Summary: The three types of severe anaemic crises recognised in sickle-cell anaemia (SCA) are aplastic, acute splenic sequestration and hyperhaemolytic. However, among 104 consecutive SCA cases admitted to the Children Emergency Ward of the University College Hospital, Ibadan with severe anaemic crises recently, were ten (9.6 percent) children who had mixed features and did not fall neatly into any of the three recognised categories. The distributions of the sex and admission haematocrits in these ten children with mixed' anaemic crises were similar to those of the 94 others with easily classified (pure) anaemic crises. However, using statistical test appropriate for the small numbers involved, Salmonella bacteraemia was significantly more common (5/10) among the patients with ‘mixed' anaemic crises than in those (5/94) with pure crises (P=0.0006). The relative risk of Salmonella bacteraemia in ‘mixed' crises was 9.4 times that among those with pure crises (95%CI=3.28-26.98). Although none of the “mixed cases died, compared with a mortality of 9.6 percent among the 'pure cases, the difference was not significant (P=0.42). Bacteraemia appears to be associated with mixed' indeterminate) anaemic crises in SCA. This finding suggests that such patients would benefit from appropriate antibiotic therapy.

Summary: In order to evaluate the usefulness of simple pre-laparotomy parameters in differentiat ing intrahepatic cholestasis (IHC) from extrahepatic cholestasis (EHC), 27 infants with cholestatic jaundice were studied prospectively. On initial evaluation, the following data was collected: birthweight, age at observation of jaundice, presence and consistency of hepatomegaly, splenomegaly, direct serum bilirubin, alkaline phosphatase, haematocrit, prothrombin time, per oxide haemolysis test and duodenal intubation and aspiration test. The sensitivity, specificity, negative and positive predictive values of each parameter were determined, while the definitive diagnosis was confirmed by exploratory laparotomy and intra-operative cholangiography in 12 cases of the clinical course of the disease. Patients with EHC reported to hospital late while the presence of acholic 'stools within 10 days of admission, hepatomegaly of >3 cm, peroxide haemolysis of >80 percent lysis and/or the presence or absence of bilious fluid on duodenal aspiration aided differential diagnosis of infantile cholestasis in the infants. The specificity of acholic stools, hepatomegaly and duodenal aspiration tests was 73.3 percent, 66.7 percent and 93.3 percent respectively, while the corresponding negative predictive values were 78.6 percent, 100 percent and 100 percent, respectively. These simple parameters in a set-up with limied diagnostic facilities, experience and expertise, should encourage immediate exploratory laparotomy, wedge liver biopsy and intraoperative cholangiography.

Summary: In order to determine the relative frequencies of the different causes of severe anaemia among patients with sickle cell anaemia (SCA), 104 con secutive patients with SCA presenting over an eight-month period with severe anaemia (PCV 15 percent) were studied at the children's emergency ward, University College Hospital, Ibadan. They accounted for 8.2 percent of all admissions and 24.2 percent of those who had severe anaemia. Among the patients with SCA, hyperhaemolytic, acute splenic sequestration and aplastic crises constituted 49,20 and 12.5 percent of the anaemic crises, respectively. Ten patients (9.6 percent) showed mixed features and could not be definitely classified. The frequency rate of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency was similar between patients with hyperhaemolytic and those with other forms of anaemic crisis, a finding which suggests that G 6-PD deficiency neither aggravates nor ameliorates haemolysis in SCA. The mortality in the series was 8.7 percent. Six of the patients who died had hyperhaemolysis while the other three had acute splenic sequestration crisis. Five of these deaths occurred despite emergency blood transfusion.

Background Transcranial Doppler (TCD) flow velocities predict stroke risk in children with sickle cell disease (SCD) and give a chance for primary stroke prevention. Elevated velocities ≥ 170 cm/sec are present in about one in three Nigerian children with SCD.1 Abnormal risk velocities and conditional risk (CR) velocities confer an annual stroke risk of 10% and 1–3% respectively. Nearly a quarter of children with CR will convert to abnormal risk2 but there is no recommended therapy for children with CR velocities. Aims To evaluate the effectiveness of hydroxyurea therapy in reducing TCD velocities in children with SCD and TCD velocities ≥ 170 cm/sec. Methods Children with HbSS disease and elevated velocities ≥ 170 cm/sec were prospectively followed up for a period of 18 months to document response to hydroxyurea (HU) therapy. TCD studies were performed at enrolment into the study and subsequently every 3 months for a period of 18 months. Results Thirty-three children, 18 males and 15 females were enrolled. Twenty children (60.6%) and 13 (39.4%) had CR and abnormal risk velocities respectively. None of the caregivers consented to chronic blood transfusion for primary stroke prevention. Eighteen children (54.5%) received HU while 13 (45.5%) did not consent to any form of treatment for primary stroke prevention. Mean flow velocity at enrolment in the non-HU group was 189.5 cm/sec and 200.1 cm/sec in the HU group. At the end of 18 months, children on HU therapy had significantly lower TCD velocities 170.6 (SD=14.6) cm/sec (p < 0.001) while in the non-HU group, the velocities had significantly increased with a mean of 201.1 (SD=16.0) cm/sec (p = 0.003) compared with velocities at enrolment. Children with CR who did not receive HU were more likely to convert to abnormal risk (p < 0.001, 95% CI 1.373–5.847). None of the children developed a stroke. Conclusion HU reduces flow velocities in children with SCD and elevated TCD velocities ≥170 cm/sec and reduces the risk of conversion from CR to abnormal risk velocities. References Lagunju IA, Sodeinde OO, Brown BJ, Akinbami FO, Adedokun BO. Transcranial Doppler ultrasonography in children with sickle cell anemia: clinical and laboratory correlates for elevated velocities. Journal of Clinical Ultrasound 2013 Oct 26 doi; 10.1002/jcu.22099

Background Chronic blood transfusion is the standard treatment for secondary stroke prevention in sickle cell anaemia (SCA) but this treatment option poses major challenges in resource-poor countries of the world, especially malaria-endemic ones. Objective To compare the outcomes after a first clinical stroke, with and without treatment with hydroxyurea (HU). Methods Over a 6-year period, Nigerian children with SCA who had suffered a first stroke was studied. Outcomes in those who received HU (25mg/kg/day) were compared with those whose parents declined both HU and chronic transfusion. Results Thirty-two children, all with haemoglobin SS phenotype (SCA) presented with stroke and one died of haemorrhagic stroke at presentation. Age at first clinical stroke (Mean +/- SD) was 7.58 (+/-2.33) years. Thirteen children received HU while 18 declined HU therapy. The secondary stroke incidence of 7/100 person years in the HU group was significantly lower than the 28/100 person years in the non-HU group (P = 0.001, OR 3.808, 95% CI 1.556, 9.317). Children who did not receive HU were more likely to drop out of school and to have moderate-severe motor disabilities requiring caregiver assistance for activities of daily living. Conclusion In settings where facilities for chronic blood transfusion are not accessible or feasible, HU therapy should be considered for secondary stroke prevention in children with SCA. Since, as far as we are aware, this is the first use of HU in a malaria-endemic setting, the possible impact of HU on drug-resistance in malaria needs to be carefully studied. Reference Lagunju I, Sodeinde O, Telfer P. Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease. Am J Hematol. 2012 May; 87(5):544–7. doi: 10.1002/ajh.23152. Epub 2012 Mar 28. PubMed PMID: 22460323.

Background In a retrospective analysis over 15 years (1988-2002) we estimated the incidence of stroke in our paediatric sickle cell disease (SCD) patients to be 5.4%(1), significantly less than figures from North America. We now report the initial results of our prospective study, against a background of on-going Tran-Cranial Doppler (TCD) studies, which have been shown to be effective in identifying children with SCD who are at an increased risk of stroke. Objectives Using close monitoring by TCD, to estimate the annual incidence of stroke and stroke risk in a cohort of Nigerian children with SCD. Methods Sixty-six consecutive children screened for stroke risk by TCD were followed up for a period of 12 months. All those with standard risk (SR) velocities (<170 cm/sec) had a repeat TCD scan one year after the first examination while those with abnormal velocities (>170 cm/sec) had a repeat study every 3 months. All were assessed for clinical signs of stroke and any significant changes in their cerebral blood flow velocities, leading to a classification of stroke risk. All the children with high risk velocities were offered the option of periodic blood transfusion for primary stroke prevention. Results Forty-two males and 24 females were studied. Their ages ranged from 37 to 197 months, (mean +/- SD, 98 +/- 40). At first TCD examination, 40 (60.6%) had SR velocities, 21 (31.8%) had conditional risk (CR) velocities and 5 (7.6%) had high risk (HR) velocities. At subsequent TCD examinations, 4 (19%) of the 21 children with CR velocities had converted to high risk and 6 (15%) of the 40 children with SR velocities had become CR. Two children developed a stroke, one in the HR group and one in the CR group. This gives a stroke incidence rate of (2/66) 3.0% overall, but (1/21) 4.8% and (1/5) 20.0% for CR and HR, respectively. Conclusion These data suggest that the incidence of stroke in Nigerian children is actually different from the rates in North America. If similar figures are confirmed as our study progresses, it would be important to find explanations for this observation.

BACKGROUND:Sickle cell disease is a common genetic disorder in Nigeria.OBJECTIVES:To determine the steady state haematocrit, liver size and spleen size in children with sickle cell disease and the factors that influence them.METHODS:This was a retrospective study of children with sickle cell disorders who attended the anaemia clinic of the Children's Outpatient Department, University College Hospital, Ibadan between the years 2000-2009. Relevant data extracted from their case notes included socio-demographic variables, haemoglobin phenotype, steady state haematocrit and liver and splenic sizes. Means were compared with t-test and correlation tested with Pearson correlation. Statistical significance was set at p < 0.05.RESULTS:A total of 415 (Male: female ratio 1.1:1) children were studied and 385 (92.8%) and 30 (7.2%) of the children were of haemoglobin (Hb) SS and Hb SC phenotypes respectively. Their ages ranged from 0.5-17 years with a mean (SD) of 7.3 (4.4) years. Mean (SD) steady state haematocrit for children with HbSC was 28.3 (4.5) % and significantly higher than 24.1 (3.7) % in HbSS. Mean steady state haematocrit was also higher in children from higher than lower socio-economic classes. There was a negative correlation of haematocrit with age, with hepatomegaly and splenomegaly. Steady state hepatomegaly occurred more frequently in HbSS than in HbSC.CONCLUSION:Haemoglobin phenotype, age and socio-economic status have some modifying influences on the steady-state features of sickle cell disease in Nigerian children. In addition, increasing liver and spleen sizes seem to be related to a decreasing haematocrit.

Background Transcranial Doppler (TCD) ultrasonography is now a standard screening test for stroke risk in sickle cell disease (SCD). But TCD was hitherto unavailable in Nigeria despite having a huge SCD burden, with a stroke prevalence of 5.4%1. Objectives To evaluate parental uptake of TCD and the scan abnormalities present in paediatric SCD. Methods From July 2009, following a 6-weeks UK training, TCD was offered to all consecutive SCD children aged ≥36 months, attending the paediatric haematology clinic, after detailed counselling. Results TCD uptake was 100%. All eagerly consented. Ninety-three children, 66 males and 27 females, ages 37–183 months (mean±SD=108.8±44.3) were studied. All were thick blood smear-negative for malaria parasites. The highest velocities were recorded in the middle cerebral and internal carotid arteries. Seven children had high risk velocities (table 1). No parent consented to periodic blood transfusion for stroke prevention. All seven accepted oral hydroxyurea. Conclusion TCD uptake is excellent and abnormalities are frequent in Nigerian SCD children. Periodic blood transfusion for primary stroke prevention in children with SCD appears not to be a viable option in Nigeria. Alternative preventive measures are needed in resource-poor countries, where the major burden of SCD resides.

OBJECTIVES:To determine the frequency of early deaths and the associated risk factors in children suffering from cancer at the University College Hospital, Ibadan.DESIGN:A retrospective study involving review of case notes of children suffering from cancer.SETTING:Department of Paediatrics, University College Hospital, Ibadan, Nigeria.SUBJECTS:All cases of childhood cancer managed in the Department between January 1998 and December 2004. Inclusion criteria were histological or cytological confirmation of diagnosis, suggestive clinical features and availability of details about the course of the illness.MAIN OUTCOME MEASURES:Interval between diagnosis and death, rate of early death (death within 30 days of diagnosis) and risk factors for early death.RESULTS:Eighty eight cases of childhood cancer were seen out of whom 52 died during the period. Four cases with incomplete data were excluded from subsequent statistical analysis. There were 29 (34.5%) early deaths defined as death within 30 days of diagnosis. The odds of early death were increased in the presence of bilateral kidney involvement, masses in the liver, splenic masses, pulmonary metastasis and stage D of Burkitt lymphoma. Logistic regression analysis revealed that pulmonary metastasis was a significant independent predictor ofearly death.CONCLUSIONS:Early childhood cancer mortality rate is high. Early diagnosis and referral for appropriate care may reduce childhood cancer mortality in Nigeria.

There is a dearth of information on the mortality of children with cancer in Nigeria but the few available reports suggest a poor outcome. The objectives of this study were to determine the underlying and immediate causes of death from childhood cancer. The mortality summary cards of all cases of childhood cancer seen at the Department of Paediatrics, University College Hospital, Ibadan between January 1998 and December 2004 were reviewed. Eighty-eight cases of childhood cancer were seen, out of whom 52 (59.1%) died, but only the 48 deaths with complete data were analyzed. These deaths comprised of 37 males and 11 females giving a male:female ratio of 3.4:1. Their ages ranged from 1 to 13 years with a mean of 7.3 +/- 3.4 years. The majority (71.4%) of all patients presented with diffuse or metastatic disease at diagnosis and this was associated with increased risk of dying. Of the 48 cases reviewed, 39 (81.3%) died without any remission of the primary tumour including 5 (10.4%) with disease progression despite treatment and 15 (31.3%) who died before treatment; only 4 cases (8.3%) died from tumour relapse. The immediate causes of death were infections (39.6%), bone marrow suppression (29.2%), treatment-related mortality (27.1%), organ failure (22.9%), bleeding (16.7%) and other metabolic causes (8.3%). Potentially reversible factors such as infections, bone marrow suppression and treatment-related events are the commonest causes of death from childhood cancer in Ibadan. Therefore, early presentation, prompt identification and effective management of these problems may reduce childhood cancer mortality in Nigeria.

Malaria remains a major parasitic disease in Africa, with 300-500 million new infections each year. There is therefore an urgent need for the development of new effective measures, including vaccines. Plasmodium falciparum merozoite surface protein-1(19) (MSP-1(19)) is a prime candidate for a blood-stage malaria vaccine. Blood samples were collected from children aged 10 days to 15 years in the months of January-March (N = 351) and October-November (N = 369) corresponding to the dry and rainy seasons, respectively. P. falciparum infection was determined by microscopy and enzyme linked immunosorbent assay (ELISA) was used to determine the total IgG and IgG subclasses. There was a significant increase in the mean anti-MSP-1(19) antibody titre in the dry season (p < 0.05), compared to the rainy season. A significantly positive correlation between the anti-MSP-1(19) antibody titre and parasite density (p < 0.01, r = 0.138) was observed. In the rainy season, unlike in the dry season, P. falciparum positive children had higher anti-MSP-1(19) antibody titres than P. falciparum negative children and this difference was significant (p < 0.05). When all individuals were grouped together, the anti-MSP-1(19) antibody titre increased with age in both seasons (r = 0.186 and 0.002), this increase was more apparent in the dry season. However, when the study population was divided into P. falciparum positive and negative groups, it was observed that in the rainy season, there was a negative correlation between anti-MSP-1(19) titre and age in P. falciparum positive individuals, while those who were P. falciparum negative had a positive correlation between anti-MSP-1(19) titre and age. Analysis of anti-MSP-1(19) IgG subclass showed that IgG1 and IgG3 mean titres were highest in both the dry and rainy seasons with an increase in the mean antibody titres for IgG1, IgG2 and IgG3 in the rainy season. In the dry season there was a positive correlation between IgG1, IgG2, and IgG3 titres with age, while IgG4 was negative, whereas in the rainy season there was a positive correlation between IgG2 and IgG4 (non-cytophilic antibodies) with age and a negative correlation for IgG1 and IgG3 (cytophilic antibodies) with age. Seasonal differences in the level of MSP-1(19) IgG subclass titres were observed for P. falciparum negative and positive individuals. Only samples, which were positive for IgG2 and IgG4, showed positive correlation between parasitemia and total IgG. The incidence of P. falciparum infection, which increases during the rainy season, might be an important determinant of anti-MSP-1(19) antibody levels in children living in Igbo-Ora and the results point to the fact that non-cytophilic antibodies to MSP-1(19) in children might be associated with an increase in total IgG and parasitemia.

We reviewed our records over a 15-year period to determine whether or not the impression that stroke complicating sickle cell disease was less common than reported in North America. Records of children aged 16 years and below with a diagnosis of stroke seen at the University College Hospital, Ibadan, Nigeria between 1988 and 2002 were examined. Thirty-nine such patients were identified but only 31 had detailed records available for study. Twenty-seven of these had sickle cell disease, 26 with haemoglobin genotype SS and 1 with Hb S+C. Sickle cell disease was therefore responsible for 87% of stroke seen in children at our centre. With an average clinic population of about 500 patients with sickle cell disease, the hospital frequency of stroke among these patients is estimated at 5.4%. The mean age of occurrence of the first stroke was 6.8 years ranging from 17 months to 11 years. Of the 7 patients who had CT scans of the brain done, 5 had evidence of cerebral infarction while 2 had intracerebral haemorrhage. While only 2 deaths occurred among the cases reviewed, morbidity was significant with only 6 patients achieving complete recovery. Recurrent stroke occurred after an average of 25.6 months in 8 of 13 patients who were followed up (61.5%). The incidence of stroke among African children with sickle cell disease appears to be not as high as reported in patients from North America.

Malaria remains a major parasitic disease in Africa, with 300–500 million new infections each year. There is therefore an urgent need for the development of new effective measures, including vaccines. Plasmodium falciparum merozoite surface protein-119 (MSP-119) is a prime candidate for a blood-stage malaria vaccine. Blood samples were collected from children aged 10 days to 15 years in the months of January–March (N=351) and October–November (N=369) corresponding to the dry and rainy seasons, respectively. P. falciparum infection was determined by microscopy and enzyme linked immunosorbent assay (ELISA) was used to determine the total IgG and IgG subclasses. There was a significant increase in the mean anti-MSP-119 antibody titre in the dry season (p<0.05), compared to the rainy season. A significantly positive correlation between the anti-MSP-119 antibody titre and parasite density (p<0.01, r=0.138) was observed. In the rainy season, unlike in the dry season, P. falciparum positive children had higher anti-MSP-119 antibody titres than P. falciparum negative children and this difference was significant (p<0.05). When all individuals were grouped together, the anti-MSP-119 antibody titre increased with age in both seasons (r=0.186 and 0.002), this increase was more apparent in the dry season. However, when the study population was divided into P. falciparum positive and negative groups, it was observed that in the rainy season, there was a negative correlation between anti-MSP-119 titre and age in P. falciparum positive individuals, while those who were P. falciparum negative had a positive correlation between anti-MSP-119 titre and age. Analysis of anti-MSP-119 IgG subclass showed that IgG1 and IgG3 mean titres were highest in both the dry and rainy seasons with an increase in the mean antibody titres for IgG1, IgG2 and IgG3 in the rainy season. In the dry season there was a positive correlation between IgG1, IgG2, and IgG3 titres with age, while IgG4 was negative, whereas in the rainy season there was a positive correlation between IgG2 and IgG4 (non-cytophilic antibodies) with age and a negative correlation for IgG1 and IgG3 (cytophilic antibodies) with age. Seasonal differences in the level of MSP-119 IgG subclass titres were observed for P. falciparum negative and positive individuals. Only samples, which were positive for IgG2 and IgG4, showed positive correlation between parasitemia and total IgG. The incidence of P. falciparum infection, which increases during the rainy season, might be an important determinant of anti-MSP-119 antibody levels in children living in Igbo-Ora and the results point to the fact that non-cytophilic antibodies to MSP-119 in children might be associated with an increase in total IgG and parasitemia.

As the production of NADPH in the pentose phosphate pathway is the main antioxidant defence mechanism available to the Plasmodium falciparum , we have studied the expression of P. falciparum glucose 6-phosphate dehydrogenase-6-phosphogluconolactonase (PfG6PD-6PGL) in G6PD-deficient and normal erythrocyte host cells. Both erythrocytes infected in vitro with a laboratory isolate and erythrocytes from natural human infections were used. Total RNA was prepared from parasites collected from five G6PD-deficient and nine G6PD-normal children in Ibadan, Nigeria, selected after screening 189 rural schoolchildren and 68 clinical malaria patients, and was subjected to Northern blot analysis. The probe was a cDNA fragment of the G6PD domain of the PfG6PD-6PGL gene, with an internal control probe of P. falciparum 18S ribosomal RNA. Quantification was performed using a phosphoimager. Relative to internal control, the abundance of PfG6PD-6PGL mRNA (mean +/- standard deviation) was lower in parasites from G6PD-deficient children (0.29 +/- 0.27) than in G6PD-normal control subjects (0.74 +/- 0.26) (P = 0.014, Mann-Whitney U -test). Although confirmation in a larger study is required, our results suggest a lower relative abundance of PfG6PD-6PGL, and presumably antioxidant activity, in malaria parasites from G6PD-deficient hosts, thus extending the current knowledge of the mechanism of G6PD-deficiency related host protection.

Plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (G6PD-6PGL) is a bifunctional enzyme with significant sequence similarity in both the 6PGL and G6PD domains to the Plasmodium falciparum enzyme. A recombinant form of the P. berghei enzyme was found to have both G6PD and 6PGL activities, and therefore catalyses the first two steps in the pentose phosphate pathway. Genes encoding very similar proteins are also found in three other malarial parasites, Plasmodium yoelii, Plasmodium chabaudi and Plasmodium knowlesi. All of these predicted enzymes contain unique parasite insertions in corresponding positions in the G6PD domain but the insertions differ in size and sequence. Such insertions are a common feature of malarial proteins but their origin and function is unknown. Excision of the insertion sequence in the P. berghei protein renders the G6PD domain inactive, although the 6PGL activity is unaffected. Replacing the insertion sequence in P. berghei with the insertion sequence from P. falciparum restores some of the G6PD activity and also enhances 6PGL activity. We conclude that although the insertions are evolving rapidly they have an essential role in the activity of the bifunctional enzyme.

ABSTRACT Malaria merozoite surface protein 1 (MSP1) is cleaved in an essential step during erythrocyte invasion. The responses of children to natural malaria infection included antibodies that inhibit this cleavage and others that block the binding of these inhibitory antibodies. There was no correlation between the titer of the antibody to the 19-kDa fragment of MSP1 and its inhibitory activity. These findings have implications for the design of MSP1-based vaccines.

The hypothesis that chloroquine-induced pruritus (CIP) may be determined by certain genetic factors was tested by investigating the epidemiology of CIP with respect to certain genetic red cell markers namely, haemoglobin genotype, glucose-6-phosphate dehydrogenase (G6PD) deficiency and the ABO blood groups. Three hundred consecutive patients treated for malaria with chloroquine at the University College Hospital, Ibadan, Nigeria were recruited into the study. They were observed over 3 days for presence of CIP. ABO blood groups, G6PD and Hb genotypes were determined appropriately for each patient. One hundred and twenty four (41.3%) of the patients responded positively to CIP. There was a reduced frequency of the sickle cell trait (HbAS) among itchers relative to non-itchers. This suggests that the trait may be protective against CIP. G6PD deficiency was also found to be relatively more common among itchers than non-itchers. This indicates that G6PD deficiency may increase susceptibility to CIP. There was however no difference in the distribution of itchers among the different ABO blood groups. It was concluded that CIP may be associated with certain genetic red cell markers particularly Hb and G6PD types which are known malaria markers but not ABO blood groups.

Plasmodium falciparum glucose 6-phosphate dehydrogenase (Pf Glc6PD), compared to other Glc6PDs has an additional 300 amino acids at the N-terminus. They are not related to Glc6PD but are similar to a family of proteins (devb) of unknown function, some of which are encoded next to Glc6PD in certain bacteria. The human devb homologue has recently been shown to have 6-phosphogluconolactonase (6PGL) activity. This suggests Pf Glc6PD may be a bifunctional enzyme, the evolution of which has involved the fusion of adjacent genes. Further functional analysis of Pf Glc6PD has been hampered because parts of the gene could not be cloned. We have isolated and sequenced the corresponding Plasmodium berghei gene and shown it encodes an enzyme (Pb Glc6PD) with the same structure as the P. falciparum enzyme. Pb Glc6PD is 950 amino acids long with significant sequence similarity in both the devb and Glc6PD domains with the P. falciparum enzyme. The P. berghei enzyme does not have an asparagine-rich segment between the N and C halves and it contains an insertion at the same point in the Glc6PD region as the P. falciparum enzyme but the insertion in the P. berghei is longer (110 versus 62 amino acids) and unrelated in sequence to the P. falciparum insertion. Though expression of this enzyme in bacteria produced largely insoluble protein, conditions were found where the full-length enzyme was produced in a soluble form which was purified via a histidine tag. We show that this enzyme has both Glc6PD and 6PGL activities. Thus the first two steps of the pentose phosphate pathway are catalysed by a single novel bifunctional enzyme in these parasites.

This short report describes the results of a rapid, simple and cost effective immunodiagnostic test for malaria in Ibadan, Nigeria. A total of 77% patients presenting at the children outpatient clinic, University College Hospital with malaria symptoms were screened for malaria parasites by microscopy using Giemsa stain and by the immunochromatographic card test. The immunodiagnostic test had a sensitivity of 93.1% and a specificity of 95.8%, making a good alternative for malaria diagnosis especially in rural areas without electricity, where microscopy is not possible, and a decision is to be made on when to start treatment.

The pharmacokinetics of chloroquine and its main metabolite desethylchloroquine have been carried out in volunteers with and without chloroquine-induced pruritus. It was shown that the volunteers with pruritus tended to metabolize chloroquine slower than the volunteers without pruritus because the metabolic ratio was lower in the volunteers with pruritus than that in the volunteers without pruritus. However, the overall pharmacokinetic patterns were comparable between the two groups and agreed with published data. The 24-hour urinary collections in the two groups of volunteers indicated that the volunteers with pruritus excreted more chloroquine (although not statistically significant) than the volunteers without pruritus. This also indicates that they metabolized less chloroquine. There were no side effects of note in any of the volunteers. The volunteers who gave positive histories of chloroquine-induced pruritus had mild episodes of itching after intake of the drug; the pruritus subsided within 48 hours in all instances.