AWARENESS OF ONCHOCERCIASIS

805 4. Bauer AW, Kirby WMM, Sherris JC, Turck M. Antibiotic susceptibility

testing by a

standardized single disk method. Am J Clin Pathol 1966; 45: 493-98. 5. Price KE, Kresel PA, Farchione LA, Siskin SB, Karpow SA. Epidemiological studies of aminoglycoside resistance in the USA. J Antimicrob Chemother 1981; 8 (suppl A): 89-105. 6. Noriega ER, Leibowitz RE, Richmond AS, et al. Nosocomial infection caused by gentamicin-resistant streptomycin sensitive Klebsiella. J Infect Dis 1975; 131

(suppl): S45-50. 7. Weinstein RA, Kabins SA. Strategies for prevention and control of multiple drug-resistant nosocomial infection. Am J Med 1981; 70: 449-54. 8. Levine JF, Maslow MJ, Leibowitz RE, et al. Amikacin resistant Gram-negative bacilli: Correlation of occurrence with amikacin use. J Infect Dis 1985; 151: 295-300.

CONSENSUS ANALYSIS

SiR,—The consensus analysis described by Professor Bull and his colleagues (Aug 16, p 377) appears to be an effective technique. However, the article does not describe the statistical procedure in sufficient detail to enable other potential users to apply it. What quantitive criteria are used for the initial rank ordering? How is the rank ordering modified by the results of patient visits? How is the consensus average calculated? 4077 Olive Hill

Drive, Claremont, California 91711, USA

SYLVAN GOLLIN

B*This letter has been shown to Professor Bull and Mr Westengard, whose reply follows.-ED.L .

SiR,-Our

paper

seems to

have confused several readers; in

particular, the terms ranking, rank order, and consensus have been frequently misinterpreted. "Ranking" as used in the title is in the commonly understoodsense of comparing one test with another. "Rank ordering" as described in Methods is used in the technical sense of taking all of the results obtained by one test method during the entire study and arranging them in order from lowest to highest. "Consensus" is used to refer to the average rank-order value of all the tests done on a patient at a single visit except for the test under scrutiny. It expressly excludes any clinical evaluation of the patient by one or more

physicians. Consider the hypothetical case of three patients on whom four (A, B, C, and D) are done every time at five clinic visits. For consensus analysis to be applicable the condition of the patients change for better or for worse, over the course of the five visits, for it is against this changing condition as reflected in the consensus that the correlation with each individual test is determined. This hypothetical study provides 15 results for test A, test B, and test C, over the 15 clinic visits and is large enough to illustrate steps 1 - 3 of the analytical procedure. Steps 4 and 5 require a data set of the size described in our Lancet paper. Step 1: To compare results that are measured in different units and on different scales the 15 results for test A are rank-ordered from low to high. Then each result is replaced for all subsequent statistical analysis by its rank-order number (here 1-15). Tests B, C, and D are treated similarly. Step 2.-The rank order of result A, B, C, and D is correlated (Spearman’s r) with the average rank order of the remaining tests done on that patient at that visit (consensus). Step 3.-After all 15 patient-visit records have been analysed all data from the test method with the poorest average correlation to the consensus are dropped and the 15 patient-visit records are reanalysed for the remaining three test methods. Step 4.-Surviving test methods from the above analysis are grouped into families of related tests by the behaviour of their Spearman’s r as the number of tests in the consensus decreases. Step S.-Finally, each surviving test is correlated with a new consensus limited to the survivors from steps 1-4. This consensus, to avoid the obvious hazard of circularity, excludes both the test under scrutiny and all other members of its family. It is this final consensus, tailor-made for each test, that determines how well or how poorly a test reflects the changes in patient’s disease. tests

Department of Pathology and Laboratory Medicine, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA

BRIAN S. BULL J. C. WESTENGARD

TREATMENT OF ACUTE LYMPHOBLASTIC LEUKAEMIA: A TERMINOLOGICAL PLEA

SiR,—The realisation that disease in the central nervous system

(CNS) was a major obstacle to cure in children with acute lymphoblastic leukaemia (ALL) led to the systematic use, by Pinkel and colleagues at St Jude Hospital, of treatment directed specifically at the CNS.l The result was a major improvement in the proportion of disease-free survivors.2The term "CNS prophylaxis" is still frequently used to describe this phase of ALL treatment, whether with chemoradiotherapy or with chemotherapy alone.33 "Prophylaxis" means prevention, and in other medical contexts the word is used to describe treatment which, it is hoped, will prevent a disease or complication of which the patient is at risk. Craniocervical irradiation and a short course of intrathecal methotrexate might alter the cellular permeability of the bloodbrain barrier, making it more difficult for leukaemic blasts to invade the CNS, and this would constitute true prophylaxis. However, histopathological studies4,5 indicate that such treatment is eradicating disease already present within the CNS but clinically silent. Such subclinical tumour escapes detection by cytological examination of the cerebrospinal fluid and is inadequately treated by systemically delivered drugs because of poor penetration of the blood-brain barrier,but it can be eradicated by craniocervical irradiation and intrathecal methotrexate. The term "maintenance treatment" to describe chemotherapy given to patients with ALL who have achieved complete remission, via induction therapy with or without intensification, also needs reappraisal. When the phrase was introduced, some 20 years ago, the outlook for children with ALL was poor and the choice of words was perhaps influenced by the then prevalent belief that such treatment was more likely to prolong (maintain) the remisssion than eradicate residual disease and thus cure the patient. Old habits die hard but we suggest that both terms are discarded. As a substitute for "CNS prophylaxis", "CNS-directed therapy" (or "CNS therapy", the description used in the original article from St Judel) is brief and accurate. To come up with a satisfactory alternative to "maintenance therapy" is more difficult, but "continuing treatment" or "treatment in remission" are possible alternatives. J. PRITCHARD Hospital for Sick Children, London WC1N 3JH J. M. CHESSELLS 1. Aur RJA, Simone J, Hustu HO, et al. Central nervous system therapy and combination chemotherapy of childhood acute lymphocytic leukemia. Blood 1971; 37: 272-81. 2. Hustu HO, Aur RJA, Verzosa MS, et al. Prevention of central nervous system leukaemia by irradiation. Cancer 1973; 32: 585-97. 3. Green DM, Freeman AI, Sather HN, et al. Comparison of three methods of centralnervous-system prophylaxis in childhood acute lymphoblastic leukaemia. Lancet 1980; i: 1398-402. 4. Thomas LB, Chirigos MA, Humphreys SR, Goldin A. Development of meningeal leukaemia (L1210) during treatment of subcutaneously inoculated mice with methotrexate. Cancer 1964; 17: 352-60. 5. Moore EW, Thomas LB, Shaw RK, Freireich EJ. The central nervous system in acute leukemia: a post-mortem study of 117 cases with particular reference to hemorrhage, leukemic infiltrations and the syndrome of meningeal leukemia. Arch Intern Med 1960; 105: 451-68. 6. Rall DP. Experimental studies of the blood-brain barrier. Cancer Res 1962; 25: 1572-77.

AWARENESS OF ONCHOCERCIASIS

SIR,—Your Sept 6 editorial on Loa loa notes that the study of this pathogenic parasite was neglected in the west until US Peace Corps workers brought the disease to Washington ten years ago. Similar studies on the clinical and pathological effects of that other filarial parasite, Onchocerca volvulus, may also be stimulated as more workers travel to affected areas. Onchocerciasis has been studied in areas of high endemicity, but perhaps more by epidemiologists and ophthalmologists than by general clinicians. Standard textbooks on tropical disease emphasise the late signs, such as widespread dry dermatitis, hanging groin, and

806

blindness, and clinicians have not been encouraged to look for the earlier evidence of disease.l-6 These early and persisting signs and symptoms include chronic backache, shoulder, chest, and hip pains, non-pitting oedema, deep muscle abscesses, enlarged glands in the groin, and patches of epidermal oedema, visible as peau d’orange only when viewed in a cross-light on an otherwise perfectly normal skin. Musculoskeletal symptoms cause a major amount of incapacitating morbidity, especially amongst farmers and manual workers. In an endemic area of Nigeria, when these symptoms were taken as an indication for skin-snips, many puzzling cases were diagnosed for the first time71J and at last given relief. A 46-year-old Nigerian roadworker with a 6-year history of unexplained abdominal discomfort and backache had been labelled "? hypochondriac". He had enlarged lymph glands in the groin and peau d’orange on the abdomen and back. Spinal movements were normal. Skin snips were strongly positive. A course of diethylcarbamazine citrate (DEC) gave him his first real relief in years.

Many cases are missed in Nigeria through waiting for severe dermatitis or ocular problems to appear. How much more likely is the diagnosis to be missed when people return to the west having worked in an endemic area? Looking mainly for late signs is like restricting ourselves to diagnosing syphilis only at the onset of general paralysis of the insane or leprosy only when we can see foreshortened fingers. An obstetrician, who had worked in West Africa for several years, returned to the United States with backache and peau dorange on one hand. A rheumatologist in Washington diagnosed ankylosing spondylitis and a dermatologist at the National Institute of Health diagnosed scleroderma. The obstetrician went to Australia, where visual symptoms developed and microfilariae of 0 volvulus were found in the anterior chamber. DEC cured the eyes, and the musculoskeletal and dermatological symptoms as well, this link being realised only in retrospect. An anthropologist who had worked in an area of East Africa endemic for onchocerciasis had pruritus in Britain 15 months after probable exposure while living in the bush. Symptomatic treatment only was given. 9 months later chronic low backache started and a lumbar support was prescribed. After a further 16 months the pruritus intensified, a rash appeared on her trunk and buttock, and then pains started in the right hip. Now began 9 years of chronic low backache, hip pain, general rheumatic symptoms, pruritus, intermittent dermatitis, and insomnia. Despite many referrals, mainly to orthopaedic surgeons, no all-embracing diagnosis was reached, except a suggestion of hypochondria. Arthropathies developed in the right ankle and left knee, but it was not until itching in the eyes developed, with headache and paraesthesia from behind the eyes, over the head to the back of the neck, that an ophthalmologist was called in, and found signs suggestive of onchocerciasis and a positive filarial antigen test. It had taken 12 years to reach the

diagnosis.

When DEC and suramin was started, there was a strong Mazzotti reaction. Nodules appeared on her chest and right knee, and there was exacerbation of hip pain. Further courses of DEC and suramin were given over the next 2 Y2 years, with diminishing Mazzotti reactions. There was marked improvement not only in the ocular symptoms and pruritus, but also in the musculoskeletal symptoms. The lumbar support, which she had expected to wear for the rest of her life, was discarded 18 months after starting treatment, and she has been free from low back and hip pain since. Once more the significance of this was not realised until later. Onchocerciasis is still endemic over large areas of West and East Africa and Central and South America. All doctors treating patients who have travelled to these countries should be made aware of the early signs and symptoms of the disease. General practitioners,

dermatologists, rheumatologists, and orthopaedic surgeons, should be particularly on the alert, and not just the ophthalmologists and specialists in tropical medicine. 2 Springfield Road, Bury St Edmunds, Suffolk

IP33 3AN

MJ, Gabathuler AW. Report of onchocerciasis (May): 188-95. E Afr Med 1947 J

1. Gabathuler

C. A. PEARSON in the

Ulanga District.

2. 3.

Jopling WH. Onchocerciasis presenting without dermatitis. Br Med J 1960; i: 861. Lamp HC. Musculo-skeletal symptoms in onchocerciasis. W Afr MedJ 1967; 16: 60-62.

on an oil palm estate. Trans Roy Soc Trop Med Hyg 1971; 65: 484-89. 5. Buck AA, ed. Onchocerciasis: Symptomatology, pathology, diagnosis. Geneva: World

4. Thomson IG. Onchocerdasis

Health Organisation, 1974: 12. 6. Mahoney JL. Management of onchocerciasis. S Afr Med J 1982; 61: 50-52. 7. Pearson CA. Are we missing cases of onchocerciasis? Trop Doctor 1985; 15: 140-41. 8. Pearson CA, Brieger WR, Ramakrishna J, Kale OO, Adeniyi JD. Improving recognition of onchocerciasis: Non-classical symptoms. Trop Doctor 1985; 15: 160-63.

MENINGOCOCCAL DISEASE IN SOUTH-WEST OF ENGLAND

and co-workers

SIR,-Dr Cartwright (Sept 6, p 558) report a continuing outbreak of sulphonamide-resistant group B type 15 meningococcal disease in Gloucestershire with particular localisation of cases in certain communities. A comparable excess of cases, mostly with the same group and serotype, was seen during a similar period in the Plymouth Health District managed population (figure).

Quarterly

cases

of meningococcal infection in Plymouth Health

District managed population (Plymouth, West and South Devon, and East Cornwall).

The peak incidence in both outbreaks was early, with that of Plymouth in the first quarter and that of Gloucester in the last quarter of 1983. The total number of cases over the period October, 1981, to March, 1986, was also comparable (Gloucester 65, Plymouth 57). We have detailed information on 53 of these 57 cases, 37 of whom (70%) lived within Plymouth city. Although this proportion is similar to that reported from Stroud (66% or 43/65) there was no clustering either within urban Plymouth or in other towns and villages in the area. Until 1986, there was no excess meningococcal activity in other health districts in south-west England. To help general practitioners recognise cases early, bulletins summarising the presenting signs and symptoms and the management of contacts have been issued. Vomiting (86%) and rash (65%) were far more common as presenting features in 51 patients admitted to hospital in 1982-85, headache being recorded in 39%, confusion in 12 %, and joint pains in 10 %. When a vaccine becomes available, priority should be given to high-risk groups. In the absence of other known risk factors, agespecific incidence rates are useful in formulating vaccination policies (table). Despite the wide confidence limits, the priority risk groups for this

area

would be 15-19-year age group, followed

CUMULATIVE AGE-SPECIFIC INCIDENCE RATES (AND

95%

CONFIDENCE LIMITS) OF MENINGOCOCCAL GROUP B 15 AND C INFECTIONS

(1982-85) PER 100 000 MANAGED POPULATION

by