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Biomedical subjects

Peter Aaby

Publications and source records attributed to Peter Aaby.

At least 19 recordsLinked to original sources
PubMed2007

Survival bias in observational studies of the impact of routine immunizations on childhood survival.

OBJECTIVES: In situations with vaccination coverage high enough to control pertussis, observational studies have reported divergent effects of diphtheria-tetanus-pertussis (DTP) vaccination on childhood survival. We examined whether this could be because of methodological differences. METHODS: Some studies of the impact of DTP updated information on vaccination retrospectively (retrospective updating approach) while others kept vaccination status fixed for the time between follow-up visits (landmark approach). First, we conducted simulations with these approaches to investigate the impact of different mortality levels, vaccination incidence rates, intervals between data collection visits, and the proportion of children whose vaccination card had not been seen after death. Second, we re-analysed data from Guinea-Bissau using the retrospective updating approach. RESULTS: In simulations, the retrospective updating approach produced rate ratio (vaccinated/unvaccinated) estimates biased towards zero because of a differential misclassification which created survival bias as risk-free observation time was allocated to the vaccinated group. The landmark approach produced rate ratio estimates biased towards one. Biases increased with interval between data collection visits and incidence of vaccination, but were unaffected by the underlying mortality level. Survival bias increased with the proportion of dead children whose vaccination status could not be updated. The re-analysis of data from Guinea-Bissau changed the estimated impact of DTP from an 84% higher mortality using the landmark approach to a 37% lower mortality using the retrospective updating approach. CONCLUSIONS: The apparent contradiction between DTP studies could be because of methodological differences. To assess child survival associated with routine vaccinations, studies minimizing the effect of biases are warranted.

BCG Vaccine↗
PubMed2007

DTP vaccination and child survival in observational studies with incomplete vaccination data.

BACKGROUND: Observational studies of diphtheria-tetanus-pertussis (DTP) vaccine from longitudinal study sites have reported divergent effects on child survival, ranging from 10-fold reduction to threefold increased mortality. None of these studies had complete information on DTP vaccinations from both survivors and children who died. We reviewed the data analysis methodology to assess whether methodological differences could explain the divergent results. DESIGN: Studies have used case-control design, survival analysis with interval-fixed vaccination status (landmark approach), and survival analysis with retrospective updating of vaccination status. RESULTS: Seven studies using a case-control design or a landmark approach found a negative effect of DTP on child survival. Eight of nine survival analyses with retrospective updating of vaccination status reported a beneficial effect. This beneficial effect of DTP increased with the length of the interval between data collection visits. Studies with long interval between visits had very high mortality rates among unvaccinated children, low mortality rate ratios for vaccinated compared with unvaccinated children, and strongly beneficial estimates of DTP. CONCLUSION: The divergent results in observational studies of the impact of DTP on child survival are partly because of methodological differences. To assess the impact on mortality of routine vaccinations, observational study designs which minimize the effect of bias are warranted. Randomized trials should be considered.

BCG Vaccine↗
PubMed2006

Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau.

BACKGROUND: In urban Guinea-Bissau, adults with a vaccinia scar had better survival but also a higher prevalence of HIV-2 infection. We therefore investigated the association between vaccinia scar and survival and HIV infection in a rural area of Guinea-Bissau. METHODOLOGY/PRINCIPAL FINDINGS: In connection with a study of HIV in rural Guinea-Bissau, we assessed vaccinia and BCG scars in 193 HIV-1 or HIV-2 infected and 174 uninfected participants. Mortality was assessed after 2(1/2)-3 years of follow-up. The analyses were adjusted for age, sex, village, and HIV status. The prevalence of vaccinia scar was associated with age, village, and HIV-2 status but not with sex and schooling. Compared with individuals without any scar, individuals with a vaccinia scar had better survival (mortality rate ratio (MR) = 0.22 (95% CI 0.08-0.61)), the MR being 0.19 (95% CI 0.06-0.57) for women and 0.40 (95% CI 0.04-3.74) for men. Estimates were similar for HIV-2 infected and HIV-1 and HIV-2 uninfected individuals. The HIV-2 prevalence was higher among individuals with a vaccinia scar compared to individuals without a vaccinia scar (RR = 1.57 (95% CI 1.02-2.36)). CONCLUSION: The present study supports the hypothesis that vaccinia vaccination may have a non-specific beneficial effect on adult survival.

Adult↗
PubMed2006

Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for malaria in children in Guinea-Bissau.

BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later. METHODS: Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine. Parasitological and clinical failures were evaluated during a 35-day follow-up. During the first study period whole blood sulfadoxine concentrations were measured on day 7. RESULTS: Altogether, 56 children failed the initial treatment and were included in 1995/1996 as well as 55 children in 2002/2004. The PCR-uncorrected adequate clinical and parasitological response rates on day 28 were 94% and 91%, and on day 35 they were 89% and 91%, respectively, in the two periods. No difference between median blood drug concentration in children with and without treatment failure was observed. INTERPRETATION: The efficacy of S/P as second line treatment for uncomplicated malaria has remained unchanged in spite of a relatively high level of genetic markers associated with Plasmodium falciparum resistance to S/P previously found in the area.

Adolescent↗
PubMed2006

Psychiatric hospitalizations in a cohort of Danish polio patients.

Although previous polio infection remains a considerable cause of long-term morbidity worldwide, few studies have examined the psychiatric consequences of poliomyelitis. The authors followed 4,660 polio patients hospitalized at the primary infectious disease hospital in Copenhagen, Denmark, between 1922 and 1954 as well as 19,017 age- and gender-matched Danes for psychiatric hospitalizations from January 1, 1977, to December 31, 1993. Incidence rates of all psychiatric disorders combined and of separate diagnostic groups of psychiatric diseases in the two cohorts were compared, yielding the incidence rate ratio, a measure of relative risk. Overall, polio patients had a 40% increased risk of being hospitalized for a psychiatric disorder (incidence rate ratio = 1.43, 95% confidence interval: 1.23, 1.66). Apparently, the overall increased risk of psychiatric hospitalizations could not be confined to specific groups of psychiatric disorders but seemed to be explained by slightly increased risks of several different disorders, especially milder psychiatric disorders. Finally, psychiatric morbidity did not differ between paralytic and nonparalytic polio patients. History of hospitalization for polio might be associated with subsequent risk of hospitalization for psychiatric disorders. The underlying mechanism for this association remains uncertain.

Adult↗
PubMed2006

Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau.

OBJECTIVE: To investigate whether prophylactic antibiotics can prevent complications of measles. DESIGN: Community based, randomised, double blind, placebo controlled trial. SETTING: Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. PARTICIPANTS: 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). INTERVENTIONS: Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. MAIN OUTCOME MEASURES: Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. RESULTS: The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. CONCLUSIONS: The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. TRIAL REGISTRATION: Clinical trials NCT00168532.

Adolescent↗
PubMed2006

DTP with or after measles vaccination is associated with increased in-hospital mortality in Guinea-Bissau.

BACKGROUND: The sequence of routine immunisations may be important for childhood mortality. Three doses of diphtheria-tetanus-pertussis vaccine (DTP) should be given at 6, 10, and 14 weeks and measles vaccine (MV) at 9 months of age. The sequence is not always respected. We examined in-hospital mortality of children having received DTP with or after measles vaccine. SETTING: The only paediatric ward in Bissau, Guinea-Bissau. PARTICIPANTS: Children hospitalised during two periods in 1990-1996 and 2001-2002 who had received MV prior to hospitalisation. MAIN OUTCOME MEASURE: The all-cause case fatality at the hospital for children aged 6-17 months. RESULT: The case fatality was increased for children who had received DTP with or after measles vaccine compared with children who had received measles vaccine as the most recent vaccine, the ratio being 2.53 (1.37-4.67) and 1.77 (0.92-3.41) in the two periods, respectively. The combined estimate was 2.10 (1.34-3.28). These results were not explained by differences in nutritional status, number of doses of DTP or discharge policy. CONCLUSION: Administration of DTP with, or after MV, may reduce the beneficial effect of MV.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed2006

[International health at home: bringing the experiences back home with you].

International Health research conducted under extreme conditions in low-income countries may lead to a better understanding of epidemics in high-income countries, by questioning assumptions which are important in these countries. Examples are given of how observations in Guinea-Bissau have led to reinterpretation of the decline in measles mortality, of the polio model, and of the impact of stopping vaccinations after eradication in the industrialised countries.

Child↗
PubMed2006

[Gender differences in response to preventive health care interventions. Do we have to treat girls and boys differently to treat them equally?].

In spite of well-recognised differences in morbidity patterns among boys and girls, differences in their response to common interventions like vaccinations have rarely been considered. Our research in vaccinations and vitamin A supplementation has suggested sex differences in the response to these interventions. If these observations reflect a general pattern, it may be that, in order to be treated equally, boys and girls should be treated differently.

Bacterial Vaccines↗
PubMed2006

Different doses of amodiaquine and chloroquine for treatment of uncomplicated malaria in children in Guinea-Bissau: implications for future treatment recommendations.

The aim of the present study was to compare different doses of chloroquine (CQ) and amodiaquine (AQ) for the treatment of falciparum malaria in children. Children with Plasmodium falciparum monoinfection were allocated by block randomisation to treatment with CQ 50/kg mg or 25 mg/kg or AQ 15 mg/kg or 30 mg/kg. The main outcomes were the cumulative adequate clinical and parasitological response (ACPR) rates and the number of true recrudescences as determined by PCR. A total of 729 children were included. In an evaluability analysis, the PCR-uncorrected cumulative ACPR rates on Day 28 for the treatment groups CQ 50/kg mg or 25 mg/kg and AQ 15 mg/kg or 30 mg/kg were 90%, 76%, 92% and 94%, respectively; the PCR-adjusted ACPR rates on Day 28 were 92%, 80%, 94% and 94%, respectively. No differences in adverse effects were observed. AQ has a high cure rate given as 30 mg/kg and 15 mg/kg, although it is not superior to treatment with CQ 50 mg/kg. However, 25 mg/kg of CQ is less efficient. As an interim option, Guinea-Bissau could change the recommended first-line treatment of uncomplicated malaria to CQ 50 mg/kg, reserving AQ as a partner drug for a future combination therapy.

Adolescent↗
PubMed2006

Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa.

The sst1 locus has been identified in a mouse model to control resistance and susceptibility of Mycobacterium tuberculosis infection. Subsequent studies have now identified Ipr1 (intracellular pathogen resistance 1) to be the gene responsible. Ipr1 is encoded within the sst1 locus and is expressed in the tuberculosis lung lesions and macrophages of sst1-resistant, but not sst1-susceptible mice. We have therefore examined the closest human homologue of Ipr1, SP110, for its ability to control susceptibility to M. tuberculosis infection in humans. In a study of families from The Gambia we have identified three polymorphisms that are associated with disease. On examination of additional families from Guinea-Bissau and the Republic of Guinea, two of these associations were independently replicated. These variants are in strong linkage disequilibrium with each other and lie within a 31-kb block of low haplotypic diversity, suggesting that a polymorphism within this region has a role in genetic susceptibility to tuberculosis in humans.

Africa↗
PubMed2006

Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau.

BACKGROUND: Live vaccines including BCG and measles may have non-targeted beneficial effects on childhood survival in areas with high mortality. The authors therefore undertook a survey of vaccinia scars to evaluate subsequent mortality. SUBJECTS: Based on a population census, a cohort of 1893 adults in urban Guinea-Bissau was examined in 1998 and followed until 2002. MAIN OUTCOME MEASURE: All cause mortality, excluding accidents. RESULTS: The median age of vaccinia vaccinations had been 16-18 years. Adults with a vaccinia scar had a mortality ratio (MR) of 0.60 (0.41-0.87) compared to those without any scar. The effect was stronger for women. Mortality decreased with each additional vaccinia scar (MR=0.73 (0.56-0.95)). Among 502 individuals with information on HIV infection, the age-adjusted HIV-2 prevalence was 2.45 (1.06-5.65) for those with a vaccinia scar. Control for district, ethnic group, schooling, place of birth, quality of housing and HIV status had little effect on the estimate. Since vaccinia and BCG scars could have been confused, mortality for adults with vaccinia and/or BCG scar was compared to those without, the MR being 0.61 (0.41-0.89). CONCLUSION: Known cultural or socio-economic factors possibly associated with access to vaccination had no influence on the mortality ratio for having a vaccinia scar. Hence, vaccinia vaccination may have a prolonged beneficial effect on adult survival.

Adult↗
PubMed2006

Community cohort study of rotavirus and other enteropathogens: are routine vaccinations associated with sex-differential incidence rates?

OBJECTIVE: Community studies in West Africa have demonstrated that routine vaccinations may have non-targeted effects, the female-male mortality ratio being reduced after administration of BCG and increased after diphtheria-tetanus-pertussis (DTP). We examined whether immunisation status was associated with infection with rotavirus and other enteropathogens. METHODS: We recruited 200 children shortly after birth and followed them until 2 years of age with weekly morbidity interviews and stool sampling. Vaccination status for each child was classified according to the most recent vaccination as documented by vaccination card. MAIN OUTCOME MEASURES: The female-male incidence rate ratios (IRR) of infection with an enteropathogen and of enteropathogen-associated diarrhoea were estimated for children according to whether they had received BCG or DTP as their last vaccination. RESULTS: For children who received BCG as their last vaccine, the adjusted female-male IRRs for primary rotavirus-infection and diarrhoea were 1.05 (95% CI: 0.21-5.28) and 0.0 (95% CI: 0-3.02), respectively. For children who received DTP as their last vaccine, the adjusted female-male IRRs were 1.93 (0.89-4.21) and 1.92 (0.70-5.32), respectively, for rotavirus-associated infection and diarrhoea. Restricted to the rotavirus season, the female-male IRRs for rotavirus infection and diarrhoea were 2.56 (1.17-5.63) and 2.63 (0.94-7.34), respectively. The female-male IRR for rotavirus-associated diarrhoea differed significantly among BCG and DTP recipients (p=0.02). Infections with enteropathogens not associated with diarrhoea were associated with lower female-male IRRs after BCG of 0.82 (0.55-1.23) and higher female-male IRRs after DTP vaccination of 1.32 (1.03-1.70) for primary infection (p=0.05). Though there were few infections with other diarrhoea-causing enteropathogens, these were also associated with a lower female-male IRR after BCG of 0.62 (0.26-1.52) and a higher female-male IRR after DTP vaccination of 1.51 (1.04-2.20) for all infection. CONCLUSION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with lower risk for girls, whereas, DTP is associated with higher risk for girls relative to boys.

BCG Vaccine↗
PubMed2006

Age-specific changes in the female-male mortality ratio related to the pattern of vaccinations: an observational study from rural Gambia.

BACKGROUND: According to studies from Guinea-Bissau and Senegal, live vaccines may reduce the female-male mortality ratio (MR) whereas inactivated vaccines increase this ratio. We used data from The Gambia to examine whether similar tendencies could be found in a different setting. SETTING: Forty villages in the Farafenni area in rural Gambia. SUBJECTS: A population of 17,000 was followed with demographic surveillance between 1998 and 2002; 537 children less than 5 years of age died in this period. METHODS: We used two vaccination surveys and community mortality data to examine, first, the female-male mortality ratio (MR) in the age groups in which DTP and MV are recommended and have a high coverage. Second, using vaccination cards seen post-mortem, we examined the distribution of live or inactivated vaccines as last vaccination in different age groups. Third, we examined the effect of DTP and MV administered simultaneously. MAIN OUTCOME MEASURES: The female-male MR in different age groups and for different vaccines. RESULTS: Vaccination coverage was high for BCG, third dose of DTP (DTP3) and MV, reaching a level of 80-90% within a few months of the recommended age of vaccination. First, the female-male MR was 0.93 (0.63-1.38) in the first 2 months of life when children had received no vaccination or the combination of BCG, HBV and OPV. From 2 to 8 months of age, with DTP and HBV being the main vaccinations, the female-male MR was 1.28 (0.86-1.89). Between 9 and 17 months of age, with MV as the main vaccination, this ratio dropped to 0.73 (0.50-1.07), a significant inversion of the female-male MR (p=0.045). Second, using information from vaccination cards of dead children, boys who died at 2-4 months of age were more likely to have received live BCG and girls to have received inactivated DTP and HBV as last vaccination (p<0.001). At 5-8 months of age, essentially all dead children had received DTP as last vaccination and the female-male MR was 1.68 (0.96-2.93), whereas the MR was 0.70 (0.43-1.15) at 12-17 months of age when nearly all dead children had received MV (p=0.022). Third, compared with the general population of children who had received MV, dead children who had received MV were more likely to have received DTP3 simultaneously with MV (relative risk (RR)=5.59 (2.10-14.8)) or after MV (RR=2.61 (1.13-6.05)). CONCLUSION: Most children dying at a specific age had received the recommended vaccines. BCG and MV as last vaccination was associated with a low female-male MR, whereas DTP as last vaccination was associated with a high female-male MR. These trends are consistent with observations from other African countries.

Age Factors↗
PubMed2006

[Reduced post-partum bleeding after treatment with sublingual misoprostol: a randomized double-blind clinical study in a developing country--secondary publication)].

Post-partum haemorrhage is the most common cause of maternal death in third-world countries. The objective of this study was to evaluate whether routine administration of sublingual misoprostol, 600 g, reduces post-partum haemorrhage. Significantly fewer women in the misoprostol group experienced a loss of > or = 1,000 ml (11% vs. 17%; 0.66 (0.45-0.98)) or > or = 1,500 ml (2% vs. 8%; 0.28 (0.12-0.64)) of blood. We conclude that sublingual misoprostol reduces the frequency of severe post-partum haemorrhage.

Administration, Sublingual↗
PubMed2006

Community cohort study of Cryptosporidium parvum infections: sex-differential incidences associated with BCG and diphtheria-tetanus-pertussis vaccinations.

OBJECTIVE: Community studies in West Africa have suggested that routine vaccinations may have sex-differential non-targeted effects, the female-male mortality ratios being increased after receiving diphtheria-tetanus-pertussis (DTP) vaccination and reduced after administration of BCG or measles vaccine (MV). Using an existing data set, we examined whether vaccinations were associated with gender-differential incidences of Cryptosporidium parvum infection. METHODS: Two hundred children had been recruited shortly after birth and followed until 2 years of age or until follow-up was interrupted by a war. We performed weekly morbidity interviews and collected stool specimens, irrespective of whether the children had diarrhoea. Vaccination status for each child was classified according to the most recent vaccination with BCG, DTP, or MV. FINDINGS: The female-male incidence rate ratio (IRR) for Cryptosporidium infection among children who had received BCG as their last vaccine was 0.0 (95% CI: 0-3.49). However, among those who had received DTP as their last vaccine, the female-male IRR was 6.25 (2.06-18.9) for Cryptosporidium infection and 3.60 (0.91-14.2) for Cryptosporidium-associated diarrhoea. The female-male IRRs for Cryptosporidium infection differed significantly among BCG and DTP recipients (p=0.01). Among children who had received measles as their last routine vaccine, the female-male IRR was 1.57 (0.60-4.11) for Cryptosporidium infection and 0.98 (0.28-3.52) for Cryptosporidium-associated diarrhoea. The female-male IRRs for Cryptosporidium infection differed among DTP and MV recipients (p=0.02). For girls, early DTP vaccination compared with late or no DTP vaccination was associated with increased incidence rate of Cryptosporidium infection (IRR=4.23 (1.04-17.2)). For girls, the incidence rate decreased when they received MV. INTERPRETATION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with a low risk for girls relative to boys, whereas DTP is associated with a high female-male IRR of C. parvum infection.

Animals↗