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Biomedical subjects

F Nosten

Publications and source records attributed to F Nosten.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine.

Following a marked decline in the efficacy in vivo of mefloquine between 1990 and 1994, a combination of artesunate (4 mg/kg/d for 3 d) and mefloquine (25 mg/kg) has been used as first line treatment of uncomplicated falciparum malaria in camps for displaced persons located along the north-western border of Thailand. Antimalarial drug susceptibility of fresh isolates of Plasmodium falciparum from this population was evaluated using a radioisotope microdilution assay between 1995 and 1999. In total, 268 isolates were collected, of which 189 were from primary infections and 79 from recrudescent infections. The geometric mean 50% inhibitory concentration (IC50) values from primary infections were: dihydroartemisinin 1.2 ng/mL, artesunate 1.6 ng/mL, artemether 4.8 ng/mL, atovaquone 0.4 ng/mL, lumefantrine 32 ng/mL, chloroquine 149 ng/mL, quinine 354 ng/mL, mefloquine 27 ng/mL and halofantrine 4.1 ng/mL. A significant positive correlation was found between the susceptibility in vitro to artesunate and quinine (r = 0.43, P < 0.001), mefloquine (r = 0.46, P < 0.001), and halofantrine (r = 0.51, P < 0.001). These levels of resistance in vitro are among the highest reported and confirm continuing high level multidrug resistance in this area. Despite intensive use of the combination between 1995 and 1999 there has been a significant improvement in mefloquine sensitivity (P < 0.001) and artesunate sensitivity (P < 0.001). This supports observations in vivo that the combination of artesunate and mefloquine has reversed the previous decline in mefloquine sensitivity.

Adolescent↗
PubMedDate not supplied

Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria.

The efficacy and safety of the 6-dose regimen of artemether-lumefantrine were assessed in an open randomized trial in children and adults presenting with acute, uncomplicated Plasmodium falciparum malaria in Thailand between November 1997 and March 1998. 200 patients were enrolled in 2 centres: 150 received artemether-lumefantrine (i.e., a median total dose of 9.6 mg/kg [interquartile range 8.7-10.7] and 57.9 mg/kg of lumefantrine [52.4-64.0]) and 50 the standard combination of artesunate (12 mg/kg over 3 d) and mefloquine (25 mg/kg). All patients had rapid initial clinical and parasitological responses. The 28 d cure rates were high: 97.7% (95% confidence interval [95% CI] 93.5-99.5%) for artemether-lumefantrine and 100% (95% CI 92.5-100%) for artesunate-mefloquine. The 6-dose regimen of artemether-lumefantrine was better tolerated than, and as effective as, artesunate-mefloquine, the current standard treatment in this area of multidrug-resistant P. falciparum malaria.

Adolescent↗
PubMedDate not supplied

Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy.

Since no effective malaria prevention measures have been identified for pregnant women living on the western border of Thailand, prompt diagnosis and efficient treatment are paramount, although drug resistance in Plasmodium falciparum has narrowed the treatment options. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) for 7 days (Q7) versus mefloquine 25 mg base/kg (total dose) plus artesunate 4 mg/kg per day for 3 days (MAS3) was conducted in 1995-97 in 108 Karen women with acute uncomplicated falciparum malaria in the second or third trimesters of pregnancy. The MAS3 regimen was more effective than the Q7 regimen: day 63 cure rates were 98.2% (95% CI 94.7-100) (n = 65) for MAS3 and 67.0% (95% CI 43x3-90x8) (n = 41) for Q7, P = 0x001. The MAS3 regimen was also associated with less gametocyte carriage; the average person-gametocyte-weeks for MAS3 was 2.3 (95% CI 0-11) and for Q7 was 46x9 (95% CI 26-78) per 1000 person-weeks, respectively (P < 0.001). MAS3 was significantly better tolerated. These evident advantages must be balanced against a possible increased risk of stillbirth with the use of mefloquine in pregnancy. Further randomized studies assessing the safety and efficacy of other artemisinin-containing combination regimens in pregnancy are needed urgently.

Adolescent↗
PubMedDate not supplied

Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy.

In areas where multidrug-resistant Plasmodium falciparum (MDR-Pf) is prevalent, only quinine is known to be safe and effective in pregnant women. On the western border of Thailand, 7 days of supervised quinine (30 mg/kg daily) cures two-thirds of P. falciparum-infected women in the 2nd and 3rd trimesters of pregnancy. Artesunate is effective against MDR-Pf and the limited data on its use in pregnancy suggest it is safe. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) in combination with clindamycin (5 mg/kg every 8 h) for 7 days (QC7) versus artesunate 2 mg/kg per day for 7 days (A7) was conducted in 1997-2000 in 129 Karen women with acute uncomplicated falciparum malaria in the 2nd or 3rd trimesters of pregnancy. There was no difference in the day-42 cure rates between the QC7 (n = 65) and A7 (n = 64) regimens with an efficacy of 100% in both, confirmed by parasite genotyping. The A7 regimen was also associated with less gametocyte carriage; the average person-gametocyte-weeks for A7 was 3 (95% CI 0-19) and for QC7 was 39 (95% CI 21-66) per 1000 person-weeks, respectively (P < 0.01). There was no difference in gastrointestinal symptoms between the groups but there was significantly more tinnitus in the QC7 group compared to the A7 group (44.9% vs 8.9%; RR 5.1; 95% CI 1.9-13.5; P < 0.001). The favourable results with quinine-clindamycin mean that there is a useful back-up treatment for women with falciparum malaria who experience quinine and artesunate failures in pregnancy. Adherence to the 7-day regimen and cost (US$18.50 per treatment) are likely to be the main obstacles to this regimen.

Adolescent↗
PubMedDate not supplied

Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria.

The new OptiMAL-IT(R) rapid diagnostic test for malaria was evaluated in 271 patients in Thailand with uncomplicated malaria between June and July 2002. The sensitivity and specificity for the diagnosis of Plasmodium falciparum parasites were 88% and 92%, respectively. For species other than P. falciparum, the sensitivity was 65% and specificity was 99%. The performance of the new test decreased markedly at low levels of parasitaemia.

Adolescent↗
PubMedDate not supplied

The epidemiology of malaria in a Karen population on the western border of Thailand.

From November 1991 to November 1992 a prospective, descriptive study of malaria epidemiology was conducted in a Karen population on the western border of Thailand. Two study groups were selected at random and more than 80% of the subjects were followed for one year. In Group 1, comprising 249 schoolchildren (aged 4-15 years), daily surveillance for illness was combined with fortnightly malaria surveys. These children experienced 1.5 parasitaemic infections per child-year (95% confidence interval [CI] 1.3-1.7), of which 68% (193/285) were symptomatic (Plasmodium falciparum 84%, P. vivax 57%). The estimated pyrogenic densities were 1460/microL for P. falciparum and 181/microL for P. vivax. In Group 2, comprising subjects of all age from 428 households, malaria was diagnosed during two-monthly surveys, at weekly home visits, and otherwise by passive case detection. Malaria and splenomegaly prevalence rates were low in all age groups (spleen index 2-9%; P. falciparum prevalence rate 1-4%; P. vivax 1-6%). Group 2 subjects had 1.0 infections per person-year (95% CI 0.9-1.1), most of which were symptomatic (312/357; 87%). Malaria infections clustered in households. Overall, P. vivax caused 53% and P. falciparum 37% of the infections (10% were mixed), but whereas P. vivax was most common in young children, with a decline in incidence with increasing age, P. falciparum incidence rates rose with age to a peak incidence between 20 and 29 years, although the risk of developing a severe malaria decreased with increasing age. There was no death from malaria during the study. P. falciparum infections were more common in males, subjects with a history of malaria before the study, and in those who had travelled outside their village. These findings suggest a higher transmission rate for P. vivax than P. falciparum, although adults still suffered symptomatic malaria due to both species. The 2 malaria parasites found in this area contribute approximately 50% of infections each, but their clinical epidemiology is very different.

Adolescent↗
PubMedDate not supplied

Electrocardiographic monitoring in severe falciparum malaria.

Electrocardiographic monitoring over 24 h was performed with 53 patients with severe Plasmodium falciparum malaria (11 adults and 42 children) to assess the frequency of unrecognized cardiac arrhythmias. Nine patients (17%) died, 5 during the monitoring period and 4 afterwards. Pauses lasting 2-3 s were observed in 3 children, a single couplet in one, and a further child experienced frequent supraventricular ectopic beats which had not been detected clinically. In none of the patients who died could death be attributed to cardiac arrhythmia. Furthermore, no abnormality was detected which could have resulted from the often large doses of quinine, chloroquine or the artemisinin derivatives used for treatment. These results suggest that the heart is remarkably resilient even in the face of heavy parasite sequestration and other vital organ dysfunction, and that deaths from cardiac arrhythmias in severe malaria are rare. The need for routine cardiac monitoring of patients with severe and complicated P. falciparum malaria is questionable.

Adolescent↗
PubMedDate not supplied

Artesunate/mefloquine treatment of multi-drug resistant falciparum malaria.

On the western border of Thailand, in an area endemic for multi-drug resistant Plasmodium falciparum malaria, therapeutic responses were assessed in 1967 patients with uncomplicated falciparum malaria treated with 3 d of artesunate (total dose 12 mg/kg) plus mefloquine (total dose 25 mg/kg). The regimen was well tolerated and resulted in a rapid clinical response; within 48 h, 96% of patients were aparasitaemic and 94% were afebrile. After correcting for reinfections, the cure rate by day 42 was 89% (95% confidence interval [95% CI] 87-91%). Three independent factors were found to predict recrudescence: age < 14 years (adjusted hazards ratio [AHR] = 1.6, 95% CI 1.1-2.3), initial parasitaemia greater than > 40,000/microL (AHR = 1.6, 95%, CI 1.2-2.2), and pure P. falciparum infections (AHR = 1.8, 95% CI 1.3-2.7). These 3 factors combined accounted for 62% of all treatment failures. Patients who received mefloquine on admission with a high admission parasitaemia (> 40,000/microL) had a three-fold (95% CI 1.3-7) risk of subsequent recrudescence compared with those who received their mefloquine on the second or third day (P = 0.01). There has been no decline in the efficacy of the 3 d artesunate plus mefloquine regimen since it was introduced in 1992. This regimen is safe, well tolerated, and highly effective in the treatment of multi-drug resistant falciparum malaria.

Adolescent↗
PubMedDate not supplied

The epidemiology of severe malaria in an area of low transmission in Thailand.

The predisposing factors, clinical presentation, and outcome of severe malaria in a Karen community living on the western border of Thailand were studied over a period of 2 years. This was an area of low malaria transmission (approximately one infection per person per year), where asymptomatic malaria is unusual. In a population of 4728 persons, who had good access to facilities for malaria diagnosis and treatment, there were 2573 cases of vivax malaria, none of whom died, and there were 5776 cases of falciparum malaria, 303 (5%) of whom had severe malaria and 11 (0.2%) of whom died-a case fatality rate of 1.9 per 1000 (95% confidence interval [CI] 1.0-3.3). The risks of developing severe malaria and dying declined steadily with age. The clinical features of severe malaria differed between children and adults. Anaemia was more common in children under 5 years old than in older children and adults, whereas the incidence of cerebral involvement increased with age. Severe malaria was 3 times (95% CI 1.4-6.2) more common in pregnant than in non-pregnant women, but was 4.2 times (95% CI 2.3-7.9) less common in patients with mixed Plasmodium falciparum and P. vivax infections than in those with P. falciparum alone, suggesting that P. vivax may attenuate the severity of P. falciparum malaria.

Adolescent↗
PubMedDate not supplied

Artesunate and mefloquine in the treatment of uncomplicated multidrug-resistant hyperparasitaemic falciparum malaria.

Oral artesunate is the most effective treatment for uncomplicated hyperparasitaemia in falciparum malaria. To assess the contribution of mefloquine to therapeutic efficacy in an area endemic for mefloquine-resistant Plasmodium falciparum, an open randomized comparison of a 5 d course of oral artesunate (total dose 12 mg/kg) with and without a single dose of mefloquine (25 base mg/kg) was conducted in 100 adults and children with uncomplicated hyperparasitaemia (> 4% parasitized red blood cells). Both regimens were well tolerated and gave equally rapid clinical responses (84% of patients were aparasitaemic and 96% were afebrile within 48 h), but the recrudescence rate assessed at day 42 was 6% in those receiving artesunate with mefloquine compared to 36% in those receiving artesunate alone (adjusted hazard ratio 7, 95% confidence interval [95% CI] 2-32; P < 0.01). In addition, the efficacy of a 7 d course of artesunate, with and without the addition of mefloquine, was monitored in 178 patients who were not part of the randomized comparison. The failure rate was again lower in those receiving artesunate and mefloquine--7% (95% CI 2-13) compared with 26% (95% CI 8-44) in patients treated with artesunate alone. An oral regimen of 5 d or more of artesunate, together with mefloquine (25 mg/kg) given on day 2, is an effective treatment for uncomplicated hyperparasitaemic falciparum malaria in this area of high level multidrug resistance.

Administration, Oral↗
PubMedDate not supplied

Clinical features cannot predict a diagnosis of malaria or differentiate the infecting species in children living in an area of low transmission.

The differentiation of malaria from other causes of fever in the absence of microscopy is notoriously difficult. Clinical predictors of malaria have been studied in an area of low and unstable transmission on the western border of Thailand. In 1527 children aged 2-15 years who were followed prospectively for 7 months, 82% (1254) had at least one febrile episode. Malaria caused 24% (301) of the first febrile episodes (Plasmodium falciparum 128, P. vivax 151, P. malariae 1, mixed infections with P. falciparum and P. vivax 21). Each malaria case was matched with the next child of similar age presenting to the dispensary with another cause of fever. Clinical symptoms or signs associated with a final diagnosis of malaria were: confirmed fever (> or = 38 degrees C) (odds ratio [OR] 1.6, 95% confidence interval [95% CI] 1.4-1.9), headache (OR 1.5, 95% CI 1.3-1.9), muscle and/or joint pain (OR 2.0, 95% CI 1.6-2.8), nausea (OR 1.7, 95% CI 1.4-2.3), clinical anaemia (OR 1.4, 95% CI 1.3-3.3), palpable spleen (OR 1.3, 95% CI 1.1-1.7), palpable liver (OR 1.4, 95% CI 1.1-2.1), absence of cough (OR 1.6, 95% CI 1.4-2.0), and absence of diarrhoea (OR 1.5, 95% CI 1.2-2.4). None of these signs alone or in combination proved a good predictor of malaria. The best diagnostic algorithms (history of fever and headache without cough, and history of fever with an oral temperature > or = 38 degrees C [sensitivity 51% for both, specificity 72 and 71%, respectively]) would result in prescription of antimalarial drugs in 28-29% of the non-malaria febrile episodes, and only 49% of the true malaria cases. Thus half of the potentially life-threatening P. falciparum infections would not be treated. Although multivariate analysis identified vomiting, confirmed fever, splenomegaly and hepatomegaly as independent risk factors for a diagnosis of falciparum malaria, use of these signs to differentiate falciparum from vivax malaria, and thus to determine antimalarial treatment, was insufficiently sensitive or specific. Malaria diagnosis should be confirmed by microscopical examination of a blood slide or the use of specific dipstick tests in areas of low transmission where highly drug-resistant P. falciparum coexists with P. vivax.

Adolescent↗
PubMedDate not supplied

Artemisinin derivatives in the treatment of falciparum malaria in pregnancy.

An artemisinin derivative (artesunate or artemether) was used for the treatment of multidrug-resistant Plasmodium falciparum malaria in 83 Karen pregnant women in Thailand; 55 women were treated for recrudescent infection following quinine or mefloquine, 12 for uncomplicated hyperparasitaemic episodes, and 16 had not declared their pregnancy when treated. The women were followed weekly until delivery. Artesunate and artemether were well tolerated and there was no drug-related adverse effect. Recrudescence within 42 d occurred in 16% of the treated episodes. Overall 73 pregnancies (88%) resulted in live births, 3 (4%) in abortions and 2 (3%) in still births, and 5 women were lost to follow-up before delivery. There was no congenital abnormality in any of the newborn children, and the 46 children followed for more than one year all developed normally.

Adolescent↗