Etchegorry, M.G., F. Matthys, M. Galinski, N.J. White, and F. Nosten, Malaria epidemic in Burundi. Lancet, 2001. 357(9261): p. 1046-7. [PubMed Link]

Leonardi, E., G. Gilvary, N.J. White, and F. Nosten, Severe allergic reactions to oral artesunate: a report of two cases. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2001. 95(2): p. 182-3.[PubMed Link]

Luxemburger, C., R. McGready, A. Kham, L. Morison, T. Cho, T. Chongsuphajaisiddhi, N.J. White, and F. Nosten, Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. American Journal of Epidemiology, 2001. 154(5): p. 459-65. [PubMed Link]
Malaria during pregnancy reduces birth weight, and low birth weight is a major determinant of infant mortality. The authors estimated the impact of malaria during pregnancy on infant mortality in a Karen population living in Thailand. Between 1993 and 1996, a cohort of 1,495 mothers and their infants was followed weekly from admission of the mother to antenatal clinics until the first birthday of the infant. Both falciparum malaria and vivax malaria during pregnancy were associated with low birth weight but did not shorten gestation. Febrile illness in the week before delivery was associated with premature birth. Preterm and full-term low birth weight and fever in the week before delivery were associated with neonatal mortality. Maternal fevers close to term were also associated with the deaths of infants aged between 1 and 3 months, whereas no risk factors could be identified for deaths that occurred later in infancy. Thus, malaria during pregnancy increased neonatal mortality by lowering birth weight, whereas fever in the week before birth had a further independent effect in addition to inducing premature birth. The prevention of malaria in pregnancy and, thus, of malaria-attributable low birth weight should increase the survival of young babies.

McGready, R., J.A. Simpson, M. Htway, N.J. White, F. Nosten, and S.W. Lindsay, A double-blind randomized therapeutic trial of insect repellents for the prevention of malaria in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2001. 95(2): p. 137-8. [PubMed Link]

McGready, R., J.A. Simpson, T. Cho, L. Dubowitz, S. Changbumrung, V. Bohm, R.G. Munger, H.E. Sauberlich, N.J. White, and F. Nosten, Postpartum thiamine deficiency in a Karen displaced population. American Journal of Clinical Nutrition, 2001. 74(6): p. 808-813. [PubMed Link]
Background: Before its recognition, infantile beriberi was the leading cause of infant death in camps for displaced persons of the Karen ethnic minority on Thailand's western border. Objective: This study aimed to document thiamine status in the peripartum period to examine the current supplementation program and the correlation between the clinical manifestations of thiamine deficiency and a biochemical measure of thiamine status. Design: Women were enrolled prospectively at 30 wk of gestation and were followed up weekly until delivery and at 3 mo postpartum. Thiamine supplementation during pregnancy was based on patient symptoms. Results: At 3 mo postpartum, thiamine deficiency reflected by an erythrocyte transketolase activity (ETKA)[>=] 1.20% was found in 57.7% (15/26) of mothers, 26.9% (7/26) of whom had severe deficiency (ETKA > 1.25%). No significant associations between ETKA and putative maternal symptoms or use of thiamine supplements were found. Conclusions: Biochemical postpartum thiamine deficiency is still common in Karen refugee women. This situation may be improved by educating lactating women to reduce their consumption of thiaminase-containing foods and by implementing an effective thiamine supplementation program.

McGready, R., T. Cho, N.K. Keo, K.L. Thwai, L. Villegas, S. Looareesuwan, N.J. White, and F. Nosten, Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clinical Infectious Diseases, 2001. 33(12): p. 2009-16. [PubMed Link]
The emergence and spread of multidrug-resistant Plasmodium falciparum compromises the treatment of malaria, especially during pregnancy, where the choice of antimalarials is already limited. Artesunate (n=528) or artemether (n=11) was used to treat 539 episodes of acute P. falciparum malaria in 461 pregnant women, including 44 first-trimester episodes. Most patients (310 [57.5%]) received re-treatments after earlier treatment with quinine or mefloquine. By use of survival analysis, the cumulative artemisinin failure rate for primary infections was 6.6% (95% confidence interval, 1.0-12.3), compared with the re-treatment failure rate of 21.7% (95% confidence interval, 15.4- 28.0; P=.004). The artemisinins were well tolerated with no evidence of adverse effects. Birth outcomes did not differ significantly to community rates for abortion, stillbirth, congenital abnormality, and mean gestation at delivery. These results are reassuring, but further information about the safety of these valuable antimalarials in pregnancy is needed.

McGready, R., T. Cho, Samuel, L. Villegas, A. Brockman, M. van Vugt, S. Looareesuwan, N.J. White, and F. Nosten, Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2001. 95(6): p. 651-6. [PubMed Link]
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.

McGready, R., K.A. Hamilton, J.A. Simpson, T. Cho, C. Luxemburger, R. Edwards, S. Looareesuwan, N.J. White, F. Nosten, and S.W. Lindsay, Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy. American Journal of Tropical Medicine and Hygiene, 2001. 65(4): p. 285-9. [PubMed Link]
The safety of daily application of N, N-diethyl-m-toluamide (DEET) (1.7 g of DEET/day) in the second and third trimesters of pregnancy was assessed as part of a double-blind, randomized, therapeutic trial of insect repellents for the prevention of malaria in pregnancy (n = 897). No adverse neurologic, gastrointestinal, or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy (range = 0-345.1 g). DEET crossed the placenta and was detected in 8% (95% confidence interval = 2.6-18.2) of cord blood samples from a randomly selected subgroup of DEET users (n = 50). No adverse effects on survival, growth, or development at birth, or at one year, were found. This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy. The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy.

Mutabingwa, T.K., L. Villegas, and F. Nosten, Chemoprophylaxis and other protective measures: Preventing pregnancy malaria, in Malaria in Pregnancy, Deadly Parasite, Susceptible Host, P.E. Duffy and M. Fried, Editors. 2001, Taylor & Francis: London & New York. p. 189-221.[PubMed Link]

Newton, P., S. Proux, M. Green, F. Smithuis, J. Rozendaal, S. Prakongpan, K. Chotivanich, M. Mayxay, S. Looareesuwan, J. Farrar, F. Nosten, and N.J. White, Fake artesunate in southeast Asia. Lancet, 2001. 357(9272): p. 1948-50. [PubMed Link]
Artesunate is a key antimalarial drug in the treatment of multidrug- resistant Plasmodium falciparum malaria in southeast Asia. We investigated the distribution of counterfeit artesunate tablets by use of the validated, simple, and inexpensive Fast Red TR dye technique. We also aimed to identify distinguishing characteristics of the fake drugs. Of 104 shop-bought "artesunate" samples from Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, 38% did not contain artesunate. Characteristics such as cost and physical appearance of the tablets and packaging reliably predicted authenticity. The illicit trade in counterfeit antimalarials is a great threat to the lives of patients with malaria. The dye test will assist national malaria control authorities in urgently needed campaigns to stop this murderous trade.

Nosten, F. and R. McGready, The treatment of malaria in pregnancy, in Malaria in Pregnancy; Deadly Parasite, Susceptible Host, P.E. Duffy and M. Fried, Editors. 2001, Taylor & Francis: London & New York. p. 223-240.[PubMed Link]

Price, R.N. and F. Nosten, Drug resistant falciparum malaria: clinical consequences and strategies for prevention. Drug Resistance Updates, 2001. 4(3): p. 187-96. [PubMed Link]
The rising prevalence of multidrug resistant falciparum malaria is occurring at an alarming rate and has serious implications for the health of many of the world's poorest countries. The dangers of not changing treatment practices immediately are huge and irreversible, threatening to both exacerbate the scale and scope of the malaria pandemic, and deprive policymakers of future options against the disease. If a health care disaster is to be avoided then massive and long term funding is urgently required. Funds need to be applied in a cohesive manner, accountable to funding bodies and tailored to the specifics of each endemic region. The key elements of such an approach should be improving early diagnosis and treatment of infection and the deployment of combination regimens containing an artemisinin derivative.These short term measures will need to be accompanied by a longer term strategy to encourage antimalarial drug research and development.

Price, R.N., J.A. Simpson, F. Nosten, C. Luxemburger, L. Hkirjaroen, F. ter Kuile, T. Chongsuphajaisiddhi, and N.J. White, Factors contributing to anemia after uncomplicated falciparum malaria. American Journal of Tropical Medicine and Hygiene, 2001. 65(5): p. 614-22. [PubMed Link]
The factors contributing to anemia in falciparum malaria were characterized in 4,007 prospectively studied patients on the western border of Thailand. Of these, 727 patients (18%) presented with anemia (haematocrit < 30%), and 1% (55 of 5,253) required blood transfusion. The following were found to be independent risk factors for anemia at admission: age < 5 years, a palpable spleen, a palpable liver, recrudescent infections, being female, a prolonged history of illness (> 2 days) before admission, and pure Plasmodium falciparum infections rather than mixed P. falciparum and Plasmodium vivax infections. The mean maximum fractional fall in hematocrit after antimalarial treatment was 14.1% of the baseline value (95% confidence interval [CI], 13.6- 14.6). This reduction was significantly greater in young children (aged < 5 years) and in patients with a prolonged illness, high parasitemia, or delayed parasite clearance. Loss of parasitized erythrocytes accounted for < 10% of overall red blood cell loss. Hematological recovery was usually complete within 6 weeks, but it was slower in patients who were anemic at admission (adjusted hazards ratio [AHR], 1.9, 95% CI, 1.5-2.3), and those whose infections recrudesced (AHR, 1.2, 95% CI, 1.01-1.5). Half the patients with treatment failure were anemic at 6 weeks compared with 19% of successfully treated patients (relative risk, 2.8, 95% CI, 2.0-3.8). Patients coinfected with P. vivax (16% of the total) were 1.8 (95% CI, 1.2-2.6) times less likely to become anemic and recovered 1.3 (95% CI, 1.0-1.5) times faster than those with P. falciparum only. Anemia is related to drug resistance and treatment failure in uncomplicated malaria. Children aged < 5 years of age were more likely than older children or adults to become anemic. Coinfection with P. vivax attenuates the anemia of falciparum malaria, presumably by modifying the severity of the infection.

Proux, S., L. Hkirijareon, C. Ngamngonkiri, S. McConnell, and F. Nosten, Paracheck-Pf: a new, inexpensive and reliable rapid test for P. falciparum malaria. Tropical Medicine and International Health, 2001. 6(2): p. 99-101. [PubMed Link]
We compared the performance of Paracheck-Pf, a new and cheap rapid malaria test, with ICT-Pf/PvR and microscopy in two malaria surveys in Thai villages on the Thai-Burmese border. The specificity, sensitivity, predictive positive and negative values of the Paracheck-PfR and ICT- PfR tests were calculated taking microscopy results as the gold standard. The 294 ICT-Pf/Pv tests resulted in two invalid (no control line) and 11 doubtful results. Both the ICT-Pf/PvR and Paracheck-PfR tests reliably detected P. falciparum infections. However, Paracheck- PfR failed to detect three P. falciparum cases and likewise, ICT-Pf/PvR failed to detect the same three cases and an additional four cases. These seven cases were detected by microscopy and had a parasitaemia under 150 parasites/microl. At a cost of c. US $1.00, the Paracheck-PfR test, based on the detection of the P. falciparum specific HRP-2 protein, is a reliable, easy to use and affordable tool for the diagnosis of P. falciparum malaria.

Rowland, M. and F. Nosten, Malaria epidemiology and control in refugee camps and complex emergencies. Annals of Tropical Medicine and Parasitology, 2001. 95(8): p. 741-54. [PubMed Link]
Owing to the breakdown of health systems, mass population displacements, and resettlement of vulnerable refugees in camps or locations prone to vector breeding, malaria is often a major health problem during war and the aftermath of war. During the initial acute phase of the emergency, before health services become properly established, mortality rates may rise to alarming levels. Establishing good case management and effective malaria prevention are important priorities for international agencies responsible for emergency health services. The operational strategies and control methods used in peacetime must be adapted to emergency conditions, and should be regularly re-assessed as social, political and epidemiological conditions evolve. During the last decade, research on malaria in refugee camps on the Pakistan-Afghanistan and Thailand-Burma borders has led to new methods and strategies for malaria prevention and case management, and these are now being taken up by international health agencies. This experience has shown that integration of research within control programmes is an efficient and dynamic mode of working that can lead to innovation and hopefully sustainable malaria control. United Nations' humanitarian and non-governmental agencies can play a significant part in resolving the outstanding research issues in malaria control.