A modified leukocyte nitroblue tetrazolium test in acute bacterial infection.

The increased ability to leukocytes to reduce nitroblue tetrazolium (NBT) has been used to detect the presence of systemic bacterial infection. This test has been utilized to evaluate infections and leukocyte dysfunction in children, but has not been extensively applied to traumatized patients or infected volunteers. Moreover, the technic as originally described presented methodologic difficulties. In this study of 889 such patients, a modified NBT test provided excellent differentiation of 63 systemic bacterial infections (NBT score greater than or equal to 10%) from non-infectious fevers, local enteric diseases, and certain viral and plasmodial infections (NBT score less than or equal to 9%). Splenectomy was associated with a transient false-positive score and clinical typhoid fever with a false-negative response

Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites.

With strict adherence to ethical guidelines, a volunteer was immunized against sporozoites of Plasmodium falciparum and P. vivax, the antigen consisting of attenuated sporozoites of each species inoculated through bites of mosquitoes X-irradiated at a minimum dosage of 15,000 rads. On one occasion this dosage did not render all P. vivax sporozoites noninfective. Species specificity of antigen and antibody was demonstrated, but within each species a wide geographical diversity of strains proved interchangeably antigenic and susceptible to the antibody. Once immunized, the volunteer was protected for not more than 3 months and 6 months, respectively, from infective P. falciparum and P. vivax sporozoites, the duration of protection being reflected by a positive species-specific circumsporozoite reaction. Studies in this volunteer, and in two others immunized with P. falciparum sporozoites, did not reveal any increase in serum levels of immunoglobulins G and M.

Radical cure of Chesson strain vivax malaria in man by 7, not 14, days of treatment with primaquine.

Glucose-6-phosphate dehydrogenase-normal adult volunteers infected with mosquito-bone Chesson strain vivax malaria were treated with chloroquine and primaquine during the initial attack. Administration of 60 mg (base) of primaquine daily for 7 days was as effective in preventing relapse as is the regimen customarily used for the radical cure of infections produced by this strain, namely, 30 mg daily for 14 days. However, it is stressed that because of the risk of primaquine-induced hemolysis in individuals having genetically-transmitted erythrocyte abnormalities this high dosage should not be used routinely.

Plasmodium falciparum: responses of a semi-immune individual to homologous and heterologous challenges, and non-infectivity of gametocytes in Anopheles stephensi.

With strict adherence to ethical guidelines, a semi-immune volunteer was exposed to homologous and heterologous blood challenges with strains of Plasmodium falciparum from Vietnam and Tanzania. On both occasions infections developed, but clinical manifestations were moderated, prepatent periods increased, and parasitemias limited. Gametocytes produced by these infections failed to infect Anopheles stephensi. Possible reasons for this are discussed.

Antimalarial effects of clindamycin in man.

Clindamycin 450 mg every 8 hours for 3 days cured three non-immune patients of falciparum malaria, although the response was slow. The addition of quinine to this regimen provided an accelerated response and cured 3 of 5 other patients. Single doses of clindamycin given daily for 3 days, with or without quinine, cured 1 of 3 patients. Gastric intolerance to the drugs, probably accentuated by the clinical condition, was pronounced in some cases, the course of treatment being interrupted in three patients for this reason. Chesson strain Plasmodium vivax relapses in man were not inhibited by ingestion of 450 mg of clindamycin every 6 hours for 14 days.

Estimate of Plasmodium falciparum sporozoite content of Anopheles stephensi used to challenge human volunteers.

Plasmodium falciparum infected Anopheles stephensi, taken from a group of mosquitoes which had been used to challenge recipients of (NANP)3-TT vaccine, were tested for P. falciparum sporozoite content by an immunoradiometric assay. Seventy-six percent were infected with mean and median sporozoite equivalents per mosquito of 220,994 and 217,398, respectively (SD = 54,911). This sporozoite density is greater than that usually found in the field. These data suggest that this challenge for evaluating P. falciparum sporozoite vaccines is a demanding test of immunity.

Effects of ingested human anti-sporozoite sera on Plasmodium falciparum sporogony in Anopheles stephensi.

We investigated the effects of human anti-sporozoite antibodies on the sporogonic development of Plasmodium falciparum in Anopheles stephensi. Equal volumes of washed human erythrocytes and human sera from 1) volunteers with protective immunity induced by immunization with irradiated P. falciparum sporozoites, 2) the same volunteers before immunization, or 3) Kenyans exposed to natural sporozoite transmission, were fed to cohorts of P. falciparum-infected A. stephensi on either day 5, 8, or 11 after infection. A fourth group of infected mosquitoes from the same cohort were not refed. In two experiments, the effects of anti-sporozoite antibodies were evaluated by determining the infection rates and parasite densities for oocysts and salivary gland sporozoites. There was no evidence that anti-sporozoite antibodies had any effect on the development or intensity of P. falciparum infection in A. stephensi. However, accelerated oocyst maturation was associated with mosquitoes taking a second blood meal, independent of serum source. Salivary gland sporozoites from mosquitoes that fed on immune human sera contained bound human IgG, which was detectable by indirect immunofluorescence assay. The infectivity and transmission potential of human IgG-coated sporozoites is unknown.

Urinary neopterin in volunteers experimentally infected with Plasmodium falciparum.

To investigate the kinetics of monocyte/macrophage activation in falciparum malaria we determined urinary neopterin values serially in experimentally infected volunteers. Three subjects who had been immunized with irradiated sporozoites via mosquito bites served as controls. These individuals remained aparasitaemic, afebrile and without a rise in neopterin after challenge by infective mosquitoes. Four non-immune subjects developed Plasmodium falciparum parasitaemia, fever (3 of 4) and sharp rises in neopterin. Parasite densities reached 10-100 parasitized erythrocytes per microliter before elevations in temperature or neopterin levels were detected. Onset of fever preceded the rise in neopterin excretion by one day. Prompt chemotherapy was associated with the clearance of parasites from the blood and the return of temperature and neopterin levels to normal.

Estimate of anti-Plasmodium falciparum sporozoite activity in humans vaccinated with synthetic circumsporozoite protein (NANP)3.

A mathematical model was defined to estimate the degree of in vivo activity against Plasmodium falciparum sporozoites expressed by volunteers vaccinated with a synthetic peptide comprising the immunodominant epitope of the circumsporozoite protein. Relative to the course of infection in non-immunized controls, infections in vaccinated volunteers corresponded to the neutralization or delay of development of greater than 99% of challenge sporozoites.