The American Journal of Tropical Medicine and Hygiene - Volume 1, Issue 3, 1952

Hans Zinsser, in 1935, when louse-borne typhus was of no concern to health workers in the United States and DDT was still unknown as an insecticide, wrote:

“Typhus is not dead. It will live for centuries, and it will continue to break into the open, whenever human stupidity and brutality give it a chance as, most likely, they occasionally will. But its freedom of action is being restricted and, more and more, it will be confined, like other savage creatures, in the zoological garden of controlled diseases.”

I have taken the long-memoried elephant as the symbol of the savage communicable diseases, whose activities are being more and more restricted but which have never lost their instinct and capacity for human destruction.

Within five years of Zinsser's prophecy, World War II, with its excess of “human stupidity and brutality,” unleashed typhus in Poland, Russia, Iran, Egypt, North Africa, Italy; in the concentration camps of Germany and Austria, and in Japan.

There could hardly be a more timely subject in the entire field of insect vector control than the present one.

Within the last decade we were within sight of realizing our fondest hopes in the eradication of, or at least effective control of, many arthropod borne diseases and pestiferous insects. The last few years of this decade, however, have dealt a blow to these aspirations by the fact that insects have developed resistance to our most potent chemical weapons. We now must go back and reorganize our forces for a new attack. The following speakers were asked to participate in this Panel not only because of their preeminence in the field, but because their respective interests and work combine to cover almost all phases of the problem confronting us.

First, Dr. A. D. Hess, of the U. S. Public Health Service, discusses the “Significance of Resistance to Insecticides in Vector Control Programs.”

Introduction. The occurrence of resistance to insecticides is not new. John B. Smith apparently observed resistance to kerosene in the San Jose scale in 1887 (Babers and Pratt, 1951). Since 1914, when Melander asked his now famous question “Can insects become resistant to sprays”, at least a dozen agricultural species have developed varying degrees of resistance to insecticides. The problem of insecticide resistance did not, however, become of general concern to medical entomologists until some time after DDT had come into widespread use.

It is the purpose of the present paper to present a summary review of the impact of insecticide resistance upon vector control and related programs in various parts of the world and its implications for the future. Pertinent information has been obtained from literature, from personal correspondence and discussions, and from the results of recent investigations being conducted by the Communicable Disease Center.

Several species of culicine mosquitoes, including Culex pipiens autogenicus, C. tarsalis, Aedes taeniorhynchus, A. sollicitans, A. nigromaculis, and A. dorsalis, have developed resistance to DDT in localized areas. This resistance is sufficiently high to make control measures with DDT impractical. Moreover, some of the species have developed resistance to substitute insecticides used for their control, including toxaphene, benzene hexachloride and aldrin.

Resistance to DDT among natural populations of Anopheles mosquitoes has not yet been established, even though intensive control operations have been carried out for several years in many areas, but we have no assurance that insecticide-resistant strains of Anopheles cannot develop.

It is my opnion that intensive and widespread application of DDT and other insecticides to both larval and adult culicine mosquitoes is the primary reason for the appearance of resistant strains in certain areas. Antilarval measures other than the use of insecticides and the application of antiadult measures to minimum size localized areas may prevent or delay the appearance of insecticide-resistant mosquitoes. Further research to develop new mosquito insecticides and an expanded program of basic studies on the resistance problem are needed.

It is no doubt significant that housefly resistance to DDT was first recognized and reported in Europe, where DDT came into commercial use in 1944 and was used extensively by civil and military personnel in 1945. In 1947, Sacca and Missiroli attributed the failure of DDT to control flies in Italy to the presence of a variety of house fly which had become resistant to DDT. About the same time Wiesmann (1947) reported house fly resistance in Sweden. Two years later Keiding and Van Deurs (1949) in three short paragraphs summarized the course of events which was apparently common throughout Europe, as follows:

“Already in 1946 there were some isolated complaints of failing effect, and in the summer of 1947 the fly control failed in a great many places.

Introduction. Insecticide resistance, a development first noticed some fifty years ago (Smith, 1897), is a major problem confronting the medical and economic entomologist today. Realization of this unpleasant fact is growing rapidly (Babers, 1949, 1951), thanks mainly to the conspicuous failure of DDT to provide satisfactory control of flies in some areas where earlier this agent was highly effective. Disconcerting as this situation is, still more so is the experience that empirical attempts at solution of the difficulty have served to emphasize the gravity of the present state of affairs rather than to provide the practical answers sought. Attention has thus been directed anew toward the need for a better understanding of the basic phenomena involved. It is the purpose of this discussion to present a brief evaluation of the physiological data which are now available for application to the problem.

• 1.  The use of media treated with streptomycin or penicillin increased the number of positive cultures of E. histolytica obtained from stool specimens containing cysts.
• 2.  It seemed that the favorable influence on amebic cultivation was due to the inhibition of the mixed bacterial flora induced by these drugs.
• 3.  Streptomycin suppressed the aerobic bacteria in some of the cultures and it was observed that slants of Endamoeba medium overlaid with serum-saline supported the growth of certain anaerobic bacteria under aerobic conditions.
• 4.  In some instances, failure of amebic cultivation may have been related to antibiotic influences created by the microbiologic population.

The studies of Dobell (1931), Kessel (1928), and others established the fact that the “histolytica-like” amebae found in monkeys are identical with E. histolytica in man. While it has been shown by many investigators that this parasite can be transmitted to a wide variety of hosts, in none of these can the infection be considered a normal one. Thus, dogs, kittens, rats, pigs, rabbits, guinea pigs and even chicks have been infected experimentally with E. histolytica. But in such cases infection is usually achieved only under special conditions. Also, the regular production of cysts is rarely seen, and it seems logical to assume that cyst-production here is good evidence of a normal host-parasite relationship For a proper understanding of the host-parasite relationships of E. histolytica the parasite must be studied in its normal host.

Five cases of amebic liver abscess in male Africans in which characteristic pus was obtained were treated with Aureomycin in a dose of 500 mgm. 6 hourly for 10 days.

In two cases there was no response, in two cases possibly some response, and in one case an apparently good result was followed by recurrence in six weeks.

The results have been compared with those obtained in similar cases with emetine and chloroquin diphosphate and it is concluded that Aureomycin is a much less effective drug.

A reorientation of historical source material is necessary before conclusions can be drawn concerning the antiquity of sylvan yellow fever. During the building of the Panama Railroad (1850–1855) yellow fever was singularly absent from the mainland, but during the operation of the first French Canal Company (1881–1889) it took a heavy toll of human lives. After 1889 it remained endemic in Panama City until its eradication by Gorgas in 1905. From 1906–1919 only imported cases developed in the Canal Zone and from 1920 to 1948 no further cases were encountered. Surveys of the human population indicate that sylvan yellow fever has been enzoötic in eastern Panama since 1929.

In November and December 1948 a wave of sylvan yellow fever began moving westward from this enzoötic center, following the Atlantic rain forest, and reached northern Costa Rica in July 1951. Early in October 1951 an offshoot of this wave had crossed the Cordillera of southern Costa Rica to the Pacific side and has moved eastward again, re-entering western Panama, but now on the heretofore uninvolved Pacific watershed, west of the Canal. The main front of the wave is expected to continue moving into Nicaragua.

Leptospirosis in North America may be caused by any of at least seven antigenically distinct strains of leptospirae. Of these, L. icterohemorrhagiae, L. canicola, L. pomona and L. bataviae are known to exist in the United States. Methods for serological and bacteriological diagnosis of leptospirosis have been discussed. The need for more adequate diagnostic laboratory services, improved diagnostic procedures, a definitive therapy and epidemiological surveys has been set forth.

Results of an investigation designed to ascertain the status of Histoplasma capsulatum on the Isthmus of Panama have been presented. The remarkable prevalence of intradermal sensitivity to histoplasmin, the high prevalence of pulmonary calcific foci in histoplasmin-positive, tuberculin-negative individuals, and the striking similarity of these findings to those reported from known histoplasmosis-endemic areas of North and Latin America, seemed to justify the deduction that unrecognized histoplasmosis was endemic in this region.

This deduction was confirmed by the subsequent recognition of a fatal infection in a four month old child from Chilibre, Republic of Panama. The first human infection since the three original cases described here by Darling nearly 45 years ago, it was the first unquestionably indigenous one to be reported from the Isthmus of Panama.

We have already reported (Thetford et al., 1948) the apparently successful treatment with arsenamide 1 of six adult negro males infected with the periodic form of Wuchereria bancrofti in St. Croix, the Virgin Islands. This paper summarizes similar treatment of twelve additional cases in the same area.

These subjects were, as the previous six, all adult male Negroes who had lived all or most of their lives on St. Croix. They were selected because microfilariae had been found in their night blood. Of the twelve, eight were asymptomatic and four (J. G., J. J., R. D., and E. B.) had right scrotal hydroceles but were otherwise asymptomatic. The microfilariae were counted in thick smears made from 0.1 cc. of venous blood drawn between 10 and 12 o'clock at night. Such counts were made before treatment, immediately after the completion of treatment, and periodically thereafter as the patients were available up to a year after treatment.

• 1.  A case of non-symptomatic microfilaremia due to Wuchereria bancrofti is reported approximately seven and a half years after exposure to infection.
• 2.  The objective residuals of infection in 87 cases of filariasis in veterans consist of lymph node enlargement in all cases, especially axillary. Rarely, slight swelling of the affected limbs was demonstrable.
• 3.  The subjective symptoms were complaints of dull pain and swelling of the affected parts after exertion, and anxiety related to the genital organs. The patients were not exercised so that it is possible that some of the complaints concerning swelling may have a foundation in fact.

The identity of the Anopheles species with the pale-tipped wing in the vicinity of Hamilton, Montana, is considered to be A. earlei. The egg of this species differs from that of A. occidentalis in that it possesses two dark transverse bars on the dorsal surface. A. earlei thus appears to be closely related to A. maculipennis (type species) of Europe, but differences in cage behavior of the male is evidence that these two are not the same. A. earlei appears to be adaptable to colonization; the writer's colony failed perhaps because of the inability to send enough living eggs to Baltimore from Montana.

In North America it now appears that the maculipennis complex is composed of at least four species; occidentalis Dyar and Knab, aztecus Hoffman, freeborni Aitken, and earlei Vargas, which can be recognized in the majority of cases on adult, larval, and pupal characters.

A description of the initiation of the program of epidemiologic appraisal of malaria in the United States in 1947 has been presented elsewhere (Quinby 1950). At the 1950 meeting of the National Malaria Society, the results of appraisals of reported malaria for 1949 and preliminary data for the first nine months of 1950 were presented. Since then, data for 1950 cases appraised through March 1951 have been assembled and analyzed for this paper.

Scope of Coverage. The primary function of the appraisal program was to measure the actual incidence of malaria. Later this became an integral part of the Malaria Surveillance and Prevention Program of the Communicable Disease Center and the state health departments concerned. Although this program is carried out principally through the investigation of officially reported cases, more and more emphasis has been given to finding and confirming unreported malaria.

In the early 1930's, as soon as TVA began planning for development of the Tennessee River, it was confronted by a malaria problem. Despite advances up to that time in knowledge concerning control of malaria, the disease still constituted one of the most important public health problems of the southeastern United States, and the relationship of impoundages and malaria was well documented. Reservoir impoundments in the region had proved in virtually every instance to be ideal breeding grounds for anopheline mosquitoes, and some had resulted in serious epidemics of malaria. The TVA project envisioned creation of a system of artificial lakes potentially totalling over 600,000 acres of water area and over 10,000 miles of shoreline. Impoundage of this magnitude in an area where malaria existed to a serious degree presented an unprecedented control problem.

A survey of the city of Ribeirão Preto in the State of São Paulo, Brazil, revealed four species of scorpion: Tityus serrulatus, Tityus bahiensis, Bothriurus bonariensis, and Bothriurus magalhaensis. The first species was predominant, and because of its urban and domestic habits, was responsible for the majority of accidents to human beings through scorpion stings, of which 1,331 were reported over a period of 7 years, with 8 deaths in small children.

Ortho BHC, and DDT in solution were used in an experimental eradication campaign and both were effective. BHC was more rapidly lethal, but the period of observation was too short to permit an evaluation of the comparative duration of residual toxicity of the two poisons.

The morphology exhibited in the sections of arthropod bite reactions permits a dynamic interpretation. In the search for the blood meal, the biting mechanism of the arthropod appears to penetrate through the epidermis with minimal difficulty. Some spreading factor in the saliva is suggested by the rapid spread of the tissue reaction. The perivascular phases of the reaction also suggest a rapid vascular transportation of the material injected. The sensitivity of an individual to the bite of a given arthropod influences the intensity of the inflammatory response. However, an individual may be sensitive to one arthropod and insensitive to the bites of others. The insensitive individual who develops no clinical bite reaction may be bitten without being aware of it. The histological studies of Boltz (1951) of the skin reactions following injections of needle puncture show that the changes in the skin following a bite by an arthropod is not one of simple “mechanical” puncture even in a non-reactive individual. The persistent late nodular response may be due to the intrinsic nature of the bite (including retained cuticular fragments?) or to a neurodermatitic response secondary to the scratch reaction to itching.

Histopathologic methods are valuable in the study of bite reactions. Improvements such as vacuum freeze drying technics and histochemical studies may permit more detailed studies of the variations in the cellular response of the individual to the bites of arthropods. With better fixation technics it may be possible to pick up fine bodies retained after the insect bite. Improvement in the technic of study of the biting parts in situ, will make possible observations relating to the effect of the artificially induced retention of a piece of the biting apparatus within the skin. It is also possible that isotopic studies with other isotopes and more refined autoradiographic technics may enable us to follow the path of the bite more accurately. Progress in the study of the peripheral mechanisms of reaction of Compound F deposited locally may also help in the analysis of the bite reaction.

With the bite reaction of an individual determined, it should then be possible to study in detail local and systemic factors which may modify some parts of the bite reaction, as for example, the vascular response, the inflammatory cell response, the degree of pruritus, additive local trauma, etc.