Observations on Induced Falciparum Malaria

Mark F. BoydStation for Malaria Research, Tallahassee, Florida

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S. F. KitchenStation for Malaria Research, Tallahassee, Florida

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Discussion and Summary

The employment of P. falciparum is necessary to make malaria therapy available to negro patients through mosquito inoculation. Successful propagation of falciparum by this means is more difficult than that of vivax. Among 60 patients successfully inoculated in this manner, there were only 46 in whom inoculation took on the first application of the mosquitoes. The remaining twenty patients in the series, on whom further applications were failures, were, from the standpoint of expediency, for the most part subsequently inoculated with blood.

Four of the 60 successfully inoculated patients were white, but it has not been deemed advisable to segregate them in the analyses presented.

Although five strains of P. falciparum of local origin were employed, two-thirds of the inoculations were performed with one. No noteworthy differences that might be attributed to strain characteristics were observed, except in so far as they might relate to the susceptibility of the patients.

Although varying numbers of infected mosquitoes were employed, there is nothing to indicate that presumable increases in the number of sporozoites, as indicated by the application of several positive mosquitoes, resulted in any greater number of takes. This suggests that in the absence of a homologous immunity to the strain employed, the susceptibility to this parasite is very great, and that the application of one infected mosquito will usually be more than ample to provide the minimal infecting dose.

The data suggest that the season at which an inoculation is performed may influence the resulting infection in several respects. Patients inoculated in the last quarter of the year (October to December) have shorter incubation periods and longer attacks, and they present fewer instances of renewed activity after the cessation of the primary attack. Inoculations made during the winter present long incubations, the shortest attacks and the greatest likelihood of renewed activity.

Where data relating to birthplace is available, it would indicate that the patients have come from the southeastern states or the adjacent West Indies. The data are too limited to justify comments on possible variation in susceptibility in relation to place of origin.

There is some suggestion that the intrinsic incubation period may vary with the strain of parasite as well as with the season. In general, parasites are detectable in the peripheral blood before the onset of symptoms. The minimal period between inoculation and the detection of falciparum parasites in the blood is 6 days, 2 days less than in the case of vivax infections. The longest period observed has been 25 days. They are most commonly first found from the eleventh to the thirteenth day, while the clinical onset takes place most commonly on the twelfth day, although it has occurred as early as the seventh.

Clinically, falciparum cases may present a remittent or an intermittent temperature. Remittent fever, if present, is observed at the onset and may last for a week or more. Its presence suggests a high degree of susceptibility on the part of the patient and great invasiveness on the part of the parasites in that individual. If the evolution of the illness is not interfered with, it may continue until the infection overwhelms the patient, or may spontaneously transform into an intermittent type. Most commonly the infection begins and continues as an intermittent one of a tertian type. The thermal curves of the paroxysms however are broken into a number of secondary peaks.

Falciparum infections possess remarkable powers of invasiveness, and must be closely watched so that they are at all times kept within bounds. Apparent safe limits for their evolution are temperatures not exceeding 104° to 105°F., especially if intermittent, and parasite counts not exceeding 100,000 per cubic millimeter. The occurrence of either or both these indications calls for the immediate administration of 5 to 10 grains of quinine, to be repeated within an hour if the effect on the temperatures is not apparent within that interval. Such interference will usually terminate a remittent fever and the subsequent manifestations will be intermittent. It is unusual for interference to be required more than twice in the course of an attack. Interference may bring about the cessation of the attack within five days, a circumstance that is less likely if the drug is administered within the first few days following the onset.

Even discounting the possible effect of the small dose of quinine employed, the primary falciparum attack tends to be shorter than that of vivax. Its mean duration has been 10.8 days, while the maximum attack noted lasted 36 days. As previously stated duration tends to vary with the season.

A renewal of clinical activity after spontaneous or induced cessation of the primary attack is common, being noted in 58 per cent of the cases. Some patients may experience a series of as many as four such recurrences. Nearly all are observed within a period of eight weeks following the termination of the primary attack. In duration they may be shorter or longer than the primary attack and occur without relation to the duration of the latter.

Thorough intensive quininization after termination of the primary attack makes the appearance of recurrences unlikely.

In this paper we have not considered the subsequent duration of the infection at subclinical levels.

It may be noted in conclusion, that from the standpoint of the therapy of neurosyphilis, the employment of falciparum malaria has, in the Florida State Hospital, given as good results as those secured from vivax malaria.