Clinical outcomes of HIV-infected patients with Kaposi's sarcoma receiving nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy in Uganda.

BACKGROUND: Clinical outcomes for patients with Kaposi's sarcoma (KS) using nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) in resource-limited settings have not previously been described. METHODS: We evaluated HIV-infected patients aged ≥ 18 years, who initiated HAART in the Home-Based AIDS Care (HBAC) project in Tororo, Uganda, between May 2003 and February 2008 and were diagnosed with KS at baseline or during follow-up. We examined independent risk factors for having either prevalent or incident KS and risk factors for death among patients with KS. RESULTS: Of 1121 study subjects, 17 (1.5%) were diagnosed with prevalent KS and 18 (1.6%) with incident KS over a median of 56.1 months of follow-up. KS was associated with male sex [adjusted odds ratio (AOR) 2.41; 95% confidence interval (CI) 1.20-4.86] and baseline CD4 cell count < 50 cells/µL (AOR 3.25; 95% CI 1.03-10.3). Eleven (65%) of 17 patients with prevalent KS and 13 (72%) of 18 patients with incident KS experienced complete regression (P = 0.137). Eighteen (64%) of 28 patients who remained on NNRTI-based HAART experienced regression of their KS and six (86%) of seven patients who were switched to protease inhibitor-containing HAART regimens had regression of their KS (P = 0.23). Mortality among those with KS was significantly associated with visceral disease (hazard ratio 19.22; 95% CI 2.42-152). CONCLUSION: Prevalent or incident KS was associated with 30% mortality. The resolution of KS lesions among individuals who initiated HAART with NNRTI-based regimens was similar to that found in studies using only protease inhibitor-based HAART.

Developing WHO guidelines with pragmatic, structured, evidence-based processes: A case study.

Many guidelines, including those produced by the World Health Organisation (WHO), have failed to adhere to rigorous methodological standards. Operational examples of guideline development processes may provide important lessons learned to improve the rigour and quality of future guidelines. To this end, this paper describes the process of developing WHO guidelines on prevention and care interventions for adults and adolescents living with HIV. Using a pragmatic, structured, evidence-based approach, we created an organising committee, identified topics, conducted systematic reviews, identified experts and distributed evidence summaries. Subsequently, 55 global HIV experts drafted and anonymously submitted guideline statements at the beginning of a conference. During the conference, participants voted on statements using scales evaluating appropriateness of the statements, strength of recommendation and level of evidence. After review of voting results, open discussion, re-voting and refinement of statements, a draft version of the guidelines was completed. A post-conference writing team refined the guidelines based on pre-determined guideline writing principles and incorporated external comments into a final document. Successes and challenges of the guideline development process were identified and are used to highlight current issues and debates in developing guidelines with a focus on implications for future guideline development at WHO.

A simple screening tool for active tuberculosis in HIV-infected adults receiving antiretroviral treatment in Uganda.

SETTING: Reliable clinical algorithms that screen for active tuberculosis (TB) in human immunodeficiency virus (HIV) infected people initiating or receiving antiretroviral treatment (ART) in sub-Saharan Africa could reduce the need for diagnostic procedures. METHODS: We estimated the utility of six TB-related signs and symptoms, alone or in combination, compared with the Uganda Ministry of Health diagnostic guidelines for participants with prevalent (baseline), early ART (< or = 3 months on ART) and incident TB (>3 months on ART). RESULTS: Of 1995 participants screened for ART eligibility, 71 (3.6%) had prevalent TB. The presence of any one of the following: cough > or = 3 weeks, fever > or = 4 weeks, lymphadenopathy or baseline body mass index < or = 18 kg/m(2) had a sensitivity of 99% (95%CI 96-100), a specificity of 66% (95%CI 64-68) and a negative predictive value (NPV) of 100% (95%CI 99-100) for predicting active TB. During ART follow-up, TB incidence was 2.4 (95%CI 1.6-3.4)/100 person-years. The presence of cough > or = 3 weeks or general weakness was 100% sensitive (95%CI 99-100), 66% specific (95%CI 59-74) and had an NPV of 100% (95%CI 99-100). CONCLUSION: Use of a simple TB screening algorithm can accurately identify, in a resource-poor African setting, HIV-infected individuals who require further procedures to diagnose active TB.

Aetiology of diarrhoea among persons with HIV and their family members in rural Uganda: a community-based study.

OBJECTIVES: To identify pathogens associated with diarrhoea in HIV-infected persons and their HIV-uninfected family members. DESIGN: Prospective cohort study. SETTING: Rural community in eastern Uganda. SUBJECTS: Eight hundred and seventy nine HIV-infected adults (74% females and median age 35 years (IQR, 29-41) and 2771 HIV-uninfected family members (51% females and median age 11 years (IQR 6-16) were included. MAIN OUTCOME MEASURES: Using microscopy and culture, stools were tested for parasites, bacteria and bacterial-antimicrobial-susceptibility. Logistic regression models, adjusting for age, CD4 cells, season, household clustering and use of safe-water system were used for relationships between pathogens, diarrhoea and HIV. RESULTS: Persons with HIV had similar pathogens in diarrhoeal (69%) and nondiarrhoeal stools (57%). Most diarrhoea was not associated with identifiable aetiology; the population attributable risk of diarrhoea for known diarrhoea pathogens was 32%. Enteric bacteria (19%), enteropathogenic or enterotoxigenic E. coli (8%), Aeromonas species (7%), Strongyloides stercoralis (8%) and Cryptosporidium parvum (5%). HIV-infected, stools had more Cryptosporidium parvum than HIV-uninfected (OR 2.64, 95% CI 1.43-4.87). Most bacteria were resistant to commonly used antimicrobials irrespective of HIV status. CONCLUSIONS: Irrespective of HIV-status, aetiologies of majority of their diarrhoea in Uganda cannot be identified by microscopy and culture. Bacterial pathogens isolated have high resistance to common antimicrobials. Empiric treatment should be tailored to local bacterial-resistance patterns.

Utilization of a basic care and prevention package by HIV-infected persons in Uganda.

Opportunistic infections are the leading cause of mortality among HIV-infected people. Several simple interventions prevent illness, prolong life, or prevent HIV transmission from HIV-infected people in Africa. These include: cotrimoxazole prophylaxis; insecticide-treated bed nets; supplies for household water treatment and safe storage; materials promoting family voluntary counselling and testing (VCT); and condoms. We provided these interventions to adults and children with HIV who were members of the AIDS Support Organization in Uganda. To evaluate use of this basic care and prevention package, we surveyed a representative sample of 112 clients of TASO in their homes. Among respondents, 95% reported taking cotrimoxazole everyday, 89% said they had slept under a bednet the night before, 65% reported current treatment of household drinking water, 89% of sexually active respondents reported using condoms, and 96% reported family use of VCT. Household observations verified that use of cotrimoxazole, bednets, and water treatment products were consistent with reported use. This evaluation suggests successful distribution and use of basic care and prevention services at an AIDS organization in Uganda.

Cost-utility of tuberculosis prevention among HIV-infected adults in Kampala, Uganda.

SETTING: Treatment of latent tuberculosis (TB) infection using isoniazid preventive therapy (IPT) in a human immunodeficiency virus (HIV) volunteer counseling and testing center in Kampala, Uganda. OBJECTIVE: To analyze the cost-utility of an IPT program for persons newly diagnosed with HIV. DESIGN: The cost-utility analysis of the IPT program was conducted using Markov cohort simulation methods. Newly diagnosed HIV-infected persons were evaluated using tuberculin skin test (TST); those with positive TST were offered IPT for 9 months (targeted testing strategy). An alternative strategy of offering IPT to all HIV-infected clients without TST screening was also evaluated (treat all strategy). The cost-utility of targeted testing was compared to the 'no program' and the 'treat all' strategies. RESULTS: The IPT program with the targeted testing strategy would produce 11 quality-adjusted life-years (QALYs) per 100 HIV-infected clients compared to no program. Offering IPT using the treat all strategy gained an additional 30 QALYs per 100 clients compared to targeted testing. Compared to no program, the incremental cost-utility of the targeted testing program was US$102/QALY gained. The cost-utility of the IPT program under the treat all strategy was US$106/QALY gained compared to the targeted testing strategy. CONCLUSIONS: The provision of IPT for HIV-infected persons was cost-effective. The use of TST screening prior to IPT reduced costs per QALY gained, but saved fewer overall QALYs.

Trends and predictors of quality of life among HIV-infected adults taking highly active antiretroviral therapy in rural Uganda.

We examined trends and predictors of quality of life (QOL) over 12 months among a prospective cohort of 947 HIV-1-infected adults initiating highly active antiretroviral therapy (HAART) between May 2003 and May 2004 in rural Uganda. Participants provided clinical, demographic and psychosocial data at baseline and every three months thereafter. Outcome measures included physical and mental health summary scores based on the Medical Outcomes Study-HIV Health Survey (MOS-HIV). Generalised estimating equations were used to assess magnitude of change in summary scores and factors associated with QOL. Of 710 women and 237 men enrolled, the mean age was 38.7 years and mean baseline CD4 cell count was 124.1 cells/microL. At enrollment, physical and mental health summary scores were 39.2 and 40, respectively. By 12 months of HAART, scores increased by 11.2 points (p <0.001) and 7.4 points (p <0.001), respectively. For both scores, most gains were achieved by the third month of therapy. While several clinical, psychosocial and sociodemographic factors predicted QOL at HAART initiation, financial dependence on others was the only remaining predictor after controlling for time on HAART. Interventions to enhance the economic and employment opportunities of patients taking HAART in rural Africa may help maximise gains in QOL.

Tuberculosis case finding and preventive therapy in an HIV voluntary counseling and testing center in Uganda.

SETTING: A large, urban human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) center in Kampala, Uganda. OBJECTIVE: Tuberculosis (TB) is a leading cause of morbidity and mortality in persons with HIV infection in sub-Saharan Africa. Intensified TB case finding and use of isoniazid preventive therapy (IPT) for latent infection reduces the burden of TB, but few programs have been implemented due to concerns about feasibility. DESIGN: Retrospective evaluation of a TB case finding and IPT program. RESULTS: Over a 25-month period, 6305 patients newly diagnosed with HIV infection underwent evaluation: 293 (5%) had TB disease; 1955 (37%) patients were not eligible for preventive therapy because they lived > 20 km away, had advanced HIV disease, or had previously had TB. Of 3366 who had a tuberculin skin test (TST) placed, 2548 (76%) had the TST read; 894 (35%) of these were positive. Of 506 persons who started treatment, 335 (66%) completed it. CONCLUSION: This unique program was feasible, detected a high proportion of undiagnosed TB, and successfully treated persons with latent infection. Expanding access to HIV VCT as well as collaboration between HIV/ AIDS and TB programs can increase the proportion of HIV-infected persons who can benefit from these programs.

Cost-effectiveness of including tuberculin skin testing in an IPT program for HIV-infected persons in Uganda.

SETTING: Tuberculosis (TB) is the most common opportunistic infection among persons with human immunodeficiency virus or the acquired immune-deficiency syndrome (HIV/AIDS). Isoniazid preventive therapy (IPT) effectively treats latent TB infection (LTBI) and prevents progression to active TB. OBJECTIVE: To analyse the costs and cost-effectiveness of tuberculin skin testing (TST) prior to offering IPT. DESIGN: We implemented a program for LTBI screening and IPT using TST for persons with HIV at a voluntary counseling and testing (VCT) center in Kampala, Uganda. Cost-effectiveness analyses using Markov methods were adopted to compare strategies of using and not using TST before offering IPT. RESULTS: The program enrolled 7073 persons with HIV. Based on the prevalence of LTBI in the population, 34/100 HIV-infected patients would benefit from IPT. The results showed that 28% of LTBI patients would be treated using the TST strategy, and 40% would be treated with a non-TST strategy. Compared to no intervention, the estimated incremental cost of identifying and providing IPT using TST was dollars 211 per patient; the incremental cost using a non-TST strategy was dollars 768 per patient. CONCLUSION: At a large VCT center in Uganda, the inclusion of TST to identify the HIV-infected persons who will most benefit from IPT is cost-effective.

Prevalence and screening costs of hepatitis C virus among Ugandan blood donors.

BACKGROUND: Screening donated blood for hepatitis C virus (HCV) is important for HCV prevention and is routinely practiced in North America and Europe. However, in many African countries little is known about HCV prevalence or cost-effectiveness of HCV antibody (anti-HCV) screening. METHODS: We investigated 2592 plasma specimens collected consecutively from blood donors in central Uganda in 1999. Routine screening by the blood bank included human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and syphilis. To assess HCV prevalence and cost-effectiveness of testing, specimens were additionally tested for anti-HCV IgG by enzyme immunosorbent assay (EIA). Specimens repeatedly reactive (RR) on EIA were tested with a recombinant immunoblot assay (RIBA). RESULTS: Overall, 107 (4.1%) specimens were HCV EIA RR. Fifteen EIA RR specimens (0.6%, 95% confidence interval = 0.3-0.9%) were RIBA positive and 47 (1.8%) were RIBA indeterminate. Most (80%) RIBA-positive specimens were non-reactive for HIV, HBsAg, and syphilis. RIBA positivity was not associated with donor age, sex, number of donations, HIV, or HBsAg positivity. Costs of screening donors for anti-HCV by using EIA were estimated at US Dollars 782 per potential transfusion-associated HCV infection (exposure to RIBA-positive blood) averted. CONCLUSIONS: Current screening tests for other infections are ineffective in removing HCV-positive donations. Testing costs are considerable; cost-effectiveness of identifying HCV-infected donors will be critical in decision making about HCV screening in Uganda.

Chronic herpes simplex virus type-2 infection and HIV viral load.

By December 2003, the estimated adult HIV/AIDS prevalence rate in sub-Saharan Africa was 7.5-8.5%, and rates of herpes simplex virus type-2 (HSV-2) infection among adults aged >30 years ranged from 60% to 82%. However, little is known about the natural history of HIV/HSV-2 co-infection in this population. We evaluated HIV viral load and CD4+ cell counts among persons with and without chronic HSV-2 co-infection in a cross-sectional study of HIV-infected persons not receiving antiretroviral therapy. HSV-2 and HIV co-infection was associated with a 0.3 log copies/mL higher HIV viral load compared with persons without HSV-2 infection (P=0.014). Chronic HSV-2 infection may have a negative effect on the clinical course of persons with HIV.

Living with discordance: knowledge, challenges, and prevention strategies of HIV-discordant couples in Uganda.

Prevalence of HIV-discordance among couples in sub-Saharan Africa is high. Negative partners are at high risk of HIV infection but few HIV/AIDS service providers have developed effective counseling messages for HIV-discordant couples. To identify clients' explanations for discordance, challenges, and prevention strategies, 24 in-depth interviews and 4 focus group discussions were conducted with 32 female and 35 male members of HIV-discordant couples who sought HIV voluntary counseling and testing (VCT) in Uganda. In addition, counselor explanations for discordance were gathered from 62 counselor trainers during 3 interactive workshops. Misconceptions about discordance were widespread among clients and counselors. Common explanations included: the concept of a hidden infection not detectable by HIV tests, belief in immunity, the thought that gentle sex protected HIV-negative partners, and belief in protection by God. Such explanations for discordance reinforced denial of HIV risk for the negative partner within discordant couples and potentially increased transmission risk. Couples identified negotiation of sexual relations as their most formidable challenge. Prevention strategies included condom use, abstinence and separation of beds, contractual agreements for outside sexual partners, and relationship cessation. Discordant couples represent a critical risk group and improved counseling protocols that clearly explain discordance, emphasize high risk of transmission, and support risk reduction are urgently needed.

Immunoglobulin levels amongst persons with and without human immunodeficiency virus type 1 infection in Uganda and Norway.

CD4+-cell count and viral load monitoring are expensive and unavailable to most human immunodeficiency virus (HIV)-infected people in Africa. In an attempt to evaluate alternative methods for monitoring antiretroviral (ARV) therapy, we measured concentrations of immunoglobulin (Ig)A, IgM, IgG and IgG1 amongst adults with and without HIV in Uganda and Norway. We adjusted for disease severity by stratifying HIV-positive subjects on CD4+-cell counts above and below 200 cells/ micro l. Median serum levels of IgG, IgG1 and IgA were significantly higher in HIV-positive persons compared with HIV-negative persons in both countries (P < 0.001 and P = 0.018 for IgA in Ugandan patients). Levels of IgA in Ugandan HIV-negative subjects were significantly lower than those in HIV-positive subjects with low CD4+ compared with those with high CD4+-cell counts (P < 0.001 and P = 0.069, respectively). IgM levels were different between the HIV-negative and the two HIV-positive groups in Norway (P < 0.001). The mean levels of IgM, IgG and IgG1 in HIV-negative and -positive African subjects were generally higher than those in comparable groups of Western subjects. Our results verify that levels of IgA, IgG and IgG1 vary between HIV-negative and -positive individuals in both study populations. Their determination may be useful in monitoring both disease progression and response to ARV therapy.

A multistate outbreak of Escherichia coli O157:H7 infections associated with consumption of mesclun lettuce.

BACKGROUND: An outbreak of Escherichia coli O157:H7 infections in Connecticut and Illinois during May 28 to June 27, 1996, was investigated to determine the source of infections. METHODS: Independent case-control studies were performed in both states. Pulsed-field gel electrophoresis (PFGE) was performed on E. coli O157:H7 isolates. A case-patient was defined as a Connecticut or northern Illinois resident with diarrhea whose stool culture yielded E. coli O157:H7 of the outbreak-associated PFGE subtype. Controls were town-, age-, and sex-matched to case-patients. We traced implicated lettuce to the farm level and performed environmental investigations to identify unsafe lettuce production practices. RESULTS: In Connecticut and Illinois, infection was associated with consumption of mesclun lettuce (Connecticut matched odds ratio [MOR], undefined; 95% confidence interval [CI], 3.4 to infinity; and Illinois MOR, undefined; 95% CI, 1.4 to infinity). We traced implicated lettuce to a single grower-processor. Cattle, a known E. coli O157:H7 reservoir, were found near the lettuce fields. Escherichia coli (an indicator of fecal contamination) was cultured from wash water and finished lettuce. A trace-forward investigation identified 3 additional states that received implicated lettuce; E. coli O157:H7 isolates from patients in 1 of these states matched the outbreak-associated PFGE subtype. CONCLUSIONS: This multistate outbreak of E. coli O157:H7 infections was associated with consumption of mesclun lettuce from a single producer. Molecular subtyping facilitated the epidemiological investigation. This investigation increased the knowledge about current production practices that may contribute to the contamination of lettuce by microbial pathogens. Lettuce production practices should be monitored for microbiological safety.

A massive epidemic of multidrug-resistant typhoid fever in Tajikistan associated with consumption of municipal water.

From 1 January through 30 June 1997, 8901 cases of typhoid fever and 95 associated deaths were reported in Dushanbe, Tajikistan. Of 29 Salmonella serotype Typhi isolates tested, 27 (93%) were resistant to ampicillin, chloramphenicol, nalidixic acid, streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. In a case-control study of 45 patients and 123 controls, Salmonella Typhi infection was associated with drinking unboiled water (matched odds ratio, 7; 95% confidence interval, 3-24; P<.001). Of tap water samples, 97% showed fecal coliform contamination (mean level, 175 cfu/100 mL). Samples taken from water treatment plants revealed that fecal coliform contamination occurred both before and after treatment. Lack of chlorination, equipment failure, and back-siphonage in the water distribution system led to contamination of drinking water. After chlorination and coagulation were begun at the treatment plants and a water conservation campaign was initiated to improve water pressure, the incidence of typhoid fever declined dramatically.

Factory outbreak of Escherichia coli O157:H7 infection in Japan.

To determine the cause of a July 1996 outbreak of Escherichia coli O157:H7 among factory workers in Kyoto, Japan, we conducted cohort and case-control studies. Eating radish sprout salad during lunch at the factory cafeteria had been linked to illness. The sprouts were traced to four growers in Japan; one had been associated with an outbreak of E. coli O157:H7 among 6,000 schoolchildren in Sakai earlier in July.

Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance.

BACKGROUND: Typhoid fever is a potentially fatal illness common in the less industrialized world. In the United States, the majority of cases occur in travelers to other countries. METHODS: We reviewed surveillance forms submitted to the Centers for Disease Control and Prevention, Atlanta, Ga, for patients with culture-confirmed typhoid fever between 1985 and 1994. RESULTS: The Centers for Disease Control and Prevention received report forms for 2445 cases of typhoid fever. Median age of patients was 24 years (range, 0-89 years). Ten (0.4%) died. Seventy-two percent reported international travel within the 30 days before onset of illness. Six countries accounted for 80% of cases: Mexico (28%), India (25%), the Philippines (10%), Pakistan (8%), El Salvador (5%), and Haiti (4%). The percentage of cases associated with visiting Mexico decreased from 46% in 1985 to 23% in 1994, while the percentage of cases associated with visiting the Indian subcontinent increased from 25% in 1985 to 37% in 1994. The incidence of typhoid fever in US citizens traveling to the Indian subcontinent was at least 18 times higher than for any other geographic region. Complete data on antimicrobial susceptibility to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were reported for 330 (13%) Salmonella Typhi isolates. Isolates from 1990 to 1994 were more likely than isolates from 1985 to 1989 to be resistant to any of these antimicrobial agents (30% vs 12%; P<.001) and to be resistant to all 3 agents (12% vs 0.6%; P<.001). CONCLUSIONS: American travelers to less industrialized countries, especially those traveling to the Indian subcontinent, continue to be at risk for typhoid fever. Antimicrobial resistance has increased, and a quinolone or third-generation cephalosporin may be the best choice for empirical treatment of typhoid fever.

Iguanas and Salmonella marina infection in children: a reflection of the increasing incidence of reptile-associated salmonellosis in the United States.

OBJECTIVE: To investigate clinical aspects and risk factors for Salmonella serotype Marina infection in the United States. METHODS: We identified all isolates of S Marina reported in 1994 to the National Salmonella Surveillance System. Patients were interviewed about demographic information, clinical course, diet, travel history, and contact with reptiles before illness. RESULTS: Twenty-six (81%) of 32 patients were infants (<1 year of age) and 24 (75%) were male. This differs from other Salmonella isolates reported to the Centers for Disease Control and Prevention in 1994, of which 14% were from infants and 49% from male patients. Eleven patients (34%) were hospitalized for a median of 3.5 days (range: 2 to 21 days), and 1 died. Of 28 patients (88%) with reported iguana exposure, only 4 (14%) touched the reptile, and only 12 respondents (43%) realized that it might have been the source of infection. Seven (32%) of 22 families who owned an iguana at the time of illness continued to own an iguana when contacted a median of 28 weeks later. Persons who thought that the iguana was the source of infection were more likely to have given away or sold the pet than those who did not. Four isolates (13%) were from blood. Bacteremia was associated with taking antibiotics during the 30 days before S Marina infection (odds ratio: 24; 95% confidence interval: 1.2-1309). CONCLUSION: S Marina infection is a potentially serious illness associated with iguana exposure, and it reflects the larger problem of reptile-associated salmonellosis. Many parents do not know that owning an iguana puts their children at risk for Salmonella infection. Pediatricians, veterinarians, and pet store owners should inform their patients and customers of the potential risks of owning reptiles and provide appropriate preventive education.