Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57–restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus–infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.

The impact of the HIV epidemic on child health globally is beginning to be appreciated. With the burden of new infections falling on young women, there is a skyrocketing number of AIDS orphans, and a rapidly increasing number of children infected via mother-to-child-transmission (MTCT). An estimated 600,000 new paediatric infections occur each year, of which some 1500/day (> 90%) occur in sub-Saharan Africa. But whereas children account for only 4% of those currently living with HIV infection, 20% of AIDS deaths have been in children. This reflects the rapid progression to disease in paediatric HIV infection. Whereas a dramatic reduction in viraemia follows acute adult infection, corresponding to the appearance of a vigorous anti-HIV cytotoxic T lymphocyte response, virtually no impact of the immune response is observed in acute paediatric infection following MTCT. Two specific challenges for the paediatric immune response are: (i) infection occurs before the immune system itself is fully developed; and (ii) the viruses transmitted by MTCT have already evaded an immune system sharing close genetic relatedness to that of the child. Accumulating evidence indicates that the immune system is potentially capable of effective control of HIV infection, and that events occurring in acute infection critically determine the ultimate outcome. Technological advances that have transformed the study of T-cell immunity now enable the developing immune system in childhood to be better understood. Via novel immunotherapeutic approaches described, it may be possible to modulate the infant's immune response to reach effective and durable suppression of HIV, as can be achieved by the rare long-term non-progressors of HIV infection. The feasibility of adopting these approaches globally are as yet untested. Finally, the striking disparity between the burden of paediatric HIV infection and access to the necessary infrastructure and therapeutic options required for its optimal management is addressed in a comparison between three sites of paediatric HIV care: Durban, South Africa; London, UK; and Boston, USA.

Antimicrobial abuse is a serious risk factor for the emergence of multi-drug-resistant (MDR) pathogens. We report on the emergence of multi-drug-resistant Acinetobacter anitratus species over two 8-week periods in 1999 in the neonatal and paediatric intensive care units (NICU and PICU) of King Edward VII Hospital, Durban, South Africa. The source, transmission dynamics, microbiological evaluations, antibiotic utilization patterns and outcome were evaluated. MDR Acinetobacter anitratus was isolated from different body sites in 23 infants less than 2 months of age, 18 in the PICU and five in the NICU. The mortality was 56.5% and two survivors required re-admission. Ten of the 23 cases had entered the ICU with MDR Acinetobacter anitratus. Eleven of the study infants had received broad-spectrum antimicrobial agents before entering the ICU, while all infants with nosocomially acquired MDR Acinetobacter anitratus had received broad-spectrum antimicrobial agents. All the surgical cases with MDR Acinetobacter anitratus died. Microbiological data from both ICUs for 1999 indicated that gram-negative bacteria accounted for two-thirds of isolates, Acinetobacter anitratus and Klebsiella pneumoniae accounting for 33% and 27% of the isolates, respectively. Only 53% and 57% of all Acinetobacter spp isolates were susceptible to piperacillin/tazobactam and carbepenems, respectively. MDR Acinetobacter anitratus is an emerging problem to which antimicrobial abuse contributes.

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Cytomegalovirus (CMV) pneumonitis is a significant cause of morbidity and mortality of children in Africa. The current practice for diagnosing CMV pneumonitis in this setting is based on interpretation of clinical, laboratory, and radiological findings. There is a need for a sensitive and specific laboratory test to objectively distinguish between patients with CMV pneumonitis and those with CMV infection, and non‐CMV pneumonia. In this study, we compared plasma and non‐bronchoscopic bronchoalveolar lavage (NBBAL) CMV viral loads in patients with CMV pneumonitis and those with CMV infection and non‐CMV pneumonia. Receiver operator characteristic curve analysis was used to establish a threshold and assess utility of viral loads in the diagnosis of CMV pneumonitis. We assessed the urea dilution method, and expression of viral loads relative to the total amount of extracted nucleic acids in correcting for NBBAL dilution. CMV quantification in NBBAL specimens was more predictive of CMV pneumonitis than blood CMV quantification. The threshold of 4.03 log IU/ml in NBBAL specimens has good predictive value and can be used to guide management of infants with suspected CMV pneumonitis. Adjusting for dilution of NBBAL specimens by using the urea dilution method or by expressing the viral load relative to the total nucleic acids extracted did not provide additional analytical benefits. J. Med. Virol. 89:1080–1087, 2017. © 2016 Wiley Periodicals, Inc.