MALARIA

1.                  Beare NA, Taylor TE, Harding SP, Lewallen S, Molyneux ME.  Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg. 2006  Nov;75(5):790-7. Review. 

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi. nbeare@btinternet.com

Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria.

2.                  Kasehagen LJ, Mueller I, McNamara DT, Bockarie MJ, Kiniboro B, Rare L, Lorry K, Kastens W, Reeder JC, Kazura JW, Zimmerman PA.  Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg. 2006 Oct;75(4):588-96.

Center for Global Health & Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-7286, USA.

In Papua New Guinea (PNG), complex patterns of malaria commonly include single and mixed infections of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale. Here, we assess recent epidemiologic characteristics of Plasmodium blood-stage infections in the Wosera region through four cross-sectional surveys (August 2001 to June 2003). Whereas previous studies performed here have relied on blood smear/light microscopy (LM) for diagnosing Plasmodium species infections, we introduce a newly developed, post-polymerase chain reaction (PCR), semi-quantitative, ligase detection reaction-fluorescent microsphere assay (LDR-FMA). A direct comparison of the two methods for > 1,100 samples showed that diagnosis was concordant for > 80% of the analyses performed for P. falciparum (PF), P. vivax (PV), and P. malariae (PM). Greater sensitivity of the LDR-FMA accounted for 75% of the discordance between diagnoses. Based on LM, the prevalence of blood-stage PF, PV, and PM infections was found to be markedly reduced compared with an early 1990s survey. In addition, there were significant shifts in age distribution of infections, with PV becoming the most common parasite in children < 4 years of age. Consistent with previous studies, prevalence of all Plasmodium species infections increased significantly in samples analyzed by the PCR-based LDR-FMA. This increase was most pronounced for PM, PO, and mixed infections and in adolescent (10-19 years) and adult age groups, suggesting that LM may lead to under-reported prevalence of less common Plasmodium species, infection complexity, and a skewed distribution of infections towards younger age groups. This study shows that the application of LDR-FMA diagnosis in large epidemiologic studies or malaria control interventions is feasible and may contribute novel insights regarding the epidemiology of malaria.

3.                  Mens PF, Schoone GJ, Kager PA, Schallig HD.  Detection and identification of human Plasmodium species with real-time quantitative nucleic acid sequence-based amplification. Malar J. 2006 Oct 3;5:80.

Koninklijk Instituut voor de Tropen/Royal Tropical Institute, KIT Biomedical Research, Meibergdreef 39, 1105 AZ Amsterdam, The Netherlands. p.mens@kit.nl

BACKGROUND: Decisions concerning malaria treatment depend on species identification causing disease. Microscopy is most frequently used, but at low parasitaemia (<20 parasites/mul) the technique becomes less sensitive and time consuming. Rapid diagnostic tests based on Plasmodium antigen detection do often not allow for species discrimination as microscopy does, but also become insensitive at <100 parasites/microl. METHODS: This paper reports the development of a sensitive and specific real-time Quantitative Nucleic Acid Sequence Based Amplification (real-time QT-NASBA) assays, based on the small-subunit 18S rRNA gene, to identify the four human Plasmodium species. RESULTS: The lower detection limit of the assay is 100-1000 molecules in vitro RNA for all species, which corresponds to 0.01-0.1 parasite per diagnostic sample (i.e. 50 microl of processed blood). The real-time QT-NASBA was further evaluated using 79 clinical samples from malaria patients: i.e. 11 Plasmodium. falciparum, 37 Plasmodium vivax, seven Plasmodium malariae, four Plasmodium ovale and 20 mixed infections. The initial diagnosis of 69 out of the 79 samples was confirmed with the developed real-time QT-NASBA. Re-analysis of seven available original slides resolved five mismatches. Three of those were initially identified as P. malariae mono-infection, but after re-reading the slides P. falciparum was found, confirming the real-time QT-NASBA result. The other two slides were of poor quality not allowing true species identification. The remaining five discordant results could not be explained by microscopy, but may be due to extreme low numbers of parasites present in the samples. In addition, 12 Plasmodium berghei isolates from mice and 20 blood samples from healthy donors did not show any reaction in the assay. CONCLUSION: Real-time QT-NASBA is a very sensitive and specific technique with a detection limit of 0.1 Plasmodium parasite per diagnostic sample (50 microl of blood) and can be used for the detection, identification and quantitative measurement of low parasitaemia of Plasmodium species, thus making it an effective tool for diagnostic purposes and useful for epidemiological and drug studies.

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

15438.  Briggs C, Da Costa A, Freeman L, Aucamp I, Ngubeni B, Machin SJ. Development of an automated malaria discriminant factor using VCS technology. Am J Clin Pathol. 2006 Nov;126(5):691-8. 

15439.  Chen LH, Wilson ME, Schlagenhauf P.  Prevention of malaria in long-term travelers. JAMA. 2006 Nov 8;296(18):2234-44. Review.

15440.  Jamjoom MB, Azhar EA, Tonkol AK, Al-Harthi SA, Ashankyty IM.  Detection of malaria in Saudi Arabia by real-time PCR. J Egypt Soc Parasitol. 2006 Dec;36(3):737-48. 

15441.  Mendiratta DK; Bhutada K; Narang R; Narang P. Evaluation of different methods for diagnosis of p. falciparum malaria Indian Journal of Medical Microbiology. 2006 Jan; 24(1): 49-51.

15442.  Mharakurwa S, Simoloka C, Thuma PE, Shiff CJ, Sullivan DJ. PCR detection of Plasmodium falciparum in human urine and saliva samples. Malar J. 2006 Nov 8;5:103. 

15443.  Prakash JA, Abraham OC, Mathai E. Evaluation of tests for serological diagnosis of scrub typhus. Trop Doct. 2006 Oct;36(4):212-3.  

15444.  Ringsted FM, Bygbjerg IC, Samuelsen H.  Early home-based recognition of anaemia via general danger signs, in young children, in a malaria endemic community in north-east Tanzania. Malar J. 2006 Nov 20;5:111. 

Pathogenesis:

15445.  Awandare GA, Goka B, Boeuf P, Tetteh JK, Kurtzhals JA, Behr C, Akanmori BD.   Increased levels of inflammatory mediators in children with severe Plasmodium falciparum malaria with respiratory distress. J Infect Dis. 2006 Nov 15;194(10):1438-46.

15446.  Taoufiq Z, Pino P, Dugas N, Conti M, Tefit M, Mazier D, Vouldoukis I. Transient supplementation of superoxide dismutase protects endothelial cells against Plasmodium falciparum-induced oxidative stress. Mol Biochem Parasitol. 2006 Dec;150(2):166-73.

Vaccines:

15447.  Imoukhuede EB, Berthoud T, Milligan P, Bojang K, Ismaili J, Keating S, Nwakanma D, Keita S, Njie F, Sowe M, Todryk S, Laidlaw SM, Skinner MA, Lang T, Gilbert S, Greenwood BM, Hill AV.  Safety and immunogenicity of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men. Vaccine. 2006 Oct 30;24(42-43):6526-33.

Therapy:

15448.  Abu-Raddad LJ, Patnaik P, Kublin JG.  Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science. 2006 Dec 8;314(5805):1603-6. 

15449.  Adjei GO, Goka BQ, Kurtzhals JA.  Neurotoxicity of artemisinin derivatives. Clin Infect Dis. 2006 Dec 15;43(12):1618.

15450.  D'Alessandro U, ter Kuile FO.  Amodiaquine, malaria, pregnancy: the old new drug. Lancet. 2006 Oct 14;368(9544):1306-7.

15451.  Gligorijevic B, McAllister R, Urbach JS, Roepe PD.  Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites. 1. Quantification of hemozoin development for drug sensitive versus resistant malaria. Biochemistry. 2006 Oct 17;45(41):12400-10. 

15452.  Kaiser A, Ulmer D, Goebel T, Holzgrabe U, Saeftel M, Hoerauf A.  Inhibition of hypusine biosynthesis in plasmodium: a possible, new strategy in prevention and therapy of malaria. Mini Rev Med Chem. 2006 Nov;6(11):1231-41. Review. 

15453.  Mendez F, Munoz A, Plowe CV. Use of area under the curve to characterize transmission potential after antimalarial treatment. Am J Trop Med Hyg. 2006 Oct;75(4):640-4. 

15454.  Noedl H, Krudsood S, Chalermratana K, Silachamroon U, Leowattana W, Tangpukdee N, Looareesuwan S, Miller RS, Fukuda M, Jongsakul K, Sriwichai S, Rowan J, Bhattacharyya H, Ohrt C, Knirsch C.  Azithromycin combination therapy with artesunate or quinine for the treatment of uncomplicated Plasmodium falciparum malaria in adults: a randomized, phase 2 clinical trial in Thailand. Clin Infect Dis. 2006 Nov 15;43(10):1264-71.

15455.  Sidibe M, Ramiah I, Buse K.  The Global Fund at five: what next for universal access for HIV/AIDS, TB and malaria? J R Soc Med. 2006 Oct;99(10):497-500.

15456.  Van Geertruyden JP, Mulenga M, Kasongo W, Polman K, Colebunders R, Kestens L, D'Alessandro U.  CD4 T-cell count and HIV-1 infection in adults with uncomplicated  malaria. J Acquir Immune Defic Syndr. 2006 Nov 1;43(3):363-7. 

15457.  Vogel G. Malaria. Chloroquine makes a comeback. Science. 2006 Nov 10;314(5801):904. 

15458.  Wiseman V, Kim M, Mutabingwa TK, Whitty CJ. Cost-effectiveness study of three antimalarial drug combinations in Tanzania. PLoS Med. 2006 Oct;3(10):e373.