Le Syndrôme d'Alagille à propos d'un cas au CNHU-HKM de Cotonou, Bénin

Le syndrome d'Alagille, est une affection multisystémique héréditaire de transmission autosomique dominante. Sa prévalence est estimée à 1 pour 70 000 à 100 000 naissances vivantes. Nous rapportons l'observation d'un jeune nourrisson de 6 semaines suivi au CNHU-HKM de Cotonou, Bénin. Le diagnostic est basé sur l'association de la dysmorphie faciale, des atteintes hépatiques, cardiaques, et oculaires. L'évolution a été défavorable avec décès au bout d'une semaine témoignant du pronostic sombre des formes avec cardiopathie complexe associée. Le syndrome d'Alagille reste un diagnostic différentiel des syndromes de cholestase chronique en pédiatrie et mérite d'être connu

[Economic hardship and fallout on households of the management of hydrocephalus in Benin]. / Impact socio-économique et familial du traitement de l'hydrocéphalie au Bénin.

Objectives: The socioeconomic profile of households and families of children attending hospital for hydrocephalus were documented and analysed. Main costs related to diagnosis and care were reviewed. The emotional fallout and social well-being of families were also analysed. Methods: This retrospective cross-sectional study (January 2006 to January 2015) was based on costs borne by households and families for neurosurgical care of children with hydrocephalus. Results: Sixty children (1 day to 12 years old) had been hospitalized for hydrocephalus in Cotonou-Benin. In 19 cases, the families were single-parent families. In 44 cases, the parents were self-employed workers or private company employees. Public servants, eligible for national health system assistance, accounted for a mere 16 cases. Twenty six children did not receive any financial support, whereas the total average care-related out-of-pocket expenditure for families during the hospital stay was approximately €1,777 (1,117,500 FCFA), i.e. almost 14 times the average monthly income reported by the parents (82,600 FCFA ­ approximately €120). After hospitalization, 31 mothers had lost their jobs and 21 couples experienced marital issues and their plans to have children. Twelve recent separations were recorded, as well as one indirect maternal death related to depression. Conclusion: In Benin Republic, surgical care for paediatric hydrocephalus represents catastrophic out-of-pocket expenditures for households and families and other living expenses. Families experience significant emotional fallout with effects on couple relationships and survival.

Peritoneal Dialysis to Treat Patients with Acute Kidney Injury-The Saving Young Lives Experience in West Africa: Proceedings of the Saving Young Lives Session at the First International Conference of Dialysis in West Africa, Dakar, Senegal, December 2015.

In December 2015, as part of the First African Dialysis Conference organized in Dakar, Senegal, 5 physicians from West African countries who have participated in the Saving Young Lives Program reviewed their experiences establishing peritoneal dialysis (PD) programs to treat patients with acute kidney injury (AKI). Thus far, nearly 200 patients have received PD treatment in these countries. The interaction and discussion amongst the participants at the meeting was meaningful and informative. The presentations highlighted the creativity, conviction, and determination of the physicians in overcoming the various barriers and challenges they encountered to establish PD/AKI programs. Hopefully, these successes and the increased awareness of the importance of early diagnosis and treatment of AKI will inspire much needed support from government, hospital, and international organizations.

Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin.

BACKGROUND: Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection. METHODS: Parasite isolates from Beninese children or women presenting with, respectively, CM or PAM were collected along with samples from patients with uncomplicated malaria (UM). We assessed the transcript level of var genes by RT-qPCR and the expression of PfEMP-1 proteins by LC-MS/MS. RESULTS: Var genes encoding DC8 and Group A PfEMP-1 were transcribed more often and at higher levels in cerebral malaria vs. uncomplicated malaria patients. LC-MS/MS identified peptides from group A, DC8 PfEMP-1 more frequently in cerebral malaria than in uncomplicated malaria and pregnancy-associated malaria samples. CONCLUSION: This is the first study to show association between PfEMP-1 subtype and disease outcome by direct analysis of parasites proteome. The results corroborate that group A and specifically the PfEMP-1 types DC8 are universally associated with cerebral malaria. This is a crucial observation for promoting studies on malaria pathogenesis.

Possible association of the Plasmodium falciparum T1526C resa2 gene mutation with severe malaria.

BACKGROUND: Plasmodium falciparum exports proteins that remodel the erythrocyte membrane. One such protein, called Pf155/RESA (RESA1) contributes to parasite fitness, optimizing parasite survival during febrile episodes. Resa1 gene is a member of a small family comprising three highly related genes. Preliminary evidence led to a search for clues indicating the involvement of RESA2 protein in the pathophysiology of malaria. In the present study, cDNA sequence of resa2 gene was obtained from two different strains. The proportion of P. falciparum isolates having a non-stop T1526C mutation in resa2 gene was evaluated and the association of this genotype with severity of malaria was investigated. METHODS: Resa2 cDNAs of two different strains (a patient isolate and K1 culture adapted strain) was obtained by RT-PCR and DNA sequencing was performed to confirm its gene structure. The proportion of isolates having a T1526C mutation was evaluated using a PCR-RFLP methodology on groups of severe malaria and uncomplicated patients recruited in 1991-1994 in Senegal and in 2009 in Benin. RESULTS: A unique ORF with an internal translation stop was found in the patient isolate (Genbank access number : JN183870), while the K1 strain harboured the T1526C mutation (Genbank access number : JN183869) which affects the internal stop codon and restores a full length coding sequence. About 14% of isolates obtained from Senegal and Benin harboured mutant T1526C parasites. Some isolates had both wild and mutant resa alleles. The analysis excluding those mixed isolates showed that the resa2 T1526C mutation was found more frequently in severe malaria cases than in uncomplicated cases (p = 0.008). The association of the presence of the mutant allele and parasitaemia >4% was shown in multivariate analysis (p = 0.03) in the group of Beninese children. CONCLUSIONS: All T1526C mutant parasites theoretically have the ability to give rise to a full-length RESA2 protein. This study raises the hypothesis that the RESA2 protein could favour high-density infections. Other studies in various geographic settings and probably including more patients are now required to replicate these results and to answer the questions raised by these results.

Plasmodium falciparum parasites causing cerebral malaria share variant surface antigens, but are they specific?

BACKGROUND: Variant surface antigens (VSA) expressed on the surface of Plasmodium falciparum-infected red blood cells constitute a key for parasite sequestration and immune evasion. In distinct malaria pathologies, such as placental malaria, specific antibody response against VSA provides protection. This study investigated the antibody response specifically directed against VSA expressed by parasites isolated from individuals presenting a given type of clinical presentation. METHODS: Plasma and isolates were obtained from four groups of Beninese subjects: healthy adults, patients presenting uncomplicated malaria (UM), cerebral malaria (CM), or pregnancy-associated malaria (PAM). The reactivity of plasma samples from each clinical group was measured by flow cytometry against parasites isolated from individuals from each clinical group. RESULTS: Antibody responses against VSAUM were predominant in CM, UM and HA plasmas. When analysed according to age in all plasma groups, anti-VSACM and -VSAUM antibody levels were similar until six years of age. In older groups (6-18 and >19 years of age), VSAUM antibody levels were higher than VSACM antibody levels (P = .01, P = .0008, respectively). Mean MFI values, measured in all plasmas groups except the PAM plasmas, remained low for anti-VSAPAM antibodies and did not vary with age. One month after infection the level of anti-VSA antibodies able to recognize heterologous VSACM variants was increased in CM patients. In UM patients, antibody levels directed against heterologous VSAUM were similar, both during the infection and one month later. CONCLUSIONS: In conclusion, this study suggests the existence of serologically distinct VSACM and VSAUM. CM isolates were shown to share common epitopes. Specific antibody response to VSAUM was predominant, suggesting a relative low diversity of VSAUM in the study area.