Malaria
Some selected abstracts: |
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1 |
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. |
2 |
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.
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3 |
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. |
4 |
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. |
5 |
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. |
6 |
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. |
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