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Biomedical subjects

P Aaby

Publications and source records attributed to P Aaby.

At least 91 records · Page 5Linked to original sources

9-year HIV-2-associated mortality in an urban community in Bissau, west Africa.

BACKGROUND: Community studies with 1-3 years of follow-up have reported four to five times higher mortality in HIV-2-infected than in uninfected adults. In a cohort study of HIV-1, an increasing difference in mortality rates of HIV-1-infected and uninfected individuals is expected over time, because of rising mortality with advancing HIV-1 infection. We therefore investigated long-term survival of HIV-2-infected adults. METHODS: Adults enrolled in 1987 in a community study of HIV-2 infection in Guinea-Bissau were followed up with serological surveys in 1989 and 1992. Survival was assessed in 1995, 9 years after enrollment. FINDINGS: The annual incidence of HIV-2 was 0.7% for adults and tended to be higher for older individuals than for participants aged 15-44 years (relative risk 3.21 [95% CI 0.91-11.37]). With control for age, HIV-2-infected adults had twice as high mortality as uninfected individuals (mortality ratio 2.32 [1.18-4.57]); the mortality ratio was highest in the first year of the study (4.50 [1.31-15.43]). The difference between infected and uninfected individuals was stronger for adults under 45 years of age (mortality ratio 4.72 [1.86-11.97]) than for older people (1.35 [0.51-3.56]). HIV-2-infected individuals living with an infected spouse had significantly higher mortality than HIV-2-infected individuals living with an uninfected spouse (p = 0.027). INTERPRETATION: HIV-2-associated mortality is not increasing with length of follow-up. Mortality in HIV-2-infected adults is only twice as high as that in uninfected individuals. In the majority of adults, HIV-2 has no effect on survival.

Acquired Immunodeficiency Syndrome↗

Population based study of rates of multiple pregnancies in Denmark, 1980-94.

OBJECTIVE: To study trends in multiple pregnancies not explained by changes in maternal age and parity patterns. DESIGN: Trends in population based figures for multiple pregnancies in Denmark studied from complete national records on parity history and vital status. POPULATION: 497,979 Danish women and 803,019 pregnancies, 1980-94. MAIN OUTCOME MEASURES: National rates of multiple pregnancies, infant mortality, and stillbirths controlled for maternal age and parity. Special emphasis on primiparous women > or = 30 years of age, who are most likely to undergo fertility treatment. RESULTS: The national incidence of multiple pregnancies increased 1.7-fold during 1980-94, the increase primarily in 1989-94 and almost exclusively in primiparous women aged > or = 30 years, for whom the adjusted population based twinning rate increased 2.7-fold and the triplet rate 9.1-fold. During 1989-94, the adjusted yearly increase in multiple pregnancies for these women was 19% (95% confidence interval 16% to 21%) and in dizygotic twin pregnancies 25% (21% to 28%). The proportion of multiple births among infant deaths in primiparous women > or = 30 years increased from 11.5% to 26.9% during the study period. The total infant mortality, however, did not increase for these women because of a simultaneous significant decrease in infant mortality among singletons. CONCLUSIONS: A relatively small group of women has drastically changed the overall national rates of multiple pregnancies. The introduction of new treatments to enhance fertility has probably caused these changes and has also affected the otherwise decreasing trend in infant mortality. Consequently, the resources, both economical and otherwise, associated with these treatments go well beyond those invested in specific fertility enhancing treatments.

Adult↗

Decline in measles case fatality ratio after the introduction of measles immunization in rural Senegal.

The epidemiology of measles has been investigated in Niakhar, a rural area of Senegal, during two periods, 1983-1986 and 1987-1990. Following a major increase in immunization coverage beginning in 1987, the case fatality ratio for all ages declined fourfold from the first to the second period (relative risk (RR) = 0.24, 95% confidence interval (CI) 0.13-0.46). The measles incidence for children under 10 years of age declined by 69% (95% CI 65-72) and the risk of dying of measles by 91% (95% CI 82-95). Vaccinated children who contracted measles had significantly lower case fatality ratio than unvaccinated children with measles (p = 0.038). Children infected by an immunized case tended to have lower case fatality ratio than those infected by an unimmunized index case (p = 0.104) and immunized index cases generated fewer secondary cases than unimmunized index cases (p < 0.001). Respiratory complications were more common in secondary cases infected by an index case with respiratory complications than by an index case without such complications (RR = 1.60, 95% CI 1.08-2.37), which suggests that severe cases give rise to further severe cases. As expected, there was a significant increase in the proportion of vaccinated cases in the second period (RR = 1.41, 95% CI 1.00-1.98). Mean age at infection increased from 4 to 7 years between the two periods and the change in age structure accounted for 20% of the decline in case fatality ratio. Measles immunization may contribute to lower mortality directly through reduced incidence and indirectly through increases in age at infection, less severe infection for immunized cases and changes in transmission patterns leading to reduced severity of measles.

Child↗

T-lymphocyte subsets in West African children: impact of age, sex, and season.

OBJECTIVE: There has been no reference material for T-lymphocyte subsets for normal children in developing countries. We therefore used T-lymphocyte subset determinations among children in three different studies in Guinea-Bissau to construct age-related reference material and to examine possible determinants of T-lymphocyte subset levels. METHODS: A total of 803 healthy West African children younger than 6 years were included in the three community studies of T-lymphocyte subsets among twins and singletons, after measles infection and after measles immunization. We used the immunoalkaline phosphatase method to determine T-lymphocyte subsets. RESULTS: We found differences by age, sex, and season, whereas there were no significant differences by birth order, twinning, or ethnic group. The CD4+ percentage declined from birth to age 2 years, at which time it started to increase to higher levels at age 4 to 5 years. The CD8+ percentage increased gradually from early infancy to age 2 to 4 years. The leukocyte count peaked at age 12 to 23 months and declined thereafter, whereas the lymphocyte percentage peaked at age 1 to 5 months and declined gradually thereafter. Compared with dry-season results, the lymphocyte percentage, the absolute lymphocyte count, the absolute CD4+ T-lymphocyte count, and the CD4+/CD8+ ratio were significantly lower during the rainy season, whereas the CD8+ percentage was increased during the rainy season. Girls had higher CD4+/CD8+ ratios and lower CD8+ percentages than did boys. CONCLUSIONS: Compared with the limited data on T-lymphocyte subsets available from healthy children in developed countries, Guinean children have markedly lower CD4+ percentages and CD4+/CD8+ ratios and higher lymphocyte percentages during the first 2 years of life, when the pressure of infections is particularly high in Africa.

Age Factors↗

Evaluation of T cell subsets by an immunocytochemical method compared to flow cytometry in four countries.

The authors tested an alternative method for CD4 and CD8 T lymphocytes enumeration, the immunoalkaline phosphatase method (IA), in three African countries and in Denmark. The IA determinations from 136 HIV antibody positive and 105 HIV antibody negative individuals were compared to the corresponding results obtained by flow cytometry (FC) performed in the respective countries. The authors found good correspondence between the two methods for measurements of CD4 and CD8 T lymphocytes independent of serological status and geographical site. However, the CD4 and CD8 T lymphocytes values obtained by the two methods are not interchangeable as IA compared to FC consistently gives higher percentage of CD4 T lymphocytes, and lower percentage of CD8 T lymphocytes. Mean differences between the two methods did not differ between the three African countries indicating that the IA method provides systematic results. Replicate measurements suggested good correspondence between results obtained by IA. By using an IA level of < 300 CD4 T lymphocytes/microliter, the sensitivity was 81% and specificity 96% for detecting an FC level of < 200 CD4 T lymphocytes/microliter. Using an IA level of < 20% CD4 T lymphocytes, the sensitivity was 89% and specificity 95% for detecting an FC level of < 14% CD4 T lymphocytes. The FC and IA methods had the same internal correspondence between low absolute CD4 T cell count and low CD4 percentages; the sensitivity and specificity for detecting a low absolute CD4 T cell counts with a low CD4 percentage was 92% and 68% for FC and 91% and 73% for IA, respectively. The IA method is 10-fold cheaper than FC, is independent of advanced laboratory facilities, and does not need immediate processing of samples as blood smears can be stored for long periods. The IA method is therefore suitable for use in areas with limited resources and laboratory facilities where there is a need for immunological surveillance in hospital or community studies.

Alkaline Phosphatase↗

Cryptosporidium infection in infancy as a cause of malnutrition: a community study from Guinea-Bissau, west Africa.

Cryptosporidium parvum causes persistent diarrhea in young children in developing countries. To determine the interaction between nutritional status and cryptosporidiosis, an open cohort of 1064 children younger than 3 y of age was followed for 1441 child-years by weekly diarrhea recall visits. A total of 5072 weight and 4264 height measurements was made. There were no tendencies of low weight (P = 0.38) or height (P = 0.16) in children who acquired cryptosporidiosis. Cryptosporidiosis in infancy was accompanied by an estimated weight loss of 392 g (95% CI: 247, 538 g) in boys and 294 g (95% CI: 109, 479 g) in girls, corresponding to 3.7% and 2.9% of mean weight, respectively, at 2 y of age. No significant catch-up growth covered for this loss in weight. A similar effect in linear growth was shown (P = 0.02). Although it has been suggested that the effect of infections on nutrition is usually transient because of catch-up growth, the present study suggests that cryptosporidiosis in infancy has a permanent effect on growth.

Africa, Western↗

Identification of an immunodominant neutralizing and protective epitope from measles virus fusion protein by using human sera from acute infection.

Polyclonal sera obtained from African children with acute measles were used to screen a panel of 15-mer overlapping peptides representing the sequence of measles virus (MV) fusion (F) protein. An immunodominant antigenic region from the F protein (p32; amino acids 388 to 402) was found to represent an amino acid sequence within the highly conserved cysteine-rich domain of the F protein of paramyxoviruses. Epitope mapping of this peptide indicated that the complete 15-amino-acid sequence was necessary for high-affinity interaction with anti-MV antibodies. Immunization of two strains of mice with the p32 peptide indicated that it was immunogenic and could induce antipeptide antibodies which cross-reacted with and neutralized MV infectivity in vitro. Moreover, passive transfer of antipeptide antibodies conferred significant protection against fatal rodent-adapted MV-induced encephalitis in susceptible mice. These results indicate that this epitope represents a candidate for inclusion in a future peptide vaccine for measles.

Amino Acid Sequence↗

High mortality despite good care-seeking behaviour: a community study of childhood deaths in Guinea-Bissau.

The care-seeking behaviour of mothers of 125 children deceased aged 1-30 months was investigated by verbal autopsy in an urban area of Guinea-Bissau. A total of 93% of the children were seen at a health centre or hospital during the 2 weeks before death. In a previous survey covering the period 1987-90 we found that 78% of the children who died had presented for consultation (8); despite this increase in care seeking, infant mortality had not decreased. Comparison of elapsed time from disease onset to first consultation between children who died and matched surviving controls indicated that the interval was shorter for children who died than for those who survived (odds ratio (OR) = 0.7; 95% confidence interval (CI): 0.5-0.99). Of the 125 terminally ill children, 56 were hospitalized. A total of 20 children died on the way to hospital or while waiting in the outpatient clinic. Lack of hospital beds resulted in 15 mothers being refused hospitalization for their child. Of hospitalized children, 42% were discharged as improved or recovered during the 30 days preceding death. These results reveal a need for improved hospital admission criteria, improved recognition of the symptoms of serious illness, better discharge criteria, and the implementation of quality assurance systems for health services.

Case-Control Studies↗

Serial CD4 and CD8 T-lymphocyte counts and associated mortality in an HIV-2-infected population in Guinea-Bissau.

In an urban community in Guinea-Bissau, we followed a cohort of human immunodeficiency virus type 2 (HIV-2) seropositive individuals (N = 47) and seronegative controls (N = 82). T-lymphocyte subset determinations were done in 1988, 1990, and 1992. Serial determinations of CD4 percentages, CD8 percentages, and CD4/CD8 ratios for the same individual were stable for 31 seropositive and 51 seronegative individuals with repeated measurements. We found no significant differences in the changes during a 2- or 4-year period in CD4 percentages, CD8 percentages, absolute CD8 T-lymphocyte counts, CD4/CD8 ratio, white blood cell counts, lymphocyte percentages, and absolute lymphocyte counts for HIV-2-seropositive compared with HIV-2-seronegative individuals. Only absolute CD4 T-lymphocyte counts changed more for the HIV-2-seropositive than for HIV-2-seronegative individuals (p = 0.037). HIV-2-infected individuals who lived with an HIV-2-infected spouse had a lower CD4/CD8 ratio and had higher mortality than HIV-2 infected individuals who lived with an uninfected spouse. However, there were no significant differences in immunological and hematological values for the 8 HIV-2 seropositive individuals who died and the 39 who survived in the 8-year follow-up period. In conclusion, progression of immunosuppression in HIV-2 infection seems to be slower than in HIV-1 infection and may not be inevitable in all individuals.

Adult↗

Cell mediated immunity after measles in Guinea-Bissau: historical cohort study.

OBJECTIVE: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles. DESIGN: Historical cohort study. SETTING: Bissau, Guinea-Bissau. SUBJECTS: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles. MAIN OUTCOME MEASURES: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens. RESULTS: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the case of measles. CONCLUSION: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.

Adolescent↗

Measles and atopy in Guinea-Bissau.

BACKGROUND: Epidemiological studies have led to speculation that infections in early childhood may prevent allergic sensitisation but evidence to support this hypothesis is lacking. We investigated whether measles infection protects against the development of atopy in children of Guinea-Bissau, West Africa. METHODS: We conducted a historical cohort study in Bandim, a semi-rural district of Bissau, the capital of Guinea-Bissau. 395 young adults, first surveyed in 1978-80 aged 0-6 years, were followed up in 1994. Our analyses were restricted to 262 individuals still living in Bandim for whom a measles history, documented in childhood, was judged to be reliable. We defined atopy as skin-prick test positivity (> or = 3 mm weal) to one or more of seven allergens. FINDINGS: 17 (12.8 percent) of 133 participants who had had measles infection were atopic compared with 33 (25.6 percent) of 129 of those who had been vaccinated and not had measles (odds ratio, adjusted for potential confounding variables 0.36 [95 percent CI 0.17-0.78], p=O.O1). Participants who had been breastfed for more than a year were less likely to have a positive skin test to housedust mite. After adjustment for breastfeeding and other variables, measles infection was associated with a large reduction in the risk of skin-prick test positivity to housedust mite (odds ratio for Dermatophagoides pteronyssinus 0.20 [0.05-0.81], p=0.02; D farinae 0.20 [0.06-0.71], p=0.01). INTERPRETATION: Measles infection may prevent the development of atopy in African children.

Allergens↗

No long-term excess mortality after measles infection: a community study from Senegal.

Because measles immunization has been found in all studies to reduce mortality with more than the share of deaths attributed to acute measles, the authors examined mortality after measles infection in a study in a rural area of Senegal that included 6,924 unimmunized children, whom 1,118 developed measles. Age-adjusted post-measles mortality was similar to the mortality of unvaccinated, uninfected children (mortality ratio (MR) = 1.04, 95% confidence interval (CI) 0.80-1.35). When controlling for source of infection, mortality rate was significantly different for children who contracted measles from a person outside the home (index cases vs. unvaccinated, uninfected MR = 0.27, 95% CI 0.09-0.85) and for children infected at home (secondary cases vs. unvaccinated, uninfected MR = 1.10, 95% CI 0.80-1.51). Hence, secondary cases had markedly higher long-term mortality than did index cases (MR = 4.13, 95% CI 1.26-13.58). These estimates were essentially unchanged when the effects of season, period, separation from mother, size of community, and size of compound were investigated using a multivariate Cox regression model. The authors conclude that measles infection was not associated with increased mortality after the acute phase of infection and that index cases had lower mortality than uninfected, unvaccinated children. The reduction in mortality after measles immunization can therefore not be explained by the prevention of post-measles mortality.

Age Factors↗

T-lymphocyte subsets and prolonged diarrhea in young children from Guinea-Bissau.

In a community-based prospective study of 380 children conducted between 1987 and 1990, the rate of diarrhea was significantly associated with percentage of CD8 T-lymphocytes and the CD4:CD8 ratio. After adjustment for age and previous diarrhea, the relative incidence of diarrhea with a duration of > or = 7 days was 2.10 (95% confidence interval (CI) 1.15-3.85) in children with 20-29.9% CD8 T-cells and 3.41 (95% CI 1.29-9.01) in children with > or = 30% CD8 T-cells (in comparison with children who had less than 20% CD8 cells) (p for trend = 0.004). There was a nonsignificant tendency for rates of diarrhea of > or = 7 days to decrease according to increasing proportions of CD4 cells (p = 0.194). The authors found no significant association between T-cell subsets and diarrhea which resolved within 6 days. The association between the incidence of prolonged diarrhea and T-cell subset proportions could not be explained as a confounding effect of low weight, breastfeeding, or previous infection with measles or Cryptosporidium. However, other prior infections or micronutrient deficiencies may explain the findings, and these host factors may be significant targets in intervention against diarrheal diseases.

CD4 Lymphocyte Count↗

Five year follow-up of morbidity and mortality among recipients of high-titre measles vaccines in Senegal.

At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.

Female↗

Nutritional status and delayed mortality following early exposure to measles.

Community studies in Guinea-Bissau have found that exposure to measles prior to 6 months of age is associated with delayed mortality later in childhood. In an attempt to understand the underlying mechanism, we examined the role of pre-exposure nutritional status and the impact of exposure to measles on growth and subsequent mortality in these outbreaks. Though exposed children were lighter than controls, there was no association between pre-exposure weight-for-age and subsequent mortality adjusting for age. Although exposure was strongly associated with excess mortality, it did not have a negative impact on growth. Adjustment for state of nutrition did not alter the mortality ratio (MR) between 6 and 59 months of age for exposed children and controls; exposed children examined anthropometrically between 6-17 months had a MR of 3.70 compared with controls. This trend was the same for anthropometric measurements obtained at 18-59 months of age. Among the controls, there was a significant association between weight-for-age and subsequent mortality to the age of 5 years. However, for exposed children there was no association; the relation between weight-for-age and subsequent mortality was significantly different for exposed children compared with controls (tests for interaction between exposure and anthropometric measurements at 6-17 months: P = 0.05). Growth faltering as a consequence of early exposure to measles does not explain the marked excess mortality among these children. Further studies of the process underlying delayed mortality after early exposure to measles are warranted.

Anthropometry↗

Reason for termination of breastfeeding and the length of breastfeeding.

BACKGROUND: In third world countries the length of breastfeeding often has a major influence on child mortality, morbidity and nutritional status. When evaluating the impact of length of breastfeeding the reason why a mother terminates breastfeeding is usually not taken into consideration. METHODS: Risk factors for termination of breastfeeding were studied in a prospective community study following 1678 children in Guinea Bissau, West Africa from birth to cessation of breastfeeding, migration or death. RESULTS: The median weaning age was 22.6 months. Illness of the child, new pregnancy of the mother and illness of the mother were associated with significantly shorter lactation period compared with children weaned because they were 'healthy' or 'old enough'. These explanations had an impact independent of other determinants for weaning, including ethnic group, mother's age, mother's education, birth order and number of dead siblings. Weaning before 12 months of age was only associated with illness of the mother or child and new pregnancy and not with any socioeconomic or cultural factors. CONCLUSIONS: Health workers should pay special attention to the encouragement of breastfeeding in connection with illness of the mother or child; these considerations may also be important in the planning of breastfeeding promotion campaigns. Since premature termination of breastfeeding is associated with new pregnancy, family planning should be part of any breastfeeding promotion programme.

Adolescent↗