The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study.

BACKGROUND: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso.

In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.

Correction: Performance of PfHRP2­RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso.

[This corrects the article DOI: 10.1007/s12639-023-01566-x.].

Performance of PfHRP2-RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso.

In this study, we evaluated the performance of a P. falciparum Histidine Rich Protein 2 (PfHRP2)-based rapid diagnostic test (RDT) used for malaria case detection (SD-Bioline malaria RDT P.f®) along with light microscopy (LM) against qPCR among children during the first year of life in a high and seasonal malaria transmission area in Burkina Faso. A total of 723 suspected malaria cases (including multiple episodes) that occurred among 414 children participating in a birth-cohort study were included in the present analysis. Factors including age at the time of malaria screening, transmission season and parasite densities were investigated for their potential influence in the performance of the RDT. Clinical malaria cases as detected by RDT, LM and qPCR were 63.8%, 41.5% and 49.8%, respectively. Compared with qPCR, RDT had a false-positive results rate of 26.7%, resulting in an overall accuracy of 79.9% with a sensitivity of 93%, a specificity of 66.1%, a Positive Predictive Value of 73.3% and a Negative Predictive Value of 91.6%. Its specificity differed significantly between high and low transmission seasons (53.7% vs 79.8%; P < 0.001) and decreased with increasing age (80.6-62%; P for trend = 0.024). The overall accuracy of LM was 91.1% and its performance was not significantly influenced by transmission season or age. These findings highlight the need to adapt malaria diagnostic tools recommendations to face the challenge of adequate malaria detection in this population group living in high burden and seasonal malaria transmission settings.

Genetic variation in the immune system and malaria susceptibility in infants: a nested case-control study in Nanoro, Burkina Faso.

BACKGROUND: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). RESULTS: Genetic variants in IL-1ß (rs1143634) and FcγRIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells. CONCLUSIONS: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.

Kyste valléculaire de l'enfant : à propos de 3 cas

Le kyste valléculaire est une pathologie rare. Il est responsable de détresse respiratoire avec stridor et de décès chez le nouveau-né et le nourrisson. La nasofibroscopie est un outil performant pour le diagnostic.Nous rapportons 3 cas de kystes de la vallécule chez un nouveau-né et deux nourrissons. La détresse respiratoire et le stridor ont été les symptômes rencontrés.La nasofibroscopie a permis le diagnostic. Les deux nourrissons ont bénéficié d'une marsupialisation par voie trans-orale. Le troisième patient est décédé avantla prise en charge

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life.

Malaria incidence and prevalence during the first year of life in Nanoro, Burkina Faso: a birth-cohort study.

BACKGROUND: Infants are thought to be protected against malaria during the first months of life mainly due to passage of maternal antibodies. However, in high transmission settings, malaria in early infancy is not uncommon and susceptibility to the infections varies between individuals. This study aimed to determine malaria morbidity and infection during early childhood in rural Burkina Faso. METHODS: Malariometric indices were determined over 1-year follow-up in a birth cohort of 734 infants living in Nanoro health district. Clinical malaria episodes were determined by passive case detection at peripheral health centres while asymptomatic malaria infections were identified during  4 cross-sectional surveys at 3, 6, 9 and 12 months of age. Plasmodium falciparum infections were detected by rapid diagnostic test and/or light microscopy (LM) and quantitative PCR (qPCR). RESULTS: In total, 717 clinical episodes were diagnosed by qPCR over 8335.18 person-months at risk. The overall malaria incidence was 1.03 per child-year and increased from 0.27 per child-year at 0-3 months of age to 1.92 per child-year at 9-12 months of age. Some 59% of children experienced at least one clinical episode with a median survival time estimated at 9.9 months, while 20% of infants experienced the first episode before 6 months of age. The majority of the clinical episodes were attributable to microscopic parasitaemia (84.2%), and there was a positive correlation between parasite density and age (Spearman's rho = 0.30; P < 0.0001). Prevalence of asymptomatic infections was similar at 3, 6 and 9 months of age (17.7-20.1%) and nearly 1.6 times higher at 12 months (31.3%). Importantly, gametocyte prevalence among the LM-positive study population was 6.7%, but increased to 10% among asymptomatic infections. In addition, 46% of asymptomatic infections were only detected by qPCR suggesting that infants below 1 year are a potential reservoir for sustaining malaria transmission. Both symptomatic and asymptomatic infections showed marked seasonal distribution with the highest transmission period (July to December) accounting for about 89 and 77% of those infections, respectively. CONCLUSIONS: These findings indicate high and marked age and seasonal-dependency of malaria infections and disease during the first year of life in Nanoro, calling for intensified efforts to control malaria in rural Burkina Faso.

Additional Screening and Treatment of Malaria During Pregnancy Provides Further Protection Against Malaria and Nonmalarial Fevers During the First Year of Life.

Background: Although consensus exists that malaria in pregnancy (MiP) increases the risk of malaria in infancy, and eventually nonmalarial fevers (NMFs), there is a lack of conclusive evidence of benefits of MiP preventive strategies in infants. Methods: In Burkina Faso, a birth cohort study was nested to a clinical trial assessing the effectiveness of a community-based scheduled screening and treatment of malaria in combination with intermittent preventive treatment with sulfadoxine-pyrimethamine (CSST/IPTp-SP) to prevent placental malaria. Clinical episodes and asymptomatic infections were monitored over 1 year of follow-up to compare the effect of CSST/IPTp-SP and standard IPTp-SP on malaria and NMFs. Results: Infants born during low-transmission season from mothers receiving CSST/IPTp-SP had a 26% decreased risk of experiencing a first clinical episode (hazard ratio, 0.74 [95% confidence interval, .55-0.99]; P = .047). CSST/IPTp-SP interacted with birth season and gravidity to reduce the incidence of NMFs. No significant effects of CSST/IPTp-SP on the incidence of clinical episodes, parasite density, and Plasmodium falciparum infections were observed. Conclusions: Our findings indicate that CSST/IPTp-SP strategy may provide additional protection against both malaria and NMFs in infants during the first year of life, and suggest that malaria control interventions during pregnancy could have long-term benefits in infants.

Connaissance des signes de danger de la grossesse, du postpartum et du nouveau-né par les gestantes et accouchées récentes du District sanitaire de Sig-Noghin, Ouagadougou, Burkina Faso

L'objectif était d'étudier la connaissance des signes de danger de la mère et du nouveau-né ainsi que les facteurs associés parmi les femmes du district sanitaire de Sig-Noghin. Il s'est agi d'une étude transversale analytique menée du 1er avril au 30 mai 2016. Elle a concerné un échantillon de 429 femmes. L'entretien a été la technique d'enquête utilisée. Pour l'identification des facteurs associés, une régression logistique fut réalisée. Parmi les participantes 16,5 % ; 11,1 % et 6,3 % ont pu citer au moins trois (3) signes de danger respectivement de la grossesse, du postpartum et du nouveau-né. L'âge de la femme (OR aj 6,14 [1,06-35,61]), le niveau d'instruction (OR aj 3,19 [1,59-6,38]), le nombre de grossesses (OR aj 3,30 [1,13-9,62]) et le nombre de consultations prénatales (OR aj 1,77 [1,09-3,46]) étaient les facteurs statistiquement associés à la connaissance des signes de danger de la mère. Aucun des facteurs étudiés n'était associé à la connaissance des signes de danger du nouveau-né. En somme, le niveau de connaissance des signes de danger de la mère et du nouveau-né reste faible. Il est impératif de promouvoir davantage la sensibilisation des femmes enceintes et accouchées tout en impliquant la communauté dans laquelle celles-ci vivent

Diagnosing congenital malaria in a high-transmission setting: clinical relevance and usefulness of P. falciparum HRP2-based testing.

Congenital malaria diagnosis is challenging due to frequently observed low parasite density infections, while their clinical relevance during early infancy is not well characterized. In Nanoro health district (Burkina Faso), we determined the prevalence of congenital malaria by real-time quantitative PCR and we assessed the performance of rapid diagnosis test (RDT) and light microscopy (LM) to detect Plasmodium falciparum infections in cord-blood samples. In addition, we examined the usefulness of P. falciparum Histidine Rich Protein2 (PfHRP2) as surrogate biomarker of infection and explored association between congenital malaria and clinical outcomes. A prevalence of congenital malaria by qPCR of 4% (16/400) was found, which increased to 10% among newborns from mothers infected at delivery. RDT and LM showed poor performances indicating limited utility for congenital malaria screening in cord blood. Because PfHRP2 detection in cord blood could be affected by transplacental passage of parasite antigens, PfHRP2 might not be used as a surrogate biomarker of congenital malaria infections. There was no evidence of a significant clinical impact of congenital malaria on infant's health from birth to 59 days of life. Case control studies including long-term follow up may provide additional understanding on the relevance of neonatal malaria infections.

Therapeutic effects of exogenous surfactant enriched with dextran in newborn rabbits with respiratory failure induced by airway instillation of albumin.

The aim of the study was to investigate lung function and morphology in newborn rabbits with acute respiratory failure induced by airway instillation of albumin and to test whether the therapeutic effect of exogenous modified natural surfactant could be enhanced by addition of dextran. Rabbits (gestational age 29 days) were ventilated with 100% O2 and tidal volume 8-10 ml/kg. Respiratory failure was induced by tracheal instillation of albumin (50 or 100mg/ml; 2 ml/kg) and the instillation was repeated 15 min later. Surfactant (Curosurf, 200mg/kg) with or without addition of dextran (30 mg/ml) was administered 15 min after the second dose of albumin and animals were then ventilated for another 60 min. In one series of experiments, instillation of albumin was followed by administration of diluted Curosurf (40 mg/kg) with or without dextran (30 mg/ml). Animals with initial lung-thorax compliance (CLT)<0.6 ml/kg cm H2O were directly treated with surfactant without previous instillation of albumin. Animals treated with a larger dose of Curosurf (200mg/kg) showed a significant increase in CLT at 60 min with no difference between groups receiving high or low dose of albumin. Addition of dextran to Curosurf at high dose (200mg/kg) reduced the therapeutic response (P<0.05 vs. Curosurf without dextran). After treatment with low-dose Curosurf (40 mg/kg) CLT increased more prominently after Curosurf+dextran than after non-enriched surfactant (P<0.05). Dextran potentiated the treatment effect of Curosurf at suboptimal dose (40 mg/kg) but not at high dose (200mg/kg) in animals with low-grade surfactant deficiency or respiratory failure induced by airway instillation of albumin.

Biophysical and physiological properties of porcine surfactant enriched with polymyxin B.

OBJECTIVE: We examined whether the biophysical and physiological properties of Curosurf were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). METHODS: Curosurf was diluted to 1-5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (gammamin) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. RESULTS: At surfactant concentration 2 mg/ml, gammamin was high (17 +/- 8.9 mN/m) but remained low (2.7 +/- 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. CONCLUSION: Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.

Dietary serotonin and alcohol combined may provoke adverse physiological symptoms due to 5-hydroxytryptophol.

The urinary excretion products of serotonin (5-hydroxytryptamine, 5HT) are 5-hydroxyindole-3-acetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL), and the ratio of 5HTOL to 5HIAA is normally very low (< 0.01 ) in man. Intake of foods rich in 5HT (high amounts in banana, pineapple, and walnuts) induces a general increase in the output of 5HT metabolites, without affecting the 5HTOL/5HIAA ratio. In contrast, during metabolism of ethanol there is a shift in the catabolic pattern of 5HT, and the formation of 5HTOL increases appreciably at the expense of 5HIAA. Accordingly, the urinary 5HTOL/ 5HIAA ratio increases and does not recover to baseline levels until several hours after ethanol has been cleared from the body. When 10 healthy subjects ingested a moderate dose of ethanol (0.5 g/kg), the urinary 5HTOL/SHIAA ratio was increased approximately 70-fold on average at 4 h after intake. When the same amount of ethanol was ingested together with 3 bananas (approximately 10 mg 5HT), this ratio was increased approximately 100-fold at 4 h and still significantly higher than baseline levels at 24 h. Starting at 3-4 h after the combined intake of ethanol and banana, 7 subjects experienced one or more unpleasant symptoms (diarrhea, headache, and fatigue) which are associated with the 5HT system. The events were transient but typically lasted for several hours, and the duration correlated with the time period during which 5HTOL levels were raised. Intake of ethanol and banana separately produced much lower increases in 5HTOL output and caused no corresponding effects. This observation indicate that dietary 5HT intake together with even a moderate dose of ethanol can provoke unpleasant physiological symptoms. The symptoms may be attributed to the high concentration of 5HTOL.

Studies on the interaction between ethanol and serotonin metabolism in rat, using deuterated ethanol and 4-methylpyrazole.

The metabolic interaction between ethanol and serotonin (5-hydroxytryptamine) via alcohol dehydrogenase (ADH; EC 1.1.1.1) was studied in tissue homogenates of Sprague-Dawley rats by following the transfer of deuterium from deuterated ethanol over endogenous NADH to 5-hydroxytryptophol (5HTOL). Homogenates of whole brain, lung, spleen, kidney, liver, stomach, jejunum, ileum, colon, and caecum were incubated in the presence of [2H2]ethanol and 5-hydroxyindole-3-acetaldehyde (5HIAL), and the [2H]5HTOL formed was identified and quantified using gas chromatography-mass spectrometry. ADH activity was most abundant in liver, kidney, and within the gastrointestinal tract. The highest incorporation of deuterium was obtained in homogenates of kidney, lung, and colon, whereas in brain, which contains very low ADH activity, no incorporation could be demonstrated. Addition of extra NAD+ (2.4 mM) increased the formation of [2H]5HTOL 2.6-fold in liver homogenates, but only 1.2-fold in kidney homogenates. 4-Methylpyrazole, a potent inhibitor of class I ADH, inhibited the 5HIAL reduction in homogenates of lung, kidney, jejunum, ileum, and colon, and caused a marked drop in 5HTOL oxidation in all tissues except stomach and spleen. These results demonstrate that in the rat a metabolic interaction between ethanol and serotonin via the ADH pathway may take place in several tissues besides the liver, which is the main tissue for ethanol detoxification.

Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin.

Alcohols and aldehydes in the metabolic pathways of ethanol and serotonin are substrates for alcohol dehydrogenases (ADH) of class I and II. In addition to the reversible alcohol oxidation/aldehyde reduction, these enzymes catalyse aldehyde oxidation. Class-I gammagamma ADH catalyses the dismutation of both acetaldehyde and 5-hydroxyindole-3-acetaldehyde (5-HIAL) into their corresponding alcohols and carboxylic acids. The turnover of acetaldehyde dismutation is high (kcat = 180 min-1) but saturation is reached first at high concentrations (Km = 30 mm) while dismutation of 5-HIAL is saturated at lower concentrations and is thereby more efficient (Km = 150 microm; kcat = 40 min-1). In a system where NAD+ is regenerated, the oxidation of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid proceeds with concentration levels of the intermediary 5-HIAL expected for a two-step oxidation. Butanal and 5-HIAL oxidation is also observed for class-I ADH in the presence of NADH. The class-II enzyme is less efficient in aldehyde oxidation, and the ethanol-oxidation activity of this enzyme is competitively inhibited by acetate (Ki = 12 mm) and 5-hydroxyindole-3-acetic acid (Ki = 2 mm). Reduction of 5-HIAL is efficiently catalysed by class-I gammagamma ADH (kcat = 400 min-1; Km = 33 microm) in the presence of NADH. This indicates that the increased 5-hydroxytryptophol/5-hydroxyindole-3-acetic acid ratio observed after ethanol intake may be due to the increased NADH/NAD+ ratio on the class-I ADH.

Elevated brain 5-hydroxytryptophol levels in experimental portal-systemic encephalopathy.

Brain tissue levels of the two serotonin metabolites 5-hydroxytryptophol and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured in porta-caval shunted rats, an in vivo model of portal-systemic encephalopathy. An intraperitoneal challenge of L-tryptophan (280 mg/kg body weight) to sham-operated rats was also instituted to increase the brain serotonin metabolism in these rats. The results revealed significant increases in 5-hydroxytryptophol (by 31% and 5-HIAA (by 87%) brain levels in porta-caval shunted rats as compared to sham-operated controls. The brain 5-hydroxytryptophol-to-5-HIAA ratio was lower in the porta-caval shunted rats. The 5-hydroxytryptophol levels in sham rats after the L-tryptophan challenge were intermediate between the porta-caval shunted and sham rats but not statistically significant for either group. These results suggest that increased brain 5-hydroxytryptophol levels might be associated with the pathogenesis of portal-systemic encephalopathy. Further, the elevated brain 5-hydroxytryptophol levels in experimental portal-systemic encephalopathy are probably a result of the increased brain serotonin metabolism prevailing in this condition rather than changes in the brain redox potential.

Acute interaction between ethanol and serotonin metabolism in the rat.

The effect of acute ethanol on peripheral serotonin (5HT) metabolism was studied in Sprague-Dawley rats. Four hours after a single dose of ethanol (1.0 g/kg) administered into the stomach, a significant increase in the 5HT level in stomach tissue and a decrease in ileum was observed. The level of 5-hydroxyindole-3-acetic acid (5HIAA) was increased in urine, while increased concentrations of 5-hydroxytryptophol (5HTOL) occurred in jejunum, ileum, spleen and urine. After 7-9 h when the blood ethanol concentration had returned to zero, 5HTOL levels were still higher than control values in jejunum, ileum and urine. At 4 h, an elevated ratio of 5HTOL to 5HIAA was observed in urine and ileum (by approximately 2-fold), liver (approximately 3-fold), and spleen (approximately 5-fold), whereas the ratio was reduced in stomach. In urine and spleen, this metabolic shift persisted after 7-9 h. The 5HTOL level in bile was increased by approximately 3.5-fold after 8 h. 5HIAA was not detectable in bile. The present results indicate that the rat has a much higher proportion of 5HTOL formation than man under normal conditions. The rat does not appear to be an ideal model for studying the interaction between ethanol and 5HT metabolism in man.

Morbidite et mortalite dans le service interne du Centre Hospitalier National de Ouagadougou sur 4 ans (Janvier 1990 a Decembre 1993)

Le service de medecine interne de Ouagadougou est un service pluridiscilinaire; de dernier recours; les auteurs ont realise une etude retrospective de janvier 1990 a decembre 1993 afin d'apprecier la mortalite et la morbidite dans le service. 2891 patients ont ete concernes par cette etude. Il s'agissait de sujets jeunes; d'age moyen 36 ans avec 44;94 pour cent de sujets ages de 20 a 39 ans. 61;86 pour cent etant de sexe masculin. Sur le plan de la morbidite; la pathologie observee etait variee avec predominance d'affections neurologiques; infectieuses; nephrologiques; hematologiques et endocrino-metaboliques temoin du caractere pluridisciplinaire du service. Pres de 55 pour cent des affections observees relevaient de la pathologie d'urgence alors que le service n'est pas equipe en consequence. Ceci explique en partie; un taux de mortalite de 25;21 pour cent dont 40;94 pour cent de deces survenant dans les 48 heures suivant l'hospitalisation

Serological evidence in sheep suggesting phlebovirus circulation in a Rift Valley fever enzootic area in Burkina Faso.

Within the Phlebovirus serogroup, Rift Valley fever (RVF) virus is endemo-enzootic in the African sahelian zone. Recently an RVF epizootic in West Africa prompted a serosurvey in the major sheep and cattle raising areas. Because of the close antigenic relationship between the phleboviruses it appeared of interest to evaluate the prevalence of the other phleboviruses also. In 1987, 482 sheep serum samples were collected in 2 different ecological zones of Burkina Faso and tested for the presence of phlebovirus antibodies. A sensitive but non-specific immunofluorescent antibody test and a specific enzyme-linked immunosorbent assay (ELISA) were used, with the following African phlebovirus antigens: Rift Valley fever (RVF), Arumowot, Gabek Forest, Gordil, Saint Floris and Odrenisrou. A total of 15.8% of the sera sampled had anti-RVF antibody in the ELISA. RVF virus appeared to be more active in drier areas such as the sahelian region, known to be an enzootic area for the disease. Antibodies to other phleboviruses were found in 11.8% of the samples, independent of RVF virus activity. It is assumed that sheep can be infected by different phleboviruses.