Search

Peripheral blood samples obtained from patients during an outbreak of Ebola virus (Sudan species) disease in Uganda in 2000 were used to phenotype peripheral blood mononuclear cells (PBMC), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. It was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. Blood smears revealed thrombocytopenia, a left shift in neutrophils (in some cases degenerating), and atypical lymphocytes. Infected patients who died had reduced numbers of T cells, CD8 + T cells, and activated (HLA-DR + ) CD8 + T cells, while the opposite was noted for patients who survived the disease. Expression levels of cytokines, Fas antigen, and Fas ligand (TaqMan quantitation) in PBMC from infected patients were not significantly different from those in uninfected patients (treated in the same isolation wards), nor was there a significant increase in expression compared to healthy volunteers (United States). This unresponsive state of PBMC from infected patients despite high levels of circulating antigen and virus replication suggests that some form of immunosuppression had developed. Ebola virus RNA levels (virus load) in PBMC specimens were found to be much higher in infected patients who died than patients who survived the disease. Similarly, blood levels of nitric oxide were much higher in fatal cases (increasing with disease severity), and extremely elevated levels (≥150 μM) would have negatively affected vascular tone and contributed to virus-induced shock.

Traditional medical practices persist today in Northern Uganda; for example, the operations of ebino and tea-tea are frequently performed in childhood. Ebino, or "false teeth", refers to gingival swellings during the eruption of the primary canine teeth in infants, and consists of the extraction of deciduous canine tooth buds. Tea-tea consists of systematic cuts made on the chest wall when the child has difficulty in breathing. The objectives of this study are to describe the morbidity and mortality related to complications arising from the ebino and tea-tea procedures among children admitted to the paediatric ward of St. Mary's Hospital Lacor in 1999, and to estimate the prevalence of ebino and tea-tea among children aged 0-4 years attending, for any cause, the child welfare department (CWD) of the hospital. The prevalence survey consisted of the examination of 1,995 children attending CWD during a four-week period in 1999 to look for missing primary canine teeth (ebino), and for "therapeutic" cuts on the chest wall (tea-tea). In the difficult context of war and social disruption prevailing in Northern Uganda, sustainable methods of data collection and analysis should be utilised to support evidence-based decision-making.

Background: In sub-Saharan Africa, co-infection with HIV and malaria is probably very common. Although an interaction between the two infections is biologically plausible, it has not been investigated thoroughly. Objectives: To evaluate the association firstly between co-infection with HIV and malaria parasites and the occurrence of acute fever, and secondly between HIV infection and clinical malaria, defined as the presence of acute fever and malaria parasites. Methods: A hospital-based case‐control study was conducted in Gulu District (northern Uganda), an area endemic for malaria and with a high HIV prevalence. HIV testing and malaria parasite quantification were performed on 167 consecutive adult outpatients with acute fever and no signs or symptoms of localized infection, and on 134 consecutive adult in-patients without fever who were admitted for non-HIV-related trauma or elective surgery. Results: No significant association with acute fever was observed for single infection with either malaria parasites [adjusted odds ratio (AOR), 1.75; 95% confidence interval (CI), 0.73‐4.21] or HIV (AOR, 1.01; 95% CI, 0.51‐2.03), whereas a significant association was observed for co-infection (AOR, 9.75; 95% CI, 1.19‐80.00). An association was found between HIV infection and clinical malaria (AOR, 2.34; 95% CI, 0.89‐6.17); the association became statistically significant when the definition of clinical malaria included a cut-off for parasite density (50 th percentile; i.e., 586 parasites/Il; AOR, 3.61; 95% CI, 1.04‐12.52). Conclusions: Despite the limited statistical power, the results of our study show an association between HIV infection and clinical malaria; if confirmed, this finding could be important for public health in sub-Saharan Africa.

To evaluate the impact of infectious diseases on hospital services in Northern Uganda, a retrospective analysis of discharge records concerning 70,304 inpatients admitted to the Lacor Hospital (Gulu, Uganda) during the period 1992-1997 was performed. Children less than five years old represented 46.5% of the admissions, and the burden of infectious diseases on pediatric admissions increased over time, especially due to malaria and measles. Infectious diseases accounted for 7 of the 10 leading causes of admission. The most frequent cause was malaria (21.8% of total). The second leading infectious disease resulting in admission was respiratory tuberculosis (6.2%); given the long hospital stay, this is the most important disease in terms of hospital bed days (24.6%). Infectious diseases have represented a progressively heavy burden on hospital services, mostly due to pediatric admissions. Respiratory tuberculosis and malaria represent nearly one-third of the overall burden in terms of hospital bed days.

In northern Uganda, unerupted primary canine teeth are commonly extracted because they are believed to cause diarrhoea, vomiting, and fever. This practice, known as ebino, is performed under very crude conditions often using unclean tools. To evaluate the morbidity and mortality of complications related to ebino, we retrospectively analysed discharge records from the paediatric ward of Lacor Hospital, Gulu. In the period 1992-98, ebino-related complications, mainly sepsis and anaemia, were among the leading causes of admission (n = 740) and hospital death (n = 156, case fatality rate = 21.1%, proportional mortality rate = 3.3%). Discouraging the adoption of deeply rooted traditional practices that are potentially hazardous to health should be a public health priority in northern Uganda. This could be done by educating not only the general public, but also traditional healers and community and religious leaders, who could convey the knowledge to their people.

The concentration of type 1 and type 2 cytokines and fibroblast-associated apoptosis-1 soluble receptor (sAPO-1/Fas) was analysed in the sera of Ugandan and Italian HIV-1-seropositive and seronegative individuals. The data were compared to determine whether the immunological status of these groups was different.Sixty-seven Ugandan and 30 Italian HIV-positive patients were analysed and stratified according to CD4 counts (group 1,500 x 10(6)/l; group 2, 200-500 x 10(6)/l; group 3,200 x 10(6)/l). Sera from 15 Ugandan and 11 Italian HIV-negative blood donors were also analysed. Serum concentration of type 1 cytokines [interleukin (IL)-2, IL-12, and interferon (IFN)-gamma] and type 2 cytokines (IL-4 and IL-10), and sAPO-1/Fas were measured by enzyme-linked immunosorbent assay.Serum levels of IL-2, IFN-gamma and IL-10 but not of IL-4 and IL-12, were elevated in HIV-positive group 1 and 2 Africans compared with HIV-positive Italian individuals. IL-4 was mildly augmented in HIV-positive group 3 African patients. Serum concentration of sAPO-1/Fas was reduced in HIV-positive Africans compared with HIV-positive Italian individuals. Finally, serum levels of IL-2 and IL-10 were increased and sAPO-1/Fas reduced when sera of HIV-negative African healthy controls were compared with their Italian counterparts. The ratio of type 1/type 2 cytokines was roughly 1.0 in HIV-negative African controls, and much greater than 1.0 in HIV-negative Italian controls.These preliminary findings indicate that immune activation is present in African HIV infection. Furthermore, these data raise the possibility that abnormal immune activation and increased susceptibility to antigen-induced cell death is present even in HIV-negative African controls.

Although Ebola virus (EBOV) is transmitted by unprotected physical contact with infected persons, few data exist on which specific bodily fluids are infected or on the risk of fomite transmission. Therefore, we tested various clinical specimens from 26 laboratory-confirmed cases of Ebola hemorrhagic fever, as well as environmental specimens collected from an isolation ward, for the presence of EBOV. Virus was detected by culture and/or reverse-transcription polymerase chain reaction in 16 of 54 clinical specimens (including saliva, stool, semen, breast milk, tears, nasal blood, and a skin swab) and in 2 of 33 environmental specimens. We conclude that EBOV is shed in a wide variety of bodily fluids during the acute period of illness but that the risk of transmission from fomites in an isolation ward and from convalescent patients is low when currently recommended infection control guidelines for the viral hemorrhagic fevers are followed.

A retrospective analysis of the discharge records of 186,131 inpatients admitted to six Ugandan hospitals during 1992-1998 was performed to describe the disease patterns and trends among the population of Northern Uganda. In all hospitals, malaria was the leading cause of admission and the frequency of admissions for malaria showed the greatest increase. Other conditions, such as malnutrition and injuries, mainly increased in the sites affected by civil conflict and massive population displacement. Tuberculosis accounted for the highest burden on hospital services (approximately one-fourth of the total bed-days), though it showed a stable trend over time. A stable trend was also observed for acquired immunodeficiency syndrome (AIDS), which is in contrast to the hypothesis that AIDS patients have displaced other patients in recent years. In conclusion, preventable and/or treatable communicable diseases, mainly those related to poverty and poor hygiene, represent the leading causes of admission and death, reflecting the socioeconomic disruption in Northern Uganda.

The objective was to estimate HIV-1 prevalence among women attending an antenatal clinic in the Gulu District (North Uganda) and based on these data among the districts female population. Anonymous HIV-1 screening was performed for 8555 antenatal clinic attendees aged 15-39 years in the period 1993-97. The results were used to estimate the prevalence among the districts female population accounting for differences in fertility rates by HIV-1 serostatus. Among antenatal clinic attendees HIV-1 prevalence showed a significant linear decrease (P < 0.001) from 26.0% in 1993 [95% confidence interval (CI) 23.2-29.0%] to 16.1% in 1997 (95% CI 14.8-17.5%). This decrease was mostly due to a marked decrease until 1995 (14.3%; 95% CI 12.7-16.0%) and was more pronounced among women aged under 30 years (P < 0.001) from both urban and rural areas (P < 0.001). The risk of being infected was higher among women from urban areas (Gulu Municipality) both over the entire period (adjusted prevalence proportion ratio = 1.54; 95% CI 1.40-1.68) and by individual year. The estimated prevalence for the 15-39 year old female population standardized by age and area of residence decreased from 25.4% in 1993-94 to 17.8% in 1996-97; these rates were 1.22 and 1.28 times higher respectively than those among antenatal clinic attendees. The trend of decrease among young women for whom changes in HIV-1 prevalence more closely reflect incidence could be partially due to a reduction in risk behavior and a consequent decreasing incidence. Differences in fertility rates by HIV-1 serostatus should be addressed when using antenatal clinic data to estimate prevalence among the general female population. (authors)

From January 1989 to April 1996 15568 individuals (5057 inpatients 3466 outpatients 5438 women attending the antenatal clinic and 1607 secondary students) were screened for HIV-1 virus at St. Marys Lacor Hospital northern Ugandas main hospital. For inpatients estimated prevalence rates with exact binomial 95% confidence intervals were 57.9 (53.3-62.4) for 1989 52.1 (49.0-55.1) for 1990 51.9 (48.1-55.6) for 1991 64.2 (60.2-68.2) for 1992 56.0 (51.7-60.1) for 1993 65.4 (62.3-68.5) for 1994 57.2 (52.6-61.8) for 1995 and 56.1 (50.0-62.1) for 1996. For outpatients they were 44.5 (38.8-50.2) for 1989 53.3 (49.6-56.9) for 1990 60.1 (51.6-8.2) for 1991 64.1 (55.3-72.3) for 1992 45.8 (39.1-52.7) for 1993 44.1 (40.1-47.6) for 1994 39.3 (36.0-42.8) for 1995 and 43.7 (38.0-49.6) for 1996. For pregnant women they were 27.1 (24.4-30.0) for 1993 21.9 (20.2-23.8) for 1994 14.7 (13.1-16.4) for 1995 and 11.7 (8.8-15.1) for 1996. For secondary school students they were 2.0 (1.1-3.3) for 1994 1.4 (0.7-2.5) for 1995 and 1.8 (0.4-5.1) for 1996. Adjusted odds ratios (ORs) were calculated using a logistic regression model that controlled for gender group and year tested. Logistic regression models were also used to test for each group the presence of a significant linear change over time in risk of being infected controlling for gender. The adjusted OR per group with a 95% confidence interval for inpatients was 79.1 (53.6-116.6); for outpatients it was 68.4 (46.3-101.1); for pregnant women it was 14.3 (9.7-21.1); and for secondary school students it was 1.0. 48.4 % of students were not yet sexually active. The adjusted OR with a 95% confidence interval/year tested was 1.1 (0.9-.4) for 1989 1.1 (1.0-1.4) for 1990 1.1 (0.9-1.4) for 1991 1.8 (1.5-2.2) for 1992 1.6 (1.3-1.9) for 1993 1.7 (1.4-2.0) for 1994 1.0 (0.9-1.2) for 1995 and 1.0 for 1996. A significant decrease was found for pregnant women (OR = 0.69; p < .001). Stable or decreasing HIV-1 seroprevalence over time does not necessarily imply decreasing incidence; increasing mortality and migration among HIV-1 infected persons can obscure increasing incidence. The data indicate a homogeneity in the epidemic throughout Uganda.

Immune activation has been observed in HIV-infected and uninfected Africans, among whom it is thought to modify interaction between the immune system and HIV. To characterize this phenomenon accurately, in-depth immunologic analyses were performed in a rural African population. Freshly drawn peripheral blood mononuclear cells (PBMCs) of HIV-infected African (from Gulu, Uganda) and Italian antiviral-naive patients and those of uninfected Ugandan and Italian study subjects were analyzed. Individuals were matched for age and sex and determined to be free from parasitic infections. Intracellular cytokines were measured in mitogen (M)- and gp160 peptides + staphylococcal enterotoxin B and alpha CD28 (env)-stimulated T lymphocytes. Interferon (IFN)-gamma-producing CD8(+) T cells were quantified in an enzyme-linked immunosorbent assay. Results showed that M-stimulated production of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha increases in CD4(+) and CD8(+) cells of African infected patients and uninfected study subject; and that env-stimulated IL-10 and TNF-alpha production is increased in CD8(+) T lymphocytes of African HIV-infected patients. M- and env-stimulated IFN-gamma-producing CD8(+) T cells were reduced in African participants and not increased by preincubation with alpha IL-10 monoclonal antibody. This is the first set of data that has reported immune activation in rural Africa by single-cell analysis of cytokine production. These results help in defining the immunologic background to be considered in the design of therapeutic and vaccine-based approaches to HIV infection in an African setting.