Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children

Molecular mechanisms of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease

Quantiferon Gold-in-tube assay for TB screening in HIV infected children: influence of quantitative values

Abstract Background HIV infected children are at increased risk of TB disease and require annual TB screening. Data on use of IGRA for TB screening in them are limited. We retrospectively evaluated the usefulness of Quantiferon Gold-in-tube test (QFT), an IGRA in screening for LTBI in relatively healthy, immunologically stable HIV infected children. Methods HIV infected children with no prior history of TB were screened for latent TB as part of routine care. They underwent risk of TB assessment, TST and QFT. QFT was repeated twice or three times depending on the quantitative values. Independent test validation was also performed. Results Eighty one children had 109 QFT tests. All had adequate mitogen responses. The initial QFT was positive in 15 (18.5%) children; quantitative IGRA responses were 0.35-1.0 IU/mL in 9 (60%), 1.0-10 IU/mL in5 (33.3%) and >10 IU/mL in 1 (6.7%). None that tested positive had documented TB exposure or TB disease. Baseline characteristics in the QFT positive and negative groups were similar. Repeat testing within 17 weeks demonstrated reversion to negative in 79% of cases. Repeat blinded independent testing of all QFT positive results and a random selection of initial negative tests demonstrated concordance in 96% of cases. Seven children (QFT > 1.0 IU/mL or positive TST) were offered INH preventive therapy. In no case has TB disease developed in 2 years of close follow-up. Conclusions QFT is a valid method for LTBI screening relatively healthy, immunologically stable HIV infected children. However, reversion to negative on repeat testing and lack of correlation with TST results and risk of TB exposure makes interpretation difficult