The Diagnostics and Treatment of Tropical Diseases

CHAPTER I. Malaria

MALARIA

DEFINITION AND SYNONYMS

=Definition.=—Malaria is a protozoal disease caused by three species of Plasmodium. In the clinically benign types of malaria we have that of benign tertian, due to P. vivax, with a tertian periodicity and that of quartan, due to P. malariae and showing a quartan or seventy-two hour periodicity. The clinically malignant type of malaria is due to P. falciparum, the parasite of malignant tertian or aestivo-autumnal malaria.

The benign malarial fevers are characterized by a frank chill and well marked distinctions of cold, hot and sweating stages. In malignant tertian there is an indefinite or dumb chill with prolonged hot stage. Diagnostic of malaria are periodicity, parasites and splenic enlargement. The malignant tertian parasite is the one responsible for the so-called cerebral and algid manifestations of perniciousness. Man is the intermediate host of the parasite while the sexual cycle or sporogony goes on in some species of mosquito of the anopheline subfamily, the definitive host.

=Synonyms.=—Remittent Fever, Intermittent Fever, Ague, Marsh Fever, Paludism, Jungle Fever.

French: Paludisme. German: Wechselfieber.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—Hippocrates, who considered malaria as intimately connected with bile, divided the disease into quotidian, tertian and quartan, differentiating such types of fever from continuous fevers. It is interesting to note that Celsus recognized two types of tertian fever, the one benign and similar to quartan fever, the other far more dangerous, with a fever occupying thirty-six of the forty-eight hours, not entirely subsiding in the remission, but being only mitigated.

In the time of Caesar views were expressed by Varro that swamp air might be the cause of malaria and furthermore that animals, so small that the eye could not follow them, might transmit diseases by way of the mouth or nose.

In the view of our present knowledge it is remarkable that Lancisi, in 1718, should have associated marshes with the development of gnats, which insects he thought could not only introduce with their proboscides the putrefying organic matter of such swamps but animalcules as well.

In 1638 Countess del Chinchon, the wife of the Viceroy of Peru, was cured of an intermittent fever by the employment of the bark of certain trees which bark was introduced into Europe in 1640. The origin of the name cinchona is thus explained.

While Morton and Sydenham in 1666 noted the specific action of cinchona in certain fevers it remained for Torti, in 1753, by the use of cinchona, clinically to differentiate those fevers which were cured by cinchona from those which failed to yield to this specific. Quinine was not introduced until after 1820. Audouard, in 1803, was the first to draw attention to the splenic enlargement of malaria.

The views of Nott and Beauperthuis as to transmission of malaria and yellow fever by insects are considered under the latter disease.

In 1847 Meckel announced that the dark color of malarial organs was due to a pigment and in 1848 Virchow noted that this pigment was contained in cells. In 1875, Kelsch observed pigmented bodies in malarial blood and in 1880 came to the conclusion that these pigmented cells were diagnostic of malaria.

The year 1880 is the most important one in the history of malaria for on November 6, 1880, Laveran, at Constantine, first saw the parasites of malaria while carrying on investigations as to the origin of the pigmented bodies and melaniferous leucocytes. He not only noted the findings of spherical pigmented bodies but also of crescents and in particular the flagellation of the male gamete which demonstrated to him that these were living bodies.

The name Oscillaria malariae was proposed on account of the movements of the flagellate body, but had to be dropped as not valid, the generic name Oscillaria having been previously applied.

When these bodies were demonstrated to various Italian authorities, in 1882, they were thought by them to be degenerated red cells.

It may be stated that at this time the Italians, influenced by the work of Pasteur, were convinced that an organism, Bacillus malariae, reported by Klebs and Crudeli (1879) to have been isolated from water and soil of malarious districts, was the cause of malaria. This bacillus was said to be cultivable on ordinary media and to be capable, when injected into man, of producing malaria.

By 1885 the Italians were convinced that the bodies discovered by Laveran were the cause of malaria and Marchiafava, by staining with methylene blue, noted the ring forms and the increase in size up to that of the sporulating parasites. To Golgi we not only owe the discovery that the malarial paroxysm coincides with the period when the sporulating forms (merocytes) simultaneously reach maturity but also the exact working out of the cycle of quartan malaria. He even showed three stages of development of the parasites in a triple quartan. It may be stated that Golgi, Marchiafava and Celli are the ones to whom we owe our first knowledge of the existence of different species of parasites for different kinds of malaria. In these investigations they showed that as a rule they could reproduce a certain type of malaria by injecting the blood of such a case of malaria into a well man. Gerhardt, in 1884, was the first to produce malaria by the injection of malarial blood. Laveran insisted all this time that there was but a single species of malaria. About this period a great deal of research was carried on as to the origin of malarial parasites and it was found that many animals harbored parasites similar to the malarial parasites of man. In 1891 the chromatin staining method of Romanowsky was introduced which by bringing out the variations in chromatin distribution led to more accurate study of species and cycles.

Our present exact knowledge as to the existence of 3 species of malaria is largely due to the careful examinations made by Koch of fresh and stained malarial blood preparations.

In 1894 Manson formulated the hypothesis of the mosquito transmission of malaria. He based this upon the fact that the flagellation of the male gamete does not take place for several minutes after the removal of the blood from the peripheral circulation. He also suggested that larvae might feed upon infected mosquitoes dying upon the water and thus acquire the disease.

Ross for two years had mosquitoes feed upon the blood of malarial patients which contained crescents but as he used insects of the genera Culex and Stegomyia he failed to observe development in the tissues of the mosquitoes. In 1897 he used 8 dappled-wing mosquitoes (Anopheline) and in two of these, upon dissection, he noted pigmentary bodies different from anything he had observed in hundreds of dissections of other mosquitoes. At this time he was forced to discontinue this work for about six months.

In 1886 Metschnikoff from observation of sporulating parasites in the brain capillaries at the autopsy of a malarial case considered them to be coccidial in nature. In 1892 Pfeiffer, studying the Coccidia showed that there was an endogenous cycle going on in the epithelial cells as well as the long known exogenous cycle connected with the ingestion of oocysts passing out in the feces of an animal infected with coccidiosis. He suggested that malaria might similarly have an exogenous cycle as well as the well-known endogenous one. Opie noted hyaline and granular forms of parasites in the blood of crows and MacCallum, working with this malaria-like disease of birds (Halteridium), observed the fecundation of a granular female parasite by the flagellum-like process of the hyaline male cell.

In 1898, in India, working with a malarial disease of sparrows (Proteosoma), Ross infected 22 out of 28 healthy sparrows by mosquitoes which had previously fed on sick sparrows. He noted in the culicine mosquito employed for transmission the same cycle of development as that subsequently worked out for human malaria, in anopheline mosquitoes, by Grassi and Bignami, in Italy.

Koch’s great work in connection with malaria was to demonstrate that the malaria-like infections of other animals had no part in the causation of human malaria and that the malarial parasite could only circulate between man and certain mosquitoes.

In order to demonstrate conclusively the connection between infected mosquitoes and malaria Sambon and Low lived for three of the most malarious months of 1900, in one of the most malarious sections of the Roman Campagna, in a mosquito screened hut and did not contract malaria.

Infected mosquitoes were also sent to London from Italy and allowed to feed upon Doctor P. T. Manson and Mr. George Warren. After a period of incubation these volunteers came down with typical malaria with parasites in the blood.

In 1911 Bass first cultivated the parasites of malaria.

=Geographical Distribution.=—Malaria is so widely distributed over all parts of the tropical and subtropical world that it would require too much space to give its geographical distribution other than as given in the accompanying chart. The malaria belt may be said to extend from 60° N. to 40° S. Many of the islands of the Pacific are exempt.

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