In a series of 375 white patients naturally inoculated with vivax malaria, renewed or secondary clinical activity was more frequently observed following therapeutic interference with the primary attack, than when the latter terminated spontaneously. Clinical reactivation was not noted subsequent to attacks which came to spontaneous termination after 55 days of clinical activity, or in those which attained 48 days duration before interruption. Patients receiving adequate therapy subsequent to a spontaneous termination of their primary attack, did not experience subsequent secondary attacks; but of those not treated 46.5 per cent had further activity. Therapeutic interruption without further therapy resulted in secondary attacks in 73 per cent of the patients, but with adequate therapy in not over 25 per cent.
There is not evident any tendency to effect therapeutic interference at one rather than another period of the illness. It does not appear that the period at which therapy was initiated influenced the likelihood of bringing about a termination. Full therapy (i.e., 14 grams of quinine or 1.5 grams of atabrine) terminated the infection in 77.8 per cent of the patients, while smaller amounts only effected this result in 29.0 per cent. When the effect of interference was the production of a remission rather than termination, small amounts of parasiticidal drugs produced remissions not exceeding four weeks; but after full therapy in seven out of 10 instances they exceeded 180 days in duration. The duration of the remission tends to vary directly with the amount of the particular drug administered.
Spontaneous remissions are usually not over 2 weeks in duration, and none was observed exceeding 61 days. Second or third remissions do not materially differ from the first. Induced remissions (usually the first) often exceed the spontaneous in duration, but the subsequent secondary clinical activity does not materially differ in duration. Remissions varying from 67 to 282 days in duration accounted for 22.8 per cent of those experienced by the interrupted group. The shorter remissions in the latter group present a frequency incidence similar to those observed in the spontaneous group, while the longer are peculiar to the latter group alone. It is suggested that remissions whose length is in odd-numbered days are terminated by the reactivation of the parasite brood, the suppression of which produced it. The remissions which lasted 61 days or less, more frequently were of an odd number of days in duration, while in those exceeding this limit the duration was more often of an even number of days.
Some of the attacks which came to spontaneous termination were in general milder than those which were interrupted, an opinion based on the lower proportion of the former which were quotidian throughout, and the larger proportion of quotidian attacks which became tertian and of those which were tertian throughout. However on reactivation of the interrupted attacks, a larger proportion of the secondaries were tertian than were observed in the group the primary attacks of which terminated spontaneously.
The initiation of secondary clinical activity exhibits two frequency distributions. One distribution range is common to both the spontaneous and interrupted groups. In the former its maximum extension is marked by the 132nd day following inoculation, in the latter group it extends to the 174th day. The second frequency range begins about the 204th day, and our observations carry it on to the 415th day; it has as yet only been observed in the interrupted group. While it is not unreasonable to ascribe the activity in the first range to the primary parasitemia, difficulties arise in the case of the second range. It is noteworthy that the onsets of conspicuous examples of protracted incubation fall in the second range.
Most of the infections analyzed were induced with the McCoy strain, which during the period considered experienced 60 uninterrupted mosquito-human passages. No changes were observed in its characteristics during this time.