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Background: Human Respiratory Syncytial Virus (HRSV) is a major viral pathogen associated with acute lower respiratory tract infections (ALRTI) in children. Using monoclonal antibodies against virus proteins, it is categorized into two distinct major groups, A and B. The second hypervariable region of the G protein ectodomain gene provides a reliable surrogate for phylogenetical studies. We carried out a phylogenetic analysis of the HRSV strains isolated from children hospitalized with ALRTI in Malaysia.Methods: Nasopharyngeal aspirates (NPA) were taken from children less than five years of age hospitalized with ALRTI to Hospital Serdang, Malaysia. RT-PCR was used to detect HRSV. The second hypervariable region at the carboxyl-terminal of the G gene was amplified and sequenced using primer sets GPA/F1 and GPB/F1. Neucleotide sequences were edited and aligned with Bioedite software and Clustal X program. The phylogenetic relationships of the samples were determined separately for group A and B using neighbor joining (NJ), maximum parsimony (MP) and Bayesian methods (BI).Results: HRSV was detected in 83 of 165 (50.3%) patients studied. Sequence analysis of 32 isolates showed that multiple lineages of HRSV group A and B serotypes co-circulated. The topologies resulting from the different methods (NJ, MP and BI) congruent with each other. Phylogenetic analysis of nine retrieved sequences showed that all the HRSV-A strains were clustered into the NA1 genotype. All the 23 HRSV-B strains belonged to BA genotypes consisted of a 60-nucleotide duplication region. They were classified into three different genotypes of BA10, BA9 and BA4, respectively.Conclusion: HRSV played a prominent role for hospitalization of children in our study. The sequences of the second hypervariable region of G protein ectodomain gene from HRSV A and B demonstrated remarkable genetic diversity. The present finding seems to be consistent with other studies which found the newly emerged HRSV genotypes of NA1 and BA genotypes are replacing the previously dominant genotypes. This is the first documentation of the phylogenetic relationship and genetic diversity of HRSV isolates among hospitalized children diagnosed with ALRTI in Malaysia.

NTS bacteraemia has a high mortality (47%) and recurrence (43%) rate in HIV-infected African adults. Recurrence is caused by recrudescence rather than re-infection. As focal infections were rarely found, recrudescence may often be a consequence of intracellular tissue sequestration. There is an urgent need for improved primary treatment and secondary prophylaxis in Africa.

Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load.

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We prospectively collected laboratory details and outcome data on all patients with laboratory-confirmed cases of meningitis that presented to our unit in Blantyre, Malawi, from 1 April 1998 through 31 March 1999. There were 502 patients with cases of meningitis; the most common causative organisms were Cryptococcus neoformans and Streptococcus pneumoniae. This pattern probably reflects the local human immunodeficiency virus (HIV) seroprevalence (31%) and is different from the pattern in 1974, when Neisseria meningitidis was the most common isolate. There has been an 8-fold increase in the number of meningitis cases per year since 1974, and a doubling of the percentage of medical admissions due to meningitis. The inpatient mortality rate among patients with cases of pneumococcal meningitis was 61%, and in the group as a whole was 41%. Despite the HIV-related pattern of infecting pathogens among these cases of meningitis and the increased incidence of the condition, there was evidence that the typical seasonal pattern of pneumococcal meningitis, which peaks in the cold, dry season, was preserved.

Rationale: We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain.Objectives: To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model. Methods:We identified healthy volunteers that were naturally colonized with pneumococcus and, after clearance of their natural carriage episode, challenged them with a heterologous 6B strain. In another cohort of volunteers we assessed 6BPS-specific, PspA-specific, and PspC-specific IgG and IgA plasma and memory B-cell populations before and 7, 14, and 35 days after experimental pneumococcal inoculation.Measurements and Main Results: Heterologous challenge with 6B resulted in 50% carriage among volunteers with previous natural pneumococcal carriage. Protection from carriage was associated with a high number of circulating 6BPS IgG-secreting memory B cells at baseline. There were no associations between protection from carriage and baseline levels of 6BPS IgG in serum or nasal wash, PspA-specific, or PspC-specific memory B cells or plasma cells. In volunteers who did not develop carriage, the number of circulating 6BPS memory B cells decreased and the number of 6BPS plasma cells increased postinoculation.Conclusions: Our data indicate that naturally acquired PS-specific memory B cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition.

Pseudomonas aeruginosa colonization and infection was studied over a 6-mo period in a 36-bed mixed general medical-oncology unit. We used selective media for serial surveillance cultures on 283 patients, the environment, and personnel. Twelve percent of patients were colonized on admission and 10% acquired P. aeruginosa. Using serotyping and multilocus enzyme electrophoresis, we identified 63 genetically distinctive strains; four prevalent strains accounted for 21% of isolates. Only 5 of 33 nosocomial acquisitions were due to horizontal transmission. Nine acquisitions were linked to environmental sources (e.g., sink surfaces), which often harbored antibiotic-resistant strains but posed a risk only to oncology patients. Although significant Pseudomonas infections occurred in only 11% of colonized patients, 63% of colonized severely neutropenic patients--predominantly those who had acquired the prevalent, often environmentally linked strains--developed infections. Thus, P. aeruginosa was a significant pathogen in oncology patients; typing by multilocus enzyme electrophoresis allowed the detection of important environmental sources.