Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa.

There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era.

Clinical predictors of Pneumocystis carinii pneumonia, bacterial pneumonia and tuberculosis in HIV-infected patients.

BACKGROUND: Clinicians are frequently faced with the differential diagnosis between Pneumocystis carinii pneumonia (PCP), bacterial pneumonia, and pulmonary tuberculosis in HIV-infected patients. OBJECTIVES: To identify features that could help differentiate these three pneumonia types at presentation by evaluating the clinical characteristics of the three diagnoses among patients at two urban teaching hospitals. DESIGN: Retrospective chart review. METHODS: Cases were HIV-infected patients with a verified hospital discharge diagnosis of PCP (n = 99), bacterial pneumonia (n = 94), or tuberculosis (n = 36). Admitting notes were reviewed in a standardized manner; univariate and multivariate analyses were used to determine clinical predictors of each diagnosis. RESULTS: Combinations of variables with the highest sensitivity, specificity, and odds ratios (OR) were as follows: for PCP, exertional dyspnea plus interstitial infiltrate (sensitivity 58%, specificity 92%; OR, 16.3); for bacterial pneumonia, lobar infiltrate plus fever < or = 7 days duration (sensitivity 48%, specificity 94%; OR, 14.6); and for tuberculosis, cough > 7 days plus night sweats (sensitivity 33%, specificity 86%; OR, 3.1). On regression analysis, independent predictors included interstitial infiltrate (OR, 10.2), exertional dyspnea (OR, 4.9), and oral thrush (OR, 2.9) for PCP; rhonchi on examination (OR, 12.4), a chart mention of 'toxic' appearance (OR, 9.1), fever < or = 7 days (OR, 6.6), and lobar infiltrate (OR, 5.8) for bacterial pneumonia; and cavitary infiltrate (OR, 21.1), fever > 7 days (OR, 3.9), and weight loss (OR, 3.6) for tuberculosis. CONCLUSIONS: Simple clinical variables, all readily available at the time of hospital admission, can help to differentiate these common pneumonia syndromes in HIV-infected patients. These findings can help to inform clinical decision-making regarding choice of therapy, use of invasive diagnostic procedures, and need for respiratory isolation.