Public health
Iodination of irrigation water as a method of supplying iodine to severely iodine-deficient population in XinJiang, China
Summary Severe iodine deficiency still occurs in many countries, and causes cretinism and mental impairment. In southern Xinjiang province, China, after usual methods of iodine supplementation had failed, we iodinated irrigation water to increase iodine in soil, crops, animals, and human beings. 5% potassium iodate solution, dripped into an irrigation canal for 12 or 24 days, increased soil iodine 3-fold, and crop and animal iodine 2-fold. Median urinary iodine excretion in children increased from 18 to 49 µg/L (two groups of similar age). The cost for iodine was US $0·05 per person per year. Soil iodine remained stable over one winter, and dripping of iodine during the second year (US $0·12 per person per year) resulted in a further 4-fold increase in soil iodine and a 1·8-fold increase in iodine in crops. We conclude that iodination of irrigation water is an advantageous and costeffective method of supplying iodine in southern Xinjiang, and may be useful in other areas dependent on irrigation.
a
Introduction Worldwide, iodine deficiency is possibly the most common preventable cause of mental retardation, manifested as endemic
cretinism and lesser degrees of mental impairment.1-5Such diseases can be prevented by provision of iodine, particularly to women of child-bearing age and young children.6 In most countries iodine is usually added to salt. However, this strategy is impractical for many remote and indigenous populations.7 Much of the southern part of Xinjiang Autonomous Region, China, is a rural area of severe iodine deficiency (figure 1). The area is entirely irrigated by run-off water from the surrounding Kunlun, Pamir, and Tian Shan mountains. The irrigation systems are highly efficient. Repletion of iodine by any available method has been unsuccessful. The traditional and preferred salt is rock salt obtained from the Taklamakan desert floor, which has a negligible iodine content (0-2 parts per million [ppm]). Iodised salt is offered in a few stores in the towns, but most people are not aware of it, refuse it as less savoury, or prefer the cheaper rock salt. Attempts to provide intramuscular iodine in oil in 1984 or oral iodine in oil in 1988 were ineffective. We thought that the best way to give iodine uniformly to the entire population would be to add iodine to the irrigation water. Initial calculations suggested that iodinated irrigation water would leave iodine in the soil, increase crop and livestock iodine content, and eventually increase the amount of iodine ingested by people. An upper limit of cost of 1 yuan (US$0-15) per person per year was thought of as being supportable by the local communities (average annual family income is about US$108).
Methods County, on the southern margin of the Taklamakan desert (figure 1), is densely populated and people there have severe iodine deficiency. In Long Ru township, mean (SD) iodine in water was 1-3 (0-35) ug/L (n=41) and in soil 7-0 (2-4) J.1g/kg (n=40). These concentrations are extremely low. 193 children under 13 years of age were examined: 54% had goitre (thyroid gland visible with neck extended) and 6% had cretinism on the basis of deaf mutism, proximal rigid-spastic motor disorder, and mental retardation not explained by other neurological disease. Mean urinary iodine excretion of 3-year-old children was 28-07 (253) pg/L (n= 141), with 47% having under 25 pg/L (ie, severe iodine deficiency). We chose a test site of about 9 km2 supplied by a single canal of which an estimated 3-7 km2 is cropland and 1 55 km2 was iodinated during the first year of our study. 5600 people lived in seven villages. After extensive preliminary study and having obtained informed permission from the local, county, and provincial officials, we began a trial in June, 1992. 10 kg potassium iodate as a 5% solution was dripped over 12 days into a canal that had a flow of 1.1m3/s. In a second dripping in August, 1992, 20 kg potassium iodate was used over 24 days. In a second year (1993) at Long Ru,
Hotien
Xinjiang Health and Anti-Epidemic Station, Urumchl, XinJlang (X-Y Cao MD, X-M Jiang MD, Z-H Dou MD, M Abdul Rakeman MD); Institute for Endemic Disease Control and Research, Urumchl,
Xinjlang (A Kareem MD, M-L Zang MD, X-M Jiang MD); Tlanjin Medical College, Tianjin (T Ma MD); and Duke University Medical Center, Durham NC 27710, USA (K O’Donnell PhD, N DeLong BA, G R DeLong MD) Correspondence to: Dr G Robert DeLong
107
Figure 2: Mean (SD) water-soluble Iodine In soil before, during, and after Iodate dripping into Irrigation water n = 40 except for Oct
(34),
Nov
(15), Dec (14),
and Mar
(14).
25 m apart. Iodine was measured by Barker’s modified incineration technique and catalytic reduction of ceric ion by arsenite salt" at the Institute of Endemic Diseases Research, Urumchi. Measurement of iodine in test water samples showed a mean error of 3%. We assessed iodine in various foodstuffs before iodination and after harvest of crops grown during iodination. Urinary iodine was measured in a sample of 2-6-year-old children before iodination and in a separate sample 1 year later (May, 1993), when children had been exposed to crops from the first dripping. The second dripping had been done, but no crops had been harvested. (Thus children may have been exposed to iodine in drinking water, but not to 1993 crops. In general, 10% of iodine intake comes from water and 90% from foodstuffs.9) We also studied a control group of children from an adjacent non-iodinated area. We used the unpaired t test for statistical analysis. In figure 3, we plotted the frequency distribution of urine iodine determination, and used the &khgr;2 test for group comparisons.
Results Mean
water
dripping,
80 kg potassium iodate was added to irrigation water: 40 kg between March 8 and April 1, and the rest between April 21 and June 10. During the first period (24 days) dripping continued day and night whereas during the second period (48 days) dripping was done during daylight only since farmers in this area irrigate their fields during the day. The estimated cost of this iodination was US$0 12 per person per year. Water and soil samples for iodine assay were collected at forty sites that were roughly equidistant over the test area. Each soil sample consisted of a mixture of five 10 cm cores, 40 cm deep, taken
After dripping
After dripping
(September, 1992)
(June, 1993)
001 <0001
20
94(23)
<0025
12
129(1-1)
<0001
66(20)
21
120(30)
<0001
20
206(61)
<0.001
33(069)
22
103(31)
<0001
20 22
13
56(18)
28
Oil crops
Vegetables
108
(SD)
65(55) 104(22)
32(18) 54(33)
11 18
(SD)
1992 vs June,1993.
before
expected,
No
Mean
90
g/L As
p*
No
Mean
*March, 1992
(3-1) µg/L during dripping.
(March, 1992) No
Table : Mean
7-5
Before dripping
Cereals Wheat Other
vs
iodine increased from 1-3 (0-35)
iodine subsided quickly after dripping stopped. After dripping, soil iodine increased from 7-0 (2-4) to 23-3 (12-7) µg/kg (figure 2). Over the next 4 weeks, soil iodine remained stable (25-7 µg/kg 2 weeks after the end of dripping, 27-0 at 3 weeks, and 20-6 at 4 weeks). The distribution of water and soil iodine among the forty sites was reasonably uniform, as indicated by the SDs. The second period of dripping produced similar results in water (8-1µg/L) without higher concentrations in soil (24-6 [6’8] µg/kg, n=35). Soil was sampled until March, 1993 (figure 2). Thus 6 months after the last application, soil iodine content remained 25 times higher than the original. Several cores were divided into three by depth. The portions showed a typical pattern: for example, in March,
Figure 1: Long Ru In Hotien County
Meat, eggs, and milk
to
Mean
September, 1992. tSeptember, (SD) Iodine (µg/100 g) In various foods before and after lodination of Irrigation water In Long Ru
(SD)
pt
(6-4) µg/kg in March, 1993, before the second year of dripping began. Iodine data to date in crops showed a 1 8 times increase compared with the results of the first year of iodination (table 1). 18-6
Figure 3: Urinary Iodine (µg/L) In Long Ru children 2-6 years old In Long Ru test and control sites. Before dripping (May 1992) and after dripping (May 1993)
(upper third), 14-0 (middle), and 23 8 µg/kg (lower third). Iodine in grain crops, oil crops, and vegetables, and in 9-3
meat, eggs, and milk increased about 2-fold after iodination (table 1). The mean iodine content of sheep thyroid increased from 4615 (2250) (n = 7) to 7633 (1599) (n 4) µg per 100 g (p < 005), and that of chicken thyroid from 2467 (915) to 7475 (2627) µg per 100 g (n 4) (p < 0-05). In 1992 before dripping, the median urine iodine excretion of 102 children aged 2-6 years in the test villages was 18 ug/L. 71 % had urine iodine excretion of 25 ug/L or less. 9 % had excretion of 100 ug/L or more; this presumably reflected the maximum extent of penetration of iodised salt use in these villages, which included the town offices and shops (the comparable value in the control non-iodinated villages was 3%). In May 1993, one year after the first dripping, the median urine iodine excretion value in a comparable sample of children in the test villages had increased to 49 µg/L. 16% had excretions greater than 100 g/L, 27% 50-100 µg/L, 28% 25-50%, and 29% less than 25 µg/L (figure 3). This change is highly significant (X2 23, p < 0001 ). Even so, an important proportion of children did not benefit, presumably because not all fields were irrigated during the dripping periods; this may be remedied by further dripping. The median iodine excretion and distribution did not change in the control villages. On June 24, 1993, 2 weeks after completion of dripping, soil iodine was 86-6 (36-4) µg/kg (n = 16) and in September, 1993, iodine was 50-2 (27) ug/kg (n = 30), compared with =
=
=
Discussion Our study showed that we can supply iodine to a rural irrigation-dependent population by adding potassium iodate to irrigation water, and that added iodine progresses through a chain to soil, crops, and animals back to human beings. The method replicates an iodine-sufficient natural environment. Thus, there is no concern about an effect on palatability of water, because the added levels in water are no higher than in many iodine-sufficient areas, or of excess ingestion of iodine-as in oral oil or injection programmes, where the subject receives a large excess of iodine at one time with possible risks of hypothyroidism or hyperthyroidism. Potassium iodate is the limiting factor in the costeffectiveness of this method. The cost of the project in 1992, based on the current international market price (US$8-50/kg) is US$0-05 per person per year (about 1/3 Chinese yuan). The increase in median urinary iodine excretion from 18 to 49 Jlg/L in young children, if paralleled by similar increases in women of child-bearing age, is adequate to prevent cretinism. Higher iodine levels (100 µg intake per day) are desirable10 and should be attainable. The method appears to be economically feasible. Other indirect benefits may accrue, including improved livestock production. 11,12 Dripping in the second year was more liberal (cost US$0-12 per person per year) and achieved higher iodine in soil and crops. Results in human beings are not yet available. The optimum iodination still needs to be defined. Co-ordination of dripping with the time of crop growth and irrigation may improve efficiency (eg, dripping during the day when farmers let water into the fields). An important question that relates to the ultimate cost is the fate of added iodine in the soil, which remained stable over one winter; whether it will persist over a full year or longer is unknown. Iodine might be lost from the surface or move deeper in the soil over time. Without further iodination, non-iodinated irrigation water might leach the iodine from the soil. We plan to clarify these questions by withholding iodine at Long Ru during the next year and monitoring persistence. We have now expanded the project to a second site, 20 km distant, with a population of 15 600. Preliminary results are similar to those in Long Ru. Iodination of irrigation water, in an area where the population relies entirely on irrigation, is a feasible and cost-effective method of supplying iodine. There are several advantages: it is simple to institute and administer, does not require trained medical personnel, is inexpensive, and is easily adapted to the local culture. The method provides iodine naturally, at physiological values, reaches all rural residents (including the poorest and most remote) on an ongoing basis, and needs few personnel and resources. Livestock may also benefit. Iodine, once added to the soil, persisted over one winter season and may remain longer. Iodination of irrigation water is a practical method for iodine supplementation in deficient areas throughout southern Xinjiang, and may be useful in other areas with extensive irrigation and iodine deficiency. This study USA.
was
supported by the Thrasher Fund, Salt Lake City, Utah,
109
References 1 Hetzel BS, Maberly GF. Iodine. In: Merzt W, ed. Trace elements in human and animal nutrition. Vol 2. 5th ed. Orlando: Academic Press, 1986: 139-208. 2 DeLong GR. Effects of nutrition on brain development in humans. Am J Clin Nutr 1993; 57 (suppl): 286S-90S. 3 DeLong GR. Neurological involvement in iodine deficiency disorders. In: Hetzel BS, Dunn JT, Stanbury JB, eds. The prevention and control of iodine deficiency disorders. Amsterdam: Elsevier, 1987: 49-63. 4 Halpern J-P, Boyages SC, Maberly GF, Collins JK, Eastman CJ, Morris JGL. The neurology of endemic cretinism. Brain 1991; 114: 825-41. 5 DeLong GR, Robbins J, Condliffe PG. Iodine and the brain. New York: Plenum Press, 1989. 6 Delange FM. Relation of thyroid hormones to human brain development In: Hetzel BS, Smith RM, eds. Fetal brain disorders— recent approaches to the problem of mental deficiency. Amsterdam: Elsevier, 1981: 285-96.
Dunn JT. Alternatives to salt and oil for iodine supplementation. In: Hetzel BS, Dunn JT, Stanbury JB, eds. The prevention and control of iodine deficiency disorders. Amsterdam: Elsevier, 1987: 135-38. 8 Fisher KD, Carr CJ. Iodine in foods: chemical methodology and sources of iodine in the human diet. Bethesda, Maryland: Life Sciences Research Office, Federation of American Societies for Experimental Biology (National Technical Information Service, Springfield, Virginia), PB-233 599, 1974. 9 Anke M, Groppel B. Iodine supplements of livestock and their influence on the iodine supply of humans. In: The elimination of iodine deficency disorders. (Greasimor G, ed.) International Symposium, Tashkent, Uzbekistan, 1991: 1-94 (abstr). 10 Delange F. Disorders due to iodine deficiency. Acta Clin Belg 1990; 45: 394-411. 11 Hemken RW, Vandersall JH, Oskarsson MA, Fryman LR. Iodine intake related to milk iodine and performance of dairy cattle. J Dairy Sci 1972; 55: 931. 12 Anonymous. Iodine. In: Mineral tolerance of domestic animals. Washington, DC: National Academy of Sciences, 1980: 227-41. 7
Disseminated Penicillium marneffei infection in Southeast Asia
Summary Disseminated infection with the fungal pathogen Penicillium marneffei is, after extrapulmonary tuberculosis and cryptococcal meningitis, the third most common opportunistic infection in HIV disease in northern Thailand. We report the clinical, microbiological, and therapeutic features of a large series of HIV-infected adults with disseminated P marneffei infection. From August, 1987, to June, 1992, 92 patients with P marneffei infection confirmed by culture were seen at Chiang Mai University Hospital, of whom 86 were also infected with HIV. Clinical information was available for 80 of these patients. The most common presenting symptoms and signs were fever (92%), anaemia (77%), weight loss (76%), and skin lesions (71%). 87% of patients presenting with skin lesions had generalised papules with central umbilication. Presumptive diagnosis was made in 50 patients by microscopic examination of Wright’s-stained bone-marrow aspirate and/or touch smears of skin biopsy or lymph-node biopsy specimens. Most patients who were diagnosed responded initially to
Introduction Penicillium marneffei is the only Penicillium species that is dimorphic and can cause systemic mycosis in human beings; this is endemic in Southeast Asia and China.1,2, Prevalence of P marneffei infection has increased substantially during the past few years.3-15 This increase has occurred exclusively among patients infected with HIV.6,11 However, the clinical, microbiological, and therapeutic features of a large series of well-documented cases have not been reported. Here, we describe the clinical and laboratory features of 80 HIV-infected adults with disseminated P marneffei infection.
Patients and methods All HIV-infected patients with disseminated P marneffei infection who were seen at Chiang Mai University Hospital from August, 1987, to June, 1992, were included in the study. Diagnosis of HIV infection was made if the patient’s serum was repeatedly reactive by both enzyme-linked immunosorbent assay (ELISA) (EnzymunTest, Anti-HIV 1 + 2, Boehringer Mannheim Gmbh Diagnostica, Germany) and particle-agglutination test (Serodia-HIV, Fujirebio
amphotericin or itraconazole, whereas most who were not diagnosed and treated died. 12 patients relapsed within 6 months of cessation of treatment. P marneffei has become an important pathogen of HIVassociated opportunistic infection in Thailand.
Faculty of Medicine, Chiang Mai University, Chiang Mai 50002, Thailand (K Supparatpinyo MD, C Khamwan BSc, V Baosoung MSc, T Sirisanthana MD) and Department of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland, USA (Prof K E Nelson MD) Correspondence to: Dr Thira Sirisanthana, Section of Infectious Disease, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50002, Thailand 110
Figure 1: Number of patients with P mameffel Infection seen at Chiang Mal University Hospital and time of diagnosis Bars represent patients with
(open)
and without
(closed)
HIV infection.