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Biomedical subjects

P Aaby

Publications and source records attributed to P Aaby.

At least 73 records · Page 4Linked to original sources

Increased long term mortality associated with rash after early measles vaccination in rural Senegal.

OBJECTIVES: To examine whether clinical symptoms, including rash, were more common after measles immunization compared with placebo and to study the association between postvaccination symptoms and later mortality. DESIGN: Examination of side effects in the 3 weeks after immunization in a trial of high titer and standard titer measles vaccines. PATIENTS: Two hundred twenty-four children randomly selected to be included in the surveillance for diarrhea, fever and rash. RESULTS: There was no difference in fever and diarrhea between recipients of high titer vaccines and recipients of placebo. However, high titer recipients tended to have more measles-like rashes than placebo recipients [relative risk, 2.12 (range, 0.90 to 5.03)]. Among recipients of high titer vaccines, children who presented a rash had higher mortality in the following 5 to 7 years than those who did not develop rash [mortality rate ratio, 3.85 (range, 1.52 to 9.79)]. High titer recipients without a rash had the same mortality as children in the placebo group who were given standard doses of measles vaccine at 10 months of age [mortality rate, 0.76 (range, 0.35 to 1.62)]. CONCLUSIONS: These observations suggest that in this particular study, rash after high titer measles vaccine may identify children who received a particularly high dose of vaccine or children with more severe and persistent postvaccination immunosuppression. Whether high titer vaccine is more likely than standard titer measles vaccine to provoke such reaction is not known, given that we did not compare side effects after different titers of measles vaccine. Future trials of live measles vaccine should monitor the development of rash.

Cause of Death↗

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Antibodies, Viral↗

Community-based randomized controlled trial of reduced osmolarity oral rehydration solution in acute childhood diarrhea.

OBJECTIVE: The standard oral rehydration solution (ORS) recommended by WHO and UNICEF does not reduce the volume or frequency of stools or the length of the episode. Hospital-based studies from developing and developed countries and intestinal perfusion studies suggest a beneficial effect on water and sodium absorption with reduced osmolarity ORS as compared with standard ORS. We conducted a community-based study comparing the efficacy of reduced osmolarity ORS (224 mmol/l) with standard ORS (311 mmol/l) in acute childhood diarrhea in a West African community. METHODS: Infants and toddlers age 0 to 30 months having 738 episodes of diarrhea identified by weekly household visits were randomly assigned to treatment with either standard ORS (n = 376) or reduced osmolarity ORS (n = 362). The children were followed by daily home visits to assess ORS intake and clinical characteristics. Duration of diarrhea was compared by proportional hazards regression analysis, the hazard ratio being interpreted as the relative recovery rate between the children receiving the two types of ORS. Because earlier reports have suggested that weaning status might be an important modifier for the performance of reduced osmolarity ORS, the effect was assessed overall and as an interaction between type of ORS and weaning status and age. Maternal satisfaction was assessed in a paired analysis among mothers whose children participated at least twice in the study. RESULTS: In the overall analysis reduced osmolarity ORS was as efficacious as standard ORS as assessed by duration of diarrheal episode and total number of stool evacuations on Days 1 and 2. Non-breast-fed toddlers (i.e. children ages 12 to 30 months) treated with reduced osmolarity ORS had significantly shorter diarrheal episodes [1.14 days vs. 1.78 days with standard ORS; hazard ratio, 1.50; 95% confidence interval (CI), 1.07 to 2.09] and lower total number of stool evacuations on Days 1 and 2 (3.9 stool evacuations vs. 5.0 stool evacuations with standard ORS; ratio of geometric means, 0.77; 95% CI 0.60 to 1.01). No significant difference was found for breast-fed toddlers or for infants. There was no statistically significant difference in the ORS intake between the two treatment groups. The odds ratio for the mother preferring reduced osmolarity ORS to standard ORS was 1.92 (95% CI 0.97 to 3.85). CONCLUSIONS: Reduced osmolarity ORS was as efficacious as standard ORS. Non-breast-fed children treated with reduced osmolarity ORS had significantly shorter diarrheal episodes and a tendency toward lower stool frequency. These findings may be of importance, especially in developing countries where early weaning is common.

Acute Disease↗

Management of childhood diarrhea and use of oral rehydration salts in a suburban West African community.

In a household survey in Guinea-Bissau, 319 episodes of diarrhea in children were followed by interviews every second day with the aim of investigating perceived morbidity and subsequent actions taken. The majority of the mothers had good knowledge of oral rehydration salts (ORS). However, only 58% of the episodes were treated with ORS and the amount given was insufficient. Mothers with no knowledge of ORS did not use it during the observed attack of diarrhea regardless of contact with a health center, which suggests that maternal knowledge is an important determinant of whether health personnel provide ORS. Children with diarrhea considered to be caused by teething were less likely to receive ORS in the acute phase (risk ratio = 0.6, 95% confidence interval [CI] = 0.5-0.9). Univariate analyses showed that the use of ORS was related to number of reported symptoms, the mother being the care taker, consultations, previous use of ORS, good knowledge of ORS, and having ORS sachets at home. Multivariate Cox regression analyses showed that the presence of ORS sachets at home at the onset of diarrhea was the strongest predictor of use (hazard ratio = 3.3, 95% CI = 1.9-3.6). Improved health education should focus more on the quantity of ORS needed, early signs of dehydration, treatment of teething diarrhea, and breast feeding, and address mothers who have no prior knowledge of ORS. Management of diarrhea may be improved by a more liberal distribution of ORS sachets.

Administration, Oral↗

Malaria parasitemia and childhood diarrhea in a peri-urban area of Guinea-Bissau.

To examine the association between diarrhea in early childhood and malaria parasitemia, we conducted a nested case-control study in Guinea-Bissau of 297 children with diarrhea and a similar number of children without diarrhea matched for age, season, and residential area. There were no associations between diarrhea and parasite rate, parasite density, or clinical malaria. However, anti-malarials were easily available and frequently used, which was reflected by a 0.7% prevalence of children with a parasite density > 100/200 leukocytes. Thus, the findings do not preclude that diarrhea may be a sign of clinical malaria or high-parasite density in endemic areas with lower use of antimalarials.

Animals↗

[Multiple pregnancies in Denmark 1980-1994].

The objective was to study trends in national rates of multiple pregnancies that were not explained by changes in maternal age and parity. Information on childbirths to Danish-born women were obtained from national registers. The national incidence of multiple pregnancies increased 1.7-fold during 1980-1994, the increase primarily in 1989-1994 and almost exclusively in primiparous women > or = 30 years, for whom the adjusted population-based twinning rate increased 2.7-fold and the triplet rate 9.1-fold. The proportion of multiple births among infant deaths in primiparous women > or = 30 years increased from 11.5% to 26.9%. In conclusion, the marked increase in the rate of multiple pregnancies, which in particular was observed during the 1990s and in primiparous women > or = 30 years, could not be explained by changes in maternal age or parity. Fertility-enhancing treatments are believed to have caused this increase.

Adult↗

Declining HIV-2 prevalence and incidence among men in a community study from Guinea-Bissau.

OBJECTIVE: To assess the present level of HIV-2 infection in an adult population in Bissau and to evaluate sex and age-specific changes in HIV-2 prevalence and incidence between 1987 and 1996. DESIGN AND METHODS: Sex and age-specific changes in HIV-2 prevalence were evaluated comparing a survey from 1987 in a sample of 100 houses with a survey performed in 1996 in an independent sample of 212 houses from the same study area. HIV-2 incidence rates were examined in an adult population (age > or = 15 years) from 100 randomly selected houses followed with four consecutive HIV serosurveys from 1987 to 1996. RESULTS: The HIV-2 prevalence in 1996 was 6.8% (men, 4.7%; women, 8.4%). Compared with the 1987 survey there was a significant decrease in prevalence among men [age-adjusted relative risk (RR), 0.50; 95% confidence interval (CI), 0.31-0.83], whereas it remained unchanged in women (RR, 1.00; 95% CI, 0.67-1.48). The male-to-female RR decreased from 0.99 (95% CI, 0.61-1.61) in 1987 to 0.51 (95% CI, 0.34-0.76) in 1996. The overall annual incidence rate was 0.54 per 100 person-years of observation (PYO), being higher in women (0.72 per 100 PYO) than in men (0.31 per 100 PYO). With the observation time divided into an early and a late period, there was a decrease in incidence with time among men (0.66 to 0.00 per 100 PYO), but no major change among women (0.59 to 0.85 per 100 PYO). The two trends differed significantly (P = 0.03). We observed a higher annual incidence rate amongst older women aged > 44 years (1.77 per 100 PYO) than among younger women (0.55 per 100 PYO; P = 0.05). CONCLUSION: There are no signs of an epidemic spread of HIV-2 in Bissau even though the HIV-1 prevalence is increasing rapidly. A significant reduction in the male HIV-2 prevalence and incidence rates has resulted in a major shift in the pattern of spread of HIV-2, from being equally distributed to being predominantly a female infection. Currently, older women in particular seem to have a high risk of getting infected.

Adolescent↗

HTLV-1 infection in a population-based cohort of older persons in Guinea-Bissau, West Africa: risk factors and impact on survival.

In 1989, a population-based cohort of persons aged > or = 50 years was established in an urban area of Guinea-Bissau, West Africa. Overall, 346 persons were interviewed in detail about risk behaviors and had capillary blood drawn. Among women, 12.4% were HTLV-1 seropositive, compared with 4.6% in men. No HTLV-2 was found. Seropositivity varied considerably according to place of birth and ethnic group. In women, but not in men, HTLV-1 seropositivity was strongly associated with early sexual debut (10-14 yrs, 33.3%; 15-17 yrs, 26.0%; 18-20 yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend = 0.006), and the male partner's number of co-wives (ptrend = 0.006). There was also a 3.1-fold increased risk of being HTLV-1 seropositive if the woman was also HIV-2 seropositive. In a multivariate-risk-factor analysis, the strongest association with HTLV-1 was a history of having been bitten by a monkey (n = 11; combined OR adjusted = 10.1; 95% CI 2.3-44.4). Ornamental scarification was associated with a 3.3-fold increased risk. Ethnic affiliation also significantly influenced the risk of being HTLV-1 seropositive. Follow-up performed in January 1996 revealed no difference in survival between HTLV-1-seropositive and -seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7-2.8). In conclusion, this population, which has very high HIV-2 seroprevalence, is also highly endemic for HTLV-1. Whereas sexual behaviors are clearly important for HTLV-1 spread in women, non-sexual risk factors were the only ones of potential importance in men. HTLV-1 had no impact on survival in this older population.

Aged↗

Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal.

To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non-seroresponders. These changes were more marked among girls, since they had significantly higher CD4 percentages and CD4/CD8 ratios than boys in the convalescence phase. In conclusion, measles infection is not associated with a long-term suppression of CD4+ or CD8+ T-lymphocytes.

Adolescent↗

Mortality among human immunodeficiency virus type 2-positive villagers in rural Guinea-Bissau is correlated with viral genotype.

We present the results of a 6-year study of 131 human immunodeficiency virus (HIV) type 2 (HIV-2)-infected individuals from a rural population in Guinea-Bissau. Proviral DNA sequences 1.3 kb in length were obtained from each individual and, together with clinical data, including proviral load and CD4 and CD8 levels, were used to assess whether viral genotype influences clinical outcome. With a phylogenetic model, a correlation was found between viral genotype and mortality; this correlation was not due to confounding factors, such as age-specific viral strains or cohabitation of patients. The data provide strong evidence for the involvement of viral genetic factors in determining HIV disease progression in vivo. The pattern of association found suggests that virulence factors are multiple and scattered throughout the HIV-2 genome and can be rapidly gained or lost by the virus through a combination of mutation and recombination. These findings may lead to the identification of viral determinants of HIV disease progression.

Adolescent↗

HIV-2 genetic variation and DNA load in asymptomatic carriers and AIDS cases in Guinea-Bissau.

The purpose of this study was to document which genetic subtypes of HIV-2 are present in Guinea-Bissau and to investigate whether asymptomatic HIV-2 carriers and AIDS patients carry distinct genetic variants. A secondary aim was to correlate proviral DNA load to clinical and immunologic status of the patients. Thirty-eight asymptomatic HIV-2 carriers and 11 AIDS patients from Bissau, Guinea-Bissau were included in a cross-sectional study in which HIV-2 env V3 sequences, HIV-2 DNA load, and CD4-positive (CD4+) lymphocyte counts were determined. Phylogenetic analyses showed that all investigated subjects carried subtype A HIV-2 variants and that the sequences from AIDS patients and asymptomatic carriers did not form distinct subclusters in the tree. As expected, patients with AIDS had significantly higher median HIV-2 DNA load than did asymptomatic carriers (4.6 vs. 2.0 log10 HIV-2 DNA copies/10(6) CD4+ lymphocytes). Our study indicates that the HIV-2 epidemic in Guinea-Bissau is almost exclusively caused by subtype A HIV-2 variants and that the HIV-2 infections among the asymptomatic carriers and AIDS cases included in the study do not have distinct epidemiologic histories.

Acquired Immunodeficiency Syndrome↗

Risk factors for diarrheal disease incidence in early childhood: a community cohort study from Guinea-Bissau.

To determine risk factors for diarrhea, the authors followed an open cohort of 1,314 children from Guinea-Bissau by weekly diarrhea recall interviews between April 1987 and March 1990. Data on feeding practices and measles infection were available for all children and, for 531 children, comprehensive data on explanatory variables were recorded. Of 57 variables, seven were independently associated with an increased incidence of diarrhea. These were a recent (in the past 14 days) diarrheal episode, male sex, being weaned from breast milk, not being looked after by the mother, head of the household being < 30 years old, eating cold leftovers, and drinking water from an unprotected public water supply. In breastfed children, only three variables were associated with diarrhea, including prior diarrhea, male sex, and not being looked after by the mother. Among weaned children, six variables delineated increased rates of diarrhea, including unprotected public water supply, eating of cold leftovers, and lack of maternal education. Major determinants of persistent diarrhea included weaning, lack of maternal education, and having pigs in the home. It is concluded that, in addition to the promotion of breastfeeding, important interventions against diarrhea include improvements in water supply, hygiene, and food handling. However, because of effect modification by breastfeeding, the largest effects of these interventions will probably be among weaned children.

Breast Feeding↗

Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, west Africa.

BACKGROUND: WHO has recommended vitamin A supplementation for children aged 6 months or older in developing countries at the same time as immunisation. One study has reported significantly lower seroconversion ratios among children who have received vitamin A supplements with measles vaccine at age 6 months. The aim of our study was to assess the effect of vitamin A supplementation on antibody response to measles vaccination at age 9 months, which is the more common age for immunisation in developing countries. METHODS: In an urban community in Guinea-Bissau, we did a randomised, double-blind, placebo-controlled study of the effect of simultaneous vaccination and vitamin A supplementation in 462 children who received either a two-dose schedule of measles vaccine at the ages of 6 months and 9 months (150 infants) or one dose of measles vaccine at age 9 months (312 infants). Children were followed up to the age of 18 months and a blood sample was then collected to assess the antibody response. FINDINGS: 397 (86%) of the children took part in the follow-up (52 [11%] had moved and 13 [3%] had died). Among children who received a two-dose vaccine schedule, seroconversion was 98%. There was no difference in seroconversion or geometric mean titre (GMT) for children receiving vitamin A compared with children receiving no supplement. Among children receiving only one dose of measles vaccine at age 9 months, seroconversion was 95%. The GMT was significantly higher in children receiving vitamin A than in those receiving no supplement (3704 vs 2439 mIU; GMT ratio 1.52 [1.22-1.88]). The effect on plasma antibody concentration in the blood was stronger for boys (3902 vs 1916 mIU; GMT ratio 2.04 [1.53-2.72]) than for girls (3502 vs 3017 mIU; GMT ratio 1.16 [0.85-1.58]) who had received vitamin A with measles vaccine. In a multivariate analysis of variance adjusted for sex, vitamin A supplementation was associated with higher antibody titres (p < 0.001). There was a significant interaction between vitamin A supplementation and sex (p = 0.02). INTERPRETATION: There is no indication that simultaneous administration of measles vaccine and vitamin A supplements has a negative effect on measles immunity. Among the children who had received two doses of measles vaccine at the ages of 6 months and 9 months, supplements of vitamin A had no significant effect. Among children only receiving one dose of measles vaccine at age 9 months, 100,000 IU vitamin A increased antibody concentrations, especially for boys.

Antibodies, Viral↗