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Biomedical subjects

P Aaby

Publications and source records attributed to P Aaby.

At least 19 recordsLinked to original sources

Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country.

OBJECTIVE: To compare detection of respiratory syncytial virus (RSV) for diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in different clinical settings in a community study in Guinea-Bissau. METHOD: During 1996-98 paired specimens were obtained from 635 children under 5 years of age (median: 274 days; interquartile range: 144-453 days) with symptoms of lower respiratory infections (LRI). The specimens were analysed by an enzyme-linked immunosorbent assay for RSV antigen in Guinea-Bissau and re-analysed in Denmark using the same assay. The gold standard for RSV antigen detection was defined as any test being positive. RESULTS: RSV antigen was detected in 84 (13%) children, the prevalence being 19% (41/219) among infants aged < 6 months, 12% (22/184) in infants aged 6-11 months, and 9% (21/230) in older children. Sensitivity of antigen detection was higher in NPA (92% in analyses in Guinea-Bissau and 98% in Denmark) than in NS (63% in analyses in Guinea-Bissau, 71% in Denmark). Specificity of RSV antigen detection was equally high in NPA and NS (99-100%). Time since onset of symptoms was significantly shorter in RSV antigen positive than negative samples. Sensitivity did not depend on clinical setting or age of the child. CONCLUSION: Using NS samples was associated with a 27-31% reduction in sensitivity compared with NPA specimens. As NPAs are costly and considered a nuisance by the population, it might be cost-effective in larger epidemiological studies to lose 25-30% in sensitivity but be able to collect samples from a much larger population.

Antigens, Viral↗

A household study of chickenpox in Guinea-Bissau: intensity of exposure is a determinant of severity.

OBJECTIVE: To determinate the relative importance of state of nutrition and intensity of exposure for clinical severity of chickenpox in a developing country. METHODS: A prospective household study was performed in a semi-urban area in Bissau, the capital of Guinea-Bissau, between December 1994 and June 1995. Antibodies were measured in the acute and the convalescence phase to assess validity of clinical diagnoses. The clinical severity of infection was assessed by number of pox, fever response and skin infections. Severity was compared for index cases, i.e. the first case in the house, and secondary and tertiary cases infected following exposure at home. RESULT: Chickenpox was diagnosed in 165 persons. The clinician's and the mothers' diagnoses corresponded well with the serological results. Median age was 36 months (range 3 months to 30.3 years). There was no correlation between nutritional status measured by arm-circumference and severity of infection. The number of pox was higher for secondary cases than for index cases (median 106 vs. 89, P<0.01), the difference being more pronounced for girls (P=0.018) than for boys (P=0.575). The risk of skin infection as a complication was correlated with the number of pox (P<0.001). CONCLUSION: Chickenpox was recognised correctly by Guinean mothers. The age distribution in Guinea-Bissau resembled the pattern in developed countries. The intensity of exposure was a major determinant of severity, especially for girls.

Adolescent↗

Thymus size at birth is associated with infant mortality: a community study from Guinea-Bissau.

UNLABELLED: A few studies have suggested that thymus atrophy is associated with severe malnutrition and increased morbidity; however, no study of thymus size has been undertaken in countries with high mortality. This study examined the relation between thymus size at birth and subsequent mortality in an urban West African community. The size of the thymus was assessed by sonography as a volume estimate, the thymus index. A total of 278 children born at the local health centre in Bandim in Bissau, Guinea-Bissau, was enrolled in the study. Children were followed to the age of 2 y. Thymus size at birth was associated with most strongly weight, as well as with length and arm circumference. Controlling for weight and other risk factors, boys had larger thymus indices than girls [means ratio (MR) = 1.07, 95% confidence interval (95% CI) 1.01-1.14)]. Thymus size was also associated with prematurity, ethnic group, season and investigator, but not with birth order, mother's age, socioeconomic factors or the use of health services. Infant mortality was 117/1000. In a multivariate analysis, excluding premature infants and adjusting for age, gender, ethnic group, season of birth and investigator, higher birthweight (MR = 0.35, 95% CI 0.16-0.74) and larger thymus size (MR = 0.17, 95% CI 0.06-0.48) were independently associated with lower infant mortality. When both indices were estimated in the same model, the thymus index was associated with infant mortality (MR = 0.27, 95% CI 0.07-1.00), whereas birthweight had a non-significant effect (MR = 0.59, 95% CI 0.24-1.47). After 1 y of age neither birthweight nor thymus size at birth was associated with mortality. CONCLUSION: As all deaths were due to infectious diseases, thymus size at birth may be an important predictor of immune competence. Future studies should examine the determinants of thymus growth.

Analysis of Variance↗

Factors associated with maternal mortality in rural Guinea-Bissau. A longitudinal population-based study.

OBJECTIVE: To assess demographic and obstetric risk factors for pregnancy-related death in a multiethnic rural population in a developing country. DESIGN: A prospective survey of women in the fertile age-range. SETTING: Rural Guinea-Bissau. POPULATION: More than 15,000 women living in 100 clusters were visited at six-monthly intervals over a period of more than six years. A total of 10,931 pregnancies were registered prospectively; 85 of these pregnancies resulted in maternal or late maternal death. MAIN OUTCOME MEASURE: Maternal mortality ratio. METHOD: In the rural areas of Guinea-Bissau, we conducted a prospective survey of women in the fertile age range. More than 15,000 women living in 100 clusters were visited at 6-monthly intervals over a period of more than six years. An analysis of demographic, environmental and obstetric risk factors for maternal death was performed based on 10,931 prospectively registered pregnancies; 85 of these pregnancies resulted in maternal or late maternal death. RESULTS: In the adjusted model maternal mortality ratio increased with increasing distance from the regional hospital (OR>25 km = 7.4 [95% CI: 1.6-132]). Multiple pregnancy was found to increase the risk of maternal death (OR = 3.4 [95% CI: 1.3-7.5]). The risk of subsequent maternal death was increased if the fetus was stillborn (OR = 5.3 [95% CI: 2.8-9.4]). Women living in the region of Gabu had higher mortality than those living in Biombo (OR = 2.5 [95% CI: 1.3-5.1]). No category of age or parity were associated with an increased risk of maternal mortality. Predictive values did not exceed 3% for any of the significant risk factors. CONCLUSIONS: For the purpose of reducing maternal mortality, the screening approach of antenatal care is of limited value. Age and parity should not be used routinely as selection criteria for transfer of otherwise healthy pregnant women to higher-level health institutions. Twin pregnancy seems to be the only operational risk factor identified in this study. Stillbirth is associated with an increased risk of maternal death. Regional differences must be studied further. The distance to emergency obstetric care (EOC) may determine the outcome of a complicated delivery.

Adult↗

The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau.

OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based on suspicion of active tuberculosis and in 101 individuals after 8 months of follow-up. RESULTS: The suPAR levels were elevated in patients with active TB compared to TB-negative individuals (P < 0.001). suPAR levels were highest in patients positive for TB on direct microscopy (n = 84, median suPAR 3.17 ng/ml, P < 0.001), followed by patients negative on direct microscopy but culture positive (n = 35, median suPAR 2.41 ng/ml, P = 0.005) and by patients diagnosed on clinical grounds (n = 63, median suPAR 2.13 ng/ml, P = 0.06) compared to 64 TB-negative individuals (median suPAR 1.73 ng/ml). During the 8-month treatment period, 23 TB cases died. In a multivariate Cox model controlling for HIV status, age, sex, CD4 count and type of TB diagnosis, the mortality increase per ng suPAR was 1.25 (95%CI 1.12-1.40). After treatment, suPAR levels had decreased to the levels of TB-negative individuals. CONCLUSIONS: suPAR levels are elevated in TB patients and associated with mortality. Furthermore, suPAR may be a potential marker of treatment efficacy.

Adult↗

The frailty hypothesis revisited: mainly weak children die of measles.

It has been suggested that measles infection mainly kills frail children who are likely to die anyhow of other infections. If that were true, the proportion of frail children should increase after the introduction of measles vaccination and post-measles mortality compared with mortality in uninfected children should increase when the case fatality declines and frail children are no longer dying of measles. The latter deduction was investigated in Niakhar, Senegal, where the measles case fatality has declined markedly. Measles has been studied in Niakhar during 12 years from 1983 to 1994. We compared long-term mortality after measles infection in periods with both high and low case fatality. The acute measles case fatality rate (CFR) declined from 6.5% in 1983-1986 to 1.5% in 1987-1994, an age-adjusted decline of 66% (RR=0.34 (0.19-0.58)). Between 1983-1986 and 1987-1994, mortality in the first year after measles infection declined by 35% (RR=0.65 (0.37-1.16)), the pattern being the same in the second and third year after infection (RR=0.63 (0.33-1.21)). This reduction could not be related to introduction of immunization, treatment of measles with Vitamin A, or prophylactic use of antibiotics. Controlling for age, immunization, and season, the decline in post-measles mortality was similar to the fall in non-measles-related mortality between the two periods (mortality rate ratio=0.72 (0.64-0.80)). Since the mortality decline in survivors of measles was as large as the decline in mortality among uninfected children, reduction in acute measles mortality did not lead to accumulation of frail children. We doubt measles infection ever eliminated mainly weak children; it always killed a broad spectrum of children, most of whom were "fit to survive". Hence, it seems unlikely that measles vaccination has contributed to the survival of more frail children.

Child↗

HIV-2 does not protect against HIV-1 infection in a rural community in Guinea-Bissau.

OBJECTIVE: To examine the putative protective effect of HIV-2 infection against subsequent HIV-1 infection. DESIGN: Retrospective analysis of data from two cross-sectional surveys in the same community. METHODS: Two surveys between 1989 and 1998 in a rural area in northwestern Guinea-Bissau provided data from residents aged 15-59 years. HIV testing was done in the first survey. In the second survey, tests were made for both HIV and syphilis, and data on sociodemographic factors and sexual behaviour, including commercial sex work, were gathered. Qualitative polymerase chain reaction amplification of HIV-1 and HIV-2 viral DNA was performed on serologically dually reactive samples. RESULTS: Of the 2276 eligible adult villagers initially tested, 60% (1360) provided a second sample. Of 110 HIV-2-infected subjects, 17 became additionally infected with HIV-1 [incidence rate (IR), 26.3/1000 person-years observation]. Of the 1250 HIV-seronegative subjects, 24 became infected with HIV-1 (IR, 2.8/1000 person-years observation). The incidence rate ratio (IRR), comparing the incidence rate in HIV-2-infected people with the rate in HIV-seronegative subjects, was > 1 in all three "risk groups": men, female commercial sex workers, and other women. The overall estimate of the IRR, adjusted for age group and risk group, was 3.24 (confidence interval, 1.5-7.1). CONCLUSIONS: There was no protective effect of HIV-2 in this population. HIV-2 cannot be regarded as a vaccine, but, instead, may be a risk factor for HIV-1 infection.

Adolescent↗

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.

BCG Vaccine↗

Tuberculosis mortality during a civil war in Guinea-Bissau.

CONTEXT: Tuberculosis (TB) is an increasing global problem, despite effective drug therapies. Access to TB therapy during conflict situations has not been studied. OBJECTIVE: To determine the effect of irregular TB treatment due to an armed conflict in Guinea-Bissau, West Africa. DESIGN, SETTING, AND PATIENTS: Ongoing retrospective cohort study conducted in the capital city of Bissau among 101 patients with TB who received irregular or no treatment during the civil war (war cohort; June 7-December 6, 1998) and 108 patients with TB who received treatment 12 months earlier (peace cohort; June 7-December 6, 1997) and comparison of an additional 42 patients who had completed treatment before June 6, 1998, and 69 patients who had completed treatment before June 6, 1997. MAIN OUTCOME MEASURE: Mortality rates, compared by irregular (war cohort) vs regular (peace cohort) access to treatment, by intensive vs continuation phase of treatment, and by those who had previously completed treatment for TB. RESULTS: Irregular treatment was associated with an increased mortality rate among patients with TB. The mortality rate ratio (MR) was 3.12 (95% confidence interval [CI], 1.20-8.12) in the war cohort, adjusting for age, sex, human immunodeficiency virus (HIV) infection, residence, and length of treatment. Each additional week of treatment before the war started increased probability of survival by 5% (95% CI, 0%-10%). In the intensive phase of treatment, the adjusted MR was 3.30 (95% CI, 1.04-10.50) and in the continuation phase it was 2.26 (95% CI, 0.33-15.34). Increased mortality among the war cohort was most marked in HIV-positive patients, who had an adjusted MR of 8.19 (95% CI, 1.62-41.25). Mortality was not increased in HIV-positive or HIV-negative patients who had completed TB treatment when the war started. CONCLUSIONS: Interruption of treatment had a profound impact on mortality among patients with TB during the war in Guinea-Bissau. Regular treatment for TB was associated with significantly improved survival for HIV-infected individuals. In emergencies, it is crucial to ensure availability of TB drugs.

Adult↗

Cancer risk in a cohort of polio patients.

Poliomyelitis has hypothetically been associated with an increased risk of central nervous system (CNS) tumors. The present study was performed to examine not only the risk of CNS tumors but also the overall risk of cancer among a cohort of 5,883 polio patients. Patients diagnosed with acute poliomyelitis in the Danish capital, Copenhagen, between 1919 and 1954 were identified and followed with respect to cancer. Information on vital status and cancer diagnoses was obtained through linkage with the Danish Civil Registration System and the Danish Cancer Registry, respectively. The ratio of observed number of cancers to the number expected from population-based incidence rates, i.e., the standardized incidence ratio (SIR), served as measure of the relative cancer risk. Overall, 717 cases of cancer were observed among 5,883 polio patients during 249,084 person-years of follow-up vs. an expected number of 645 (SIR = 1.11 [95% confidence interval 1.03 to 1.20])). The increased risk was restricted to female polio patients (SIR = 1.18 [1.07 to 1.30]), among whom the risk was particularly high for breast cancer (SIR = 1.35 [1.12 to 1.61]) and for skin cancer (SIR = 1.66 [1.32 to 2.07]). The risk of breast cancer was highest among women with a history of paralytic polio (SIR = 1.62 [1.24 to 2.10]). The observed number of CNS tumors did not exceed the expected (SIR = 1.09 [0.72 to 1.60]). Women diagnosed with poliomyelitis, in particular paralytic polio, may be at increased risk of breast cancer. There was no association between malignancies of the CNS and poliomyelitis.

Age Factors↗

Measles antibody responses after early two dose trials in Guinea-Bissau with Edmonston-Zagreb and Schwarz standard-titre measles vaccine: better antibody increase from booster dose of the Edmonston-Zagreb vaccine.

In Guinea-Bissau, children were randomised at 6 months of age to receive either two doses of standard-titre measles vaccine at 6 and 9 months of age or an inactivated polio vaccine at 6 months and standard-titre measles vaccine at 9 months of age. During the first 5 months, children received Edmonston-Zagreb (EZ) vaccine and during the following 11 months, the Schwarz (SW) vaccine. Five percent of the mothers, 74% of children at 6 months of age, and 92% of unvaccinated children at 9 months of age had unprotective levels (<125 mIU/ml) of measles antibodies. Among children receiving EZ vaccine, 1% were unprotected at 18 months of age after either two (3/240) or one (3/211) doses of vaccine, the geometric mean measles antibody titre (GMT) being approximately 1550 mIU/ml in both groups. Among those receiving SW vaccine 9% (34/365) and 3% (9/310) were unprotected at 18 months of age in the two-dose and the one-dose groups (RR = 3.21 (95% confidence interval (CI) 1.56-6.58)), respectively. The GMT was higher after one dose of SW vaccine at 9 months of age (2491 mIU/ml) than after two doses of SW vaccine (1125 mIU) (P < 0.001). In the EZ vaccine group, there was no significant difference in antibody level for children vaccinated in the presence of high or low levels of maternal antibodies, whereas there was a marked difference in the SW group. The second EZ vaccine induced a significant antibody increase between 9 months of age (1191 mIU) and 18 months of age (1602 mIU, P=0.011), whereas antibody levels tended to decline from 9 months (1243 mIU) to 18 months of age (998 mIU, P = 0.124) after the second dose of SW vaccine. Conclusively, after two doses of EZ measles vaccine more children were protected at 18 months of age than after two doses of SW. One dose of SW provided the highest antibody response, but a higher proportion of unprotected than one or two doses of EZ. The EZ vaccine was less sensitive to maternal antibodies, and able to increase the antibody response by revaccination, while the second SW vaccine resulted in an unchanged or lower antibody response.

Age Factors↗

Thymus size and head circumference at birth and the development of allergic diseases.

BACKGROUND: The positive association between a large head circumference at birth and total serum IgE levels has been suggested to be due to negative associations between head circumference at birth and thymus development and between thymus development and total serum IgE levels. OBJECTIVES: To examine the associations between head circumference and thymus size at birth and the development of allergic disease. METHODS: The size of the thymus was assessed by sonography during the first week of life in 149 healthy term infants. Information on birth characteristics and mode of delivery was collected at delivery. The presence of allergic disease was assessed 5 years later by mailed questionnaires, which were returned by 85% of the eligible families. RESULTS: At birth, head circumference was positively associated with thymus size (P < 0.001). In all, 27 (23%) of the children had developed at least one allergic disease. Multivariate analysis revealed that both parental allergy (Prevalence Ratio and 95% CI) = 3.18 (1.49-6.78)) and caesarean delivery (2.62 (1.48-4.64)) were independently correlated with allergic disease, whereas thymus size was not. CONCLUSIONS: Our study does not support that a large head circumference is associated with a small thymus size, nor that a small thymus size is associated with allergic disease. Whether thymus size at birth is related to total serum IgE levels still remains to be elucidated.

Birth Weight↗

Intensity of exposure and severity of whooping cough.

OBJECTIVE: To study the association between intensity of exposure and mortality due to pertussis. METHODS: Overall 3233 historical records from the main fever hospital in Copenhagen were examined. Exposure status of the whooping cough cases was coded as primary, secondary or multiple cases according to information in the hospital records. Primary cases, infected outside the home, were presumably exposed less intensively to the infectious agent compared to secondary cases, who were infected in the family. Multiple cases were from families with several simultaneous cases, but no clear information on transmission between cases. RESULTS: Case fatality was strongly related to age, being highest among the infants. Other risk factors were sibship size, exposure status and calendar period. In a multivariate analysis, period, age, and exposure status remained significant. Compared to primary cases, secondary cases and multiple cases had a 2.8 [RR = 2.76 (1.37 - 5.56)] and a two-fold [(RR = 1.99 (1.33 - 2.96)] higher risk of dying. CONCLUSION: Intensity of exposure may be a major determinant of the severity of pertussis infection.

Adolescent↗

Intensive exposure as a risk factor for severe polio: a study of multiple family cases.

To examine the importance of intensity of exposure for the outcome of the poliomyelitis infection 429 polio cases were identified belonging to families with 2, 3 or 4 polio cases, all hospitalized in Copenhagen from 1919 to 1953. Furthermore, 87 pairs of polio cases living on the same stairway, but not in the same household, were identified. Severity among multiple cases in families analysed according to time of appearance showed a U-shaped curve. Initial cases had a higher risk of developing paralysis [relative risk (RR) = 1.5, 95% confidence interval (CI) 1.2-1.91 and of dying (RR = 2.5, 95% CI 0.9-6.9). Decreased severity was observed among subsequent cases appearing within 11 d after the initial case (RR = 1.0); however, severity increased again, with higher mortality for cases likely to have been infected by the initial case (cases appearing more than 11 d later) (RR = 5.7, 95% CI 1.8-17.8). The pattern described among multiple family cases was not found among cases from the same stairway. Since family cases appearing within 11 d were probably infected simultaneously, a short incubation period is associated with severe disease and a prolonged incubation period with milder infections. Furthermore, intensive exposure from being infected in the household increased severity. These observations therefore suggest that intensity of exposure and dose of infection are important factors in the severity of poliomyelitis.

Denmark↗

Seven years' experience with Cryptosporidium parvum in Guinea-Bissau, West Africa.

In community-based studies conducted from 1991 to 1997 in Guinea-Bissau, West Africa, stool specimens from children aged less than 5 years with diarrhoea were routinely examined for enteric parasites. Cryptosporidium parvum, found in 7.7% of 4,922 samples, was the second most common parasite, exceeded only by Giardia lamblia which was found in 14.8% of the samples. The highest prevalence of cryptosporidium was found in children aged 6-11 months, whereas the prevalence of other enteric parasites increased with age. Cryptosporidiosis showed a marked seasonal variation, with peak prevalences found consistently at the beginning of or just before the rainy seasons, May through July. By contrast, no seasonality was found for the enteric parasites Giardia lamblia or Entamoeba histolytica. We conclude that Cryptosporidium parvum is an important pathogen in children with diarrhoea.

Age Factors↗