[Advances in the study of AIDS].
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Biomedical subjects
Publications and source records attributed to M Ho.
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The effect of sera on the cytoadherence in vitro of Plasmodium falciparum-infected erythrocytes to melanoma cells was examined. Sera from 19 healthy individuals living in endemic malarious areas in Thailand and 24 patients with P. falciparum malaria were tested against four local P. falciparum isolates. Out of 57 sera examined, 12 (21%) showed significant inhibition (greater than 50%) of cytoadherence for at least one isolate. Anti-malarial IgG antibody titres were determined for all 57 sera and although 11 of the 12 inhibitory sera had relatively high titres, 36 out of 47 sera with similarly high titres showed no significant inhibitory activity. Convalescent sera were no more effective than corresponding acute sera in inhibiting the cytoadherence of erythrocytes infected with any of the four heterologous isolates examined. Sera which significantly inhibited cytoadherence were also capable of reversing cytoadherence, and pooled plasma, from healthy individuals living in malarious areas, was effective in significantly reversing the in vitro cytoadherence of all the five parasite isolates examined. The results confirm the antibody mediated strain-specific nature of the inhibition of cytoadherence and stress the difficulty in selecting immune sera potentially useful for the immunotherapy of cerebral malaria patients in Thailand.
Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.
We conducted a study to assess the effect of human immunodeficiency virus (HIV) infection on humoral immunity. Fifty-five homosexual men and 19 heterosexual men had four- to six-week postimmunization antibody responses measured to trivalent influenza vaccine and 23-valent pneumococcal vaccine. The homosexual men were divided into three groups: 20 asymptomatic HIV-seronegative men, 10 asymptomatic HIV-seropositive men, and 25 HIV-seropositive men with persistent generalized lymphadenopathy. Antibody responses to influenza antigens in the subgroups of homosexual men did not significantly differ from those of heterosexual controls. The IgG antibody responses to pneumococcal capsular types 9N and 18C in men with lymphadenopathy, and type 18C in HIV-seronegative homosexual men, were lower than those of heterosexual controls. Otherwise, responses to other ten capsular types showed no significant differences. There was no evidence of an immunosuppressive effect of vaccination on T-cell numbers, or deterioration of clinical status associated with vaccination. This study demonstrates that HIV-infected homosexual men, asymptomatic or with persistent generalized lymphadenopathy, are able to mount appropriate antibody responses to two commonly used vaccines.
The ability of an enzyme linked immunosorbent assay (ELISA) to detect venom was evaluated in 251 patients bitten by four of the commonest poisonous snakes in Thailand. Serum was tested only from patients who brought the snakes that had bitten them. About one third of all bitten patients had detectable venom antigenaemia, though a smaller proportion were symptomatic. Serum venom concentrations on admission correlated with the severity of clinical manifestations. The test was sensitive and specific even for specimens that had been collected and stored under suboptimal conditions. The technique is suitable for forensic use in cases of suspected snakebite. The combination of snake identification and venom antigen detection should be a more reliable means of studying the epidemiology of snakebite than the measurement of venom antibodies in a population.
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Disseminated infection with herpes simplex virus type 2 was identified in two patients 20 days after they had received kidney transplants from the same organ donor. Neither patient had neutralizing antibody to herpes simplex virus before transplantation, and both had herpes simplex virus isolated from surveillance cultures of urine before the onset of clinical symptoms. A clear focus of primary infection was not found in either patient. Analysis of the patients' isolates by DNA restriction endonuclease analysis strongly suggested that the strains were identical. These data implicate the allografts as the source of the viral infection.
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We studied 51 consecutive pediatric patients for the frequency and morbidity of viral infections after liver transplantation. The incidence of primary (67%) and reactivation (48%) Epstein-Barr virus (EBV) infections and reactivation (88%) cytomegalovirus (CMV) infection was comparable to that seen in adult transplant recipients. However, fewer pediatric than adult transplant recipients experienced primary CMV infection (P less than .01). Five (38%) of 13 CMV infections were symptomatic and included hepatitis, pneumonitis, enteritis, and mononucleosis. Two of 14 patients with primary EBV infection subsequently developed, at two months and two years after initial infection, an EBV-associated lymphoproliferative syndrome, and one of 10 patients with reactivated EBV infection developed a possible EBV-associated febrile encephalopathy. Other viruses causing infection in these children included herpes simplex virus, varicella-zoster virus, adenovirus, parainfluenza virus, respiratory syncytial virus, and rotavirus.
Women experiencing their first episodes of genital herpes were treated, beginning within three days of the onset of lesions, with 5 X 10(4) units of human leukocyte interferon/kg of body weight for 12 doses over 14 days (total, approximately 3.6 X 10(7) units) or with placebo in equivalent volumes. Life-table analysis revealed quicker healing and significant reductions in the duration of shedding of virus in interferon-treated patients. Maximum daily geometric mean titers of virus and total area of unhealed lesions also decreased more quickly. No statistically significant difference in resolution of pain was seen between the two groups. Interferon had no effect on onset or frequency of subsequent recurrences recorded over one year of follow-up. Moderate, transient neutropenia occurred in 13 of 34 interferon-treated patients. A therapeutic effect of human leukocyte interferon on initial genital herpes was documented, but the clinical usefulness of interferon treatment of genital herpes is limited at this time.
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Erythrocyte survival times were measured in healthy Thai controls and in patients following clearance of asexual P. falciparum or P. vivax parasitaemia. In five controls the mean cell life (MCL) of compatible donor erythrocytes was 89.6 d (mean range 73-101 d) compared with a mean MCL of 56.8 d (range 30-66 d) for autologous erythrocytes in 12 falciparum patients. In one of these patients the survival curve was biphasic with a rapid loss of some labelled cells. The survival of compatible donor erythrocytes was also studied in 10 patients and two types of survival curve could be distinguished. In five patients the cells had a mean MCL of 64.4 d (range 42-90 d). In the others survival curves were curvilinear, suggesting a complex mechanism of cell clearance or the presence of more than one cell population. There was initially a more rapid rate of destruction. In P. vivax malaria the MCL of autologous erythrocytes in seven patients was a mean of 67.2 d (range 34-74 d) and that of compatible donor cells in six patients was 66.8 d (range 54-76 d). In all except one of these patients both autologous and donor cell survival curves could be fitted to straight lines. No increase in cell-bound IgG or C3 was evident in 12 patients tested. The differences between the mean MCL in all the groups of patients and the controls were statistically significant at the 5% level. This indicates an increased rate of erythrocyte destruction following clearance of P. falciparum or P. vivax parasites which is not antibody or complement mediated. The mechanism is unknown, but appears to be extrinsic to the erythrocytes themselves and may result from nonspecific activation of the reticuloendothelial function associated with the parasitic infection.
Interferon, both natural and recombinant, has been shown in controlled clinical studies to be effective against herpes simplex virus infections, herpes zoster, the common cold caused by rhinoviruses, and some papilloma virus infections. In some cases, it is in competition with other antivirals, and in others its precise clinical indication is still unclear. Thus, further work and developments are required before interferon becomes a clinically recognized antiviral agent.
Mice fed a basal diet which contained 0.018% ciclosporin (CsA) achieved immunosuppressive blood levels of 1,400-2,200 ng/ml. Observations for 84 days of mice placed on this diet and infected at the same time with murine cytomegalovirus (MCMV) showed elevated virus titers and more widespread infection of various organs. An enhancing effect on acute MCMV infection measured by virus titers in the spleen 5 days after infection was evident only after 14 days of prior CsA ingestion. In groups of mice which were already infected with virus for 14 or 21 days, 14 days of CsA ingestion was needed before enhanced MCMV titers were noted in organs tested. Pretreatment with CsA of donor mice, which provided MCMV-specific immune spleen cells in passive protective experiments, eliminated the protective effect of transferred cells for recipient mice challenged with MCMV. These results suggest that CsA enhanced virus titers and helped maintain chronic persistent infection in certain organs by affecting the development or function of immune cells. Regardless of whether CsA was given before or after virus infection, about 2 weeks of CsA administration was required before elevation of virus titer was observed.
Adherent cells and serum components from Kenyan patients with visceral leishmaniasis were examined with the view to evaluating their contribution to cell-mediated immune suppression. Mitogens (phytohemagglutinin and concanavalin A) and antigens (purified protein derivative, streptokinase-streptodornase, and leishmania) were used as stimulants. Compared to the controls, the contribution of serum components to suppression in presence of any of the mitogens and antigens was not significant. The same applied to adherent cells, except in the presence of leishmania antigen where adherent cells contributed significantly (P less than 0.001). Removal of adherent cells from peripheral blood mononuclear cells of patients and controls considerably increased in vitro lymphocyte responses to both mitogens and antigens (by about twice), suggesting that in this study, the inhibition of in vitro lymphocyte responses to antigens and mitogens by adherent cells was a general phenomenon independent of the presence of the disease.
Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.
During a prospective study of the natural history of human immunodeficiency virus (HIV) infection in a cohort of gay/bisexual men, information on self-reported symptoms lasting for 3 or more days during the previous 6 months was collected without knowledge of the subject's HIV serological status. Twenty-two people were retrospectively found to have seroconverted to HIV during the interval. Each seroconverter was matched to two seronegative and two seropositive controls. Matched case-control analyses using the seronegative controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. Matched case-control analyses using the seropositive controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fatigue, fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. It was notable that the majority of seroconversions were not associated with any symptoms lasting for 3 or more days. Due to their non-specificity, symptoms associated with seroconversion are not likely to have a high positive predictive value. In high risk populations, however, appearance of these symptoms may facilitate identification of early infection that may be important for studies of natural history or for optimal timing for initiating antiviral therapy.
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