Emerging Aspergillus Species Almost Exclusively Associated With Primary Immunodeficiencies.

Invasive aspergillosis (IA) is the most serious mold infection encountered in patients with iatrogenic immunosuppression. IA is also a major cause of mortality and morbidity in individuals with primary immunodeficiency (PID). Although Aspergillus fumigatus is the most common etiologic agent of IA reported in PID patients, followed by A. nidulans, multiple poorly recognized Aspergillus species such as A. udagawae, A. quadrilineatus, A. pseudoviridinutans, A. tanneri, A. subramanianii, and A. fumisynnematus have been reported almost exclusively from patients with inborn defects in host antifungal defense pathways. Infection in PID patients exhibits patterns of disease progression distinct from those in iatrogenic immunosuppression. Specifically, the disease can be extrapulmonary and chronic with a tendency to disseminate in a contiguous manner across anatomical planes. It is also more refractory to standard antifungal therapy. This synopsis summarizes our understanding of emerging rare Aspergillus species that primarily affect patients with PIDs but not those with acquired immunodeficiencies.

Molecular strain typing of Mycobacterium tuberculosis complex in Bamako, Mali.

OBJECTIVE: To identify strains of Mycobacterium tuberculosis complex (MTC) circulating in Bamako and to examine the relationship between the strains and their drug susceptibility profiles. METHODS: Between 2006 and 2010, we conducted a cross-sectional study using spoligotyping to identify strains of MTC recovered from 126 tuberculosis (TB) patients under treatment in Bamako, Mali. RESULT: Three members of the MTC were isolated: M. tuberculosis (71.4%), M. africanum (27.8%) and M. bovis (0.8%). Of these, three strains were found to be the most prevalent: M. tuberculosis T1 (MTB T1; 38.9%), M. africanum F2 (MAF2; 26.2%) and M. tuberculosis Latin American and Mediterranean 10 (MTB LAM 10; 10.3%). MAF2 and MTB LAM 10 strains have a lower risk of multidrug resistance (MDR) than MTB T1 (respectively OR 0.1, 95%CI 0.03-0.4 and OR 0.1, 95%CI 0.01-0.8). Age ≥ 32 years (OR 1.4, 95%CI 0.4-3.9), negative human immunodeficiency virus status (OR 0.4, 95%CI 0.1-2.5) and male sex (OR 4, 95%CI 0.9-16.5) were not associated with MDR. The prevalence of MDR among treatment and retreatment failure patients was respectively 25% and 81.8% compared to new patients (2.9%). CONCLUSION: This study indicates a low level of primary drug resistance in Bamako, affirms the importance of using correct drug regimens, and suggests that the MTB T1 strain may be associated with the development of resistance.

Impact of adopting minimum inhibitory concentration as the determinant of susceptibility to cephalosporins and carbapenems in multi-drug resistant Enterobacteriaceae.

The Clinical and Laboratory Standards Institute has recommended that Enterobacteriaceae susceptibility to most cephalosporins and carbapenems be reported according to minimum inhibitory concentration (MIC) alone. We analyzed our record of multi-drug resistant Enterobacteriaceae to assess the impact of these changes. We compared susceptibilities of ceftriaxone-resistant Enterobacteriaceae when using the 2009 and new 2010 MIC standards. Vitek2® (BioMerieux), was used to assess the changes in susceptibility. Klebsiella pneumoniae, Proteus sp., and Escherichia coli were the major species from urine, sputum, blood, and other sterile sites. The new breakpoint for cephalosporins increased resistance in E. coli and P. mirabilis. Many Proteus categorized as resistant by extended-spectrum beta-lactamase (ESBL) detection or inferred resistance have MICs to ceftriaxone ≤ 1 mcg/ml. New carbapenem breakpoints increased resistant Klebsiella pneumoniae and Proteus mirabilis. The increased ceftriaxone resistance from lowering breakpoints was almost balanced by the loss of resistance in ESBL isolates with MICs ≤ 1 mcg/ml. MIC-based susceptibility for multi-drug resistant Enterobacteriaceae increases the number of resistant isolates. Inferring mechanisms of resistance has a disproportionate effect on the susceptibility of Proteus mirabilis to cephalosporins, and the MIC-based standard has an almost equivalent but opposite effect on Proteus mirabilis susceptibility to carbapenems.

Retrospective surveillance of HIV prevalence in blood donors can help in the selection of the best social group for blood donation in Mali.

The National Centre for Blood Transfusion, Bamako, Mali has collected data that characterizes trend in HIV prevalence over 10 years by gender, age, occupation, marital status and donor category. These data help to describe national HIV prevalence and assist in formulating blood donation policies. Donations from 1993 to 2002 were categorized by donor age (decade), occupation (student, military and other), marital status (single, married and other), gender and donor status (volunteer, occasional and family). Comparisons were made using conservative estimates of donation frequency/donor category. Donations increased by more than 400%. By 1999, increased HIV prevalence in donations from women was consistently present. Donations from the age group of 30-39 years showed an increased prevalence beginning in 2000, which by 2002 was almost 10 times greater than in the low-prevalence (<20 years) group (5.9 vs. 0.6%). By 2000, both categories - students and military were less likely to be HIV positive than those from other occupational categories, and donations from married persons were less likely to be HIV positive by 1997. The highest prevalence was observed in the 'occasional' donor category, which increased to >14% by 2001; volunteer donation HIV positive peaked at 2.3% in 1999. HIV prevalence in blood donations in Bamako, Mali, demonstrates important trends from 1993 to 2002. The prevalence of > 14% in donations from occasional donors and significant trends by decade, gender, marital status and occupation argue for increased analysis of the blood donor population to improve blood safety and to understand the demographics of HIV infection in Mali.

Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: determinants of high virus loads and CD4 cell killing.

Chimeric simian-human immunodeficiency viruses (SHIVs) carrying envelope glycoproteins derived from a T cell-macrophage dual-tropic primary isolate (human immunodeficiency virus type 1 [HIV-1] strain DH12) were constructed. When inoculated into macaque monkeys, SHIV(MD14) carrying simian immunodeficiency virus-derived nef established significantly higher virus loads than did SHIV(MD1), which contains the HIV-1 nef gene. Three patterns of CD4 cell depletion were observed in infected monkeys: exponential and irreversible loss to undetectable levels within 10 weeks of infection; marked reduction during acute infection followed by partial recovery and stabilization (lasting from 10 weeks to > 1 year), with a later decline to undetectable levels in some animals; and a transient loss during acute infection. The induced immunodeficiency was accompanied by CD4 cell counts of < 50 cells/microL and was associated with Pneumocystis carinii pneumonia, cytomegalovirus meningoencephalitis, lymphoid depletion, and thymic atrophy.

HYP1, a hydrophobin gene from Aspergillus fumigatus, complements the rodletless phenotype in Aspergillus nidulans.

Aspergillus fumigatus produces conidia that are highly dispersable and resistant to degradation. We have sought to analyze these properties by studying the rodlets which form the outer spore coat protein. Degenerate primers based on hydrophobins in other fungi were applied to genomic DNA from A. fumigatus in PCR. A product of this reaction with similarity to an Aspergillus nidulans gene as judged by Southern hybridization was chosen for further study. Cloning and sequencing revealed a gene with two introns which encodes a protein of 159 amino acids. Structural characteristics consistent with those of other fungal hydrophobin genes, especially conserved cysteine residues, are present. The expression of the gene is limited to the developmental stages in which maturing conidiophores are present. This A. fumigatus gene, HYP1, was used to transform a mutant strain of A. nidulans that lacks rodlets. Transformants with a single copy of HYP1 expressed a rodlet layer on their conidia as observed by freeze-fracture electron microscopy.

The role of bacterial cultures from bronchoscopy washings in AIDS related patients.

The clinical significance of bronchoscopy washing cultures for bacteria had been questioned before the era of the acquired immune deficiency syndrome (AIDS), and the procedure was felt to be misleading more than helpful. Little has been mentioned of its utility in AIDS patients undergoing fiberoptic bronchoscopy. The correlation of these cultures was retrospectively reviewed for 30 bronchoscopies performed in 26 patients with advanced AIDS related illnesses. Normal respiratory flora was the most common finding in 14/28 (50%) of the cultures submitted, followed by Staphylococcus aureus in 7/28 (25%). Correlating chest radiographs with culture results revealed that in only five cases were cultures definitely or possibly relevant. All five had radiographic changes compatible with bacterial processes, and clinical findings suggestive of disease. The routine submission of bronchoscopy washings for bacterial culture in patients with HIV associated disease should be discouraged without clinical and radiologic correlation.