Measuring exposure to Schistosoma japonicum in China. III. Activity diaries, snail and human infection, transmission ecology and options for control.

We used activity diaries and snail detection to relate water contact and Schistosoma japonicum infection among a cohort of 178 residents on two islands in the Dongting Lake, China. Water exposure to each of 12 mapped water zones around the islands was calculated (m(2) min/day) for each subject. Infected Oncomelania hupensis hupensis snails in this area are focal and were found in only five of the 12 zones, with the highest rate being 5.7%. Thirty-one subjects (17%) were re-infected with a mean intensity of 63.2 epg. Mean water contact was 7.9 m(2) min/day; 98% of water exposure was due to economic activity and only 2% due to swimming or bathing, washing and other necessities of daily life. Males had more exposure and infection than females (P<0.05). Infected subjects had more exposure (10.2 m(2) min/day) than those not infected (7.44 m(2) min/day) (P<0.05). Compared with uninfected subjects, those infected had 2.9 times more exposure in infected-snail zones (P<0.01). Also, human infection intensity (epg) correlated well with exposure to infected snail zones (r=0.552, P<0.01). People <20 years old had the highest re-infection (21.4%) and intensity (3.77 epg). Median exposure for 20-49-year-olds (9.00 m(2) min/day) was nearly double that of those aged <20 or >50 years old (5.5 m(2) min/day). We conclude that map-referenced water contact and snail evaluation boosts accuracy of activity-diary measurements in large transmission foci for the Asian schistosome. Protecting against faecal contamination of snail inhabited sites, and against occupational exposure for island residents, should be a priority of future research. Potential strategies for migrating buffaloes and families living on visiting fishing boats are explored.

A 2-year prospective study in China provides epidemiological evidence for resistance in humans to re-infection with Schistosoma japonicum.

In 1996, 250 people living in the Dongting-Lake region of China were selected for a 2-year study. All had been or were infected with Schistosoma japonicum. All were treated with praziquantel, although eggs of S. japonicum were only detected in stool samples from 75 of the subjects. In 1998, 213 (85.5%) of these subjects, then with a mean (S.D.) age of 40.2 (14.2) years, provided stool samples for final assessment. Forty-nine (23%) of the 213 were found to be re-infected in 1998, with a geometric mean intensity of infection among the infected of 64.5 eggs/g faeces. The rate of re-infection was highest among those aged < 10 years, declining with increasing age, and higher in males than females (27.3% v. 8.3%; P < 0.005). The mean intensity of infection among the infected males was also higher than that among the infected females [72.4 (4.8) v. 17.8 (2.5) eggs/g; P < 0.005]. Water contact by the subjects was estimated from activity diaries, for 141 days over the 2-year study period, and expressed as skin exposure, in m2-min/day. The mean exposure of a group of subjects was calculated by detransforming the mean of the fourth-root-transformed (i.e. normalized) values for the exposures of each subject within the group. Overall, the 213 individuals had a mean exposure of 6.2 m2-min/day. Differences in occupation led to males having much higher mean water exposures than females (9.2 v. 1.1 m2-min/day). As there was an inverse association between age-specific exposure and age-specific re-infection intensity, the marked reduction seen in intensity of re-infection with increasing age is not attributable to decreasing exposure to water. Instead, the results of this 2-year cohort study provide evidence for age-dependent resistance to re-infection with S. japonicum. The 213 subjects who were followed up were classified, according to epidemiological outcome at the end of the study and the data on water contact, as 'susceptible' (N = 49; 23%), 'insusceptible' (N = 29; 13.6%) or of 'uncertain status' (N = 135; 63.4%). Thus, 78 subjects who are potentially informative in terms of immunogenetics were identified. Further investigation of these individuals should help to shed some light on the role of immunogenetic status in human immunity to Schistosoma japonicum.

Epidemiological identification of Chinese individuals putatively susceptible or insusceptible to Schistosoma japonicum: a prelude to immunogenetic study of human resistance to Asian schistosomiasis.

An epidemiological method, field-tested in Hunan, China, to identify residents potentially susceptible or insusceptible to endemic schistosomiasis japonica is described, as a prelude to selection of subjects for immunogenetic studies. After an initial cross-sectional survey on two islands (Qingshan and Niangashan--population 2990) in 1995-1996, an informative cohort (N = 249) was selected for treatment and 9-month follow-up to measure exposure and re-infection. Both the population prevalence (15.8%) and the geometric mean intensity of infection (26.2 eggs/g faces) indicated that the islands were moderately endemic for schistosomiasis. Exposure measurements revealed a strong, positive, linear association (r = 0.70) between daily activity diaries and direct water-contact observation. Individuals identified as stool-positive for schistosomiasis had significantly more water contact than those who were egg-negative (P = 0.03). Almost all (93%) of the cohort had ultrasonographic evidence of periportal fibrosis before treatment but in only 1.2% was this fibrosis scored > 1 in terms of the stages identified by the World Health Organization. At the follow-up it was possible to classify the 249 subjects into three, distinct, exposure-infection epidemiological groups. The first group (N = 20) was susceptible to re-infection and constituted 8% of the cohort. The second group (N = 61) was apparently insusceptible to re-infection despite the continuing high levels of exposure and included 24% of the cohort. The other 68% of the cohort (N = 168) remained uninfected but were at most only moderately exposed, or had a status indeterminate due to non-compliance. This epidemiological identification of susceptibles and insusceptibles for schistosomiasis japonica' links field and ongoing laboratory studies aimed at characterising the genetic and immunological factors associated with resistance to re-infection and/or disease.

Measuring exposure to S. japonicum in China. I. Activity diaries to assess water contact and comparison to other measures.

We introduce a new method, activity diaries, in order to evaluate human water contact among fishing communities in an area moderately endemic for Schistosoma japonicum in the Dongting Lake region of Southern China. Two hundred and forty-nine subjects (76% male) were followed prospectively over a 9-month-period in order to verify exposure and reinfection. Exposure was determined crudely with questionnaires, direct 12-h water observations, and more precisely with activity diaries and an adjusted exposure model which took into account the time of day, the duration of contact and the percent body surface area in contact with water. Cohort subjects filled in activity diaries for an average of 85 days as compared with 2 days for the direct water observations. The typical unadjusted mean daily water contact (duration) based on the activity diaries was 53 min with 62% of this time spent in fishing. In contrast, the direct water observations revealed an average daily duration of 149 min with 53% of the time spent in fishing. Human water contact patterns (min/day) by site, activity and body part exposed were examined with the activity diaries. Individuals in the 36-49-year-old age range had the highest degree of water contact. Most of this daily contact occurred by males on the hands (mean+/-S.D.; 83.53+/-67.80 min/day) while fishing (mean+/-S.D.; 87.84+/-8.88 min/day) on the lake (mean+/-S.D.; 85.98+/-69.90 min/day). There was a strong positive log correlation (r=0.95) between the crude and adjusted (based on our derived exposure model) diary outcomes for the entire study sample, however, at higher exposure levels this relationship was differentially weaker (r=0.70). Results from this study suggest that current methods used in evaluating schistosomiasis exposure in China may overestimate and bias measures of the risk of infection. Activity diaries adjusted for the time of day, duration and the percent body surface area exposed are cost-effective and practical instruments to accurately quantify human exposure in the vast lake regions of Southern China where most of the endemic schistosomiasis japonica occurs.

Measuring exposure to S. japonicum in China. II. Activity diaries, pathways to infection and immunological correlates.

In this study we examine the pathways to schistosomiasis exposure and infection among residents residing on two islands (large, Qingshan; small, Niangashan) in the Dongting Lake region (Hunan province) of China. An exposure model, based on activity diaries, was used to quantify an individual's square-metre-minute (sq.m.min) daily water contact. Subjects living on the small island had a significantly higher (P=0.0002) degree of exposure (mean+/-S.D., 13.2+/-11.0 sq.m.min) than individuals dwelling on the large island (mean+/-S.D., 5.5+/-7.1 sq.m.min). Participants identified as stool egg positive (mean+/-S.D., 8.3+/-10.4 sq.m.min) had higher exposures than for those never treated (mean+/-S.D., 2.2+/-3.4 sq.m.min) for schistosomiasis, and these high exposures rose steadily to peak at 35-49 years of age and decline after age 50. This exposure pattern differs markedly from those reported for African or South American schistosomiasis. The majority of human water contact occurs on the lake. Egg-positive subjects reported significantly higher (P < 0.05) episodes of water contact on the lake versus their egg-negative counterparts, who reported significantly higher (P < 0.01) exposure at the aquaculture ponds. The results of path analysis revealed that sex, age, island of residence and whether a fisherman or not were the most highly significant independent predictors of lake exposure. This accounted for approximately 40% (R2=0.39) of the total lake exposure. Exposure to lake water was a strong predictor (P=0.0006) of past infection and a modest predictor (P=0.05) of current infection.

Familial systemic lupus erythematosus: evidence for separate loci controlling C4 deficiency and formation of antibodies to DNA, nRNP, Ro and La.

A family has been identified in the Canadian province of Prince Edward Island in which 2 sisters have systemic lupus erythematosus in a sibship of 14. Studies are reported on 11 of the siblings and 16 other family members. The affected siblings, and 4 other members of their sibship, are halfnull homozygotes for the C4A component of complement. We studied the distribution in family members of antibodies to ss and dsDNA, and to Ro(SSA), La(SSB), Sm and nRNP. Eight of 11 members of the affected sibship are antibody producers, compared to only 3 of 13 members of the parental generation. Our study provides further evidence for an association between null genes for C4A and familial lupus, and suggests, in an unusually large kindred, that several other genetic factors are involved in the production of antinuclear antibodies.

Post-secretory acquisition of apolipoprotein E by nascent rat hepatic very-low-density lipoproteins in the absence of cholesteryl ester transfer.

Previous work has shown that nascent hepatic very-low-density lipoproteins (VLDL) in the rat are biosynthesized without the obligatory co-factor (apolipoprotein C-II) for lipoprotein lipase-mediated hydrolysis of their core triacylglycerols. Upon secretion, apolipoproteins C-II and C-III are rapidly transferred to the particles from high-density lipoprotein (HDL) within the space of Disse and upon the entry into the plasma. Here we extend those studies to include observations on the apolipoprotein E content and lipid composition of nascent hepatic VLDL before and after exposure to plasma components. We have elected to use hepatic secretory vesicle VLDL rather than liver perfusate VLDL as truly representative of the nascent lipoproteins. Nascent VLDL from fed rats has an apolipoprotein B/E ratio of 6.6 +/- 0.5, whereas that from fasted animals is 13.9 +/- 2.3. Incubation of nascent VLDL from fed and fasted rats with d greater than 1.063 g/ml rat serum, HDL or the d greater than 1.21 g/ml fraction resulted in a mass transfer of apolipoprotein E to the VLDL such that the apolipoprotein B/E ratio decreased to at least that of serum VLDL (3.4 +/- 0.3). The d greater than 1.21 g/ml fraction appeared to contain a species of apolipoprotein E which most actively transferred to VLDL. The acquisition of apolipoprotein E by nascent secretory vesicle VLDL was attended by a loss of phospholipids, particularly the C40 (stearoylarachidonyl) molecular species, and an increase in the cholesterol-to-phospholipid ratio from 0.11 +/- 0.01 to 0.18 +/- 0.03. No evidence was obtained to suggest a simultaneous acquisition of cholesteryl esters upon incubation of nascent VLDL with VLDL-free serum. We conclude that nascent hepatic VLDL is modified after secretion by acquisition of apolipoproteins C-II, C-III and E with a concomitant loss of phospholipids.

Alcohol research in Papua New Guinea: implications for health care workers.

Over the last 5 years a substantial amount of research and publication has been completed on the subject of alcoholic beverage consumption and its consequences for Papua New Guinea. This work can be grouped under four topical headings: anthropological, epidemiological (including public health), psychological and sociological. These recent findings will be summarized below and their relevance for health care personnel in helping to prevent some of the negative results of alcohol abuse will then be discussed.

Cross-cultural perspectives on teenage attitudes to alcohol.

Six hundred and seventy-seven indigenous Papua New Guinean, 315 Australian, and 166 American high school teenagers completed a series of measures on attitudes to alcohol. Papua New Guinean students differed most from other students in considering that money was wasted on alcohol and that preventive steps should be adopted to ban sales of take-away alcohol. In addition, Papua New Guinean males and females were more likely than other teenagers to feel that women should not drink alcoholic beverages. Within countries, males and females had fairly similar attitudes about alcohol and alcohol-related issues, and where differences occurred, males generally were less likely to highlight the costs of alcohol abuse.

Nascent hepatic lipoproteins in hypothyroid rats.

Cholesterol-feeding of hypothyroid Long-Evans rats results in a marked hypercholesterolemia and hepatic secretion of cholesteryl ester and apoE-rich VLDL and LDL which accumulate in the serum compartment (J. Lipid Res. 1981 22: 971-989). The present study segregates the effects of hypothyroidism from the combined effects reported above. Hypothyroidism alone does not result in the secretion of cholesteryl ester-rich lipoproteins by the liver which, in contrast, contains depressed quantities (30%) of triglyceride-rich (71% of lipid mass) VLDL and low levels of LDL which is also triglyceride-rich when compared to the nascent lipoproteins of euthyroid rat livers. The nascent lipoproteins from the hepatic Golgi cisternae and secretory vesicles of hypothyroid rats all had pre-beta or slow pre-beta migration on agarose gel electrophoresis and were very dissimilar in lipid and apoprotein composition from the beta-migrating LDL that accumulates in the sera of these animals and contains 13.8% triglyceride, 51.3% cholesteryl ester, and has an apoB/apoE ratio of 32.7. We conclude that the serum LDL in hypothyroid rats, which contains only apoB100, is not secreted directly by the liver but represents a normal catabolite of triglyceride-rich VLDL that may accumulate due to reduced receptor-mediated clearance rather than an overproduction of its immediate precursor, hepatic VLDL.

Assessment of nutrition education: urban mother understanding of weight for age graphs.

One third (34.5%) of 319 mothers attending four urban Maternal and Child Health clinics in Lae, Morobe Province, Papua New Guinea succeeded in correctly identifying all four test weight for age graphs. Mothers were more accurate in identifying weight graphs if they were educated, if their child was older than 12 months, and if their last visit to an MCH clinic had been during a scheduled clinic week. In regard to weight for age status of 321 children sampled at the four clinics 18.6% were less than 80% of the Harvard standard weight for their age, with 3.8% less than 70% of the standard. Mothers' ability to identify weight graphs was not directly related to their children's nutritional status. Children had better weight for age if their fathers had employment, and if their family lived in professionally built housing. Weight for age tended to decline after 12 months of age. Analysis of the results suggested that mothers with children older than 12 months who understood weight graphs were more likely to have well nourished children than those who did not.