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Biomedical subjects

A M Rønn

Publications and source records attributed to A M Rønn.

At least 19 recordsLinked to original sources
PubMed2005

The roles of the pfcrt 76T and pfmdr1 86Y mutations, immunity and the initial level of parasitaemia, in predicting the outcome of chloroquine treatment in two areas with different transmission intensities.

The resistance of Plasmodium falciparum to chloroquine (CQ) is probably mediated by point mutations in two genes: pfcrt and pfmdr1. The aim of the present study was to investigate, in patients treated with CQ, the association between host factors, such as immunity and initial level of parasitaemia, and the ability to clear P. falciparum parasites carrying the key chloroquine-resistance (CQR) mutations, pfcrt 76T and pfmdr1 86Y. Identical CQ-efficacy trials were performed in 51 young children (aged <5 years) from Kibaha, in north-western Tanzania, and 44 patients (aged 3-57 years) from Darawish, in eastern Sudan. In both areas, all the CQ-treatment failures had infections with the 76T and 86Y alleles before treatment. Although the presence of these two alleles was significantly associated with treatment failure in Sudan (P=0.001), the corresponding association in Tanzania did not reach statistical significance (P=0.1). Of the 39 patients from Darawish and 44 from Kibaha who harboured parasites with the CQR mutations, 12 and 19, respectively, managed to clear their parasitaemias. The ability to clear CQR parasites was significantly associated with the initial level of parasitaemia (with P-values of 0.05 in Tanzania and 0.01 in Sudan) and with age-- the best surrogate for protective immunity in endemic areas (with P-values of 0.02 in Tanzania and 0.001 in Sudan). These results confirm previous observations that indicated that the 76T and 86Y alleles play a role in the mechanism of CQR, although other factors, such as level of parasitaemia when treated and age, are also important. The 76T and 86Y alleles could still be used as predictive markers for CQR, in non-immune individuals and low-transmission areas.

ATP-Binding Cassette Transporters↗
PubMed2005

The use of nominal group technique in identifying community health priorities in Moshi rural district, northern Tanzania.

This article highlights issues pertaining to identification of community health priorities in a resource poor setting. Community involvement is discussed by drawing experience of involving lay people in identifying priorities in health care through the use of Nominal Group Technique. The identified health problems are compared using four selected village communities of Moshi district in Kilimanjaro region, Tanzania. We conducted this study to trace the experience and knowledge of lay people as a supplement to using 'health experts' in priority setting using malaria as a tracer condition. The patients/caregivers, women's group representatives, youth leaders, religious leaders and community leaders/elders constituted the principal subjects. Emphasis was on providing qualitative data, which are of vital consideration in multi-disciplinary oriented studies, and not on quantitative information from larger samples. We found a high level of agreement across groups, that malaria remains the leading health problem in Moshi rural district in Tanzania both in the highland and lowland areas. Our findings also indicate that 'non-medical' issues including lack of water, hunger and poverty heralded priority in the list implying that priorities should not only be focused on diseases, but should also include health services and social cultural issues. Indeed, methods which are easily understood and applied thus able to give results close to those provided by the burden of disease approaches should be adopted. It is the provision of ownership of the derived health priorities to partners including the community that enhances research utilization of the end results. In addition to disease-based methods, the Nominal Group Technique is being proposed as an important research tool for involving the non-experts in priority setting in Tanzania.

Community Networks↗
PubMed2004

Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria.

This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.

Amodiaquine↗
PubMed1999

[Long-lasting neuropsychiatric side-effects following mefloquine prophylaxis. A case after six weeks of initiating and lasting six months].

Neuropsychiatric side-effects from mefloquine are well known. When used for prophylaxis, the side-effects have been claimed to be relatively rare, mild and transient, most often arising within two to three weeks, and in patients with a previous history of neuropsychiatric disorders. We here describe a case of severe neuropsychiatric side-effects arising six weeks after initiating mefloquine prophylaxis, requiring repeated hospitalization, and not resolving completely after six months, in a previously healthy 30 year-old female.

Adult↗
PubMed1999

A reversed-phase high-performance liquid chromatography method for the determination of cotrimoxazole (trimethoprim/ sulphamethoxazole) in children treated for malaria.

A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sample. 60 microL supernatant was added to 60 microL mobile phase, modified with 50microL 1 M sodium hydroxide/mL. The mobile phase consisted of 20% acetonitrile and 80% phosphate buffer adjusted to pH 6.15. Using 125 microL of the sample, limits of quantitation were 0.1 microg/mL for TMP, 1.0 microg/mL for SMX, and 1.0 microg/mL for AcSMX. The precision of the method was 2% to 11% over the range of concentrations tested, 0.5-30 microg/mL for TMP, 5-300 microg/mL for SMX, and 2.5-150 microg/mL for AcSMX, respectively. No interference with other commonly used drugs was observed. The method is rapid, simple, specific, and sensitive enough for pharmacokinetic studies. The small amount of blood required makes it suitable for pediatric patients. The method was used to analyze samples from Tanzanian children aged 6-59 months participating in a cotrimoxazole (TMP/SMX)/chloroquine randomized trial for the treatment of uncomplicated malaria. Venous blood samples from 68 children were collected 2 hours after the first dose of TMP/SMX (4 mg/kg TMP/20 mg/kg SMX at two divided doses for 5 days) and again at treatment day 4. Individual variations in plasma concentrations of TMP, SMX, and AcSMX were considerable. The mean and SEM plasma concentrations (g/mL) of TMP, SMX, and AcSMX 2 hours after the first treatment dose were 2.0 +/- 1.0 (range 0.5-6), 53 +/- 22 (range 24-146), and 13.5 +/- 12 (range 0-65), respectively. On the fourth day the attained plasma concentrations were not significantly different from samples collected after the first dose.

Acetonitriles↗
PubMed1998

Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: comparing a retrospective and a prospective study.

UNLABELLED: Mefloquine has been increasingly used for treatment of chloroquine-resistant malaria since its introduction in the late 1970s. In 1987 the first case of toxic encephalopathy was published, and in 1989 the WHO initiated reporting and investigation of neuropsychiatric adverse reactions of mefloquine. Neuropsychiatric adverse drug reactions are now well documented. We compared an open prospective 3 year study including all patients with P. falciparum treated with mefloquine with an earlier published, retrospective study on a comparable population from our department covering the period up to 1989. In the retrospective study neuropsychiatric adverse effects were not specifically asked for, while in the prospective study possible adverse reactions were registered daily according to a specified questionnaire. No case of neuropsychiatric adverse reaction was registered in the retrospective study. In the prospective study, 28% had one or more neuropsychiatric adverse reactions, although severity was mostly mild to moderate. Other adverse reactions occurred in 96% in the retrospective study compared to 81% in the prospective study. IN CONCLUSION: one often finds only what one looks for, e.g adverse events may be overlooked for a decade, if relatively uncommon. This report also shows that retro- and prospective studies may give very different results.

Adult↗
PubMed1998

Polymorphisms in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes of Plasmodium falciparum and in vivo resistance to sulphadoxine/pyrimethamine in isolates from Tanzania.

The efficacy of sulphadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Africa is increasingly compromised by development of resistance. The occurrence of mutations associated with the active site sequence in the Plasmodium falciparum genes coding for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) is associated with in vitro resistance to pyrimethamine and sulphadoxine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results show that alleles of DHPS (436-alanine, 437-alanine and 540-lysine) were significantly reduced in prevalence on day 7 after S/P treatment. In this area, a DHPS with 436-serine, 437-glycine and 540-glutamate appears to play a major role in resistance to S/P in vivo. Evidence for the influence of mutations in the DHFR gene in this investigation is not clear, probably because of the high prevalence of 'resistance-related' mutations at day 0 in the local parasite population. For apparently the same reason, it was not possible to show a statistical association between S/P resistance and the presence of particular polymorphisms in the DHFR and DHPS genes before treatment.

Animals↗
PubMed1997

High prevalence of mutations in the dihydrofolate reductase gene of Plasmodium falciparum in isolates from Tanzania without evidence of an association to clinical sulfadoxine/pyrimethamine resistance.

Recently the efficacy of sulfadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Tanzania has been seriously compromised by the development of resistance. The occurrence of active site mutations in the Plasmodium falciparum gene sequence coding for dihydrofolate reductase (DHFR) is known to confer resistance to pyrimethamine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results confirm the occurrence of one or more DHFR mutations in all the samples, but no relationship was found with the presence of parasites in the blood at day 7. The results suggest that alterations in the coding region for dihydropteroate synthetase (DHPS), the enzyme target for sulfadoxine, should be studied in order to predict resistance to the S/P combination. It has been proposed earlier that sulfadoxine could itself act on DHFR, because of a false dihydrofolate produced by drug metabolism through DHPS and dihydrofolate synthase. The results of this treatment study suggest that such a possibility is unlikely.

Animals↗
PubMed1997

Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections.

The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may be used to monitor the course of these common and potentially life-threatening infections.

Acute Disease↗
PubMed1996

[Contributing causes of malaria among Danish travellers].

A retrospective evaluation of contributing causes of malaria among Danish travellers, based on patient files and telephone interviews, is presented. Four centres participated, and 33% of all malaria cases reported to the Danish authorities in 1993 and 1994 were included (in total 82 patients). Ten out of 52 patients with falciparum malaria had not taken any chemoprophylaxis at all. Among the 42 patients who had, only 14 were both correctly advised and fully compliant. Within the remaining 28 patients, lack of compliance concerning the chemoprophylaxis was reported in 16, inadequate chemoprophylaxis was prescribed to 12 patients, and a further eight (19%) were underdosed. Only four out of 30 patients with vivax, ovale or malariae malaria had not used chemoprophylaxis. The distribution of contributing causes of chemoprophylaxis failure was similar to that of falciparum malaria, although noncompliance was more predominant in patients developing vivax, ovale or malariae malaria (58% compared to 38% in falciparum malaria).

Africa↗
PubMed1995

High-performance liquid chromatography determination of dapsone, monoacetyldapsone, and pyrimethamine in filter paper blood spots.

A high-performance liquid chromatography method for the simultaneous analysis of dapsone (DDS), the major metabolite of DDS, monoacetyldapsone (MADDS), and pyrimethamine (PYR) was modified for capillary blood samples obtained by finger prick and dried on filter paper. Limit of quantitation using 150 microliters whole blood dried on filter paper was found to be 20 ng/ml for DDS and PYR and 15 ng/ml for MADDS (precision < 15%). The clinically relevant concentrations of DDS are 50-2,000 ng/ml and for PYR 25-150 ng/ml. No interference from several drugs were observed. The accuracy of the filter paper method and the original whole-blood method was almost comparable. Standardization could therefore be obtained by the more simple whole-blood method. Dried filter paper samples stored at 19-22 degrees C were stable for months and for 2 weeks stored at 35 degrees C. The concentrations of simultaneously collected capillary blood and conventional venous blood samples correlated well. The present method using capillary blood dried on filter paper is reliable, simple, sensitive, and applicable in the field with limited technical facilities.

Anti-Infective Agents↗
PubMed1994

[Acute brain syndrome after mefloquine treatment].

It is known that the antimalarial drug mefloquine may cause neurological side-effects. Only few cases of encephalitis ascribed to mefloquine treatment have been reported. We here describe a 34 year-old female patient with symptoms of acute brain syndrome. The patient was initially treated with mefloquine for infection with P. falciparum. She was rehospitalized 12 days after mefloquine treatment with fever, nausea, dizziness and headache. Her condition worsened and her temperature rose and 15 days after treatment she had generalized convulsions and went into a coma. The EEG was severely abnormal. The patient was discharged 37 days after mefloquine treatment, but it was two months before the EEG was normal and the patient in her usual condition.

Acute Disease↗
PubMed1993

[Recurrence problems with preventive primaquine treatment in patients with malaria].

Standard treatment of P. ovale and P. vivax malaria is 1500 mg of chloroquine base given over three days followed by 15 mg of primaquine base daily for 14 days. At the Department of Infectious Diseases, Rigshospitalet, Copenhagen an increasing number of cases of relative by primaquine-resistant malaria have been observed. The side effects of primaquine are mainly gastrointestinal. Primaquine may also cause serious toxic side effects, including methaemoglobin formation and haemolytic anaemia, especially in individuals with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. We present six patients who developed relapses of P. vivax after taking standard doses of primaquine. When increasing primaquine dosage, patients must be informed about the possibility of more severe side effects.

Adult↗
PubMed1993

[Invasive fibrous thyroiditis--Riedel's goiter. A review of the literature and a case report].

Invasive fibrous thyroiditis (Riedel's goitre) is a rare condition of an unknown aetiology. The condition was first described by Riedel in 1883. In 1904 Hashimoto described another condition of invasive fibrous thyroiditis. Since then it has been discussed if Hashimoto's thyroiditis and Riedel's goitre were one disease in different states or two different diseases. Hashimoto's thyroiditis is known to have an autoimmune aetiology and it can be seen together with pernicious anaemia. Co-existence of Riedel's goitre and pernicious anaemia has never been reported. The patient mentioned had both Riedel's goitre and pernicious anaemia, and was first treated with subtotal thyroidectomy, relapsed after one year and consequently received steroids. Such coexistence and the very good effect of steroids could be explained on the basis of Hashimoto's and Riedel's thyroiditis being one condition in different states and with an autoimmune aetiology. It is recommended that patients with Riedel's goitre are postoperatively treated with steroids.

Diagnosis, Differential↗
PubMed1992

[Malaria and pregnancy].

In regions where malaria is endemism, the disease is a recognised cause of complications of pregnancy such as spontaneous abortion, premature delivery, intrauterine growth retardation and foetal death. Malaria is seldom seen in pregnant women in Denmark but, during the past two years, the authors have treated four patients in the University Hospital in Copenhagen. These pregnancies were all successful but two of the mothers required emergency Caesarean section on account of threatening intrauterine asphyxia. The patients came relatively late for treatment which may be because not only the patients but also their practitioners were unaware that malaria can occur several years after exposure. Three out of the four patients had employed malaria prophylaxis. As resistance to malarial prophylactics in current use is increasing steadily, chemoprophylaxis should be supplemented by mechanical protection against malaria and insect repellents. As a rule, malaria is treated with chloroquine. In cases of Falciparum malaria in whom chloroquine resistance is suspected, treatment with mefloquine may be employed although this should only be employed in cases of dire necessity in pregnant patients during the first trimester. Severe cases should be treated with infusion of quinine. During pregnancy, benign malaria may run a violent course and pregnant women with malaria should be monitored in maternity departments and should be treated in cooperation with specialists in tropical medicine.

Adult↗
PubMed1989

[Complicated malaria].

An increasing number of cases of malaria, imported to Denmark, are caused by Plasmodium falciparum and severe and complicated cases are more often seen. In the Department of Infectious Diseases, Rigshospitalet, 23 out of 32 cases, hospitalized from 1.1-30.6.1988, i.e. 72%, were caused by P. falciparum; of these, seven (30%) were complicated, according to the definition by WHO. The importance of prompt diagnosis and treatment with intravenous quinine is stressed, and more recent supporting therapies including blood exchange transfusion are reviewed.

Blood Transfusion↗
PubMedDate not supplied

High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania.

In many areas of tropical Africa affected by chloroquine-resistant Plasmodium falciparum, a combination of sulfadoxine and pyrimethamine (S-P) is used for alternative medication, especially in young children. In Magoda village in Muheza District, north-eastern Tanzania, 38 children 1-10 years of age were enrolled in a therapeutic study of S-P in July 1994. All had monoinfections of P. falciparum and an asexual parasite count of 1000-80,000/microL of blood. S-P was given as a single dose corresponding to 0.8-1.4 mg pyrimethamine/kg body weight. Of the 38 children followed up to day 7, 10 showed an S/RI response, 26 an RII response, and 2 an RIII response. Older children had lower pre-treatment parasitaemia and a better therapeutic response than younger children. Among the various contributory factors responsible for the poor therapeutic result, drug pressure from a prophylactic intervention with weekly dapsone-pyrimethamine between May 1993 and May 1994 seems to have been the most important.

Animals↗