Seroprevalence and risk factors for HIV, HCV, HBV and syphilis among blood donors in Mali.

BACKGROUND: HIV, HBV and HCV remain a global public health concern especially in Africa. Prevalence of these infections is changing and identification of risk factors associated with each infection in Mali is needed to improve medical care. METHODS: We conducted a cross-sectional study of all individuals donating blood (n = 8207) in 2018 to the blood bank at university hospital in Bamako, Mali, to assess prevalence and risks factors associated with HIV, HBV, HCV and syphilis infections. RESULTS: HIV-seroprevalence was 2.16% and significantly increased with age, being married and decreasing education level. In multivariate analysis, after adjustements with age, marital status and geographical setting, only education level was associated with HIV-infection (OR, 1.54 [95% CI, 1.15-2.07], p = 0.016). HBsAg prevalence was 14.78% and significantly increased with to be male gender. In multivariate analysis, adjusting for age, marital status and type of blood donation, education level (OR, 1.17 [95%CI, 1.05-1.31], p = 0.02) and male gender (OR, 1.37 [95%CI, 1.14-1.65], p = 0.005) were associated with HBV-infection. HCV-prevalence was 2.32% and significantly increased with living outside Bamako. In multivariate analysis, adjusting for gender, age and education level, living outside Bamako was associated with HCV-infection (OR, 1.83 [95% CI, 1.41-2.35], p < 0.001). Syphilis seroprevalence was very low (0.04%) with only 3 individuals infected. Contrary to a prior study, blood donation type was not, after adjustments, an independent risk factor for each infection. CONCLUSIONS: Overall, HIV and HBV infection was higher in individuals with a lower level of education, HBV infection was higher in men, and HCV infection was higher in people living outside of Bamako. Compared to studies performed in 1999, 2002 and 2007 in the same population, we found that HIV and HCV prevalence have decreased in the last two decades whereas HBV prevalence has remained stable. Our finding will help guide infection prevention and treatment programs in Mali.

Genetic polymorphisms with erythrocyte traits in malaria endemic areas of Mali.

African populations are characterized by high degree of genetic diversity. This high genetic diversity could result from the natural selection pressure. Several studies have described an association between some genetic diversities and difference of susceptibility to infectious diseases like malaria. It seems therefore important to consider genetic diversity impact when interpreting results of clinical trials in malaria endemic areas. This study aimed to determine the genetic polymorphism with erythrocyte traits in different populations of malaria endemic area in Mali. The cross-sectional surveys were carried out in different ethnic groups living in malaria endemic areas in Mali. Six milliliters of whole blood were collected in EDTA vials from each participant after informed consent has been obtained. The ABO, RH, Kell, MNSs, Kidd and Duffy systems phenotypes were assessed by the technique of gel filtration. A total of 231 subjects were included from six villages. The blood groups phenotypes O (40.7%) and A (31.2%) were more frequent with respective allele frequencies of 0.65 and 0.21. In the RH system the haplotypes R0 (0.55), r (0.20) and R1 (0.13) were the most frequent. Seven percent (7%) of Duffy positive and 4% of Glycophorin B deficiency (S-s-) were observed among participants. All participants were Kell negative. ABO and RH systems were polymorphic in these ethnic groups in Mali. Their implication in susceptibility to malaria should be taken into account in clinical trials interpretation, and for prevention of blood transfusion risks during anemia frequently caused by malaria in children.

Phase 1 randomized controlled trial to evaluate the safety and immunogenicity of recombinant Pichia pastoris-expressed Plasmodium falciparum apical membrane antigen 1 (PfAMA1-FVO [25-545]) in healthy Malian adults in Bandiagara.

BACKGROUND: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel(®) was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel(®), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin. METHODS: A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed. RESULTS: Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group. CONCLUSION: The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.

Killer bee molecules: antimicrobial peptides as effector molecules to target sporogonic stages of Plasmodium.

A new generation of strategies is evolving that aim to block malaria transmission by employing genetically modified vectors or mosquito pathogens or symbionts that express anti-parasite molecules. Whilst transgenic technologies have advanced rapidly, there is still a paucity of effector molecules with potent anti-malaria activity whose expression does not cause detrimental effects on mosquito fitness. Our objective was to examine a wide range of antimicrobial peptides (AMPs) for their toxic effects on Plasmodium and anopheline mosquitoes. Specifically targeting early sporogonic stages, we initially screened AMPs for toxicity against a mosquito cell line and P. berghei ookinetes. Promising candidate AMPs were fed to mosquitoes to monitor adverse fitness effects, and their efficacy in blocking rodent malaria infection in Anopheles stephensi was assessed. This was followed by tests to determine their activity against P. falciparum in An. gambiae, initially using laboratory cultures to infect mosquitoes, then culminating in preliminary assays in the field using gametocytes and mosquitoes collected from the same area in Mali, West Africa. From a range of 33 molecules, six AMPs able to block Plasmodium development were identified: Anoplin, Duramycin, Mastoparan X, Melittin, TP10 and Vida3. With the exception of Anoplin and Mastoparan X, these AMPs were also toxic to an An. gambiae cell line at a concentration of 25 µM. However, when tested in mosquito blood feeds, they did not reduce mosquito longevity or egg production at concentrations of 50 µM. Peptides effective against cultured ookinetes were less effective when tested in vivo and differences in efficacy against P. berghei and P. falciparum were seen. From the range of molecules tested, the majority of effective AMPs were derived from bee/wasp venoms.

Transfusion safety in francophone African countries: an analysis of strategies for the medical selection of blood donors.

BACKGROUND: The goal of selecting a healthy blood donor is to safeguard donors and reduce the risks of infections and immunologic complications for recipients. STUDY DESIGN AND METHODS: To evaluate the blood donor selection process, a survey was conducted in 28 blood transfusion centers located in 15 francophone African countries. Data collected included availability of blood products, risk factors for infection identified among blood donor candidates, the processing of the information collected before blood collection, the review process for the medical history of blood donor candidates, and deferral criteria for donor candidates. RESULTS: During the year 2009, participating transfusion centers identified 366,924 blood donor candidates. A mean of 13% (range, 0%-36%) of the donor candidates were excluded based solely on their medical status. The main risk factors for blood-borne infections were having multiple sex partners, sexual intercourse with occasional partners, and religious scarification. Most transfusion centers collected this information verbally instead of having a written questionnaire. The topics least addressed were the possible complications relating to the donation, religious scarifications, and history of sickle cell anemia and hemorrhage. Only three centers recorded the temperature of the blood donors. The deferral criteria least reported were sickle cell anemia, piercing, scarification, and tattoo. CONCLUSIONS: The medical selection process was not performed systemically and thoroughly enough, given the regional epidemiologic risks. It is essential to identify the risk factors specific to francophone African countries and modify the current medical history questionnaires to develop a more effective and relevant selection process.

Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.

BACKGROUND: The objective was to evaluate the safety and immunogenicity of the AMA1-based malaria vaccine FMP2.1/AS02(A) in children exposed to seasonal falciparum malaria. METHODOLOGY/PRINCIPAL FINDINGS: A Phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02(A) is a recombinant protein (FMP2.1) based on apical membrane antigen 1 (AMA1) from the 3D7 clone of P. falciparum, formulated in the Adjuvant System AS02(A). The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). One hundred healthy Malian children aged 1-6 years were recruited into 3 cohorts and randomized to receive either 10 microg FMP2.1 in 0.1 mL AS02(A), or 25 microg FMP2.1 in 0.25 mL AS02(A), or 50 microg FMP2.1 50 microg in 0.5 mL AS02(A), or rabies vaccine. Three doses of vaccine were given at 0, 1 and 2 months, and children were followed for 1 year. Solicited symptoms were assessed for 7 days and unsolicited symptoms for 30 days after each vaccination. Serious adverse events were assessed throughout the study. Transient local pain and swelling were common and more frequent in all malaria vaccine dosage groups than in the comparator group, but were acceptable to parents of participants. Levels of anti-AMA1 antibodies measured by ELISA increased significantly (at least 100-fold compared to baseline) in all 3 malaria vaccine groups, and remained high during the year of follow up. CONCLUSION/SIGNIFICANCE: The FMP2.1/AS02(A) vaccine had a good safety profile, was well-tolerated, and induced high and sustained antibody levels in malaria-exposed children. This malaria vaccine is being evaluated in a Phase 2 efficacy trial in children at this site. TRIAL REGISTRATION: ClinicalTrials.gov NCT00358332 [NCT00358332].

[Quality assurance set-up in a blood transfusion facility: the experience of the National Blood Transfusion Center of Mali]. / Mise en Place de L'Assurance Qualite dans un Etablissement de Transfusion Sanguine: L'Experience du Centre National de Transfusion Sanguine du Mali.

AIM: The aim of this study was to help National Center for Blood Transfusion of Bamako in implementation of a quality assurance system. MATERIALS AND METHODS: Study was conducted in 2007 and 2008 at the National Center for Blood Transfusion of Mali in Bamako. We first evaluated the state of the quality system and studied the Knowledge, Attitude and Practices of the staff about quality assurance then carried out an plan of actions. We also made a check out of 2 critical processes in Blood transfusion: the whole blood collection process in fixed cabin and the temperature-monitored storage facilities for blood and reagents. RESULT: From the analysis of the state of assurance quality system, we found numerous failures. A policy of quality and guidelines for blood transfusion were absent. Most of the mains procedures and the flow chart of the center were also lacking. Sixty six of the personnel were aware about the notion of quality assurance and 36.7% were trained in this matter. The plan of actions was executed at 57.4%. Several failures were recorded in the processes of blood collection and in the temperature-monitored storage system. Corrective actions should be taken by training the staff in application of procedures. CONCLUSION: Despite of the great progress made in implementation of quality assurance at the CNTS of Mali, some insufficiencies were remaining. Development of quality system across all the stages of the blood transfusion chain is vital for CNTS. This require an adoption of national blood policy.

Phase 1 study of a combination AMA1 blood stage malaria vaccine in Malian children.

BACKGROUND: Apical Membrane Antigen-1 (AMA1) is one of the leading blood stage malaria vaccine candidates. AMA1-C1/Alhydrogel consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 microg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area. DESIGN: This was a Phase 1 dose escalating study in 36 healthy children aged 2-3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2 ratio 1 to receive either 20 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Two weeks later 18 children in the second cohort were randomized 2 ratio 1 to receive either 80 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript. RESULTS: Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received Hiberix. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine. CONCLUSION: AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived. TRIAL REGISTRATION: Clinicaltrials.gov NCT00341250.

Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

BACKGROUND: The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria. METHODOLOGY/PRINCIPAL FINDINGS: A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively. CONCLUSION/SIGNIFICANCE: The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

[The malignant hemopathies in children: epidemiologic aspects in the Haematology and Medical Oncology Ward of Point G Hospital, Bamako, Mali (1996-2003)]. / Les hemopathies malignes de l'enfant: aspects epidemiologiques dans Le Service D'Hematologie Oncologie Medicale de L'Hopital Du Point G, Bamako, Mali (1996-2003).

Data from developed countries place the malignant hemopathies among the most frequent cancers in children. The epidemiologic and prognostic aspects of these diseases are not well known in developing countries notably in Africa sub-Saharan countries because of lack of registry and clinical collaborative studies. Nevertheless, the good progress in the management of paediatric diseases that were a big concerns in former times authorize to think that in future, these countries will be engaged in programs to fit malignant diseases as major health problems in children. A good knowledge of epidemiologic aspects of these diseases must be therefore an important concern. This study describes epidemiologic and prognosis particularities of malignant hemopathies in children diagnosed in a last referral hospital ward, Bamako, Mali (West Africa) during height years. Fifty-nine cases of malignant hemopathies were diagnosed by January 1996 to December 2003 in 19 females and 40 males. Data were analysed retrospectively with SPSS 11.0. These children were aged from 4 to 15 years and the modal class of age was 6-10 years. The mean recruitment of cases per year was 7.37. Lymphomas were more frequent (70%) particularly the Burkitt lymphoma. The Hodgkin's lymphoma was not observed under 5 years of age but represents 24% of cases over this age and was more frequent in male. This study emphasizes the need to put in place strategies for a better understanding of epidemiological aspects of malignant hemopathies in children and for developing policies to improve management and prevention of cases in Mali.

Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult Malians.

BACKGROUND: Apical Membrane Antigen 1 (AMA1) of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses. STUDY DESIGN/RESULTS: A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax). Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort) and randomized 2:1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 microg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 microg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels. CONCLUSIONS: Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum. TRIAL REGISTRATION: ClinicalTrials.gov NCT00343005.

Apport de l'hemogramme dans le diagnostic de l'anemie par carence martiale

Notre etude avait pour objectif d'etudier l'apport de l'hemogramme dans le diagnostic de l'anemie par carence martiale. Le taux d'hemoglobine le nombre de globules rouges et les constantes erythrocytaires ont ete analysees chez 54 sujets souffrant d'une anemie microcytaire par carence en fer definie par une ferritinemie 30 ng / ml de serum et chez 46 sujets souffrant d'une anemie sans critere de carence martiale. Les parametres de l'hemogramme ont ete obtenus par comptage automatique (Coulter T890); le coefficient de saturation a ete determine par methode biochimique; la ferritine serique a ete dosee par la methode du Nichols Advantage (Reagent Cartridge for 100 Tests - Catalog No 62-7023). Nous n'avons pas trouve une bonne correlation entre le coefficient de saturation de la transferrine et la ferritinemie des malades. L'anemie grave n'etait pas plus frequente en cas d'anemie par carence martiale qu'en l'absence de carence martiale. Aucun des parametres de l'hemogramme n'a a lui seul de valeur predictive satisfaisante. Nous en concluons qu'en l'absence de bilan martial; l'association d'un rapport V.G.M/ G.R (?14) et V.G.M (60); et C.C.M.H / G.R (?10) et V.G.M (60) peuvent etre des outils fiables pour decider d'un traitement martial devant une anemie microcytaire observee dans un contexte clinique predictif

[Breast cancer: factors influencing the therapeutic itinerary of patients in a medical oncology unit in Bamako (Mali)]. / Cancer du sein: facteurs influençant l'itinéraire thérapeutique des usagers d'un service d'oncologie médicale à Bamako (Mali).

Early therapy is a determining factor to the recovery in patients with breast cancer. The situation in Mali is characterized by the delayed diagnosis of this cancer which raises the hypothesis that medical itinerary of patients received in specialized oncology unit is particular. In order to verify this hypothesis, 44 patients including 43 women and one man aged 25 to 80 years (mean age 46.0 19.6 years), seen in medical oncology unit in Point G, were subjects of an interview about the motivation of their therapeutic itinerary. 22.7% was initially seen by a traditional physician and 77.3% by a health care professional. The request of care was influenced by the patient's representation of the disease and by their neighboring. The therapeutic itinerary: "from traditional medicine to conventional medicine" was the more frequently observed in our patients with a long delay between the first consultation and the specialized one. Very few patients have received information about their illness before their specialized consultation. We conclude that the medical itinerary of our patients is particular, that this itinerary is influenced by the patient's representation of the cancer and by difficulty in the relationship between patients and health professional. This raise questions about the quality of both the communication and the provided health care. So, health care for patients with breast cancer in Mali might widely consider the anthropological dimension of the disease.