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Biomedical subjects

B Nahlen

Publications and source records attributed to B Nahlen.

13 recordsLinked to original sources
PubMed2001

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.

Blood Banks↗
PubMed2001

Tumor necrosis factor-alpha promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX.

A polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene, with a guanine to adenine nucleotide change at position -308, TNF2 is associated with increased TNF-alpha production. TNF2 homozygotes have a higher risk of severe disease and/or death due to cerebral malaria and other infectious diseases. We investigated the impact of this allele on malaria morbidity and mortality in young children who participated in an immuno-epidemiologic cohort study of malaria in an area of intense perennial Plasmodium falciparum transmission in western Kenya. A total of 1,048 children were genotyped. Poisson regression and Cox proportional hazards models were used to determine the relationship between TNF-308 variants and morbidity and mortality. The gene frequencies of the TNF1 and TNF2 alleles were 0.90 and 0.10, respectively. TNF2 homozygosity was associated with pre-term birth when compared with TNF1 homozygotes [relative risk (RR) 7.3, 95% CI, 2.85-18.9, P = 0.002) and heterozygotes (RR 6.7, 95% CI 2.0-23.0, P = 0.008). Among children born prematurely, the TNF2 allele was significantly associated with a higher risk of death in infancy compared with TNF1 (RR 7.47, 95% CI 2.36-23.6). The risk of death was higher among TNF2 homozygotes than among heterozygotes. The TNF2 allele was significantly associated with high density P. falciparum parasitemia (RR 1.11, 95% CI 1.0-1.24). Among low birth weight children, the TNF2 allele was associated with severe anemia (RR 2.16, 95% CI 1.17-4.01) and showed a trend toward a risk for severe malaria anemia (RR 1.99, 95% CI 0.89-4.46). These data suggest that TNF2 is a risk factor for pre-term birth and early childhood mortality and malaria morbidity in children in this region. Further understanding of the pathogenic mechanisms underlying this association is required.

Alleles↗
PubMed1999

A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya.

The balance between Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma) and Th2 cytokines (interleukin [IL]-10, -4) may be critical in the development of severe falciparum malaria. Therefore, plasma concentrations of these cytokines were determined in children with various manifestations of malaria. Plasma levels of IFN-gamma and IL-4 were undetectable in most children. However, TNF-alpha and IL-10 were significantly elevated in children with high-density parasitemia and malaria anemia compared with children in control groups. In children with mild malaria, IL-10, but not TNF-alpha, was significantly elevated. While the highest concentrations of TNF-alpha were found in children with malaria anemia, IL-10 levels were highest in children with high-density uncomplicated malaria. The mean ratio of IL-10 to TNF-alpha was significantly higher in children with mild and high-density parasitemia (4.64, P<.005) than in children with malaria anemia (1.77). Thus, higher levels of IL-10 over TNF-alpha may prevent development of malaria anemia by controlling the excessive inflammatory activities of TNF-alpha.

Anemia↗
PubMed1999

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission I. Description of study site, general methodology, and study population.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. The primary purpose of the project was to study Plasmodium falciparum malaria in a highly endemic area using a comprehensive and multidisciplinary approach, which included epidemiology, entomology, and immunology. Between June 1992 and July 1994, pregnant women living in 15 rural villages were identified during a monthly census and 1,164 were enrolled. The women were followed-up throughout their pregnancy and they, along with their newborn infants and direct siblings of the infants' less than 15 years of age, were monitored over time. As of May 1995, 1,017 infants had been born to these women. This paper presents the design and general methodology used in this study and describes the initial experience with intense monitoring of a large population over a prolonged period.

Child, Preschool↗
PubMed1999

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative. Parasite prevalence (all species) decreased with age (from a high of 83% among children 1-4 years old to 60% among children 10-14 years old). Even more dramatic decreases were noted in the prevalence of high density falciparum infection (from 37% among children 12-23 months old to < 1% among 10-14-year-old children) and in clinical malaria (20% to 0.3% in the same age groups). Children < 1 year of age accounted for 55% of all cases of anemia detected. Anemia was consistently associated with high density infection in children < 10 years of age (20% to 210% increased risk relative to aparasitemic children). These results demonstrate the relationship between high-density malaria infection and two clinical manifestations of malarial illness.

Adolescent↗
PubMed1998

Risk of severe malaria among African infants: direct evidence of clinical protection during early infancy.

Little empirical evidence from field-based studies exists on the relative magnitude or duration of clinical protection from Plasmodium falciparum malaria in infancy. A prospective study was undertaken to examine the age distribution of hospital admissions in four geographically and demographically well-defined areas with differing intensities of P. falciparum transmission. Where transmission was perennial, significant clinical protection from severe morbidity was observed up to the third month of life; in the seasonal transmission area, disease rates rose after the sixth month of life. Infants exposed to the highest rates of P. falciparum exposure demonstrated significant declines in the risks of severe malaria from 6 months of age. These data provide direct evidence for the very early acquisition of clinical immunity and for the existence of a period of clinical protection, which together may explain why, in these communities, the cumulative risk of malarial disease throughout childhood appears to decline with increasing transmission intensity.

Age Factors↗
PubMed1997

A simple perfusion technique for isolation of maternal intervillous blood mononuclear cells from human placentae.

A noninvasive perfusion method for the recovery of maternal placental (intervillous) blood for use in immunologic assays is described. 60% of the perfused blood samples tested for fetal red blood cell (RBC) contamination were found to be pure maternal blood; in the remainder, fetal RBC contamination, with a single exception, was less than 6%. The intervillous mononuclear cells (IVBMC) isolated from this blood were of predominantly maternal origin as demonstrated by a polymerase chain reaction-based DNA typing technique. The number of IVBMC obtained was within the range of 9 to 55 X 10(6) cells. Phenotypic analysis of IVBMC surface antigens revealed that 61% of the cells were CD3 + T-cells and 18% were CD19 + B-cells. The CD4 + and CD8 + T-lymphocyte subsets accounted for 28 and 26% of the IVBMC, respectively. The IVBMC were functionally competent as evidenced by in vitro lymphoproliferation and cytokine production in response to mitogen and PPD stimulation. This technique allows for rapid and safe isolation of large numbers of IVBMC which are functionally active up to 12 h post-delivery, thus representing a significant improvement over previously described methods. It should facilitate more vigorous research in the study of uteroplacental immunity and infectious disease research, particularly in field settings where sample collection and laboratory facilities are distant.

Chorionic Villi↗
PubMed1997

Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa.

BACKGROUND: Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted. METHODS: We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory-tract infections (ARI) as a comparison. FINDINGS: 3556 malaria admissions were recorded for the five sites. Marked differences were observed in age, clinical spectrum and rates of severe malaria between the five sites. Paradoxically, the risks of severe disease in childhood were lowest among populations with the highest transmission intensities, and the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. For severe malaria, for example, admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3.9, 25.8, 25.9, 16.7, and 18.0 in the five communities; the forces of infection estimated for those communities (new infections per infant per month) were 0.001, 0.034, 0.050, 0.093, and 0.176, respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing transmission intensity. INTERPRETATION: We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate. In highly endemic areas measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.

Anemia↗
PubMed1996

An evaluation of clinical indicators for severe paediatric illness.

To help reduce paediatric morbidity and mortality in the developing world, WHO has developed a diagnostic and treatment algorithm that targets the principal causes of death in children, which include acute respiratory infection, malaria, measles, diarrhoeal disease, and malnutrition. With this algorithm, known as the Sick Child Charts, severely ill children are rapidly identified, through the presence of any one of 13 signs indicative of severe illness, and referred for more intensive health care. These signs are the inability to drink, abnormal mental status (abnormally sleepy), convulsions, wasting, oedema, chest wall retraction, stridor, abnormal skin turgor, repeated vomiting, stiff neck, tender swelling behind the ear, pallor of the conjunctiva, and corneal ulceration. The usefulness of these signs, both in current clinical practice and within the optimized context of the Sick Child Chart algorithm in a rural district of western Kenya, was evaluated. We found that 27% of children seen in outpatient clinics had one or more of these signs and that pallor and chest wall retraction were the signs most likely to be associated with hospital admission (odds ratio (OR) = 8.6 and 5.3, respectively). Presentation with any of these signs led to a 3.2 times increased likelihood of admission, although 54% of hospitalized children had no such signs and 21% of children sent home from the outpatient clinic had at least one sign. Among inpatients, 58% of all children and 89% of children who died had been admitted with a sign. Abnormal mental status was the sign most highly associated with death (OR = 59.6), followed by poor skin turgor (OR = 5.6), pallor (OR = 4.3), repeated vomiting (OR = 3.6), chest wall retraction (OR = 2.7), and oedema (OR = 2.4). Overall, the mortality risk associated with having at least one sign was 6.5 times higher than that for children without any sign. While these signs are useful in identifying a subset of children at high risk of death, their validation in other settings is needed. The training and supervision of health workers to identify severely ill children should continue to be given high priority because of the benefits, such as reduction of childhood mortality.

Cause of Death↗
PubMed1994

Municipal drinking water and cryptosporidiosis among persons with AIDS in Los Angeles County.

To assess unfiltered drinking water as a source of cryptosporidium infection in patients with the acquired immunodeficiency syndrome (AIDS) the prevalence of cryptosporidiosis among persons with AIDS in Los Angeles County was assessed by water service area. One water distributor, serving approximately 60% of the county's residents (area B), has consistently employed filtration. The other company, which serves the remainder of the county (area A), did not institute filtration until mid-December 1986. This difference provided a 'natural experiment' in which to assess the effect of municipal water filtration on the level of cryptosporidiosis among persons with AIDS. The prevalence of cryptosporidiosis among AIDS patients was compared for the two water service areas for the time period (1983-6) preceding the implementation of filtration in area A. From 1983 to 1986 the age-standardized prevalence of cryptosporidiosis among AIDS patients was 32% lower in area A (4.2%), which received unfiltered water, than in area B (6.2%). Following addition of filtration in area A, the prevalence of cryptosporidiosis among AIDS patients decreased by 20%; however, a decline, of 47%, was also observed in area B. The similar baseline levels of cryptosporidiosis and the corresponding post-filtration decline in both areas suggest that filtration had no effect on levels of cryptosporidiosis among persons with AIDS. Thus it does not appear that municipal drinking water is an important risk factor for cryptosporidiosis in AIDS patients residing in Los Angeles County.

AIDS-Related Opportunistic Infections↗
PubMed1992

Swimming-associated cryptosporidiosis.

In July and August 1988, an outbreak of gastroenteritis affected 44 of 60 (73%) persons from 5 separate swimming groups who had used the same swimming pool in Los Angeles. Cryptosporidium was identified in 5 of 8 (63%) stool specimens, and the clinical picture was consistent with Cryptosporidium infection. Resistance of Cryptosporidium to chlorine, an inadequately maintained pool filtration system, repeated exposure to pool water, and possible continuing pool contamination may have contributed to ongoing transmission. Cryptosporidium should be considered a potential etiologic agent of gastroenteritis associated with recreational water use.

Adolescent↗
PubMedDate not supplied

Group A streptococcal postvaricella osteomyelitis.

Osteomyelitis as a complication of varicella has been rarely reported. We report two individual cases of postvaricella osteomyelitis in which group A beta-hemolytic Streptococcus was implicated. In the first case group A beta-hemolytic Streptococcus was isolated from blood cultures and bone aspirate cultures from the femoral metaphysis. The second case of postvaricella osteomyelitis involved the distal fibula and was diagnosed by characteristic radiographic changes in the distal fibula, a positive bone scan, purulent varicella lesions that contained group A beta-hemolytic Streptococcus, and a prompt response to penicillin therapy. These cases have implications for the choice of appropriate antimicrobial therapy in the treatment of osteomyelitis complicating varicella.

Chickenpox↗