Substance use by indigenous and non-indigenous primary school students.

OBJECTIVE: Recent Australian research with adolescents aged 13 to 17 years has found that Indigenous youth are more likely than non-Indigenous adolescents to smoke tobacco and cannabis, although they may be less likely to use alcohol. The objective of this study was to examine whether this pattern exists among younger children. METHOD: A school-based, self-report survey was conducted in primary schools that had high proportions of Aboriginal and Torres Strait Islander children. Four schools were located in metropolitan Brisbane and three in Far North Queensland (sample n = 507 students: 270 girls, 237 boys, aged 9-13 years). RESULTS: Significant numbers of these children had started to experiment with recreational drugs. Twenty-two per cent had attempted to smoke at least one cigarette, 14% smoked in the preceding year, while 3% had smoked more than 10 cigarettes in their lives. Thirty-eight per cent had had at least one drink of alcohol, while 6% had smoked marijuana at least once. There was no significant association between Indigenous/non-Indigenous background and risk of smoking tobacco or marijuana, while Indigenous children were less likely than non-Indigenous children to report experience with alcohol. CONCLUSIONS: Contrary to data from secondary school students, Indigenous youth in primary schools were not more likely than non-Indigenous children to have experimented with tobacco or marijuana, or to be frequent tobacco smokers. It appears therefore that the excessive uptake of drug use among Indigenous youth occurs in the early stages of secondary school. This finding underlines the importance of preventive education in primary schools, especially for Indigenous children who have a high risk of making the transition to drug use in adolescence.

Relaying the message of safer sex: condom races for community-based skills training.

This paper describes a community-based HIV prevention program designed to improve confidence in condom use skills by giving community members 'hands-on' experience in using condoms correctly. A condom race activity which had been effective in increasing condom skills confidence among university students in the US was modified and implemented with the general population in rural Northeast Thailand. In addition to providing training in condom use skills, the condom race was part of an integrated condom promotion and distribution campaign which responded to needs identified by the community, built upon the credibility and influence of local leaders and peers, and extended access to condoms into rural communities. Local leaders who had participated in a training-of-trainers program organized condom races in their communities, serving as positive role models for community acceptance of condom use. The condom race stimulated community discussion about condoms and increased participants' feelings of self-efficacy in correct condom use. Participation in the condom race activity was particularly empowering to women, who reported increased confidence in their ability to use condoms and to suggest using condoms with their partners after the race.

PIP: Incorrect condom use results in decreased confidence in the ability to use condoms and the perception that condoms are less effective in disease prevention. A community-based HIV prevention program in northeast Thailand sought to improve condom use skills and confidence through "hands-on" experience. Teams of men and women from rural villages participated in a relay race by properly putting a condom on a penis model while blindfolded, then removing the condom and passing the model and blindfold on to the next player on the team. The race coincided with the introduction of condom boxes at local shops. Trained village leaders were responsible for organizing the race in collaboration with local public health officials. To assess program impact, 160 interviews were conducted in 8 villages 6 weeks after the races. About 50% of those interviewed had attended the races and 22.7% of men and 14.9% of women had participated. Over 75% were aware condoms were now available in shops and 28.4% of men and 7.9% of women had accessed condoms through the boxes. A separate set of interviews held immediately before and after the race with 164 participants from 29 villages revealed significant changes--especially among women--in confidence in condom use self-efficacy and the ability to discuss condom use with a partner. Overall, the race created an environment of social support for condom use in rural communities in Northeast Thailand by stimulating community discussion.

Relationships between the synthesis of N-nitrosodimethylamine and immune responses to chronic infection with the carcinogenic parasite, Opisthorchis viverrini, in men.

This study investigated the relationship between immune responses to infection with the liver fluke, Opisthorchis viverrini, and the synthesis of the carcinogen, N-nitrosodimethylamine (NDMA) in humans. It also examined associations between synthesis of nitric oxide (NO) and nitrosation of amines, in vivo. Antibody and T cell responses to fluke antigens and post-alcohol urinary NDMA excretion were assessed among three groups of 40-50 men with no, moderate and heavy liver fluke infection. Markers of NO synthesis (nitrate, nitrite) and nitrosation (nitrosamino acids) were also measured in biological fluids. Assessments were carried out under controlled conditions which minimised intake of exogenous nitrate and nitrite and were carried out at two time points, namely before and 4 months after elimination of the infection with praziquantel treatment. No statistically significant variation was observed in the amount of NDMA excreted between the 3 groups. However, during active infection, a strong negative association was observed between in vitro lymphoproliferative responses to some liver fluke antigens and NDMA excretion. After treatment this association was reduced. Multivariate statistical models revealed a highly significant relationship between NDMA levels and urinary nitrate, stimulation indices for two T cell responses to two parasite antigens (MW 37 kDa and 110 kDa) and gall bladder dimensions. NDMA levels after treatment were best described by the ratio between parasite-specific IgG2 and IgE, background levels of T cell proliferation, a urinary marker of nitrosation (N-nitrosothioproline) and usual level of alcohol consumption. These results suggest that individual background immunologic activity, parasite-specific responses and/or parasite products and NO synthesis are important determinants of endogenous generation of nitrosamines in O. viverrini-infected humans.

Cattle markets and local festivals: development of HIV/AIDS prevention interventions for specific risk situations in rural northeast Thailand.

In rural Northeast Thailand, risk of sexual transmission of HIV is popularly perceived to be site-specific. Risk of HIV transmission in local scenarios like cattle markets and village festivals has not been adequately addressed. This paper assesses the use of community consultation and formative research to overcome prevailing assumptions about HIV risk by involving community members in the process of identifying risks and developing HIV prevention strategies. This participatory approach can be used to develop prevention programs that are responsive to the specific context of risk behavior in rural environments.

Seasonal variation of Opisthorchis viverrini infection in cyprinoid fish in north-east Thailand: implications for parasite control and food safety.

Reported is the seasonal pattern of Opisthorchis viverrini metacercariae in cyprinoid fish in north-east Thailand. Samples of fish were collected in 1991-92 at monthly intervals from two areas-Khon Kaen Province, where the opisthorchiasis transmission rate was high, and Mahasarakham Province, where the rate was low. Metacercarial loads in both study areas had similar seasonal patterns. High burdens occurred in the late rainy season and winter (July to January) with low burdens during the summer (March to June). The average burden for Puntius leiacanthus in Khon Kaen was 1.68 metacercariae per fish (127.43 per kg), higher than for all species of cyprinoid fish from the low transmission area. The intensities of infection among P. leiacanthus and Cyclocheilichthys armatus collected in Mahasarakham were comparable, but lower than the intensity of Hampala dispar (0.75 metacercariae per fish) concurrently sampled from the same area (P < 0.05). There was no significant difference in metacercarial load per kg between fish species from Mahasarakham. The results indicate that seasonal variation in metacercariae was a common phenomenon in areas with both high and low endemicity of infection. Also, the metacerarial load in fish was positively associated with infection levels among humans.

PIP: Food-borne trematode infections such as Opisthorchis viverrini are a major cause of morbidity in Asia. Samples of cyprinoid fish collected at monthly intervals during 1991-92 in two provinces (Khon Kaen and Mahasarakham) in North East Thailand revealed substantial seasonal variation of O viverrini metacercariae. The former province is a low transmission area (29.7% average infection rate), while the latter is a high transmission area. Metacercarial intensity was highest from January-March 1991 and October 1991-April 1992, with maximum intensities during February and December 1991. Puntius leiacanthus fish from Khon Kaen bore the highest density of metacercariae per individual fish (1.68). Differences in the intensity of infection for the same species of fish captured in two different geographic areas presumably reflect variations in environmental conditions such as local levels of human and snail infections. Fecal contamination of the study reservoirs is greatest during the early parts of the rainy season as a result of run-off drainage and coincides with the rapid increase in snail populations. The optimal time for large-scale community-based parasite control programs is when the probability of rapid reinfection is lowest and the prevalence and intensity of infection in people are highest (e.g., April-June or the summer months). Most effective is a program that integrates parasite control, environmental management, health education, and food safety.

Letters to loved ones: please don't bring HIV home.

PIP: While away from their families and communities, migrant workers often engage in behavior which puts them at increased risk of HIV infection. Such behavior includes drug and alcohol use, and sex with multiple partners or prostitutes. A significant proportion of northeast Thailand's rural population works away from home in either Thailand or abroad for at least part of the year. The risk behavior of this subpopulation while away from home and their subsequent behavior upon their return home has contributed to the spread of HIV in the region. In the "Letters to Loved Ones" program, women in northeast Thailand write letters to their loved ones who are working away from home to remind them of the risks of HIV/AIDS and teach them about prevention. This program and other AIDS prevention strategies grew out of the Multisectoral AIDS Prevention Strategy in Northeast Thailand. Through the program, a considerable number of women can now play important roles in sexual negotiation and health education for themselves, their families, and their communities.^ieng

Cross-sectional patterns of hepatobiliary abnormalities and possible precursor conditions of cholangiocarcinoma associated with Opisthorchis viverrini infection in humans.

The liver fluke, Opisthorchis viverrini, is both highly prevalent and closely associated with cholangio-carcinoma in northeast Thailand. This study measured associations between intensity of liver fluke infection and nonmalignant hepatobiliary disease diagnosed by ultrasonography among 1, 807 largely asymptomatic adult residents drawn from endemic communities. Abnormalities significantly associated with intensity of infection included gallbladder enlargerment in all dimensions, presence of sludge, irregular gallbladder wall, liver enlargement, and enhanced portal vein radicle echoes. While gallbladder enlargement was not sex-specific, the prevalence odds of the other abnormalities were 2-3 times higher among males compared with females. Those recently treated with the anthelmintic praziquantel had higher odds of these abnormalities compared with others with the same infection status who were untreated. The low prevalence of gallstones suggests that this impairment of gallbladder structure and function does not frequently stimulate gallstone formation. However, gallbladder disturbances, together with chronic inflammation and fibrosis of the bile ducts, which are visualized as enhanced portal vein radicle echoes, may contribute to the strikingly enhanced susceptibility to cholangiocarcinoma among people, especially males, with heavy liver fluke infection.

Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection.

Infection with the liver fluke, Opisthorchis viverrini, is a causative agent of cholangiocarcinoma. One possible contributing factor in this carcinogenesis is the chronic, local generation of nitric oxide by inflammatory cells expressing inducible nitric oxide synthase and the production of N-nitroso compounds via the reaction between amines and nitrosating agents derived from nitric oxide. Our previous studies provided evidence that nitric oxide synthesis is elevated during human liver fluke infection. Here we present data on the same sample of men which definitively demonstrates increased nitrosation of proline and thioproline (thiazolidine-4-carboxylic acid) among infected men compared to uninfected control subjects on a low nitrate diet. This difference was specifically abolished by co-administration of ascorbic acid with proline and by elimination of parasites by praziquantel treatment. Multivariate statistical models demonstrate the importance of salivary thiocyanate levels to variation in the nitrosation of proline among uninfected individuals, but not among those with current fluke infection. This suggests that considerable generation of nitrosating agents (N203/N204) in infected people may be occurring via oxidation of arginine by nitric oxide synthase in inflamed tissue which is thiocyanate insensitive. Analyses revealed positive associations between N-nitrosoproline excretion and nitrate/nitrite levels in urine, plasma and saliva and with usual alcohol intake; with variation in these trends between groups. In conclusion, we have confirmed the relationship between O.viverrini infection and enhanced endogenous nitrosation, showing evidence of its extragastric site. New information is also provided on the determinants of N-nitrosamino acid excretion in men on a controlled low nitrate diet without smoking, conditions which reduce exogenous sources of nitrosating agents.

Multisectoral strategy for AIDS prevention at community level.

In north-east Thailand a five-act drama is broadcast on the village sound system to catalyse involvement in planning and carrying out AIDS prevention activities. Each community's own suggestions for an effective strategy are presented to the relevant government and nongovernmental agencies for endorsement and support.

PIP: The multisectoral AIDS prevention strategy (MAPS) was implemented in four northeastern provinces of Thailand where a very developed infrastructure for health, education, and social welfare exists. (MAPS entails use of integrated government and nongovernmental AIDS-related services to conduct community-defined initiatives.) An audio-drama was used to introduce MAPS at the community level. It included risks, precautions, local beliefs, and modes of personal interaction pertaining to prevention of the spread of AIDS. The five-act audio-drama was entitled On the Brink and was broadcast over each of the 43 communities' public address systems. It revolved around the needs of married women in relation to AIDS prevention and addressed how men and rural people in general are involved. The stages of the MAPS program were a pre-drama subdistrict meeting, a week of drama in the communities, a post-drama community meeting to discuss a community AIDS strategy, a post-drama subdistrict meeting to present and consolidate the strategy, and implementation of the strategy. Three teams implemented MAPS. The post-drama community meetings began with games and a quiz on AIDS with small prizes to encourage participation in discussions. Identified local HIV risk situations included brothels, cattle auctions, certain festivals during which prostitution occurs, and intravenous drug use among young men. The first priority identified in all the subdistricts was open and free availability of condoms (e.g., available where alcohol is sold). Other suggested interventions were publicity about the danger of commercial sex work and training for women whose husbands travel in developing sexual negotiation skills. During the post-drama subdistrict meeting, an AIDS implementation committee was chosen to coordinate AIDS prevention activities conducted by both the government and nongovernmental organizations' staff in the subdistrict.

Evaluation of a monoclonal antibody-based enzyme linked immunosorbent assay for the diagnosis of Opisthorchis viverrini infection in an endemic area.

A monoclonal antibody-based enzyme-linked immunosorbent assay (MAb-ELISA) was evaluated for its potential in the diagnosis of opisthorchiasis in an area endemic for Opisthorchis viverrini infection. The method, based on the detection of the 89-kD O. viverrini metabolic antigen in the feces (coproantigen), was previously estimated to be sensitive enough to detect antigen excreted by a single mature fluke. In the present study, fecal specimens from 207 apparently healthy villagers in northeastern Thailand were analyzed in a double-blind test for the presence of O. viverrini eggs by microscopic examination and for antigen by MAb-ELISA. The microscopic examination was carefully done to minimize false-positive results due to eggs of Lecithodendriid trematodes. The specimens were divided into six groups based on the number of eggs per gram of feces, namely, egg negative, 1-500, 501-1,500, 1,501-3,000, 3,001-6,000, and more than 6,000. The results showed that the ELISA is sufficiently sensitive and specific for the diagnosis of O. viverrini infection. The slightly higher rate of coproantigen positive by the ELISA compared with microscopic examination may reflect lower specificity of the ELISA or its higher sensitivity over microscopic examination in detecting light infections. Different lines of evidence presented here support the latter explanation.

Cross-sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high-risk area in northeast Thailand.

We describe an innovative strategy to quantify risk of cancer associated with varying levels of exposure to chronic parasitic infection through the identification of asymptomatic cases of cholangiocarcinoma within a population-based survey of Opisthorchis viverrini infection. Stool samples from 12,311 adults over age 24 years from 85 villages in northeast Thailand were examined for intensity of liver fluke infection. People from varying egg count categories were selected for ultrasound examination to identify hepatobiliary disease. Fifteen preclinical cases of cholangiocarcinoma were diagnosed from a total of 1,807 people based on ultrasonographic evidence with confirmation by endoscopy where possible. The prevalence odds of the diagnosis of cholangiocarcinoma increased gradually within the light and moderate intensity groups. In contrast, sharply elevated prevalence odds [age-, sex- and locality-adjusted prevalence odds ratio (POR) 14.1, p < 0.05] were observed within the most heavily liver fluke-infected group compared with the uninfected group. Males were more frequently affected than females (crude POR 4.5), but after controlling for intensity of infection, age and locality, the magnitude and significance of this measurement was reduced. Our data clearly demonstrate a significant relationship between intensity of liver fluke infection and cholangiocarcinoma and a strikingly high prevalence of the disease among heavily infected males.

Parasite-associated morbidity: liver fluke infection and bile duct cancer in northeast Thailand.

Infection with the liver fluke, Opisthorchis viverrini, remains a major public health problem in Northeast Thailand, where approximately one-third of the population is infected. The northeast region is largely populated by Laos-descendent Thais who enjoy eating raw fish, which harbour the infective stage of the fluke. The parasite has maintained its presence in the population despite the widespread use of praziquantel and dissemination of health education material throughout the region by vigorous government-sponsored programs in recent years. The most severe consequence of liver fluke infection is cholangiocarcinoma, i.e. cancer of the bile duct epithelium. Although mortality due to the parasites alone appears to be uncommon, cholangiocarcinoma arising as a result of infection is one of the leading causes of death in the region. This paper reviews the pathogenesis of infection and the geographic, hospital-based and community studies which demonstrate the close relationship between infection and cancer. In addition, data from the Cancer Registry of Khon Kaen, Northeast Thailand and population-based studies using ultrasonography to visualize early tumours which illuminate the very high frequency of the cancer among heavily infected individuals and communities are discussed. Finally, the paper will close with a brief commentary on the prospects for control of the parasite and its likely impact on the frequency of cancer given the current epidemiological situation of liver fluke infection.

Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis.

Cancers arising during bacterial, viral and parasitic infection provide useful models to investigate the link between inflammation and carcinogenesis. Because the inflammatory agent is known, relationships between immune responses, the production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N-nitroso compounds, and cancer risk can be explored. This paper first describes the close relationship between infection with the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma in humans. Data are then presented which demonstrate an elevation in levels of salivary nitrite and urinary and plasma nitrate among men with moderate and heavy liver fluke infections compared to uninfected controls which was absent 4 months after the parasites were cleared with praziquantel. Because of the strict control over subject selection and dietary intake plus the absence of the increase following treatment, we conclude that the higher levels of nitrate and nitrite reflect endogenous generation of nitric oxide resulting from liver fluke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N-nitroso compounds mediated by activated macrophages. Further work will attempt to demonstrate a link between this increase and both parasite-specific immune responses and the risk of cancer.

Reversal of biliary tract abnormalities associated with Opisthorchis viverrini infection following praziquantel treatment.

We recently demonstrated a number of biliary tract abnormalities associated with moderate to heavy Opisthorchis viverrini infection among 95 selected village residents in north-east Thailand, who were treated with praziquantel immediately after initial examination and re-examined by abdominal ultrasonography 10 months later. Dramatic improvement in the gall-bladder status of previously infected individuals was observed, including reduction of gall-bladder length and width and regained contractibility of the organ following fatty meal consumption. The frequency of severe enhanced portal vein radicle echoes and gall-bladder sludge and wall irregularities also decreased following treatment, but persisted in many individuals. Two masses were observed in the right hepatic lobe of one individual who was previously considered normal. The findings suggest that gall-bladder abnormalities are reversible following elimination of liver fluke infection, but malignancies, once initiated, are not likely to be affected by treatment.

Immunoepidemiology of Ascaris lumbricoides: relationships between antibody specificities, exposure and infection in a human community.

The serum antibody responses of 124 people naturally exposed to Ascaris lumbricoides infection were analysed by immunoprecipitation of radio-isotope labelled 3rd- and 4th-stage larval Ascaris suum excretory and secretory antigens (L3/4 ES). Profiles of antigens recognized were visualized by polyacrylamide gel electrophoresis (SDS-PAGE), and the band intensities of the 12 major precipitated antigens were individually scored. Most subjects were seropositive, but considerable variation was observed in the amount of total and individual ES antigens precipitated. The sex- and age-related profiles of antibody levels followed similar patterns to those of egg output. In addition, total antibody scores of individuals were closely correlated (r = 0.47-0.52) with their eggs per gram of faeces (e.p.g.) collected 4 months after blood samples were taken. These findings suggest that antibody levels against larval ES antigens reflect recent exposure and are consistent with the hypothesis that establishment of adult worms is proportional to the number of larvae that recently migrated through the lung.

Relationship between intensity of Opisthorchis viverrini infection and hepatobiliary disease detected by ultrasonography.

Twenty-four locality-, age- and sex-matched groups of village residents with no light, moderate and heavy Opisthorchis viverrini infection were examined by ultrasonography. Highly significant differences were observed between the groups in the relative size of the left lobe of the liver and the fasting and post-meal size of the gall-bladder. In addition, indistinct gall-bladder wall, the presence of gall-bladder sludge and strongly enhanced portal vein radicle echoes were most frequently observed in the heavily infected group. Two suspected cases of cholangiocarcinoma were identified from the heavy group. The results highlight the importance of intensity of infection on the frequency and severity of fluke-associated hepatobiliary disease.

Comparative studies on the morphology of the eggs of Opisthorchis viverrini and lecithodendriid trematodes.

Iodine staining and scanning electron microscopy were used to determine the morphological features distinguishing Opisthorchis viverrini from lecithodendriid eggs in human feces. The embryonated eggs of lecithodendriid trematodes differ from O. viverrini by the presence of an iodophilic body, a large mass at the posterior end of miracidium that stains brown in 0.2% iodine solution and the curved miracidium of Phaneropsolus bonnei. All forms of lecithodendriid eggs can be differentiated from those of O. viverrini by a set of morphological features of the shell surface, the knob, the operculum, the shoulder, the shape and size. On the basis of these differences, it is possible to perform differential egg counts.

Distribution patterns of Opisthorchis viverrini within a human community.

This paper describes patterns of infection with Opisthorchis viverrini within a human community assessed by egg count, parasite-specific antibody levels and worm burden determined by expulsion chemotherapy. All three measurements increased significantly with age, reaching a plateau in young adults. There were no significant sex-associated differences in the prevalence or intensity of infection, antibody levels, or in the frequency of heavy worm burdens. A striking 81.5% of the total Opisthorchis population and 74% of the total egg output were expelled by the most heavily infected 10% of the humans sampled. This extreme over-dispersion, together with recent findings that hepatobiliary disease frequently accompanies heavy infections, argues that the priority for community-based parasite control programmes should be to maximize treatment and health promotion efforts toward heavily infected individuals.