Implementing haemophilia care in Senegal, West Africa.

Despite significant progres on haemophilia care in developed world, this disease remains unknown in many sub-Saharan African countries. The objectives of this article were to report Senegalese experience on the management of haemophilia care through 18 years of follow-up. This cohort study included 140 patients (127 haemophilia A, 13 haemophilia B), followed in Dakar's haemophilia treatment centre from 1995 to 2012. Our study reported a prevalence of 2.3/100,000 male births, accounting for 11.6% of what is expected in Senegal. From the period 1995-2003 to 2004-2012, significant progress was seen including 67.9% increase in new patient's identification, 11.3 years reduction in mean age at diagnosis (from 15.5 to 4.2 years), lower mortality rate (from 15.3% to 6.8%) and age at death evolved from 6.5 to 23.3 years. Of the 50 haemophilia A patients who were tested for inhibitor presence, 10 were positive (eight severe and two moderate) that is prevalence of 20%. All patients were low responders since inhibitor titre was between 1.5 and 3.8 BU. Disabilities were seen in 36.5% of patients above 20 years old who had musculoskeletal sequels and 39% had no scholar or professional activities in our setting. Implementing haemophilia care in sub-Saharan Africa is a great challenge as this disease is not yet counted in national health problems in many countries. Lessons learned from this study show a significant improvement in diagnosis and prognosis parameters. This emphasizes the needs to set up such follow-up initiatives and to enhance medical and lay cooperation for better results.

[Predictive factors of chronic complications in adult sickle cell anemia patients in Dakar, Senegal]. / Facteurs prédictifs des complications chroniques de la drépanocytose homozygote chez l'adulte à Dakar (Sénégal).

PURPOSE: Chronic complications of sickle cell disease (SS) usually involve irreversible organ damage. Several genetic factors have been shown to have predicative value for chronic complications but these data are not always available. The purpose of this study was to assess the value of sociodemographic and clinicobiological features in predicting chronic complications. METHODS: This study included a total of 229 adult SS patients who underwent quarterly follow-up examinations for at least 10 years (range, 10 - 16). All sociodemographic and clinicobiological data were recorded. Screening for complications was performed at least once every three years. The risk of developing chronic complications was analyzed in function of patient follow-up data. RESULTS: Mean patient age was 28.6 years (range, 20 - 57) and sex ratio was 1.3. Prevalence of chronic complications was 34.9% (80/229). The most common complication was bone necrosis in 27 cases (11.7%) followed by gallstones in 24 (10.4%). The only sociodemographic factor with predictive value was patient age (p=0.0008). Multivariate analysis identified two clinicobiological factors with predictive value. History of transfusion was associated with a 3-fold higher risk while hemoglobin F level was associated with decreased risk. CONCLUSION: In this study, age and low hemoglobin F level were the only predictive factors of chronic complications in SS patients.

[Residual risk of transmission of HIV and HBV, in Senegalese national blood bank from 2003 to 2005]. / Risque résiduel de transmission du VIH et du VHB par transfusion sanguine entre 2003 et 2005 au Centre national de transfusion sanguine de Dakar (Sénégal).

BACKGROUND AND AIM: Using of safety blood products did not stop improving these last years. The use of effective methods as well immunologicals as virologicals ones really reduces risk associated to blood transfusion. However, it persists residual risk (RR) of transfusion transmitted viral diseases. The aim of our study was to detect cases of seroconversion for HIV,and HBV among donors in the Senegalese national blood bank. And then, we estimated the RR of these virus. METHODS: We led a transverse retrospective study from 2003 (January 1st) to 2005 (December 31st). Had been included donors with at least two donations of blood during the period of study. They had to be seronegative for HIV and HBV after the first donation. All donors with only one donation had been excluded. RR was estimated by multiplying incidence rates by the durations of the window periods. RESULTS: During 3 years, we collected 425,503 donations; 388 were positive for HIV and 4240 for HBV. But we noted only two cases of seroconversion for HIV and 23 for HBV. So, RR estimated was 3,5 in 100,000 donation for HIV and 102,45 in 100,000 donations for VHB. CONCLUSION: It emerges from this study that the risk of blood transmitted virus is always high. Introduction of more sensitive tests (as nucleic acid testing) would allow us to deliver more safety products.

[Prevention of transfusion transmitted malaria in endemic area]. / Prévention du paludisme post-transfusionnel en zone d'endémie.

BACKGROUND: Malaria is a real public health problem in Africa; more than 300 million new cases and approximately two million deaths arise every year. In spite of the blood transfusion is a potential way of Plasmodium transmission, there is no consensus for measures to prevent post-transfusion malaria in endemic area. This work aimed at comparing some tools and to discuss various strategies to be implemented. MATERIAL AND METHODS: The study concerned 3001 blood donors recruited in seven blood transfusion centers in Senegal during two periods: dry season (June-July, 2003) and rainy season (October-November, 2003). We evaluated the efficiency of the selection questionnaire for the blood donors to exclude those who are potentially asymptomatic carriers of the Plasmodium. Every donation was screened for pLDH antigen and antibodies against Plasmodium by Elisa technique (DiaMed, Cressier sur Morat, Suisse), morphological tests was also performed, as well as the screening of HIV, HBs Ag, HCV Ab and syphilis. RESULTS: Median age of blood donors was of 27.7 years. Anti-Plasmodium antibodies prevalence was 65.3% and pLDH antigen was of 0.53%, all positivity was confirmed by microscopy. The prevalence of the other infectious markers was 11.7% for HBs Ag; 0.83% for syphilis; 0.49% for HCV Ab and 0.46% for HIV Ab. The risk factors associated with an asymptomatic carrier of Plasmodium were: the rainy season, irregular character of the blood donations, high frequency of malaria attacks in the past, and absence of treatment during the last episode. CONCLUSION: Plasmodium represents the third risk of blood transmitted infectious agents after hepatitis B virus, syphilis, and before HCV and HIV in Senegal. The medical questionnaire is not useful enough for asymptomatic carriers deferral, and we propose to introduce Plasmodium screening. The screening for Plasmodium pLDH by Elisa technique seems to be the best tool in endemic area and the strategy of systematic screening is the most suited in terms of blood transfusion safety.

[Monoclonal gammapathy of undetermined significance and autoimmune disease: description of three cases in Senegal]. / Gammapathies monoclonales de signification indéterminée et maladies auto-immunes: étude de trois observations sénégalaises.

Monoclonal gammapathy of undetermined significance (MGUS) has rarely been reported in African literature. The purpose of this article is to describe 3 cases of MGUS observed in women aged 63, 54, and 44 years in Senegal. All three patients had previously documented autoimmune disease, i.e., auto-immune thrombopenia, multiple auto-immune disease (comprising Sjögren's syndrome, polymyositis and vitiligo), and Sjögren's syndrome. Diagnosis of MGUS was made thanks to routine protein electrophoresis that demonstrated a monoclonal peak in the gammaglobulin area in all patients. Serum protein binding showed the IgG lambda subtype in one case and IgG kappa subtype in two cases. Medullogram findings were unremarkable with nondystrophic plasma cell rates ranging from 1 to 4%. Bisphophonate therapy was undertaken along with the recommended treatments for the associated autoimmune diseases, i.e., prednisone, hydroxychloroquine, and methotrexate. Treatment was successful in all three patients with stabilization of the associated diseases and of the monoclonal peak on subsequent electrophoresis. As of this writing, the mean duration of follow-up was 3 years. MGUS that has been uncommon in the African hospital setting should be screened for in all older patients or in patients presenting infection (especially due to virus) or autoimmune disease (as in the three cases presented herein). More systematic use of serum protein electrophoresis should reveal an increased incidence of MGUS. Diagnosis of MGUS requires regular clinical and laboratory surveillance due to the risk for complications of malignant hemopathies, especially multiple myeloma.

[Periodontal conditions in young sickle cell anemia Senegalese patients]. / Etat parodontal du jeune sénégalais drépanocytaire homozygote.

INTRODUCTION: The oral cavity holds a complex microbial flora including periodontal pathogens. The infectious complications are common in sickle cell anaemia, which reaches 1% of the population in Senegal. The objective of this study is to assess periodontal conditions in young Senegalese sickle cell anaemics. PATIENTS AND METHODS: A sample of 82 subjects aged between 15 and 34 years with mean at 25.2 years +/- 4.6 was made up, including 35 homozygous and 47 non homozygous. Plaque index, gingival index and papillary bleeding index, tooth mobility and clinical attachment loss were assessed. Partial correlation between periodontal indexes and haemoglobin and hematocrit controlling for plaque index was performed. RESULTS: No significant statistical differences were found for periodontal indexes and clinical attachment loss between the two groups, even if homozygous show higher values. Periodontitis is less frequent in homozygous and odd ratio show protective effect of sickle cell anaemia (OR = 0.381, IC at 95% = [0.130; 1.1 18]). Tooth mobility is significantly increased in homozygous with mean at 1.0 +/- 0.8 versus 0.5 +/- 0.4 in control group (p = 0.000). Partial correlation show significant negative association between haematocrit and papillary bleeding index in homozygous (p = 0.045). CONCLUSIONS: The hypothesis that sickle cell anaemia can affect periodontal conditions and worsen periodontal diseases is to be considered even if it has not been proved as risk factor. Increased tooth mobility could be marker of periodontal risk in homozygous.

[Von Willebrand disease and menorrhagia]. / Maladie de Willebrand et ménorragie.

INTRODUCTION: Known since over than seventy years, von willebrand disaese is the most common herediary bleeding disorder. This condition was first described by Pr. Willebrand in 1926 in a family with (positive) history of excesive bleeding tendency. Von Willebrand desease is characterized by a lifelong tendency toward easy spontaneous mucosal or post operative bleeding. In females, excessive or prolonged menorrhagia could be a sign of von willebrand desease; symptoms that are often misunderstood to be gynecologic rather than hematologic problem. In the present work, we have tried to screen for this anomaly in females with menorrhagia, following a simple anamnestic, clinical and biological protocol. PATIENTS AND METHOD: In a seventeen month study, fifty two procreating females with menorrhagia were recruited in the haematology laboratory of Aristide le Dantec hospital with the cooperation of gynecology and obstetric departements of Aristide Le Dantec, Abass Ndao and grand yoff Hospitals. RESULTS: Eight patients were revealed to be von willebrand positive (prevalence: 15%). The diagnosis was retained on the basis of epidemiological, clinical and biological data. CONCLUSION: These simple and accessible criteria should allow better handling of patients with hemorragic disorders.

[Seroprevalence of hepatitis C virus (HCV) in Senegalease blood donors]. / Seroprevalence du virus de l'hepatite C (VHC) chez les donneurs de sang au Senegal.

INTRODUCTION: Hepatitis C virus (HCV) is an important problem of public health in the world according to its transmission mode and its pathogenesis. The risk of blood transmission has led to be the systematic screening of blood donors in the world. In Senegal no study about HCV prevalence on the general population and also has been done. The aim of our study was to determine HCV prevalence in blood donors and the rate of co-infection with hepatitis B (HCV/HBV) or with HIV infection (HCV/HIV). MATERIALS AND METHODS: This study had been done in the National Blood Transfusion Centre (CNTS) in Dakar. Two different techniques has been used for the assessment HCV: 1/ ELISA technique and 2/ Immunoblot RIBA as confirmation test. RESULTS: Our study relates to 1565 blood donors recruited in CNTS during 2002. 369 of them were new blood donors with 365 females and 1200 males. The mean average was 30.5 +/- 9.5 years, ranged from 18 to 59 years. HCV ELISA test were positive in 22 plasma samples and one of them were co-infected with hepatitis B (HCV/HBV). Four out of these 22 samples have been confirmed positive to RIBA test and three of them were not determined. HCV seroprevalence were 1.4% after ELISA and 0.25% after RIBA testing. This seroprevalence were similar in male and in female and higher in new blood donors than in regular blood donors. CONCLUSION: Our results reinforce the necessity to screen hepatitis C virus in all Senegalese blood transfusion centres.

[Relation between lupus-antiphospholipids antibodies and heart disorders]. / Relation lupus-anticorps antiphospholipides et cardiopathie lupique.

BACKGROUND AND AIM: Antiphospholipids antibodies (APL) are autoantibodies found in lupus erythematosus and disorders like. Their frequency varies between 2 and 62% according to the literature. An increased frequency of cardiac disorders in antiphospholipids (APL) positive lupus has been reported. The aim of our study was to evaluate the role of APL as an independent risk factor of cardiac disorders in patients with systemic lupus erythematosus. MATERIAL AND METHOD: A prospective study during 14 months has been designed with the cooperation of dermatologic, internal medicine and cardiology departments of the Aristide Le Dantec hospital of Dakar. Platelets count (Beckmann Coulter analyzer), activated partial thromboplastin time (Diagnostiga stago analyzer) and antiphospholipids antibodies (Elisa) were determined. RESULTS: 37 patients affected by lupus were included in this study with a net feminine prevalence (89%); 8 (14.6%) had APL's significant results and 20 presented an echographic heart abnormality. The analysis of our data did not reveal an increased risk of cardiac diseases among APL positive lupic patients as compared to the negative group (p = 1). CONCLUSION: The presence of APL in patients with systemic lupus does not so seem to be an independant risk factor of heart diseases.

[Physical performance and thermoregulatory study of subjects with sickle cell trait during a sub-maximal exercise]. / Etude de la performance physique et de la thermoregulation des sujets porteurs du trait drepanocytaire au cours d'un exercice sous maximal.

The sickle cell trait is a genetic abnormality of red blood cells. It is due to the mutation of a parental gene, which rest Its to the substitution of glutamic acid by valin on beta globin chain of haemoglobin. The possibility for sickle cell trait carriers (SCT) to present any disturbance during predominantly anaerobic and aerobic exercises is unclear. Ten (10) subjects with sickle cell trait and 10 subjects control were studied during exercise test on cycloergometer. They were all students of the National Institute of Popular Education and Sport of Dakar. The mean of environmental temperature was 26 degrees C and humidity was 60 to 80%. After haematological analysis, a submaximal muscular exercise for one hour with 75% of maximal heart rate was done. We have determined heart rate, blood pressure, rectal and skin temperature during exercise. Haematological parameters shown any significant difference between the two groups. No significant difference was found in cardiocirculatory variables during maximal exercise in cycloergometer between control group and sickle cell trait group. The two groups have done submaximal exercise during 1 hour without particular difficulty. We have not observed a significant difference between the two groups in cardiovascular variables, rectal and skin temperature during exercise, and after 3 minutes of rest. These results show that subjects with SCT have physical capacity comparable with control subjects during a sub maximal exercise for 1 hour. We can assure that subjects with SCT in our country may participate in sports competition, as well as normal subjects (HbAA).

[Prevalence and morbidity of G6PD deficiency in sickle cell disease in the homozygote]. / Prevalence et morbidite du deficit en g6pd au cours de la drepanocytose homozygote.

Sickle cell disease and G6PD deficiency have similar prevalence of 8 to 10% in Senegalese population. Our objectives were to determine the prevalence of G6PD deficiency in Hb S carriers and normal subjects, and to assess the interaction of G6PD deficiency on clinical severity of sickle cell disease. G6PD activity was measured in 319 sickle cell patients and in 318 subjects without HbS. Clinical severity was compared in male homozygous sickle cell patients (11 with G6PD deficiency and 19 without deficit). In homozygous sickle cell patients, the G6PD status was assessed after correction of reticulocyte count following the micro-centrifugation method of Herz. We found that prevalence of G6PD deficiency was higher in sickle cell disease patients (21.6 %) than in normal subjects (12.3 %) (p = 0.001). No difference was found in the two groups of male sickle cell disease patients concerning number of vaso-occlusive crisis, number of transfusion, frequency of infectious episodes, number of chronic complications, disturbances on patient's activity and total index severity.

[Expression of proliferation marker Ki 67 in chronic lymphocytic leukemia]. / Expression du marqueur de proliferation Ki 67 dans les leucemies lymphoides chroniques.

Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of low proliferating mature B and T lymphocytes in the bone marrow and peripheral blood. The nuclear antigen Ki 67 is a protein detected in G1, S, G2 and M phases of the cell cycle, but not in G0, and thus, is a widely accepted proliferation marker of Human tumors. The aim of this study was to evaluate Ki 67 monoclonal antibody in CLL. We studied 48 patients diagnosed as CLL on the presence of clinical signs, over 4.109/l circulating lymphoid cells and immunophenotyping by flow cytometry using CD19, CD5, CD22, CD23, FMC7 and immunoglobulin light chains monoclonal antibodies. Ki 67 immunostaining was determined by Avidin Biotin Complex method. Our results allows to characterize between CLL: one group which proliferation rate (percentage of Ki 67 positive cells) was equal or less than 2%, represented by 14 cases (29,2%) with morphological aspect of typical CLL, one group which proliferation rate was between 3% and 9% represented by 32 cases (66,6%) with morphological aspect of polymorph CLL or prolymphocytic leukemia, and a last group with proliferation rate equal or up to 10% and corresponding to two cases (4,2%) of transformation of CLL to high grade Non Hodgkin lymphoma. There were no correlation between Matutes immunological score and proliferation rate, as this rate was 2.9% in score < 3 and 2.7% in score > 3. This study confirm the Ki 67 usefulness in studying cellular proliferation, and underline that CLL with polymorphic cytology are more proliferate than typical CLL. These data reinforce the notion that CLL is a disease with heterogeneity in clinical behavior, immunophenotype, cytogenetic, molecular aspects, and thus, prognostic.

[Non-Hodgkin's lymphoma in Dakar: study of 107 cases diagnosed between 1986 and 1998]. / Les lymphomes non hodgkiniens à Dakar: étude réalisée sur 107 cas diagnostiqués entre 1986 et 1998.

Non-Hodgkin's Lymphomas (NHL) are the most prevalent malignant hemopathies in Senegal. In this study we have investigated the epidemiological aspects considering the HIV infection pandemic, and evaluated the diagnosis means and evolutive features of this disease in Dakar. Between 1986 and 1998 (13 years), we collected 107 cases of NHL, all histologically confirmed. Average age of patients was 31.4 years (2-85 years) and sex ratio was 21. HIV infection was found in three out of 62 patients tested (4.8%). At moment of diagnosis, 72% of patients were in stage III or IV according to the Ann Arbor Staging System. Large cell lymphomas were predominant (67.2%), followed by small lymphocyte lymphomas (24.2%) and follicular lymphoma with 8.4% of cases. Localization of lymphomas was exclusively nodal (30.8%) or extra nodal (31.7%) or mixed (37.3%). In therapeutical field, 21.5% of patients were treated with only symptomatical means. Chemotherapy was used in 54 patients (78.2% of treated patients), surgery was performed in 6 patients (8.6%), association of radiotherapy and chemotherapy in 5 patients (7.2%) and 4 patients (5.7%) were treated with surgery + chemotherapy. The average survival time was 344 days. Four patients (3.7%) were alive 3 years after diagnosis and only 2 patients (1.8%) after 5 years.

[Maternal anaemia: effect on the newborn]. / Anémie par carence en fer maternelle: retentissement sur le nouveau-né.

Pregnancy increases considerably iron needs in mother and her foetus. The purpose of our study is to measure the effect of maternal anaemia on the foetus and the effect of iron supplementation on the maternal and foetal reserves. Therefore, we conducted a three-month cross sectional study at the gynaecological and obstetrics clinics of Aristide Le Dantec Hospital. Ninety-five women aged 16 to 43 years old and having an haemoglobin rate < 11 g/dl were recruited. Most of them were primipares. Among them 69 had a low ferritinemia (< 50 ng/ml), 36, a ferritinemia collapsed (< 30 ng/ml) and 13 virtually non-existent reserves (< 12 ng/ml). All newborns were born in terms with an apgar score >/= in 93 of them. Among them 24 had anemia (rate of haemoglobin < 14 g/dl) and 54.7% a low ferritinemia. There is no relationship between the maternal and foetal rates of haemoglobin; 74% of newborn had a normal rate of haemoglobin. Among 36 women with low ferritinemia only two gave birth to a newborn without iron reserves. In our study, among 68 women who received iron regularly, 41 had normal reserves and 43 gave birth to a newborn with high ferritinemia. There is significant difference between the women having received iron during their pregnancy and those not supplemented as regards the effect on newborn (p = 0.00001). The prevention of iron deficiency and anaemia can be done by the iron systematic and premat supplementation.

[Bone marrow aspiration in diagnosis of hemopathies in Dakar, Senegal]. / Intérêt du myélogramme dans le diagnostic des hémopathies au CHU de Dakar: a propos de 1000 ponctions réalisées de 1991 a 1999.

The cytological study of bone marrow aspirate, is a useful technique in diagnosis and epidemiological surveillance of hemopathies. Between January 1991 and February 1999, we realized 1000 bone marrow puncture in Dakar hospitals, this study aims to analyze the frequency of diagnosed hemopathies, and to appreciate justification of prescription. Mean age was 31.6 (1 to 88 years). Bone marrow puncture was safe because no incident was observed. Interpretation was possible in 937 cases while the 33 authors was diluted by blood. Bone marrow was normal in 550 cases (57.3%) whereas abnormality was detected in 417 cases (42.7%). The more frequent pathology were quantitative or qualitative defect of bone marrow production with respectively 25.8% and 20.1%, followed by chronic myeloid leukemia (16%), lymphoproliferative disorders (16%), acute leukemias (13.9%), bone marrow metastasis (5.9%), and storage diseases (1.9%). The best justification of the prescription was obtained when done on the basis of hemogram abnormalities or signs in hematopoietic organs with a pathology found in 90% of cases. Prescription on the basis of non hematological signs or to search for metastasis when primitive tumor was not identified were less efficient with respectively 20% and 42% of normal bone marrow. These results emphasize the interest of bone marrow aspiration in epidemiological surveillance of hemopathies, and the advantage to respect the rights indications, in consideration of pain and intolerability of the puncture by patients.

[Homozygous sickle cell disease in patients above 20 years of age: follow-up of 108 patients in Dakar]. / La drépanocytose homozygote après l'âge de 20 ans : suivi d'une cohorte de 108 patients au CHU de Dakar.

CONTEXT: The progress realized in the treatment of sickle cell anemia has resulted to a better and longer life for these patients in developed countries. Ongoing challenge are to manage complication and social living for these patients. The purpose of this study was to determine morbidity, mortality and socioprofessional insertion of homozygous sickle cell patients, followed up in Dakar university hospital. PATIENTS AND METHODS: We performed a longitudinal and prospective study including 108 homozygous sickle cell anemia patients, whose age were above 20 years, followed in a regular basis (at least 3 times per year), during 5 years on average (3 to 12 years). All patients had a quarterly hematological check-up and a annual statement to detect chronic complications. Clinic and paraclinical data, as information in socioprofessional insertion were noted in medical records for analysis. RESULTS: Mean age was 27 years (20-51 years). The age between 20-29 years was represented by 67.5%, 26.9% aged 30-39 years and 5.6% were above 40 years of age. Men were slightly predominant with a sex-ratio of 1.25. Concerning morbidity, 96.3% of patients had at least 1 vaso-occlusive crisis per year, 26.9% were transfused and 64.8% had been hospitalized during the follow-up. A chronic complication was found in 49% of patients (53/108). The more frequent of these complications were gall stone (10%), femoral head necrosis (9.2%), priapism (11.6% of men), chronic leg ulceration (4.6%), ophthalmic involvement (3.7%), renal and cardiac complications (2.7% for each one). The presence of complications was not significantly influenced by patient's sex. Five patients died during a mean follow-up of 5 years. Concerning school attendance, 13% reach university level whereas 47% stop their education on the secondary level and 40% on primary level. Professionally, 36.2% of patients had no exercise any activity. CONCLUSION: Our results emphasize that life expectancy can be prolonged in sickle cell anemia patients in Africa, when they have a benefit of a regular follow-up. We show also the respective frequency of chronic complications and then, the necessity of multidisciplinary teams to optimize the take care of sickle cell anemia patients in Africa.