Molecular identification of Mycobacterium bovis from cattle and human host in Mali: expanded genetic diversity.

BACKGROUND: Bovine tuberculosis (BTB) is a contagious, debilitating human and animal disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex. The study objective were to estimate the frequency of BTB, examine genetic diversity of the M. bovis population in cattle from five regions in Mali and to determine whether M. bovis is involved in active tuberculosis (TB) in humans. Samples from suspected lesions on cattle at the slaughterhouses were collected. Mycobacterial smear, culture confirmation, and spoligotyping were used for diagnosis and species identification. Mycobacterium DNA from TB patients was spoligotyped to identify M. bovis. RESULTS: In total, 675 cattle have been examined for lesions in the five regions of Mali. Out of 675 cattle, 79 specimens presented lesions and then examined for the presence of M. bovis. Thus, 19 (24.1 %) were identified as M. bovis; eight (10.1 %) were non-tuberculous Mycobacterium (NTM). Nineteen spoligotype patterns were identified among 79 samples with five novel patterns. One case of M. bovis (spoligotype pattern SB0300) was identified among 67 TB patients. CONCLUSION: This study estimates a relatively true proportion of BTB in the regions of Mali and reveals new spoligotype patterns.

Nontuberculous Mycobacteria Isolated from Tuberculosis Suspects in Ibadan, Nigeria.

In Nigeria, one of the highest tuberculosis (TB) burdened nations, sputum smear microscopy is routinely employed for TB diagnosis at Directly Observed Treatment Short-Course (DOTS) Centers. This diagnostic algorithm does not differentiate Mycobacterium tuberculosis complex (MTC) from nontuberculous mycobacteria (NTM). Between December 2008 and January 2009, consecutive patients diagnosed with TB were screened for inclusion at 10 DOTS centers in Ibadan, Nigeria. To verify Mycobacterium species in patients diagnosed, we cultured and identified mycobacterial isolates using PCR, line probe assay, and spoligotyping techniques. From 48 patients screened, 23 met the inclusion criteria for the study. All the 23 study patients had a positive culture. Overall, we identified 11/23 patients (48%) with MTC only, 9/23 (39%) with NTM only, and 3/23 (13%) with evidence of both MTC and NTM. Strains of MTC identified were Latin American Mediterranean (LAM) genotype (n = 12), M. africanum (n = 1), and the genotype family T (n = 1). Four M. avium-intracellulare-M. scrofulaceum complexes, one M. chelonae complex, one M. abscessus, and one M. intracellulare were identified. Our findings underscore the need to incorporate molecular techniques for more precise diagnosis of TB at DOTS centers to improve clinical outcomes and safe guard public health, particularly in TB endemic countries.

Adjuvant host-directed therapy with types 3 and 5 but not type 4 phosphodiesterase inhibitors shortens the duration of tuberculosis treatment.

BACKGROUND: Shortening tuberculosis treatment could significantly improve patient adherence and decrease the development of drug resistance. Phosphodiesterase inhibitors (PDE-Is) have been shown to be beneficial in animal models of tuberculosis. We assessed the impact of PDE-Is on the duration of treatment in tuberculous mice. METHODS: We analyzed the time to death in Mycobacterium tuberculosis-infected mice receiving type 4 PDE-Is (rolipram and cilomilast) and the impact on bacterial burden, time to clearance, and relapse when types 3 and 5 PDE-Is (cilostazol and sildenafil, respectively) and rolipram were added to the standard treatment. We investigated pharmacokinetic interactions between PDE-Is (cilostazol and sildenafil) and rifampin. RESULTS: The type 4 PDE-Is rolipram and cilomilast accelerated the time to death in tuberculous mice. The addition of rolipram to standard tuberculosis treatment increased bacterial burden and did not decrease the time to bacterial clearance in the lung, while the addition of the cilostazol and sildenafil reduced the time to clearance by 1 month. Cilostazol and sildenafil did not have negative pharmacokinetic interactions with rifampin. CONCLUSIONS: Type 4 PDE-Is may increase the severity of tuberculosis and should be carefully investigated for use in patients with latent or active tuberculosis. Cilostazol and sildenafil may benefit tuberculosis patients by shortening the duration of therapy.

Transmitted antiretroviral drug resistance in newly HIV-infected and untreated patients in Ségou and Bamako, Mali.

The WHO recommends regular surveillance for transmitted antiretroviral drug-resistant viruses in HIV antiretroviral treatment (ART)-naive patients in resource-limited settings. This study aimed to assess the prevalence of mutations associated with resistance in ART-naive patients newly diagnosed with HIV in Bamako and Ségou in Mali. HIV-positive patients who never received ART were recruited in Bamako and Ségou, Mali. The reverse transcriptase (RT) and protease (PR) genes of these patients were sequenced by the "ViroSeq" method. Analysis and interpretation of the resistance were made according to the WHO 2009 list of drug resistance mutations. In all, 51/54 (94.4%) sample patients were sequenced. The median age (IQR) of our patients was 24 (22-27) years and the median CD4 count was 380 (340-456) cells/mm(3). The predominant subtype was recombinant HIV-1 CRF02_AG (66.7%) followed by CRF06_cpx (12%) and CRF09_cpx (4%). Four patients had mutations associated with resistance, giving an overall prevalence of resistance estimated at 7.9%. There were two (4%) patients with nucleoside reverse transcriptase inhibitor (NRTI) mutations (one M184V and one T215Y), two (4%) with non-NRTI mutations (two K103N), and one (2%) with a protease inhibitor mutation (one I54V). The prevalence of primary resistance in newly infected patients in Mali is moderate (7.9%). This indicates that the standard NNRTI-based first-line regimen used in Mali is suboptimal for some patients. This study should be done regularly to inform clinical practice.

Sickle cell trait protects against Plasmodium falciparum infection.

Although sickle cell trait protects against severe disease due to Plasmodium falciparum, it has not been clear whether sickle trait also protects against asymptomatic infection (parasitemia). To address this question, the authors identified 171 persistently smear-negative children and 450 asymptomatic persistently smear-positive children in Bancoumana, Mali (June 1996 to June 1998). They then followed both groups for 2 years using a cohort-based strategy. Among the 171 children with persistently negative smears, the median time for conversion to smear-positive was longer for children with sickle trait than for children without (274 vs. 108 days, P < 0.001; Cox hazard ratio = 0.56, 95% confidence interval: 0.33, 0.96; P = 0.036). Similar differences were found in the median times to reinfection after spontaneous clearance without treatment (365 days vs. 184 days; P = 0.01). Alternatively, among the 450 asymptomatic children with persistently positive smears, the median time for conversion to smear-negative (spontaneous clearance) was shorter for children with sickle trait than for children without (190 vs. 365 days; P = 0.02). These protective effects of sickle trait against asymptomatic P. falciparum infection under conditions of natural transmission were demonstrable using a cohort-based approach but not when the same data were examined using a cross-sectional approach.

Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting.

OBJECTIVES: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. METHODS: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. RESULTS: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm(3). Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). CONCLUSION: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.

Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.

Mutations in the connection domain (CD) of reverse transcriptase have been implicated in reverse transcriptase inhibitor (RTI) resistance, but this is controversial and little is known in non-B subtype HIV-1. We determined CD mutations prevalence in a population infected predominantly with CRF02_AG and investigated associations with phenotypic RTI resistance. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). Mutations were largely polymorphic and did not confer RTI resistance. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further.

Failure to recognize nontuberculous mycobacteria leads to misdiagnosis of chronic pulmonary tuberculosis.

BACKGROUND: Nontuberculous mycobacterial (NTM) infections cause morbidity worldwide. They are difficult to diagnose in resource-limited regions, and most patients receive empiric treatment for tuberculosis (TB). Our objective here is to evaluate the potential impact of NTM diseases among patients treated presumptively for tuberculosis in Mali. METHODS: We re-evaluated sputum specimens among patients newly diagnosed with TB (naïve) and those previously treated for TB disease (chronic cases). Sputum microscopy, culture and Mycobacterium tuberculosis drug susceptibility testing were performed. Identification of strains was performed using molecular probes or sequencing of secA1 and/or 16S rRNA genes. RESULTS: Of 142 patients enrolled, 61 (43%) were clinically classified as chronic cases and 17 (12%) were infected with NTM. Eleven of the 142 (8%) patients had NTM disease alone (8 M. avium, 2 M. simiae and 1 M. palustre). All these 11 were from the chronic TB group, comprising 11/61 (18%) of that group and all were identified as candidates for second line treatment. The remaining 6/17 (35.30%) NTM infected patients had coinfection with M. tuberculosis and all 6 were from the TB treatment naïve group. These 6 were candidates for the standard first line treatment regimen of TB. M. avium was identified in 11 of the 142 (8%) patients, only 3/11 (27.27%) of whom were HIV positive. CONCLUSIONS: NTM infections should be considered a cause of morbidity in TB endemic environments especially when managing chronic TB cases to limit morbidity and provide appropriate treatment.

False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene.

We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered.

Adverse drug reactions to antiretroviral therapy: prospective study in children in sikasso (mali).

OBJECTIVES: Adverse events during antiretroviral treatment are frequent and various. Their diagnosis incurs some various difficulties according to the geographic context. Our aim was to describe the frequency, nature, and preventability of adverse drug reactions (ADRs) due to antiretroviral treatment in Malian outpatient children. METHODS: The study was a 6-month (June 1 to November 30, 2010) prospective, observational study of 92 children admitted to a pediatric hospital in Sikasso, Mali. The patients were treated with a generic drug and/or drug combinations. Prior to treatment initiation, demographic characteristics, clinical history, and biologic parameters, including CD4 cell counts, were collected for each patient. The World Health Organization's adverse drug reactions classification was used to characterize the side effects. Adverse effects and toxicities were graded 1, 2, and 3. Analysis of data was performed using SPSS Version 17.0 software. RESULTS: Ninety-two human immunodeficiency virus-infected children met the criteria of inclusion. After 24 weeks of treatment, we observed that 14.1% of children had at least one side effect during our study. Side effects were many and varied, with the most frequent being cutaneous rash, nausea, vomiting, and diarrhea (38.5%, 23.1%, 15.4%, and 15.4%, respectively). Side effects were grade 1 in most cases. One case of grade 2 and one case of grade 3 were observed with rash. We observed one case of grade 3 side effects during our study. The treatment regimen was changed in 15.2% of cases, including one case because of side effects. CONCLUSION: ADRs are not rare in Mali, particularly in children. These ADRs have an impact on quality of life for patients. We recommend a pharmacovigilance system for sustainable management of side effects in patients infected with human immunodeficiency virus in Mali.

[Prevalence of maternal and placental malaria and of neonatal low birth weight in a semi-urban area of Bamako (Mali)]. / Prévalence du paludisme maternel, placentaire et du petit poids de naissance au cours du travail d'accouchement et en post-partum en milieu périurbain à Bamako (Mali).

In 2006, the Malian government established a program for free insecticide-treated net (ITNs) distribution during antenatal care visit (ANC) and intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) for pregnant women. In March to November of 2009, we conducted a cross-sectional study in peri-urban areas of Bamako, Mali to determine the malaria prevalence among pregnant women and their newborn children in the context of this policy. We included 379 pregnant women aged 15 to 45 years. At delivery, malaria was diagnosed using peripheral thick smears in mothers and newborns, as well as umbilical cord blood and placental blood. The prevalence of Plasmodium falciparum malaria was 2.4, 1.6 and 0.5% respectively in mother, placenta and cord samples; we observed a low birth weight rate of 12.1%. Approximately 77% of our parturient were housewives. The illiteracy rate among this group was 72.3%. Of the 379 women, 73% had at least three prenatal visits, 83% had received at least one free ITNs and 72% had received IPTp-SP during antenatal visit. Among them, 81% claimed to have complied with IPTp-SP. No congenital malaria was found. The prevalence of malaria in both mother and newborn has show a significant decrease in Bamako, compared with previous studies before the implementation of IPTp-SP policy in Mali. A high rate of coverage and use of IPTp-SP and ITNs correlate with lower malaria prevalence in pregnant women.

Knops blood group polymorphism and susceptibility to Mycobacterium tuberculosis infection.

BACKGROUND: Complement receptor 1 (CR1) protein carries the Knops blood group antigens and is the receptor for the major ligand involved in Mycobacterium tuberculosis (Mtb) adhesion to macrophages. Erythrocyte CR1 binds immune complexes (ICs) formed during Mtb invasion, facilitating their clearance by the host immune system. The occurrence of specific Knops blood group genotypes among African populations was investigated to evaluate their impact on resistance or susceptibility to Mtb infection. STUDY DESIGN AND METHODS: The distribution of the Knops blood group genotypes (McC and Sl) was compared between tuberculosis (TB) patients with confirmed diagnosis of Mtb in isolates and negative controls. Conditional logistic regression was used to access the association between genotypes distribution and susceptibility to Mtb infection. RESULTS: At the McC locus, individuals heterozygous (McC(a) /McC(b) ) were more resistant to Mtb infection (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.22-0.81; p = 0.007). Although less significant, a similar effect was conferred by Sl1/Sl2 genotype (OR, 0.05; 95% CI, 0.28-0.9; p = 0.02). This protective effect was maintained among individuals presenting the McC(b) /Sl2 haplotype (OR, 0.25; 95% CI, 0.08-0.74; p = 0.008). CONCLUSION: Acquisition of McC(b) and Sl2 alleles among African population is correlated with resistance to Mtb infection, adding this bacterium to the list of mechanisms underlying the selection of the Knops blood group polymorphism among these populations.

[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.

Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes.

Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02_AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02_AG than in other non-B subtypes (P=0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility.

Identification and characterization of CRF02_AG, CRF06_cpx, and CRF09_cpx recombinant subtypes in Mali, West Africa.

Abstract Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to cocirculate in Africa. In West Africa, the high prevalence of CRF02_AG, and cocirculation of subtype A, CRF01_AE, CRF06_cpx, and other complex intersubtype recombinants has been well documented. Mali, situated in the heart of West Africa, is likely to be affected by the spread of recombinant subtypes. However, the dynamics of the spread of HIV-1 recombinant subtypes as well as nonrecombinant HIV-1 group M subtypes in this area have not been systematically assessed. Herein, we undertook genetic analyses on full-length env sequences derived from HIV-1-infected individuals living in the capital city of Mali, Bamako. Of 23 samples we examined, 16 were classified as CRF02_AG and three had a subsubtype A3. Among the remaining HIV-1 strains, CRF06_cpx and CRF09_cpx were each found in two patients. Comparison of phylogenies for six matched pol and full-length env sequences revealed that two strains had discordant subtype/CRF designations between the pol and env regions: one had A3(pol)CRF02_AG(env) and the other had CRF02_AG(pol)A3(env). Taken together, our study demonstrated the high prevalence of CRF02_AG and complexity of circulating HIV-1 strains in Mali. It also provided evidence of ongoing virus evolution of CRF02_AG, as illustrated by the emergence of more complex CRF02_AG/A3 intersubtype recombinants in this area.

Novel approach for differential diagnosis of HIV infections in the face of vaccine-generated antibodies: utility for detection of diverse HIV-1 subtypes.

Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from >3,000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at >99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide.

Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria.

Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.

[Seroprevalence of the human cytomegalovirus among blood donors and AIDS patients in Bamako]. / La séroprévalence de l'infection par le cytomégalovirus humain chez les donneurs de sang et les malades atteints du sida à Bamako.

Our aim was to study the prevalence of the human cytomegalovirus (HCMV) among blood donors and AIDS patients and to examine a clinical correlation between AIDS and HCMV seroprevalence in Bamako (Mali, West Africa). We have used Elisa kits for detecting HIV and HCMV specific antibodies. The HCMV seroprevalence was 89% among AIDS patients, 71% among HIV-infected blood donors and 58% among HIV-uninfected blood donors. The HCMV seroprevalence rate was higher among AIDS patients than among HIV-uninfected blood donors (p=0.0000007) and than among HIV-infected blood donors (p=0.00146). There was no significant difference between the HCMV seroprevalence among HIV-infected blood donors and among HIV-uninfected blood donors (p=0.0547). There was no relationship between HCMV seroprevalence and sex or age among AIDS patients and blood donors. There was a significant difference on pneumonia among HCMV-infected AIDS patients and among HCMV-uninfected AIDS patients (40% versus 0%; p=0.005). Buccal and phaiyngal candidosis, dermatosis, Kaposi's sarcoma and nervous system diseases had the same frequency among HCMV-infected and HCMV-uninfected AIDS patients.

RHD allele distribution in Africans of Mali.

BACKGROUND: Aberrant and non-functional RHD alleles are much more frequent in Africans than in Europeans. The DAU cluster of RHD alleles exemplifies that the alleles frequent in Africans have evaded recognition until recently. A comprehensive survey of RHD alleles in any African population was lacking. RESULTS: We surveyed the molecular structure and frequency of RHD alleles in Mali (West Africa) by evaluating 116 haplotypes. Only 69% could be attributed to standard RHD (55%) or the RHD deletion (14%). The aberrant RHD allele DAU-0 was predicted for 19%, RHDPsi for 7% and Ccdes for 4% of all haplotypes. DAU-3 and the new RHD allele RHD(L207F), dubbed DMA, were found in one haplotype each. A PCR-RFLP for the detection of the hybrid Rhesus box diagnostic for the RHD deletion in Europeans was false positive in 9 individuals, including all carriers of RHDPsi. Including two silent mutations and the RHD deletion, a total of 9 alleles could be differentiated. CONCLUSION: Besides standard RHD and the RHD deletion, DAU-0, RHDPsi and Ccdes are major alleles in Mali. Our survey proved that the most frequent alleles of West Africans have been recognized allowing to devise reliable genotyping and phenotyping strategies.