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.

Is drinking water in Abidjan, Côte d'Ivoire, safe for infant formula?

OBJECTIVE: To survey knowledge, attitudes, and practices regarding water use and infant feeding in the Koumassi District of Abidjan, Côte d'Ivoire, and to evaluate the microbiologic quality of source and stored drinking water. DESIGN: Random-cluster household survey. METHODS: We randomly selected 20 clusters, each comprising six households with at least 1 child aged < or =3 years. In each household, we administered a questionnaire and collected source and stored drinking water samples and tested these for chlorine levels and for total coliform and fecal bacteria count ( Escherichia coli ). RESULTS: Municipal water was used for drinking in 112 (93%) of 120 households, and in 99 (83%), it was stored for later use. By 1 month of age, 97 (90%) of 108 infants given drinking water were given stored water for drinking. In 8 (66%) of 12 households where children were receiving artificial feeding, formula was prepared from municipal water without additional treatment. Stored water had lower levels of free chlorine than source water (median of 0.05 versus 0.2 mg/dl; p <.001), and E. coli was detected in 36 (41%) of 87 stored water samples and 1 (1%) of 108 source water samples ( p <.001). CONCLUSIONS: In the Koumassi District of Abidjan, where municipal water is widely available and of good quality, drinking water is stored in most households, is often contaminated with E. coli, and is given to children at a young age. If replacement feeding is to be more widely used to prevent postnatal transmission of HIV-1, communities using stored water need interventions to make stored water safer.

Estimated risk of HIV transmission by blood transfusion in Kenya.

BACKGROUND: During the past decade, developing countries have received limited support for blood safety programmes. The Kenya Ministry of Health did a collaborative multicentre assessment to establish the risk of HIV transmission by transfusion in Kenya, to promote awareness of blood safety issues in this country with a mature HIV epidemic, and to identify methods to reduce the risk of HIV transmission by blood transfusion in Kenya. METHODS: For 12 weeks, from April to July 1994, we collected information and blood samples from all blood donors, and pretransfusion samples were collected from all recipients in six government hospitals in Kenya. Blood donations were collected and screened for HIV according to standard practice in the hospital laboratories. Test results at a reference laboratory were compared with those of the hospital laboratories and risk of transfusion-associated HIV transmission was calculated. FINDINGS: The prevalence of HIV among blood donors was 6.4% (120 of 1877) and varied by hospital (range 2-20%). HIV test results were available for 1290 donor-recipient pairs. Of these, 26 HIV-positive donations were given to HIV-negative patients. We estimate that 2.0% of transfusions transmitted HIV. Problems in the hospitals that contributed to transfusion risk included inconsistent refrigeration, data entry errors, equipment failure, and lack of a quality-assurance programme. INTERPRETATION: A high proportion of blood transfusions transmitted HIV in this high-prevalence area of Africa, primarily because of erroneous laboratory practices. On the basis of these results, the Kenya Ministry of Health introduced a number of practical and inexpensive interventions to improve national blood safety.

Resistance to antiretroviral therapy among patients in Uganda.

OBJECTIVE: To characterize HIV-1 phenotypic resistance patterns and genotypic mutations among patients taking antiretroviral medications in Uganda. METHODS: We reviewed charts and retrieved archived plasma specimens from patients at an AIDS specialty center in Uganda where antiretroviral therapy has been used since 1996. Phenotypic and genotypic resistance testing was done on specimens associated with a viral load of 1000 copies/ml. RESULTS: Resistance testing of specimens was completed for 16 patients. Among 11 specimens collected before initiation of antiretroviral therapy, no phenotypic resistance or primary genotypic mutations were found. Among 8 patients taking lamivudine, phenotypic resistance was found for 9 (90%) of 10 specimens and was associated with an M184V mutation in all nine cases. Among 12 patients taking zidovudine, no phenotypic resistance and few primary mutations were found. For 6 patients who were receiving protease inhibitors, we observed no phenotypic resistance and only one primary genotypic mutation associated with resistance. CONCLUSIONS: The absence of apparent resistance among samples collected before antiretroviral therapy supports the notion that a similar approach to selection of antiretroviral therapy can generally be used against non-B subtypes. A genotypic marker of antiretroviral resistance to lamivudine in HIV-1 subtypes A, C, and D was similar to those in subtype B infections. These results suggest that the methods used for monitoring for the emergence of drug resistance in antiretroviral programs in Africa may be similar to those used in developed settings.

Surveillance of HIV-1 genetic subtypesand diversity in the US blood supply.

BACKGROUND: Recent reports of variant (non-subtype B) HIV infections in US populations have raised concerns about the sensitivity of subtype B virus-based donor screening and diagnostic assays. This study was designed to determine the prevalence and genetic diversity of HIV subtypes in US blood donors over the last two decades. STUDY DESIGN AND METHODS: Three groups were studied: hemophiliacs infected by clotting factor concentrates in the early 1980s (n = 49), blood donors retrospectively identified as being seropositive in 1985 (n = 97), and blood donors identified as seropositive between 1993 and 1996 (n = 405). Subtype assignment was based primarily on heteroduplex mobility analysis (HMA) of HIV-1 env, with DNA sequence confirmation of selected specimens. HIV peptide-based EIA serotyping was used to rule out HIV-2 and group O infections and to serotype HMA-refractory specimens. RESULTS: Of 551 specimens, 535 (97%) were assigned subtypes; 532 (99%) of these were subtype B. Three postscreening donations (1%) were assigned non-B subtypes (2 A, 1 C). Two of these three donors were born in Africa; the third was born in the United States and reported no risk factors other than heterosexual activity. HMA distribution plots showed an increase in env diversity among HIV-1 group B strains over time. CONCLUSION: The results support the need for continued surveillance of HIV subtype diversity and ongoing validation of the sensitivity of HIV diagnostic assays to non-B subtype infections.

Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire: a randomised trial.

BACKGROUND: In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire. METHODS: From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population. FINDINGS: 280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months. INTERPRETATION: Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen.

Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.

BACKGROUND: There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS: Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS: Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION: In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

Prevention of HIV transmission by blood transfusion in the developing world: achievements and continuing challenges.

In industrialized countries, the use of sensitive HIV screening tests, donor deferral, and more conservative use of blood have resulted in a dramatic decrease in the transmission of HIV infection by blood transfusion. The risk of HIV transmission in the USA by blood screened negative for HIV antibody was recently estimated at one in 440,000-660,000 donations. Despite this low risk, continued public concern has compelled blood collection agencies and policy makers to continue to search for more sensitive HIV screening tests. Genome amplification techniques are receiving increased attention and are being piloted in Germany. HIV-1 p24 antigen testing was implemented in the USA in March 1996. In the first 18 months of p24 antigen testing, an estimated 18 million blood donations were tested at a cost of US$90 million to detect three antigen-positive, antibody-negative donations. However, in many developing countries where severe anemia is widespread and the prevalence of HIV infection among blood donors is orders of magnitude greater than in industrialized countries, the blood supply is either incompletely screened or not screened at all for HIV antibody. Although the contribution of transfusion-transmitted infection to the HIV epidemic has not been accurately assessed, an estimated 5-10% of HIV infections in developing countries are due to blood transfusion. In a study conducted 1 year after implementation of HIV blood screening in the largest hospital in the capital city of the Democratic Republic of the Congo, an estimated 25% of pediatric HIV infections, and 40% of infections among children over 1 years of age, were due to transfusion. Lack of commitment by national governments and international aid organizations to this fundamental element of HIV prevention has resulted in a shortage of basic equipment, supplies, and trained personnel for blood screening. Moreover, provision of test kits alone cannot prevent HIV transmission by transfusion in resource-poor areas. More comprehensive programs are needed to improve the recruitment and retention of safe donors, essential laboratory services for blood banking and screening, technical training and supervision, appropriate use of transfusions, and the prevention of severe anemia. This article summarizes the steps being taken by developing countries to prevent HIV transmission by blood transfusion, lessons learned, and the work that still lies ahead.

PIP: Screening of the blood supply, a cost-effective strategy for reducing HIV transmission, has not been implemented consistently in developing countries. An estimated 5-10% of HIV transmission in these countries remains attributable to blood transfusion. Lack of commitment by national governments and international aid organizations has resulted in a shortage of basic equipment, supplies, and trained personnel for blood screening. The situation is further complicated by problems recruiting and retaining safe donors, a lack of essential laboratory services for blood banking and screening, the nonavailability of rapid tests, inadequate supervision of personnel, and widespread need for blood transfusions for malaria-related severe anemia. International donor organizations, government agencies, and health care providers are urged to give renewed attention to the issue of blood safety in resource-poor areas of the world so that this effective method of HIV prevention can be universally accessible.

Value and cost-effectiveness of screening blood donors for antibody to hepatitis B core antigen as a way of detecting window-phase human immunodeficiency virus type 1 infections. The HIV Blood Donor Study Group.

BACKGROUND: The value of screening donors for antibody to hepatitis B core antigen (anti-HBc) for the prevention of posttransfusion hepatitis has declined markedly. However, anti-HBc screening may still be useful as a surrogate marker for the window period (WP) of human immunodeficiency virus type 1 (HIV-1) infection. STUDY DESIGN AND METHODS: First, the relationship between anti-HBc reactivity and HIV-1 WP infections was examined among 225 donors who had seroconverted to anti-HIV-1 positivity between 1987 and 1990. In addition, data from 1654 HIV-1 seropositive donors were analyzed to characterize the relationship among anti-HBc reactivity, donor demographics, and HIV-1-related risk factors. The yield and cost-effectiveness of anti-HBc for HIV-1 prevention were then projected on the basis of a published decision analysis model. RESULTS: Forty (18%) of 225 HIV-1-seroconverting donors tested anti-HBc-reactive on the donation preceding anti-HIV-1 seroconversion; in contrast, 341 (34%) of 1014 HIV-1-seropositive donors interviewed tested anti-HBc-reactive (chi-square test; p < 0.001). Anti-HBc reactivity was more common among HIV-1-seropositive donors reporting male-to-male sexual contact (169/360, 47%) and injection drug use (44/83, 53%) than among those with heterosexual contacts known to be HIV-1-positive (31/190, 16%) or transfusion exposure (3/21, 14%) or among females with no identified risk factors (21/124, 17%). The estimates of 18 to 34 percent sensitivity for anti-HBc in detecting HIV-1 WP donations and a current rate of 1 in 676,000 HIV-1 WP donations (after p24 antigen screening) suggest that continued use of anti-HBc screening could result in the transfusion of 5 to 12 fewer HIV-1-infected units per year in the United States, which would add 19 to 48 quality-adjusted years of life for the 3.5 million annual transfusion recipients at a cost of $992,020 to $2,345,000 per quality-adjusted life-year saved. CONCLUSION: The low yield and very poor cost-effectiveness of anti-HBc screening indicate that this test is not an effective screening test for HIV-1 WP donations.

Longitudinal evaluation of severely anemic children in Kenya: the effect of transfusion on mortality and hematologic recovery.

OBJECTIVE: To determine the effect of transfusion on hematologic recovery and mortality among severely anemic children during and after hospitalization in rural Kenya. DESIGN: Prospective cohort. METHODS: We collected clinical and laboratory information on all severely anemic children (hemoglobin < 5.0 g/dl) and a 33% sample of children with hemoglobin < or = 5.0 g/dl who were admitted to the pediatric ward of a rural Kenyan hospital during a 6 month study period. Children were followed during hospitalization and at 4 and 8 weeks after admission. RESULTS: Overall, 303 (25%) of the 1223 hospitalized children had hemoglobin < 5.0 g/dl, 30% of whom died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than non-transfused children (5.8 g/dl, P < 0.001) and maintained a higher mean hemoglobin during the 8-week follow-up period. However, the presence of malaria parasitemia on follow-up negated the benefit of transfusion on hematologic recovery at both 4- and 8-week visits (longitudinal linear model, least square means, P > 0.05). Transfusion was associated with improved survival among children with respiratory distress who received transfusions within the first 2 days of hospitalization. CONCLUSIONS: The use of transfusion can be improved by targeting use of blood to severely anemic children with cardiorespiratory compromise, improving immediate availability of blood, and treating severely anemic children with effective antimalarial therapy.

PIP: The effect of blood transfusion on hematologic recovery and mortality both during and after hospitalization was investigated in a survey of children admitted to Siaya District Hospital (Kenya) in a 6-month period in 1991 with hemoglobin under 5.0 g/dl (n = 303) or 5.0 g/dl and above (n = 303). Children with hemoglobin under 5.0 g/dl (severe anemia) were younger and more likely to have malaria parasitemia and respiratory compromise than controls. 88 severely anemic children (30%) died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than nontransfused children (5.8 g/dl) and maintained a higher mean hemoglobin in the 8-week post-discharge follow-up period. 15% of transfused and 17% of nontransfused children died after hospital discharge. Transfusion was associated with significantly improved survival among children with respiratory distress who were transfused within 2 days of hospital admission. However, the presence of malaria or parasitemia at follow-up negated the benefit of transfusion on hematologic recovery. These findings suggest that the effectiveness of transfusion can be enhanced by targeting severely anemic children with cardiorespiratory compromise, improving immediate access to blood, and effective antimalarial therapy. In addition, more information is needed on the causes of death among anemic children and the prevention of severe anemia.

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors.

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T-lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window-period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window-period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window-period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.

Childhood mortality during and after hospitalization in western Kenya: effect of malaria treatment regimens.

Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Increasingly, the contribution of P. falciparum-associated severe anemia to pediatric mortality is being recognized while the impact of chloroquine resistance on mortality has not been evaluated. To address the issues of pediatric mortality, causes of death among hospitalized children less than five years of age in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were conducted to determine the child's clinical status posthospitalization. Of the 1,223 children admitted to Siaya District Hospital from March to September 1991, 293 (24%) were severely anemic (hemoglobin level < 5.0 g/dL). There were 265 (22%) deaths; 121 (10%) occurred in-hospital and 144 (13%) occurred out-of-hospital within eight weeks after admission; 32% of all deaths were associated with malaria. Treatment for malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens (pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for five days). The risk of dying was associated with younger age (P < 0.0001) and severe anemia (relative risk [RR] = 1.52, 95% confidence interval [CI] = 1.22, 1.90), and was decreased by treatment with an effective antimalarial drug (RR = 0.33, 95% CI = 0.19, 0.65). Effective drug therapy for P. falciparum with regimens that are parasitocidal in areas with a high prevalence of severe anemia and chloroquine resistance can significantly improve the survival of children in Africa.

PIP: Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Causes of death among hospitalized children less than age 5 years in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were then conducted to determine the child's clinical status posthospitalization. 293 of the 1223 children admitted to Siaya District Hospital during March-September 1991 were severely anemic. 265 children died; 32% of the deaths were associated with malaria. 121 of the deaths occurred in-hospital and 144 out-of-hospital within 8 weeks after admission. The treatment of malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens of pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for 5 days. The risk of dying was associated with younger age and severe anemia, and was decreased by treatment with an effective antimalarial drug.

Surveillance for human immunodeficiency virus type 1 group O infections in the United States.

BACKGROUND: Reports that the human immunodeficiency virus type 1 (HIV-1) group O variants are not reliably detected by some commercial diagnostic tests have raised concerns about the sensitivity of existing screening tests, especially with regard to blood safety. Although it is unlikely that these divergent strains are prevalent in North America, systematic, continuous surveillance is needed to monitor the potential spread of HIV variants into that region. STUDY DESIGN AND METHODS: Stored serum samples (n = 1072) from both high- and low-risk population groups at several sites in the United States and Puerto Rico were tested by peptide enzyme immunoassays specific for the prototypic HIV-1 group O strains, MVP5180 and ANT70. RESULTS: None of the 1072 samples examined had peptide reactivity that was consistent with HIV-1 group O infection. CONCLUSION: While no evidence of specific HIV-1 group O (MVP5180 or ANT70) infection was found in this study, the sensitivity of current tests has not been fully evaluated against the wide range of genetic variation of HIV. Therefore, it is important to continue active surveillance for HIV-1 and HIV type 2 strains, to characterize any divergent strains, and to judiciously modify tests to correct for any deficiencies in sensitivity.

Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States.

BACKGROUND: In the United States, transmission of the human immunodeficiency virus (HIV) by blood transfusion occurs almost exclusively when a recently infected blood donor is infectious but before antibodies to HIV become detectable (during the "window period"). We estimated the risk of HIV transmission caused by transfusion on the basis of the window period associated with the use of current, sensitive enzyme immunosorbent assays and recent data on HIV incidence among blood donors. METHODS: We analyzed demographic and laboratory data on more than 4.1 million blood donations obtained in 1992 and 1993 in 19 regions served by the American National Red Cross, as well as the results of HIV-antibody tests of 4.9 million donations obtained in an additional 23 regions. RESULTS: We estimated that, in the 19 study regions, 1 donation in every 360,000 (95 percent confidence interval, 210,000 to 1,140,000) was made during the window period. In addition, it is estimated that 1 in 2,600,000 donations was HIV-seropositive but was not identified as such because of an error in the laboratory. We estimated that 15 to 42 percent of window-period donations were discarded because they were seropositive on laboratory tests other than the HIV-antibody test. When these results were extrapolated to include the additional 23 Red Cross service regions, there was a risk of one case of HIV transmission for every 450,000 to 660,000 donations of screened blood. If the Red Cross centers are assumed to be representative of all U.S. blood centers, among the 12 million donations collected nationally each year an estimated 18 to 27 infectious donations are available for transfusion. CONCLUSIONS: The estimated risk of transmitting HIV by the transfusion of screened blood is very small and nearly half that estimated previously, primarily because the sensitivity of enzyme immunosorbent assays has been improved.

The effectiveness of the confidential unit exclusion option.

BACKGROUND: The confidential unit exclusion (CUE) option is intended to reduce human immunodeficiency virus (HIV) transmission by excluding donors newly infected with HIV who have not yet developed HIV antibody (window-period donors); however, its efficacy in excluding window-period donors has not been evaluated. STUDY DESIGN AND METHODS: The use of the CUE option was studied among the donors of 3.7 million units at 18 American Red Cross blood services regions during 1991 and 1992 and among 322 previously HIV-1-seronegative donors who subsequently donated a seropositive unit between 1987 and 1990 at 40 United States blood centers. These seroconverting donors had previously been shown to be highly likely to donate during their window period. RESULTS: On the basis of data from these two populations, it was estimated that only 3 to 5 percent of units donated by window-period donors were not transfused because of the CUE option, that 0.4 percent of all donations were from donors who confidentially excluded their blood from transfusion, and that donors who confidentially excluded their blood were 21 times more likely to be HIV antibody-positive than donors who did not use the CUE option. It is estimated that, if all US blood centers used the CUE option, a total of 2 to 17 otherwise acceptable units donated by window-period donors would not be transfused annually. CONCLUSION: Although donors who confidentially exclude their blood from transfusion are 21 times more likely to have HIV antibody, the rarity of window-period donors and the infrequency of confidential exclusion by window-period donors cause the CUE option to have minimal impact on transfusion safety.

Anaemia, blood transfusion practices, HIV and mortality among women of reproductive age in western Kenya.

Severe anaemia among women in sub-Saharan Africa is frequently treated with blood transfusions. The risk of transmission of human immunodeficiency virus (HIV) through blood products has led to a re-evaluation of the indications for transfusions. Prospective surveillance of women admitted to a district hospital in western Kenya was conducted from 1 December 1990 to 31 July 1991, for haemoglobin (Hb) transfusion status, and outcome. Of the 2986 enrolled women (mean Hb 10.4 g/dL, SD +/- 2.6, median age 24.4 years), 6% were severely anaemic (Hb < 6.0 g/dL). Severe anaemia was associated with a higher mortality rate (10.7% vs. 1.4%, odds ratio (OR) = 8.2, 95% confidence interval (CI) 2.6, 34.2) compared with women with Hb > or = 6.0 g/dL. Decreased mortality rates in hospital were observed with increasing Hb values (OR = 0.43, 95% CI 0.19, 0.98), but blood transfusions did not improve survival in hospital (OR = 1.56, 95% CI 0.22, 11.03). The attributable mortality due to HIV infection and severe anaemia was 75% and 31%, respectively. Maternal/child health care services must include prevention strategies for HIV transmission and the prevention, recognition, and treatment of severe anaemia.

PIP: This paper reports the findings of an evaluation of Western Kenyan blood transfusion practices used with a cohort of severely anemic women of child-bearing age. The potential of receiving HIV-infected blood puts these women at a definite health risk. Characteristics of severely anemic women included being older (P = 0.03, Wilcoxon rank sum test), lower likelihood of being pregnant when admitted to hospital (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.35-0.81), and greater likelihood of being HIV seropositive (OR = 2.92; 95% CI, 1.52-5.60) when compared to non-anemic women. Severely anemic women were also less likely to have malaria (OR = 0.58; 95% CI, 0.35-0.96). Women who had a transfusion ordered had a higher mortality rate than women who did not (25/240, 10.4% vs. 18/933, 1.9%)(OR = 5.91; 95% CI, 3.04-11.53). In this study, positive benefits were restricted to women who had a transfusion only for them. These were the severely anemic women. The attributed mortality caused by HIV infection and severe anemia was 75% and 31%, respectively. Detection of HIV infected blood is very critical. Prevention of anemia is considered more important than transfusing concerns. Preventing the need for transfusions would reduce the HIV transmission risk from potentially infectious blood during transfusion.

Blood transfusion practices and blood-banking services in a Kenyan hospital.

OBJECTIVES: To identify ways to improve the operation of blood-screening programs and to decrease the inappropriate use of blood by evaluating blood-transfusion practices and blood-banking services in a Kenyan hospital. DESIGN: Prospective cohort. SETTING: The study was conducted in a rural district hospital in western Kenya between September 1990 and July 1991. METHODS: We collected data on all transfusion requests (blood donation, grouping, HIV screening) and blood recipients (age, sex, diagnosis, and for a 3-month period on the pediatric, maternity, and female wards, admission hemoglobin and outcome). RESULTS: During the 11-month study period, 799 patients received 927 transfusions: 67% were children < 15 years of age, 27% were adult women and 6% were adult men. Transfusions were often delayed due to reliance on patient-recruited donors. Patients who received blood donated on or after the date of request waited longer for transfusion (median, 3 days) than patients who received blood that had been banked and screened before the request (median, 1 day). Patient-recruited donors had a higher HIV-seropositivity rate than volunteer donors (13.4 and 4.6%, respectively; chi 2 test, P < 0.001). Overall, 47% of pediatric transfusions were classified as inappropriate: 23% did not meet the criteria of having hemoglobin < 5.0 g/dl and clinical evidence of respiratory distress, and 27% were transfused 2 or more days after requested. Among adults, 68% received one unit of blood or less. CONCLUSIONS: Improved laboratory services, reduction of unnecessary transfusions, and increased recruitment of volunteer donors are critical for improving the appropriate and timely use of blood and reducing transfusion-associated HIV transmission.

PIP: Between September 1990 and July 1991, health workers and/or laboratory personnel at Siaya District Hospital in rural western Kenya (about 60 km northwest of Kisumu) gathered data on 799 patients who received 927 blood transfusions, including blood donation, grouping, and HIV screening. Most blood recipients were children (under 15 years old). Only 6% of all recipients were men. Just 30% of transfusions were performed the day of request. Blood donors recruited when it was most needed for survival. Their blood tended to be available 3 days after the request. The volunteer donated blood tended to be available for transfusion the day of request, however, because it had already been banked and screened. Patient-recruited donors were more likely to be HIV infected than volunteer donors (13.4% vs. 4.6%; relative risk = 2.91; p .001). 47% of the pediatric transfusions should not have taken place because 23% of these children did not suffer respiratory distress and their hemoglobin levels were greater than t gm/dl and because 27% received the transfusion 2 days after the day of request. 90% of all adult transfusions were inappropriate (i.e., transfusion of no more than 1 unit of blood or received the transfusion 2 days after the day of request). 30% of blood units that had been banked and screened at the time of request were not transfused until at least 2 days after request. These findings identified those areas which must be targeted to improve the appropriate and timely use of blood and reducing transfusion-induced HIV transmission: reduction of inappropriate transfusions, increased recruitment of volunteer donors, and improved laboratory services.

Beyond chloroquine: implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa.

Emphasis on retaining chloroquine as the first-line therapy for Plasmodium falciparum infections in most of sub-Saharan Africa for as long as it remains effective has resulted in widespread reliance on chloroquine in areas where it can have little effect on P. falciparum parasitemia. To address this issue, clinical, parasitologic, and hematologic responses to chloroquine or pyrimethamine/sulfadoxine treatment were assessed among very young children in Malawi (n = 153) and Kenya (n = 73). The median time to resumption of clinical symptoms in chloroquine-treated children was 13.5 days in Malawi and 9.5 days in Kenya. Children treated with pyrimethamine/sulfadoxine maintained clinical improvement and had greater increases in their hemoglobin concentration during the follow-up period than did children treated with chloroquine. Treatment with chloroquine failed to produce either a durable clinical improvement or optimal hematologic recovery. Consequently, chloroquine can no longer be considered adequately effective therapy of clinical P. falciparum malaria in very young children in these areas of Africa.

Risk of HIV infection from transfusion with blood negative for HIV antibody in a west African city.

OBJECTIVE: To estimate the risk of infection with HIV (HIV 1 or HIV 2, or both) from transfusion of a screened unit of blood in a high prevalence area in west Africa. DESIGN: Retrospective cohort study for January-July 1991. SETTING: National Blood Transfusion Centre, Abidjan, Côte d'Ivoire. SUBJECTS: Repeat donors (5831 units of blood) and first time donors (5076 units) in the first five months of 1991. MAIN OUTCOME MEASURES: Prevalence and estimated incidence of HIV infection in repeat and first time donors; estimated rate of potentially infected, HIV antibody negative units; and rate of (false negative) potentially infected units assuming a laboratory test sensitivity of 99%. RESULTS: Overall HIV prevalence was 11.0% in first time donors and 2.1% in repeat donors. In the first seven months of 1991, 29 HIV antibody positive (27 HIV 1, 1 HIV 2, 1 dually reactive) donors with a seronegative unit of blood earlier in the year were identified; 26 had donated blood eight weeks or less before their estimated dates of seroconversion and may have been infectious (minimum rate 26/5831 (4.5/1000 potentially infected units)). Estimated incidence of infection in repeat donors was 1.2-2.5%. Laboratory test insensitivity would result in an estimated 1.1/1000 false negative units from first time donors and 0.2/1000 units from regular donors. The overall rate of potentially infected units (all donors, seroconversions, and errors) was estimated at 5.4-10.6/1000. CONCLUSIONS: The risk of HIV infection from a single unit of blood remains substantial (5.4-10.6/1000 units). To prevent infection from blood transfusion in areas of high incidence and prevalence of HIV all but absolutely essential transfusions should be avoided, and donors with low incidence of HIV infection should be selected.