The American Journal of Tropical Medicine and Hygiene - Volume s1-12, Issue 6, 1932

The general similarity of the functional disturbances seen in the cases of tropical blackwater fever, hemoglobinuria from other causes and the experimental hemoglobinuria produced in dogs by transfusion with their own laked blood, indicate that both clinical symptoms and pathological lesions are essentially referable to intravascular hemolysis. This view is supported by pathological evidence secured from post mortem examinations of human cases (7, 3) and of the dogs used in these experiments.

Anuria and lesser grades of renal functional impairment seem to be referable primarily to occlusion of the renal tubules with coagulated blood pigment debris. Actual cellular injury appears to play a minor part. The functional disturbances which attend the initial phase of the disease, vomiting and shock, provide conditions peculiarly unfavorable for the secretion of urine and, therefore, may play an important secondary rôle in the production of anuria or oliguria. The shock is seen only in severe cases with massive hemolysis and may well be quite similar in its origin to that following hemorrhage. The logical therapeutic procedure would seem to be early blood transfusion, where this is not precluded, as it was in case A-5680, by the appearance of abnormal blood agglutinins. Transfusions have already been recommended and utilized with some success (9, 28, 29).

The initial vomiting, like the chill and temperature, resembles the symptoms that follow intravenous injections of any foreign protein. The cause of the subsequent vomiting is not clear. The result of emesis is, however, inevitably to deplete the salt and water stores of the body and thereby to diminish the materials required for the prdouction of urine. The rational way to meet this situation would seem to be the parenteral administration of glucose and saline solutions. Such measures may, however, fail to achieve their purpose if the vomiting is permitted to continue. Oral administration of fluids, in the face of vomiting, may only wash more salt from the body. The withdrawal of all fluids by mouth and the substitution of parenteral saline and glucose solutions may, in these circumstances, put an end to vomiting, restore the body fluids to their proper composition and, by providing conditions more favorable to urine formation, accelerate the return of normal renal function and recovery.

The actual effects of the intravascular hemolysis appear to be extremely transitory. Even without the intervention of the kidneys, in cases with the most massive hemolysis, both the pigment and the protein radicles of the released hemoglobin are removed from the blood with the greatest rapidity. This affords a further reason for believing that early treatment by transfusion and infusion, might, by preventing suppression of urine and minimizing impairment of renal function, eliminate the later secondary effects of the disease.

No support has been found for the theory that acidosis occurs in blackwater fever to offer an indication for alkaline therapy. The administration of bicarbonate in the cases described led to the development of alkalosis. In the more severe cases the alkali reserve was already somewhat above normal, before bicarbonate was given, presumably as a result of vomiting. Baker and Dodds (3), in experimental studies of hemoglobinuria, in rabbits, find that in an alkaline urine hemoglobin remains unprecipitated and unchanged, while in a highly acid urine (pH < 5.8) it is converted to methemoglobin and is precipitated if the salt concentration in the urine is excessively high. These observations have been cited as new support for alkaline therapy (28, 30) and do afford a more rational basis for this mode of treatment than the acidosis theory did. They also seem to offer an argument against the use of excessive amounts of salt solution. It must be borne in mind, however, that the patient with extreme base depletion from vomiting will excrete an acid urine, even when the serum bicarbonate is extremely elevated and that the administration of sodium chloride will, in this case, render the urine alkaline (31, 32). Furthermore, the urine after excessive vomiting contains minimal amounts of sodium chloride and the urinary concentration of this salt is not greatly increased by the administration of enough sodium chloride to restore the normal concentration in the serum. Finally dilution of the hemoglobin in the urine by the provision of a large urine volume may more than offset the effects of both reaction and salt concentration.

The experiments reported describe the actual cultivation of Mycobacterium leprae on artificial culture medium in a gaseous tension of carbon dioxide and oxygen through sixteen generations over a period of eighteen months. Several new mediums have been prepared and inoculated but no growth appeared after six weeks incubation. Organisms from the ninth, tenth and eleventh serial transfers failed to produce experimental tissue changes in older monkeys then were used several months earlier when the culture which was not so distant from the host produced granulomatous lesions by intradermal injection. Guinea pigs and several varieties of mice manifested no pathologic changes when injected intracutaneously with these cultures. Serological data are given as a matter of record. A discussion of the possible mechanism of infection in human leprosy is presented.

These studies are being continued.

By working with numerous strains of various species of Leishmania Ross, 1903, and with one species of Leptomonas Kent, 1880, it was possible for us to verify differences in the agglutination between the two above named genera, by the method proposed by Noguchi. An immune serum against Leishmania brasiliensis Vianna, 1911, did not agglutinate a strain of Leptomonas ctenocephali (Fantham, 1912). This verification was made but once and was not checked out; but it agrees with the experiments of Noguchi (9, 10) Kligler (43), and Wagner and Koch (44).

With this method differences were always noticed in the behaviour of different species of Leishmania, in the presence of anti-Leishmania brasiliensis serum. Immune sera against Leishmania brasiliensis have never agglutinated Leishmania tropica, Leishmania donovani, Leishmania infantum and Leishmania canis, a finding that agrees with Noguchi's verification.

The behaviour of different strains of Leishmania brasiliensis cultivated in Noguchi's medium with anti-brasiliensis sera demonstrated an intimate correlation among the various strains, as agglutination frequently takes place. Results were not so clear as in Noguchi's findings and we can see from table 1 and 2 that homologous sera not always agglutinated the same strain or other strains of Leishmania brasiliensis. Positive reactions were, in addition to this, frequently weak and after a superficial examination one would conclude that immunological differences exist between various strains of Leishmania brasiliensis. Microscopical examination of the cultures show that the lack of agglutination is due to the dying of the flagellates in the culture media containing homologous sera, a fact that will be discussed more in detail in a future paper. Agglutination occurs probably only in tubes in which flagellates were inoculated in an amount sufficient to be visible, or in cases in which the sera were not sufficiently potent to kill the flagellates immediately after inoculation, thus allowing the mass of flaggelates to increase.

Lysis of the flagellates is also a cause of failure of Noguchi's method, so one will be led to conclude that immunization of the rabbits must not be too prolonged, as lysins can appear in the blood in amounts that will mask the agglutinating power of the serum. To avoid this, it is sufficient to heat the immune serum and the hemoglobin before preparing the culture media for this reaction.

A relatively high incidence of amebiasis (E. histolytica) presumably exists in Guatemala, Costa Rica, and the interior of Panama. In the Hospital Santo Tomas in Panama City, however, only 13.9 per cent of a selected group of patients (from the men's medical, women's medical, and obstetrical wards) were found to harbor E. histolytica. In recent California surveys where comparable laboratory methods were used (wet fixed iron hemotoxylin stained smears examined) there has been reported an incidence of 9.8 to 16 per cent. Eighty-eight of the 101 Panama cases of amebiasis found on 1834 examinations were treated with Carbarsone (carbamino-phenyl-arsonic acid containing 28.8 per cent arsenic) given orally in average dosage of 5.0 grams for ten days. This amebacide was effective without adjuvant in clearing all but one of 37 cases that could be followed during the month of therapy. No evidence of arsenic toxicity was noted when total doses to 300 mgm. per kilogram were given orally.

The examination of a representative sample of the population for splenic enlargement is a method that has been widely used in estimating the incidence, and to some extent the severity, of malaria in a community. Such examinations are usually made on children. Palpation for enlarged spleen, if it will give a reasonably accurate idea of the extent of infection, is a much easier and more rapid method of malariometry than the collection and examination of specimens of the peripheral blood. Attention has been drawn recently, however, to the influence of race in determining whether or not the spleen will present rather constant enlargement in subacute and chronic malaria.

Clark (1), in a report of a study of spleen and malaria parasite rates in Haitian negroes, says that not more than one-eighth of the cases of malaria in adults, proved by blood examination, would have been found if reliance had been placed solely on splenic tumor, and in children only about half of the cases would have been discovered.

In 16 smear-positive patients with malaria hydroquinidine sulphate in dose of 10 grains (0.65 grams) daily for four days about four hours before chill time, caused in every case disappearance of parasites from the blood and cessation of symptoms by the fifth day. There were 4 cases of estivo-autumnal infection, 12 of benign tertian.

In so far as concerns the immediate results of a short course of treatment, the conclusion of Giemsa and Werner (4) is confirmed, that hydroquinidine appears equal to quinine in antimalarial activity.

Hydroquinidine in single 10-grain (0.65 grams) dose of the sulphate daily was well tolerated, producing cinchonism (vertigo) in only 1 case. In 1 case this dose was given daily for forty-eight days, and a 5 grain dose daily for the following twenty-five days, without ill effect.

Of all the parasitic affections of man those caused by organisms inhabiting the intestinal tract are the most important. First, because they comprise the bulk of parasitic diseases, usually estimated at about two-thirds of the total number; secondly, because they are, generally speaking, much more widespread geographically than are other parasitic affections; thirdly, intestinal parasitism of late years has become an important factor in clinical differential diagnosis, especially in the more northerly latitudes, whereas heretofore they have been generally thought of as tropical affections; and lastly, because of the simplicity and efficiency with which they can be treated.

DIAGNOSIS In discussing the diagnosis of intestinal parasitism two factors must be considered: The first, that parasitic infestations, contrary to most bacterial infections, such as diphtheria, typhoid fever etc. are generally characterized by what may be called “silent lesions,” that is, they are slow in their development and consequently when manifested as a rule have no definite clear cut symptoms.

• 1.  A cultural examination of one hundred consecutive abscesses in Jamaica shows that only 6 per cent contain the β-haemolytic streptococcus, the remainder containing the staphylococcus.
• 2.  A filarial census of 250 unselected persons together with routine laboratory observations over many years reveals that while Filaria bancrofti is occasionally introduced it does not spread in Jamaica although the requisite mosquito vector abounds in the island.
• 3.  There is, thus, in Jamaica a parallel low incidence of the β-haemolytic streptococcus and of Filaria bancrofti comparable to the parallel high incidence of these agents in British Guiana and in st. Kitts.
• 4.  Lymphangitis and elephantiasis are both very rare in Jamaica.
• 5.  Histological, clinical and bacteriological evidence from a case of elephantiasis in Jamaica appearsto support the hypothesis that elephantiasis in the Caribbean tropics is associated with the presence of many minute foci of the β-haemolytic streptococcus in the corium of the affected part.
• 6.  Intramuscular abscesses, whose relation to Filaria bancrofti is still in dispute, are practically unknown in Jamaica.

In 1924 Veador Leonard introduced into the practice of medicine a hexyl derivative of resorcinol as a urinary antiseptic which has since come into use under the name “caprokol.” Several years later (Leonard and Feirer, 1931) the next higher homologue, heptyl resorcinol, was developed by him as an intestinal antiseptic. This is called di-hydranol. Its chemical name is 2-4-dihydroxyphenyl-n-heptane. Experiments of Leonard have shown that increase in the weight of the alkyl chain resulted in greater bactericidal power of the drug without apparent increase in toxicity when administered to rabbits.

Because of a small outbreak of cholera in Manila in 1930, it was thought opportune to try the sterilizing power of di-hydranol on cholera carriers.

Through the permission of the Director of Health and the Director of the San Lazaro Hospital and the coöperation of its resident physicians, Drs. A. Barcelon-Guevara and E. Roxas-Pineda, experiments were carried out on 70 patients.

This elaborate and pretentious manual on the natural history of parasitic worms of German mammals and birds will undoubtedly prove to be an extremely important and valuable source of information in the field of Helminthology. The book is written by a Professor of Veterinary Parasitology and Comparative Zoology in the University of Leipzig. It is therefore not primarily a source for the medical Parasitologist but treats the subject from a broader point of view. The introductory section of 176 pages on the natural history of helminths takes up in orderly fashion the following subjects: (1) Parasites and Parasitism, (2) The Origin of Parasitism, (3) Nomenclature, (4) The Skeletal System of Classification of the Worms and (5) The Life History of Helminths. This last subject is presented quite thoroughly under the class groups (a) Trematodes, (b) Cestodes, (c) Nematodes, (d) Acanthocephala and (e) Pentastomes.

The monograph which was presented before the International Neurological Congress in Berne, Switzerland, typifies Dr. Cushing's work in that it is based upon his own personal experience of intracranial neoplasia and consists of a critical analysis of his cases. It comprises a study of 2,023 verified tumors, which Dr. Cushing has had in his clinic. In each instance, the type of tumor and the result obtained is illustrated by means of a particular case or group of cases. In the monograph of 149 pages, obviously diagnosis and surgical technic cannot be given, but a consideration of the results obtained in the various types of tumors is beautifully presented and in a way in which only Dr. Cushing could do. A detailed review of the work is impossible, and to attempt to abstract such a monograph, every word of which is significant, is out of the question.