Eve M. Lackritz

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 Abidjans 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.

The Contribution of Preterm Birth to Infant Mortality Rates in the United States

OBJECTIVE. Although two thirds of infant deaths in the United States occur among infants born preterm (<37 weeks of gestation), only 17% of infant deaths are classified as being attributable to preterm birth with the standard classification of leading causes of death. To address this apparent discrepancy, we sought to estimate more accurately the contribution of preterm birth to infant mortality rates in the United States. METHODS. We identified the top 20 leading causes of infant death in 2002 in the US linked birth/infant death file. The role of preterm birth for each cause was assessed by determining the proportion of infants who were born preterm for each cause of death and by considering the biological connection between preterm birth and the specific cause of death. RESULTS. Of 27970 records in the linked birth/infant death file for 2002, the 20 leading causes accounted for 22273 deaths (80% of all infant deaths). Among infant deaths attributable to the 20 leading causes, we classified 9596 infant deaths (34.3% of all infant deaths) as attributable to preterm birth. Ninety-five percent of those deaths occurred among infants who were born at <32 weeks of gestation and weighed <1500 g, and two thirds of those deaths occurred during the first 24 hours of life. CONCLUSIONS. On the basis of this evaluation, preterm birth is the most frequent cause of infant death in the United States, accounting for at least one third of infant deaths in 2002. The extreme prematurity of most of the infants and their short survival indicate that reducing infant mortality rates requires a comprehensive agenda to identify, to test, and to implement effective strategies for the prevention of preterm birth.

Effect of blood transfusion on survival among children in a Kenyan hospital

In Africa, blood transfusions are frequently given to treat severe paediatric anaemia. Because of the risk of HIV transmission, identification of when transfusion will reduce the risk of death for severely anaemic children has become increasingly important. For all children admitted to a Kenyan hospital from October, 1989, to October, 1990, we collected data on clinical presentation, haemoglobin (Hb), receipt of transfusion, and in-hospital survival. Of 2433 admissions, 29% (684) had severe anaemia (Hb less than 5.0 g/dl), and 20% (483) received blood transfusions. Based on laboratory criteria only, children with Hb less than 3.9 g/dl who were transfused had lower mortality than those with Hb less than 3.9 g/dl who were not transfused, but this finding applied only to children transfused on the day of admission (odds ratio [OR] 0.30; 95% Cl 0.14, 0.61) or the day after admission (OR 0.37; 95% Cl 0.14, 1.00). Based on a combination of laboratory and clinical criteria, children with clinical signs of respiratory distress and Hb less than 4.7 g/dl who were transfused had lower morality than those who were not (OR 0.19; 95% Cl 0.09, 0.41). Among children without respiratory distress, there was no association between receipt of transfusion and mortality, irrespective of admission Hb. The frequency of blood transfusion can be reduced and survival enhanced by targeting blood to those children with severe anaemia and clinical signs of respiratory distress, and by using transfusion early in the course of hospitalisation.

Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries

Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ill newborn babies), have low and inequitable coverage and are the most sensitive markers of health system function. In eight of the 13 countries with the most neonatal deaths (55% worldwide), we undertook a systematic assessment of bottlenecks to essential maternal and newborn health care, involving more than 600 experts. Of 2465 bottlenecks identified, common constraints were found in all high-burden countries, notably regarding the health workforce, financing, and service delivery. However, bottlenecks for specific interventions might differ across similar health systems. For example, the implementation of kangaroo mother care was noted as challenging in the four Asian country workshops, but was regarded as a feasible aspect of preterm care by respondents in the four African countries. If all high-burden countries achieved the neonatal mortality rates of their regions fastest progressing countries, then the mortality goal of ten or fewer per 1000 livebirths by 2035 recommended in this Series and the Every Newborn Action Plan would be exceeded. We therefore examined fast progressing countries to identify strategies to reduce neonatal mortality. We identified several key factors: (1) workforce planning to increase numbers and upgrade specific skills for care at birth and of small and ill newborn babies, task sharing, incentives for rural health workers; (2) financial protection measures, such as expansion of health insurance, conditional cash transfers, and performance-based financing; and (3) dynamic leadership including innovation and community empowerment. Adapting from the 2005 Lancet Series on neonatal survival and drawing on this Every Newborn Series, we propose a country-led, data-driven process to sharpen national health plans, seize opportunities to address the quality gap for care at birth and care of small and ill newborn babies, and systematically scale up care to reach every mother and newborn baby, particularly the poorest.

Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States

OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. LEVEL OF EVIDENCE: III

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.

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

Kaposi's sarcoma in Uganda: Risk factors for human herpesvirus 8 infection among blood donors

Human herpesvirus 8 (HHV-8) is etiologically linked to Kaposis 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.

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

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

Development of phenotypic and genotypic resistance to antiretroviral therapy in the UNAIDS HIV Drug Access Initiative--Uganda.

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