Crise vaso-occlusive drépanocytaire sévère: aspects cliniques, étiologiques et thérapeutiques au CHU Sylvanus Olympio de Lomé / Clinical, aetiological and therapeutic features of severe sickle cell related vaso-occlusive crisis at the Sylvanus Olympio University Hospital, Lomé

Introduction: la crise vaso-occlusive (CVO) est la plus fréquente manifestation de la drépanocytose et la première cause d´hospitalisation des enfants atteints. L´objectif de cette étude est de décrire les aspects cliniques des CVO sévères, de déterminer les étiologies des syndromes infectieux qui les accompagnent et de décrire leur prise en charge. Méthodes: il s'agit d'une étude transversale descriptive portant sur 137 drépanocytaires majeurs hospitalisés pour CVO sévères du 1er janvier 2009 au 31 décembre 2011 dans le service de pédiatrie du CHU Sylvanus Olympio. Résultats: les drépanocytaires homozygotes SS étaient les plus nombreux (n=98; 71,5%), suivis des doubles hétérozygotes SC (n=28; 20,5). Le délai moyen de consultation était de 4,7 ± 4,4 jours. Le traitement avant l´admission comportait des antibiotiques (28,5%). Les CVO étaient surtout ostéo-articulaires (70,8%). Dans 98,5% des cas, une infection bactérienne associée a été confirmée (48,9%) ou présumée (49,6%). Les principales étiologies étaient le syndrome thoracique aigu (26,3%), l´ostéomyélite aiguë (10,9%), l´infection urinaire (6,6%), la septicémie (3,6%). Un germe a été isolé chez 14,6% des patients, Escherichia coli (30%) étaient en tête suivi de Klebsiella pneumoniae (25%), Staphylococcus aureus (15%), Salmonella typhi (10%), Streptococcus pneumoniae (5%), le Streptocoque D (5%), l´Enterobacter (5%) et l´Acinetobacter (5%). Le taux de mortalité était de 2,2%. La durée moyenne d´hospitalisation était de 11,4 ± 8,8 jours. Conclusion: les CVO drépanocytaires sévères sont en majorité associées aux infections bactériennes en milieu tropical. Une antibiothérapie adaptée et précoce constitue le moyen thérapeutique indispensable pour prévenir ou traiter ces patients.

Introduction: vaso-occlusive crisis (VOC) is the most common manifestation of sickle cell disease and the leading cause of hospitalization among affected children. The purpose of this study is to describe the clinical features of severe VOCs, to determine the etiologies of infectious syndromes that accompany them and to describe their management. Methods: we conducted a descriptive cross-sectional study of 137 adult patients with sickle cell disease hospitalised for severe VOC in the Paediatric Department of the Sylvanus Olympio University Hospital from 1 January 2009 to 31 December 2011. Results: the majority of patients (n=98; 71.5%) had homozygous sickle cell (SS), followed by double heterozygous SC disease (n=28; 20.5). The median of consultation time was 4.7 ± 4.4 days. Treatment before admission was based on antibiotics (28.5%). VOCs were mainly osteoarticular (70.8%). In 98.5% of cases, an associated bacterial infection was confirmed (48.9%) or suspected (49.6%). The main etiologies included acute chest syndrome (26.3%), acute osteomyelitis (10.9%), urinary tract infection (6.6%) and septicaemia (3.6%). One germ was isolated from 14.6% of patients: Escherichia coli (30%), followed by Klebsiella pneumoniae (25%), Staphylococcus aureus (15%), Salmonella typhi (10%), Streptococcus pneumoniae (5%), Streptococcus D (5%), Enterobacter (5%) and Acinetobacter (5%). Mortality rate was 2.2%. The average length of stay in hospital was 11.4 ± 8.8 days. Conclusion: severe sickle cell related vaso-occlusive crisis is mainly associated with bacterial infections in tropical environments. Appropriate and early antibiotic therapy is the essential therapeutic means to prevent or treat these patients.

Severe Acute Bacterial Infections in Children With Sickle Cell Disease in Togo.

BACKGROUND: Bacterial infections are considered a major cause of morbidity and mortality in patients, especially children, with sickle cell disease. OBJECTIVES: This study aims at determining, a year after the introduction of the 13-valent pneumococcal conjugate vaccine the distribution of severe acute bacterial infections and germs in children with sickle cell disease. PATIENTS AND METHODS: Records of children 0 to 15 years of age and admitted from January 1, 2015 to December 31, 2019 (5 y), were examined retrospectively in the four sickle cell monitoring units in Lomé. RESULTS: The main infections found were pleuropulmonary (46.1%), urinary tract (32.8%), and osteoarticular (9.3%). A germ was isolated in 139 of the 265 cases (52.4%). 65.5% of the microorganisms isolated were Gram-negative organisms, with mostly Escherichia coli (31.6%) , and Klebsiella pneumoniae (18%) being the main germs. They were mainly responsible of urinary tract and osteoarticular infections. The majority of these Enterobacteriaceae was Extended-Spectrum Beta-Lactamase-Producing (41.1%, n = 37). Gram-positive cocci were represented by Staphylococcus sp (25.9%), Streptococcus sp (4.3%), Streptococcus pneumoniae (2.9%), and Enterococcus (1.4%). Staphylococcus aureus was the most common germ in pleuropulmonary (40%), osteoarticular (47.3%), and sepsis (28.6%) infections. CONCLUSION: Even if the infections found remained classic, there is a redistribution of germs with a decline in Salmonella and increase of Escherichia coli , Klebsiella pneumoniae , and Staphylococcus aureus .

Management of acute sickle cell priapism in an African (Togo) pediatric department includes conservative measures and intracavernous epinephrine which is safe and efficacious.

Priapism is a well-known urologic complication of sickle cell anemia. This study describes the results of a protocol for the treatment of acute priapism by intracavernous injection of epinephrine due to unavailability of etilefrine. A descriptive cross-sectional study of 18 cases of acute priapism in sickle cell patients treated in the pediatric department of the Sylvanus Olympio CHU from January 1 to December 31, 2020. The average age was 21.7 ± 7.7 years, the youngest patient was 8 and the oldest was 32 years old. Students represented 61.1% of the patients. The hemoglobin profiles were homozygous SS (n = 14) and double heterozygous SC (n = 4). Most of the crisis (83.3%) occurred at night. Most of the patients (66.7%) came to the hospital before the sixth hour of crisis, one patient came by the 48th hour. Walking was the most self-relief method tried by patients (67%). It was followed by a cold penile bath, attempted urination, body bath, and lastly lukewarm bath. Fourteen patients had a history of chronic intermittent priapism. The average pain intensity was 9.5 ± 0.9 with restlessness (33.3%) and crying (33.3%). Fifteen patients were treated upon admission with an intracavernosal injection of epinephrine, and three patients were first drained. Thirteen patients achieved remission immediately, while five patients required a second injection and only one had to be drained before remission. Tolerance was good. One patient had a borderline systolic blood pressure. One erectile weakness case was noticed and no cases of sexual impotence. Epinephrine by intracavernosal injection is an efficient treatment for acute priapism in sickle cell patients. Epinephrine, which has a good tolerance in pediatric and young adult patients, should be used in lieu of etilefrine due to its unavailability in areas where it is unavailable.

MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients' Cells.

Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A ∆50 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease. Some patients with PS carry other LMNA mutations and are named "HGPS-like" patients. They produce progerin and/or other truncated prelamin A isoforms (∆35 and ∆90). We previously found that MG132, a proteasome inhibitor, induced progerin clearance in classical HGPS through autophagy activation and splicing regulation. Here, we show that MG132 induces aberrant prelamin A clearance and improves cellular phenotypes in HGPS-like patients' cells other than those previously described in classical HGPS. These results provide preclinical proof of principle for the use of a promising class of molecules toward a potential therapy for children with HGPS-like or classical HGPS.

The development of an international childhood cancer hospital register database in 13 African countries. A project of the French African Pediatric Oncology Group (GFAOP).

BACKGROUND AND AIM: The establishment of an international hospital-based register (HBR) for the French African Pediatric Oncology Group (GFAOP) was a necessary step in the group's clinical research program. With help from the Sanofi Espoir Foundation's "My Child Matters" program, the GFAOP resolved to develop an international HBR network to collect quality data on children attending the Pediatric Oncology Units (POUs). METHODS: All children entering POUs from January 2016 to December 2018 were registered using an online questionnaire. Data collection included information on diagnosis, disease stage, demographics, socioeconomic status, and outcome. An intensive training program was developed to improve both data quality and quantity. RESULTS: Among the 3348 children registered, 3230 had a suspected cancer, 681 were not confirmed. A diagnosis was confirmed on radiological, clinical, or histological examination for 2549 children including Burkitt lymphoma (516: 20%)-the most frequent diagnosis, Wilms' tumor (459: 18%), retinoblastoma (357: 14%), and acute lymphoblastic leukemia (345: 13%). Of these, 2187 children were treated. Early deaths, abandonment, economic difficulties, and lack of equipment were some of the reasons offered to explain the numbers of undiagnosed and untreated children. Vital status is known for 1994 children: 1187 died and 807 were alive, 551 of these with a follow-up > 12 months. CONCLUSION: This work has provided reliable data on children attending the POUs, especially clarifying reasons and occasions for care rupture. The data will help to identify material, human resources, and staff training needs, to evaluate progress, and to encourage consideration of pediatric cancer in national cancer plans.

Hutchinson-Gilford Progeria syndrome: Report of the first Togolese case.

The aim of this article is to describe the first case of Hutchinson-Gilford Progeria Syndrome (HGPS) in Togo and review all Africans cases. Our patient was a 12.8-year-old Togolese boy followed in our unit till he was 15-year-old for HGPS. He was the only child of non-consanguineous parents. The phenotypic findings were craniofacial dysmorphy, dwarfism, lipodystrophy, diffusely scattered hyperpigmented foci, pyriform thorax, nail dystrophy, decreased joint mobility, and camptodactyly. He had characteristic facies with prominent forehead, prominent eyes, absent ear lobule, thin nasal skin, convex nasal profile, micrognathia, and crowded teeth. Radiologicals findings were bilateral coxa valga, pyriform thorax, and acro-osteolysis. We sequenced the entire coding region of LMNA gene, and mutation analysis revealed a heterozygous mutation c.1824C>T (p.Gly608Gly). Our patient is therefore the fifth African and the fourth with classical mutation, first of Western Africa, and second of (sub-Saharan) African black race. The recurrence of HGPS is low like the cause is neomutation or germinal mosaicism.

Advanced Burkitt Lymphoma in Sub-Saharan Africa Pediatric Units: Results of the Third Prospective Multicenter Study of the Groupe Franco-Africain d'Oncologie Pédiatrique.

PURPOSE: To evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-Saharan African pediatric centers. PATIENTS AND METHODS: Children with advanced-stage BL (stages II bulky, III, and IV) treated with the GFAOP-Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015 were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2 induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 consolidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the dose of 3 g/m2. RESULTS: Four hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease. Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment. Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110 are known to be in CR with a follow-up > 1 year, indicating a high rate of loss to follow-up. Twelve-month overall survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus 57% (P = .0062) beyond 34 days. CONCLUSION: The GFA-LMB2009 protocol improved patients' survival. Early dose intensity of treatment is a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.

Treatment of Wilms Tumor in Sub-Saharan Africa: Results of the Second French African Pediatric Oncology Group Study.

PURPOSE: Multidisciplinary management of Wilms tumor has been defined through multicenter prospective studies and an average expected patient cure rate of 90%. In sub-Saharan Africa, such studies are uncommon. After the encouraging results of the first Groupe Franco-Africain d'Oncologie Pédiatrique (GFAOP) study, we report the results of the GFAOP-NEPHRO-02 study using an adaptation of the International Society of Paediatric Oncology 2001 protocol. PATIENTS AND METHODS: From April 1, 2005, to March 31, 2011, seven African units participated in a nonrandomized prospective study. All patients who were referred with a clinical and radiologic diagnosis of renal tumor were screened. Those older than age 6 months and younger than 18 years with a unilateral tumor previously untreated were pre-included and received preoperative chemotherapy. Patients with unfavorable histology or with a tumor other than Wilms, or with a nonresponding stage IV tumor were excluded secondarily. RESULTS: Three hundred thirteen patients were initially screened. Two hundred fifty-seven patients were pre-included and 169 with histologic confirmation of intermediate-risk nephroblastoma were registered in the study and administered postoperative treatment. Thirty-one percent of patients were classified as stage I, 38% stage II, 24% stage III, and 7% stage IV. Radiotherapy was not available for any stage III patients. Three-year overall survival rate was 72% for all study patients and 73% for those with localized disease. CONCLUSION: It was possible to conduct sub-Saharan African multicenter therapeutic studies within the framework of GFAOP. Survival results were satisfactory. Improvements in procedure, data collection, and outcome are expected in a new study. Radiotherapy is needed to reduce the relapse rate in patients with stage III disease.

[Etiological and evolving profile of renal disability of children in hospital in Togo]. / Profil étiologique et évolutif de l'insuffisance rénale de l'enfant en milieu hospitalier au Togo.

OBJECTIVE: To determine the etiological and evolutionary profile of renal failure of chidren in Togo. METHODS: This is a cross-sectional study over the period of 12 months (2016-2017) including children aged 1 to 18 years hospitalized in the pediatric ward of Sylvanus Olympio university teaching hospital of Lome (Togo) for renal failure. RESULTS: Of 2374 patients hospitalized in our unit, 58 (2.4%) had renal failure. The mean age was 8.17±4 years with a sex ratio of 1.32. The average consultation time was 11.9 days. The mean duration of hospitalization was 12.7±7.7 days. Thirty-seven patients (63.8%) were referred from a peripheral center. Thirty-seven children out of 58 (63.1%) were oligoanuric. Renal failure was acute in 94.8% and chronic in 5.2%. Anemia was found in 84.4% of children. The main etiologies found were severe malaria (63.8%), glomerulonephritis (10.3%) and nephrotic syndrome (10.3%). Thirteen children (22.4%) benefited from dialysis sessions. The evolution was favorable in 79.3% of the cases. CONCLUSION: The renal failure of child is relatively common in our daily practice. The low socio-economic level and the lack of adapted equipment make the care difficult.

Evidence of the impact of monovalent rotavirus vaccine on childhood acute gastroenteritis hospitalization in Togo.

BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in the immunization schedule of Togo in June 2014. We evaluated the impact of rotavirus vaccines on acute gastroenteritis (AGE) and rotavirus-associated hospitalizations in Togolese children. METHODS: Sentinel surveillance for AGE (defined as ≥3 liquid or semi-liquid stools/24 h lasting <7 days) hospitalizations among children <5 years of age was conducted in two sites in the capital city, Lome. ELISA was used for diagnosis of rotavirus infection in children with AGE. Additionally, review of hospitalization registers was performed at five hospitals to assess trends in AGE hospitalizations among children aged <5 years. For the vaccine impact assessment, pre-rotavirus vaccine introduction (July 2010-June 2014) and post-rotavirus vaccine introduction (July 2014-June 2016) periods were compared for annual changes in proportions of hospitalizations associated with AGE and rotavirus. RESULTS: During the pre-vaccine period, sentinel surveillance showed that 1017 patients were enrolled and 57% (range, 53-62%) tested positive for rotavirus, declining to 42% (23% reduction) in the first post-vaccine year and to 26% (53% reduction) in the second post-vaccine year; declines were most marked among infants. The patient register review showed that, compared with pre-vaccine rotavirus seasons, declines in hospitalizations due to all-cause AGE during post-vaccine rotavirus seasons were 48% among <1 year age-group in both first and second years following vaccine introduction. Among 1-4 year olds no reduction was noted in the first year and a 19% decline occurred in the second year. CONCLUSIONS: We report rapid and marked reduction in the number of AGE hospitalizations and the proportion of AGE hospitalizations attributable to rotavirus in the first two years post- RV1 implementation in Togo. It is necessary to monitor long-term vaccine impact on rotavirus disease burden through continued surveillance.

Child mortality infected with HIV1 followed in 40 pediatric care sites in Togo.

INTRODUCTION: The infection in pediatric HIV is the reason a lot of problems in Africa The objective of our study were to identify factors associated with mortality during follow-up of children receiving antiretroviral therapy in Togo. METHODS: It was a cross-sectional study of 870 children aged files from 7 weeks to 15 years infected with HIV on antiretroviral treatment, covering the period 1 January 2001 to 31 December 2010 taking in 40 sites medical management in Togo. Data processing was done with the software Epi-Info 6.04d and duplicates were treated by the Software ESOPE. RESULTS: All patients were infected with HIV-1. In total forty six (46) deaths is 5.29% of the overall cohort were reported in our series. The lethality of the overall cohort followed for 60 months was 5.29%. The survival rate of the overall effective monitoring in our study was 89.2%. Fifty-eight percent (58%) of deaths had affected children in a state of severe malnutrition and forty two percent (42%) in a state of moderate malnutrition. Sixty two percent (62%) of children under HAART treatment died benefited monitoring a psychologist. CONCLUSION: The diagnostic inadequacies of pediatric HIV strike the prognosis of infected children. Efforts still needs to be done to improve the load take pediatric HIV in Togo.

Knowledge, attitude and practice of the mothers with anemia of children under five years old in the peadiatric department at Sylvanus Olympio teaching hospital in Lomé.

BACKGROUND: Anemia remains a major cause of morbidity and mortality of children in Togo despite of prevention effort, due to the parents lack of implication. AIM: To determine the knowledges, attitudes and practices of mothers, with anemia ofchildren under five years old Methods : Knowledge Attitudes and Practice survey from the first of february to 31 ofmarch 2012, about an interview of a hundred mothers with children under 5, randomly selected in the consultation, vaccination waiting rooms and in the hospitalisation. RESULTS: Forty mothers had never heard about anemia. Health personnel was the main source of mother's information (29%), mass media represented 8% of mothers information source (radio 5%; television 3%). The decreased of blood in the body is the most given definition from the mothers (44%). Malaria (24%) and malnutrition (19%) were the main causes cited by mothers. Iron deficiency has been mentioned by 3% of the mothers. Palmar - plantar pallor (32%) was the clinical signe the best known by the mothers. Most of the mothers (90%) had never assist to an information education and communication message about anemia prevention. When their children had anemia, 25 mothers (65,8%) took their children to the health center, five mothers (13,2%) had given tomatoes. The use of iron in prophylactic treatment was known by 43% of the mothers. The blend tomatoes and milk was the prophylactic treatment mentioned by 3% of the mothers. Most of the mothers (77%) would advice a mother with a children suffering from anemia to take him to the hospital. The knowledge of anemia by the mothers was correlated to then level of instruction. But the knowledge of prevention did not depend on the instruction level. CONCLUSION: anemia is not well known by the mothers of under five children. It's causes, it's treatment are not well known. Mass media are not very implicated on the subject. The reduction of it's frequency goes by information education and communication activities.

Antisense-Based Progerin Downregulation in HGPS-Like Patients' Cells.

Progeroid laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS, OMIM #176670), are premature and accelerated aging diseases caused by defects in nuclear A-type Lamins. Most HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type Lamins. This mutation activates a cryptic splice site leading to the deletion of 50 amino acids at its carboxy-terminal domain, resulting in a truncated and permanently farnesylated Prelamin A called Prelamin A Δ50 or Progerin. Some patients carry other LMNA mutations affecting exon 11 splicing and are named "HGPS-like" patients. They also produce Progerin and/or other truncated Prelamin A isoforms (Δ35 and Δ90) at the transcriptional and/or protein level. The results we present show that morpholino antisense oligonucleotides (AON) prevent pathogenic LMNA splicing, markedly reducing the accumulation of Progerin and/or other truncated Prelamin A isoforms (Prelamin A Δ35, Prelamin A Δ90) in HGPS-like patients' cells. Finally, a patient affected with Mandibuloacral Dysplasia type B (MAD-B, carrying a homozygous mutation in ZMPSTE24, encoding an enzyme involved in Prelamin A maturation, leading to accumulation of wild type farnesylated Prelamin A), was also included in this study. These results provide preclinical proof of principle for the use of a personalized antisense approach in HGPS-like and MAD-B patients, who may therefore be eligible for inclusion in a therapeutic trial based on this approach, together with classical HGPS patients.