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Biomedical subjects

P B McGreevy

Publications and source records attributed to P B McGreevy.

At least 19 recordsLinked to original sources
PubMed1997

Evaluation of selected antiprotozoal drugs in the Babesia microti-hamster model.

The presently used therapy for Babesia microti infections, a combination of quinine and clindamycin, does not always result in parasitologic cures. To identify possible alternative chemotherapeutic agents for such infections, we screened, in the hamster-B. microti system, 12 antiprotozoal drugs that have either recently been released for human use or were in experimental stages of development at the Walter Reed Army Institute of Research for the treatment of malaria and leishmaniasis. Several well-recognized antimalarial drugs, such as mefloquine, halofantrine, artesunate, and artelenic acid, exhibited little or no effect on parasitemia. Two 8-aminoquinolines, WR006026 [8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride] and WR238605 [8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5 -(3-trifluoromethylphenoxy-7) quinoline succinate], produced clearance of patent parasitemia. Furthermore, blood from infected hamsters treated with WR238605 via an intramuscular injection failed to infect naive hamsters on subpassage, thus producing a parasitologic cure. These two compounds merit further screening in other systems and may prove useful in treating human babesiosis.

Aminoquinolines↗
PubMed1987

Leishmania braziliensis: protein, carbohydrate, and antigen differences between log phase and stationary phase promastigotes in vitro.

When Leishmania species are grown in vitro, parasites from the stationary phase differ from those in log phase growth in being more infective and more resistant to complement and macrophage mediated killing. In the present study, log phase and stationary phase promastigotes of Leishmania braziliensis panamensis were compared at the molecular level. Differences in polypeptide and glycoprotein composition and antigenicity between log and stationary phase promastigotes of L. b. panamensis were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting; the former showed that two polypeptides were unique to log phase promastigotes and one was unique to stationary phase promastigotes. There were also differences in surface lectin binding characteristics of log and stationary phase promastigotes. Live stationary phase promastigotes bound more concanavalin and lentil lectin than log phase promastigotes, indicating a greater number of mannose residues on their surfaces.

Animals↗
PubMed1987

Detection and enumeration of Leishmania in sand flies using agar-based media.

An agar plating technique was used to determine the number of amastigotes ingested by Lutzomyia longipalpis fed on papules on Mesocricetus auratus caused by Leishmania mexicana amazonensis and on lesions on Mystromys albicaudatus caused by Leishmania braziliensis panamensis. The technique involved homogenizing sand flies after bloodfeeding on the infected animals and spreading the homogenate over the surface of agar plates. A great variation in the number of amastigotes ingested by individual sand flies was demonstrated. Not all amastigotes ingested developed anterior stomodeal infections.

Animals↗
PubMed1985

Human cutaneous leishmaniasis acquired in Texas.

Four cases of autochthonous human cutaneous leishmaniasis have been identified in south-central Texas since 1980. The patients presented with chronic ulcerating papules on the face, earlobe, and lateral thigh. In two patients, the infections healed without treatment. In the other two patients, the lesions healed following treatment with intramuscular sodium stibogluconate or topical antimony potassium tartrate. Serologic testing of family members, using four different techniques, indicates that asymptomatic infections may occur. These are the first reported cases of cutaneous leishmaniasis acquired in Texas since 1974. Organisms isolated from patients in 1974 and 1980 belonged to the Leishmania mexicana complex when tested by the isoenzyme technique. Although no animal reservoir or insect vector has been identified, six species of sand flies belonging to the genus Lutzomyia do inhibit this part of Texas. Accumulated evidence strongly suggests that cutaneous leishmaniasis is endemic in south-central Texas.

Antibodies↗
PubMed1985

Growth cycle-dependent generation of complement-resistant Leishmania promastigotes.

The ability of in vitro grown Leishmania promastigotes to resist lysis by complement and survive in undiluted human serum was related to the species of Leishmania and the growth phase in culture. Promastigotes from log phase cultures were always killed in undiluted serum, whereas survival of stationary phase promastigotes varied among species. All L. major and L. m. amazonensis were killed, while up to 30% of L.b. panamensis and 10% of L. donovani survived. Lysis of promastigotes by human serum was inhibited in heat-inactivated serum and EDTA-chelated serum, indicating that activation of complement was responsible for killing. Therefore, during growth in vitro, some strains of Leishmania promastigotes can undergo development from a complement-susceptible to -resistant stage. Stationary phase promastigotes of L.b. panamensis which survived in undiluted human serum were capable of subsequent growth in culture, and were also able to initiate infection in Mystromys albicaudatus. Organisms selected on the basis of complement resistance were more infective for M. albicaudatus than either log phase promastigotes or unselected promastigotes from stationary cultures. These data support the notion that the life cycle of Leishmania includes an infective stage promastigote which is generated during growth within the sandfly and which, on inoculation, is able to survive the potentially lethal effect of normal serum before uptake by host macrophages.

Adult↗
PubMed1984

The effect of humidity on the transmission of Brugia pahangi infective larvae to mammalian hosts by Aedes aegypti.

The transmission of Brugia pahangi by Aedes aegypti to the mammalian host was compared at low and high humidity. There was no statistical difference between the number of infected mosquitoes feeding or the egress of infective larvae from these mosquitoes at high or low humidity. The penetration of the host by the infective larvae was however significantly greater (p less than 0.05) at high than at a low humidity.

Aedes↗
PubMed1984

Pathology of experimental infection with Brugia malayi in ferrets: comparison with occult filariasis in man.

Ferrets experimentally infected with Brugia malayi (subperiodic strain) developed eosinophilia at patency and usually became amicrofilaremic. Ferrets necropsied within 3 months after becoming amicrofilaremic had granulomas and focal reactions to degenerating microfilariae in their livers, lungs and lymph nodes essentially identical to those of tropical eosinophilia. Four of 7 ferrets that received multiple inoculations of larvae, developed edema of the inoculated paw and leg after becoming amicrofilaremic and 6 of these 7 ferrets had granulomatous lymphangitis and lymphadenitis of inoculated limbs but not the lesions of lung and liver characteristic of occult infection.

Animals↗
PubMed1983

The resistance to re-infection of cats repeatedly inoculated with infective larvae of Brugia pahangi.

Seven microfilaraemic and five amicrofilaraemic cats which had been repeatedly infected with Brugia pahangi were challenged along with normal cats 28, 14 and 1 day before autopsy. The lymphatics of the amicrofilaraemic cats contained no female adult worms originating from the repeat infections and only two adult males (both from the same cat). Only 5.2% of the worms in the control cats were recovered from the amicrofilaraemic cats. Most of the challenge worms were killed in the first 24 h. The microfilaraemic cats all contained fertile adult male and female worms derived from the repeated infection but in such low numbers as to indicate considerable resistance to infection. Compared to their controls 26.4% of the challenge worms were recovered. Analysis of the life-cycle stages recovered showed that in both groups there was attrition of all stages and that although a number of worms reached L5 these were all killed later in the amicrofilaraemic cats.

Animals↗
PubMed1983

Evaluation of promastigote and amastigote antigens in the indirect fluorescent antibody test for American cutaneous leishmaniasis.

Leishmania braziliensis panamensis promastigotes, temperature-induced in vitro-cultivated amastigotes, Vero cell-derived amastigotes, and rodent lesion-derived amastigotes were evaluated as antigens in the indirect immunofluorescent antibody (IFA) test for American cutaneous leishmaniasis. Test sensitivity was determined using sera from 34 U.S. soldiers with leishmaniasis diagnosed by demonstrating parasites in their skin lesions. Sera were collected from 3 to 24 months after exposure to Leishmania. Positive IFA reactions among patient sera were 82% with promastigotes or lesion amastigotes, 79% with in vitro amastigotes, and 76% with Vero cell amastigotes (P = N.S.). Positive titers ranged from 1:8 to 1:128 using all antigens. Test specificity was determined with 30 sera from healthy individuals. False positive reactions ranged from 0-5% depending on the antigen and all titers were less than or equal to 1:8. Test cross-reactivity was assessed with 47 sera from patients with other diseases. Depending on the antigen, cross-reactions occurred with sera from patients with Chagas' disease, lupus erythematosus, malaria, toxoplasmosis and amebiasis. None of the antigens cross-reacted with sera from patients with viral hepatitis, coccidioidomycosis, syphilis, schistosomiasis, and trichinosis. In replicate experiments, 99-100% of the sera varied no more than +/- 1 titer dilution. As sensitivity, specificity, cross-reactivity, and reproducibility of the four antigens were statistically similar, promastigotes, which can be easily and economically cultured in large numbers in vitro are recommended for use in the IFA test for American cutaneous leishmaniasis.

Adult↗
PubMed1982

The ferret (Mustela putorius furo) as an experimental host for Brugia malayi and Brugia pahangi.

Ferrets inoculated subcutaneously with 150--200 infective larvae of Brugia malayi (subperiodic strain) usually developed patent infection during the 3rd month post inoculation. Microfilaremia was transient, and most animals became amicrofilaremic after the 6th month of infection. Ferrets developed a persistent eosinophilia at the time of patency. At necropsy, 5--8 months post infection, adult worms were recovered principally from lymphatic vessels and recovery ranged from 0.5--13% of the inoculated larvae. The inflammatory response of ferrets to microfilariae was characterized by nodules 1--5 mm in diameter in the liver, lungs, spleen, and submucosa of the gastrointestinal tract. The center of these lesions contained a degenerated microfilaria or the cast of a microfilaria embedded in Splendore-Hoeppli substance. The Splendore-Hoeppli substance was surrounded by eosinophils and/or foreign body giant cells. Identical lesions were observed in ferrets experimentally infected with Brugia pahangi. Sera from ferrets infected with B. malayi demonstrated a 3- to 5-fold increase in IgG by the 4th month of infection and these sera produced 2--3 precipitin bands in double gel diffusion assays with an extract of B. malayi microfilarial antigen. Skin tests with B. malayi microfilarial antigen showed that the majority of the infected ferrets had immediate hypersensitivity responses, but none had Arthus or delayed hypersensitivity responses.

Animals↗
PubMed1982

The number and distribution of Brugia pahangi in cats at different times after a primary infection.

The number of larvae and adults of Brugia pahangi and their distribution throughout the lymphatics and extra-lymphatic tissue were studied in cats infected by subcutaneous injection of larvae into their hind feet. For the first 20 days approximately 55% of the inoculum is recovered as living worms. After 25 days the recovery falls by a half. It is suggested that this loss of worms may be due to either the developing immunological response or the moult from the 4th to the 5th stage. Larvae penetrate the lymphatics rapidly (50% within 3 h) and migrate to the popliteal lymph node after about 20 days they migrate back down into the afferent lymphatic.

Animals↗
PubMed1981

Estimate of the risk of post transfusion hepatitis B in Jakarta, Indonesia.

The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were determined in blood donors and transfusion recipients in Jakarta, Indonesia. In blood donors the prevalence of HBsAg was 10% while anti-HBs was 43%. In transfusion recipients the prevalence of HBsAg and anti-HBs was 67%. The prevalence of susceptible recipients or those without detectable HBsAg or anti-HBs was 33%. Thus, the probability that a susceptible recipient would receive HBsAg from a blood donor was calculated at 3.3%. Published data from other studies were used to estimate the risk of clinical post transfusion hepatitis in Jakarta at between 0% and 2%.

Adolescent↗
PubMed1981

Effect of treatment with diethylcarbamazine on immune responses to filarial antigens in patients infected with Brugia malayi.

We studied the effect of treatment with diethylcarbamazine (DEC) on immune responses to parasite antigens in humans infected with Brugia malayi. In vitro lymphocyte proliferative responses to microfilarial antigens increased in patients who became amicrofilaremic after treatment with DEC. No changes in reactivity were observed in amicrofilaremic individuals who were given DEC or in a small number of patients who remained microfilaremic after treatment. Reactions to other antigens (PPD and SKSD) were not affected by drug treatment. Serum titers of antibodies to the sheath of B. malayi microfilariae did not significantly change during the period of observation. These findings indicate that DEC partially reverses the state of cellular unresponsiveness to parasite antigens associated with patient filarial infections.

Adult↗
PubMed1980

Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens.

We evaluated the cellular immune competence of 101 subjects living in an area of South Kalimantan (Borneo) where Malayan filariasis is endemic. All patients with elephantiasis but none with other clinical stages of filariasis reacted with adult worm antigens. The majority of subjects without clinical or parasitological evidence of filariasis and approximately one-half of those with amicrofilaremic filariasis reacted with microfilarial antigens. In contrast, most patients with patent microfilaremia did not respond to microfilarial antigens. The in vitro reactivity of all patient categories to nonparasite antigens was similar to that of the distant control group. These results indicate that patent microfilaremia is associated with a state of specific cellular immune unresponsiveness and are consistent with the current hypothesis that the various clinical manifestations of filariasis result from different types of immune responses to distinct antigens associated with different developmental stages of filarial worms.

Adolescent↗
PubMed1980

Brugia malayi: relationship between anti-sheath antibodies and amicrofilaremia in natives living in an endemic area of South Kalimantan, Borneo.

A seroepidemiological approach was taken to elucidate the relationship between anti-microfilarial antibodies and amicrofilaremia in humans living under natural conditions of exposure to Brugia malayi. Entomological observations indicated that all of the people in the study population in South Kalimantan, Borneo, were exposed repeatedly to filarial infection. A third of the population had antibodies to the sheath of microfilariae. The prevalence and titer of anti-sheath IgM was higher than anti-sheath IgG or IgA. There was a statistically significant correlation between anti-sheath antibody and amicrofilaremia and these antibodies may play a role in regulating peripheral microfilaremia.

Adolescent↗
PubMed1979

Successful vaccination of cats against Brugia pahangi with larvae attenuated by irradiation with 10 krad cobalt 60.

Cats were vaccinated by the inoculation on 10 occasions of approximately 300 larvae of Brugia pahangi which had been irradiated with 10 krad cobalt 60. They were challenged on 3 occasions with normal larvae of either B. pahangior B. patei. The vaccinated cats were resistant to challenge as demonstrated by either longer pre-patent periods or failure to become microfilaraemic and by having fewer third, fourth or adult worms than normal controls. Although the vaccination procedure was unpractically heavy these results lend encouragement to the possibility of developing vaccines against filarial infections.

Animals↗