Reactions of Monkeys to Experimental Mixed Influenza and Streptococcus Infections

Abstract

1. The vital importance of the cellular defense forces in the resistance of the monkey to combined streptococcus and influenza virus infections has been demonstrated. 2. Some of the conditions prejudicial to the maintenance of an optimum cellular reserve in the infected animal have been revealed; viz., undernutrition, physical cold, intratracheal route of infection. 3. The potential threat exerted by latent foci of streptococci, and the importance, in relation to the combined infection with virus, of cellular and humoral immunity, together or separately, have been demonstrated. The essential rôle of optimum nutrition (notably as concerns the vitamin B complex, and folic acid specifically) in the prevention of disastrous illness from these infectious agents, individually or in combination, would seem to have been proven. 4. Signs of glomerular nephritis appeared in a significant number of monkeys receiving Streptococcus hemolyticus and influenza virus in sequence, followed by reinoculation or spontaneous reappearance of the streptococci. 5. Reinoculation of Streptococcus hemolyticus, group C, resulted in a prompt "booster" increase in the opsonic index. Virus instillation was followed by just as sudden a depression in this index. 6. Reinoculation failed to evoke either the granulocytosis or the leucopenia in monkeys which are characteristic effects of the streptococcus and the virus respectively when these agents are introduced for the first time by way of the nasal mucous membrane. 7. Simultaneous intranasal inoculation of influenza virus, type A, and Streptococcus hemolyticus, group C, in nutritionally normal Macaca mulatta failed to produce obvious signs of disease. In most of the animals, however, a streptococcus-induced leucocytosis followed by a delayed virus-induced granulopenia developed. 8. Inoculation of influenza virus followed in 4 to 17 days by streptococci produced obvious signs of disease in five of eleven animals which had become leucopenic as result of the action of the virus, and fatal streptococcal septicemia in two monkeys. 9. The development of signs of infection in previously healthy monkeys exposed to virus followed by streptococci confirms both the clinical and laboratory experience of other observers, that virus infection may predispose to secondary bacterial invasion, and, that at times, under unfavorable circumstances, the infection may become overwhelming. Although the complete mechanism of resistance is as yet not wholly clear, the depressant or inhibitory effect of the virus on both its cellular and humoral elements has been established.

Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness

“…Even though neither agent was pathogenic when administered alone, they were highly fatal in combination [68]. In rhesus monkeys, human influenza viruses given intranasally were not pathogenic, but could be made so by nasopharyngeal instillation of otherwise nonpathogenic bacteria [69]. During the 1940s, additional studies in ferrets, mice, and rats established that the influenza virus in combination with any of several pneumopathic bacteria acted synergistically to produce either a higher incidence of disease, a higher death rate, or a shortened time to death [70-73]; these effects could be mitigated or eliminated if antibiotics were given shortly after establishment of combined infection [73].…”

Depression of Rat Neutrophil Exudation and Motility by Influenza Virus

“…Depression of neutrophil chemotaxis and phagocytosis by influenza virus in vitro has been reported (1,10,11,(13)(14)(15), and studies on the elimination of bacteria from the lungs of experimental animals infected with influenza vims suggest that neutrophil phagoeytic function may be impaired locally (3,6,16). The mortality of animals that have inhaled pathogenic bacteria after a previous inhalation of influenza virus is higher than that of animals that have been given bacteria without influenza (2,4,7,17,19). High concentrations of virus can be found in lung tissue homogenates during the peak of mouse influenza (5,18).…”

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

“…In a later report, the same researchers inoculated rhesus macaques IN either with a mixture of virus and S. hemolyticus , or with virus followed 4 or 16 days later by the same bacteria (Wilson et al, 1947). As in the earlier experiments, virus alone produced no visible signs of illness, but some macaques inoculated with bacteria four days after virus challenge became listless and irritable.…”

“…In two reports from the 1940s in which rhesus macaques were infected first with influenza virus, then with Streptococcus hemolyticus , the animals developed only a transient fever, with no visible signs of illness (Merino et al, 1941;Wilson et al, 1947). Similarly, Verlinde and Makstenieks infected a large number of rhesus and cynomolgus macaques with influenza virus, followed by Staphylococcus aureus (Verlinde and Makstenieks, 1954).…”