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Ib C Bygbjerg

Publications and source records attributed to Ib C Bygbjerg.

18 recordsLinked to original sources
PubMed2006

Early home-based recognition of anaemia via general danger signs, in young children, in a malaria endemic community in north-east Tanzania.

BACKGROUND: Ethnographic studies from East Africa suggest that cerebral malaria and anaemia are not classified in local knowledge as malaria complications, but as illnesses in their own right. Cerebral malaria 'degedege' has been most researched, in spite of anaemia being a much more frequent complication in infants, and not much is known on how this is interpreted by caretakers. Anaemia is difficult to recognize clinically, even by health workers. METHODS: Ethnographic longitudinal cohort field study for 14 months, with monthly home-visits in families of 63 newborn babies, identified by community census, followed throughout April - November 2003 and during follow-up in April-May 2004. Interviews with care-takers (mostly mothers) and observational studies of infants and social environment were combined with three haemoglobin (Hb) screenings, supplemented with reports from mothers after health facility use. RESULTS: General danger signs, reported by mothers, e.g. infant unable to breast-feed or sit, too weak to be carried on back - besides of more alarming signs such as sleeping all time, loosing consciousness or convulsing - were well associated with actual or evolving moderate to severe anaemia (Hb </= 5-8 g/dl). By integrating the local descriptions of danger symptoms and signs, and comparing with actual or evolving low Hb, an algorithm to detect anaemia was developed, with significant sensitivity and specificity. For most danger signs, mothers twice as often took young children to traditional healers for herbal treatment, rather than having their children admitted to hospital. As expected, pallor was more rarely recognized by mothers, or primary reason for treatment seeking. CONCLUSION: Mothers do recognize and respond to symptoms and danger signs related to development of anaemia, the most frequent complication of malaria in young children in malaria endemic areas. Mothers' observations and actions should be reconsidered and integrated in management of childhood illness programmes.

Algorithms↗
PubMed2006

Occurrence of the Southeast Asian/South American SVMNT haplotype of the chloroquine-resistance transporter gene in Plasmodium falciparum in Tanzania.

Two main haplotypes, CVIET and SVMNT, of the Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt) are linked to 4-aminoquinoline resistance. The CVIET haplotype has been reported in most malaria-endemic regions, whereas the SVMNT haplotype has only been found outside Africa. We investigated Pfcrt haplotype frequencies in Korogwe District, Tanzania, in 2003 and 2004. The SVMNT haplotype was not detected in 2003 but was found in 19% of infected individuals in 2004. Amodiaquine use has increased in the region. The introduction and high prevalence of the SVMNT haplotype may reflect this and may raise concern regarding the use of amodiaquine in artemisinin-based combination therapies in Africa.

Adolescent↗
PubMed2006

High reinfection rate and treatment failures in children treated with amodiaquine for falciparum malaria in Muheza villages, Northeastern Tanzania.

In May 2003, we studied amodiaquine (AQ) efficacy in children < 5 years of age with uncomplicated falciparum malaria in Magoda and Mpapayu (with insecticide treated nets [ITNs]) and Mgome (without ITNs) in Muheza, Tanzania. The trial involved 28 days of follow-up, and data were adjusted by polymerase chain reaction (PCR) genotyping of msp1 and msp2 genes. Additionally, Pfcrt codon 72-76 polymorphisms were studied by PCR and sequence-specific oligonucleotide probe (SSOP) ELISA. In 54 cases with complete follow-up, a significant difference in late treatment failure (LTF) rates was seen (60.7% in ITN versus 88.5% in non-ITN villages, P = 0.02) before PCR correction. However, after PCR correction, 23 cases (60.5%) were confirmed as reinfections, giving a true LTF rate of 21.4% (6/28) and 34.6% (9/26) in the above settings, respectively. Frequency of Pfcrt CVIET haplotype mutation pretreatment was high (97.0%); the remaining samples were CVMNK. We conclude that AQ alone is no longer effective in the study area.

Amodiaquine↗
PubMed2005

Rapid screening for glucose-6-phosphate dehydrogenase deficiency and haemoglobin polymorphisms in Africa by a simple high-throughput SSOP-ELISA method.

BACKGROUND: Mutations in the haemoglobin beta-globin (HbB) and glucose-6-phosphate dehydrogenase (G6PD) genes cause widespread human genetic disorders such as sickle cell diseases and G6PD deficiency. In sub-Saharan Africa, a few predominant polymorphic variants of each gene account for a majority of these deficiencies. Examining at a larger scale the clinical importance of these independent genetic disorders, their possible association with malaria pathogenesis and innate resistance, and their relevance for antimalarial drug treatment, would be easier if an accurate screening method with limited costs was available. METHODS: A simple and rapid technique was developed to detect the most prominent single nucleotide polymorphisms (SNPs) in the HbB and G6PD genes. The method is able to detect the different haemoglobin polymorphisms A, S, C and E, as well as G6PD polymorphisms B, A and A- based on PCR-amplification followed by a hybridization step using sequence-specific oligonucleotide probes (SSOPs) specific for the SNP variants and quantified by ELISA. RESULTS: The SSOP-ELISA method was found to be specific, and compared well to the commonly used PCR-RFLP technique. Identical results were obtained in 98% (haemoglobin) and 95% (G6PD) of the tested 90 field samples from a high-transmission area in Tanzania, which were used to validate the new technique. CONCLUSION: The simplicity and accuracy of the new methodology makes it suitable for application in settings where resources are limited. It would serve as a valuable tool for research purposes by monitoring genotype frequencies in relation to disease epidemiology.

Anemia, Sickle Cell↗
PubMed2005

[Imported diseases].

In Denmark, about one third of notifiable diseases are imported, but these have had only a limited spread within the Danish community. For example, imported strains of Mycobacterium tuberculosis remain confined to the immigrant population, and the high prevalence of chronic hepatitis B among certain groups of immigrants has not resulted in a general increase in the incidence of hepatitis B. Exceptions are imported cases of hepatitis A in children, which have resulted in outbreaks in the indigenous Danish population, and the import of drug-resistant bacteria, which often pose a serious challenge to hospital hygiene.

Adult↗
PubMed2005

A simple, high-throughput method to detect Plasmodium falciparum single nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate synthase, and P. falciparum chloroquine resistance transporter genes using polymerase chain reaction- and enzyme-linked immunosorbent assay-based technology.

Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum dihydrofolate reductase (dhfr), and dihydropteroate synthetase (dhps), and chloroquine resistance transporter (Pfcrt) genes are used as molecular markers of P. falciparum resistance to sulfadoxine/pyrimethamine and chloroquine. However, to be a practical tool in the surveillance of drug resistance, simpler methods for high-throughput haplotyping are warranted. Here we describe a quick and simple technique that detects dhfr, dhps, and Pfcrt SNPs using polymerase chain reaction (PCR)- and enzyme-linked immunosorbent assay (ELISA)-based technology. Biotinylated PCR products of dhfr, dhps, or Pfcrt were captured on streptavidin-coated microtiter plates and sequence-specific oligonucleotide probes (SSOPs) were hybridized with the PCR products. A stringent washing procedure enabled detection of remaining bound SSOPs and distinguished between the SNPs of dhfr, dhps, and Pfcrt with high specificity. The SSOP-ELISA compared well with a standard PCR-restriction fragment length polymorphism procedure, and gave identical positive results in more than 90% of the P. falciparum slide-positive samples tested. The SSOP-ELISA of all dhfr, dhps, or Pfcrt SNPs on 88 samples can be performed in a single day and provides quick and reproducible results. The system can potentially be modified to detect SNPs in other genes.

Animals↗
PubMed2005

Response of Plasmodium falciparum to cotrimoxazole therapy: relationship with plasma drug concentrations and dihydrofolate reductase and dihydropteroate synthase genotypes.

We assessed the efficacy of trimethoprim/sulfamethoxazole (TRM/SMX) in vivo in relation to the frequency of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) alleles in 45 Sudanese malaria patients. Plasma levels of TRM, SMX, and acetylsulfamethoxazole (AcSMX) were measured before treatment and at days 3, 7, and 14 or upon recrudescence to ascertain drug absorption. Forty patients (89%) had an adequate clinical response, one patient (2%) had an early treatment failure response, while four patients (8%) showed late treatment failure responses. Genotyping of merozoite surface protein 1, MSP-1, MSP-2, and glutamate-rich protein before treatment and upon recrudescence showed that all recurring parasites were recrudescences. The plasma levels of TRM, AcSMX, and SMX indicated adequate drug absorption in all patients. This suggests parasite resistance as a cause of treatment failure. The presence of dhfr Ile 51 and Asn 108 alone or coupled with dhps Ala-436 among parasites that were cleared after treatment indicates that these alleles alone are insufficient to cause in vivo resistance. However, the presence of the triple mutant dhfr (Ile-51/Arg-59/Asn-108) with the dhps Gly-437 genotype in all recurring infections, suggests the importance of codon 59 and 437 alleles in susceptibility to TRM/SMX. However, the number is too little to make firm conclusions.

Animals↗
PubMed2005

Oral and constitutional manifestations of HIV-infected hospital patients in Northern Vietnam.

This study reports clinical features, with emphasis on oral lesions and constitutional signs, of 170 patients in a regional hospital in northern Vietnam, of whom 56 were HIV positive. The purpose of the study was to investigate the relationship of oral hairy leukoplakia (OHL) and oropharyngeal candidiasis (OPC) with HIV infection and late stage HIV disease. Late stage HIV disease was defined as WHO stage III or IV and/or a total lymphocyte count below 1200 cells/mm3. The 56 HIV positive patients included all patients with a positive HIV test between July 7th and September 9th 2002. A total of 114 HIV negative controls were included as well. All patients had a detailed medical history and examination as well as a thorough oral examination, which were all done without prior knowledge of the patient's HIV serostatus. HIV positive patients were then grouped according to WHO clinical stage and total lymphocyte count. Thirty-six patients (64.3%) out of 56 HIV positives were in WHO stage III+IV and 28 patients (50.0%) had a total lymphocyte count below 1200 cells/mm3. The presence of OPC, weight loss of more than 10% of body weight and/or chronic fever of more than one month's duration showed a significant association and high positive prediction with HIV infection, especially late stage HIV disease [all with odds ratio (OR) and 95% confidence interval (CI > 1)]. The presence of OHL only showed a significant association with positive HIV serostatus and WHO stage III+IV. It can be concluded that in North Vietnam, HIV positive patients and patients suspected of having HIV infection would benefit from initial and repeat oral examinations. OPC, together with other signs of progressive infection (constitutional signs, such as weight loss and chronic fever) may serve as indicators for institution of prophylactic drugs against opportunistic infections and even antiretroviral (ARV) therapy, when available. However, further research is needed to demonstrate the role of OHL in HIV patients in North Vietnam.

AIDS-Related Opportunistic Infections↗
PubMed2004

Homology building as a means to define antigenic epitopes on dihydrofolate reductase (DHFR) from Plasmodium falciparum.

BACKGROUND: The aim of this study was to develop site-specific antibodies as a tool to capture Plasmodium falciparum-dihydrofolate reductase (Pf-DHFR) from blood samples from P. falciparum infected individuals in order to detect, in a sandwich ELISA, structural alterations due to point mutations in the gene coding for Pf-DHFR. Furthermore, we wanted to study the potential use of homology models in general and of Pf-DHFR in particular in predicting antigenic malarial surface epitopes. METHODS: A homology model of Pf-DHFR domain was employed to define an epitope for the development of site-specific antibodies against Pf-DHFR. The homology model suggested an exposed loop encompassing amino acid residues 64-100. A synthetic peptide of 37-mers whose sequence corresponded to the sequence of amino acid residues 64-100 of Pf-DHFR was synthesized and used to immunize mice for antibodies. Additionally, polyclonal antibodies recognizing a recombinant DHFR enzyme were produced in rabbits. RESULTS AND CONCLUSIONS: Serum from mice immunized with the 37-mer showed strong reactivity against both the immunizing peptide, recombinant DHFR and a preparation of crude antigen from P. falciparum infected red blood cells. Five monoclonal antibodies were obtained, one of which showed reactivity towards crude antigen prepared from P. falciparum infected red cells. Western blot analysis revealed that both the polyclonal and monoclonal antibodies recognized Pf-DHFR. Our study provides insight into the potential use of homology models in general and of Pf-DHFR in particular in predicting antigenic malarial surface epitopes.

Amino Acids↗
PubMed2004

Are multilateral malaria research and control programs the most successful? Lessons from the past 100 years in Africa.

Multilateral malaria research and control programs in Africa have regained prominence recently as bilateral assistance has diminished. The transnational nature of the threat and the need for inspired leadership, good coordination, and new discoveries to decrease the impact of the disease has led to the founding of the Multilateral Initiative on Malaria, the Roll Back Malaria Project, Global Fund for HIV, Tuberculosis and Malaria (Global Fund), the Medicines for Malaria Venture, and the Malaria Vaccine Initiative, among other groups. Historically, the most striking feature of malaria control and elimination activities was the connectedness and balance between malaria research and control especially, from 1892 to 1949. A combination of scientific originality, perseverance in research, integrated approaches, and social concern were the keys for success. The elimination of Anopheles gambiae from Upper Egypt in 1942 using integrated vector control methods is a prime example of malaria control during the first half of the 20th century where those factors were brought together. After 1949, there were three decades of great optimism. Four notable landmarks characterized this period: the Kampala Conference in 1950; the Global Malaria Eradication Program beginning in 1955; the primary health care strategies adopted by most African States after attaining their political independence in the 1960s, and accelerating in the 1980s; and creation of the Special Program in Training and Research in Tropical Diseases at the World Health Organization in 1975. The initial highly encouraging operational results, largely obtained in temperate or subtropical areas where transmission was unstable, engendered undue expectations for the success of identical antimalarial measures elsewhere. Many were convinced that the eradication was in sight, such that support for malaria research virtually ceased. Young, bright scientists were discouraged from seeking a career in a discipline that appeared to soon become superfluous. It took more than three decades to modify antimalarial strategies and to rehabilitate long-term control as an intermediate objective. In Africa, although multilateral malaria programs have grown over the past half century and proved the most successful, fragmentation of co-ordination remains and is a major challenge. The proliferation of malaria programs in the late 1990s has brought substantial additional funds and expertise. However, excessive funding competition and failure of different programs to collaborate has resulted in poor communication and duplication of activities. The capacities of the African nations to conduct high-quality research and to coordinate control efforts are in great jeopardy. There is an urgent need for a non-partisan umbrella organ to coordinate and facilitate the network of alliances and programs in malaria research and control in Africa.

Africa↗
PubMed2003

Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial.

BACKGROUND: Malaria is a major cause of infant morbidity and mortality in sub-Saharan Africa, and is often complicated by severe anaemia. Resistance of Plasmodium falciparum to most affordable antimalarial drugs is an impediment to intermittent chemotherapy. We investigated the effect of presumptive intermittent treatment with amodiaquine and daily iron supplementation in infants on malarial fevers and anaemia, in a holoendemic area of Tanzania where malaria is largely resistant to chloroquine and sulfadoxine/ pyrimethamine. METHODS: 291 infants aged 12-16 weeks who attended three clinics were randomised to receive amodiaquine, iron supplementation, amodiaquine plus iron supplementation, or placebo. Over 6 months, we gave amodiaquine three times with intervals of 60 days; oral iron supplementation was given daily. Malarial fevers and anaemia were monitored at bimonthly treatment visits and by self-reporting to health centres. FINDINGS: The protective efficacy of intermittent amodiaquine treatment in prevention of malarial fevers and anaemia was 64.7% (95% CI, 42.4-77.2) and 67.0% (95% CI, 34.5-83.4), respectively. Protective efficacy was similar in the group receiving amodiaquine plus iron supplementation. Infants receiving iron supplementation only were partly protected against anaemia (protective efficacy 59.8%; 95% CI, 23.4-78.9), but not against malarial fevers. 4 months' follow-up did not show rebound morbidity. We noted no haematological or clinical adverse effects. INTERPRETATION: Presumptive intermittent treatment for malaria with amodiaquine reduced malarial fevers and anaemia in infants, in an area with high resistance to other antimalarials. Intermittent treatment strategies for malaria in highly endemic areas could be of great benefit to public health.

Amodiaquine↗
PubMed2003

Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole.

A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genotypes were determined. dhfr genotypes correlated with PYR and TRM drug responses (r = 0.93 and 0.85). Isolates with wild-type alleles showed mean half inhibitory concentrations (IC50 +/- SD) of 0.10 +/- 0.10 and 0.15 +/- 0.06 microg/100 microl for PYR and TRM. Parasites with mutations at codons 108 and 51 alone or combined with codon 59 have IC50 of 11.46 +/- 0.86 (PYR) and 2.90 +/- 0.59 microg/100 microl (TRM). For both drugs, the differences in the mean IC50 between wild and mutant parasites were statistically significant (P < 0.001). Isolates with mixed wild and mutant alleles showed an intermediate level of susceptibility. Our data show partial cross-resistance between PYR/TRM and SDX/SMX (r = 0.85 and 0.65). Correlation was not observed between different dhps genotypes and the in vitro outcome to SDX and SMX (r = 0.30 and 0.34). The lack of correlation could be due to folates and para-aminobenzoic acid in the RPMI medium and the serum used to supplement the cultures.

Adolescent↗
PubMed2003

Increasing prevalence of wildtypes in the dihydrofolate reductase gene of Plasmodium falciparum in an area with high levels of sulfadoxine/pyrimethamine resistance after introduction of treated bed nets.

In Magoda and Mpapayu villages in Tanzania, we have previously found comparable high prevalence of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine (S/P) in vivo and of mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of P. falciparum responsible for resistance to S/P. In December 1998, Magoda received insecticide-treated nets (ITNs), whereas ITNs were introduced in Mpapayu in March 2001. We have studied the effect of ITNs on P. falciparum resistance genes by monitoring the prevalence of dhfr and dhps genotypes in children less than five years old living in the villages from 1998 to 2000. In 2000, after two years of bed net use, the prevalence of wild types in codon 51, 59, and 108 of dhfr increased significantly in Magoda compared with previous years. Furthermore, the prevalence of dhfr wild types was significantly higher in Magoda than in Mpapayu in 2000. The impact of ITNs on the transmission intensity seems not only to affect the overall malaria morbidity, but may even facilitate restoration of susceptibility to antimalarial drugs.

Animals↗
PubMed2003

Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity.

Plasmodium falciparum resistance to sulfadoxine/pyrimethamine (S/P) is due to mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhfr) genes. Large-scale screening of the prevalence of these mutations could facilitate the surveillance of the level of S/P resistance in vivo. The prevalence of mutations in dhfr and dhps in relation to S/P efficacy was studied in four sites of differing endemicity in Sudan, Mozambique, and Tanzania. The sites were organized in order of increasing resistance and a significant increase in the prevalence of triple mutations in codons c51, c59, and c108 of dhfr was observed. A similar trend was observed when dhfr genotypes were combined with c437 of dhps. Since the differences in S/P resistance between the sites were minor, but nevertheless revealed major differences in dhfr genotype prevalence, the role of dhfr as a general molecular marker seems debatable. The differences may reflect variation in the duration and magnitude of S/P usage (or other antifolate drugs) between the sites. Thus, triple dhfr mutations may prove suitable only as a general guideline for detecting emerging S/P resistance in areas where S/P has been introduced recently. However, changes in susceptibility within the same area with moderate levels of resistance may be possible by longitudinal surveillance of a subset of dhfr/dhps mutations that has been associated with S/P resistance in vivo in a defined location.

Adolescent↗
PubMed2002

Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated falciparum malaria: relation between dihydropteroate synthase/dihydrofolate reductase genotypes, sulfadoxine plasma levels, and treatment outcome.

Several in vitro studies have shown the correlation between mutations in dhfr and dhps genes and resistance to pyrimethamine/sulfadoxine (PYR/SDX) combination, but the in vivo correlates of these mutations with PYR/ SDX efficacy have not been investigated fully. We assessed PYR/SDX efficacy in relation to the frequency of dhfr and dhps mutations in 37 Plasmodium falciparum isolates sampled before treatment. Plasma levels of SDX measured at days 0, 3, 7, and 14 ascertained drug absorption. Point mutations were detected only at codons 51 and 108 of dhfr and codon 436 of dhps. The frequency of dhfr 51/108 and dhps 436 mutations was 79% and 8%. The plasma levels of SDX indicated adequate drug absorption by all patients. The presence of Ile 51 and Asn 108 mutations among parasites that cleared after treatment indicates that these mutations alone are insufficient to cause in vivo resistance. In all recrudescent parasites, however, the presence of Ile 51/Asn 108 dhfr mutations was coupled with the dhps Ala 436. The findings suggest that the presence of Ile 51/Asn 108 dhfr mutations and Ala 436 dhps confers decreased susceptibility of P. falciparum to PYR/SDX in areas of low endemicity.

Adolescent↗