Complexity of the msp2 locus and the severity of childhood malaria, in south-western Nigeria.

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 polyinfection.

Association between ICAM-1 Gly-Arg polymorphism and renal parenchymal scarring following childhood urinary tract infection.

Renal parenchymal scarring (RPS) following urinary tract infection (UTI) is an important cause of renal morbidity in children. Studies have shown that the intensity of the inflammatory response following infection is related to the risk of RPS. However, genetic variability in this response has not been studied. Adhesion molecules play a crucial role in leucocyte recruitment following infection, and polymorphisms have been reported in the genes for key cell adhesion molecules. We have investigated the possibility that children who develop RPS following UTI may exhibit altered genotype or allele frequencies for polymorphisms of the intercellular adhesion molecule-1 (ICAM-1) (exons 4 and 6), E-selectin (exons 2 and 4), platelet endothelial cell adhesion molecule-1 (PECAM-1) (exon 3) and CD11b (3'UTR) genes, which may predict outcome of UTI. DNA was isolated from 99 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI and 170 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis. When the RPS group was compared with the NS group, there was a significant reduction in the frequency of the ICAM-1 exon 4 A allele (10.6 vs. 21.3%, respectively, chi2 = 6.01, P = 0.014). There was no significant difference in either allele or genotype frequency for any of the other polymorphisms studied. These data suggest that the A allele of the ICAM-1 exon 4 polymorphism may protect against the risk of RPS following UTI and may participate in the regulation of the inflammatory response following UTI.

Increased steroid responsiveness of young children with nephrotic syndrome in Nigeria.

UNLABELLED: A previous study on the nephrotic syndrome (NS) in our unit showed that the histological patterns associated with steroid resistance were more common in children over 5 years of age. AIM: The aim of the study was to determine the incidence of steroid-responsiveness amongst nephrotic children

Genetic diversity of the msp-1 locus and symptomatic malaria in south-west Nigeria.

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.

Plasmodium falciparum malaria in south-west Nigerian children: is the polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity of malaria?

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.

A review of cases of posterior urethral valves seen at the University College Hospital, Ibadan (Nigeria).

A cohort of 40 male children with Posterior Urethral Valves (PUV) seen in the Paediatric Nephrology/Urology Unit of the University College Hospital, Ibadan are presented. They were reviewed with the aim of determining the clinical course of the disease in a developing country where the facilities for active intervention are not always available. Even though 50% of the patients became symptomatic in the first week of life only 22.5% presented in the whole of the neonatal period. Thirty-seven and a half per-cent (37.5%) presented in the post-neonatal infancy period and the rest beond the first year of life. The interval between the onset of symptoms and definitive therapy was up to three years in some patients. Only 2 patients had antenatal diagnosis of the PUV by ultrasonography. The major renal complications were: (1) Urinary Tract Infections in 40%; (2) Acute Renal failure--10%; (3) Chronic Renal failure--7%; 4) Type IV Renal Tubular Acidosis--10% (5) Sustained hypertension--4.8%. The extra-renal complications were anaemia (30%), malnutrition (10%). Five of the patients died giving a case fatality rate of 12.5%, mainly from overwhelming infections and renal failure. Many of our patients had delayed presentation even though symptomatic and that may partly explain the complications and the poor outcome seen in the short term.

Chloroquine resistance of Plasmodium falciparum is associated with severity of disease in Nigerian children.

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.

A PCR-RFLP typing method for adhesion molecule gene polymorphisms and allele frequencies in a normal UK population.

We report simple and reproducible PCR-RFLP typing methods for the polymorphisms in the ICAM-1, E-selectin and PECAM-1 genes. The genotype and allele frequencies detected in a normal UK population did not deviate significantly from the Hardy-Weinberg equilibrium; neither did they differ from frequencies previously reported using SSP or SSCP methods.

Plasma and urinary soluble adhesion molecule expression is increased during first documented acute pyelonephritis.

BACKGROUND: The degree of inflammatory reaction and leucocyte trafficking during acute pyelonephritis has been related to the risk of developing renal parenchymal scarring. Adhesion molecules play a central role in leucocyte recruitment during inflammation. AIMS: (1) To determine whether circulating and urinary concentrations of E-selectin and intercellular adhesion molecule 1 (ICAM-1) were abnormal during first documented acute pyelonephritis; (2) to investigate whether circulating or urinary concentrations were predictive for the development of abnormalities on DMSA imaging. METHODS: Plasma and urine samples were collected from 40 children with a first episode of acute pyelonephritis within one week of infection (acute sample) and at six weeks (late sample). Control samples were collected from 21 healthy age matched controls and 18 age matched controls with febrile illness not secondary to urinary tract infection. RESULTS: Plasma and urinary sE-selectin were higher in acute samples (median 176.3 ng/ml and 0.12 ng/mmol respectively) compared with late (97.8 ng/ml and 0.029 ng/mmol) and both control (65.6 ng/ml and 0 ng/mmol) and febrile control (urine 0 ng/mmol) samples. Plasma sICAM-1 was higher in acute samples (428 ng/ml) than controls (365.2 ng/ml), and acute sICAM-1 urine concentrations were higher than febrile control concentrations (3.2 v 0.7 ng/mmol). No correlations were detected between sE-selectin or sICAM-1 and acute or late DMSA scan changes. CONCLUSION: Plasma and urinary sE-selectin and sICAM-1 are significantly increased during acute pyelonephritis, though no correlation exists between the presence of high plasma or urine concentrations and DMSA scan changes, both during acute infection and six weeks post-infection.

The Ibadan conjoined twins: a report of omphalopagus twins and a review of cases reported in Nigeria over 60 years.

An omphalopagus set of female conjoined twins, undiagnosed prenatally, who presented as obstructed labour needing operative delivery is reported. Their anatomic characteristics and clinical features, including overwhelming sepsis in twin II which forced early separation, and those which led to their demise are described. Twelve other cases reported in Nigeria over the past 60 years are reviewed with reference to the aetiology and epidemiology of conjoined twinning and the determinants of successful surgical separation.

The predominance of membranoproliferative glomerulonephritis in childhood nephrotic syndrome in Ibadan, Nigeria.

The histological findings in renal biopsy specimens obtained from 41 children with the nephrotic syndrome in Ibadan, Nigeria, between July, 1989 and June, 1996 are presented. The patients consisted of 26 male and 15 female children and their ages ranged from 2-13 years. The predominant histological type was membranoproliferative glomerulonephritis (MPGN) which occurred in 21 (51.2%). Membranous nephropathy and minimal change nephropathy (MCN) accounted for 4 (9.8%) patients each. The prevalence of MPGN was 33.3% in children less than 5 years of age compared with 56.2% amongst children who were > or = 5 years. All the three patients with MCN who were treated with a course of prednisolone had complete remission of the disease. It is concluded that MPGN is the predominant histological lesion seen in childhood nephrotic syndrome in Ibadan and that MCN remains an uncommon lesion. Therefore, renal biopsy is recommended as a prelude to a trial of steroid therapy in these patients since MCN (which is generally associated with steroid-responsiveness) is an uncommon finding among them.

Comparative efficacy of intramuscular artemether and intravenous quinine in Nigerian children with cerebral malaria.

The efficacy of a 5-day treatment with intramuscular artemether (3.2-mg/kg loading dose followed by 1.6 mg/kg daily) was compared to that of the standard 7-day treatment with quinine (20-mg/kg loading dose followed by 10 mg/kg every 8 h) in a randomised clinical trial including 103 children aged 12-60 months with cerebral malaria between 1994 and 1996. No statistical difference of immediate efficacy was found between the two treatments. There were 11 (20%) deaths in the artemether group and 14 (28%) in the children who received quinine. The respective artemether versus quinine median fever clearance times (h) were 39 (interquartile ranges [IQ] 30-54) vs. 48 (IQ 30-60), and parasite clearance 42 (IQ 24-60) vs. 36 (IQ 30-48). However, one patient who received artemether had a recrudescence on day 14, which was successfully treated with sulphadoxine-pyrimethamine. Times to recovery from coma were 24 h (IQ 18-45) and 33 h (IQ 19-57), respectively. The occurrence of transient neurological sequelae including motor disabilities, cortical blindness, and afebrile seizures was also similar in the two groups. No adverse reactions to the two drugs were recorded during the study period. Artemether represents an important option in the management of cerebral malaria in Nigeria especially in rural areas where facilities for intravenous administration may not yet be optimal.

Neurological features of cerebral malaria in Nigerian children.

Cerebral malaria is one of the commonest causes of an acute neurological syndrome in malaria-endemic areas. However, there are few detailed reports of findings on clinical neurological examination of the condition. The neurological features of cerebral malaria in 103 children aged 5 years or less were studied in Ibadan, Nigeria, an area of high malaria transmission. The correlation of these features with prognosis was also studied. Convulsions occurred in 87% of subjects and were in most cases of a generalized tonic-clinic nature. Abnormalities of posture were observed in 41%, abnormal tone in 70% and abnormal deep tendon reflexes in 74%. Absent corneal reflexes were found in about 14%. The time interval between the last seizure episode and presentation in hospital, abnormal posture (decerebrate or decorticate), absence of corneal reflex and depth and duration of coma were indicators of poor prognosis. In this study, cerebral malaria presented with non-specific features of diffuse, symmetrical, upper motor neurone dysfunction, and some specific neurological features were associated with poor prognosis. It is important that cerebral malaria be considered in any child with features of acute encephalopathy in a malaria-endemic area. Careful clinical examination of such children is essential as neurological features of the condition may provide a clue to prognosis.

Intraleucocytic malaria pigment and clinical severity of malaria in children.

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.

The clinical manifestations of cerebral malaria among Nigerian children with the sickle cell trait.

In order to describe the interaction between haemoglobin type and the clinical manifestations of cerebral malaria, we studied 60 children aged between 6 and 60 months at University College Hospital, Ibadan, Nigeria. Haemoglobin AS individuals with cerebral malaria did not exhibit major differences in clinical and laboratory characteristics when compared with their haemoglobin AA counterparts. There were no deaths among the Hb AS children compared with an 18% mortality in the Hb AA group. Blood transfusion rates were higher in the AS than in the AA children (86% vs 44%). The higher transfusion rates in the AS group is consistent with in-vitro observations of sickling of parasitized red cells containing Hb S which in vivo would be cleared by the reticuloendothelial system. It is concluded that the clinical manifestations of cerebral malaria are essentially similar in children with haemoglobins AS and AA but the former have higher transfusion needs and are less likely to die.

Intraosseous infusion in an emergency situation: a case report.

An 18-month-old boy who had cardiopulmonary arrest secondary to penicillin anaphylaxis was successfully resuscitated by intraosseous administration of emergency resuscitative medications because peripheral vascular access was impossible. He was discharged 2 weeks later in a satisfactory clinical condition.