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J D Chulay

Publications and source records attributed to J D Chulay.

86 records · Page 5Linked to original sources
PubMed1982

Susceptibility of clinically sensitive and resistant Leishmania to pentavalent antimony in vitro.

Standard courses of pentavalent antimonials frequently fail to cure cutaneous, mucocutaneous, and visceral leishmaniasis, and characteristically fail to cure diffuse cutaneous disease. We have determined the in vitro sensitivity of clinical isolates of Leishmania to pentavalent antimony to determine if inherent drug resistance of the parasite is responsible for treatment failures in human beings. Intracellular amastigotes resulting from promastigote-initiated infection of human macrophages were exposed to pentavalent antimony for 6 days at 34.5-35 degrees C. Amastigotes from clinically sensitive simple cutaneous lesions exhibited a range of in vitro sensitivity. Four strains were greater than or equal to 90% eliminated and two strains were 70-75% eliminated in vitro by concentrations of antimony (15-20 micrograms Sb/ml), comparable to peak achievable serum levels in humans. Amastigotes from initially clinically resistant simple cutaneous lesions showed a wider range of sensitivities. Five strains were greater than or equal to 90% eliminated, but one strain was only 40% eliminated and another strain was completely insensitive in vitro. The clinically resistant diffuse cutaneous strain was 61% eliminated. The techniques described herein permit determination of the in vitro antimicrobial susceptibility of Leishmania from all major human forms of leishmaniasis. The data from this series indicate that in a minority of initially resistant cases parasite resistance to the drug may be contributing to clinical resistance, and use of non-antimonial drugs might be recommended for future therapy.

Animals↗
PubMed1981

Inhibition of in vitro growth of Plasmodium falciparum by immune serum from monkeys.

Three owl monkeys that had been immunized against the Camp strain of Plasmodium falciparum by infection were treated with chloroquine and rechallenged with parasites. Immune serum caused a dose-dependent, time-dependent inhibition of in vitro parasite growth. Heat-inactivation eliminated nonspecific inhibition by normal monkey serum without diminishing immune inhibition. Purified IgG from immune serum inhibited parasite growth. Serum taken immediately before the second challenge did not inhibit growth in vitro at a 1:10 dilution, although the monkeys successfully resisted the in vivo challenge. However, immune sera from all three monkeys taken two to four weeks after in vivo challenges were inhibitory, but sometimes detection required 20% serum. Growth inhibition in vitro by 10% serum was a poor predictor of in vivo protective immunity. Undiluted blood containing higher antibody levels (which are boosted by challenge), combined with additional immune mechanisms, may explain the protection observed in vivo.

Animals↗
PubMed1981

Inhibitory effects of immune monkey serum on synchronized Plasmodium falciparum cultures.

We studied the effects of heat-inactivated immune monkey serum on the growth of a partially synchronized culture of Plasmodium falciparum. By light microscopy, parasites within erythrocytes were morphologically indistinguishable from those cultured in normal serum. Immune serum reduced by 90% the number of erythrocytes containing newly invaded rings. Clusters of extracellular merozoites, usually around clumps of malarial pigment, were seen frequently in cultures grown with immune serum but rarely in cultures with normal serum. Electron microscopy confirmed the normal development of intraerythrocytic parasites. In immune serum cultures, electron-dense precipitates were found on the surface of schizonts, merozoites, and the excrescences on the plasma membrane of schizont-infected erythrocytes. Merozoites in immune serum culture appeared to aggregate by adherence between adjacent surface coats. These findings support the hypothesis that immune serum agglutinates merozoites and thereby inhibits their invasion into uninfected erythrocytes.

Animals↗
PubMed1979

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.

A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum. Microtitration plates were used to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured in these plates for 42 h. Inhibition of uptake of a radiolabeled nucleic acid precursor by the parasites served as the indicator of antimalarial activity. Results of repeated measurements of activity with chloroquine, quinine, and the investigational new drug mefloquine demonstrated that the method is sensitive and precise. Several additional antimalarial drugs and compounds of interest were tested in vitro, and the results were consistent with available in vivo data. The use of P. falciparum isolates with known susceptibility to antimalarial drugs also permitted evaluation of the cross-resistance potential of each compound tested. The applications and expectations of this new test system within a drug development program are discussed.

Animals↗
PubMed1978

Cultured Plasmodium falciparum used as antigen in a malaria indirect fluorescent antibody test.

Human sera obtained from persons infected with Plasmodium falciparum were tested by a standard indirect fluorescent antibody (IFA) technique using antigen obtained from long term in vitro cultures of two strains of P. falciparum, and antibody in high titer was reproducibly detected. Sera from uninfected persons had undetectable or very low titers of antibody. The use of cultured parasites offers a convenient, stable source of antigens from different P. falciparum strains without requiring their adaptation to primates. Differences observed in IFA titers obtained by reacting immune serum with two different P. falciparum strains suggests the need for further evaluation of strain specificity.

Animals↗
PubMed1976

Splenic abscess. Report of 10 cases and review of the literature.

Ten cases of splenic abscess seen between 1964 and 1974 are reviewed. Pain referable to the abscess was the most common symptom, but was present in only five cases. Fever was present in all but one case. Tenderness in the region of the spleen was noted in six cases, in three cases the spleen was palpable and in one case a large mass in the upper left quadrant of the abdomen was palpated. Abdominal films were suggestive of the diagnosis in two cases, and the liver-spleen scan demonstrated a defect in three cases. Seven abscesses were caused by gram-negative bacilli of bowel origin; the etiologic agents in the other three were Staphylococcus aureus, Streptobacillus moniliformis and a Nocardia species. Associated conditions predisposing to splenic abscess included trauma in three cases, splenic arteritis or embolization in five cases, and foci of infection elsewhere in the body in six, including two cases of endocarditis. The mortality was 60 per cent. Half of the deaths were due to the underlying illness, but failure to diagnose splenic abscess contributed to a fatal outcome in three cases.

Abscess↗
PubMedDate not supplied

Activity of human volunteer sera to candidate Plasmodium falciparum circumsporozoite protein vaccines in the inhibition of sporozoite invasion assay of human hepatoma cells and hepatocytes.

Sera from human volunteers immunized with either synthetic peptide (NANP)3-TT or recombinant protein R32tet32 Plasmodium falciparum CS vaccines were tested in the inhibition of sporozoite invasion (ISI) assays using human hepatoma (HepG2-A16) cells or primary human hepatocytes. Sera or purified immunoglobulin (Ig) from volunteers who were completely protected against P. falciparum sporozoite challenge had higher ISI activity than sera from non-protected volunteers, or the highest titre endemic serum. However, Ig from protected and non-protected volunteers did not block sporozoite invasion of human hepatocytes, suggesting that P. falciparum sporozoites invade hepatocytes by mechanisms which differ from those concerned with invasion of HepG2-A16 cells.

Animals↗
PubMedDate not supplied

Causal prophylactic efficacy of atovaquone-proguanil (Malarone) in a human challenge model.

Plasmodia infect the liver for about 7 days before subsequently infecting the blood. Present prophylaxis against Plasmodium falciparum malaria employs agents that primarily kill blood stages and must be continued for 28 days after the last exposure. Atovaquone-proguanil (Malarone) is a new antimalarial agent that is licensed in 35 countries as treatment against blood-stage infection, but its components (atovaquone and proguanil) have separately been shown to be active also against liver stages. To determine whether atovaquone-proguanil is sufficiently active against liver stages to be discontinued 7 days after exposure, we challenged 16 volunteers with P. falciparum via infected mosquitoes. Twelve volunteers received atovaquone-proguanil (1 tablet daily) on the day prior to challenge, on the day of challenge, and for the next 6 days; 4 volunteers received matching placebo. All placebo volunteers demonstrated parasitaemia and malarial symptoms beginning on days 11-12 after challenge. No atovaquone-proguanil volunteer acquired malaria. Atovaquone-proguanil is the first licensed antimalarial agent that kills P. falciparum in the liver and that may be discontinued 7 days after the last exposure.

Adolescent↗
PubMedDate not supplied

Atovaquone and proguanil hydrochloride followed by primaquine for treatment of Plasmodium vivax malaria in Thailand.

Chloroquine-resistant Plasmodium vivax malaria has been reported in several geographical areas. The P. vivax life-cycle includes dormant hepatic parasites (hypnozoites) that cause relapsing malaria weeks to years after initial infection. Curative therapy must therefore target both the erythrocytic and hepatic stages of infection. Between July 1997 and June 1998, we conducted an open-label study in Thailand to evaluate the efficacy and tolerability of a sequential regimen of combination atovaquone (1000 mg) and proguanil hydrochloride (400 mg), once daily for 3 days, followed by primaquine (30 mg daily for 14 days) for treatment of vivax malaria. All 46 patients who completed the 3-day course of atovaquone-proguanil cleared their parasitaemia within 2-6 days. During a 12-week follow-up period in 35 patients, recurrent parasitaemia occurred in 2. Both recurrent episodes occurred 8 weeks after the start of therapy, consistent with relapse from persistent hypnozoites rather than recrudescence of persistent blood-stage parasites. The dosing regimen was well tolerated. Results of this trial indicate that atovaquone-proguanil followed by primaquine is safe and effective for treatment of vivax malaria.

Adolescent↗
PubMedDate not supplied

Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: a randomized comparative trial.

In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.

Acute Disease↗