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Biomedical subjects

Hugh Reyburn

Publications and source records attributed to Hugh Reyburn.

12 recordsLinked to original sources
PubMed2006

CD161 (human NKR-P1A) signaling in NK cells involves the activation of acid sphingomyelinase.

NK and NKT cells play a major role in both innate immunity and in influencing the development of adaptive immune responses. CD161 (human NKR-P1A), a protein encoded in the NK gene complex, is a major phenotypic marker of both these cell types and is thought to be involved in the regulation of NK and NKT cell function. However, the mechanisms of action and signaling pathways of CD161 are poorly understood. To identify molecules able to interact with the cytoplasmic tail of human CD161 (NKR-P1A), we have conducted a yeast two-hybrid screen and identified acid sphingomyelinase as a novel intracellular signaling pathway linked to CD161. mAb-mediated cross-linking of CD161, in both transfectants and primary human NK cells, triggers the activation of acid, but not neutral sphingomyelinase. The sphingomyelinases represent the catabolic pathway for N-acyl-sphingosine (ceramide) generation, an emerging second messenger with key roles in the induction of apoptosis, proliferation, and differentiation. These data therefore define a novel signal transduction pathway for the CD161 (NKR-P1A) receptor and provide fresh insights into NK and NKT cell biology.

Antigens, Surface↗
PubMed2006

The contribution of microscopy to targeting antimalarial treatment in a low transmission area of Tanzania.

BACKGROUND: There is a need for improved targeting of antimalarial treatment if artemisinin combination therapy is to be successfully introduced in Africa. This study aimed to explore why malaria slides are requested and how their results guide treatment decisions in an area of low transmission of P. falciparum. METHODS: Outpatients attending a district hospital in a highland area of Tanzania were studied over a 3-week period. Clinical and social data were collected from patients who had been prescribed an antimalarial or sent for a malaria slide. Hospital slides were re-read later by research methods. RESULTS: Of 1,273 consultations 132(10%) were treated presumptively for malaria and 214(17%) were sent for a malaria slide; only 13(6%) of these were reported positive for P. falciparum but 96(48%) of the 201 slide-negative cases were treated for malaria anyway. In a logistic regression model, adults (OR 3.86, P < 0.01), a history of fever (OR1.72, P = 0.03) and a longer travel time to the clinic (OR 1.77 per hour travelled, P < 0.01) independently predicted the request for a malaria slide. Only a history of a cough predicted (negatively) the prescription of an antimalarial with a negative slide result (OR 0.44, P < 0.01). The sensitivity and specificity of hospital slide results were 50% and 96% respectively. CONCLUSION: Progress in targeting of antimalarials in low malaria transmission settings is likely to depend on consistent use of malaria microscopy and on the willingness of health workers to be guided by negative slide results. Further studies are needed to identify how this can be achieved.

Adolescent↗
PubMed2006

The effect of altitude on parasite density case definitions for malaria in northeastern Tanzania.

OBJECTIVES: Malaria clinical trials need precise endpoints to measure efficacy. In endemic areas where asymptomatic parasitaemia is common, 'fever plus parasitaemia' may not differentiate between malaria cases and non-cases. Case definitions based on parasite cut-off densities may be more appropriate but may vary with age and transmission intensity. This study examines appropriate case definitions from parasitological surveys conducted over a broad range of transmission intensities, using altitude as a proxy for transmission intensity. METHODS: Cross-sectional data collected from 24 villages at different altitudes in an endemic area of northeastern Tanzania were used to calculate malaria-attributable fractions using a modified Poisson regression method. We modelled fever as a function of parasite density and determined the optimum cut-off densities of parasites to cause fever using sensitivity and specificity analyses. RESULTS: The optimum cut-off density varied by altitude in children aged under 5 years: a case definition of 4,000 parasites per mul at altitudes <600 m (high transmission intensity) was most appropriate, compared with 1,000 parasites per mul at altitudes >600 m (low transmission intensity). In children aged over 5 years and adults, there was little variation by altitude and a case definition of any parasites plus fever was the most appropriate. CONCLUSIONS: Locally appropriate case definitions of malaria should be used for research purposes. In our setting, these varied independently with age and transmission intensity.

Adolescent↗
PubMed2005

Altitude-dependent and -independent variations in Plasmodium falciparum prevalence in northeastern Tanzania.

BACKGROUND: Effective malaria control requires information about intensity of transmission across large areas and populations. Estimates based on entomological factors lack precision and are not cost-effective to obtain. We tested altitude and rainfall measurements as correlates of transmission intensity in different ecological settings. METHODS: We conducted 2 cross-sectional surveys of approximately 12,000 people (1-45 years old) in 6 altitude transects (150-1800 m) in the Kilimanjaro and Tanga regions of Tanzania. Data were analyzed for associations with altitude and rainfall estimates by use of appropriate regression models. RESULTS: Plasmodium falciparum prevalence showed a negative relationship with altitude (19% and 21% decrease/100-m altitude increase, respectively, in children in Kilimanjaro and Tanga) and rainfall during the 3 months before the survey (46% decrease/100-mm rainfall increase in children in Kilimanjaro). Mean hemoglobin concentrations increased with altitude (0.05 and 0.09 g/dL/100-m altitude increase, respectively, in children in Kilimanjaro and Tanga) and rainfall (0.17 g/dL/100-mm rainfall increase in children and adults in Kilimanjaro). DISCUSSION: Altitude and rainfall were correlated with parasite prevalence and mean hemoglobin concentration; however, the relationship varied according to ecological setting. Climatological variables alone cannot predict malarial outcomes. Local variations in seasonality of malaria transmission--together with vector species composition, topography, host and parasite genetics, and socioeconomic factors--may influence malaria prevalence.

Adolescent↗
PubMed2005

Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria.

CONTEXT: There are concerns that malaria control measures such as use of insecticide-treated bed nets, by delaying acquisition of immunity, might result in an increase in the more severe manifestations of malaria. An understanding of the relationships among the level of exposure to Plasmodium falciparum, age, and severity of malaria can provide evidence of whether this is likely. OBJECTIVE: To describe the clinical manifestations and case fatality of severe P falciparum malaria at varying altitudes resulting in varying levels of transmission. DESIGN, SETTING, AND PATIENTS: A total of 1984 patients admitted for severe malaria to 10 hospitals serving populations living at levels of transmission varying from very low (altitude >1200 m) to very high (altitude <600 m) in a defined area of northeastern Tanzania, studied prospectively from February 2002 to February 2003. Data were analyzed in a logistic regression model and adjusted for potential clustering within hospitals. MAIN OUTCOME MEASURES: Specific syndromes of severe malaria; mortality. RESULTS: The median age of patients was 1 year in high transmission, 3 years in moderate transmission, and 5 years in low transmission areas. The odds of severe malarial anemia (hemoglobin <5 g/dL) peaked at 1 year of age at high transmission and at 2 years at moderate and low transmission intensities and then decreased with increasing age (P = .002). Odds were highest in infants (0-1 year: referent; 2-4 years: odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.96), 5 to <15 years: OR, 0.44; 95% CI, 0.27-0.72; > or =15 years: OR, 0.44; 95% CI, 0.27-0.73; P<.001) and high transmission intensity areas (altitude <600 m: referent; 600 m to 1200 m: OR, 0.55; 95% CI, 0.35-0.84; >1200 m: OR, 0.55; 95% CI, 0.26-1.15; P for trend = .03). The odds of cerebral malaria were significantly higher in low transmission intensity areas (altitude of residence <600 m: referent; 600 m to 1200 m: OR, 3.17; 95% CI, 1.32-7.60; >1200 m: OR, 3.76; 95% CI, 1.96-7.18; P for trend = .003) and with age 5 years and older (0-1 year: referent; 2-4 years: OR, 1.57; 95% CI, 0.82-2.99; 5 to <15 years: OR, 6.07; 95% CI, 2.98-12.38; > or =15 years: OR, 6.24; 95% CI, 3.47-11.21; P<.001). The overall case-fatality rate of 7% (139 deaths) was similar at high and moderate levels of transmission but increased to 13% in low transmission areas (P = .03), an increase explained by the increase in the proportion of cases with cerebral malaria. CONCLUSIONS: Age and level of exposure independently influence the clinical presentation of severe malaria. Our study suggests that an increase in the proportion of cases with more fatal manifestations of severe malaria is likely to occur only after transmission has been reduced to low levels where the overall incidence is likely to be low.

Adolescent↗
PubMed2004

Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study.

OBJECTIVE: To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission. DESIGN: Prospective observational study of children and adults over the course a year. SETTING: 10 hospitals in north east Tanzania. PARTICIPANTS: 17,313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease. MAIN OUTCOME MEASURE: Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system. RESULTS: Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged > or = 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children. CONCLUSIONS: In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.

Adolescent↗
PubMed2004

Knowledge of malaria influences the use of insecticide treated nets but not intermittent presumptive treatment by pregnant women in Tanzania.

BACKGROUND: To reduce the intolerable burden of malaria in pregnancy, the Ministry of Health in Tanzania has recently adopted a policy of intermittent presumptive treatment for pregnant women using sulphadoxine-pyrimethamine (IPTp-SP). In addition, there is strong national commitment to increase distribution of insecticide treated nets (ITNs) among pregnant women. This study explores the determinants of uptake for both ITNs and IPTp-SP by pregnant women and the role that individual knowledge and socio-economic status has to play for each. METHODS: 293 women were recruited post-partum at Kibaha District Hospital on the East African coast. The haemoglobin level of each woman was measured and a questionnaire administered. RESULTS: Use of both interventions was associated with a reduced risk of severe anaemia (Hb<8 g/dL) compared to women who had used neither intervention (OR 0.31, 95% CI 0.14-0.67). In a logistic regression model it was found that attendance at MCH health education sessions was the only factor that predicted IPTp-SP use (OR 1.8, 95% CI 1.1-2.9) while high knowledge of malaria predicted use of ITNs (OR 2.3, 95% CI 1.1-4.9). CONCLUSION: Individual knowledge of malaria was an important factor for ITN uptake, but not for IPTp-SP use, which was reliant on delivery of information by MCH systems. When both these interventions were used, severe anaemia postpartum was reduced by 69% compared to use of neither, thus providing evidence of effectiveness of these interventions when used in combination.

Adult↗
PubMed2004

Epidemiology of anthroponotic cutaneous leishmaniasis in Afghan refugee camps in northwest Pakistan.

During November and December 1998, 16 Afghan refugee camps were surveyed for anthroponotic cutaneous leishmaniasis (ACL). Prevalence of active lesions and scars amongst the population was 2.7% and 2.4%, respectively. Between camps the prevalence of active lesions varied from 0.3 to 8.8% and that of scars from 0.3 to 5.8%. Random-effects logistic regression indicated that risk of active ACL was associated with age but not gender. This model also indicated a significant clustering at the household level. The average annual force of ACL infection was estimated to be 0.046 per year (4.6 cases/1000 persons/year) over the past 10 years. Based on the evidence from this study an intervention strategy was formulated for all camps with reported ACL cases. This includes targeting of active cases with insecticide-treated nets, sold at a highly subsidised price.

Adolescent↗
PubMed2004

DEET mosquito repellent provides personal protection against malaria: a household randomized trial in an Afghan refugee camp in Pakistan.

Synthetic repellents based on di-ethyl 3-methyl benzamide (DEET) are a popular method of obtaining protection from mosquitoes and yet clear evidence for a protective effect against malaria has hitherto never been convincingly demonstrated. A household randomized trial was undertaken among a study population of 127 families (25%) in an Afghan refugee village in Pakistan to compare the efficacy of repellent soap (Mosbar containing 20% DEET and 0.5% permethrin) vs. a placebo lotion. Cases of falciparum and vivax malaria were detected by passive case detection at the camp's clinic. At the end of the 6 month trial 3.7% (23 of 618) of individuals in the Mosbar group had presented with one or more episodes of falciparum malaria compared with 8.9% (47 of 530) of the placebo group (odds ratio 0.44, 95% CI 0.25-0.76). 16.7% of the Mosbar group (103 of 618) presented with vivax malaria compared with 11.7% (62 of 530) of the placebo group, and thus no effect was shown against vivax malaria (odds ratio 1.29, 95% CI 0.86-1.94). A considerable proportion of individuals (22%) had presented with vivax malaria during the 7 months leading up to the trial and thus any intervention effect would be partially masked by relapsed infections. The distribution of mosquitoes among households was broadly similar between Mosbar and placebo groups. The repellent was popularly received and very few side-effects were reported. There is a case for giving repellents more prominence in public health as a preventive measure in regions where vectors bite in the early evening or in emergency situations such as epidemics or newly established refugee camps.

Adolescent↗
PubMedDate not supplied

The prolonged epidemic of anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: 'bringing down the neighbourhood'.

In order to investigate the distribution and causes of the spread of anthroponotic cutaneous leishmaniasis (ACL) in Kabul, Afghanistan, a cross-sectional study was conducted during 1997-98 amongst 75,787 residents in the 13 central districts of the city. Using data on active lesions and scars with their times of onset, migration patterns and age of subjects, 2 independent methods were used to estimate, retrospectively, the annual incidence of ACL in recent years. Results indicated a rapid increase in incidence from 1987, peaking in 1996 when an estimated 12% of the population had active disease. Active prevalence was lowest in infants (aged < 2 years), and while risk was gender-independent in children and adolescents, active prevalence in those aged > 20 years was significantly higher amongst females than males (odds ratio [OR] = 1.51, 95% CI 1.34-1.70). About 44% of lesions were located on the head, 38% on upper limbs, 16% on lower limbs and 2% elsewhere. The relative frequency of head lesions dropped with age (P < 0.001), and amongst adults was lowest amongst males (P < 0.001), possibly due to the protective effect of a beard. Within the study population, 32% reported that they had immigrated from outside Kabul, 34% that they had been born in Kabul but had since migrated to another district of the city, and 34% that they had been born in the district of their present residence. Active prevalence amongst those born in their current district of residence was positively associated with the percentage of immigrants in their district (P = 0.027), indicating that a 1% increase in the percentage of immigrants increased the odds of an active lesion by 12% (OR = 1.12, 95% CI 1.01-1.24), but there was no association with the percentage of migrants from other districts in Kabul (P = 0.65) or with war damage (P = 0.33). As active prevalence was not significantly greater in immigrants than local Kabulis, these results support the hypothesis that the epidemic in Kabul has been maintained by a steady influx of susceptible immigrants. It is important that the new opportunities for social development that now exist in Kabul are not hampered by this unpleasant and stigmatizing disease. As population movement is clearly a contributing factor to its transmission, this threat is very real.

Adolescent↗