A Population Genomics Approach to Assessing the Genetic Basis of Within-Host Microevolution Underlying Recurrent Cryptococcal Meningitis Infection.

Recurrence of meningitis due to Cryptococcus neoformans after treatment causes substantial mortality in HIV/AIDS patients across sub-Saharan Africa. In order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing (WGS) to assess the genetic basis of infection in 17 HIV-infected individuals with recurrent cryptococcal meningitis (CM). Comparisons revealed a clonal relationship for 15 pairs of isolates recovered before and after recurrence showing relapse of the original infection. The two remaining pairs showed high levels of genetic heterogeneity; in one pair we found this to be a result of infection by mixed genotypes, while the second was a result of nonsense mutations in the gene encoding the DNA mismatch repair proteins MSH2, MSH5, and RAD5 These nonsense mutations led to a hypermutator state, leading to dramatically elevated rates of synonymous and nonsynonymous substitutions. Hypermutator phenotypes owing to nonsense mutations in these genes have not previously been reported in C. neoformans, and represent a novel pathway for rapid within-host adaptation and evolution of resistance to first-line antifungal drugs.

A case of emmonsiosis in an HIV-infected child.

Opportunistic fungal infections can cause significant morbidity and mortality in immunocompromised patients. We describe a paediatric case of an unusual disseminated fungal infection. A three-year-old HIV-infected child with severe immunosuppression (CD4+ T-cell count 12 × 106/L) was admitted to hospital with pneumonia, gastroenteritis and herpes gingivostomatitis. Despite antibacterial and antiviral therapy, he experienced high fevers and developed an erythematous maculopapular rash and abdominal tenderness. The child's condition progressively worsened during the admission. A thermally dimorphic fungus was cultured from bone marrow and identified as an Emmonsia species on DNA sequencing. The patient made a good recovery on amphotericin B deoxycholate and antiretroviral therapy. Itraconazole was continued for a minimum of 12 months, allowing for immune reconstitution to occur. This case is the first documented description of disseminated disease caused by a novel Emmonsia species in an HIV-infected child in South Africa.

Antimicrobial Susceptibility Patterns of Escherichia Coli Strains Isolated From Urine Samples in South Africa from 2007-2011

Escherichia coli is the most common cause of urinary tract infections. Knowledge of its local antimicrobial susceptibility patterns can be used to inform choice of empiric antimicrobial therapy. In this article; we review data on antimicrobial susceptibility patterns of E. coli isolated from unselected urine specimens; in both the private and public sectors of South Africa from 2007-2011. Between 65 000-84 000 E. coli urinary isolates were reported annually from 19 laboratories located across South Africa. Susceptibility to fluoroquinolone and beta-lactam antibiotics decreased significantly and steadily in both private and public sectors over the five-year period; although laboratory-based surveillance data may underestimate susceptibility rates due to selection bias and lack of differentiation between community- and hospital-acquired infections. Our data suggest that fluoroquinolones; co-amoxiclav and first- and second-generation cephalosporins can still be used for empiric treatment in many local settings; but clinicians should be alert to the risk of treatment failure. With the withdrawal of nitrofurantoin from the local market; other oral antibiotic options are limited; and fosfomcyin may become increasingly important. Given their sustained high susceptibility rates; aminoglycosides should be considered to treat pyelonephritis more often. Judicious use of laboratory testing is advised and further research and surveillance is warranted