Kinetics of maternally-derived serogroup A, C, Y and W-specific meningococcal immunoglobulin G in Malian women and infants.

A prospective, randomised, controlled observer-blind trial measuring the efficacy and immunogenicity of trivalent influenza vaccine (TIV) and the immunogenicity of quadrivalent meningococcal conjugate vaccine (MCV) in pregnant women and their infants up to 6 months of age was conducted in Mali. Here we reported the immunogenicity of MCV, which was used as a comparator vaccine to TIV, in this population. Third-trimester pregnant Malian women were randomized to receive TIV or MCV. Blood samples were collected from women prior to vaccination, 28 days post-vaccination, at delivery and 3 and 6 months post-delivery and from infants at birth and 3 and 6 months of age. Meningococcal-specific serogroup (Men) A, C, Y and W-specific antibodies were measured by enzyme linked immunosorbent assay in a randomly selected subset of 50 mother-infant pairs where the mother had received MCV. At birth, 94.0% (47/50) of infants had MenA specific IgG levels ≥ 2 µg/mL decreasing to 72.9% and 30.4% at 3 and 6 months of age. For MenC, 81.3% (39/48) of infants had MenC specific IgG levels ≥ 2 µg/mL at birth decreasing to 29.4% and 17.8% at 3 and 6 months of age. For MenY, 89.6% (43/48) of infants had MenY specific IgG levels ≥ 2 µg/mL at birth decreasing to 64.6% and 62.5% at 3 and 6 months of age. For MenW, 89.6% (43/48) of infants had MenW specific IgG levels ≥ 2 µg/ml at birth decreasing to 62.5% and 41.7% at 3 and 6 months of age. Maternal immunization with MCV conveyed protective levels of IgG at birth through to 3 months of age in the majority of infants.

Strengthening immunization in a West African country: Mali.

UNLABELLED: OBJECTIVES AND CONTEXT: This paper describes the preliminary outcomes of a collaborative capacity-building initiative performed in Mali to strengthen the immunization program. METHODS: We conducted baseline assessments, training and post-training assessments in four programmatic areas: vaccine management, immunization safety, surveillance, and vaccine coverage, using adapted World Health Organization (WHO) tools. Impact assessment was done by evaluation of trainee performance, programmatic impact and sustainability. RESULTS: Qualitative and quantitative improvement of trainee performance was seen after the training interventions: some knowledge improvement, greater compliance with vaccine management practices and improved vaccine coverage. Deficiencies in information transfer to the periphery were identified. CONCLUSIONS: The program involves shared responsibility for planning, implementation and financing with national stakeholders while emphasizing the training of leaders and managers to ensure sustainability. Although short-term gains were measured, our initial assessments indicate that sustained impact will require improvements in staffing, financing and guidelines to ensure delivery of information and skills to the periphery.

Genotypic analysis of invasive Streptococcus pneumoniae from Mali, Africa, by semiautomated repetitive-element PCR and pulsed-field gel electrophoresis.

As part of a large, ongoing study of invasive infections in pediatric patients in Bamako, Mali, 106 cases of invasive pneumococcal disease were identified from June 2002 to July 2003 (J. D. Campbell et al., Pediatr. Infect. Dis. J. 23:642-649, 2004). Of the 12 serotypes present, the majority of isolates were not contained in PCV7 (the 7-valent pneumococcal conjugate vaccine), including 1 isolate that was serotype 1, 12 isolates that were serotype 2, 58 isolates that were serotype 5, 7 isolates that were serotype 7F, and 1 isolate that was serotype 12F. To determine whether clonal dissemination of the predominant serotypes had taken place, genotyping was performed on 100 S. pneumoniae isolates by using two methods: pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA, and the Bacterial Barcodes repetitive-element PCR (rep-PCR) method. Criteria for delineating rep-PCR genotypes were established such that isolates of different serotypes were generally not grouped together. The two methods were equally discriminatory within a given pneumococcal serotype. PFGE separated the isolates into 15 genotypes and 7 subtypes; rep-PCR separated isolates into 15 genotypes and 6 subtypes. Using either method, isolates within serotypes 2, 5, and 7 formed three large, separate clusters containing 1 genotype each. Both methods further distinguished related subtypes within serotypes 2 and 5. Interestingly, one of the PFGE subtypes of serotype 5 is indistinguishable from the Columbia(5)-19 clone circulating in Latin America since 1994. The data support that serotypes 2 and 5 were likely to be the result of dissemination of particular clones, some of which are responsible for invasive disease over a broad population range.

[Evaluation of the clinical classification of new cases of leprosy. Study conducted at the Marchoux Institute in Bamako, Mali]. / Evaluation de la classification clinique des nouveaux cas de lèpre. Etude réalisée á l'Institut Marchoux (Bamako, Mali).

INTRODUCTION: The difficulties related to the bacilloscopic diagnosis of leprosy, providing a more reliable classification of cases, in 1995 led the WHO to recommend the use of a new classification, in endemic countries, based on clinical criteria alone, in order to simplify the poly-chemotherapeutic regimens. According to our experience in the Marchoux Institute, this classification may lead to errors in diagnosis through overzealous or mis-interpretation of the two forms of leprosy. The aim of our study was to evaluate the concordance between this clinical classification and that based on a bacilloscopic examination. PATIENTS AND METHODS: We conducted a descriptive study of new cases of leprosy seen at the Marchoux Institute, without distinction in gender or age, from January to December 2000. All the patients included underwent clinical examination and a bacilloscopic exploration to provide a double classification. The concordance between the two classifications was assessed using the Kappa test. RESULTS: Two hundred new cases of leprosy were included. Out of 126 clinically multi-bacillary cases, 61 were confirmed bacteriologically, and 65 were false positives. Out of 74 clinical cases with few bacilli, 2 were bacteriologically multi-bacilli. The concordance between the two classifications was average (Kappa=0.40). There was a significant difference between the percentages of multi-bacilli observed in both classifications (p<10(-8)). DISCUSSION: The clinical classification may well overestimate the multi-bacillary form. In the absence of a reliable bacilloscopic apparatus, a more detailed clinical classification of leprosy forms must be developed.

Evaluation de la classification clinique des nouveaux cas de lèpre. Etude réalisée à lInstitut Marchoux (Bamako, Mali) / Evaluation of the clinical classification of new cases of leprosy. Study conducted at the Marchoux Institute in Bamako, Mali

INTRODUCTION: The difficulties related to the bacilloscopic diagnosis of leprosy, providing a more reliable classification of cases, in 1995 led the WHO to recommend the use of a new classification, in endemic countries, based on clinical criteria alone, in order to simplify the poly-chemotherapeutic regimens. According to our experience in the Marchoux Institute, this classification may lead to errors in diagnosis through overzealous or mis-interpretation of the two forms of leprosy. The aim of our study was to evaluate the concordance between this clinical classification and that based on a bacilloscopic examination. PATIENTS AND METHODS: We conducted a descriptive study of new cases of leprosy seen at the Marchoux Institute, without distinction in gender or age, from January to December 2000. All the patients included underwent clinical examination and a bacilloscopic exploration to provide a double classification. The concordance between the two classifications was assessed using the Kappa test.RESULTS: Two hundred new cases of leprosy were included. Out of 126 clinically multi-bacillary cases, 61 were confirmed bacteriologically, and 65 were false positives. Out of 74 clinical cases with few bacilli, 2 were bacteriologically multi-bacilli. The concordance between the two classifications was average (Kappa=0.40). There was a significant difference between the percentages of multi-bacilli observed in both classifications (p<10(-8)). DISCUSSION: The clinical classification may well overestimate the multi-bacillary form. In the absence of a reliable bacilloscopic apparatus, a more detailed clinical classification of leprosy forms must be developed.

Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans.

Twin and family studies indicate that host genetic factors influence susceptibility to leprosy and, possibly, leprosy type. Murine studies have suggested a role for the natural resistance-associated macrophage protein 1 (Nramp1) gene, which can influence cellular immune responses to intracellular pathogens. We evaluated a variation in the human homolog, NRAMP1, recently associated with tuberculosis susceptibility in West Africa. A total of 273 patients with leprosy and 201 controls from Mali were genotyped for NRAMP1 polymorphisms previously associated with tuberculosis. No association was found with leprosy per se (P = 0.83), but the NRAMP1 3'-untranslated region 4-bp insertion/deletion polymorphism was associated with leprosy type (P = 0.007). Heterozygotes were more frequent among multibacillary than paucibacillary leprosy cases. Thus, variation in or near the NRAMP1 gene may exert an influence on the clinical presentation of leprosy, possibly by influencing cellular immune response type.

Comparison of two methods of leprosy case finding in the circle of Kita in Mali.

Kita is a health district of Mali, a leprosy-endemic country in West Africa. We conducted a comparative study of passive and active case finding of leprosy in this district in 1997. In May and June, a mobile team realized active case finding by visiting 32 villages of more than 1000 inhabitants. For 12 months, peripheral health center nurses did passive detection after information and education sessions about the signs of leprosy in the other 37 main villages of Kita. The active detection rate (4.31 per 10,000) was threefold higher than the passive rate (1.5 per 10,000) and allowed us to find earlier cases of leprosy. Active case finding identified children and single-lesion disease; the passive method did not. Cost for finding a new case was estimated at 72 US$ by mobile team detection and 36 US$ by passive case finding. Although the active method looked more expensive than the passive one, it was the only effective strategy to detect leprosy patients in remote and difficult-to-access areas. Based upon the results of the study, a flow chart is proposed for the choice of case-finding method when designing a leprosy elimination program.

Comparison of two methods of leprosy case finding in the circle of Kita in Mali

Kita is a health district of Mali, a leprosy-endemic country in West Africa. We conducted a comparative study of passive and active case finding of leprosy in this district in 1997. In May and June, a mobile team realized active case finding by visiting 32 villages of more than 1000 inhabitants. For 12 months, peripheral health center nurses did passive detection after information and education sessions about the signs of leprosy in the other 37 main villages of Kita. The active detection rate (4.31 per 10,000) was threefold higher than the passive rate (1.5 per 10,000) and allowed us to find earlier cases of leprosy. Active case finding identified children and single-lesion disease; the passive method did not. Cost for finding a new case was estimated at 72 US$ by mobile team detection and 36 US$ by passive case finding. Although the active method looked more expensive than the passive one, it was the only effective strategy to detect leprosy patients in remote and difficult-to-access areas. Based upon the results of the study, a flow chart is proposed for the choice of case-finding method when designing a leprosy elimination program.

[Nature and sensitivity of bacteria superinfecting plantar ulcers caused by leprosy at the Marchoux Institute, Bamako, Mali]. / Nature et sensibilité des bactéries surinfectant les maux perforants plantaires d'origine lépreuse à l'Institut Marchoux, Bamako, Mali.

To determine potential usefulness of antimicrobial agents and to guide their prescription in the treatment of leprosy plantar ulcers, we conducted an in vitro study about germs' nature and sensitivity to antibiotics. We took samples of plantar ulcers secretion from 107 patients at Marchoux Institute. 92.5% of those ulcers were infected. These samples revealed 145 strains of micro-organisms among those, Staphylococcus aureus (70 strains) and genus Pseudomonas (41 strains) were the most frequent. These bacteria were resistant to several antibiotics currently used at Marchoux Institute (tetracycline, penicillin, cotrimoxazol and erythromicin). Antibiotics, efficient at 80% on tested strains, were expensive for patients. They cannot be recommended for the treatment of local infections. These results outline that the main treatment in plantar ulcers is based upon antiseptic solutions and keeping feet at rest. Antibiotherapy in case of extension of local infection would be based on the results of a previous study of sensitivity.

[Disabilities observed in new cases of leprosy diagnosed in the Bamako district (Mali) in 1994]. / Les infirmités observées chez les nouveaux cas de lèpre dépistés dans le district de Bamako (Mali) en 1994.

Our study concerns 244 new cases of leprosy diagnosed in the Bamako district in 1994. 154/244 patients could be contacted and were examined in the Leprosy Department of the Marchoux Institute in Bamako. Results showed that the presence of leprosy induced physical disabilities was associated with male gender (59%), advanced age (68%) and multibacillary disease (68%). Disabilities were also more frequent among patients having a rural or manual occupation at the time of screening or afterwards. There was a significant increase (p < 0.001) in the prevalence of disabilities when comparing patients at the time of diagnosis (29%) and thereafter (48%). This means that in 40% of disability cases, lesions developed during or after the treatment. Disabilities were predominantly observed in hands (33%) and feet (29%) with more frequent lesions in lateral popliteal, superior ulnar and posterior tibial nerves. Our results seem to demonstrate the inadequacy of preventive measures and management. This stresses the need for adequate prevention and therapy of leprosy induced disabilities in order to obtain proper eradication of leprosy induced health problems.

[Leprosy as a cause of physical disability in rural and urban areas of Mali]. / Place de la lèpre parmi les handicaps physiques en zones rurale et urbaine au Mali.

We performed a cross-sectional study of populations from two areas of Mali, in May and June 1996. The aim of the study was to assess the extent to which leprosy causes physical disability in Mali. One area was rural (Circle of Bougouni), the other urban (Bamako District). We used a cluster sampling method, with 500 households selected for study in each of the two areas. All members of the households randomly selected were included in the study. For all survey sites, the number of households was proportional to the number of inhabitants. The total study population was 8,175, including 172 cases of physical handicap, 76 in Bamako and 96 in Bougouni. The prevalence of physical handicap was 21 per 1,000 inhabitants (25.3 per 1,000 in rural areas and 17.3 per 1,000 in the city). The difference in the prevalence of physical handicap between the two areas was statistically significant (p = 0.01). Ten per cent of the disabilities were caused by leprosy. The most common causes of disability other than leprosy were trauma and poliomyelitis. Leprosy mostly caused disabilities in rural areas. In both areas, leprosy caused more disabilities in men and boys (64% of cases) than in women and girls. The frequency of disabilities caused by leprosy increased with age, whereas the frequency of handicaps with other causes decreased with age. This study shows that leprosy is still a major cause of disability in countries in which it is endemic, such as Mali. Disability prevention measures and physical rehabilitation programs should be incorporated into the national program for the elimination of epilepsy.

[Evaluation of the elimination of leprosy in Burkina Faso]. / Evaluation de l'élimination de la lèpre au Burkina Faso.

During May and June 1997, we conducted a rapid survey on leprosy prevalence in 30 villages. It was to assess reaching of the leprosy elimination threshold (one case per 10,000 inhabitants) in Burkina Faso. We drew lots for the villages in ten provinces among which five had the highest prevalence rates of leprosy in 1996 and five had the lowest prevalence rates. We added a leprosy elimination monitoring to the survey. This monitoring consisted of visits to the health centers covering the 30 villages. We interviewed and clinically examined 33 cases of leprosy in treatment in those health centers. We found fifty-one patients of leprosy in visited villages. The prevalence rate of leprosy (6.74 per 10,000 inhabitants) was twice higher than the prevalence rate registered in the same villages. We detected 28 new cases of leprosy during the survey. Proportion of hidden cases of leprosy were 54.9%. We estimated geographical coverage of MDT at 75% in the 10 provinces. Eight of the 27 visited health centers (29.6%) did not get sufficient supply. The cure rate has fallen from 93 to 73 per cent between 1992 and 1997. Our results show that leprosy elimination threshold is not reached in Burkina Faso. Leprosy control activities that were declining during the last five years need to be reinforced.

Effect of HIV infection on leprosy: a three-year survey in Bamako, Mali.

From February 1992 until June 1994, all patients with histologically proven leprosy examined at the Leprology Unit of the Institut Marchoux in Bamako, Mali, were screened for HIV serology. In total, 740 leprosy patients have been tested; 553 known, previously treated leprosy cases and 187 new cases, mainly self-reporting and referred cases. The global seroprevalence in the sample was 1.5% (11/740), and increased from 1.3% in 1992 to 3.1% in 1994. HIV seroprevalence was higher in paucibacillary (PB) than in multibacillary (MB) cases (3.8% versus 0.8%, p < 0.05), and was slightly higher in new cases than in known, already treated cases (2.1% versus 1.3%), although not significantly. Among the 553 known, already treated leprosy patients, 1 out of 7 HIV-seropositive patients relapsed, as opposed to 34 out of 546 HIV-seronegative cases (14.2% versus 6.2%, p = 0.36). Among the new cases, none of the 37 patients with reaction and/or neuritis was HIV positive. In known, treated leprosy cases, there was no difference in the frequency of reactions and/or neuritis between HIV-positive and HIV-negative cases. Migration in a neighboring country appeared to be a risk factor for HIV seropositivity in our sample (chi 2 = 4.5, p = 0.04). In order to estimate the association of HIV with leprosy as compared to the general population, a control group of blood donors was set up, matched for age and sex. There was, however, no difference in HIV seroprevalence between the control group (9/735, 1.2%) and the leprosy group (1.5%). Although leprosy patients recruited for this study constitute a highly selected sample, it appears that HIV infection has little effect on leprosy, particularly on the PB/MB ratio, leprosy reactions and neuritis, but there is a suggestion the HIV infection might be associated with increased frequency of relapse.

PIP: HIV infection is a major risk factor for tuberculosis and other mycobacteria, but its association with leprosy remains unclear. From February 1992 to June 1994, all leprosy patients examined at the Leprology Unit of the Institut Marchoux, a reference center for leprosy in Mali, were screened for HIV infection. 740 leprosy patients were tested over the period; 553 known, previously treated cases and 187 newly diagnosed leprosy cases. 584 patients were multibacillary (MB) cases and 156 were paucibacillary (PB), with a large majority of MB cases among the known cases, due to the selected recruitment of those patients. There were 539 men of mean age 39.3 years and 201 women of mean age 37.7. New and known cases were of mean ages 30.7 and 41.6 years. Overall, 1.5% (11/740) were identified as HIV seropositive, increasing from 1.3% in 1992 to 3.1% in 1994. HIV seroprevalence was 3.8% among PB cases and 0.8% among MB cases, and was slightly higher in new cases than in known, already treated cases. Among the 553 known, already treated leprosy cases, 1 out of 7 HIV-seropositive patients relapsed, compared to 34 of 546 HIV-seronegative cases. Among the new cases, none of the 37 patients with reaction and/or neuritis was HIV positive. It appears that HIV infection has little effect upon leprosy, especially upon the PB/MB ratio, leprosy reactions and neuritis, but HIV infection may be associated with increased frequency of relapse.

Infirmites lepreuses observees chez les patients de l'Essai/OMS/OFLO/MALI a l'inclusion

Cette etude decrit les infirmites lepreuses observees chez les 275 nouveaux patients de l'essai multicentrique; OMS/THMYEC des regions combines associant l'oflaxacine rifampicine dans le traitement de la lepre; au moment de l'inclusion. Cet essai a debute en octobre 1992 et a ete realise dans la region de Koulikoro au Mali. Sur les 275 inclus 76 (26;7 pour cent) etaient porteurs d'infirmites au depistage dont 40 (14;5 pour cent) de degre 2. La repartition de ses infirmites a montre une predominance masculine 47 cas (33;8 pour cent p=0.02); une predominance dans la forme MB 36 cas (43;9 pour cent p=0.01) et une augmentation en fonction de l'age de 21 cas (20;6 pour cent) chez les sujets jeunes a 30 cas (41;7 pour cent) chez les sujets ages (p=0.01)