Malarial Paroxysms Research Articles

Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p < 0.005 and < 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted < or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p < 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.

Malaria tertiana bei Kindern und Erwachsenen aus dem Epidemiegebiet der südlichen Türkei

Since 1974 an epidemic of tertian malaria has been spreading around the Adana and Tarsus townships in southern Turkey, with a peak incidence of 115 500 cases in 1977. A further increase is to be expected because the insect vectors have become resistant to insecticides. Since 1975 eleven children and three adults have been treated for P. vivax malaria. They had all stayed in the epidemic area during the transmission season which lasts from July to October. Because of a long primary latent period seven patients only developed first manifestations of the disease six to nine months after leaving Turkey. The classical malarial paroxysms were missing during the first weeks of the primary attack. Several children had a febrile illness over weeks with headache, vomiting, abdominal pain, hepatosplenomegaly, high blood-sedimentation rate and severe haemolytic anaemia, so that appendicitis or septicaemia had been suspected. Tetracyclines and trimethroprimsulphamethoxazole were able to suppress the disease without preventing relapses.

Relationship of serum complement levels to events of the malarial paroxysm.

Malarial paroxysms due to Plasmodium vivax were studied for alterations in whole serum complement (C') and certain C' components. The objective was to relate C' values with events of the parasite cycle during schizogony and with the febrile pattern. Substantial decreases in C' were found in 9 of 18 paroxysms studied during relapse. In contrast, only one of 22 paroxysms occuring during the primary attack was associated with a striking depression in C', and this case exhibited certain characteristics of a relapse paroxysm. The mean change in C' levels during paroxysms in relapse (-23%) was significantly different from paroxysms of the primary attack (-2%). Depletion of C' was associated directly with degree of parasitemia and presence of complement-fixing (CF) antibody. Lowest levels of C' were found within a few hours after completion of schizont repture and peak fever. C4 levels reflected changes in whole serum C' and appeared to be a more sensitive indicator of C' alterations during malaria. While the alterations in C4 as well as C1 and C2 indicated that the classical C' pathway was involved, some preliminary results showed little or no depletion of late components, C3 and C6. Overall results are compatible with C' activation and depletion during or soon after schizont repture if parasite density is sufficiently high and if CF antibody is present.

USE OF QUANTITATIVE PARASITE INOCULATION DOSES IN PLASMODIUM VIVAX MALARIA THERAPY

CUMULATIVE experience with therapeutic malaria in the management of neurosyphilis during the past twenty-five years has resulted in refinement of technics and in a clearer understanding of the characteristics of induced malarial infection. The febrile course of Plasmodium vivax malaria, following either natural or artificial inoculation, in most instances does not display the regular tertian paroxysms commonly described in textbooks. The majority of infections exhibit quotidian cycles with varying degrees of irregularity. At the onset of clinical activity, following mosquito inoculation or the usual administration of a 5 to 10 cc. inoculum of blood at institutions utilizing therapeutic malaria, a period of several days of remittent fever, characterized by continuous low grade elevations of temperature, to 101 or 103 F., is experienced. This period of remittent fever is commonly accompanied with severe malaise and exhaustion, often debilitating the patient prior to the establishment of true malarial paroxysms. Since the accepted

ORTHOSTATIC HYPOTENSION ACCOMPANYING THE TABETIC FORM OF DEMENTIA PARALYTICA

In 1925, Bradbury and Eggleston¹first described orthostatic hypotension under the title "postural hypotension." Previous to the present writing about 40 apparently acceptable cases have been recorded in the medical literature. The following case is the first one found in which this condition accompanied the tabetic form of dementia paralytica and is also the first one known in which treatment consisted of a course of malarial paroxysms. At least 5²cases of orthostatic hypotension associated with tabes dorsalis have been reported, but none of this condition with typical tabetic dementia paralytica. Since the malarial therapy was unexpectedly well tolerated and the patient apparently received considerable benefit from it, a report was deemed worthy of being on record. <h3>REPORT OF CASE</h3> S. V., aged 42, a shoemaker of Italian descent, had been in good health until about one year before his admission to the dermatologic service, on Jan. 7,

THE SIGNIFICANCE OF GAIN IN WEIGHT IN THE MALARIA TREATMENT OF GENERAL PARALYSIS

In a preliminary report, published a year ago, on the malaria treatment of general paralysis,1it was mentioned that a large proportion of patients gained considerable weight after completing the course of malaria, and that, on the whole, the patients who did especially well in a clinical sense made a somewhat greater eventual gain in weight than the others. Continued observation of these and of additional patients now makes it possible to say something more definite of the further course of the weight curve in these patients, and to deal less tentatively with the question whether this gain in weight, striking as it often is, has any actual importance in prognosis. The material on which the present observations are based comprises sixty-two patients whose weight has been recorded at weekly intervals for an extended period of time subsequent to the final malarial paroxysm. Of these sixty-two cases, forty-seven have

THE USE OF SODOKU IN THE TREATMENT OF GENERAL PARALYSIS

This is a preliminary report of the use of sodoku in the treatment of general paralysis. The series consists of twelve paretic patients who were inoculated withSpirochaeta morsus-muris, the etiologic agent of sodoku. This work was undertaken in an attempt to improve on the malarial method which has been used for eight or nine years in the treatment of general paralysis. It therefore seems advisable to preface the report of our investigations with an account of the treatment of general paralysis by malaria and other febrile producing methods. In 1917 von Jauregg1introduced the malarial method. Since that time it has been quite generally utilized in most of the countries of Europe and also in the United States, the results reported being extremely favorable. The method usually consists of inoculating a patient with malarial blood, which leads to the development of malarial paroxysms. The patient is generally allowed to

CLINICAL CALORIMETRY XXXII

During the last seven or eight years, many clinicians have been treating arthritic patients by means of intravenous injections of foreign protein. These produce chills which resemble malarial paroxysms and afford an ideal opportunity for studying in man the phenomena of temperature regulation. In 1917 the chills and fever in several cases of malaria were studied in the Sage calorimeter. 1 The present investigation was undertaken as a supplement to the work in malaria in order to study in more detail the mechanism of the rise and fall of body temperature. The gaseous exchanges of patients have been studied by Kraus and Chvostek 2 after giving tuberculin, and in animals by Freund and Grafe, 3 Versar, who gave infusions of sodium chlorid, 4 and by Berrar, 5 who used aloin. In general, these animal experiments showed a rise in total oxidative processes accompanying the rise in temperature. Sometimes this increase amounted to 130 per Tie

On the alleged role of hematin in the production of the malarial paroxysm

The view has been advanced that the symptoms of the malarial paroxysm are due to the toxic action of hematin1. The basis for this view rests, (1) in the alleged identity of hematin and malarial pigment, and (2) in the effect produced by intravenous injections of hematin solutions in rabbits. Inasmuch as hematin has not yet been isolated from the fresh organs of an undoubted case of malaria, malarial pigment cannot be justly identified with hematin. The present communication deals chiefly with the temperature curve in rabbits after intravenous injection of from 0.0023 g. to 0.0370 g. of hematin per kilo body weight.The hematin was prepared from hemin by the method of Piloty.2 The hemin was prepared from ox blood by the Piloty modification3 of the Schalfejeff method and recrystallized from pyridin. The hematin was dissolved in 0.9 per cent. NaCl solution containing 1.5 per cent. NaHCO3. All solutions used contained 0.5 g. hematin in 100 c.c., were microscopically clear, and were sterile.The rectal temperatu...

MALARIAL PIGMENT (HEMATIN) AS A FACTOR IN THE PRODUCTION OF THE MALARIAL PAROXYSM

The paroxysm of hematin intoxication in the rabbit undoubtedly presents many features of striking similarity to the paroxysm of human malaria; still one must hesitate to apply such results unreservedly in an attempt to identify the causative agent of the malarial paroxysm. When, in addition to the character of the paroxysm, we consider the sequence of events in the two instances, the analogy becomes so close that it seems impossible to regard the matter as a mere coincidence. The injection of hematin, especially in fractional doses, is in a measure comparable to the liberation of hematin into the human circulation by the malarial parasite. In these experiments, See PDF for Structure both solution and finely divided suspensions of hematin have been found equally effective in eliciting the phenomena of the paroxysm, and while it seems possible that a portion of the malarial pigment might be dissolved in the alkaline human serum, such an assumption is probably not essential. It might be objected that the toxic action of foreign hematin thus injected into the circulation would probably be greater than that of hematin derived from an animal's own blood, but as far as I have been able to determine, this objection does not seem valid, as rabbit hematin, dog hematin, and ox hematin produce in the rabbit effects that are alike in both character and degree. The dose of hematin remains as the one factor to which it is possible to attach some degree of uncertainty, but even here the author feels that the range of experimental conditions has been kept within the bounds of legitimate analogy with conditions existing in the human subject of malarial infection. Finally, the most conservative estimate of the value of such experiments points strongly to the fact that we have at least a potentially toxic substance in the pigment hematin as liberated by the malarial parasite into the circulation of the human host. There is also abundant evidence to show that the action of hematin is not confined to the paroxysmal phenomena of malaria, but that other features of the disease may find their explanation in the action of this pigment. For the present, however, it seems advisable to confine the discussion to this one phase of the question.

STUDIES OF MALARIA IN PANAMA: 1.—CLINICAL STUDIES OF MALARIA IN THE WHITE RACE

During my service in 1905 and 1906 in Dr. Gorgas' in Ancon Hospital, I was particularly interested in certain phases of malarial infections, and I analyzed the cases admitted during the six months of my service with reference to the following points : 1. Incidence of malarial infections and mortality. 2. Results of examinations of blood for malarial parasites. 3. The relative value of several systems of quinin administration. 4. The time of day when malarial paroxysms occurred. 5. Malarial immunity. 6. The quinin test in differentiating malarial from other fevers. 7. Chronic malaria or malarial cachexia. INCIDENCE AND MORTALITY There were admitted to the white fever wards during the six months 1,300 patients; 1,107 of these cases were clinically malarial. That is, at this time a little more than 85 per cent. of the morbidity among the whites was due to malaria. Among the 1,300 patients there were 15