Biomedical subjects

Jens Nielsen

Publications and source records attributed to Jens Nielsen.

At least 19 recordsLinked to original sources

PubMed2007

Optimization of heterologous production of the polyketide 6-MSA in Saccharomyces cerevisiae.

Polyketides are a group of natural products that have gained much interest due to their use as antibiotics, cholesterol lowering agents, immunosuppressors, and as other drugs. Many organisms that naturally produce polyketides are difficult to cultivate and only produce these metabolites in small amounts. It is therefore of general interest to transfer polyketide synthase (PKS) genes from their natural sources into heterologous hosts that can over-produce the corresponding polyketides. In this study we demonstrate the heterologous expression of 6-methylsalicylic acid synthase (6-MSAS), naturally produced by Penicillium patulum, in the yeast Saccharomyces cerevisiae. In order to activate the PKS a 4'-phosphopantetheinyl transferase (PPTase) is required. We therefore co-expressed PPTases encoded by either sfp from Bacillus subtilis or by npgA from Aspergillus nidulans. The different strains were grown in batch cultures. Growth and product concentration were measured and kinetic parameters were calculated. It was shown that both PPTases could be efficiently used for activation of PKS's in yeast as good yields of 6-MSA were obtained with both enzymes.

Aspergillus nidulans↗

PubMed2007

A comparison of direct infusion MS and GC-MS for metabolic footprinting of yeast mutants.

Recent technical advances in mass spectrometry (MS) have propelled this technology to the forefront of methods employed in metabolome analysis. Here, we compare two distinct analytical approaches based on MS for their potential in revealing specific metabolic footprints of yeast single-deletion mutants. Filtered fermentation broth samples were analyzed by GC-MS and direct infusion ESI-MS. The potential of both methods in producing specific and, therefore, discriminant metabolite profiles was evaluated using samples from several yeast deletion mutants grown in batch-culture conditions with glucose as the carbon source. The mutants evaluated were cat8, gln3, ino2, opi1, and nil1, all with deletion of genes involved in nutrient sensing and regulation. From the analysis, we found that both methods can be used to classify mutants, but the classification depends on which metabolites are measured. Thus, the GC-MS method is good for classification of mutants with altered nitrogen regulation as it primarily measures amino acids, whereas this method cannot classify mutants involved in regulation of phospholipids metabolism as well as the direct infusion MS (DI-MS) method. From the analysis, we find that it is possible to discriminate the mutants in both the exponential and stationary growth phase, but the data from the exponential growth phase provide more physiological relevant information. Based on the data, we identified metabolites that are primarily involved in discrimination of the different mutants, and hereby providing a link between high-throughput metabolome analysis, strain classification, and physiology.

Fermentation↗

PubMed2007

A systems biology approach to study glucose repression in the yeast Saccharomyces cerevisiae.

Glucose repression in the yeast Saccharomyces cerevisiae has evolved as a complex regulatory system involving several different pathways. There are two main pathways involved in signal transduction. One has a role in glucose sensing and regulation of glucose transport, while another takes part in repression of a wide range of genes involved in utilization of alternative carbon sources. In this work, we applied a systems biology approach to study the interaction between these two pathways. Through genome-wide transcription analysis of strains with disruption of HXK2, GRR1, MIG1, the combination of MIG1 and MIG2, and the parental strain, we identified 393 genes to have significantly changed expression levels. To identify co-regulation patterns in the different strains we applied principal component analysis. Disruption of either GRR1 or HXK2 were both found to have profound effects on transcription of genes related to TCA cycle and respiration, as well as ATP synthesis coupled proton transport, all displaying an increased expression. The hxk2Delta strain showed reduced overflow metabolism towards ethanol relative to the parental strain. We also used a genome-scale metabolic model to identify reporter metabolites, and found that there is a high degree of consistency between the identified reporter metabolites and the physiological effects observed in the different mutants. Our systems biology approach points to close interaction between the two pathways, and our metabolism driven analysis of transcription data may find a wider application for analysis of cross-talk between different pathways involved in regulation of metabolism.

Gene Expression Profiling↗

PubMed2007

Elucidating the mode-of-action of compounds from metabolite profiling studies.

Metabolite profiling has been carried out for decades and is as such not a new research area. However, the field has attracted increasing attention in the last couple of years, and the term metabolome is now often used to describe the complete pool of metabolites associated with an organism at any given time. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the best candidates for comprehensive analysis of the metabolome and the application of these technologies is presented in this chapter. In this relation, the importance of efficient metabolite screening for discovery of novel drugs is discussed. Related to metabolite profiling, the principals underlying the application of labeled substrates to quantify in vivo metabolic fluxes are introduced, and the chapter is concluded by discussing the perspectives of metabolite measurements in systems biology.

Anti-Infective Agents↗

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

The metabolic response of heterotrophic Arabidopsis cells to oxidative stress.

To cope with oxidative stress, the metabolic network of plant cells must be reconfigured either to bypass damaged enzymes or to support adaptive responses. To characterize the dynamics of metabolic change during oxidative stress, heterotrophic Arabidopsis (Arabidopsis thaliana) cells were treated with menadione and changes in metabolite abundance and (13)C-labeling kinetics were quantified in a time series of samples taken over a 6 h period. Oxidative stress had a profound effect on the central metabolic pathways with extensive metabolic inhibition radiating from the tricarboxylic acid cycle and including large sectors of amino acid metabolism. Sequential accumulation of metabolites in specific pathways indicated a subsequent backing up of glycolysis and a diversion of carbon into the oxidative pentose phosphate pathway. Microarray analysis revealed a coordinated transcriptomic response that represents an emergency coping strategy allowing the cell to survive the metabolic hiatus. Rather than attempt to replace inhibited enzymes, transcripts encoding these enzymes are in fact down-regulated while an antioxidant defense response is mounted. In addition, a major switch from anabolic to catabolic metabolism is signaled. Metabolism is also reconfigured to bypass damaged steps (e.g. induction of an external NADH dehydrogenase of the mitochondrial respiratory chain). The overall metabolic response of Arabidopsis cells to oxidative stress is remarkably similar to the superoxide and hydrogen peroxide stimulons of bacteria and yeast (Saccharomyces cerevisiae), suggesting that the stress regulatory and signaling pathways of plants and microbes may share common elements.

Arabidopsis↗

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

Integration of metabolome data with metabolic networks reveals reporter reactions.

Interpreting quantitative metabolome data is a difficult task owing to the high connectivity in metabolic networks and inherent interdependency between enzymatic regulation, metabolite levels and fluxes. Here we present a hypothesis-driven algorithm for the integration of such data with metabolic network topology. The algorithm thus enables identification of reporter reactions, which are reactions where there are significant coordinated changes in the level of surrounding metabolites following environmental/genetic perturbations. Applicability of the algorithm is demonstrated by using data from Saccharomyces cerevisiae. The algorithm includes preprocessing of a genome-scale yeast model such that the fraction of measured metabolites within the model is enhanced, and thus it is possible to map significant alterations associated with a perturbation even though a small fraction of the complete metabolome is measured. By combining the results with transcriptome data, we further show that it is possible to infer whether the reactions are hierarchically or metabolically regulated. Hereby, the reported approach represents an attempt to map different layers of regulation within metabolic networks through combination of metabolome and transcriptome data.

Algorithms↗

PubMed2006

Transcription analysis using high-density micro-arrays of Aspergillus nidulans wild-type and creA mutant during growth on glucose or ethanol.

Here, we describe how the recently published Aspergillus nidulans genome sequence [Galagan, J.E., Calvo, S.E., Cuomo, C., Li-Jun, M., Wortman, J.R., et al., 2005. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438 (7071), 1105-1115] was used to design a high-density oligo array with probes for 3,278 selected genes using the Febit Geniom One array system. For this purpose, the program OligoWiz II was used to design 24,125 probes to cover the 3,278 selected genes. Subsequently, the Febit system was used to investigate carbon catabolite repression by comparing the gene expression of a creA deleted mutant strain with a reference strain grown either with glucose or ethanol as the sole carbon source. In order to identify co-regulated genes and genes influenced by either the carbon source or CreA, the most significantly regulated genes (p<or=0.01) were grouped in eight clusters based on their expression profile. Analysis of the clusters allowed identification of numerous genes that are presumably not regulated by CreA, or alternatively are either directly or indirectly regulated by CreA. Surprisingly, we found evidence that more than 25% of the genes (54 out of the 200 significantly regulated) that are repressed by glucose are not completely de-repressed during growth on ethanol, as deletion of the creA resulted in increased expression of the genes in question even during growth on ethanol. Thus, the expression profiles obtained in the eight clusters indicate that the carbon catabolite repression is not a simple on/off switch but a more complex system not only dependent on the presence or absence of CreA but also on the carbon source.

Aspergillus nidulans↗

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

[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

Hap4 is not essential for activation of respiration at low specific growth rates in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the heme-activated protein complex Hap2/3/4/5 plays a major role in the transcription of genes involved in respiration. Thus, overexpression of HAP4 has been shown to result in a 10% increase in the respiratory capacity. Here the physiology of a HAP4-deleted S. cerevisiae strain was investigated, and we found that the hap4delta S. cerevisiae exhibited poor growth on ethanol, although the growth rate on glucose was indifferent from the wild type in aerobic as well as anaerobic cultures. Moreover, it exhibited a large (75%) reduction in the critical glucose uptake rate at which fermentative metabolism is onset, indicating a substantial reduction in respiratory capacity. We also performed whole genome transcription analysis for the hap4delta and the wild type, grown in carbon-limited chemostat cultures operated at a dilution rate of 0.05 h(-1). Although both strains exhibited respiratory metabolism, there was significant change in expression of many genes in the hap4delta strain. These genes are involved in several different parts of the metabolism, including oxidative stress response, peroxisomal functions, and energy generation. This study strongly indicates that Hap4 activation only occurs at intermediate specific growth rates, below which the transcription of genes responsible for respiration is dependent on the Hap2/3/5 complex and above which the Hap4 protein augments the transcription. Furthermore, statistical analysis of the transcription data and integration of the data with a genome scale metabolic network provided new insight and evidence for the role of Hap4 in transcriptional regulation of mitochondrial respiration.

Biomass↗

PubMed2006

Fungal metabolite analysis in genomics and phenomics.

Metabolomics consists of strategies to quantitatively identify cellular metabolites and to understand how trafficking of these biochemical messengers through the metabolic network influences phenotype. The application of metabolomics to fungi has been strongly pursued because these organisms are widely used for the production of chemicals, are well known for their diverse metabolic landscape and serve as excellent eukaryotic model organisms for studying metabolism and systems biology. Within the context of fungal systems, recent progress has been made in the development of analytical tools and mathematical strategies used in metabolite analysis that have enhanced our ability to crack the code underpinning the cellular inventory, regulatory schemes and communication mechanisms that dictate cellular function. Metabolomics has played a key role in functional genomics and strain classification.

Fungi↗

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↗

PubMed2006

Correlation between the presence of neutralizing antibodies against porcine circovirus 2 (PCV2) and protection against replication of the virus and development of PCV2-associated disease.

BACKGROUND: In a previous study, it was demonstrated that high replication of Porcine circovirus 2 (PCV2) in a gnotobiotic pig was correlated with the absence of PCV2-neutralizing antibodies. The aim of the present study was to investigate if this correlation could also be found in SPF pigs in which PMWS was experimentally reproduced and in naturally PMWS-affected pigs. RESULTS: When looking at the total anti-PCV2 antibody titres, PMWS-affected and healthy animals seroconverted at the same time point, and titres in PMWS-affected animals were only slightly lower compared to those in healthy animals. In healthy animals, the evolution of PCV2-neutralizing antibodies coincided with that of total antibodies. In PMWS-affected animals, neutralizing antibodies could either not be found (sera from field studies) or were detected in low titres between 7 and 14 DPI only (sera from experimentally inoculated SPF pigs). Differences were also found in the evolution of specific antibody isotypes titres against PCV2. In healthy pigs, IgM antibodies persisted until the end of the study, whereas in PMWS-affected pigs they quickly decreased or remained present at low titres. The mean titres of other antibody isotypes (IgG1, IgG2 and IgA), were slightly lower in PMWS-affected pigs compared to their healthy group mates at the end of each study. CONCLUSION: This study describes important differences in the development of the humoral immune response between pigs that get subclinically infected with PCV2 and pigs that experience a high level of PCV2-replication which in 3 of 4 experiments led to the development of PMWS. These observations may contribute to a better understanding of the pathogenesis of a PCV2-infection.

Animals↗

PubMed2006

Yeast systems biology to unravel the network of life.

Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design of advanced cell factories for production of fuels, chemicals, food ingredients and pharmaceuticals. The yeast Saccharomyces cerevisiae represents an excellent model system; the density of biological information available on this organism allows it to serve as a eukaryotic model for studying human diseases. Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single laboratory has access to all the necessary competences. For this reason the Yeast Systems Biology Network (YSBN) has been established. YSBN will coordinate research efforts in yeast systems biology and, through the recently obtained EU funding for a Coordination Action, it will be possible to set appropriate guidelines, establish an appropriate infrastructure for the network and organize courses, meetings and conferences that will consolidate the network and promote systems biology. This paper discusses the impacts of systems biology and how YSBN may play a role in the future development of the field.

European Union↗

PubMed2006

Cytokine and C-reactive protein profiles induced by porcine circovirus type 2 experimental infection in 3-week-old piglets.

The purpose of this study was to determine serum profiles of cytokines at a protein level and Creactive protein (CRP) during the development of postweaning multisystemic wasting syndrome (PMWS) in experimentally inoculated pigs. Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a 35-day period in 10 piglets experimentally infected with PCV2 at 3 weeks of age. Four of the infected piglets developed severe PMWS at 14 to 21 days post-infection (d.p.i.) and died prior to termination of the experiment. The remaining six PCV2-infected piglets experienced transient fever, but did not display overt clinical signs of PMWS and were considered as subclinically infected. A bioassay was used to detect IL-6 and ELISAs were used to detect IFN-alpha, IL-10, and CRP. There were no significant differences in cytokine or CRP expression from 0 to 7 d.p.i. between the PMWS-affected and the subclinically infected piglets. Levels of IL-10 and CRP were elevated from 10 and 14 d.p.i. respectively in the PMWS-affected piglets compared to the subclinically infected piglets. There were no significant differences in IFN-alpha and IL-6 expression between the PMWS-affected piglets and the subclinically infected piglets. The present study shows that elevated levels of serum CRP and IL-10 were associated with PCV2-infected piglets that subsequently developed severe PMWS. This may help to provide further insight into the immunoaetiogenesis of this syndrome.

Animals↗

PubMed2006

Sex differential effects of routine immunizations and childhood survival in rural Malawi.

BACKGROUND: Recent studies from West Africa suggest that routine vaccinations may have sex differential nontargeted effects. To answer whether these patterns are found elsewhere, we reanalyzed data about vaccinations and mortality in a Malawian cohort. METHODS: Children were followed from birth with monthly home visits until 18 months of age. Anthropometric measurements and vaccination information were obtained at these visits. We investigated survival in relation to vaccination status using 2 different methods. First, we included all children updating vaccination information retrospectively. Second, we included only those present at monthly home visits for whom prospective vaccination information was likely to be most complete. SUBJECTS: This study included 751 children surviving the first week of life. MAIN OUTCOME MEASURES: Main outcome measures consisted of mortality rate ratios (MR) for BCG, diphtheria-tetanus-pertussis (DTP) and measles-vaccinated children compared with children who had not received these vaccines and female-male MRs among children who had received the same vaccine. RESULTS: In all analyses, BCG and MV were associated with lower mortality. Children with better nutritional status received DTP1 significantly earlier (P = 0.02). However, DTP1-vaccinated children did not have lower mortality, the MR being 0.99 (0.45-2.19) and 3.19 (0.80-12.8), respectively, using the 2 analyses with retrospective updating or with prospective determination of vaccination status. The female-male MR varied significantly with age, being increased at 3 to 8 months of age, the age of DTP vaccination, and reduced between 9 and 17 months of age, the age of measles vaccination (MV). Using prospective vaccination information, the MR for girls declined after BCG vaccination of unvaccinated girls but increased after DTP1 (P = 0.10) and declined after MV (P = 0.01). Children who received DTP and MV simultaneously had a MR of 5.27 (1.11-25.0) compared with children who received MV only. CONCLUSION: The female-male mortality ratio varied with age. The mode of analysis was important. Using prospective vaccination information like in previous studies from West Africa, BCG, DTP1 and MV had differential effects for girls and boys.

Diphtheria-Tetanus-Pertussis Vaccine↗