Les molécules antipaludiques rencontrées et prélevées dans les différentes régions du Mali et du district de Bamako, ont été analysées au Laboratoire National de la Santé. Les échantillons analysés provenaient d'Afrique, d'Europe, d'Asie et d'Amérique. L'échantillonnage a concerné 303 échantillons analysés, dont 260 étaient conformes, soit un taux de 85,8% et 43 étaient non conformes, soit 14,2%. Les non conformités décelées provenaient toutes des formes comprimés et injectables et concernaient spécifiquement les molécules de quinine. Les non-conformités décelées étaient de 03 types : l'absence de principe actif indiqué, le surdosage et le sous-dosage. Suivant le circuit de prélèvement dans la chaîne de distribution, les nonconformités ont été décelées en majorité dans les hôpitaux et les Centres de santé (40 échantillons) et secondairement au niveau des dépôts de vente privés (03 échantillons).

The fixed-dose combination artesunate (AS)–amodiaquine (AQ) is one of the most widely used treatments for uncomplicated falciparum malaria. It is currently proposed to the inclusion in the model list of essential medicines of World Health Organization and has been recently prequalified. Until now, no satisfactory method for the simultaneous determination of the two active ingredients had been available. Thus, a reversed phase high performance liquid chromatography for the quantitative determination of AQ and AS was developed and validated. Chromatography was performed using an end-capped octadecylsilyl silica gel column (100 × 4.6 mm, 3 μm) with a binary gradient using aqueous phase containing potassium dihydrogen phosphate (10 mM) and acetonitrile. Taking into consideration the physico-chemical characteristics of the two compounds related to their ionization, the use of a counter ion was necessary to ensure the retention of AQ in a reversed phase system simultaneously to AS. Thus, aqueous mobile phase was adjusted to pH 3.0 and the chosen counter ion was sodium 1-octanesulfonate (100 mM). In these conditions, the retention times were about 4 min for AQ and 10 min for AS with UV detection at 300 and 210 nm, respectively. Method was then validated according to ICH guideline (specificity/linearity/accuracy/precision) and potential interferences with excipients and degradation products were checked. It has also been used for an interlaboratory study involving seven African National Quality Control Laboratories and Afssaps (Agence française de sécurité sanitaire des produits de santé) laboratory. The results demonstrate that this rapid and simple method can be easily used by official laboratories for routine control, market survey and for the detection of potential substandard medicines which are very frequent in African countries.

SUMMARY Objective: To study the factors associated with the observance of treatment ARV among patients followed in hospital medium to Bamako Method: Inquire longitudinal with collection of the data near the patients followed in one of the three greater sites of assumption of responsibility of the people reached with the VIH/SIDA to Mali. The people were regarded as observing if they took at least 95% of their treatment the moment of the investigation. Results: The patients were between 1 and 40 months of treatment the moment of the investigation. The average age was 44 years with extremes going from 19 to 70 years. Association Lamivudine +Stavudine + Nevirapine (triomune) was the most prescribed antiretroviral therapy (34.2%). The bad observance was noted at 58.5% of the patients. The principal causes of bad observance were: the lapse of memory 47.5% (96/202) and difficulties of access to the hospital 34.6% (70/202). The changes of molecules were due primarily to the out-of-stock condition, and the side effects. The factor associated with a good observance was the assistance of the patient by a member of the family informed of seropositivity. Conclusion: The interest of HIV patient to his treatment could contribute to enhance antiretroviral Adherence particularly in this hospital and generally in Mali Keys words: observance, antiretroviral therapy, Mali.

Neisseria meningitidis serogroup W 135 (N.m. W 135) has caused sporadic infections and small epidemics such as those that occurred during religious pilgrimages in Saudi Arabia in 2000 and in 2001. It is routinely isolated from specimens coming from African countries. The first major epidemic involving N.m. W 135 occurred in Burkina Faso between January and May 1992. There were more than 1300 cases including 1500 deaths. Enhanced surveillance of circulating strains showed that N.m. W 135 accounted for 83% of the 203 positive cerebrospinal fluid specimen cultures. The offending organism was identical to the strain that caused the smaller epidemic in Saudi Arabia in 2000. Due to the shortage of tetravalent meningococcal vaccine against N.m. W 135, the Health Ministry based its response to the epidemic on treatment of symptomatic patients using chloramphenicol and ampicillian. These drugs were distributed free. The emergence of N.m. W135 has impacted public health in Africa. Repeated identification of this serogroup in Burkina Faso during 2002 raises the risk that similar outbreak will occur in the meningitis belt during the next epidemic season. The high cost of tetravalent meningococcal vaccine compounded with the only progressive increase in production capacity underline the need to reinforce surveillance of circulating strains and available treatment facilities. Control strategy for epidemic meningitis is currently the focus of close collaboration between the WHO and the health authorities and corresponding institutions in the countries involved.

In this sequence note we describe the full-length genome sequence of an HIV-1 isolate originating from the west African country of Mali. The phylogenetic tree analysis from the near full-length genome shows that the 95ML84 strain forms a separate cluster, supported by 100% of the bootstrap values, with the previously described A/G/J/? mosaic virus BFP90 from Burkina Faso. Additional analysis showed that throughout the genome the lowest diversity was seen between the 95ML84 and the BFP90 viruses, and bootscan analysis showed a similar complex genomic structure. In addition to the initial report describing the BFP90 virus as an A/G/J/? recombinant, our data show that for the BFP90 and 95ML84 strains the unclassified region corresponds to subtype I. The A/G/I/J BFP90 and 95ML84 strains represent the fifth and most complex circulating recombinant form of HIV-1 detected so far, and our data show its presence in various West African countries. Subtype I and J sequences, initially considered rare, seem to have broadened their geographical spread by way of these recombinant forms.

The global HIV pandemic is extremely heterogenous and dynamic. Preliminary data however suggest that HIV-1 subtype A represents 60-90% of HIV subtypes circulating in West and Central Africa. Results are presented from an exercise conducted to rapidly identify subtype A samples in the regions using a subtype A-specific polymerase chain reaction (PCR) followed by heteroduplex mobility assay (HMA) for samples not recognized by PCR. 424 HIV-positive samples genetically characterized in the env region by HMA or sequencing or both were tested with subtype A-specific primers. 276 samples were identified as subtype A and 148 were identified as non-A representing the other HIV-1 subtypes B-H. The genetic subtypes of the different samples were determined in the envelope region by HMA or sequencing or both. 201 of the 276 subtype A samples were detected for an overall sensitivity of 72.8%. The sensitivity changed according to the geographical origin of the samples and ranged from 50% to 87.5%. The highest number of subtype A strains was detected in samples from West African countries; 87.5% in Burkina Faso 84.8% in Senegal and 80.0% in Mali and Nigeria. The lowest numbers were in samples of Central African origin such as those from Cameroon and the Democratic Republic of Congo. Only 2 of the 148 non-A samples were reactive with the subtype A-specific primers for an overall specificity of 98.6%. Those 2 reactive samples were identified as subtype C by HMA and by the sequence of the C2-V3 region.

Despite considerable experience with single-dose, live, oral cholera vaccine CVD 103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in sub-Saharan Africa or on individuals infected with human immunodeficiency virus (HIV). We therefore conducted a randomized, placebo-controlled, double-blind, cross-over clinical trial in 38 HIV-seropositive (without clinical acquired immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and vomiting) were observed with similar frequency among vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV-seropositives with CD4+ counts below 500 per microliter. Following immunization, the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV-seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV-seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although serological responses were significantly attenuated among HIV-seropositives (particularly in those with CD4+ counts < 500 per microliter) relative to HIV-seronegatives. These results encourage further evaluations of this single-dose, oral cholera vaccine in high-risk populations such as refugees in sub-Saharan Africa.

In Africa the highest HIV infection rate has been reported among female commercial sex workers (CSWs) who are at increasing risk of acquiring and transmitting HIV infection. In October 1995, 176 CSWs were studied in Bamako, the capital city of Mali. The ages of the CSWs ranged from 15 to 50 years old (mean, 28.8 years). Only 20.45% of the 176 CSWs were Malian; the majority were from Nigeria (32.9%) and Ghana (31.8%), and the remaining were from other African countries. Forty-one percent were active for less than 1 year as a commercial sex worker, and the length of prostitution for the remaining women ranged from 1 to 15 years (mean, 2.76). A total of 81 (46.02%) of the 176 CSWs were positive for HIV antibodies; 63 (35.8%) were HIV-1 positive, (3.9%) were HIV-2 positive, 11 (6.2%) had antibodies to HIV-1 and HIV-2, and none of them had antibodies to group O viruses. For all HIV antibody-positive samples, PBMCs were separated and genetic subtypes of HIV-1 were determined using the heteroduplex mobility assay (HMA), with ED5-ED12 as outer and ES7-ES8 as inner primers. Among the 66 HIV-1 strains characterized, 53 (80.3%) were subtype A, 2 (3.1%) belonged to subtype C, 1 (1.5%) belonged to subtype D, and 10 (15.1%) were identified as subtype G. Among the 10 subtype G strains, 8 were obtained from women who were very recent CSWs, with an activity of 1 year or less, assuming that there is a high probability that these infections occurred recently. Genetic subtypes of five HIV-2 viruses were determined by sequencing of the env and/or gag genes followed by phylogenetic analysis, and all of them belonged to subtype A. Comparison of HIV-1 and HIV-2 seroprevalence data from our study with previous data from Mali shows a significant rise in HIV-1 prevalence and a significant decrease in HIV-2 prevalence and confirms similar trends observed in neighboring countries. We have found four different genetic subtypes of HIV-1; however, subtype A is predominant and accounts for 80% of the cases and 15% of the HIV-1 infections were subtype G. It is important to continue the surveillance of subtypes on a systematic basis in order to see to what extent the proportions of the different subtypes will change over time.

OBJECTIVE:To determine to what extent HIV-1 group O strains are present in different African countries.MATERIALS AND METHODS:A total of 14,682 samples of sera from a range of patients from 12 different African countries were tested. All the sera were tested with an enzyme-linked immunosorbent assay (ELISA) using a combination of V3 peptides from ANT-70 and MVP-5180. Samples reactive in ELISA were retested in a line immunoassay (LIA-O). Samples reactive in ELISA were also retested with an in-house Western blot to determine the presence of antibodies to gp120 of HIV-1 ANT-70. Polymerase chain reaction was performed on HIV-1 group O and group O indeterminate sera.RESULTS:Of all the sera samples tested, only 19 sera had antibodies to group O V3 peptides exclusively and 46 were indeterminate for group O infection in LIA-O. The highest prevalence of HIV-1 group O infection among HIV-positive sera was observed in Cameroon (2.1%) and neighbouring countries, 1.1% in Nigeria and 0.9% in Gabon. The lowest rates were seen in west Africa: 0.07% in Senegal, 0.14% in Togo, 0.16% in Chad and 0.3% in Niger. Group O sera were observed in almost all the population categories tested. The ANT-70 V3 peptide in LIA-O was reactive with all of the sera considered to be HIV-1 group O antibody positive by LIA, versus 78.9% for the MVP-5180 peptide. Thirteen out of 19 group O samples of sera were tested in PCR. Eight samples were identified as group O by specific group O pol and/or V3 primers; in the remaining five samples no HIV RNA could be detected. Of the indeterminate sera samples, two were identified as group O.CONCLUSION:In eight of the 12 countries tested, antibodies to group O viruses were identified. Numbers of HIV-1 group O viruses are low. Their presence is not restricted to Cameroon and neighbouring countries but can also be found in west and south-east Africa.

aI'aide d'anticorps monoclonaux produits al'lnstitut MaxPlanck. Ainsi nousavonstrouv6 quepourles6rogroupe A,letypedeprot6ine declasse 1existant estleP1.7pourlessouches isol6es avant 1994etleP1.9pourlessouches isol6es en1994. P1.7d6finit leclone IV-1etP1.9lecloneI-1responsable del'6pid6mie de1994.Toutes lessouches des6rogroupe C isol6es duLCRetlamajorit6 dessouches provenant delagorgepossedent unnouveau typedelaprot6ine declasse 1auquel nousavonsdonn6le nomP1.y. LeP1.yestcaract6ristique dessouches maliennes duserogroupe C;ilestrareouabsent dans lessouches provenant d'autres payscommelesEtats-Unis d'Amerique, leGhana, leBurkina Fasoetl'Italie. Las6quence nucl6otidique dugenecodant pourlevariant P1.yetlas6quence d'aminoacides quien r6sulte ont6t6d6termin6es parMaidenauNational Institute forBiological Standards andControl au Royaume-Uni.

The study deals with 570 strains of Neisseriaceae isolated between 1989 and 1994 in Mali: 396 of the strains were isolated from samples of cerebrospinal fluid and 174 from the throat. Serogroup C accounted for 55% of all strains. Antigenic structure was determined by ELISA, SDS-PAGE and transfer to nitrocellulose membrane for immunoblotting with monoclonal antibodies produced at the Max Planck Institute for Molecular Genetics. For serogroup A, the class 1 protein types found were P1.7 for strains isolated prior to 1994 and P1.9 for strains isolated in 1994. P1.7 is specific to clone IV-1 and P1.9 to clone III-1, which was responsible for the 1994 epidemic. All strains of serogroup C isolated from fluid CSF and most strains isolated from the throat exhibit a new type of class 1 protein which the authors have designated P1.y. P1.y is characteristic of Malian strains of serogroup C; it is rare or absent in strains from other countries (Burkina Faso, Ghana, Italy, USA). The nucleotide sequence of the gene expressing P1.y and the corresponding amino acid sequence were determined at the National Institute for Biological Standards and Control, England.

The study deals with 570 strains of Neisseriaceae isolated between 1989 and 1994 in Mali: 396 of the strains were isolated from samples of cerebrospinal fluid and 174 from the throat. Serogroup C accounted for 55% of all strains. Antigenic structure was determined by ELISA, SDS-PAGE and transfer to nitrocellulose membrane for immunoblotting with monoclonal antibodies produced at the Max Planck Institute for Molecular Genetics. For serogroup A, the class 1 protein types found were P1.7 for strains isolated prior to 1994 and P1.9 for strains isolated in 1994. P1.7 is specific to clone IV-1 and P1.9 to clone III-1, which was responsible for the 1994 epidemic. All strains of serogroup C isolated from fluid CSF and most strains isolated from the throat exhibit a new type of class 1 protein which the authors have designated P1.y. P1.y is characteristic of Malian strains of serogroup C; it is rare or absent in strains from other countries (Burkina Faso, Ghana, Italy, USA). The nucleotide sequence of the gene expressing P1.y and the corresponding amino acid sequence were determined at the National Institute for Biological Standards and Control, England.

Notre étude a porté sur 337 souches de méningocoques isolées au Mali entre 1989 et 1992. Parmi ces souches, 163 proviennent de LCR et 174 de prélèvements de gorge. Le sérogroupe C représente 90 % des souches isolées de LCR et 33 % de celles isolées de la gorge. Nous avons pu déterminer la formule antigénique de ces différentes souches. Ainsi nous avons trouvé que pour le sérogroupe A, le type de protéine de classe 1 existant est le Pl.9 caractéristique du clone IV.1 responsable d'épidémies en Afrique entre 1981 et 1984 mais existant actuellement à l'état endémique. Toutes les souches de sérogroupe C isolées du LCR et une majorité de souches provenant de la gorge, possèdent un nouveau type de la protéine de classe 1 auquel nous avons donné le nom Pl.y. Le Pl.y est caractéristique des souches maliennes de séro-groupe C; il est rare ou absent dans les souches provenant d'autres pays (Etats-Unis, Ghana, Burkina Faso, Italie).

Peripheral blood lymphocytes from meningitis patients and healthy meningococcal carriers were fused by electrofusion with the three human-murine heteromyeloma cell lines CB-F7, K6H6B5 and H7NS. 934 hybridomas producing human immunoglobulins were obtained in 30 fusions. Heteromyeloma K6H6B5 yielded a significantly higher proportion of hybridomas producing IgG antibodies than did the two other cell lines. CB-F7 and K6H6B5 yielded comparable numbers of hybridomas whose supernatants reacted with homologous bacteria, whereas the cell line H7NS was less efficient.

This study showed that the carriage rate is nul or low in collectivity not in close contact, but high in collectivity in close contact (schools, particularly coranic schools). In this later case, the duration of the carriage may reach several weeks (2 to 6 in our study) at variable rates (3.7 to 9.6 %; 12.5 to 62.5 %; 14.3 to 42.9 % according to the coranic school visited). For the strains of N. meningitidis serogroup C isolated, the rate of resistance to sulfamides and cotrimoxazole is 86.8 %. These results explain why during epidemics, it is necessary to close schools and avoid to use for the chemoprophylaxis, sulfamids and their associations because of resistance.

This study showed that the carriage rate is nul or low in collectivity not in close contact, but high in collectivity in close contact (schools, particularly coranic schools). In this later case, the duration of the carriage may reach several weeks (2 to 6 in our study) at variable rates (3.7 to 9.6%; 12.5 to 62.5%; 14.3 to 42.9% according to the coranic school visited). For the strains of N. meningitidis serogroup C isolated, the rate of resistance to sulfamides and cotrimoxazole is 86.8%. These results explain why during epidemics, it is necessary to close schools and avoid to use for the chemoprophylaxis, sulfamids and their associations because of resistance.

Five murine epitopes were defined and mapped within IgA1 protease produced by Neisseria meningitidis. Epitopes 1 and 2 were present in IgA1 protease from all strains, and from Neisseria gonorrhoeae. Epitopes 3 through to 5 varied between subgroups of serogroup A meningococci, but have remained constant over decades within the subgroups, except for epitope 4, which changed between 1983 and 1987 during the spread of subgroup III meningococci from Asia to Africa. Binding of monoclonal antibodies to epitopes 1, 4 and 5 neutralized enzymatic function. Human sera containing antibodies to IgA1 protease as a result of natural infection inhibited binding of monoclonal antibodies to epitope 4 but not to the other epitopes.

Cette etude qui porte sur 251 souches bacteriennes isolees au Mali, compare l'activite antibacterienne d'une cephalosporine de 1ere generation le Cefacetrile et de deux cephalosporines de 3e generation: le cefotaxime et la ceftriaxone. Aucune des cephalosporines etudiees n'est active sur Pseudomonas aeruginosa. Sur les souches de Staphylococcus aureus etudiees, le cefacetrile est plus actif que les 2 cephalosporines de 3e generation. Vis a vis des autres especes etudiees, la Ceftriaxone et le Cefotaxime sont plus actifs que le Cefacetrile, l'activite de la Ceftriaxone etant d'une facon generale superieure a celle du Cefotaxime