Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression.

Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NOx excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.

Delayed-type hypersensitivity testing in Tanzanian adults with HIV infection.

Delayed-type hypersensitivity (DTH) testing and total lymphocyte counts as measures of cell-mediated immune function were assessed for medical patients in Dar es Salaam, Tanzania. DTH testing was performed with the Multitest CMI device which simultaneously administers seven antigens. Of 201 patients completing DTH testing, 90 were HIV seropositive. Anergy occurred more frequently among HIV-seropositive patients (39 of 90) as compared with HIV-seronegative patients (17 of 111). DTH skin test reactivity, measured by anergy, the number of positive antigens, and the combined DTH response induration, was significantly related to the clinical stage of HIV disease. Median total lymphocyte counts were significantly lower in HIV-seropositive patients than in HIV-seronegative patients (1,130 vs. 1,680 lymphocytes x 10(6)/L). Total lymphocyte counts decreased with increasing severity of HIV disease. In multivariable analysis, the number of positive antigens in DTH testing and lymphopenia significantly predicted HIV infection. The findings suggest that DTH testing and total lymphocyte counts may be useful, inexpensive tests of immune function in African patients with HIV disease.

Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria.

Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable of oxygen transport, have been previously found during Plasmodium vivax infections and in acidotic infants. We measured methaemoglobin in the following 5 groups of children with P. falciparum malaria admitted to Muhimbili Medical Centre, Dar es Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n = 50), including 32 with complete recovery (CMCR) and 18 with death or neurological sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean methaemoglobin levels were elevated in all groups with malaria, forming up to 16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated with disease severity and severity of anaemia. Mean methaemoglobin levels in children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8% respectively; the mean levels in those with clinical disease were significantly higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was found in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS, respectively. In the presence of parasite sequestration, impaired tissue perfusion, and a reduction in oxygen carrying capacity of blood due to anaemia, a further reduction in oxygen carrying capacity from even a modest concentration of methaemoglobin is likely to exacerbate tissue hypoxia, perhaps critically so in a minority of anaemic and acidotic patients with severe falciparum malaria.

Diagnosis and screening of HIV/AIDS using clinical criteria in Tanzanian adults.

The clinical utility of the World Health Organization (WHO) clinical case definition (CCD) of acquired immune deficiency syndrome (AIDS) in Africa, several proposed modifications of the WHO CCD, and two proposed screening algorithms for human immunodeficiency virus (HIV) infection were examined in adult medical inpatients in Dar es Salaam, Tanzania. Sensitivity, specificity, and positive and negative predictive values were determined for the CCDs and screening algorithms. Multivariable analysis identified factors with high accuracy for HIV infection. Of 223 patients enrolled in the study, 95 were seropositive for HIV infection. The WHO CCD and the modified CCDs had low sensitivities (14.7-32.6%) but high specificities (95.3-99.2%) and positive predictive values (83.8-94.7%). The screening algorithms had moderate sensitivities (66.3-77.9%) and poor specificities (46.1-79.7%). Multivariable analysis consistently identified oral candidiasis and lymphadenopathy as the best predictors of HIV infection. Although patients with asymptomatic or early HIV infection may be missed by clinical criteria, in a high prevalence population, AIDS may be diagnosed accurately clinically because of the effect of prevalence on the positive predictive values of the CCDs. Furthermore, selection of patients for HIV serologic testing may be guided by simple combinations of clinical features.