PubMed Health⌕ Search

Biomedical subjects

I Felger

Publications and source records attributed to I Felger.

At least 19 recordsLinked to original sources
PubMed2006

Age and seasonal variation in the transition rates and detectability of Plasmodium falciparum malaria.

The effect of acquired immunity on the duration of Plasmodium falciparum infections is unclear, although this is an important term in models of malaria transmission. It is problematical to determine the duration of infections because of the difficulty of distinguishing persisting infections from new ones, and because parasite densities are often transiently below the limit of detection. We recently developed a dynamic model for infection incidence, clearance and detection of multiple genotype P. falciparum infections and fitted it to a panel dataset from a longitudinal study in Northern Ghana. We now extend this model to allow for seasonal and age variation in infection rates and also age dependence in clearance and in detectability of infections. These models indicate that there is seasonal variation in the infection rate, and age dependence in detectability. The best fitting models had no age dependence in infection or clearance rates, suggesting that acquired immunity mainly affects detectability.

Adolescent↗
PubMed2006

[Prevalence, genetic diversity and multiplicity of Plasmodium falciparum infection in school children in central Cote d'Ivoire].

A study was carried out in the village of Taabo, located in the vicinity of a large man-made lake in central Côte d'Ivoire. The objectives were (i) to determine the level of prevalence, genetic diversity and multiplicity of Plasmodiumfakiparum infection in schoolchildren and (ii) to compare the diagnostic performance of light microscopy and polymerase chain reaction (PCR). A total of 424 schoolchildren ranging in age from 5 to 15 years underwent diagnostic testing using both light microscopy of blood smears and PCR. Multiplicity of P. falciparum infection was investigated in 196 children (46.2%). The prevalence of malaria was 54.7% based on light microscopy and 83.9% based on PCR. Genotyping based on polymorphism in the length of the restriction fragment of the gene encoding the merozoite surface protein-2 (msp2) showed that 86.5% of cases involved multiple infection with a geometric mean of 3.87 genotypes per positive child. There was a strong positive correlation between multipcity of infection and parasite density in the 56-year old age group. A total of 50 genotypes including six observed for the first time were identified and classified into families with similar-sized sequence groups: 26 x FC27 (52%) and 24 x 3D7 (48%). In comparison with PCR, the sensitivity and specificity of light microscopy for diagnosis of P. falciparum was 81.3% and 88.2% respectively. Data are discussed in the light of similar studies carried out in sub-Saharan Africa and elsewhere. These findings can serve as a basis for monitoring the longterm effect of major water resource management projects on the prevalence, genetic diversity and multiplicity of P. falciparum infection.

Adolescent↗
PubMed2004

A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children.

Several studies suggest that in individuals with substantial previous exposure to malaria, co-infection with multiple clones of Plasmodium falciparum can protect against subsequent clinical malaria attacks. Other studies, mainly of individuals with little previous exposure, found the converse relationship. To test whether acquisition of such cross-protection tracks the acquisition of clinical immunity in general, 610 Tanzanian children aged 0-6 years were enrolled in a nine-month prospective study of the risk of morbidity in relation to parasitological status and merozoite surface protein 2 genotypes on enrolment. Prevalence of parasitaemia and multiplicity of infection increased with age. In the first year of life, the incidence of clinical malaria was almost three times higher in children with parasites at baseline than in those without. In older children, baseline P. falciparum infections appeared to protect against both parasitaemic and non-parasitaemic fever episodes. In children aged less than three years, baseline multiple infection tended to be associated with higher prospective risk of clinical malaria than single infection while in children aged more than three years the converse was found, but these effects were not statistically significant. These results provide further evidence that relationships between asymptomatic malaria infections and clinical malaria change with cumulative exposure.

Age Distribution↗
PubMed2002

Molecular epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana.

Age dependence of malaria infection was assessed in an age-stratified cluster sample of 308 individuals from Kassena-Nankana District of northern Ghana during June and July 2000. Overall prevalence of Plasmodium falciparum by microscopy was 70%, with the maximum among 5-9 year olds. Parasite density was highest (geometric mean 1922/microl blood) in 1-2 year olds. Eighty-two per cent of samples were positive by polymerase chain reaction (PCR), and restriction fragment length polymorphism typing of the P. falciparum msp2 revealed a mean msp2 multiplicity of 3.4 (range: 1-8) genotypes per PCR positive sample. Multiplicity increased with age until 5-9 years and then started to reduce again into adulthood. About 49.3% of infections belonged to the msp2 FC27 allelic family and 50.7% to the 3D7 family. On the day of the survey, only 3.6% of the participants had fever (axillary temperature >or= 37.5 degrees C) and 2.3% had fever associated with parasitaemia. The correlation between parasite density and msp2 multiplicity was 0.42; highest among infants, and decreased with age to a minimum among 5-9 year olds. Contrasting with results from Tanzania, this correlation increased with age in adolescents and adults. Parasite multiplicity is very high in this community, and the patterns of age dependence are similar to those in other holoendemic sites in Africa, validating the use of the age-multiplicity relationship as an indicator of malaria endemicity.

Adolescent↗
PubMed2001

Prospective risk of morbidity in relation to multiplicity of infection with Plasmodium falciparum in São Tomé.

The prospective risk of acute morbidity was analysed in relation to multiplicity of Plasmodium falciparum infection in 491 individuals in a peri-urban community in São Tomé. In an initial cross-sectional survey, 40.5% of individuals were recorded by microscopy as infected with P. falciparum, and by PCR 60.5%, with the maximum prevalence in children aged 5-10 years. PCR-RFLP typing of the msp-2 gene of P. falciparum found a mean of 2.4 parasite genotypes per infected person, with little age dependence in this multiplicity and a total of 43 different msp-2 alleles identified. None of these were unique for São Tomé. Study participants were encouraged to report to a project worker whenever they suffered a febrile illness. During the 3 months following the parasitological survey the recorded incidence rates decreased with increasing baseline msp-2 multiplicity, both for P. falciparum-positive episodes and for fever without parasitaemia. While this is consistent with suggestions that multiple P. falciparum infections may protect against super-infecting parasites, confounding by patterns of health service usage is an alternative explanation. The incidence of clinical malaria episodes was only a little higher in children than in adults. This weak age-dependence in clinical immunity might be a consequence of a cohort effect resulting from resurgence of the disease after the breakdown of malaria control programs in the 1980s.

Adolescent↗
PubMed2000

Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5' flanking sequences.

Approximately 50 highly diverse var genes distributed throughout the haploid genome of the malaria parasite Plasmodium falciparum code for PfEMP1 variants located on the surface of infected erythrocytes. PfEMP1 is involved in cytoadherence of parasitised red blood cells and undergoes antigenic variation through differential expression of var genes. Members of the var gene family are located in chromosome-internal positions on chromosomes 4, 7, 8 and 12, and in subtelomeric regions of all chromosomes. Here we show that there are two distinct and conserved types of 5' upstream regions (var17-type and 5B1-type) of var genes, and suggest that most subtelomeric var genes are flanked by a var17-type 5' upstream sequence. In contrast, 5B1-type 5' upstream are localised to chromosomes that have been shown to contain var genes within chromosome-internal regions. Transcriptional analysis using RT-PCR revealed that var genes flanked by either type of 5' upstream sequence are transcribed in in vitro cultured trophozoite stage parasites. In addition, we have shown that the 5' flanking sequences of four different var genes are able to drive transient expression of the cat reporter gene. Our results suggest that at least the minimal regulatory sequences required for transcription of var genes are conserved among both subgroups of the var gene family. Furthermore, these sequences provide new markers for the investigation of the chromosomal organisation of var genes.

5' Untranslated Regions↗
PubMed2000

Analysis of Plasmodium falciparum infections in a village community in Northern Nigeria: determination of msp2 genotypes and parasite-specific IgG responses.

The genetic diversity of P. falciparum and multiplicity of infection has been studied in a village in Northern Nigeria at the end of the rainy season, when transmission is high. We analysed blood samples from 104 individuals aged 5-70 years by polymerase chain reaction (PCR) amplifying the gene for the merozoite surface protein MSP2 followed by genotyping based on restriction fragment length polymorphism (RFLP). 94.2% of all samples were parasite positive by PCR and over 80% of those had multiple infections. The age distribution of the average number of parasite clones present in P. falciparum infections showed an initial increase, then reached a peak multiplicity in children 8-10 years of age, and afterwards decreased significantly with age. Mean multiplicity in those 8-10-year-old children was 5.4 clones per carrier. Peak multiplicity and parasite diversity in Nigerian individuals is compared to findings from other study sites in Africa and PNG. The prevalence of IgG antibodies against the circumsporozoite protein (CSP), an indicator for malaria exposure, was over 85% in all age groups showing a high exposure of villagers to P. falciparum. OD values in ELISA were positively correlated with age. There was no correlation between the level of IgG against CSP and the multiplicity of P. falciparum infections determined by PCR of msp2. These results imply that in highly endemic areas multiplicity of infection is not directly correlated with exposure to P. falciparum.

Adolescent↗
PubMed2000

Plasmodium falciparum: expression of gametocyte-specific genes in monolayer cultures and malaria-positive blood samples.

In order to facilitate molecular epidemiological studies on the transmission of the malaria parasite Plasmodium falciparum a sensitive assay for gametocyte detection based on RT-PCR was developed. The transcription of the sexual stage-specific genes Pfs16, Pfs48/45, Pfs230, and Pfs25, as well as the sexual stage- and sporozoite-specific S 18S rRNA, was detected by RT-PCR. S 18S rRNA was present in seven of nine P. falciparum-positive blood samples, despite the lack of microscopic detection of gametocytes and a parasitemia below 0.1%. Expression of the other four gametocyte-specific genes was detected less frequently in malaria-positive blood samples. These findings indicate that RT-PCR of S 18S rRNA is a highly sensitive method for gametocyte detection and, furthermore, that gametocytes are present in the peripheral blood of most malaria carriers, even if the parasitemia is below 0.1%. To determinate the expression pattern of sexual stage-specific genes in more detail, RT-PCR was performed at consecutive time points of highly synchronized monolayer cell cultures. Transcripts of all examined genes except Pfs25 were detected directly after invasion of merozoites of the strain NF54 in red blood cells.

Animals↗
PubMed1999

Rapid DNA extraction for molecular epidemiological studies of malaria.

DNA isolation from blood samples collected in molecular epidemiological studies is crucial for the quality and reproducibility of data. Blood samples from two malaria endemic sites have been prepared by four different DNA isolation methods with subsequent PCR amplification of the msp2 locus of Plasmodium falciparum. We tested a rapid boiling method; the guanadine isothiocyanate DNA extraction; QIAmp blood kit; and the ISOCODE STIX PCR template preparation dipstick, and analysed the numbers of concurrent infections/sample. The rapid boiling method and the ISOCODE STIX provided overall the best sensitivity combined with ease of handling. The possibility to store and ship the ISOCODE STIX at ambient temperature adds further advantage to this method.

Animals↗
PubMed1999

Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania.

The merozoite surface protein 2 (MSP2) of Plasmodium falciparum is extremely polymorphic: 82 different msp2 alleles were found in 4 studies of molecular epidemiology conducted in Tanzania. This diversity renders msp2 suitable as a marker gene for the genotyping of P. falciparum infections. Amplification of msp2 by the polymerase chain reaction (PCR), and subsequent restriction digests of the PCR product (PCR-restriction fragment length polymorphism genotyping), has proved to be an informative tool for enumerating multiple concurrent infections in a blood sample, and distinguishing individual alleles. Depending on the specific questions asked in a genotyping study, analytical techniques of different degrees of complexity are employed. The restriction fragments resulting from a single HinfI digest generally allow the enumeration of multiple concurrent infections and the determination of their allelic families. When a restriction pattern is too complex to be resolved, owing to the high number of concurrent infections, or due to the appearance of previously undescribed alleles, one or more additional digests (DdeI, RsaI, ScrfI) may be necessary. To determine individual alleles unequivocally, in particular in longitudinal studies, when several consecutive samples need to be compared with each other, a more detailed analysis involving all 3 additional digests is applied. The methodological experience and results gained in 4 epidemiological field studies involving msp2 genotyping are summarized. We also provide the HinfI restriction patterns and some nucleotide sequences of the alleles found so far in our studies in Tanzania.

Alleles↗
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

Effect of insecticide-treated bed nets on haemoglobin values, prevalence and multiplicity of infection with Plasmodium falciparum in a randomized controlled trial in Tanzania.

A randomized controlled trial of insecticide-treated bed nets (ITNs) was conducted in an area of high malaria transmission in Tanzania in order to assess the effects of ITNs on infection and anaemia. One hundred and twenty-two children, aged 5 to 24 months, were randomly allocated to 2 groups, one of which received ITNs. Outcome measures were assessed in 6 consecutive months with monthly cross-sectional surveys. These measures were haemoglobin values, Plasmodium falciparum prevalence and density, and multiplicity of infection determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) of the msp2 locus. There was a significant increase in mean heamoglobin values and a significant decrease of 16.4% in microscopically determined P. falciparum prevalence in children in the ITN group six months after the start of the trial. Both effects were more pronounced in younger children. However, no significant difference was observed in parasite density or multiplicity of infection among infected children. Comparison with PCR results indicated that microscopically subpatent parasitaemia was more frequently found in children in the ITN group. This, together with the observed similar multiplicity in the 2 groups, suggests that infections are maintained despite ITN use, owing to the chronicity of infections. This study shows that ITNs reduce the risk of anaemia in highly exposed young children. The virtually unchanged multiplicity of infection indicates that the potentially protective concomitant immunity is not compromised.

Anemia, Iron-Deficiency↗
PubMed1999

Effect of insecticide-treated bed nets on the dynamics of multiple Plasmodium falciparum infections.

The rates of acquisition and loss of individual genotypes belonging to the FC27 family of the Plasmodium falciparum merozoite surface protein 2 (msp2) gene were studied in 120 children aged 5 months to 2.5 years, in a randomized controlled trial of insecticide-treated bed nets (ITNs) in Kiberege village, Tanzania. Analysis of longitudinal changes in positivity for individual alleles in samples collected at intervals of one month indicated that the average duration of infections, allowing for undetected parasite genotypes, was 73 d in those aged < 18 months and 160 d in children aged > or = 18 months, consistent with a shift from acute to chronic infection with age. Overall, 51% of genotypes infecting the host were estimated to be detected by polymerase chain reaction-restriction fragment length polymorphism analysis in any one sample of 0.5 microL of packed peripheral blood cells. In children less than 18 months old this sensitivity was 61% (SE = 6%) compared with 41% (SE = 6%) in older children. Conversely, the rate of appearance of new parasite genotypes was higher in children < 18 months of age than in older children, but this partly reflected the difference in sensitivity. The overall incidence of new infections was estimated to be reduced by 17% in ITN users. There was no statistically significant difference between users and non-users in observed infection multiplicity, sensitivity, recovery rate, or estimated infection rates for individual alleles. This suggests that, in areas of high P. falciparum endemicity, ITNs have little effect on the establishment of chronic malaria infection.

Alleles↗
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↗