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Primary prevention of hepatocellular carcinoma in developing countries.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with 80% of cases occurring in developing countries. The cancer is rapidly fatal in almost all cases with survival generally less than 1 year from diagnosis. The major risk factors for this cancer have been identified as chronic infection with hepatitis B (HBV) and hepatitis C (HCV) viruses and dietary exposure to aflatoxins. There is a safe and effective vaccine to prevent chronic HBV infection. Given estimates that approximately 70% of HCC in developing countries is attributable to HBV then vaccination could prevent more than 250,000 cases per year in these areas of the world. A major challenge now is to ensure the availability of vaccine in countries with endemic infection. Development of a vaccine against HCV is more problematic due to the genetic heterogeniety of the virus. However, with 24% of HCC in developing countries attributable to HCV (approximately 93,000 cases per year) a vaccine would make a major contribution to cancer prevention. Aflatoxins contaminate dietary staple foods (groundnuts, maize), are potent animal hepatocarcinogens and are carcinogenic in humans with particularly high risks in individuals with a concomitant infection with HBV. Reduction of exposure can be addressed at the community level either pre- or post-harvest by limiting fungal contamination of crops; approaches may involve low technology post-harvest measures to limit fungal growth or genetic engineering of crops to be resistant to fungal infection or toxin biosynthesis. An alternative measure is to modulate the metabolism of aflatoxins once ingested using chemopreventive agents e.g., oltipraz. The resources available in countries with endemic hepatitis infection and fungal contamination of foods are often severely limited. Clearly HBV vaccination has to be the priority in the reducing the incidence of HCC. However, there are currently 360 million chronic HBV carriers worldwide and HBV vaccine is still not incorporated into many national immunisation programs. Thus measures to reduce food spoilage by fungi and the associated dietary exposure to aflatoxins is also a desirable public health goal.

Aflatoxins↗

Risk factors for injuries in young children in four developing countries: the Young Lives Study.

OBJECTIVE: To assess the occurrence of child injury in four developing country settings and to explore potential risk factors for injury. METHODS: Injury occurrence was studied in cohorts of 2000 children of age 6-17 months at enrolment, in each of Ethiopia, Peru, Vietnam and India (Andhra Pradesh). Generalized estimating equation models were used to explore potential risk factors for child injury. RESULTS: Occurrence of child injury was high in all countries. Caregiver depression emerged as a consistent risk factor for all types of injury measured (burns, serious falls, broken bones and near-fatal injury) across all countries. Other risk factors also showed consistent associations, including long-term child health problems, region of residence and the regular care of the child by a non-household member. CONCLUSIONS: This report provides further evidence of the importance of childhood injury in developing countries and emphasizes the importance of including infants in injury research and prevention strategies. It provides strong evidence of an association between caregiver mental health and child injury risk and contributes to the limited knowledge base on risk factors for child injury in developing countries.

Accidental Falls↗

Factors impacting on drug choices. Issues for developing countries.

In considering factors that impact on drug choices for children in developing countries, it is important to learn from the advances in antiretroviral therapy that have been made in the United States and other developed countries. Abundant clinical data indicate that monotherapy with antiretroviral agents, no matter how potent, is inadequate and the children should be treated with three or more drugs. When treatment regimens are changed, at least two new drugs should be started simultaneouly to avoid the rapid development of resistance. Understanding the impact of host and viral genotypes may provide information as to how best to treat the individual child. However, at present, I believe that with limited resources, the best use of antiretrovirals for children is in disease prevention. Thus, antiretrovirals to prevent mother-to-infant transmission should be given the highest priority. Second, children in the first year of life are at highest risk of progression and should be treated with trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, and targeted for receiving antiretrovirals. Moreover, treating children without an overall plan is unacceptable. Treatment with drugs because they are available will have little impact on the quality of life or disease progression unless they are used in combination. There should be no reason for children, no matter where they might live, to receive suboptimal antiretroviral therapy. For this reason, I call upon industrialized countries and the World Bank to help provide resources for the care and treatment of HIV-infected children. Additionally, I would propose that pharmaceutical companies provide support for the care and treatment of HIV-infected children. The drugs and financial support provided by pharmaceutical companies should go to a central foundation or group that will optimize the use of these resources for children in developing countries. I would also propose that in the United States, Europe, and other industrialized countries the patents on antiretroviral drugs be extended according to a formula based on the donation of a pharmaceutical company. It is only through a unified effort that we will be able to adequately treat all children infected with HIV regardless of where they might live.

Acquired Immunodeficiency Syndrome↗

Blood safety in developing countries.

This study, based on responses to a questionnaire, was undertaken to define problems in and formulate solutions for improving blood safety in developing countries as part of an effort to monitor the status of blood transfusion services globally. Despite improvements between 1988 and 1992, only 66% of developing countries (DGCs) and 46% of least developed countries (LDCs) screen all blood donations for antibodies to human immunodeficiency viruses; 72% DGCs and 35% LDCs test all donations for hepatitis B surface antigen and 71 and 48%, respectively, for syphilis. The antihuman globulin test is performed routinely in 62% DGCs and 23% LDCs, and inadequate quality assurance in all aspects of preparatory testing is a major weakness in many countries. The blood supply is usually insufficient: none of the LDCs and 9% of the DGCs collect 30 units or more per 1,000 of the population annually. Blood donor systems are totally voluntary and non-remunerated in 15% DGCs and 7% LDCs; 80% DGCs and 93% LDCs rely totally or partially on replacement donors and 25% of both groups on paid donations. The proportion of repeat donors is low (medians: 47% in DGCs, 20% in LDCs), and discard rates for collected blood are often high (up to 33%). Most of the blood collected is transfused as whole blood, and most DGCs and LDCs have inadequate supplies of plasma substitutes for management of acute haemorrhage. The reasons for these problems and suggested solutions are discussed.

AIDS Serodiagnosis↗

Impact of HIV on childhood respiratory illness: differences between developing and developed countries.

The main differences of the impact of HIV on childhood respiratory illness between developed and developing countries, and particularly some countries in Africa, are the scale of the problem and the lack of resources to address problems of prevention, diagnosis, and management. Recent data from HIV-infected African children are reviewed and show that the pattern of respiratory disease in these children is not markedly different to the pattern that was reported from the USA and Europe prior to the use of antiretroviral therapy and routine Pneumocystis jiroveci pneumonia (PCP) prophylaxis for HIV-exposed infants. Bacterial pneumonia is very common in all age groups. PCP and cytomegalovirus (CMV) are especially common in infants, and lymphoid interstitial pneumonitis (LIP) is common in older children. One difference is that pulmonary tuberculosis (PTB) is relatively more common in HIV-infected African children. This is likely to reflect the higher prevalence of smear-positive PTB in the region and therefore of exposure/infection compared to developed countries. Autopsy studies have provided a lot of useful data, but more prospective clinical and intervention studies from different parts of the region are needed in order to improve clinical diagnosis and management.

Child↗

Epidemiology of traumatic brain injury in Johannesburg--I. Methodological issues in a developing country context.

Incidence studies in the developing countries present epidemiologists with unique methodological challenges for which novel solutions must be found. These challenges arise from archival inadequacies, hospital overcrowding, high violence rates, and limited research funding that necessitates low cost epidemiology. This paper describes the methods devised in Johannesburg, South Africa, in order to develop incidence estimates of determinable reliability of the morbidity and mortality arising from traumatic brain injury, and its etiology. Results are reported in Part II of the paper (p. 289).

Age Factors↗

A simplified screening test for identifying people with low vision in developing countries.

Simple but effective tests have been produced for screening subjects with low vision in developing countries. These tests of distance and near vision, based on the E test, were evaluated and validated in trials with people aged 4-90 years, and have been field tested in the health, education and rehabilitation services in 32 developing countries. Their sensitivity and specificity as screening tools for low vision have been calculated; sensitivity of 85% and specificity of 96% for the distance vision test, and sensitivity of 100% and specificity of 84% for the near vision test. The content and format of the tests have been demonstrated to be appropriate for developing countries, and their effectiveness for screening for low vision has been confirmed.

Adolescent↗

Organizational aspects and implementation of data systems in large-scale epidemiological studies in less developed countries.

BACKGROUND: In the conduct of epidemiological studies in less developed countries, while great emphasis is placed on study design, data collection, and analysis, often little attention is paid to data management. As a consequence, investigators working in these countries frequently face challenges in cleaning, analyzing and interpreting data. In most research settings, the data management team is formed with temporary and unskilled persons. A proper working environment and training or guidance in constructing a reliable database is rarely available. There is little information available that describes data management problems and solutions to those problems. Usually a line or two can be obtained in the methods section of research papers stating that the data are doubly-entered and that outliers and inconsistencies were removed from the data. Such information provides little assurance that the data are reliable. There are several issues in data management that if not properly practiced may create an unreliable database, and outcomes of this database will be spurious. RESULTS: We have outlined the data management practices for epidemiological studies that we have modeled for our research sites in seven Asian countries and one African country. CONCLUSION: Information from this model data management structure may help others construct reliable databases for large-scale epidemiological studies in less developed countries.

Computer Security↗

[A simplified screening test for the identification of individuals with diminished vision in developing countries].

Simple but effective tests have been produced for screening subjects with low vision in developing countries. These tests of distance and near vision, based on the E test, were evaluated and validated in trials with people aged 4-90 years, and have been field tested in the health, education and rehabilitation services in 32 developing countries. Their sensitivity and specificity as screening tools for low vision have been calculated: sensitivity of 85% and specificity of 96% for the distance vision test, and sensitivity of 100% and specificity of 84% for the near vision test. The content and format of the tests have been demonstrated to be appropriate for developing countries, and their effectiveness for screening for low vision has been confirmed.

Adolescent↗

Mortality of epilepsy in developing countries.

During the last two decades, there has been a renewed interest in studying epidemiology of epilepsy in developing countries. While there are data on prevalence of epilepsy from many developing countries, there is very little information on the mortality of epilepsy in these same populations. This is because incidence studies of epilepsy are difficult to perform, death certificates are unreliable and often unavailable, and the cause of death is difficult to determine. We report on several studies of mortality in epilepsy in developing countries: Ecuador; the Parsi community of Bombay; a semiurban community in Vasai, India; Mali; Martinique; and Africa. Overall, these studies in general illustrate excess mortality among people with epilepsy when compared with the general population.

Adult↗

Asia-Pacific mussel watch: monitoring of butyltin contamination in coastal waters of Asian developing countries.

Butyltin compounds (BTs) including mono-, di-, and tributyltin and total tin (sigmaSn), were determined in green mussels (Perna viridis) from various Asian developing countries, such as Cambodia, China (Hong Kong and southern China), Malaysia, India, Indonesia, the Philippines, and Vietnam, to elucidate the contamination status, distribution, and possible sources and to assess the risks on aquatic organisms and humans. Butyltin compounds were detected in green mussels collected from all the sampling location investigated, suggesting widespread contamination of BTs along the coastal waters of Asian developing countries. Among butyltin derivatives, tributyltin (TBT) was the predominant compound, indicating its ongoing usage and recent exposures in Asian coastal waters. Higher concentrations of BTs were found in mussels collected at locations with intensive maritime activities, implying that the usage of TBT as a biocide in antifouling paints was a major source of BTs. In addition, relatively high concentrations of BTs were observed in mussels from aquaculture areas in Hong Kong and Malaysia, as it has been reported in Thailand. With the recent improvement in economic status in Asia, it is probable that an increase in TBT usage will occur in aquaculture. Although contamination levels were generally low in mussel samples from most of the Asian developing countries, some of those from polluted areas in Hong Kong, India, Malaysia, the Philippines, and Thailand revealed levels comparable to those in developed nations. Furthermore, the concentrations of TBT in some mussels from polluted areas exceeded the threshold for toxic effects on organisms and estimated tolerable average residue levels as seafoods for human consumption. A significant correlation was observed between the concentrations of sigmaBTs and sigmaSn in mussels, and sigmaBTs were made up mostly 100% of sigmaSn in mussels taken from locations having intensive maritime/human activities. This suggests that anthropogenic BTs represent the major source of tin accumulation in mussels. To our knowledge, this is a first comprehensive report on butyltin pollution monitoring in developing countries in the Asia-Pacific region.

Animals↗

Research priorities for the reduction of perinatal and neonatal morbidity and mortality in developing country communities.

Although post-neonatal and child mortality rates have declined dramatically in many developing countries in recent decades, neonatal mortality rates have remained relatively unchanged. Neonatal mortality now accounts for approximately two-thirds of the 8 million deaths in children less than 1 year of age, and nearly four-tenths of all deaths in children less than 5 years of age. Worldwide, 98% of all neonatal deaths occur in developing countries, mostly at home, and largely attributable to infections, birth asphyxia and injuries, and consequences of prematurity, low birth weight and congenital anomalies. We review principal determinants of neonatal morbidity and mortality during the antenatal, intrapartum and postpartum periods, and propose priority community-based research activities to develop, test and adapt inexpensive, practical and sustainable interventions during these periods to reduce perinatal and neonatal morbidity and mortality in developing countries.

Cause of Death↗

Simple clinical prognostic model for hepatocellular carcinoma in developing countries and its validation.

PURPOSE: More than 80% of hepatocellular carcinomas (HCCs) worldwide occur in developing countries, especially in Asia. It often presents at an advanced stage beyond treatment. In this circumstance, a simple prognostic model is useful. Previous prognostic models require radiologic and laboratory investigations that are not readily available in developing countries. Our aim is to formulate and then validate a simple clinical prognostic model for HCC in an Asian population using only clinical parameters and with serum alpha-fetoprotein (AFP) as the sole laboratory test. PATIENTS AND METHODS: Cox regression modeling was performed on several clinical parameters and serum AFP level in 397 patients with HCC who received only supportive care in Singapore. A later group of 324 HCC patients from an Asia-Pacific-wide randomized trial was then used to validate the model. RESULTS: Ascites, physical performance status, and serum AFP were independently predictive of survival. Cox analysis yielded a simple score based on these three variables that categorizes patients into low-, medium-, and high-risk groups with 6-month survivals of 43%, 21%, and 5%, respectively. The prospective validation data provided corresponding estimates of 33%, 15%, and 3% and give confirmation of the utility of the simple model. CONCLUSION: We have formulated and prospectively validated a simple prognostic score for untreated HCC that only requires a clinical evaluation for ascites and physical performance status and measurement of serum AFP. This simple model is particularly apt for developing country circumstances and can also be used to select patients for treatment trials.

Adult↗

[Status and perspectives of agrarian production and food supply in developing countries].

In the early 1980s the agrarian-economic situation and the food supply of most developing countries is characterized by serious complications and vast contradictions. Contrary to the predictions made at the world food conferences in 1970 and 1974, a general retardation has taken place in the rates of increase of food production, and the nutrient crisis has extended. The FAO prognosis 'Agriculture: Toward 2000'- based on annual growth rates of 4%--outlines the enormous problems to be solved in the struggle against hunger and malnutrition in the developing countries. Because of its inadequacies and contradictions this document of the FA cannot, however, be considered as a complex strategy for the fight against hunger, poverty, and underdevelopment, or as a general orientation for shaping the agrarian and nutritional policy in the developing countries.

Agriculture↗

The use of knowledge-based systems in medicine in developing countries: a luxury or a necessity?

Knowledge-based systems (KBSs) in medicine have received much attention over the past two decades, mainly because of the potential benefits that can be gained from using them. They may facilitate in increasing productivity in a medical environment, support the making of diagnoses and other types of medical decisions, assist in the training of medical professionals, and can even handle some routine tasks in a medical environment. However, some critical problems in this field have also been identified. For example, research indicated that some problems can be solved partially, but not completely, with existing artificial intelligence techniques. Another problem is that many of the existing medical information systems do not support the integration of KBSs in a natural way. Furthermore, the routine use of a medical KBS is complicated by legal issues. These and other problems contribute to what we experience today: a large proportion of the medical KB applications that are developed is never actually used in practice. This justifies questions such as: Should developing countries, having limited infrastructure and research resources, invest in medical KBSs research and development, or should this field be regarded as a luxury that only belongs to developed countries?, and: Can developing countries really benefit from the use of these systems? These questions are discussed in this paper. We highlight the main problems surrounding the development and use of medical KBSs. With the focus on developing countries we discuss potential benefits that could be obtained by investing in these systems and we offer guidelines for focusing research and development of medical KBSs.

Artificial Intelligence↗

Suicide in developing countries (1): frequency, distribution, and association with socioeconomic indicators.

OBJECTIVE: Suicide is a global public health problem, but relatively little epidemiological investigation of the phenomenon has occurred in developing countries. This paper aims to (1) examine the availability of rate data in developing countries, (2) provide a description of the frequency and distribution of suicide in those countries for which data are available, and (3) explore the relationship between country-level socioeconomic factors and suicide rates. It is accompanied by two companion papers that consider risk factors and preventive efforts associated with suicide in developing countries, respectively. METHOD: Using World Health Organization data, we calculated the average annual male, female, and total suicide rates during the 1990s for individual countries and regions (classified according to the Human Development Index [HDI]), and examined the association between a range of socioeconomic indicators and suicide rates. RESULTS: For reasons of data availability, we concentrated on medium HDI countries. Suicide rates in these countries were variable. They were generally comparable with those in high HDI countries from the same region, with some exceptions. High education levels, high telephone density, and high per capita levels of cigarette consumption were associated with high suicide rates; high levels of inequality were associated with low suicide rates. CONCLUSION: Epidemiological investigations of this kind have the potential to inform suicide prevention efforts in developing countries, and should be encouraged.

Cause of Death↗

Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS.

Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries.

Adolescent↗

Open dumping site in Asian developing countries: a potential source of polychlorinated dibenz-p-dioxins and polychlorinated dibenzofurans.

Open landfill dumping areas for municipal wastes in Asian developing countries have recently received particular attention with regard to environmental pollution problems. Because of the uncontrolled burning of solid wastes, elevated contamination by various toxic chemicals including dioxins and related compounds in these dumping sites has been anticipated. In this study, concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) were determined in soils from dumping sites in the Philippines, Cambodia, India, and Vietnam. Residue concentrations of PCDD/Fs and coplanar PCBs in dumping site soils were apparently greater than those in soils collected in agricultural or urban areas far from dumping sites, suggesting that dumping sites are potential sources of PCDD/Fs and related compounds. Observed PCDD/F concentrations in soils from dumping sites in the Philippines and Cambodia were comparable or higher than those reported for dioxin-contaminated locations in the world (e.g., near the municipal waste incinerators and open landfill dumping sites). Homologue profiles of PCDD/Fs in dumping site soils from the Philippines and, to a lesser extent, from Cambodia and India reflected patterns of samples representing typical emissions, while profiles of agricultural or urban soils were similar to those of typical environmental sinks. This result suggests recent formation of PCDD/Fs in dumping site areas and that open dumping sites are a potential source of dioxins in Asian developing countries. Uncontrolled combustions of solid wastes by waste pickers, generation of methane gas, and low-temperature burning can be major factors for the formation of dioxins in dumping sites. Elevated fluxes of PCDD/Fs to soils in dumping sites were encountered in the Philippines, Cambodia, India, and Vietnam-Hanoi, and these levels were higher than those reported for other countries. Considerable loading rates of PCDD/Fs in the dumping sites of these countries were observed, ranging from 20 to 3900 mg/yr (0.12-35 mg TEQ/yr). PCDD/F concentrations in some soil samples from the Philippines, Cambodia, India, and Vietnam-Hanoi exceeded environmental guideline values, suggesting potential health effects on humans and wildlife living near these dumping sites. The estimated intakes of dioxins via soil ingestion and dermal exposure for children were higher than those for adults, suggesting greater risk of dioxin exposure for children in dumping sites. To our knowledge, this is the first comprehensive study on PCDD/Fs contamination in open dumping sites of Asian developing countries. On the basis of the result of this study, we have addressed a new environmental issue that open dumping sites are potential sources of PCDD/Fs and related compounds, and dioxin contamination in dumping sites may become a key environmental problem in developing countries.

Administration, Cutaneous↗