No pfmdr1 amplifications in samples from Guinea-Bissau and Liberia collected between 1981 and 2004.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Lars Rombo.
Explore the source record for details and available documents.
The aim of the present study was to compare different doses of chloroquine (CQ) and amodiaquine (AQ) for the treatment of falciparum malaria in children. Children with Plasmodium falciparum monoinfection were allocated by block randomisation to treatment with CQ 50/kg mg or 25 mg/kg or AQ 15 mg/kg or 30 mg/kg. The main outcomes were the cumulative adequate clinical and parasitological response (ACPR) rates and the number of true recrudescences as determined by PCR. A total of 729 children were included. In an evaluability analysis, the PCR-uncorrected cumulative ACPR rates on Day 28 for the treatment groups CQ 50/kg mg or 25 mg/kg and AQ 15 mg/kg or 30 mg/kg were 90%, 76%, 92% and 94%, respectively; the PCR-adjusted ACPR rates on Day 28 were 92%, 80%, 94% and 94%, respectively. No differences in adverse effects were observed. AQ has a high cure rate given as 30 mg/kg and 15 mg/kg, although it is not superior to treatment with CQ 50 mg/kg. However, 25 mg/kg of CQ is less efficient. As an interim option, Guinea-Bissau could change the recommended first-line treatment of uncomplicated malaria to CQ 50 mg/kg, reserving AQ as a partner drug for a future combination therapy.
The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international experts from the public and private sectors in the Nordic countries and Germany, in order to review the epidemiological situation, the surveillance systems for infectious diseases, the immunization programmes and policy, and the monitoring of adverse events after hepatitis vaccination in those countries, to evaluate prevention and control measures, and to identify the issues that arose and the lessons learnt. Considerable progress has been made in the past decades in the prevention and control of viral hepatitis in the respective countries. Vaccination programmes have been set up, blood products' safety has significantly been improved, and outbreak investigations remain the basis for the implementation of control measures. However, additional work remains to be done. Awareness of viral hepatitis among the public and professionals should further be raised, and more political support is needed regarding the value of prevention efforts and vaccination programmes.
We have investigated pre-travel advice, behaviour, chemoprophylaxis and diagnostic delay in travellers returning to Sweden with falciparum malaria. Questionnaires were distributed to patients having been notified with falciparum malaria from 1994 to 2001. Of 408 notified patients, 237 (58%) returned the questionnaires; 62% were males and 43% above the age of 45 y. Africa was the travel destination in 90% of the cases, and 27% had travelled to Kenya. 69% had spent more than 1 night in the countryside, and 6% had stayed in modern urban areas only. 40% took an adequate dose of chemoprophylaxis, although this proportion decreased from 55% to 12% during the study period. Nine per cent used both bed nets and mosquito repellents regularly. The median time from onset of symptoms to contact with health care professionals was 2 d, and from that contact to start of malaria treatment the median time was less than 24 h.
Malaria remains one of the major public health problems for children in Guinea-Bissau and the major reason for using the health services. Little is known about factors with impact on whether the mothers seek malaria treatment for their children at a health centre. Mothers of children coming to the Bandim Health Centre in Bissau and age-matched controls selected from the registration system of the Bandim Health Project were interviewed about treatment habits, socio-economic standards and other factors associated with the mother seeking treatment for her child at a health centre. In a multivariate analysis, the controls were more often found to have chloroquine at home and had more often taken home treatment for suspected malaria. On average 2.97 persons among cases shared bed as opposed to only 2.02 among controls, bed-crowding thus, being a factor determining health seeking behaviour (P=0.0001). Low socio-economic status, as measured by the non-availability of electricity, was also a significant predicting factor (P=0.02). The possibilities of promoting home treatment should be further evaluated, not only to avoid unnecessary visits to the professional health system, but also to decrease the morbidity from acute malaria.
The antifolate drugs sulphadoxine and pyrimethamine are used for treatment of chloroquine-resistant Plasmodium falciparum in Africa. Resistance to pyrimethamine has been associated with point mutations in the dhfr-gene and resistance to sulphadoxine with mutations in the dhps-gene. There is concern that the use of the antifolates trimethoprim and sulphamethoxazole for treatment of other infectious diseases will result in the selection of malaria parasites with mutations in these genes. In Guinea-Bissau, where sulfonamide and trimethoprim-containing drugs have been used extensively, we decided to assess the prevalence of mutations in the dhfr-and dhps-gene in P. falciparum isolated from children suffering from acute malaria and to assess the resistance patterns to trimethoprim/sulphamethoxazole in Escherichia coli isolated from the same patients. A thick film and a blood sample for polymerase chain reaction (PCR) were obtained from 100 children attending the Bandim Health Centre in Bissau with symptoms compatible with malaria. Furthermore, a stool sample was collected from the same children and cultured for E. coli. Of the cultured E. coli, 67% were resistant both to sulfonamides and trimethoprim, 4% to sulfonamides alone, 3% to trimethoprim alone while 26% were fully sensitive to both drugs. PCR was successfully performed in 97 blood samples. Of these, 41% had triple mutations at the dhfr-gene (at codons 51, 59 and 108), and 15% had triple mutations plus mutation at codon 437 in the dhps-gene. Only 45% harboured the wild-type dhfr-gene. Thus both bacterial resistance and mutations in the parasitic genes were common, but not linked in the individual child. As sulphadoxine-pyrimethamine has only been used as a second line treatment for chloroquine resistant malaria in Guinea-Bissau for a few years, it is worrying to find a high prevalence of mutations in the parasitic genes coding for resistance to these drugs. Therefore, restricting the use of sulphadoxine-pyrimethamine for the treatment of chloroquine resistant malaria might not be sufficient to prevent the development of resistance in the parasites as long as antifolate drugs are used extensively.
Children with symptomatic malaria in Bissau were randomly assigned to treatment with chloroquine 25 mg base/kg given supervised at a health centre or unsupervised by the mothers at home. On day 7, a blood sample for drug analyses was drawn and the children were then followed once weekly for 5 weeks. The data were analysed on an intention to treat basis. No differences were seen in the outcome of treatment nor in the blood drug concentrations on day 7 between the two groups. Mothers in Bissau can be trusted to give adequate anti-malarial medication to their children at home.
Explore the source record for details and available documents.
Children with symptomatic malaria in Bissau, Guinea-Bissau were randomly assigned to treatment with a 25 mg/kg total dose of chloroquine as recommended by the National Malaria Program or with a higher total dose of 50 mg/kg. Sixty-seven and 62 children, respectively, completed the treatment and were then followed once a week for five weeks. Treatment with a dose of 50 mg/kg was significantly more effective than treatment with 25 mg/kg in preventing recrudescence. The cumulative relative risk (95% confidence interval) of having parasitemia in the low-dose group during follow-up was 0.20 (0.08-0.52) on day 21, 0.38 (0.17-0.86) on day 28, and 0.48 (0.23-0.98) on day 35. Few adverse events were reported, although more children complained of vomiting and diarrhea on day 2 in the high-dose group compared with those in the low-dose group. However, this difference was not statistically significant. We conclude that a dose of 50 mg/kg of chloroquine could be recommended for treatment of Plasmodium falciparum malaria in Bissau. To minimize the risk of side effects, this higher dose should be given divided into two daily doses over a three-day period.
With the increasing resistance to commonly used antimalarial drugs, different untested 'local' treatment regimens for malaria will arise. We compared commonly used treatment regimens for children in Guinea-Bissau. Symptomatic children with Plasmodium falciparum mono-infection were allocated at random to one of 4 treatments: 15 mg/kg quinine twice a day for 3 d (group 1); 10 mg/kg quinine twice a day for 3 d followed by a total dose of 25 mg chloroquine base given over 3 d (group 2); a total dose of 50 mg/kg chloroquine base given in 2 daily doses for 3 d (group 3), or sulfadoxine-pyrimethamine (group 4). On day 28 more children from group 1 (33%; relative risk [RR] = 2.9, 95% confidence interval [CI] 1.5-5.7) and group 2 (26%; RR = 2.1, CI 1.0-4.3) had had parasitaemia than in group 4 (12%), whereas no significant difference was found between group 3 (17%; RR = 1.3, CI 0.6-2.2) and group 4. No severe adverse reaction was observed in any of the groups. Chloroquine is still effective in Guinea-Bissau at an increased dose of 50 mg/kg, which appears safe when given orally in 2 daily doses for 3 d. Sulfadoxine-pyrimethamine could serve as an efficient, cheap and easy to administer second-line drug, leaving quinine to be used for third-line treatment. Quinine should not be used in short courses, nor does the combination of quinine and chloroquine have any advantage.
We have earlier obtained good results in falciparum malaria by treating children with low doses of quinine for 7 days in Guinea-Bissau. In order to further simplify treatment, we compared outcome in 100 children with falciparum malaria treated in 1999/2000 for 7 days with 15 mg quinine salt/kg/dose twice daily (group I), 100 children treated with 7.5 mg quinine salt/kg/dose twice daily (group II), and 100 children treated with one single daily dose of 15 mg/kg. One day 28, parasites had reappeared in 12%, 15%, and 9%, respectively. These results are similar to what has been found after previous successful treatment regimens. Apart from a higher incidence of vomiting during the first 24 h of treatment in the groups treated with 15 mg/kg/dose no significant differences in symptoms or side-effects were found between the groups. In patients suffering from uncomplicated malaria, treatment with quinine can be simplified to one single dose of 15 mg/kg bodyweight whenever logistics make 2 daily doses less feasible.
The use of a combination of chloroquine and artesunate has been suggested for treatment of malaria in Africa. We used concomitant as well as sequential medication with these 2 drugs in relation to each drug separately for children infected with Plasmodium falciparum in Guinea-Bissau from March 2000 to November 2001. By block-randomization, 474 children with symptomatic malaria were divided into 4 groups and given either a total of 8 mg artesunate per kg bodyweight for 3 d, a total of 25 mg chloroquine base per kg bodyweight for 3 d, both drugs concomitantly for 3 d, or both drugs in sequence. All children were followed weekly for 5 weeks. On day 28, parasites had been detected in 40% of the children who were treated with artesunate only compared with 21% treated with chloroquine, 20% treated with artesunate in combination with chloroquine, and 16% treated with artesunate and chloroquine in sequence; on day 35 the corresponding percentages were 48%, 29%, 27%, and 24%, respectively. The outcome of the combination of chloroquine and artesunate in the doses studied was similar to the outcome of chloroquine monotherapy regardless of whether the 2 drugs are given concomitantly (relative risk [RR] = 0.93, 95% CI 0.56-1.53, P = 0.76) or in sequence (RR = 0.78, 95% CI 0.47-1.28, P = 0.32). Thus, neither an antagonistic, an additive, or a synergistic effect of the 2 drugs was indicated.
Explore the source record for details and available documents.
A long tradition of successful malaria prophylaxis with chloroquine led to a dogma that drug prophylaxis should be given regardless of risk as soon as a traveler entered endemic areas. This prevailed also when resistance to chloroquine and adverse effects of alternatives became a problem. A cost/benefit analysis of the risk for malaria versus risk for adverse effects and cost of the recommended drug is not uniformly applied and drug prophylaxis is still advocated even when the risk for severe adverse effects greatly exceeds the risk for malaria, which is unethical.
Explore the source record for details and available documents.