Cryptococcal meningitis in human immunodeficiency virus (HIV)-positive and HIV-negative patients.

This study compared clinical manifestations, blood biochemistry and cerebrospinal fluid (CSF) results of HIV-positive and HIV-negative patients with cryptococcal meningitis. We collected 57 cases of cryptococcal meningitis from cytological specimens submitted to the Department of Tropical Pathology, Faculty of Tropical Medicine. Pertinent clinical data were analyzed retrospectively in 47 cases for clinical manifestations, laboratory features and outcomes of 38 HIV-positive and 9 HIV-negative patients. Headache was the most common symptom seen in all cases, of which 70.2% occurred with fever. CSF examination of both groups revealed elevated opening pressure. Increased CSF protein and depressed CSF glucose levels were seen in HIV-negative cases, which differed from HIV-positive cases, where a slight change was noted. CSF pleocytosis in HIV-positive patients was variable. Forty-eight percent of HIV-positive patients had CSF leukocyte counts below 20 cells/ mm3. None was found in the HIV-negative patients. Specific treatments with amphotericin B and fluconazole were given. Five fatal cases of cryptococcal meningitis were noted, all of which were HIV-positive. There were statistically significant differences in blood neutrophils, blood eosinophils, CSF leukocyte counts, CSF neutrophils, CSF lymphocytes, CSF glucose, and CSF total protein, in HIV-positive and HIV-negative patients (p = 0.050, p = 0.022, p = 0.002, p = 0.016, p = 0.047, p = 0.031, p = 0.009, respectively).

Lack of association between CSF nitrate and sera nitrate in falciparum malaria infection.

Nitrate levels in CSF and sera from 16 coma and 19 noncoma falciparum malaria patients were determined using nitric oxide colorometric assay. The medians (range lower, upper limits) of nitrate in sera of comatose and noncomatose patients were 0.28 (0.11, 1.24) and 0.23 (0.05, 0.87) microM, respectively. The medians of nitrate level in CSF of coma and noncoma cases were 0.09 (0.01, 0.28) and 0.15 (0, 1.18) microM, respectively. There was no difference of nitrate level in sera and CSF from comatose or noncomatose patients compared to that in normal sera and CSF. The amount of nitrate in sera and CSF of both groups was not significantly correlated with coma depth, parasitemia, parasite clearance time and time to recovery. Contrast to our in vitro study using immunoperoxidase staining, we found inducible nitric oside synthase production by brain endothelial cells during 4-24 hours of coculturing with late stage of P. falciparum infected red blood cells. These results suggests that malaria severity can not be differentiated by nitrate level in body fluid.

Cytokines associated with pathology in the brain tissue of fatal malaria.

Cytoadherence of Plasmodium falciparum-infected erythrocytes to the brain microvascular endothelial cells is believed to be an important cause of circulatory blockage in cerebral malaria. Cytokines released during acute infection may activate brain endothelial cells leading to increased binding of infected erythrocytes in the brain and reduced cerebral blood flow. This effect may be direct and more potent with the tissue-localized cytokines in the brain. In order to establish this relationship, brain tissues of cerebral and noncerebral malaria were compared. The most prominent histopathologic changes in the brain included edema, neuronal degeneration, ring hemorrhage, and percentage of parasitized erythrocytes sequestration were observed in cerebral malaria. Immunohistochemical staining of the brain sections demonstrated that tissue-localized TNF-alpha, IFN-gamma, IL-I1B, and IL-10 were associated with the histopathology. However, IL-4 was the only cytokine presented at moderate level in the brain tissue of noncerebral malaria which histopathology was the least. No tissue-localized cytokine was observed in the brain of P. vivax infection or of the car accident control cases.

Susceptibility to hepatitis A virus infection among chronic liver disease patients and healthy blood donors in Thailand.

Due to improvements in socio-economic and sanitation conditions, Thailand has undergone a change from hyperendemicity to intermediate endemicity for hepatitis A virus infection, leaving a large part of the adult population without immunity. At the same time, the country is still highly endemic for hepatitis B and especially in the northeast, hepatitis C virus infection both of which when acquired during infancy or early childhood exhibit a strong tendency to turn towards chronic liver disease, although in particular with hepatitis B virus the asymptomatic carrier state is also rather common. As no cross-immunity exists between any of these viruses, double or triple infections do occur, a situation where previously acquired immunity to HAV becomes crucial as double infections have been shown to take a more severe or even fatal course. In the present study, we investigated 820 HBV- and/or HCV-related chronic liver disease (CLD) patients and 195 blood donors, both groups divided by 10-year age intervals, for the prevalence of anti-HAV. The results showed the same age dependence of immunity for all groups tested as can be expected for an area of intermediate endemicity, in that approximately 50% of those between 21 and 30 years of age had acquired anti-HAV. These findings indicate the immune response to HAV infection not to be altered by chronic infection with either HBV or HCV. Hence, vaccination against HAV should be considered, particularly in anti-HAV-negative patients with CLD.

Antiparasite adherence activity in Thai individuals living in a P. falciparum endemic area.

Two types of antimalaria antibodies in the serum of 54 villagers living in a malaria endemic area of Thailand were determined by indirect immunofluorescence assay in order to define the status of malaria immunity within the group. Antibodies to parasite-derived antigens in the membrane of ring stage-infected erythrocytes were very high (> or = 1:1,250) in 44%, moderate to low (< or = 1:250) in 37% of the sera, and the rest did not have the antibody. However, all the sera had antibodies to antigens of the intraerythrocytic mature parasites, showing a very high level in 65% and moderate to low levels in 37% of the sera. Sera with high antibody titers to either type of antigen significantly inhibited cytoadherence of P. falciparum-infected erythrocytes. All the sera variably inhibited rosette formation of the parasites but showed no association with the antibody titers. These results suggest that the antibodies to cytoadherence and rosette formation can be elicited and sustained in the malaria experienced host while living in the endemic area. This may be a natural preventive mechanism against the severity of P. falciparum infection in the infected host. How long the antiparasite adherence activity will last remains to be investigated.

Opportunistic protozoa in stool samples from HIV-infected patients.

A retrospective study of stool samples of HIV-infected patients from January 1994 to December 1995 submitted to the Department of Tropical Pathology was analyzed. There were twenty-two cases, all of which presented with chronic diarrhea. Result showed that 50% were infected with protozoa. These include Microsporidium (27.27%), Cryptosporidium (9.09%), Isospora belli (4.54%) and Giardia intestinalis cysts (9.09%). Other infections were Candida sp, Strongyloides stercoralis larva and Opisthorchis viverrini ova. The data stress the importance of opportunistic protozoa in the HIV-infected patients. Awareness of their existence of the diseases is important areas with increasing number of HIV-infected patients for early detection and proper treatment.

Herpes simplex virus type-2, cytomegalovirus and Epstein-Barr virus infection in acute non A to E hepatitis Thai patients.

A significant number of acute non A to E hepatitis cases are reported in Thailand every year, and the etiologies of these cases are unknown. Members of the herpesviridae family have been reported to cause either a self limited or fatal hepatitis in a small proportion of patients in other parts of the world. To determine whether herpesviruses may play a role in acute non A to E hepatitis, sera from 32 acute hepatitis patients without markers for acute hepatitis A to E virus infection were examined for IgM to herpesvirus type 2 (HSV-2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) using commercially available assays. IgM to HSV-2 was detected in four sera, IgM to CMV was detected in one serum, and IgM to EBV was detected in one serum. All of the acute non A to E hepatitis patients recovered and none had underlying conditions associated with impaired immunity. These results suggest that herpesviruses should be considered in the differential diagnosis for Thai patients with hepatitis.

Etiology of acute non-A, B, C hepatitis in Thai patients: preliminary study.

To better characterize the etiology of acute non-A, B, C hepatitis, 24 sera from 50 acute hepatitis without acute markers for hepatitis A, B, and C were examined for acute markers for the hepatitis E virus (HEV), cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2), and Epstein-Barr virus. Immunoglobulin M (IgM) specific for HEV, HSV-2, and CMV was detected using ELISA and total Ig specific to EBV was determined by standard indirect immunofluorescence. IgM to CMV was not observed in sera from any of the patients; whereas, IgM to HEV was detected in sera from 2 patients and IgM to HSV-2 was detected in 5 of 24 acute hepatitis patients. In addition, high titer of antibody was found in 2 of the patients. This results indicate that HSV-2 and HEV circulate in Thailand and are responsible for a small proportion of non-A, B, C hepatitis in Thailand.