Biomedical subjects

Robert Downing

Publications and source records attributed to Robert Downing.

At least 19 recordsLinked to original sources

PubMed2006

Severe malnutrition with and without HIV-1 infection in hospitalised children in Kampala, Uganda: differences in clinical features, haematological findings and CD4+ cell counts.

BACKGROUND: The aim of this study was to describe the clinical features, haematological findings and CD4+ and CD8+ cell counts of severely malnourished children in relation to human immunodeficiency virus (HIV) infection. METHODS: The study was conducted in the paediatric wards of Mulago hospital, which is Uganda's national referral and teaching hospital. We studied 315 severely malnourished children (presence of oedema and/or weight-for-height: z-score < -3) and have presented our findings. At admission, the CD4+ and CD8+ cells were measured by the flow cytometry and HIV serology was confirmed by Enzyme linked Immunoassay for children >18 months of age, and RNA PCR was performed for those < or =18 months. Complete blood count, including differential counts, was determined using a Beckman Coulter counter. RESULTS: Among the 315 children, 119 (38%) were female; the median age of these children was 17 months (Interquartile range 12-24 months), and no difference was observed in the HIV status with regard to gender or age. The children showed a high prevalence of infections: pneumonia (68%), diarrhoea (38%), urinary tract infection (26%) and bacteraemia (18%), with no significant difference with regard to the HIV status (HIV-positive versus HIV-negative children). However, the HIV-positive children were more likely to have persistent diarrhoea than the HIV-uninfected severely malnourished children (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.6). When compared with the HIV-negative children, the HIV-positive children showed a significantly lower median white blood cell count (10700 versus 8700) and lymphocyte count (4033 versus 2687). The CD4+ cell percentages were more likely to be lower in children with non-oedematous malnutrition than in those with oedematous malnutrition even after controlling for the HIV infection. The novel observation of this study is that the CD4+ percentages in both HIV-positive and HIV-negative children without oedema were lower that those in children with oedema. These observations appear to imply that the development of oedema requires a certain degree of immunocompetence, which is an interesting clue to the pathophysiology of oedema in severe malnutrition.

Body Height↗

PubMed2006

Transmission of human herpesvirus 8 by blood transfusion.

BACKGROUND: Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic. METHODS: We enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001. Pretransfusion and multiple post-transfusion blood specimens from up to nine visits over a 6-month period were tested for HHV-8 antibody. We calculated the excess risk of seroconversion over time among recipients of HHV-8-seropositive blood as compared with recipients of seronegative blood. RESULTS: Of the 1811 transfusion recipients enrolled, 991 were HHV-8-seronegative before transfusion and completed the requisite follow-up, 43% of whom received HHV-8-seropositive blood and 57% of whom received seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients. The risk of seroconversion was significantly higher among recipients of HHV-8-seropositive blood than among recipients of seronegative blood (excess risk, 2.8%; P<0.05), and the increase in risk was seen mainly among patients in whom seroconversion occurred 3 to 10 weeks after transfusion (excess risk, 2.7%; P=0.005), a result consistent with the transmission of the virus by transfusion. Blood units stored for up to 4 days were more often associated with seroconversion than those stored for more than 4 days (excess risk, 4.2%; P<0.05). CONCLUSIONS: This study provides strong evidence that HHV-8 is transmitted by blood transfusion. The risk may be diminished as the period of blood storage increases.

Adult↗

PubMed2006

Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study.

BACKGROUND: HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets. METHODS: In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season. FINDINGS: 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). INTERPRETATION: A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Adult↗

PubMed2006

HIV, syphilis, herpes simplex virus 2, and behavioral surveillance among conflict-affected populations in Yei and Rumbek, southern Sudan.

Little is known about the HIV epidemic in conflict-affected southern Sudan. During 2002-2003, we conducted behavioral and biological surveillance surveys and sequential sampling in antenatal clinics in Yei, Western Equatoria, and Rumbek, Bar-el-Ghazal. HIV prevalence among individuals aged 15-49 years ranged between 0.4% in Rumbek town and 4.4% in Yei town, and among pregnant women between 0.8 and 3.0%, respectively. After the recent peace agreement, targeted prevention programmes are urgently needed to prevent further spread.

Adolescent↗

PubMed2006

Comparison of two alternative methods for CD4+ T-cell determination (Coulter manual CD4 count and CyFlow) against standard dual platform flow cytometry in Uganda.

BACKGROUND: In this study we evaluated alternative CD4(+) T-cell counting methods in clients of a PMTCT Programme in rural Uganda. METHODS: The Coulter Manual CD4 Count method for CD4(+) T-cell enumeration (Cyto-Spheres) and an automated method (volumetric, single-platform flow cytometry; CyFlow) were compared with a standard, dual-platform flow cytometry protocol (DPFC, FACScan). RESULTS: Correlation and precision of agreement were higher for the CyFlow method (r = 0.929 and eta = 0.08) when compared to DPFC than for the Cyto-Spheres method (r = 0.725 and eta = 0.3). Multiple linear regression analysis showed that CD4(+) cell counts by the CyFlow method were a stronger predictor for results of DPFC than those of the Cyto-Spheres method (r(2) = 0.864 and r(2) = 0.552, respectively). When compared to DPFC the CyFlow method generated higher CD4(+) cell counts than the Cyto-Spheres method, as expressed by a higher median and mean difference (+70 and +90 cells for CyFlow, +28 and -1.4 cells for Cyto-Spheres). CONCLUSION: Both, the manual Cyto-Spheres method and the CyFlow method can be used for the enumeration of CD4(+) cells in resource-limited settings. Under supervised conditions, the CyFlow method produced results more consistent with the reference method than the Cyto-Spheres method.

Algorithms↗

PubMed2006

Depression and CD4 cell count among persons with HIV infection in Uganda.

Despite the importance of mental illness and the high prevalence of HIV in Africa, few studies have documented depressive symptoms among HIV-infected persons in Africa. We assessed factors associated with depression among HIV-infected adults undergoing anti-retroviral eligibility screening in Eastern Uganda. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Univariate and multiple regression analyses were conducted to identify socio-demographic characteristics and disease-related factors associated with depression. Among 1017 HIV-infected participants assessed for depression, 47% (476/1017) reported depressive symptoms (CES-D >/= 23). Adjusting for age, gender, education, and source of income, patients with CD4 counts <50 cells/microl were more likely to be depressed (odds ratio 2.34, 95% confidence interval, 1.39-3.93, P = 0.001). Women, participants >50 years, and those without an income source were more likely to be depressed. Depression was common among HIV-infected persons in rural Uganda and was associated with low CD4 cell counts. Appropriate screening and treatment for depression should be considered for comprehensive HIV care.

Adolescent↗

PubMed2006

Within and between race differences in lymphocyte, CD4+, CD8+ and neutrophil levels in HIV-uninfected children with or without HIV exposure in Europe and Uganda.

BACKGROUND: Racial immuno-haematological differences have been reported in children but to date have not been well quantified. AIM: To investigate differences in haemato-immunological markers over age between children born and living in Europe and Uganda. SUBJECTS: HIV-uninfected children living in Uganda (n = 1633) with cross-sectional data. Black (n = 604) and white children (n = 1355) living in Europe, both with prospective data. The children born in Europe were HIV-uninfected but born to HIV-infected mothers and were included in the European Collaborative Study (ECS). METHODS: Patterns and levels of total lymphocyte (TLC), CD4+, CD8+ counts and CD4% were visualised by smoothers (a line representing the weighted average of all measurements over age by study group). Differences between groups were quantified using age-standardised Z-scores for individual TLC, CD4+ and CD8+ counts in uni- and multivariate regression models. RESULTS: In infancy, TLC, CD4+ and CD8+ counts were lower in Ugandan than black European children; neutrophil counts were similar. Thereafter, only neutrophil counts were lower in Ugandan children. To assess within-race differences, we compared Z-scores of ECS children born to Ugandan mothers with those of Ugandan children. Levels of all four markers were lower in Ugandan children at all ages. In Ugandan children, CD4+ counts were 0.5985 Z-score (p < 0.001) and neutrophil counts 0.3872 Z-score (p < 0.001) lower than in European children born to Ugandan mothers. CONCLUSIONS: There are differences in levels of haemato-immunological markers in children with comparable genetic backgrounds, suggesting that environmental factors such as nutrition and exposure to micro-organisms might have important effects on the developing immune system.

Aging↗

PubMed2006

Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members.

The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.

Animals↗

PubMed2005

TP53 codon 72 polymorphism and risk of conjunctival squamous cell carcinoma in Uganda.

BACKGROUND: The most common TP53 gene polymorphism, which alters the amino acid sequence of the oncosuppressor p53 protein, is located at the codon 72, resulting in either Pro72 or Arg72 p53 variant. Several studies have associated this polymorphism with different types of cancer. We have analyzed the distribution and the role of TP53 Arg72 and Pro72 alleles in conjunctival neoplasia. METHOD: The study included 41 invasive conjunctival squamous cell carcinoma (ICSCC), 33 conjunctival intraepithelial neoplasia of grade 3 (CIN3), 33 of moderate grade (CIN1 and CIN2), and 115 controls from Uganda, a sub-Saharan country with the highest incidence rate of conjunctival neoplasia in the World, particularly in the era of AIDS. The TP53 Arg/Arg codon 72 genotype was detected in 21.9% of ICSCC and in 18.2% of CIN3 but only in 6% of CIN1-2 and in 5.2% of controls (P<0.05). RESULTS: These data show an increased risk of ICSCC (odds ratio (OR)=6.2, 95% confidence interval (CI): 1.6-24.6) and CIN3 (OR=4.1, 95% CI: 1.0-18.0) associated with TP53 Arg homozygosity, not observed in CIN1-2 lesions (OR=0.8, 95% CI: 0.1-5.1). Moreover, the frequency of the Arg homozygosity was similar in HIV-positive and HIV-negative groups. We conclude that TP53 Arg/Arg codon 72 genotype is a relevant risk factor for invasive squamous cell carcinoma of the conjunctiva and for CIN3 in the Ugandan population. DISCUSSION: The absence of statistically significant difference in the distribution of TP53 Arg72 or Pro72 encoding alleles between HIV-positive and -negative subjects, affected by conjunctival neoplasia, suggests that HIV infection and/or the associated immunodeficiency represent further independent risk factors for ICSCC.

Adult↗

PubMed2005

Couples at risk: HIV-1 concordance and discordance among sexual partners receiving voluntary counseling and testing in Uganda.

OBJECTIVE: To determine correlates of HIV-1 concordance for couples receiving voluntary HIV counseling and testing. DESIGN: Cross-sectional study of couples receiving voluntary HIV counseling and testing in Kampala, Uganda. METHODS: An interview and physical examination were conducted for 49 HIV-1-concordant (both partners infected with HIV) and 126 HIV-1-discordant (1 partner infected with HIV and 1 partner HIV negative) couples. Blood samples from all participants were tested for HIV-1 and syphilis serology. CD4 cell count and HIV load were characterized for all HIV-infected persons. Urine samples were tested for Neisseria gonorrhoeae and Chlamydia trachomatis using ligase chain reaction. Associations between couples' HIV status and key sociodemographic, behavioral, and biomedical factors were analyzed. RESULTS: Men in HIV-concordant couples were more likely than men in HIV-discordant couples to be living together with their sexual partner (odds ratio [OR], 11.3; 95% confidence interval [CI], 2.8-53.7; P=0.004), to be uncircumcised (OR, 4.5; 95% CI, 1.1-18.8; P=0.042), and to have higher HIV loads (OR for each log increase, 3.0; 95% CI, 2.0-4.7; P<0.001). Women in HIV-concordant couples were more likely than women in HIV-discordant couples to be living together with their sexual partner (OR, 19.0; 95% CI, 3.8-84.8), to have an uncircumcised male partner (OR, 6.5; 95% CI, 1.6-26.4), to have had a sexually transmitted disease in the 6 months before enrollment (OR, 1.9; 95% CI, 0.9-4.5), and to have higher HIV loads (OR for each log increase, 2.2; 95% CI, 1.5-3.2). CONCLUSIONS: Several behavioral and biologic risk factors were associated with HIV concordance for couples. Providing early sexually transmitted disease diagnosis and treatment, antiretroviral therapy, and specially designed counseling to HIV-discordant couples may help prevent HIV transmission in couples where being in a stable sexual relationship is a major risk factor for HIV infection.

Adult↗

PubMed2005

Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members.

BACKGROUND: The effect of cotrimoxazole prophylaxis taken by persons with HIV on community health and antimicrobial resistance is unknown. OBJECTIVE: To assess the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity, mortality, and antimicrobial resistance of diarrheal pathogens infecting their HIV-negative family members. DESIGN: Prospective cohort in rural Uganda. METHODS: A total of 879 persons with HIV and 2771 HIV-negative family members received weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole prophylaxis and households were followed for an average of 17 additional months. FINDINGS: During the study, 224 participants with HIV (25%) and 29 household members (1%) died. Mortality among HIV-negative family members < 10 years old was 63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95% confidence interval (CI), 0.14-0.95; P = 0.04]. Malaria among family members was less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI, 0.53-0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45-0.76; P = 0.0001), and hospitalizations (IRR, 0.57; CI, 0.36-0.92; P = 0.02). Death of a parent with HIV was associated with a threefold increase in mortality among HIV-negative children < 10 years old (hazard ratio, 2.9; CI, 1.1-8.1; P = 0.04). Of 134 bacterial isolates from family members before cotrimoxazole treatment, 89 (66%) were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment, 54 (72%) were resistant (P = 0.41). INTERPRETATION: Cotrimoxazole prophylaxis taken by persons with HIV was associated with decreased morbidity and mortality among family members. Antimicrobial resistance among diarrheal pathogens infecting family members did not increase. Concerns regarding the spread of bacterial resistance should not impede implementation of cotrimoxazole programs.

AIDS-Related Opportunistic Infections↗

PubMed2005

Long-term experience providing antiretroviral drugs in a fee-for-service HIV clinic in Uganda: evidence of extended virologic and CD4+ cell count responses.

OBJECTIVE: To describe the long-term experience of providing anti-retroviral (ARV) therapy, including CD4 cell count and virologic response, at St. Francis Hospital, Nsambya, Uganda. METHODS: The HIV clinic established in 1998 is a fee-for-service model where patients pay for ARVs. The care of patients who started ARVs from August 1, 1998 until October 31, 2000 was evaluated through December 31, 2002. Data were collected at the HIV clinic on standardized clinical forms. These patients had free CD4 cell count and viral load testing performed at times determined by the physician. All persons who had >/=1 CD4 cell count or viral load done >/=90 days after starting therapy were evaluated. RESULTS: Three hundred twenty-one patients (49% women, 66% ARV naive, median age = 38 years, median CD4 cell count = 79 cells/mm, and median viral load = 249,489 copies/mL) attended the HIV clinic. Two hundred sixty-three (82%) patients returned at least once after the initial visit, of whom 54 (21%) had an interruption in therapy for >1 year. One hundred thirty-five patients were in care in 2002, 69 were known to have died (9 of whom died in 2002), and 68 were lost to follow-up. The probability of remaining alive and in care at 1 year was 0.56 (95% confidence interval [CI]: 0.50-0.61), 0.46 (95% CI: 0.41-0.51) at 2 years, 0.40 (95% CI: 0.34-0.45) at 3 years, and 0.35 (95% CI: 0.29-0.41) at 4 years. In an on-treatment analysis, the median CD4 cell count increase during year 1 was +55 cells/mm, +112 cells/mm during year 2, +142 cells/mm during year 3, and +131 cells/mm during year 4. The median log viral load change from baseline during year 1 was -1.4 copies/mL, -1.32 copies/mL during year 2, -1.9 copies/mL during year 3, and -1.51 copies/mL during year 4. CONCLUSIONS: This fee-for-service HIV clinic providing ARV treatment has successfully operated and managed patients for more than 4 years. Those who survived and remained on therapy derived long-term virologic and immunologic responses to ARV drugs in a manner similar to that observed in industrialized countries. Strategies to reduce the financial burden and other barriers to uninterrupted care as well as incentives to increase such practice models should be further explored in the African context.

Anti-HIV Agents↗

PubMed2005

Cryptosporidiosis and microsporidiosis in ugandan children with persistent diarrhea with and without concurrent infection with the human immunodeficiency virus.

Cryptosporidium spp. and Enterocytozoon bieneusi are enteric pathogens that have emerged as significant causes of persistent diarrhea (PD) in immunologically compromised individuals particularly in association with HIV/AIDS. We conducted a cross-sectional study on the clinical epidemiology of E. bieneusi and Cryptosporidium in children with PD, with and without HIV/AIDS, attending Uganda's Mulago National Referral Hospital. Two hundred forty-three children aged < 60 months, admitted between November 2002 and May 2003 with PD (> 14 days), were analyzed for HIV status and CD4 lymphocyte counts, and stools were screened for the presence of E. bieneusi and Cryptosporidium by microscopy and positive samples genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Eighty (32.9%) of the children were excreting E. bieneusi, and 76 (31.3%) were excreting Cryptosporidium. Ninety-one of the 243 children had HIV, of who 70 (76.9%) had E. bieneusi, versus 10 (6.6%) of the 152 without (odds ratio = 47.33; 95% CI = 19.88 to 115.97), while 67 (73.6%) had Cryptosporidium, versus 9 (5.9%) without (odds ratio = 44.36; 95% CI = 18.39 to 110.40). Children with counts < 25% CD4 cells were more likely to have either E. bieneusi (odds ratio = 7.42; 95% CI = 3.77 to 14.69) or Cryptosporidium (odds ratio = 6.45; 95% CI = 3.28 to 12.76) than those with higher CD4 percentages. However, only HIV status was independently associated with either Cryptosporidium or E. bieneusi. Among the 243 children with PD, 67 (27.8%) were infected with both enteric pathogens, with HIV being the only independent predictor of coinfection. Finally, some 81% of HIV-infected children with PD excreted one or both organisms, compared with only 10% of children with PD testing negative for HIV. Seventy-four percent of isolates were C. hominis, the anthroponotic species, 17% were C. parvum, the zoonotic species, and 8% were a mixture of the two or others.

AIDS-Related Opportunistic Infections↗

PubMed2005

Effect of home-based water chlorination and safe storage on diarrhea among persons with human immunodeficiency virus in Uganda.

Diarrhea is frequent among persons infected with human immunodeficiency virus (HIV) but few interventions are available for people in Africa. We conducted a randomized controlled trial of a home-based, safe water intervention on the incidence and severity of diarrhea among persons with HIV living in rural Uganda. Between April 2001 and November 2002, households of 509 persons with HIV and 1,521 HIV-negative household members received a closed-mouth plastic container, a dilute chlorine solution, and hygiene education (safe water system [SWS]) or simply hygiene education alone. After five months, HIV-positive participants received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P < 0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001), and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34-0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and severity among persons with HIV living in Africa and large scale implementation should be considered.

AIDS-Related Opportunistic Infections↗

PubMed2004

HIV type 1 antigen-responsive CD4+ T-lymphocytes in exposed yet HIV Type 1 seronegative Ugandans.

CD4(+) T cell help is important for the functionality of CD8(+) cytotoxic T-lymphocytes (CTLs) in limiting viral replication and may contribute to mediation of apparent resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Using five HIV-1 antigens in an intracellular cytokine assay, the presence of specific antigen-responsive interferon- gamma-positive (IFN-gamma(+)) CD69(+) CD4(+) T-lymphocytes was evaluated in ESNs, their seropositive partners, and unexposed seronegative controls. Ten ESNs (five females, five uncircumcised males) were identified from 10 HIV-1 serodiscordant couples with a history of frequent unprotected sexual intercourse. All ESNs and controls were negative on two EIAs and for HIV-1 proviral DNA. The frequency of ESNs with antigen-responsive IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes ranged from three to five of eight for the different HIV-1 antigens. Six of eight ESNs tested had a positive response to at least one of the five antigens. Responses were on average 3.5 times higher among seropositives compared to ESNs and absent in the five unexposed controls. A negative correlation was noted between responses in ESNs and the plasma viral load of their seropositive spouse. Clade-specific and cross-clade reactivity were noted in both ESNs and seropositive partners tested. The findings confirm that ESNs are in a state of HIV-1-specific immune activation and suggest that HIV-1-specific IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes in addition to HIV-1-specific CD8(+) CTLs already described by others are potential immunological correlates of protection from persistent HIV-1 infection.

Adult↗

PubMed2004

Population-based hematologic and immunologic reference values for a healthy Ugandan population.

To assess the validity of the reference values for hematologic and immunologic indices currently used in Africa, we evaluated blood samples from 3,311 human immunodeficiency virus (HIV)-negative Ugandans aged 1 week to 92 years. Erythrocyte, hemoglobin, and hematocrit levels and mean corpuscular volume all significantly increased with age (P < 0.001) and were independent of gender until the age of 13 years, after which the levels were higher in males than in females (P < 0.001). White blood cell, neutrophil, lymphocyte, basophil, and monocyte counts significantly declined with age until the age of 13 years (P < 0.001), with no differences by gender, while platelet counts declined with age (P < 0.001) and showed differences by gender only among adults older than age 24 years. CD4+- and CD8+-cell counts declined with age until the age of 18 years; thereafter, females had higher counts than males. The absolute values for many of these parameters differed from those reported for populations outside Africa, suggesting that it may be necessary to develop tables of reference values for hematologic and immunologic indices specific for the African population. This may be particularly important with regard to CD4+-cell counts among children because significant differences in absolute and percent CD4+-cell counts exist between the values for Western populations and the values for the population evaluated in our study. These differences could influence the decision to initiate antiretroviral therapy among children infected with HIV.

Adolescent↗

PubMed2004

Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome.

The largest outbreak on record of Ebola hemorrhagic fever (EHF) occurred in Uganda from August 2000 to January 2001. The outbreak was centered in the Gulu district of northern Uganda, with secondary transmission to other districts. After the initial diagnosis of Sudan ebolavirus by the National Institute for Virology in Johannesburg, South Africa, a temporary diagnostic laboratory was established within the Gulu district at St. Mary's Lacor Hospital. The laboratory used antigen capture and reverse transcription-PCR (RT-PCR) to diagnose Sudan ebolavirus infection in suspect patients. The RT-PCR and antigen-capture diagnostic assays proved very effective for detecting ebolavirus in patient serum, plasma, and whole blood. In samples collected very early in the course of infection, the RT-PCR assay could detect ebolavirus 24 to 48 h prior to detection by antigen capture. More than 1,000 blood samples were collected, with multiple samples obtained from many patients throughout the course of infection. Real-time quantitative RT-PCR was used to determine the viral load in multiple samples from patients with fatal and nonfatal cases, and these data were correlated with the disease outcome. RNA copy levels in patients who died averaged 2 log(10) higher than those in patients who survived. Using clinical material from multiple EHF patients, we sequenced the variable region of the glycoprotein. This Sudan ebolavirus strain was not derived from either the earlier Boniface (1976) or Maleo (1979) strain, but it shares a common ancestor with both. Furthermore, both sequence and epidemiologic data are consistent with the outbreak having originated from a single introduction into the human population.

Antigens, Viral↗

PubMed2004

Pneumocystis carinii in children with severe pneumonia at Mulago Hospital, Uganda.

The prevalence of Pneumocystis carinii pneumonia (PCP), its clinical and radiological features and the outcome in 121 children aged 2-60 months presenting with severe pneumonia over a 2-month period at Mulago Hospital, Kampala are described. Children presenting with severe pneumonia had sputum induction using 3% hypertonic saline. The sputum was stained using PCP monoclonal antibodies and viewed with fluorescent microscopy. Twenty children with confirmed PCP were compared with 101 without PCP. The prevalence of PCP was 16.5%, and 12 (60%) were < 6 months of age. Eighteen (42%) of 43 children infected with HIV had PCP and two of 78 not infected with HIV. The outcome in children with PCP was poor with a case fatality rate of 40% compared with 20% in those without HIV. Radiological findings were non-specific. Clinical features associated with PCP included: HIV-positive infants with a small head circumference, AIDS, a clear chest on auscultation and elevated LDH levels. PCP occurs in one in six children < 5 years with severe pneumonia in Mulago Hospital. In developing countries where investigations for PCP are not routinely available, infants suspected of PCP should be treated as an emergency.

AIDS-Related Opportunistic Infections↗