Efficacy and Safety of Manual Partial Red Cell Exchange in the Management of Severe Complications of Sickle Cell Disease in a Developing Country.

INTRODUCTION: The realization of red cell exchange (RCE) in Africa faces the lack of blood, transfusion safety, and equipment. We evaluated its efficacy and safety in severe complications of sickle cell disease. PATIENTS AND METHOD: Manual partial RCE was performed among sickle cell patients who had severe complications. Efficacy was evaluated by clinical evolution, blood count, and electrophoresis of hemoglobin. Safety was evaluated on adverse effects, infections, and alloimmunization. RESULTS: We performed 166 partial RCE among 44 patients including 41 homozygous (SS) and 2 heterozygous composites SC and 1 S/ß0-thalassemia. The mean age was 27.9 years. The sex ratio was 1.58. The regression of symptoms was complete in 100% of persistent vasoocclusive crisis and acute chest syndrome, 56.7% of intermittent priapism, and 30% of stroke. It was partial in 100% of leg ulcers and null in acute priapism. The mean variations of hemoglobin and hematocrit rate after one procedure were, respectively, +1.4 g/dL and +4.4%. That of hemoglobin S after 2 consecutive RCE was -60%. Neither alloimmunization nor viral seroconversion was observed. CONCLUSION: This work shows the feasibility of manual partial RCE in a low-resource setting and its efficacy and safety during complications of SCD outside of acute priapism.

[Evaluation of the efficacy of medical screening of blood donors on preventing blood transfusion-transmitted infectious agents]. / Évaluation de l'efficacité de la sélection médicale des donneurs de sang dans la prévention des agents infectieux.

BACKGROUND: The aim of this study was to evaluate the efficacy of medical screening to retain blood donors in window period by comparing the seroprevalence of infectious agents (HIV, hepatitis B and C, syphilis) in deferred versus accepted blood donors. MATERIALS AND METHODS: This prospective and transversal study was performed during 4 months in the National Blood Transfusion Center in Dakar (Senegal). We conducted a convenience sampling comparing the seroprevalence of infectious agents (HIV, HBsAg, HCV and syphilis) in deferred versus accepted blood donors after medical selection. RESULTS: In total, 8219 blood donors were included. Medical selection had authorized 8048 donors (97.92%) and deferred donors were 171 (2.08%). The prevalence of HIV was higher in the deferred than in accepted blood donors (1.75% vs. 0.05%) (P=0.0003; OR=35.91), as well as for HBsAg (12.87% vs. 7.35%) (P=0.006; OR=1.86). HCV antibodies were present in 0.71% of accepted blood donors and 0.58% in deferred blood donors (P=0.65; OR=0.82). Only accepted donors had brought the infection of syphilis (0.34%) (P=0.56; OR=0). CONCLUSION: Medical selection is efficient to exclude blood donors at high risk of HIV transmission and to a lesser extent of HBV. However, current medical screening procedures do not allow us to exclude donors asymptomatic carriers of HCV and syphilis.

Inbreeding within human Schistosoma mansoni: do host-specific factors shape the genetic composition of parasite populations?

The size, structure and distribution of host populations are key determinants of the genetic composition of parasite populations. Despite the evolutionary and epidemiological merits, there has been little consideration of how host heterogeneities affect the evolutionary trajectories of parasite populations. We assessed the genetic composition of natural populations of the parasite Schistosoma mansoni in northern Senegal. A total of 1346 parasites were collected from 14 snail and 57 human hosts within three villages and individually genotyped using nine microsatellite markers. Human host demographic parameters (age, gender and village of residence) and co-infection with Schistosoma haematobium were documented, and S. mansoni infection intensities were quantified. F-statistics and clustering analyses revealed a random distribution (panmixia) of parasite genetic variation among villages and hosts, confirming the concept of human hosts as 'genetic mixing bowls' for schistosomes. Host gender and village of residence did not show any association with parasite genetics. Host age, however, was significantly correlated with parasite inbreeding and heterozygosity, with children being more infected by related parasites than adults. The patterns may be explained by (1) genotype-dependent 'concomitant immunity' that leads to selective recruitment of genetically unrelated worms with host age, and/or (2) the 'genetic mixing bowl' hypothesis, where older hosts have been exposed to a wider variety of parasite strains than children. The present study suggests that host-specific factors may shape the genetic composition of schistosome populations, revealing important insights into host-parasite interactions within a natural system.

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.

Schistosome infection is associated with enhanced whole-blood IL-10 secretion in response to cercarial excretory/secretory products.

Infection of the human host by schistosome parasites follows exposure of skin to free-swimming cercariae and is aided by the release of excretory/secretory (E/S) material, which is rich in proteases and glycoconjugates. This material provides the initial stimulus to cells of the innate immune system. The study presented here is the first to examine human innate/early immune responsiveness to cercarial E/S in subjects from an area co-endemic for Schistosoma mansoni and S. haematobium. We report that in infected participants, stimulation of whole-blood cultures with cercarial E/S material (termed 0-3 hRP) caused the early (within 24 h) release of greater quantities of regulatory IL-10, compared with uninfected controls. Elevated levels of IL-10 but not pro-inflammatory TNFα or IL-8 were most evident in participants co-infected with S. mansoni and S. haematobium and were accompanied by a higher 0-3 h RP-specific IL-10: TNFα ratio. We also report that glycosylated components within 0-3 h RP appear to be important factors in the stimulation of IL-8, TNFα and IL-10 production by whole-blood cells.

Association between herpes simplex virus type 2 and HIV-1 in a population of married couples from Dakar, Senegal.

Numerous studies suggest that herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection but recent clinical trials of HSV-2 suppressive therapy failed to show an effect. We assessed the putative association between HSV-2 and HIV-1 in a population of HIV-concordant-negative, HIV-1-discordant and HIV-1-concordant-positive married couples from Dakar, Senegal. In agreement with previous studies, we observed a strong overall association between HSV-2 and HIV-1 (odds ratio 4.61; P < 0.001). However, this association was mainly determined by a low HSV-2 prevalence in HIV-concordant-negative couples compared with HIV-1-discordant and HIV-1-concordant-positive couples (23% versus 59% and 66%, respectively; P < 0.001). We observed no further differences in HSV-2 prevalence between HIV-1-discordant and HIV-1-concordant-positive couples (59% and 66%, respectively; P = 0.483). Neither the index (59% versus 62%, P = 1.000) nor recipient partners (41% versus 63%, P = 0.131) in HIV-1-discordant and HIV-1-concordant-positive couples showed significant differences in HSV-2 prevalence. HSV-2 does not constitute a clear risk factor for HIV-1 infection in this population.

[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.

[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.

Immunologic and virologic response after tetanus toxoid booster among HIV-1- and HIV-2-infected Senegalese individuals.

Twelve HIV-1-infected, nine HIV-2-infected patients and eight HIV-negative subjects were given a 40IU booster dose of tetanus toxoid (TT). Blood was collected on days 0, 7 and 30 after immunization. Changes in HIV-1 or HIV-2 RNA load were evaluated by nested PCR. TT-IgG antibody levels were quantified by ELISA. CD4 cell counts as well as activation, memory and maturation markers of T lymphocyte subsets were determined by flow cytometry. The induction of apoptosis was investigated using 7-aminoactinomycin D (AAD) and propidium iodide (PI) staining. Proliferative responses to TT and pokeweed mitogen (PWM) were determined by the level of [(3)H] thymidine incorporation. Seven and 30 days after immunization, there was no detectable increase in HIV-1 or HIV-2 plasma load. There were also no changes in CD4 cell counts, CD69, HLA-DR and memory CD45RO or naive CD45RA antigens. Immunization did not increase the spontaneous apoptosis of peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ T cells subsets neither in controls nor in HIV-infected patients. Similarly, apoptosis induced in vitro by PWM or by the specific TT recall antigen did not vary during the study period. The proliferative response to PWM and to the TT recall antigen was decreased both in HIV-1- and HIV-2-infected patients compared to HIV-negative controls. Immunization significantly increased the TT-IgG levels in healthy controls and in HIV-infected patients. However, the anti-TT-IgG response, as measured by the fold-increase index between days 0 and 30, was significantly higher in healthy controls than in HIV-1- (P=0.036) and HIV-2-infected patients (P=0.003). In conclusion, we found no deleterious immunologic or virologic effect was detected in healthy HIV-1- and HIV-2-infected individuals after antigenic challenge with a TT booster. However, the response to TT vaccination was lower in HIV-1- and in HIV-2-infected individuals than in healthy HIV-negative controls.

Spontaneous apoptosis and highly active antiretroviral therapy (HAART).

Increased programmed cell death (PCD) or apoptosis has been detected in the T cells of HIV-infected subjects; it is held partially responsible for the continuous loss of CD4+ T cells during the natural course of HIV infection. Highly active antiretroviral therapy (HAART) decreases the viral load and leads to an increase of CD4+ count in vivo. In this study we evaluated PCD in total peripheral blood mononuclear cells, CD8+ and CD4+ lymphocytes before and four weeks after initiation of HAART. Seven HIV-1-infected patients were investigated. Viral load was assessed by RT-polymerase chain reaction and PCD by flow cytometry using apoptosis by 7 amino actinomycin D (7AAD) and propidium iodide (PI). After four weeks of HAART, CD4+ T and CD8+ T cell levels were stable, and plasma HIV-RNA copies were significantly decreased. In four of the patients (4/7), HIV-RNA levels were reduced to undetectable levels (fewer than 400 copies per milliliter). A statistically significant reduction of apoptosis among CD4+ cells was observed (P < 0.03), though neither in the CD8+ T cell population nor in peripheral blood mononuclear cells (PBMCS). These results demonstrate the beneficial effect of HAART on apoptosis of CD4+ cells in the early treatment stage.

[Complement and serum immunoglobulins in homozygous and heterozygous sickle cell anemia in Senegal]. / Complément et immunoglobulines sériques chez des drépanocytaires homozygotes (SS) et héterozygotes (AS) au Sénégal.

Sickle cell disease is an hereditary hemoglobinopathy syndrome which provokes deglobulization crisis and infectious complications. These infectious diseases may be due to a permanent activation of the immune system. The aim of our study was to explore alternative pathway by measuring C3 complement and the classical pathway by C4 complement. The level of immunoglobulins IgA, IgG and IgM was also measured in the subjects sera. Thirty homozygous sickle cell anemia (SS), 25 heterozygous (AS) and 34 controls subjects (AA) were recruited in the Hôpital d'Enfants Albert Royer (HEAR), Fann hospital and Centre National de Transfusion Sanguine (CNTS). Radial Immunodiffusion (RID) technics using specific antisera for C3c, C4c, IgA, IgG and IgM were used in our study. Homozygous SS proved an increase level of IgA (50%, p < 0.003) and IgG (47%, p < 0.003), unlike of IgM level. The C3c complement decrease significantly in (27%) of homozygous SS patients (p < 0.0005) unlike of C4c level. This low level of C3 and IgG in sickle cell homozygous patients can explain the higher susceptibility to infection in these patients. Normal level of C4 and low level of C3 show activation of alternative pathway. Heterozygous AS showed a normal level of C4, C3 and immunoglobulins. Our results suggests a direct involvement of the complement system in sickle cell disease and the depletion of C3 registered was a possible cause of increased susceptibility to infections in patients with homozygous sickle cell anemia.