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Biomedical subjects

M Tanner

Publications and source records attributed to M Tanner.

At least 109 records · Page 6Linked to original sources
PubMed1999

Prevalence and mother-to-infant transmission of hepatitis viruses B, C, and E in Southern Tanzania.

Hepatitis B and C markers were tested in 980 pregnant women, in the infants born to infected mothers, and in a random sample of 42 and 50, respectively, children born to uninfected mothers in Tanzania. Sixty-two women (6.3%) were positive for HBsAg and 15 (24%) were HBeAg-seropositive. Anti-HCV was detected in 49 women (5%), 15 (31%) of whom had detectable viremia. HCV RNA serum levels were low and only genotype 4 was identified. Sixty-six women (6.7%) were positive for anti-HIV, six of whom were coinfected with HBV and one with HCV. Anti-HEV was negative in the 180 women tested. At 8 months of age, HBsAg was detected in 8% and 2% of children born to HBV-infected and noninfected mothers, respectively (P = 0.2). Corresponding figures at 18 months of age were 31% and 21% (P = 0.3). When tested at 2 months of age, HCV RNA was not detected in any of the 43 children born to anti-HCV-positive mothers nor in any of 50 children born to anti-HCV-negative mothers. At 18 months, only one child, born to an anti-HCV-positive mother, had detectable HCV RNA. None of the infants born to women with HIV coinfection were infected with hepatitis viruses. This study suggests that exposure to HEV does not occur in southern Tanzania. The prevalence of current HBV infection in pregnant women from rural Tanzania is lower than in other sub-Saharan areas. In early childhood, HBV infection appears to occur by horizontal rather than maternofilial mechanisms of transmission. The prevalence of HCV infection is similar to that in other African countries. The results of this study show for the first time in Africa that mother-to-infant transmission does not play a significant role in the acquisition of HCV infection.

Adolescent↗
PubMed1999

Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer.

Amplification at the long arm of chromosome 8 occurs in a large fraction of breast and prostate cancers. To clone the target genes for this amplification, we used suppression subtraction hybridization to identify overexpressed genes in the breast cancer cell line SK-Br-3, which harbors amplification at 8q (8q21 and 8q23-q24). A differentially expressed gene identified by SSH, the p40 subunit of eukaryotic translation initiation factor 3 (eIF3), was localized to 8q23 and found to be highly amplified and overexpressed in the breast and prostate cancer cell lines studied. High-level amplification of eIF3-p40 was found in 30% of hormone-refractory prostate tumors and in 18% of untreated primary breast tumors. In the vast majority of the cases, p40 and c-myc were amplified with equal copy numbers. Tumors with higher copy numbers of p40 than c-myc were also found. Expression of p40 mRNA was analyzed with in situ hybridization. The amplification of eIF3-p40 gene was associated with overexpression of its mRNA, as expected for a functional target gene of the amplification. These results imply that genomic aberrations of translation initiation factors, such as eIF3-p40, may contribute to the pathogenesis of breast and prostate cancer.

Blotting, Northern↗
PubMed1999

Age dependence of the multiplicity of Plasmodium falciparum infections and of other malariological indices in an area of high endemicity.

The relationship between age and various malariological indices in the Kilombero valley of Tanzania were examined by compiling data from 6 different community studies carried out between 1989 and 1996. The rate of acquisition of Plasmodium falciparum infection was highest in children 1-5 years of age, while recovery rates were lowest between the first birthday and early adolescence. As a result, peak prevalence was reached in 3-5 years old children. However, the prevalence of clinical malaria (estimated from the excess risk of axillary temperatures > or = 37.5 degrees C attributable to parasitaemia) was highest in children under one year of age. The peak in multiplicity of infection (identified by polymerase chain reaction-restriction fragment length polymorphism of the msp2 locus) occurred in 3-7 years old children. There was a significant correlation between parasite density and multiplicity of infection in infants and young children (1-2 years of age) but not in older individuals.

Adolescent↗
PubMed1999

Multiple Plasmodium falciparum infections in Tanzanian infants.

Paired blood samples from 99 Tanzanian infants were analysed to examine the infection dynamics of Plasmodium falciparum during the first year of life. Infecting parasites were genotyped by polymerase chain reaction amplification of the polymorphic gene for the merozoite surface protein 2 and subsequent analysis according to the resulting restriction fragment length polymorphism pattern. The same samples served as controls in a parallel case-control study for which an additional blood sample was taken from each child during a fever episode. The relationship of the number of concurrent infections (multiplicity) with age and morbidity was analysed and results were compared to those of a similar study on older children between 2 and 7 years of age, carried out in the same village at the same time. The mean of 2 infecting genotypes per positive blood sample from community surveys was low compared to that in older children, and there was no significant age-dependency of multiplicity within the first year of life. Multiplicity of infection in fever cases was also independent of age. In infants, multiplicity was positively associated with parasite density and risk of clinical malaria, in contrast to the situation in older children (> 2 years). The findings help in the understanding of infection dynamics, premunition, and development of semi-immunity in malaria.

Age Factors↗
PubMed1999

Dynamics of multiple Plasmodium falciparum infections in infants in a highly endemic area of Tanzania.

The force of infection and recovery rate for malaria in infants in a highly endemic area of Tanzania were analysed using polymerase chain reaction-restriction fragment length polymorphism genotyping of the Plasmodium falciparum msp2 locus in 99 paired blood samples. Overall, new genotypes were acquired at a rate of 0.064 per day, and the average duration of infections was estimated to be 23 d. The highest recovery rates were in children under 4 months of age. The higher susceptibility of infants to clinical malaria in comparison with older children, in areas of very high transmission, may be largely a consequence of the short duration of infections which precludes the establishment of concomitant immunity. The high turnover of infections also implies that infection prevalence and multiplicity approach an equilibrium even in very young children, and calls into question the use of infant conversion rates as a measure of transmission intensity.

Animals↗
PubMed1999

Effect of iron supplementation and malaria prophylaxis in infants on Plasmodium falciparum genotypes and multiplicity of infection.

During a randomized placebo-controlled trial of chemoprophylaxis against Plasmodium falciparum malaria and iron supplementation, in infants living under conditions of intense transmission, all samples of P. falciparum obtained from children aged 5 and 8 months were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis for the msp2 locus. One hundred and six blood samples were analysed for the number of concurrent infections (multiplicity), and the allelic family of each msp2 genotype was determined. Mean multiplicity of infection was, overall, 2.76 infections/child, and it was significantly reduced in infants receiving chemoprophylaxis. This finding might help to explain the rebound effect in morbidity observed after prophylaxis was ended. Iron supplementation did not affect multiplicity of infection. In infants receiving placebo only, or placebo and iron supplementation, a significant positive association was observed between the number of infections and parasite densities (Spearman's p = 0.25, P-0.047). This association was lost in the group receiving chemoprophylaxis alone, or in combination with iron. This study showed a significant association of FC27-like msp2 alleles with prospective risk of clinical malaria in children (relative risk = 1.487, P = 0.013). Such an association was also found for the present risk of clinical malaria in infants receiving prophylaxis (odds ratio = 3.84, P = 0.026), which might imply that chemoprophylaxis may impair the development of premunition.

Anemia, Iron-Deficiency↗
PubMed1999

Premunition in Plasmodium falciparum infection: insights from the epidemiology of multiple infections.

Epidemiological studies of multiple clone infections by Plasmodium falciparum in highly endemic areas have demonstrated age dependence in both the multiplicity of infection and the relationships between this multiplicity and the risk of acute illness. We hypothesize that, in infants, host defence against blood-stage infections with P. falciparum relies mainly on fever and cytokine activities, and the infections are of short duration. In older children, a high multiplicity of infection is characteristic of low-level chronic parasitaemia. This appears to confer cross-protection against newly inoculated parasites, via partially genotype-specific responses which are short-term, lasting little longer than the infections themselves. This has important implications for our understanding of immunity against P. falciparum, its ecological niche, and the epidemiological impact of interventions against it.

Adolescent↗
PubMed1999

Validation of the Kiswahili version of the SF-36 Health Survey in a representative sample of an urban population in Tanzania.

The objective of this study was to assess the validity of a Kiswahili translation of the SF-36 Health Survey (SF-36) among an urban population in Tanzania, using the method of known-groups validation. People were randomly selected from a demographic surveillance system in Dar es Salaam. The representative sample consisted of 3,802 adults (15 years and older). Health status differences were hypothesized among groups, who differed in sex, age, socioeconomic status and self-reported morbidity. Mean SF-36 scale scores were calculated and compared using t-test and ANOVA. Women had significantly lower mean SF-36 scale scores (indicating worse health status) than men on all scales and scores were lower for older people than younger on all domains, as hypothesized. On five of the eight SF-36 scales, means were higher for people of higher socioeconomic status compared to those of lower socioeconomic status. People who reported an illness within the previous 2 weeks scored significantly lower on all scales compared to those who were healthy, as did people who said they had a disability or a chronic condition.

Adolescent↗
PubMed1999

Antibodies against Plasmodium falciparum vaccine candidates in infants in an area of intense and perennial transmission: relationships with clinical malaria and with entomological inoculation rates.

Serum immunoglobulin (Ig)G1, IgG3 and total IgG were assessed by immunoabsorbent assay in 198 infants from a Tanzanian village highly endemic for Plasmodium falciparum. Antibodies were measured against epitopes of the circumsporozoite protein (the repetitive epitope (NANP)50 and a construct of the flanking regions (CS27IC)), the malaria vaccine SPf66, and two constructs of the merozoite surface protein-1 (MSP-1), a 19-kDa fragment from the C-terminal domain (MSP-119) and an N-terminal fragment spanning blocks 1-6 (H6-p190 M-1/6-H6). IgG1 and total IgG titres showed similar age profiles, all decreasing for the first 2 months of life. Anti-(NANP)50 titres remained very low throughout the first year of life, while anti-CS27IC antibody appeared to peak around 7 months of age. Only a slight tendency to increase with age was observed for levels of the other antibodies studied. IgG3 titres except for H6-p190(1/6), were very low initially and remained very low throughout the first year of life. Clinical malaria incidence at the village dispensary was analysed prospectively in relation to antibody. No IgG1 or total IgG titre showed protective effects, but low IgG3 against p190(1/6) appeared to be a risk factor in some age groups. Given the large number of antibodies tested, this single indication of possible protection could merely be chance. There were no strong associations between antibody titres and entomologically assessed sporozoite exposure suggesting that transmission-reducing interventions may have little effect on antibody levels in such children.

Aging↗
PubMed1999

Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.

BACKGROUND: Malaria control programmes need to protect young children, who bear the brunt of malaria disease and death in Africa. The development of a vaccine is a priority if improved and sustained malaria control is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered through the expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy of SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. METHODS: The study was a two-arm, double blind, individually randomized placebo controlled trial involving 1207 infants. The primary objective of the trial was to estimate the efficacy of three doses of SPf66 given at 1, 2 and 7 months of age in preventing clinical episodes of malaria. These were documented through a health facility-based passive case detection system. RESULTS: Among 1207 randomized children, overall compliance for third dose was 91%. SPf66 was safe, immunogenic and did not interfere with the humoral immune responses to EPI vaccines. There were 294 children among SPf66 recipients and 288 among placebo recipients with at least one malaria episode, yielding a vaccine efficacy estimate of 2% (95% CI: -16, 16; P = 0.84). CONCLUSION: This has been the first trial of a malaria vaccine among very young infants. It provides information on the safety of peptide vaccines administered at this early age as well as their capacity to induce immune responses without negatively interacting with EPI vaccines. Given the modest protection previously documented in older age groups and the lack of efficacy in younger infants, this vaccine in its current alum-based formulation does not appear to have a role in malaria control in sub-Saharan Africa. The lack of efficacy found in this trial also raises concerns about potential difficulties of inducing protective immune responses against malaria through immunization in infants.

Double-Blind Method↗
PubMed1999

Safety in infants of SPf66, a synthetic malaria vaccine, delivered alongside the EPI.

The most likely mechanism to deliver a malaria vaccine in African countries is through the Expanded Program of Immunization (EPI). So far only SPf66, a multistage synthetic peptide, has shown any evidence of protection in Phase III field trials. In Tanzania, SPf66 reduced the risk of clinical malaria by 31% in children aged 1-5 years. In order to progress in the critical path of vaccine development and testing towards the implementation of a new vaccine in malaria control programs, we carried out a randomized double-blind placebo controlled efficacy trial of SPf66 when given alongside the EPI scheme. Monitoring of safety and reactogenicity during this trial included detailed clinical and laboratory assessments on 98 infants and assessment of adverse effects within 1 h of vaccination for all 1207 children vaccinated. Surveillance systems monitored attendances as outpatients, admissions to hospital and fatal events in the community. No serious adverse effects were detected more frequently amongst SPf66 recipients compared to placebo. This first assessment in very young infants of a synthetic vaccine provides evidence of a good safety profile.

Double-Blind Method↗
PubMed1999

Foci of Schistosomiasis mekongi, Northern Cambodia: II. Distribution of infection and morbidity.

In the province of Kracheh, in Northern Cambodia, a baseline epidemiological survey on Schistosoma mekongi was conducted along the Mekong River between December 1994 and April 1995. The results of household surveys of highly affected villages of the East and the West bank of the river and of school surveys in 20 primary schools are presented. In household surveys 1396 people were examined. An overall prevalence of infection of 49.3% was detected by a single stool examination with the Kato-Katz technique. The overall intensity of infection was 118.2 eggs per gram of stool (epg). There was no difference between the population of the east and west shore of the Mekong for prevalence (P = 0.3) or intensity (P = 0.9) of infection. Severe morbidity was very frequent. Hepatomegaly of the left lobe was detected in 48.7% of the population. Splenomegaly was seen in 26.8% of the study participants. Visible diverted circulation was found in 7.2% of the population, and ascites in 0.1%. Significantly more hepatomegaly (P = 0.001), splenomegaly (P = 0. 001) and patients with diverted circulation (P = 0.001) were present on the west bank of the Mekong. The age group of 10-14 years was most affected. The prevalence of infection in this group was 71.8% and 71.9% in the population of the West and East of the Mekong, respectively. The intensity of infection was 172.4 and 194.2 epg on the West and the East bank, respectively. In the peak age group hepatomegaly reached a prevalence of 88.1% on the west and 82.8% on the east bank. In the 20 schools 2391 children aged 6-16 years were examined. The overall prevalence of infection was 40.0%, ranging from 7.7% to 72.9% per school. The overalls mean intensity of infection was 110.1 epg (range by school: 26.7-187.5 epg). Both prevalence (P = 0.001) and intensity of infection (P = 0.001) were significantly higher in schools on the east side of the Mekong. Hepatomegaly (55.2%), splenomegaly (23.6%), diverted circulation (4. 1%), ascites (0.5%), reported blood (26.7%) and mucus (24.3%) were very frequent. Hepatomegaly (P = 0.001), splenomegaly (P = 0.001), diverted circulation (P = 0.001) and blood in stool (P = 0.001) were significantly more frequent in schools of the east side of the Mekong. Boys suffered more frequently from splenomegaly (P = 0.05), ascites (P = 0.05) and bloody stools (P = 0.004) than girls. No difference in sex was found for the prevalence and intensity of infection and prevalence of hepatomegaly. On the school level prevalence and intensity of infection were highly associated (r = 0. 93, P = 0.0001). The intensity of infection was significantly associated only with the prevalence of hepatomegaly (r = 0.44, P = 0. 05) and blood in stool (r = 0.40, P = 0.02). This comprehensive epidemiological study documents for the first time the public health importance of schistosomiasis mekongi in the Province of Kracheh, Northern Cambodia and points at key epidemiological features of this schistosome species, in particular the high level of morbidity associated with infection.

Adolescent↗
PubMed1999

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania.

To investigate the effects of host polymorphisms on malaria morbidity and infection, the frequency distributions of TNF alpha promotor gene and sickle cell trait were studied in infants in an area highly endemic for Plasmodium falciparum transmission in Tanzania. Differences in parasite prevalence, density, febrile episodes with and without parasitaemia, PCV levels and the frequencies of different MSP-2 parasite infections were assessed by genotype. The frequency of the TNF alpha promotor allele 2 was 0.09, and the trait was in Hardy-Weinberg equilibrium. There were no differences in malariametric indices between infants with the normal TNF alpha promoter gene and those who were heterozygous for this trait. Infants heterozygous for the TNF alpha promotor gene appeared to have fewer febrile episodes when they were free of parasites. The two infants homozygous for the TNF alpha promoter allele 2 had both a much higher incidence of fever, independently of parasitaemia, than the average for the other genotypes. The frequency of the sickle cell allele S was 0.06 and the trait was also in Hardy-Weinberg equilibrium. Infants heterozygous for the sickle cell trait had significantly lower parasite densities, but similar prevalence, and MSP-2 infections compared to infants with normal haemoglobin. PCV levels, and the incidence of febrile episodes both with and without parasitaemia were also similar. In contrast to the sickle cell trait, the TNF alpha promotor polymorphism appeared not to have any protective effect on malaria in this study, and its importance in other unspecified fever-causing diseases in this population needs further investigation.

Alleles↗
PubMed1999

A 2-year prospective study in China provides epidemiological evidence for resistance in humans to re-infection with Schistosoma japonicum.

In 1996, 250 people living in the Dongting-Lake region of China were selected for a 2-year study. All had been or were infected with Schistosoma japonicum. All were treated with praziquantel, although eggs of S. japonicum were only detected in stool samples from 75 of the subjects. In 1998, 213 (85.5%) of these subjects, then with a mean (S.D.) age of 40.2 (14.2) years, provided stool samples for final assessment. Forty-nine (23%) of the 213 were found to be re-infected in 1998, with a geometric mean intensity of infection among the infected of 64.5 eggs/g faeces. The rate of re-infection was highest among those aged < 10 years, declining with increasing age, and higher in males than females (27.3% v. 8.3%; P < 0.005). The mean intensity of infection among the infected males was also higher than that among the infected females [72.4 (4.8) v. 17.8 (2.5) eggs/g; P < 0.005]. Water contact by the subjects was estimated from activity diaries, for 141 days over the 2-year study period, and expressed as skin exposure, in m2-min/day. The mean exposure of a group of subjects was calculated by detransforming the mean of the fourth-root-transformed (i.e. normalized) values for the exposures of each subject within the group. Overall, the 213 individuals had a mean exposure of 6.2 m2-min/day. Differences in occupation led to males having much higher mean water exposures than females (9.2 v. 1.1 m2-min/day). As there was an inverse association between age-specific exposure and age-specific re-infection intensity, the marked reduction seen in intensity of re-infection with increasing age is not attributable to decreasing exposure to water. Instead, the results of this 2-year cohort study provide evidence for age-dependent resistance to re-infection with S. japonicum. The 213 subjects who were followed up were classified, according to epidemiological outcome at the end of the study and the data on water contact, as 'susceptible' (N = 49; 23%), 'insusceptible' (N = 29; 13.6%) or of 'uncertain status' (N = 135; 63.4%). Thus, 78 subjects who are potentially informative in terms of immunogenetics were identified. Further investigation of these individuals should help to shed some light on the role of immunogenetic status in human immunity to Schistosoma japonicum.

Adolescent↗
PubMed1999

African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death.

Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] = 6.7, 95% confidence interval [CI] = 3.9-11.7), in children 1-7 months of age with tachypnea (OR = 8.8, 95% CI = 2.6-30.5) and dehydration (OR = 5.0, 95% CI = 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR = 4.7, 95% CI = 2.0-11.2) and inability to localize a painful stimulus (OR = 6.9, 95% CI = 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR = 2.1, 95% CI = 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume < 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.

Adolescent↗
PubMed1999

Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer.

Topoisomerase IIalpha (TOP2A) is a key enzyme in DNA replication and a molecular target for many important anticancer drugs. TOP2A is amplified or deleted together with amplification of the closely located ERBB2/HER-2/neu oncogene in breast cancer. We characterized the copy number aberrations of TOP2A and ERBB2 in 136 primary breast tumors by FISH. Among the 70 primary tumors with ERBB2 amplification, amplification of TOP2A was found in 29 (41%); 30 tumors (43%) showed a physical deletion of TOP2A; and the copy number for TOP2A was not altered in 11 tumors with ERBB2 amplification (16%). No TOP2A gene aberrations were identified in 65 primary tumors without ERBB2 amplification. Fiber FISH revealed that simultaneously amplified ERBB2 and TOP2A were not present in the same amplicon, because repetitive tandem repeat-like signals of ERBB2 and TOP2A were in separate DNA fibers. The deletion of TOP2A (seen in the MDA-361 cell line and in 31 primary tumors) was interstitial, spanning less than two megabases of DNA. Mean copy numbers of TOP2A (2.4 +/- 0.6 for TOP2A vs. 4.9 +/- 1.1 for chromosome 17 centromere) suggest that the deletion of TOP2A occurs before polyploidization of the genome. Eight primary tumors with high-level ERBB2 amplification showed a new type of intratumoral heterogeneity; two different cell clones with either high-level amplification or deletion of TOP2A were found adjacent to each other in the same tumor. These results indicate that amplification of the ERBB2 oncogene is followed by complex secondary genetic aberrations, which lead to amplification or deletion of the TOP2A gene in a majority of tumors. Genes Chromosomes Cancer 26:142-150, 1999.

Antigens, Neoplasm↗
PubMed1999

Investigation of the viability of M. bovis under different environmental conditions in the Kruger National Park.

The survival time of Mycobacterium bovis in the natural habitat of infected free ranging wildlife was investigated. Seven different experimental sites near Skukuza in the Kruger National Park, South Africa, were selected to expose macroscopically affected lung or lymph node tissue of African buffalo (Syncerus caffer) origin and spiked faecal specimens for various lengths of time over a 1-year period. Mycobacterium bovis could be isolated for a maximum period of 6 weeks from tissue specimens and 4 weeks from faeces. The longest survival of M. bovis in both specimen types was observed in winter and under moist conditions. Surprisingly, the survival time of M. bovis in buried specimens seemed greatly reduced to a maximum of 5 days.

Animals↗