Stronger host response per parasitized erythrocyte in Plasmodium vivax or ovale than in Plasmodium falciparum malaria.

OBJECTIVE AND METHODS: Fever tends to start at a lower level of parasitemia in Plasmodium vivax or ovale than in P. falciparum malaria, but hyperparasitemia and complications are more likely to occur in P. falciparum malaria. Therefore, we compared the relationship between parasitemia and host response parameters before therapy in 97 patients with P. faciparum malaria (18 with complications), and 28 with P. vivax or ovale malaria. RESULTS: In both types of malaria, parasitemia correlated with blood levels of tumour necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), Thrombin-antithrombin III (TAT) and elastase, and these parameters were higher in P. falciparum malaria than in P. vivax or ovale malaria. In contrast, the ratios of TNF-alpha, TAT, elastase, and LDH per parasitized erythrocyte were higher in P. vivax or ovale malaria than in uncomplicated P. falciparum malaria. They were lowest in complicated disease. Multivariate regression analysis confirmed that parasitemia did not affect these differences. CONCLUSION: The host response may reach full strength at lower parasitemia in Plasmodium vivax or ovale, than in P. falciparum malaria. With hyperparasitemia in P. falciparum malaria, the host response seems to be unable to control parasite multiplication.

Topographic and quantitative display of integrated human immunodeficiency virus-1 provirus DNA in human lymph nodes by real-time polymerase chain reaction.

In situ polymerase chain reaction (isPCR) has been applied in many fields that require detection of a genomic marker in combination with its topographic localization in tissue. We describe here a novel approach that circumvents the major drawbacks of in situ PCR, ie, low sensitivity, leakage of DNA from cells, and inability to quantify the DNA input. Frozen sections of a lymph node from a human immunodeficiency virus (HIV)-1-infected patient were fixed on glass microscope slides, and the glass was scored into square fragments of 0.5-mm edge length using a diamond cutting device. Slides were then attached to adhesive, elastic plastic foil and finally broken, and the foil was extended to allow sorting of fragments into PCR microtiter plates. The material was tested for HIV-1 proviral DNA by a sensitive real-time PCR protocol. Subjacent sections were stained for follicular dendritic cells to identify follicles. The fragmentation process prevented leakage of amplified DNA to neighboring areas as often experienced with in situ PCR. Provirus was clearly associated with follicular areas, in which provirus-carrying cells represented an average of 0.8% of the total cell population (peak density, 3.1% of all follicular cells). The results of this method suggest that the high density of provirus-containing cells in follicles may be important for the persistence of proviral DNA in infected persons.

Long-term follow-up after successful interferon therapy of acute hepatitis C.

Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-alpha-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-gamma) ELISPOT analysis detected HCV-specific CD4(+) T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8(+) T-cell responses were found in 4 of 5 HLA-A2-positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-alpha-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8(+) (but not CD4(+)) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment.

Procalcitonin serum levels in tertian malaria.

BACKGROUND: Procalcitonin (PCT) is closely correlated with parasite burden and clinical outcome in falciparum malaria. The role of PCT in tertian malaria has not previously been investigated. PATIENTS AND METHODS: PCT serum levels in 37 patients with tertian malaria were analysed. Clinical and laboratory parameters were assessed and statistically correlated both to the initial PCT levels and during the course of the disease. RESULTS: PCT levels rose for one day after commencing treatment and declined thereafter. However, there was no significant correlation with parasite burden, clinical parameters, laboratory values, or the presence of semi-immunity. Before treatment, the majority of patients showed normal or slightly elevated PCT levels (< 2.5 ng/ml), but PCT was markedly elevated (4.8-47 ng/ml) in one third of the population. The two groups did not differ by any other of the assessed parameters. Thus, while the post-treatment course of PCT resembles falciparum malaria, the lack of correlation between disease severity and even high PCT levels in a large proportion of patients is intriguing. CONCLUSIONS: There is a fundamental difference in the relationship of PCT with tertian malaria not seen in other infectious diseases in which elevated PCT levels have been observed. This suggests distinct pathophysiological pathways in malaria.

Virologic, immunologic, and clinical response to highly active antiretroviral therapy: the gender issue revisited.

BACKGROUND: Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis for patients with HIV. There is ongoing debate over a potential gender effect on patient outcome after HAART. METHODS: Individuals were from the EuroSIDA cohort, naive to protease inhibitors and nonnucleoside reverse transcriptase inhibitors, and had at least one viral load and CD4 measurement prior to starting HAART. Endpoints were virologic (time to <500 copies/mL, time to rebound [first of two consecutive viral loads >500 copies/mL]), immunologic (time to a 100/mm cell rise in CD4 count) and clinical (time to new AIDS and death). Hazard ratios (HR), derived using Cox regression models, compared female to male rates of achieving endpoints. RESULTS: Of 2547 patients, 20% (511) were female. Significantly more females than males were nonwhite (24% vs. 10%, p <.001). Males were older (median age 39 vs. 35 years, p <.0001), had lower CD4 counts (211 vs. 240/mm, p =.03), higher viral loads (4.6 vs. 4.4 log copies/mL, p <.0001), were more likely to have a history of AIDS (26% vs. 18%, p <.001) and were more likely to be treatment-naive (34% vs. 29%, p =.03). Adjusted HR for association between gender (comparing females with males) and the outcomes studied were as follows: for reaching <500 copies/mL 0.91 (0.81-1.03, p =.17), rebound 1.17 (0.95-1.44, p =.15), for 100 cell CD4 count rise 1.02 (0.88-1.14, p =.99), for progression to new AIDS 1.12 (0.73-1.71, p =.59) and for time to death 1.15 (0.69-1.92, p =.57). CONCLUSIONS: We found no significant evidence of a gender difference in virologic, immunologic, or clinical outcomes after starting HAART.