Malaria: from quinine to the vaccine.
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Biomedical subjects
Publications and source records attributed to R S Desowitz.
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The effects of malaria were studied in a group of parturient women of East Sepik Province, Papua New Guinea. Further information was gathered from a search of hospital records and interviews with village aid post orderlies. Examination of placental blood revealed a Plasmodium falciparum parasitaemia rate of 41% of the primiparae, 23% in parous 2, 25% in parous 3, and 3% in multiparae greater than 3. Approximately one-half of those with placental parasitaemia had a concomitant detectable peripheral parasitaemia. Placental parasitaemias were of relatively low density, averaging 1.6%. There were no instances in the observed series of births, hospital records, or village studies of the occurrence of severe malaria in the mother or its acute effects on the foetus. Neither birthweight nor maternal or cord blood haematocrit was related to the presence or absence of placental parasitaemia. Neonatal birthweight and risk of delivering a low birthweight (less than 2.5 kg) baby was statistically associated only with maternal parity. The possible reasons for the relatively benign effect of malaria in the pregnant women of this population are discussed.
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The pathologic changes in placentae of pregnant rats infected with Plasmodium berghei at different stages of gestation were studied using light and electron microscopy and immunohistochemistry. The major changes observed were thickening and duplication of the trophoblastic basement membrane, and accumulation of parasitized erythrocytes and occasional mononuclear cells in the maternal blood space. Immunohistochemical examination of nine placentae revealed that six stained positively for IgG, two for IgM, and four for P. berghei antigen. No C3 deposition was detected. The findings in this study indicate that the variable parasitologic-clinical course from benign to fatal of P. berghei infection in pregnant rats makes it a potentially valuable model of human gestational malaria infection.
In a study of malaria and pregnancy in East Sepik Province of Papua New Guinea 45 maternal and cord serum pairs were tested for Plasmodium falciparum-specific IgE antibody. There were 17 positive sera: 6 cases of maternal serum alone, 5 cases of cord serum alone and 3 pairs of maternal and cord sera. IgE antibody positivity rates in the mothers increased with parity, whereas placental parasitaemia rates decreased. Cord serum positivity was not affected by parity. Immunoblots of the sera revealed a diversity of IgE antibodies to specific antigens of the P. falciparum lysate, but an IgE antibody to a 48kd antigen was present in all positive maternal and cord sera.
This study characterizes a Plasmodium berghei white rat model of P. falciparum malaria in the pregnant human. Seventy-day-old and 114-day-old female rats, given an infecting inoculum at time of mating, had higher parasitemias and a more severe anemia than age- and sex-matched controls. Under these experimental conditions, the parasitemia went to crisis in all animals and there were no fatal infections. In contrast, all animals died when the infection was initiated 7 days after conception, a timing that brought a coincidence of peak parasitemia and term. Pregnancy during the post-crisis subpatent period did not cause recrudescence. At the time of delivery, the parasitemia was consistently higher in the placental (crush smear) blood than in the peripheral (tail) blood. This difference was greatest in animals giving birth shortly before or 1-2 days after the parasitemic crisis. Very young, compact parasite forms predominated in the placental blood, whereas trophozoites predominated in the peripheral blood.
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The Plasmodium falciparum-specific blastogenic response of cord blood lymphocytes (CBLs) from neonates born in an area of holoendemic malaria of Papua New Guinea was compared to that of CBLs from neonates born in Hawaii, where malaria transmission does not occur. The average blastogenesis stimulation index of the New Guinea CBLs was 4.5 times greater than that of the Hawaiian group of samples. Eight of the 24 New Guinea CBL samples had a stimulation index greater than ten and counts per minute ranging from 13,331-84,242, whereas all the Hawaiian CBL samples had a stimulation index less than four, and the highest count per minute was 2016. The data are interpreted as indicating that prenatal immune sensitization/priming to P. falciparum had occurred in some of the New Guinea neonates.
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Relatively few cases of humans infected with Entamoeba polecki have been reported world-wide. Where man and pig live in close association and where sanitation is poor, pig to man transmission is considered to be the most likely source of human infection. In our survey of 184 children only fresh faeces were used, thus allowing the identification of trophozoites as well as cysts. Thirty-five children (19%) were found positive for E. polecki, although in one community ten of 23 (43.4%) over five-year olds were infected. Sera from 20 positive children were tested against E. histolytica antigen, but no positive reactions were observed. We propose the possibility of man to man transmission of E. polecki where the prevalence rate and intensity of infection are high.
In the past 13 years, 24 cases of anisakiasis have been reported in the United States. Of these, 14 were infections by Phocanema sp. and found in California and Alaska, and most were of the tissue non-invasive type. The remaining 10 cases were infections by larvae of anisakis type I (L3 and L4). Of these 10 cases, 4 were found on the west coast, 5 were on the east coast and one was in Hawaii. In 3 of the 10 cases, the parasite invaded the digestive tract. A characteristic symptom of the throat named "tingling throat" was manifested in 16 of the 24 cases, and this symptom was found to be due to larvae of Phocanema in most cases. As a method for immunological diagnosis of anisakiasis, the radioallergosorbent test (RAST) is being investigated as a cooperative study with Ishikura. As a result, IgE obtained from the sera of 4 patients who had been parasitologically diagnosed as having the disease and one patient in whom the parasite had not been confirmed but was clinically diagnosed as having the disease reacted strongly with anisakis larva antigens, and this reaction was able to be distinguished from the immune response to antigens of other Ascaris. On the other hand, when RAST was applied to child bronchial asthma patients in Hawaii, they showed a strong response to the anisakis larva antigens. Because the causative factors of child bronchial asthma in Hawaii are few and the environmental conditions are also good (i.e., do not cause asthma), their asthma is surmised to be helminth-associated asthma. In view of this background, as well, the results of RAST are interesting. When anisakis larva antigens were analyzed, a strong immunosuppressive effect was confirmed in the high molecular weight fraction (MW: greater than 10,000), while the presence of a substance having mutagenicity was confirmed in the low molecular weight fraction (MW: less than 10,000). In addition, in the sea near Hawaii, we discovered a novel species of Phocanema, which were named Terranova HA.
The serum of patients with parasitologically confirmed and one patient with a clinically presumptive case of anisakiasis were tested by the radioallergosorbent test (RAST) and counter-electrophoresis (CEP) for IgE and IgG antibodies, respectively, using antigens prepared from larval (L3) stage Anisakis simplex and larval (L2) stage Toxocara canis. All sera were RAST-positive to the A. simplex antigen and RAST-negative to the T. canis antigen. All sera were CEP-negative to both antigens. The presence of a specific IgE antibody suggests that the RAST could serve as a useful technique for the serodiagnosis of anisakiasis in man.
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Counterimmunoelectrophoresis (CIE) using cell-free extracts of Leishmania donovani promastigotes and Trypanosoma brucei as antigens and indirect haemagglutination (IHA) using commercially prepared reagents were compared for their diagnostic efficacy and applicability to immunoepidemiological studies in an area of Bangladesh where kala-azar is present. The CIE was positive for all parasitologically confirmed cases whereas the IHA positivity was only 60%. The T. brucei antigen was equally as good, if not better, than the L. donovani antigen for CIE. The CIE test was negative for all of 34 apparently healthy villagers. For this same group of individuals, 10 (29%) were low titre-IHA positive. The findings suggest that CIE is the more reliable diagnostic test but both methods should be employed for immunoepidemiological investigations.
In cats infected with normal, or irradiated, infective (L3) larvae of Brugia pahangi counterimmunoelectrophoresis revealed the presence of antibody to soluble antigens derived from microfilariae, adults and infective larvae of the same parasite. Infected cats with a persistently high to moderate microfilaraemia gave positive precipitin reactions to L3, microfilarial and adult worm antigens. Cats which had become amicrofilaraemic had antibody to L3 and microfilarial antigens but not to adult worm antigen. Serum from cats inoculated with irradiated L3 larvae produced a precipitin reaction only to the L3 antigen.