the review. The findings of this scoping review underscore a notable paucity of studies exclusively dedicated to investigating the innovative and noninvasive application of binaural beat interventions among older individuals. The review delves into the applications of BB stimulation, health outcomes, and factors influencing the efficacy of BB interventions, with a particular focus on the older adults., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The meaning of dying and death are underexplored concepts for Canadian children. Subsequently, it is unclear how children and stakeholders make meaning of children's holistic health needs at the end of life., Methods: A scoping review of the international scholarly literature was conducted. Thirteen data sources were searched to search the scholarly literature without date limits until January 2022. Studies were included on the basis of population: children (aged 0-19 years), families and caregivers; setting (in Canada and end-of-life or dying phases of living) and concepts of interest (dying and death)., Results: Of the 7377 studies identified, 12 were included for data extraction and content thematic analysis. The themes and subthemes include: 1) valuing the whole person; 2) living while dying; 3) authentic death talk; 4) a supportive approach (with lack and presence of support as subthemes); and, 5) a personalist approach., Conclusions: There is a pressing need for research into the meaning of dying and death for children, their carers and families in Canada. Lack of holistic care, authentic death talk, specialized pediatric palliative care providers, a personalist approach and communities of support present major gaps in care for Canadian children. Research is urgently needed to address these knowledge gaps to generate policy and support practice for dying children in Canada., (© 2023. The Author(s).)

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Understanding the health of immigrant children from birth to 18 years of age is important given the significance of the early childhood years and complexity of factors that may influence the health status of immigrant populations. Thus, the purpose of this review was to understand the extent and nature of the literature on the health of immigrant children in Canada., Methods: We conducted a scoping review of the literature. The review was focused on studies of first-generation and second-generation immigrant children aged 0-18 years. We completed standardised data extraction of immigration status, immigration route, age of children, data source, health or clinical focus, country of origin and major findings., Results: In total, 250 published papers representing data from 237 studies met the inclusion criteria for this study. A total of 178 articles used quantitative methodologies (mostly survey and cross-sectional study designs), 54 used qualitative methodologies and 18 used mixed methodologies. The articles considered in this review included 147 (59%) focusing on physical health, 76 (30%) focusing on mental health and 37 (15%) focusing on the social aspects of health for refugee and first-generation and second-generation immigrant children across the provinces and territories of Canada., Conclusions: Several literature gaps exist with respect to child immigrant health in Canada. For instance, there are no exclusive studies on immigrant boys and limited studies on children of international students., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 Raji YR et al.)

Background: Internally displaced children are those who have been forced to flee their homes due to severe unfavourable conditions (war, violence or disasters) but have not crossed international borders. Emerging research shows these children face multiple health challenges. However, we found no review focused solely on the health of such internally displaced children. Thus, this review sought to examine what is known about their health and their health concerns., Methods: A scoping review of the literature was conducted. A total of 10 databases were searched in January 2019, yielding 6602 articles after duplicates were eliminated. Two research assistants independently selected articles that met inclusion criteria. A numerical summary and thematic analysis were conducted to facilitate data extraction and data analysis., Results: A total of 25 articles met the inclusion criteria, including 16 quantitative, 6 qualitative and 3 mixed methods studies. The findings reveal elevated mental health problems and infectious diseases in this population. Findings on the nutritional status of internally displaced children as a broad group are mixed, with some studies showing poorer nutritional status among the children in this group and others showing poorer nutritional health status among host society children. Internally displaced children also experience challenges with access to health services. Premigration factors (trauma) and postmigration factors (humanitarian assistance on displacement) all contribute to the health of internally displaced children., Conclusion: Findings provide insight into the complex array of factors influencing the health of internally displaced children. More intervention studies are required to address the needs of this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Problem: While studies have discussed the parenting practices and challenges of African immigrants, no paper has synthesized the results of these qualitative studies. We conducted a qualitative synthesis of the literature to summarize and interpret knowledge of African immigrants' parenting practices and challenges in destination countries to identify future directions for research, policy, and practice., Eligibility: We used a qualitative research synthesis method involving meta-summary and meta-synthesis of the literature. A research librarian assisted in searching ten databases. Two members of the research team independently reviewed 1794 articles. We included articles that: (a) reported a qualitative research study; (b) was written in English; and (c) provided the perspective of African immigrant parents on their parenting practices and/or challenges., Sample: A total of 24 articles met our inclusion criteria., Results: Our results indicate that parenting practices of African immigrants include the following: changes in discipline practices across transnational borders and the use of physical discipline, respect as a deeply embedded value of parenting, integration of cultural values into parenting, and integration of religious practices into parenting. We also found gender differences in parenting. Challenges faced by African immigrants in parenting their children in destination countries include lack of informal/community support, access to services and lack of formal support, cultural conflict in parenting, fear related to social services, and language barriers., Conclusion and Implications: Our study identifies a need for culturally appropriate policies and practices that build on the strengths of African immigrants in destination countries while addressing their unique challenges., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.).

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.

In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI(95%): 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group O was demonstrated with a decreased risk of severe malaria OR=0.743 (CI(95%): 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI(95%): 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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.

Plasmodium falciparum malaria remains a major public health hazard in sub-Saharan African children. While the factors that determine the variations in clinical outcome of a malaria have not been completely defined, both host and parasite factors, as well as the complex molecular interactions between them have been implicated. The cyto-adherent properties of the P. falciparum-infected red blood cells are considered as key properties in the pathogenesis of malaria and the polymorphisms of the host adhesion molecules could contribute to the severity of malaria. Clinical information and blood samples were collected from 223 children from Ibadan (south-west Nigeria), median age of 34.5 months, presenting with different clinical manifestations of malaria--clinically asymptomatic parasitism (ACP), acute uncomplicated malaria (UM) and severe malaria (SM)--as defined by WHO criteria. The polymorphisms of genes coding for four human adhesion molecules at six different loci (ICAM-1 exons 2, 4 and 6, E-selectin exon 2, CD36 exon 10, and PECAM exon 3) were studied. DNA samples were prepared for further genotyping of the six exons mentioned above by PCR-RFLPs using the appropriate restriction digests for each loci. The ICAM-1 exon 4 locus was monomorphic. All the other loci were at Hardy-Weinberg equilibrium (HWE). The E-selectin locus had very low heterozygosity (approximately 0.06) in contrast to the other loci under study (0.23-0.44). Once the data was further processed for covariates (age and parasite density) and taking as the reference category the ACP group, results show that in the presence of the G allele at the ICAM-1 exon 6 there is an increased risk (3.6 times) of severe malaria. As far as the T allele in the E-selectin exon is concerned, the number of sampled DNAs with the T allele within both the UM and SM categories is too low for drawing any relevant conclusion at this stage. In conclusion, these results suggest that genetic polymorphisms at host adhesion molecules loci are an important variable in the susceptibility to severe malaria. Further studies of host loci are needed to further delineate which polymorphisms are associated with severe malaria and increase our knowledge of the biology of host-parasite interactions.

Genetic characteristics of Plasmodium falciparum may play a role in the clinical severity of malaria infection. We have studied the association between diversity at the merozoite surface protein-1 (msp-1) locus and the severity of disease in childhood malaria in Ibadan, south-west Nigeria. Two hundred and twenty-three children (median age of 34.5 months) presenting with malaria were enrolled into the study. They comprised 53 children with asymptomatic malaria (ASM), 101 with acute uncomplicated malaria (UM) and 69 with severe malaria (SM). Genotyping of the msp-1 locus was by polymerase chain reaction. The distribution of msp-1 alleles was significantly different between the three groups. Asymptomatic malaria samples had a higher median number of alleles than the other two groups. The type of msp-1 allele detected was significantly associated with the clinical category of malaria. The absence of K1 alleles was associated with a three-fold increase risk of UM and a four-fold increased risk of SM when compared with asymptomatic malaria. The absence of MAD20 alleles was associated with a five-fold increase risk of UM and an eight-fold increase of SM. We have found an association between the msp-1 locus of P. falciparum and clinical severity of malaria in a sample of Nigerian children. Our findings show that the presence of the K1 and MAD20 alleles was significantly associated with ASM and consequently a reduced risk of developing the symptomatic disease.

Chloroquine resistance of Plasmodium falciparum in vitro was significantly higher in isolates from patients with severe malaria than those with uncomplicated disease. This association may be due to either progression of uncomplicated to severe disease following chloroquine failure or increased virulence of chloroquine-resistant parasites. The implication of this for antimalarial treatment policy is discussed.

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; P < 0.0001). 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.

While malaria pigment or haemozoin is known to be an end product of haemoglobin digestion by the malaria parasite, its clinical significance is just beginning to be elucidated. We have studied the distribution of intraleucocyte malaria pigment in 92 children, consisting of 32 children with asymptomatic malaria, 32 children with mild or uncomplicated malaria and 28 children with no malaria. Over 90% of children in each of the three groups had pigment-containing monocytes and the numbers of pigment-containing monocytes were not significantly different between the three groups. While over 90% of children in both the asymptomatic malaria and uncomplicated malaria groups had pigment-containing neutrophils, 71.4% of the no malaria group had such neutrophils. The numbers of pigment containing neutrophils was highest in the uncomplicated malaria group, followed by the asymptomatic malaria group with the no malaria group having the least numbers. The pigmented neutrophil: monocyte ratio followed the same pattern. It was concluded that the number of pigment-containing neutrophils and the pigmented neutrophil:monocyte ratio may be a marker of the severity of malaria infection when one considers the conditions: no malaria, asymptomatic malaria and mild malaria. Further work to verify this hypothesis across the full spectrum of the manifestations of malaria infection is needed.