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Biomedical subjects

Peter Aaby

Publications and source records attributed to Peter Aaby.

102 records · Page 6Linked to original sources

Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau, west Africa.

To study the natural history of rotavirus infection and to determine the protection it confers against reinfection and diarrhea, 200 newborns in Guinea-Bissau were prospectively followed for up to 2 years. Rotavirus was detected in stool specimens collected weekly. By age 2 years, the incidence of primary rotavirus infection was 74%. In the first 3 months of life, 17% of the infections were diarrhea associated, compared with 60% at 9-11 months; after age 18 months, all infections were asymptomatic. A primary infection conferred 52% (95% confidence interval [CI], 16% to 73%) and 70% (95% CI, 29% to 87%) protection against subsequent rotavirus infection and rotavirus diarrhea, respectively. The protection was 66% (95% CI, 24% to 85%) against reinfection within the same epidemic, compared with 34% (95% CI, -29% to 67%) against reinfection in any subsequent epidemic. The high level of protection against symptomatic rotavirus infection provides an important incentive for development of a rotavirus vaccine.

Cohort Studies↗

Increased prevalence of HTLV-1 among HIV-2-infected women but not HIV-2-infected men in rural Guinea-Bissau.

OBJECTIVE: To assess the prevalence of HTLV infection and its association with HIV and other potential risk factors. DESIGN AND SETTING: A cross-sectional survey and a case-control study in a rural community in Guinea-Bissau. METHODS: A total of 2770 people were included in an HIV and HTLV seroepidemiologic survey. Three hundred of these participants were selected for a case-control study on HIV-2. Sera from both studies were tested for HTLV. RESULTS: In all, 2501 and 298 subjects in the survey and case-control study, respectively, were tested for HTLV. Overall HTLV-1 prevalence was 5.2% and it was higher in women (odds ratio [OR], 1.36; confidence interval [CI], 0.92-2.02). Apart from an infected spouse, no significant risk factors could be identified for men. In women, HIV-2 infection (adjusted OR, 5.58; CI, 3.09-10.1), having an infected spouse, and area of residence were significantly associated with HTLV-1 infection. The association between HTLV-1 and HIV-2 was significantly different for men and women (test of interaction, p =.002). CONCLUSIONS: In women, the most important determinant of HTLV-1 seropositivity was HIV-2 infection. Because the pattern was significantly different for men and women, common sexual risk factors may not be sufficient to explain the co-occurrence of HIV-2 and HTLV-1 in women. These observations may have implications in geographic areas where both types of retroviruses are prevalent.

Acquired Immunodeficiency Syndrome↗

Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau.

We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.

Antibodies, Viral↗

Influence of Mycobacterium bovis bacillus Calmette-Guérin on antibody and cytokine responses to human neonatal vaccination.

The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study groups receiving BCG at birth, when infants received their first dose of hepatitis B and oral polio vaccines; at 2 mo of age, when infants received their first dose of diphtheria and tetanus vaccines; or at 4.5 mo of age, when immune responses to vaccines were measured. Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine, but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids. Although BCG induced a potent Th1-type response to mycobacterial Ags, it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. The effect of BCG was apparent at the systemic level, as it increased the Ab response to oral polio vaccine. These results demonstrate that BCG influences the immune response to unrelated Ags in early life, likely through its influence on the maturation of dendritic cells.

Age Factors↗

Does cross-sex transmission increase the severity of polio infection? A study of multiple family cases.

Previous studies have suggested that transmission of measles virus from the opposite sex increases the severity of infection; however, the role of gender in the transmission of other infections has not been examined. Multiple polio cases within a family usually occur simultaneously, and are therefore likely to be secondary to a common subclinical index case. The few clinical polio cases that appear much later than any other clinical case are likely to be tertiary cases. If cross-sex transmission increases the severity of infection then multiple polio cases would tend to affect the same sex, i.e. the opposite sex to that of the subclinical index case. In order to assess this phenomenon we identified 6345 records of individuals hospitalized with poliomyelitis in Copenhagen between 1919 and 1953. The severity and gender of suspected secondary and tertiary cases were analysed among all multiple household cases. Overall, 70% of the 133 sibling pairs having polio simultaneously were same-sex pairs, which differed significantly from the expected 52% (chi2 = 9.1; p < 0.01). Tertiary cases with exposure to the opposite sex were more likely to be paralytic than cases with exposure to the same sex [relative risk (RR) = 2.86 (95% confidence interval 1.08-7.58)1. In families with adult polio cases, possible tertiary cases were more common among fathers (7/24) than among mothers (1/35) [RR = 10.21 (1.34-77.72)]. We examined whether the excess of male polio cases was more pronounced in small families where the mother would play a relatively larger role in disease transmission and found that the male:female excess decreased with increasing birth order (p = 0.02) and family size (p = 0.09). The strong tendency towards same-sex pairs in 2-case families suggests that gender plays an important role in the severity of polio infection. Cross-sex transmission may increase the severity of polio and mothers may contribute to the higher prevalence of polio cases among boys.

Adolescent↗

The polio model. Does it apply to polio?

BACKGROUND: According to the polio model, severity of disease increases with age at infection. Firstborn children and people belonging to small families are generally infected later and should accordingly have a higher risk of severe polio. However, this model does contradict other explanations of severity of childhood infections including the intensive-exposure model. METHODS: To evaluate the deductions from the polio model we performed a study based on medical records from 5590 historical polio cases from the county of Copenhagen 1940-1953. The relative risk (RR) of polio according to age, birth order and sibship size was evaluated using census data from 1940 and 1950. RESULTS: Severity of polio measured as frequency of paralysis or mortality did not show a steady increase with age, but a U-shaped curve being highest for the youngest as well as the oldest patients. The incidence of polio and paralytic polio was higher in families with several children compared with single children (RR = 1.13, 95% CI : 1.0-1.3). Furthermore, the incidence was higher in later-born children (P(trend) < 0.0001). However, as predicted from the intensive-exposure model, second-born children aged 1-4 years in two-child families had a higher risk of paralytic polio than first-born children (RR = 1.47, 95% CI : 1.1-2.0), whereas the opposite relationship was found for those aged > or = 5 years (RR = 0.65, 95% CI : 0.5-0.9). CONCLUSION: The polio model's prediction about the impact of age, sibship size and birth order on polio incidence and severity found only limited support. A model emphasizing intensity of exposure as a risk factor for severity may account better for the epidemiology of polio infection.

Adolescent↗

Treatment of children with Plasmodium falciparum malaria with chloroquine in Guinea-Bissau.

Children with symptomatic malaria in Bissau, Guinea-Bissau were randomly assigned to treatment with a 25 mg/kg total dose of chloroquine as recommended by the National Malaria Program or with a higher total dose of 50 mg/kg. Sixty-seven and 62 children, respectively, completed the treatment and were then followed once a week for five weeks. Treatment with a dose of 50 mg/kg was significantly more effective than treatment with 25 mg/kg in preventing recrudescence. The cumulative relative risk (95% confidence interval) of having parasitemia in the low-dose group during follow-up was 0.20 (0.08-0.52) on day 21, 0.38 (0.17-0.86) on day 28, and 0.48 (0.23-0.98) on day 35. Few adverse events were reported, although more children complained of vomiting and diarrhea on day 2 in the high-dose group compared with those in the low-dose group. However, this difference was not statistically significant. We conclude that a dose of 50 mg/kg of chloroquine could be recommended for treatment of Plasmodium falciparum malaria in Bissau. To minimize the risk of side effects, this higher dose should be given divided into two daily doses over a three-day period.

Antimalarials↗

Treatment of uncomplicated malaria in children in Guinea-Bissau with chloroquine, quinine, and sulfadoxine-pyrimethamine.

With the increasing resistance to commonly used antimalarial drugs, different untested 'local' treatment regimens for malaria will arise. We compared commonly used treatment regimens for children in Guinea-Bissau. Symptomatic children with Plasmodium falciparum mono-infection were allocated at random to one of 4 treatments: 15 mg/kg quinine twice a day for 3 d (group 1); 10 mg/kg quinine twice a day for 3 d followed by a total dose of 25 mg chloroquine base given over 3 d (group 2); a total dose of 50 mg/kg chloroquine base given in 2 daily doses for 3 d (group 3), or sulfadoxine-pyrimethamine (group 4). On day 28 more children from group 1 (33%; relative risk [RR] = 2.9, 95% confidence interval [CI] 1.5-5.7) and group 2 (26%; RR = 2.1, CI 1.0-4.3) had had parasitaemia than in group 4 (12%), whereas no significant difference was found between group 3 (17%; RR = 1.3, CI 0.6-2.2) and group 4. No severe adverse reaction was observed in any of the groups. Chloroquine is still effective in Guinea-Bissau at an increased dose of 50 mg/kg, which appears safe when given orally in 2 daily doses for 3 d. Sulfadoxine-pyrimethamine could serve as an efficient, cheap and easy to administer second-line drug, leaving quinine to be used for third-line treatment. Quinine should not be used in short courses, nor does the combination of quinine and chloroquine have any advantage.

Adolescent↗

Treatment of Plasmodium falciparum malaria with quinine in children in Guinea-Bissau: one daily dose is sufficient.

We have earlier obtained good results in falciparum malaria by treating children with low doses of quinine for 7 days in Guinea-Bissau. In order to further simplify treatment, we compared outcome in 100 children with falciparum malaria treated in 1999/2000 for 7 days with 15 mg quinine salt/kg/dose twice daily (group I), 100 children treated with 7.5 mg quinine salt/kg/dose twice daily (group II), and 100 children treated with one single daily dose of 15 mg/kg. One day 28, parasites had reappeared in 12%, 15%, and 9%, respectively. These results are similar to what has been found after previous successful treatment regimens. Apart from a higher incidence of vomiting during the first 24 h of treatment in the groups treated with 15 mg/kg/dose no significant differences in symptoms or side-effects were found between the groups. In patients suffering from uncomplicated malaria, treatment with quinine can be simplified to one single dose of 15 mg/kg bodyweight whenever logistics make 2 daily doses less feasible.

Adolescent↗

No benefits from combining chloroquine with artesunate for three days for treatment of Plasmodium falciparum in Guinea-Bissau.

The use of a combination of chloroquine and artesunate has been suggested for treatment of malaria in Africa. We used concomitant as well as sequential medication with these 2 drugs in relation to each drug separately for children infected with Plasmodium falciparum in Guinea-Bissau from March 2000 to November 2001. By block-randomization, 474 children with symptomatic malaria were divided into 4 groups and given either a total of 8 mg artesunate per kg bodyweight for 3 d, a total of 25 mg chloroquine base per kg bodyweight for 3 d, both drugs concomitantly for 3 d, or both drugs in sequence. All children were followed weekly for 5 weeks. On day 28, parasites had been detected in 40% of the children who were treated with artesunate only compared with 21% treated with chloroquine, 20% treated with artesunate in combination with chloroquine, and 16% treated with artesunate and chloroquine in sequence; on day 35 the corresponding percentages were 48%, 29%, 27%, and 24%, respectively. The outcome of the combination of chloroquine and artesunate in the doses studied was similar to the outcome of chloroquine monotherapy regardless of whether the 2 drugs are given concomitantly (relative risk [RR] = 0.93, 95% CI 0.56-1.53, P = 0.76) or in sequence (RR = 0.78, 95% CI 0.47-1.28, P = 0.32). Thus, neither an antagonistic, an additive, or a synergistic effect of the 2 drugs was indicated.

Adolescent↗