The American Journal of Tropical Medicine and Hygiene - Volume 21, Issue 5, 1972

Plasmodium berghei (NYU-2 strain), a virulent rodent malarial parasite, was used to infect germfree (GF) and conventionally-reared (CV) mice. The parasitemia increased more rapidly in CV mice, and maximum parasite levels occurred 6 days after inoculation. Maximum parasitemia was reached 10 days after inoculation in GF mice, and the parasite levels were approximately the same as observed in CV mice at peak parasitemia. Serum antibody was detected earlier, and the overall antibody response was greater in GF mice than in the CV group. A greater immunoglobulin response was observed in GF mice. Most noticeable was the rapid and continuous increase in 7Sγ2b levels throughout the course of infection, whereas no significant changes in 7Sγ2b levels were detected in the CV group. In spite of the serum antibody and immunoglobulin responses elicited, these were not adequate for protection because all mice died as a result of the P. berghei infection.

Germfree (GF) and conventionally-reared (CV) mice were inoculated with a rodent blood parasite, Eperythrozoon coccoides. The parasitemia increased rapidly in GF and CV mice, and both groups of animals showed similar parasite levels 3 to 4 days after inoculation. The parasitemia started to decrease first in GF mice, but it was the CV group in which the parasitemia first became subpatent. Serum antibody to E. coccoides was first detected in CV mice, but eventually the magnitude of the antibody response was the same in both the GF and CV mice. The GF mice, however, revealed the greater immunoglobulin response in both IgM and 7Sγ globulins, whereas the CV mice manifested only an IgM response. The largest immunoglobulin response observed occurred in the 7Sγ2a and 7Sγ2b subclasses of CF mice. This study provided data on the serum antibody and immunoglobulin responses in GF and CV mice infected with E. coccoides. The inclusion of GF mice was invaluable because of the changes seen in 7Sγ globulin levels which were not observed in the CV group.

Toxoplasma gondii oocysts were isolated from the feces of one Felis yagouaroundi (jaguarundi) and two Felis pardalis (ocelot) which initially lacked antibody to Toxoplasma gondii, establishing that not only domestic cats, but other members of the family Felidae can spread Toxoplasma via their feces. These findings explain the reported occurrence of toxoplasmosis in jungle wildlife in the absence of a domestic cat population. A number of Felidae with positive antibody titers to Toxoplasma did not excrete Toxoplasma oocysts after being fed cysts of Toxoplasma. Members of the Procyonidae (raccoon family), Potos flavus, Nasua nasua, and Bassaricyon gabbii, failed to produce oocysts although they became infected and developed antibody to Toxoplasma.

Clinical trials in amebic liver abscess of three new metronidazole derivatives, nitrimidazine, tinidazole and Ro 7-0207 are reported. While all showed activity to a varying degree, none appeared to be an advance on metronidazole.

Four gibbons were inoculated subcutaneously with larvae of Dirofilaria immitis and studied for periods of time up to 14 months. Approximately 2 months following inoculation, skin test reactions converted to positive, eosinophil counts rose, and serological tests were positive for Dirofilaria-reactive antibody. Generally, these laboratory manifestations of infection persisted for the remainder of the study, but microfilaremia was never detected. Both live and dead heartworms were found in the heart and lungs of the infected animals. The pulmonary lesions associated with the infection closely resembled those reported in dogs.

Forty patients with streptocerciasis were studied. They lived in a small village near Mbandaka in the Republic of Zaire. Microfilariae of Dipetalonema streptocerca were present in the dermal collagen, and the features which distinguish these microfilariae are described and illustrated. The main clinical feature was a dermatitis characterized by pruritus, hypopigmented macules and papules. Microscopically there was incontinence of melanin, fibrosis of dermal papillae, dermal fibrosis, dilated dermal lymphatics, increased mucosaccharides around small dermal vessels and lymphocytes, and eosinophils around dermal appendages and vessels. Adult, gravid D. streptocerca were found for the first time in human tissue. They were in the dermis. Treatment with diethylcarbamazine aggravated the dermatitis and caused a reaction around the adult worms. The inguinal lymph nodes were fibrotic, had decreased germinal activity, marked histiocytic hyperplasia, dilated lymphatics, and were infiltrated by plasma cells and eosinophils. The finding of obstructive lymphadenitis suggests that streptocerciasis may be a factor in the pathogenesis of chronic lymphedema.

In vivo microscopic observations have elucidated the pathophysiology of hepatosplenic schistosomiasis mansoni in the mouse. Numerous schistosome eggs trapped in the interlobular portal venules partially or completely obstruct flow. Each egg is capable of obstructing blood flow to about 10 functional hepatic units (defined in text). In mice with severe hepatosplenic disease and portal hypertension, egg loads may reach 10,000 per gram of liver, but they block blood flow to only 6% of the total number of functional units. The host's granulomatous and fibrotic reaction to the eggs, which more than doubles the weight of the liver, imposes an extensive presinusoidal block to liver blood flow. Neovascular formation occurs in the scar tissue and provides a bridge between the presinusoidal vasculature and the sinusoids. The rapidity of the blood flow in these new vessels suggested that they were arterial; this was confirmed when ligation of the hepatic artery resulted in cessation of blood flow not only in the scar tissue but also in the adjacent sinusoids and central venules. On the basis of these studies, the pathophysiology of hepatosplenic schistosomiasis mansoni may be summed up as follows: schistosome eggs and the granulomatous inflammation and scar tissue around them gradually shut down portal venous flow. This results in portal hypertension, congestive splenomegaly, and the development of portal-systemic collateral circulation. Compensatory arterialization occurs through neovascular formation and this maintains sinusoidal perfusion and liver function within relatively normal limits.

Mice infected with Schistosoma mansoni and normal mice were exposed to viable S. mansoni cercariae, and the exposed areas were biopsied at ½, 1, 2, 4, 8, 16, 24, 36, 48, and 120 hours. The initial histologic response (2–8 hours after challenge) of previously infected animals was characterized by edema and a progressive, predominantly polymorphonuclear infiltrate. By 16 and 24 hours, the schistosomules were the foci of intense mixed cell infiltrates, and by 36 and 48 hours, dense mononuclear infiltrates were evident. Normal mice showed only edema and slight polymorphonuclear infiltrates, and by 16 hours most of the schistosomules had migrated through the dermis. Intradermal challenge of infected and uninfected mice with a crude saline cercarial extract produced reactions similar to those described for the two groups after cercarial penetration. Normal mice were also challenged by cercarial exposure or injection of cercarial extract after passive transfer of either lymphoid cells or serum from infected or normal mice. Sera from infected mice passively immunized normal mice, which then responded with an early (5-hour) polymorphonuclear infiltrate against cercariae. Lymphoid cells from infected mice passively immunized normal mice which then developed a late (30-hour) mononuclear infiltrate against either schistosomules or cercarial extract. It is concluded that mice develop both humoral and cell-mediated immune responses against the cercarial stage of S. mansoni.

A simplified in vitro technique was utilized to detect cytotoxic antibodies in serum from hosts exposed to cercariae of Schistosoma mansoni. Significant destruction of cultured schistosomules occurred in the presence of immune rat, rabbit, mouse, and monkey serum. Immune sera induced heavy precipitate formation around the schistosomules. The cytotoxic activity resided in the gamma globulin fraction of immune serum and was shown to be almost wholly complement dependent. Immune serum adversely affected the in vivo viability of schistosomules before detection by the dye exclusion technique was possible. Rabbit gamma globulin that exhibited strong in vitro cytotoxicity failed to protect mice against a challenge infection. Serum from rabbits immunized with adult worm culture antigen did not possess significant in vitro cytotoxicity, although this same antigen effectively stimulated resistance in mice to cercarial challenge. These results, coupled with the findings of other investigators, make it difficult to equate the cytotoxic titer of a host's serum with its immune status.

Five Egyptian male farmers, aged 12 to 23 years, with urinary schistosomiasis and proven Salmonella bacteriuria and bacteremia developed massive proteinuria. Treatment of the Salmonella infection with ampicillin resulted in rapid cessation of proteinuria with return of normal renal function, and improvement in maximal urine concentrating ability. All five patients had markedly depressed levels (<50 mg/100 ml) of complement C3 in serum on admission. Levels returned to normal 1 month after treatment with ampicillin. It is suggested that under certain circumstances prolonged Salmonella infection of the kidney (possibly through an immunologic mechanism) may lead to the nephrotic syndrome.

Royal Farm, a new group B virus from Argas hermanni ticks collected in Kabul Province, Afghanistan, is described. Its group relation through Powassan and Langat viruses is shown by complement fixation (CF) and neutralization tests (N). By CF test it is closely related to Powassan and by N test to Langat. Two isolations, 1 month apart, were made from ticks collected in pigeon shops in Kabul City and the Royal Farm in Kabul Province, respectively. The virus is pathogenic for hamsters but not for weanling guinea pigs and rabbits. Biologically, it differs from Powassan and Langat in its average survival time in 2-day-old mice, in its inability to kill adult mice by the intraperitoneal route, in having titers a minimum of 2 logs lower in suckling mice, and it kills chick embryos by the allantoic, amniotic, and yolk sac routes. Specific immune serum of Langat and Royal Farm reacted only with their homologous antigen in agar gel precipitation tests.

Hematologic values, including concentrations of iron and folate in blood were studied in pregnant women and in a group of patients in the puerperium period, and compared with those in a group of non-pregnant women. Except for red cell folate, which was low in all groups, and total iron binding capacity, which was high in the pregnant and puerperium groups, the mean values for all other parameters studied were within normal limits. Thirty-six percent of the pregnant and 38% of the puerperium patients, were found to be anemic, while no anemia was recorded in the non-pregnant group. In the anemic group, combined iron and folate deficiency was the most common finding (30% and 36%), followed by isolated iron deficiency in pregnant patients (17%), and serum folate deficiency alone in puerperium group (27%). In the iron anemic group, low folate values were most frequent in the pregnant and puerperium patients. In the latter there was a frequency of 22% and 44% of serum and red cell folate deficiency respectively, while in the non-pregnant patients frequency of iron deficiency was higher (13%). No correlation was found between hemoglobin and folate concentration. A good correlation was encountered between hemoglobin and the transferrin saturation index. A significant correlation between neutrophil hypersegmentation and folate was found only in iron-deficient patients, although low folate generally corresponded to increased neutrophil lobe average.

A case of anaphylaxis of the circulatory collapse type and complicated by hematuria following bite by a “slow loris” (Nycticebus coucang) is reported. Treatment consisted in supportive measures and an antihistamine. The patient made a full recovery. There was no clinical evidence of any toxic substance in the saliva of the loris in spite of a northern Thai folklore belief that Nycticebus is a venomous animal.

Treasurer of The American Society of Tropical Medicine and Hygiene The accompanying audit summarizes the financial condition of the Society for the year ended 31 December 1971. In spite of rising costs, the Society did realize an increase in cash balance of $1,714.93 and a net worth of $2,324.36. One source of rising costs can be seen in the “Schedule of Journal Income and Expenses,” wherein the excess of expenses over receipts amounted to $2,158.18. The increased cost of publishing the Journal, however, has been met by an increase in subscription rates, beginning with Volume 21.

George R. Healy, Ph.D.

Secretary-Treasurer

23 March 1972

To the Officers and Councilors of The American Society of Tropical Medicine and Hygiene:

We have examined the statements of assets, liabilities, and net worth (prepared on a cash basis with the exceptions noted below) of The American Society of Tropical Medicine and Hygiene and of the Tropical Medicine and Hygiene News as of 31 December 1971, and the related statements of cash receipts and disbursements for the year then ended.

This volume includes the contributions by 38 outstanding scientists and represents a testimonial to the memory of the late Dr. Thomas Francis, Jr. Most of the volume is in the form of general review and this feature alone makes a critical and fair evaluation difficult.

The Symposium is divided into six sections. The first, viral biology, presents detailed studies of viral morphogenesis (vaccinia virus), genetics of temperature-sensitive mutants of RNA viruses, and some biochemical aspects of enveloped DNA viruses.

The section on virus-cell interaction covers an exhaustive analysis of interferon induction, mechanism of interferon action, and the probable nature of the “interferon system.” This section is supplemented with an excellent discussion of the kinetics of virus neutralization and the mechanisms of selective inhibition of virus replication.

The section on viral oncology is brief and superb comprising a brilliant analysis of the viral gene functions involved in the maintenance of the transformed state and some insights into the probable role of viruses in human neoplasia.

This treatise on the malarial parasites of man and lower primates is the first attempt to bring together studies from this large number of species of Plasmodium (24), and the task has been so well done that there seems to be little question that it will become a classic in this field. In the first section consideration is given to theories on the evolution of the Haemosporidia, a historical review, discussion of the ecology of the parasites and their hosts, and descriptions of the life-cycles of the parasites (including their relation to relapses in the vertebrate hosts). The five sections which follow deal with parasites of a) the vivax-type (10), b) the ovale-type (3), c) the malariae-type (4), d) the falciparum-type (4), and e) other types not clearly fitting into any of these four groups (3).

The theories of early evolution are fairly presented with emphasis on the gaps still existing in factual information necessary to definitive conclusions.

Volume I. The author appears to be a biologist with a flare for mathematical models which is reflected in his approach to water pollution problems. If one of the purposes of the book is to consider waste water reuse a more scientific review of the water quality “criteria” should have been given for various uses in addition to public water supply such as recreation, shellfishing, agricultural and industrial. Table 8 on page 20 obviously is not criteria (limit for designated use) but rather “optimum goals.” Some of the water quality items are strange, for example, coliform MPN for drinking water on page 3 and temperature, page 71, since many natural waters above 80 F are optimum for swimming. Units, abbreviation and terminology in Chapter 3 should have been in the appendix and some of the definitions of terms such as “pollution,” “fecal coliforms,” coliform bacteria, and “BOD” could be tighter.