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Alpers disease

Alpers' disease, also called progressive infantile poliodystrophy, is a progressive degenerative disease of the central nervous system that occurs in infants and children. It is an autosomal recessive disorder that is sometimes seen in siblings. First signs of the disease, which include intractable seizures and failure to meet meaningful developmental milestones, usually occur in infancy, after the first year of life, but sometimes as late as the fifth year. more...

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Primary symptoms of the disease are developmental delay, progressive mental retardation, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to quadriplegia, and progressive dementia. Seizures may include epilepsia partialis continua, a type of seizure that consists of repeated myoclonic (muscle) jerks. Optic atrophy may also occur, often leading to blindness. Deafness may also occur. And, although physical signs of chronic liver dysfunction may not be present, many patients suffer liver impairment leading to liver failure. While some researchers believe that Alpers' disease is caused by an underlying metabolic defect, no consistent defect has been identified. Pathologically, there is status spongiosus of the cerebral grey matter.

Treatment

There is no cure for Alpers' disease and, currently, no way to slow its progression. Treatment is symptomatic and supportive. Anticonvulsants may be used to treat the seizures. However, caution should be used when selecting valproate as therapy since it may increase the risk of liver failure. Physical therapy may help to relieve spasticity and maintain or increase muscle tone.

Prognosis

The prognosis for individuals with Alpers' disease is poor. Those with the disease usually die within their first decade of life. Liver failure is usually the cause of death, although cardiorespiratory failure may also occur.

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Rapid diagnosis of falciparum malaria by using the ParaSight F test in travellers returning to the United Kingdom: prospective study
From British Medical Journal, 8/19/00 by I M Cropley

A simple diagnostic strip test for Plasmodium falciparum malaria (ParaSight F test, Becton Dickinson Advanced Diagnostics) detects a water soluble antigen, histidine rich protein 2, which is produced by blood stages of P falciparum. High sensitivity and specificity have been reported for the test in areas where malaria is endemic[1-3] and in studies of travellers returning from such areas.[4 5] We compared the test with standard blood film microscopy in febrile travellers returning to the United Kingdom from such areas.

Subjects, methods, and results

We studied 160 consecutive patients aged 9-77 years presenting between April 1994 and June 1996 to our unit with a history of fever and travel in the previous year to an area where malaria is endemic. Thin films were stained with Giemsa and read by an experienced microscopist. The ParaSight F test was performed in accordance with the manufacturer's instructions; a pink band indicates a positive result. Each test took less than 10 minutes to perform. Thin films and test strips were read blind to each other.

In 45 patients falciparum malaria was the final diagnosis (table). At presentation 42 cases were detected by microscopy and 42 by the ParaSight F test. Parasitaemias ranged from [is less than] 0.01% to 15% of erythrocytes parasitised. In one patient, the test was positive at presentation, and scanty ([is less than] 0.001%) P falciparum trophozoites were detected on blood film only on day 2. In two other patients both the blood film and the test gave negative results at presentation but positive results on subsequent days. One patient had a positive test with a negative blood film; three days previously he had had halofantrine treatment for presumed malaria. One patient with pneumococcal meningitis had positive tests over three days with negative daily blood films. The test was negative in one patient with a P falciparum parasitaemia of [is less than] 0.01%.

Results of tests for infection with Plasmodium falciparum and subsequent diagnosis. Values are numbers of patients

Test results were negative in all 113 other patients who did not have P falciparum infection, including 27 infected with other malarial species (23 with P vivax, 3 with P ovale, 1 with P malariae). Other diagnoses included diarrhoeal disease, dengue fever, typhoid, pneumonia, urinary tract infection, brucellosis, acute myeloid leukaemia, and infectious mononucleosis.

Compared with the final diagnosis, the ParaSight F test used at first presentation had a sensitivity of 93.3%, a specificity of 98.3%, a positive predictive value of 95.6%, and a negative predictive value of 97.4%.

Comment

The ParaSight F test is simple, rapid, and has adequate sensitivity and specificity for initial assessment of P falciparum infection in returning travellers. It identified all patients with P falciparum apart from one patient with a low parasitaemia of [is less than] 0.01% and two patients with parasites not detected on initial microscopy. Positive test results in the patient treated with halofantrine are explained by the established persistence of histidine rich protein 2 in the blood for up to 10 days. Positive results of the patient with pneumococcal meningitis were taken to be a genuine false positives.

The test does not remove the need for blood film examination as it is not 100% sensitive at low parasitaemias, and repeated daily testing may be necessary to establish the diagnosis. Nor does the test give any indication of density of parasites, essential in planning management.

The ParaSight F test has a useful role in the initial screening of febrile returning travellers with suspected falciparum malaria, particularly where laboratory staff are not experienced in diagnosing malaria. The test can be considered a "side room" investigation, as it requires no special training. It may also be used to distinguish between the benign malarias and the potentially lethal falciparum malaria.

Contributors: DNJL and RND designed the study; DNJL, DM, and IMC carried out the study; IMC wrote the first draft of the paper, with subsequent input from GP, RD, and DNJL. DNJL is the guarantor for the study.

Funding: ParaSight F test strips were provided by Becton-Dickinson.

Competing interests: None declared.

[1] Shift CJ, Premji Z, Minjas JN. The rapid manual ParaSight-F test. A new diagnostic tool for Plasmodium falciparum infection. Trans R Soc Trap Med Hyg 1993;87:646-8.

[2] Beadle C, Long GW, Weiss WR, McElroy PD, Maret SM, Oloo AJ, et al. Diagnosis of malaria by detection of Plasmodium falciparum HRP-II antigen with a rapid dipstick antigen-capture assay. Lancet 1994;343:564-8.

[3] Genton B, Paget S, Beck HP, Gibson N, Alpers MP, Hi I. Diagnosis of Plasmodium falciparum infection using ParaSight(R)-F test in blood and urine of Papua New Guinean children. J Southeast Asian J Trop Med Public Health 1998;29:35-40.

[4] Van den Ende J, Vervoort T, Van Gompel A, Lynen L. Evaluation of two tests based on the detection of histidine rich protein 2 for the diagnosis of imported Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1998;92:285-8.

[5] Pieroni P, Mills CD, Ohrt C, Harrington MA. Kain KC. Comparison of the ParaSight-F test and the ICT Malaria Pf test with the polymerase chain reaction for the diagnosis of Plasmodium falciparum malaria in travellers. Tram R Soc Trop Med Hyg 1998;92:166-9.

(Accepted 22 February 2000)

Lister Unit, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ

I M Cropley senior registrar in infection and tropical medicine

Diana N J Lockwood senior registrar in infection and tropical medicine

G Pasvol professor of infection and tropical medicine

R N Davidson senior lecturer in infection and tropical medicine

Department of Haematology, Northwick Park Hospital D Mack chief medical laboratory scientific officer

Correspondence to: D N J Lockwood, Hospital for Tropical Diseases, London WC1E 6AU diana.lockwood@ lshtm.ac.uk

BMJ 2000;321:484-5

COPYRIGHT 2000 British Medical Association
COPYRIGHT 2000 Gale Group

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