Some selected abstracts:

Barennes H, Balima-Koussoube T, Nagot N, Charpentier JC, Pussard E. Safety and efficacy of rectal compared with intramuscular quinine for the early treatment of moderately severe malaria in children: randomised clinical trial. BMJ. 2006 May 6;332(7549):1055-9.

Centre MURAZ, 01BP390 Bobo-Dioulasso, Burkina Faso. hubert.barennes@auf.org

OBJECTIVE: To compare the safety and efficacy of quinine given by the rectal route with quinine given by the intramuscular route in children with moderately severe Plasmodium falciparum malaria. DESIGN: Randomised, open, clinical trial. SETTING: Health centre in Burkina Faso. PARTICIPANTS: 898 children with moderately severe P falciparum malaria who were unable to take oral treatment. INTERVENTION: Rectal quinine (20 mg/kg diluted to 30 mg/ml in water solution) or intramuscular quinine (12.5 mg/kg) every 12 hours until oral quinine could be taken. MAIN OUTCOME MEASURES: Primary safety outcome was the presence of blood in stools and secondary safety outcome was diarrhoea. Primary efficacy outcome was early treatment failure and secondary efficacy outcomes were late clinical and parasitological failures, fever clearance time, and time to oral intake. RESULTS: Blood in stools and diarrhoea were more common in children given quinine by the rectal route than by the intramuscular route (blood in stools: 5% v 1%, absolute difference 3.9%, 95% confidence interval 1.8% to 6.1%; diarrhoea: 5% v 1%, 3.5%, 1.3% to 5.7%). On anoscopy, inflammatory lesions (9/248, 3%) were associated with bloody striations in stools. Side effects of rectal quinine were rare and transitory. Local pain (90%), inflammation (79%), and transient impairment of mobility (15%) were observed with intramuscular quinine. Early treatment failure was higher in the rectal group (6% v 3%, absolute difference 3.0%, 95% confidence interval 0.2% to 5.9%). All except two children in each group had negative blood slide results at day 5. Fever recurrence at day 7 was higher in the intramuscular group (37/375 v 18/395, absolute difference 5.3%, 1.6% to 8.9%). Other efficacy outcomes (late clinical failure, late parasitological failure, fever clearance time, time to starting oral intake and rate of deterioration to severe malaria) did not differ. CONCLUSION: Quinine given by the rectal route has an acceptable safety profile and could be used in the early management of moderately severe malaria in children in sub-Saharan Africa, halting progression to severe disease.
 

Gimnig JE, MacArthur JR, M'bang'ombe M, Kramer MH, Chizani N, Stern RS, Mkandala C, Newman RD, Steketee RW, Campbell CH. Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi. Am J Trop Med Hyg. 2006 May;74(5):738-43.

Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. hzg1@cdc.gov

We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.

Kalanda GC, Hill J, Verhoeff FH, Brabin BJ. Comparative efficacy of chloroquine and sulphadoxine--pyrimethamine in pregnant women and children: a meta-analysis. Trop Med Int Health. 2006 May;11(5):569-77.

Child and Reproductive Health Group, Liverpool School of Tropical Medicine, and Royal Liverpool Children's Hospital NHS Trust, UK.

OBJECTIVE: To compare the efficacy of chloroquine and sulphadoxine-pyremethamine against Plasmodium falciparum infection in pregnant women and in children from the same endemic areas of Africa, with the aim of determining the level of correspondence in efficacy determinations in these two risk groups. METHODS: Meta-analysis of nine published and unpublished in vivo antimalarial efficacy studies in pregnant women and in children across five African countries. RESULTS: Pregnant women (all gravidae) were more likely to be sensitive than children to both chloroquine (odds ratio: 2.07; 95% confidence interval: 1.5, 2.9) and sulphadoxine-pyrimethamine (odds ratio: 2.66; 95% confidence interval: 11.1, 6.7). Pregnant women demonstrated an almost uniform increased sensitivity for peripheral parasite clearance at day 14 compared with children. This finding was consistent across a wide range of drug sensitivities. Primigravidae at day 14 showed lower clearance to antimalarial drugs than multigravidae (P<0.05). There was no significant difference between parasite clearance in primigravidae and in children. CONCLUSION: The greater drug sensitivity in pregnant women probably indicates differences in host susceptibility rather than parasite resistance. Parasite sensitivity patterns in children may be a suitable guide to antimalarial policy in pregnant women.
 

Lopansri BK, Anstey NM, Stoddard GJ, Mwaikambo ED, Boutlis CS, Tjitra E, Maniboey H, Hobbs MR, Levesque MC, Weinberg JB, Granger DL. Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications. Infect Immun. 2006 Jun;74(6):3355-9.

Division of Infectious Diseases, VA and University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. bert.lopansri@hsc.utah.edu

Cerebral malaria is associated with decreased production of nitric oxide and decreased levels of its precursor, l-arginine. Abnormal amino acid metabolism may thus be an important factor in malaria pathogenesis. We sought to determine if other amino acid abnormalities are associated with disease severity in falciparum malaria. Subjects were enrolled in Dar es Salaam, Tanzania (children) (n = 126), and Papua, Indonesia (adults) (n = 156), in two separate studies. Plasma samples were collected from subjects with WHO-defined cerebral malaria (children), all forms of severe malaria (adults), and uncomplicated malaria (children and adults). Healthy children and adults without fever or illness served as controls. Plasma amino acids were measured using reverse-phase high-performance liquid chromatography with fluorescence detection. Several plasma amino acids were significantly lower in the clinical malaria groups than in healthy controls. Despite the differences, phenylalanine was the only amino acid with mean levels outside the normal range (40 to 84 microM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] microM; P < 0.0001) and adults with all forms of severe malaria (median [95% confidence interval], 129 [111 to 155] microM; P < 0.0001). In adults who survived severe malaria, phenylalanine levels returned to normal, with clinical improvement (P = 0.0002). Maintenance of plasma phenylalanine homeostasis is disrupted in severe malaria, leading to significant hyperphenylalaninemia. This is likely a result of an acquired abnormality in the function of the liver enzyme phenylalanine hydroxylase. Determination of the mechanism of this abnormality may contribute to the understanding of neurological complications in malaria.
 

Omari AA, Gamble C, Garner P. Artemether-lumefantrine (four-dose regimen) for treating uncomplicated falciparum malaria. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005965. Review.

Countess of Chester Hospital, NHS Foundation Trust, Paediatric Department, Countess of Chester Health Park, Liverpool Road, Chester, Cheshire, UK, CH2 1UL. aika@omari1677.freeserve.co.uk

BACKGROUND: The World Health Organization recommends artemether-lumefantrine, an expensive drug, as a treatment for uncomplicated malaria. We sought evidence of the superiority of the four-dose regimen over existing treatments. OBJECTIVES: To evaluate the four-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (1982 to October 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized controlled trials comparing four doses of artemether-lumefantrine with standard treatment regimens (single drug or combination), or six doses of artemether-lumefantrine, for treating uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS: Seven trials (2057 participants) tested a four-dose regimen. More people tended to fail treatment with artemether-lumefantrine than with other drugs, including sulfadoxine-pyrimethamine (247 participants, 1 trial), halofantrine (86 participants, 1 trial), and mefloquine (233 participants, 1 trial; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two trials (378 participants), but over 50% of the participants treated with chloroquine had total failure by day 28. Fewer people failed treatment with the six-dose regimen compared to the four-dose regimen (RR 7.71, 95% CI 2.99 to 19.88; 306 participants, 1 trial). AUTHORS' CONCLUSIONS: The four-dose regimen of artemether-lumefantrine seems to be less effective than regimens against which it has been tested. The six-dose regimen is superior to four-dose regimen.
 

Owens S, Harper G, Amuasi J, Offei-Larbi G, Ordi J, Brabin BJ.  Placental malaria and immunity to infant measles. Arch Dis Child. 2006 Jun;91(6):507-8.

MRC Laboratories, Atlantic Road, Fajara, The Gambia.

The efficiency of transplacental transfer of measles specific antibody was assessed in relation to placental malaria. Infection at delivery was associated with a 30% decrease in expected cord measles antibody titres. Uninfected women who received anti-malarial drugs during pregnancy transmitted 30% more antibody than those who received no antimalarial drugs.
 

Diagnosis , Dignostics, Immunodiagnosis & Immunodignostics:

14756.  Allan PJ, Tahir HI. How easily malaria can be missed. J R Soc Med. 2006 Apr;99(4):201-2.

14757.  Cunha BA. Typhoid fever: the temporal relations of key clinical diagnostic points. Lancet Infect Dis. 2006 Jun;6(6):318-20; author reply 320-1.

14758.  Donati D, Espmark E, Kironde F, Mbidde EK, Kamya M, Lundkvist A, Wahlgren M, Bejarano MT, Falk KI. Clearance of circulating Epstein-Barr virus DNA in children with acute malaria after antimalaria treatment. J Infect Dis. 2006 Apr 1;193(7):971-7.

14759.  Tumwline J, Luboobi LS, Mugisha J T. Modelling the effect of treatment and mosquito control onmalaria transmission. Int J Mgmt Systems 2005, 21(2), 107-124.

14760.  Jorgensen P, Chanthap L, Rebueno A, Tsuyuoka R, Bell D. Malaria rapid diagnostic tests in tropical climates: the need for a cool chain. Am J Trop Med Hyg. 2006 May;74(5):750-4.

Pathogenesis:                  

14761.  Keller CC, Davenport GC, Dickman KR, Hittner JB, Kaplan SS, Weinberg JB, Kremsner PG, Perkins DJ. Suppression of prostaglandin E2 by malaria parasite products and antipyretics promotes overproduction of tumor necrosis factor-alpha: association with the pathogenesis of childhood malarial anemia. J Infect Dis. 2006 May 15;193(10):1384-93.

14762.  McDevitt MA, Xie J, Shanmugasundaram G, Griffith J, Liu A, McDonald C, Thuma P, Gordeuk VR, Metz CN, Mitchell R, Keefer J, David J, Leng L, Bucala R. A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia. J Exp Med. 2006 May 15;203(5):1185-96.

Therapy:

14763.  A-Elbasit IE, Elbashir MI, Khalil IF, Alifrangis M, Giha HA. The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural Eastern Sudan: the interrelation between resistance, age and gametocytogenesis. Trop Med Int Health. 2006 May;11(5):604-12.

14764.  Bar-Zeev N, White N. Evidence behind the WHO guidelines: Hospital Care for Children: efficacy and safety of artemisinin derivatives in children with malaria. J Trop Pediatr. 2006 Apr;52(2):78-82.    Review.

14765.  Fried M, Domingo GJ, Gowda CD, Mutabingwa TK, Duffy PE.  Plasmodium falciparum: chondroitin sulfate A is the major receptor for adhesion of parasitized erythrocytes in the placenta. Exp Parasitol. 2006 May;113(1):36-42.

14766.  Fanello CI, Karema C, van Doren W, Rwagacondo CE, D'Alessandro U. Tolerability of amodiaquine and sulphadoxine-pyrimethamine, alone or in combination for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan adults. Trop Med Int Health. 2006 May;11(5):589-96.

14767.  Hale VG.  Supporting the use of artemisinin in combination. Nature. 2006 May 18;441(7091):282.

14768.  Hopkin M. World Bank defends efforts to curb malaria. Nature. 2006 Apr 27;440(7088):1096-7. 

14769.  Padhan P. Rectal quinine for malaria: risk of hypoglycaemia may be higher by rectal route. BMJ. 2006 May 20;332(7551):1216; author reply 1216.

14770.  Rehwagen C. WHO ultimatum on artemisinin monotherapy is showing results. BMJ. 2006 May 20;332(7551):1176.

14771.  Sowunmi A, Fateye BA, Adedeji AA, Gbotosho GO, Happi TC, Bamgboye AE, Bolaji OM, Oduola AM. Predictors of the failure of treatment with pyrimethamine-sulfadoxine in children with uncomplicated falciparum malaria. Acta Trop. 2006 Apr;98(1):6-14.

14772.  Towie N.  Malaria breakthrough raises spectre of drug resistance. Nature. 2006 Apr 13;440(7086):852-3.

14773.  White NJ.  Developing drugs for neglected diseases. Trop Med Int Health. 2006 Apr;11(4):383-4.