Changing from anonymous to confidential HIV voluntary counseling and testing in Uganda.
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Anonymous Testing↗
Biomedical subjects
Jonathan Mermin
Publications and source records attributed to Jonathan Mermin.
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↗
Nevirapine-induced Stevens-Johnson syndrome in a mother and son.
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Adult↗
Should cotrimoxazole prophylaxis be taken by all adults with HIV in Africa?
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AIDS-Related Opportunistic Infections↗
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↗
Developing an evidence-based, preventive care package for persons with HIV in Africa.
Currently, 95% of the 40 million persons with HIV live in low and middle income countries; 27 million in sub-Saharan Africa. HIV/AIDS is a leading cause of death in the region, yet access to care and treatment considered standard-of-care in the industrialized world is extremely limited. There is a need for standardized, evidence-based recommendations on preventive measures. We developed a list of potential interventions based, when possible, on documented efficacy in reducing morbidity or mortality among persons with HIV in Africa. We considered the accessibility, affordability, and potential for implementation using existing health care infrastructure. Potential components included cotrimoxazole prophylaxis, safe drinking water, isoniazid prophylaxis, insecticide-treated bed nets, micronutrients, and provision of HIV counseling and testing and condoms to family members of persons with HIV. There are several additional interventions for which further evaluation would be useful before inclusion in a standard package of care, including acyclovir prophylaxis, food supplementation, hand washing, and fluconazole prophylaxis. The provision of a basic care package could be an important step toward reducing health care disparities and gaining more control of the global HIV/AIDS epidemic.
AIDS-Related Opportunistic Infections↗
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↗
Reptiles, amphibians, and human Salmonella infection: a population-based, case-control study.
To estimate the burden of reptile- and amphibian-associated Salmonella infections, we conducted 2 case-control studies of human salmonellosis occurring during 1996-1997. The studies took place at 5 Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas: all of Minnesota and Oregon and selected counties in California, Connecticut, and Georgia. The first study included 463 patients with serogroup B or D Salmonella infection and 7618 population-based controls. The second study involved 38 patients with non-serogroup B or D Salmonella infection and 1429 controls from California only. Patients and controls were interviewed about contact with reptiles and amphibians. Reptile and amphibian contact was associated both with infection with serogroup B or D Salmonella (multivariable odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2; P<.009) and with infection with non-serogroup B or D Salmonella (OR, 4.2; CI, 1.8-9.7; P<.001). The population attributable fraction for reptile or amphibian contact was 6% for all sporadic Salmonella infections and 11% among persons <21 years old. These data suggest that reptile and amphibian exposure is associated with approximately 74,000 Salmonella infections annually in the United States.
Amphibians↗
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↗
Kaposi's sarcoma in Uganda: risk factors for human herpesvirus 8 infection among blood donors.
Human herpesvirus 8 (HHV-8) is etiologically linked to Kaposi's sarcoma, a common cancer in Uganda. The authors assessed HHV-8 seroprevalence, risk factors for infection, and HHV-8 assays in a cross-sectional study of Ugandan blood donors. Of 3,736 specimens, the authors selected 203 reactive for HIV, hepatitis B surface antigen (HBsAg), or syphilis, and, randomly, 203 nonreactive specimens. For HHV-8 testing, the authors used two peptide-based enzyme-linked immunosorbent assays (EIAs), ORFK8.1 and ORF65, and an immunofluorescence assay (IFA). Specimens reactive in at least two assays or on IFA alone were considered HHV-8-seropositive. Prevalence estimates were weighted to account for the sampling scheme. Overall HHV-8 seroprevalence was 40%. HHV-8 seroprevalence was higher among HBsAg-positive donors (53%) than HBsAg-negative donors (39%; p =.02) and higher among HIV-positive donors (63%) than HIV-negative donors (39%; p <.001). HHV-8 seroreactivity showed no trend with age. Kappa values for assay concordances were 0.68 (ORFK8.1 EIA and IFA), 0.37 (ORF65 EIA and K8.1 EIA), and 0.29 (ORF65 EIA and IFA). The association between HHV-8 and HBsAg positivity and the lack of association between HHV-8 and age point to primarily nonsexual HHV-8 transmission during childhood. The association with HIV indicates sexual transmission may also occur. The role of ORF65 EIA in testing specimens from Africa warrants further evaluation.
Adolescent↗
Home-based model for HIV voluntary counselling and testing.
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Adolescent↗
Development of phenotypic and genotypic resistance to antiretroviral therapy in the UNAIDS HIV Drug Access Initiative--Uganda.
OBJECTIVE: We describe phenotypic drug resistance, response to therapy, and genotypic mutations among HIV-infected patients in Uganda taking antiretroviral medications for > or = 90 days who had a viral load > or = 1000 copies/ml. METHODS: HIV-1 group and subtype, virologic and immunologic responses to antiretroviral therapy, phenotypic resistance to antiretroviral drugs, and associated genotypic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse transcriptase inhibitors (NRTIs) or highly active antiretroviral therapy (HAART). RESULTS: All HIV identified was HIV-1, group M, subtypes A, C, and D. Sixty-one (65%) of 94 patients with a phenotypic resistance result had evidence of phenotypic resistance including resistance to a NRTI for 51 of 92 (55%) taking NRTIs, to a non-nucleoside reverse transcriptase inhibitor (NNRTI) for nine of 16 (56%) taking NNRTIs, and to a protease inhibitor (PI) for eight of 37 (22%) taking PIs. At the time of the first specimen with resistance, the median change from baseline viral load was -0.56 log copies/ml [interquartile range (IQR), -1.47 to +0.29] and CD4+ cell count was +35 x 10(6) cells/l (IQR, -18 to +87). Genotypic resistance mutations, matched with phenotypic resistance assay results and drug history, were generally consistent with those seen for HIV-1, group M, subtype B infections in industrialized countries. CONCLUSION: Initial phenotypic resistance and corresponding genotypic mutations among patients treated in Uganda were similar to those with subtype B infections in North America and Europe. These data support policies that promote the use of HAART regimens against HIV-1, group M, non-B subtypes in a manner consistent with that used for subtype B infections.
Antiretroviral Therapy, Highly Active↗
An outbreak of food-borne illness associated with methomyl-contaminated salt.
CONTEXT: On January 5, 1999, the California Department of Health Services was notified of the repeated occurrence (December 21, 1998, and January 2, 1999) of gastrointestinal tract illness among patrons at a Thai restaurant in central California. OBJECTIVE: To identify the source of the outbreak. DESIGN: Case-control study; microbiological and toxicological laboratory testing of samples of food, stool, and vomitus. SETTING: Thai food restaurant in central California. PARTICIPANTS: Patrons of the restaurant. A case (n = 107) was defined as dizziness, nausea, or vomiting occurring in a person who ate at the restaurant between December 20, 1998, and January 2, 1999, with onset of symptoms within 2 hours of eating. A control (n = 169) was a person who ate at the restaurant during the same period but reported no symptoms. MAIN OUTCOME MEASURES: Odds ratios (ORs) of illness associated with food exposures; ORs of shifts during which illness occurred associated with certain cooks; laboratory results. RESULTS: The median latency period was 40 minutes from beginning eating to first symptom and was 2 hours to onset of diarrhea. The median duration of symptoms was 6 hours. Twenty-six persons (24%) visited the emergency department or were treated by a physician; no person required hospitalization. Patients reported nausea (95%), dizziness (72%), abdominal cramps (58%), headache (52%), vomiting (51%), chills (48%), and diarrhea (46%). Fifty-one cases (48%) included dizziness, lightheadedness, or a feeling of disequilibrium as the initial symptom. Illness was statistically associated with several foods and ingredients, but no single dish or ingredient explained a substantial number of cases. The analysis of food exposures included salt added by cooks, as estimated by using the amount of salt in the recipe for each dish and the amount of each dish eaten by respondents. This association was stronger with increasing levels of salt: ORs for illness among persons who consumed more than 0.42 to 0.84, more than 0.84 to 1.25, and more than 1.25 tsp of salt added to foods in the kitchen were 1.9 (95% confidence interval [CI], 0.6-5.7), 3.0 (95% CI, 1.0-8.8), and 4.0 (95% CI, 1.3-13.5) compared with persons who consumed less than 0.42 tsp (P value for trend =.004). Methomyl, a highly toxic carbamate pesticide, was identified in a sample of vomitus (20 ppm) and in salt taken from containers in the storeroom (mean, 5600 ppm) and the stovetop (mean, 1425 ppm). The oral toxic dose causing illness in 50% of those exposed to methomyl was estimated to be 0.15 mg/kg of body weight (estimated range, 0.09-0.31 mg/kg of body weight). The presence of cook A was associated with shifts during which cases of illness occurred (OR, 10.4; 95% CI, 1.2-157.4). CONCLUSION: This outbreak of gastrointestinal illness was associated with the consumption of food seasoned with methomyl-contaminated salt. To allow rapid assessment for further investigational and control measures by health officials, physicians should report suspected outbreaks of illness to public health departments, however trivial the symptoms or cause may seem.
California↗
Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' response, survival, and drug resistance.
BACKGROUND: Little is known about how to implement antiretroviral treatment programmes in resource-limited countries. We assessed the UNAIDS/Uganda Ministry of Health HIV Drug Access Initiative--one of the first pilot antiretroviral programmes in Africa--in which patients paid for their medications at negotiated reduced prices. METHODS: We assessed patients' clinical and laboratory information from August, 1998, to July, 2000, from three of the five accredited treatment centres in Uganda, and tested a subset of specimens for phenotypic drug resistance. FINDINGS: 912 patients presented for care at five treatment centres. We assessed the care of 476 patients at three centres, of whom 399 started antiretroviral therapy. 204 (51%) received highly active antiretroviral therapy (HAART), 189 (47%) dual nucleoside reverse transcriptase inhibitors (2NRTI), and six (2%) NRTI monotherapy. Median baseline CD4 cell counts were 73 cells/microL (IQR 15-187); viral load was 193817 copies/mL (37013-651 716). The probability of remaining alive and in care was 0.63 (95% CI 0.58-0.67) at 6 months and 0.49 (0.43-0.55) at 1 year. Patients receiving HAART had greater virological responses than those receiving 2NRTI. Cox's proportional hazards models adjusted for viral load and regimen showed that a CD4 cell count of less than 50 cells/microL (vs 50 cells/microL or more) was strongly associated with death (hazard ratio 2.93 [1.51-5.68], p=0.001). Among 82 patients with a viral load of more than 1000 copies/mL more than 90 days into therapy, phenotypic resistance to NRTIs was found for 47 (57%): 29 of 37 (78%) who never received HAART versus 18 of 45 (40%) who received HAART (p=0.0005). INTERPRETATION: This pilot programme successfully expanded access to antiretroviral drugs in Uganda. Identification and treatment of patients earlier in the course of their illness and increased use of HAART could improve probability of survival and decrease drug resistance.
Adolescent↗
Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda.
BACKGROUND: Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. METHODS: Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. FINDINGS: Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01). INTERPRETATION: Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.
AIDS-Related Opportunistic Infections↗
Systematic review of the safety of trimethoprim-sulfamethoxazole for prophylaxis in HIV-infected pregnant women: implications for resource-limited settings.
Daily prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) significantly decreases morbidity and mortality among people living with HIV. Some clinicians are reluctant to use TMP-SMZ in pregnant and breastfeeding HIV-infected women because of concerns about the possible teratogenicity when used in the first trimester and about its potential to induce hyperbilirubinemia near term and during early breastfeeding. We systematically reviewed evidence regarding the toxicity of TMP-SMZ prophylaxis in pregnant and breastfeeding women to help guide practice in resource-limited settings. We identified relevant literature by searching PubMed and MEDLINE via OVID, Embase, and Science Citation Index for data on hyperbilirubinemia, kernicterus, and teratogenicity associated with administration of sulfonamides and TMP-SMZ through July 2005. We also reviewed the reference lists of identified articles. Most studies demonstrated that TMP-SMZ was not associated with hyperbilirubinemia when administered to mothers during pregnancy and breastfeeding. No cases of kernicterus were reported in neonates after maternal ingestion of sulfonamides. There is mixed evidence linking ingestion of TMP-SMZ and other sulfonamides in early pregnancy to elevated risks of oral clefts, neural tube defects, and cardiovascular and urinary tract abnormalities, although some sources found that supplementation with folic acid might ameliorate this potential risk. Existing guidelines recommend that HIV-infected pregnant women receive prophylaxis, but they differ with regards to stage of disease at which to initiate treatment, need for CD4+ T-lymphocyte testing, and prophylaxis during the first trimester. Existing data indicate that the risk of serious injury to neonates from maternal use of daily TMP-SMZ prophylaxis during pregnancy and breastfeeding is small. Given the substantial benefits of TMP-SMZ prophylaxis for HIV-infected women living in resource-limited settings, this review indicates that it is safe to abide by the WHO guidelines recommending daily TMP-SMZ prophylaxis for HIV-infected pregnant women.
Abnormalities, Drug-Induced↗