The Major Causes of Death and Disease in Developing Countries

In comparison with the United States and other developed countries, the developing world is an area of high birth rates and high mortality, especially infant and juvenile mortality. Let us contrast some basic public health statistics of the developing world with those of the United States. Fertility rates in many developing countries are in the range 5.5 to 7.0 in recent years. The current rate in the U.S. is 2.0. (The fertility rate is the number of children a woman would give birth to in a lifetime if she experienced the birth rate for her country in a specified year.)The infant mortality rate in the U.S. is less than 10 per 1,000 live births; in many of the world's poorest countries this rate is between 100 and 150.

Even more striking is the discrepancy between mortality rates for children aged 1 to 4. In the U.S. it is about 2 per 1,000 live births; in many developing countries it is 50 to 75 times greater. To summarize, in the most wretched countries for every 1,000 births, there are 100 to 150 deaths in the first year and an additional 100 to 150 deaths before age 5. Many international health experts regard the combination of these two rates, i.e. the mortality of children under 5 per 1,000 live births, as the best single statistic for evaluating the overall health status of a developing country. Because of the extremely high death rates for infants and young children, 50% to 60% of all deaths in the poorest developing countries occur before the age of 5, as compared to about 3% in the U.S., where about 90% of deaths occur after age 45.

Although mortality rates for young children and infants are still extremely high in most developing countries, it should be noted that these rates decreased substantially in many regions between 1975 and 1990. In Latin America and the Caribbean, the rate for children under 5 went from 104 per 1,000 live births to 60; in China, from 85 to 43; in India, from 195 to 127. In sub-Saharan Africa, however, decreases were more modest - from 212 to 175. Despite the high death rates for young children, population is increasing in most developing countries. The relationship between population growth and economic development is complex, but most authorities agree that , for most developing countries, population is growing at a rate that hinders economic growth and perpetuates poverty. (Table 1a gives the population, per capita income, fertility rate, life expectancy at birth, and mortality rate for children < 5 in selected developing countries and the United States.)

The major causes of death in the developing world

Severe poverty is the root cause of the high mortality rates in the developing world. Poverty results in malnutrition, overcrowded living conditions, inadequate sanitation, and contaminated water. Routine vaccination is often unavailable for both children and adults, and basic clinical care for the acutely ill is in short supply. Thus, poverty creates a fertile environment for infectious and parasitic diseases. Poverty also leads to illiteracy and inadequate education. Deficient education, especially of females, is closely correlated with poor health in developing countries.

Attribution of deaths to specific diseases is difficult for several reasons. Most developing countries have only rudimentary national health statistics, or none at all. In addition, protein-energy malnutrition and micronutrient deficiencies, by lowering resistance to infection, are contributing factors to many deaths. Finally many children have multiple infections simultaneously, e.g. measles plus malaria. The best data on mortality in the developing world comes from a large on-going study sponsored by the World Health Organization (WHO) and the World Bank - the Global Burden of Disease study. Table 1 summarizes the mortality data from this study for 1990. The developing countries covered by this table are Mexico, and all the countries of the Caribbean region, Central and South America, Africa and Asia except Japan. This group is far from homogenous. It contains several countries with transitional economies, e.g. Mexico, Brazil, Argentina, Chile, South Korea, Thailand, whose health problems are in some ways closer to those of the industrialized countries than to those of the poorest developing countries. It also contains China, with 29% of the total population of the developing world. Although China is among the very poorest nations in terms of per capita income, it has made the public health system and birth control top priorities. Consequently it has a low birth rate and a mortality rate of about 40 per 1,000 for children under 5 - a rate comparable to that of many transitional nations. Not only are there important differences between individual countries in this group, but also within countries there are usually significant differences in health statistics between urban and rural areas, and often between regions of the country.

The statistics in table 1 are based on national health statistics (when available), on epidemiologic data concerning the various diseases, and on extrapolations from regional surveys within countries. For some of the figures, confidence intervals extending 50% in either direction would be reasonable. Infectious and parasitic diseases dominate this table. For the under 5 group, 66% of all deaths result from these diseases; for children 5 to 14, 57%; for young adults, 28%. For all ages combined 34% of deaths are attributable to infectious and parasitic diseases. By comparison, about 4.5% of all deaths in the United States fall into this category. Of the major regions of the developing world, sub-Saharan Africa is hardest hit by infectious and parasitic diseases, with 61% of all deaths for this region occurring in this category. Although only 12% of the population of the developing world lives in sub-Saharan Africa, 36% of all deaths from infection in the entire developing world occur there, including 87% of all deaths from malaria, 47% of all measles deaths, 88% of all HIV deaths, and 80 % of all syphilis deaths. In Latin America and the Caribbean the percentage of deaths attributed to infectious and parasitic disease is 23%; in India (20.6% of the population of the developing world), 35%; in China, 11.5%; in the Middle East/North Africa (including Pakistan and the former soviet republics of Central Asia) 36%; in southeast Asia, 35%; With the exception of malaria, the diseases responsible for most of these deaths are not exotic or tropical; they are diseases which are well known in the industrialized world and which dominated mortality statistics there 100 years ago. Many of these diseases are preventable by immunization with vaccines available in industrialized countries for 30 years or more.

For children under 5, acute respiratory illnesses are the leading cause of death in the infectious disease category. Most of these deaths are due to lower respiratory infections - pneumonia, influenza, bronchitis, bronchiolitis - caused by common microbes with worldwide distributions. Measles and pertussis are still important causes of acute respiratory mortality. The Expanded Programme on Immunizations (EPI) initiated by the World Health Organization (WHO) in 1974 has decreased mortality from these two diseases over the past 10 years, but apparently the success of this program, in terms of percentage of children immunized, peaked in 1990 at about 80%. There has been some backsliding since, especially in the very poorest countries. Measles should continue to be a serious problem in the developing world for many years, because of its high contagiousness, and because 20 to 30% of cases in the crowded urban areas of sub-Saharan Africa occur in children less than 9 months of age, for whom the current vaccine is only about 50% effective. The diarrheal diseases are the second leading cause of infectious disease deaths in the under five group. Rotavirus is the most common cause of diarrhea in children in the developing world. Measles is an important cause of death from diarrhea, accounting for 10% of the total.

Malaria is the most serious parasitic disease in the world. Death from malaria usually occurs in early childhood; 68% of all malaria deaths are in children under 5. The estimated 500,000,000 older children and adults who harbor the malaria parasite worldwide rarely die from it but may suffer occasional attacks of debilitating illness. Relying heavily on chloroquine for case treatment and DDT for mosquito control, WHO conducted a Global Malaria Eradication Campaign between 1954 and 1969. Even in that optimistic era, however, malaria eradication in sub-Saharan Africa was not considered feasible. The campaign was quite successful in many countries, but lack of funds and the development of parasite resistance to chloroquine and mosquito resistance to DDT has led to stagnation and, in some areas, deterioration in the worldwide fight against malaria.

Another important cause of death in the <5 age group is neonatal tetanus, resulting from unhygienic childbirth practices, especially non-aseptic cutting of the umbilical cord, and from lack of maternal tetanus immunization. Most of the deaths of children under five not due to infectious diseases result from peri-natal conditions. These include all deaths in the first week of life from abruptio placentae, compression of the umbilical cord, premature rupture of membranes, obstructed labor, birth trauma, congenital malformations, infection of the amniotic fluid, sepsis, and other poorly defined causes.

Older children and young adults also die from acute respiratory infections, malaria, and diarrheal diseases. The most serious single disease in this age group, however, is tuberculosis (TB). Without treatment, active TB has a case-fatality rate (CFR) of 50 to 60%, with almost all deaths occurring in the first 4 years. With treatment, this rate decreases to 15% or less in the developing world. In sub-Saharan Africa, where most cases go untreated, the overall CFR is estimated to be around 45%. In the 19th century, tuberculosis accounted for almost 10% of all deaths in the United States and Europe.

Death rates dropped dramatically during the first half of this century, even prior to the introduction of effective chemotherapy for TB. Economic improvements, with better nutrition and less crowded living conditions, were probably important factors in the decline of TB. The isolation of highly infectious cases in TB sanatoriums may also have been important. Seemingly intractable poverty in much of the developing world will hinder the fight against TB, as will the AIDS epidemic, and possibly the emergence of multi-drug resistant strains of M. tuberculosis. There are about 10 million HIV positive people in sub-Saharan Africa and about 40% of them are also infected with M. tuberculosis. About 5 to 10% of these 40% can be expected to develop active clinical tuberculosis each year. In many of the urban areas of sub-Saharan Africa AIDS is already the major health problem of young adults. What the demographic effect of the HIV epidemic in sub-Saharan Africa will be is unclear. The best mathematical models predict that the rate of population growth will slow over the next few decades, but will not become negative unless rates of HIV prevalence reach 45% or more. Rates of this magnitude seem very unlikely.

Another cause of death among adults which deserves special attention is complications of pregnancy. In the U.S. there are 8 maternal deaths per 100,000 live births (the maternal mortality ratio). In the developing world as a whole there are 390 maternal deaths per 100,000 live births, and in West Africa, 700. The ratio of maternal mortality in the very poorest countries as compared
to the richest is greater than 100 to 1 - a higher ratio than that for infant or early childhood mortality (see above). Because of high birth rates, the lifetime risk of dying from complications of pregnancy in the developing world is about 3.3% (excluding China with its strict birth control). Hemorrhage, sepsis and eclampsia account for 75% of the 428,000 maternal deaths in developing countries. Abortion, via the mechanisms of hemorrhage and sepsis, accounts for 15% of the total.

Hepatitis B is not listed separately in Table 1, but almost 1 million of the world's estimated 350 million carriers of Hepatitis B virus (HBV) die each year from cirrhosis or liver cancer caused by this vaccine-preventable chronic viral infection. In developing countries most of the population is infected with HBV during infancy or childhood. The probability of becoming an HBV carrier depends on the age at which the infection is acquired. If their mothers are HBeAg-positive carriers (in certain hyperendemic areas of East Asia, 7 to 10% of all pregnant women), neonates have a 70 to 90% chance of becoming infected perinatally. Almost 100% of neonates so infected become carriers. If the infection is acquired after the neonatal period, but before the age of 7, the overall risk of becoming a carrier is about 25%. After the age of seven, there is about a 5 to 10% likelihood of an acute HBV infection developing into carrier status. Hepatitis B vaccines are 75% effective in preventing perinatal hepatitis B if given in the first few days post-partum, and are 95 to 99% effective in preventing hepatitis B when administered to infants. Although the price has dropped substantially over the past ten years, hepatitis B vaccine is still much more expensive than the other childhood vaccines.

Malaria is the only tropical disease with a mortality high enough to be listed in Table 1, but there are several other tropical diseases that must be considered serious problems. Arbovirus infections, transmitted by mosquitoes, cause dengue, yellow fever, and Japanese encephalitis in epidemic patterns throughout the developing world. Dengue fever is the mild form of dengue infection; it is characterized by fever, headache, myalgias, GI symptoms, and rash and lasts 3 to 7 days. The more severe forms of dengue disease - dengue hemorrhagic fever and dengue shock syndrome - lead to 500,000 hospitalizations worldwide and tens of thousands of death annually. Related protozoal parasites of the genus Trypanosoma cause African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chaga's disease) with annual mortalities of 55,000 and 25,000 respectively. Leishmaniasis, another protozoal disease, has cutaneous, mucosal, and visceral forms. Untreated visceral Leishmaniasis (kala-azar) is highly fatal and causes an estimated 54,000 deaths annually. Amoebiasis is the cause of 70,000 deaths annually. Several of the twenty-odd helminths that spend part of their life cycle in human hosts cause significant mortality: hookworm (90,000); ascaris (60,000); schistosomiasis (38,000); onchocerciasis (30,000).

Injuries - homicide, suicide, war-related trauma, motor vehicle accidents, drowning, poisonings, falls, burns - have been called the neglected disease of the developing world. They are an important cause of death at every age, especially for males aged 15 -29. In this age group they cause 51% of all deaths. In males 30 to 44 they cause 32% of all deaths.

The burden of disease as measured by the disability-adjusted life year

For many years mortality statistics have been the most widely utilized measure of the burden of disease in public health, but for two major reasons these statistics can give a distorted view of the disease burden in a society.

First they do not take into account disability caused by disease, and many diseases can be highly disabling without being highly fatal , e.g. leprosy, mental illness and polio. Second they ignore the age of death, although years of life lost through death at an early age are surely one of the most significant burdens of disease. Over the past 15 years the Center for Disease Control (CDC) has attempted to popularize a set of statistics based on the years of potential life (YPL) lost due to disease. The Global Burden of Disease study has adopted the disability-adjusted life year (DALY), a more sophisticated version of the YPL statistic, as its principal measure of disease impact. The DALY is similar to the Quality Adjusted Life Year (QALY), a measure frequently employed in cost-effectiveness of analysis. The calculation of DALYs starts with determining the number of years of life lost due to disease mortality and the number of years lived with disability. For this calculation ideal life expectancies at birth of 80 years for males and 82.5 years for females are used. Panels of experts divided disabilities into six classes with the mildest given a weight of .096 and the most severe, 0.92. In other words, a year lived with severe disability is given 92% of the weight of a year of life lost due to death.

Because years of life in the present and near future are generally regarded as more valuable than years in the distant future, the years of life lost are discounted at an arbitrary rate of 3%. Because individuals have a greater socio-economic value between the ages of 10 and 60 than they do in childhood and old age, these years are given greater weights via a continuous mathematical function. Without these two adjustments - discounting and preferential weighting of the most productive years - the death of a male at age one would contribute 79 DALYs to the burden of disease. With the adjustments, this death contributes 33 DALYs. The two adjustments are so constructed that a death at age 12 contributes the maximum number of DALYs, 37 (4 more than a death at age 1). A death at age 20 contributes 34 DALYs; at age 30, 29 DALYs; and at age 40, 23 DALYs. Many aspects of the calculation of DALYs are arbitrary, and there are theoretical and technical problems. Nevertheless, statistics based on the DALY give a better overview of world health than do mortality statistics, and they allow meaningful comparisons between diseases that concentrate on different age groups and diseases that are significant more because of the disabilities they cause than because of their lethality.

Table 2 gives the percentages of total DALYs and deaths for each age group. (Figures for the developed world - the U.S., Canada, Australia, New Zealand, Japan, and the European countries - are included for comparison.) As one should expect from the above discussion, the DALY statistics, in comparison to mortality statistics, shift the burden of disease to the younger age groups

Major diseases causing disability in the developing world

The Global Burden of Disease study has not published DALY data in as great detail as mortality data. Table 3 summarizes the available DALY data. Several diseases not listed in the mortality table (Table 1) appear in this table. As mentioned above, several helminth infections cause significant mortality, but when one considers that one-third of the world's population is infected with one or more species of helminths, one realizes that death is a rare outcome of these infections. The major harm from these parasites occurs in school age children, in whom even asymptomatic infection may adversely affect growth and development. The intestinal helminths do not multiply in their human hosts, and the rate at which they are acquired is relatively low. Symptoms , as a rule, are proportional to the number of infecting parasites, "the worm burden." In the past control efforts have concentrated on eradication of the vectors, most commonly various species of snails, but without adequate sanitary facilities for disposal of feces and urine and without population-wide education in hygienic practices, vector control is not very effective. In the past several years the availability of three oral, single-dose, non-toxic, broad spectrum anthelmintics (benzimidazoles, praziquantel, ivermectin) has made periodic treatment of high-risk populations an attractive strategy for reducing worm burdens to relatively harmless proportions.

All the major sexually-transmitted diseases (STDs) are common in the developing world. Except for AIDS and, to a lesser extent, syphilis, they are not a serious cause of mortality, but in females aged 15 to 44 the non-HIV STDs account for 8.8% of all DALYs lost, and HIV accounts for an additional 7.9% Adding these DALYs to the DALYs attributable to pregnancy-related diseases in this age-group of females (17.8%), one finds that 34.5% of all DALYs for young adult women result from reproductive system disease. (In men aged 15 to 44, 34.6% of all DALYs result from injuries.)

The third new listing in Table 3 is neuropsychiatric diseases. These diseases have been even more neglected than injuries, but international health experts have recently begun to pay them some attention. A 1995 book - World Mental Health - is "the first systematic attempt to survey the burden of suffering" from these diseases. The data is sketchy, but all the major psychiatric problems of the developed countries - the depressive disorders, the anxiety disorders, schizophrenia, suicide, and substance abuse - seem to be prevalent in the developing world. In many cultures, however, these are not regarded as health problems. (Suicide is honorable in certain situation in some cultures, and alcoholism is commonly regarded as a moral problem.)Alcohol abuse appears to be on the rise throughout the developing world. In addition to alcohol, certain countries have specific substance abuse problems - cannabis in Nigeria, heroin in Pakistan, toxic inhalant abuse among children and adolescents in Mexico and Brazil. The authors describe at length some of the social, political, economic and cultural forces in many developing countries that contribute to the etiology of the major diseases and also cause psychic suffering that is not easily quantifiable or categorizable. These include the following: abandonment and exploitation of children, e.g. child labor and child prostitution; discrimination against and abuse of women, e.g. rape, domestic violence, forced prostitution; ethnic and political violence, e.g. torture, terrorism, war; urbanization; homelessness; poverty; hunger; dislocation of whole communities. There is little Western-style psychiatric care available in many developing countries. For example, Nigeria, with a population of more than 120 million, has 100 psychiatrists. Most of the care for psychiatric conditions is provided by traditional healers and families. The authors describe some community-based programs of psychiatric care that have been cost-effective. They propose an agenda for research and international action to develop "feasible and culturally significant policies" to improve world mental health.

Several diseases that do not appear specifically in Table 3 are important causes of morbidity and disability in developing countries. Protein-energy malnutrition (PEM) heads the list of morbidity producing diseases. From a public health viewpoint there are three measures of PEM: (1) wasting (more than two standard deviations below the median weight-for-height); (2)stunting (more than two standard deviations below the median height-for- age); (3) underweight (more than two standard deviations below the median weight-for-age). At least 500 million people worldwide are malnourished, especially children under five. By the underweight criterion, an estimated 36% of the children under five in the developing world (excluding China) are malnourished; by the stunting criterion, 39%; by the wasting criterion, 8%. In clinical medicine malnutrition has traditionally been divided into three types: marasmus (wasting); kwashiorkor (malnutrition with fluid overload and edema): marasmic-kwashiorkor. This classification is generally regarded as oversimplified at present and the term PEM is preferred, but it is important to note that, because of fluid overload, children with a kwashiorkor type of presentation may not qualify as malnourished by the underweight or wasting definitions. The leading causes of PEM are inadequate food intake and infectious diseases. The most serious consequence is death. In 1988 UNICEF estimated that PEM played a role in one-third of all deaths of children under five, but data are inadequate to evaluate the relative influences of PEM and infection in most of these deaths. The outstanding morbid consequences of PEM are growth retardation, impaired cognitive development and school performance, and, for adults, decreased labor productivity. Malnourished pregnant women have a higher than average risk of maternal mortality, and their children are more likely to have low birth weights, which in turn predisposes to higher infant mortality.

Closely linked to PEM are the diseases resulting from dietary deficiencies in micronutrients. The three most widespread and best studied of these deficiencies are iron, iodine, and vitamin A. Iron deficiency anemia occurs mainly as a result of inadequate iron in the diet, but also can occur secondary to blood loss from parasitic infection. It leads to impaired cognitive development, decreased immunocompetence, and impaired performance in school and at work. Severe iodine deficiency in pregnant women can lead to cretinism in their infants. In children iodine deficiency is associated with impaired intellectual development and growth; in adults, with goiter and decreased productivity. Vitamin A deficiency results in decreased resistance to infection, growth retardation, and the ocular disease, xerophthalmia, which causes blindness in 250,000 to 500,000 children each year. An estimated 50 to 80% of children so blinded die within one year, mostly as a result of severe malnutrition, for which severe xerophthalmia is a marker. Deficiencies of zinc, thiamine (beriberi), niacin (pellagra), and vitamin D (rickets and osteomalacia) are important problems in certain areas of the developing world.

Blindness is the most common major disability in developing countries. Cataract is the leading cause of blindness in these countries, accounting for about 40% of the 50 million cases. For reasons that are not yet entirely clear, the incidence of cataract in developing countries is greater than in the rest of the world. Possible explanations of this higher incidence are genetic factors, nutritional deficiencies, and increased exposure to sunlight. A 1986 survey found the cost of cataract extraction in the developing world to range between $15 and $33. Corneal scarring from xerophthalmia (see above) and extra-ocular infection is the second leading cause of blindness in the developing world. The most prevalent of these blinding extraocular infections is Trachoma, a chronic kerato-conjunctivits caused by Chlamydia trachomatis and spread by flies and person-to-person contact. Trachoma is frequently complicated by secondary bacterial infection leading to the formation of corneal ulcers. Keratitis (infection of the cornea) is often seen in developing countries. The most common causes are Herpes simplex, syphilis, leprosy, tuberculosis, and onchocerciasis (infection of the cornea by 0.2 millimeter long microfilariae leading to "river blindness"). After corneal scarring from extra-ocular infections and xerophthalmia, the next two most important causes of blindness are glaucoma and refractive errors.

Polio has never been one of the major causes of death but it has been a great crippler of children. Although the last case of polio in the western hemisphere was reported in 1991, there are still more than 100,000 cases of paralytic polio annually in the rest of the world, and more than 10 million people are living with polio-inflicted disability. Rheumatic heart disease, which has almost been eliminated from developed countries by penicillin treatment of streptococcal infections, is the most common form of heart disease in children and young adults in the developing world, with an estimated 300,000 new cases each year. Morbidity results from recurrent attacks of rheumatic fever, and congestive heart failure as carditis progresses. There are an estimated 600,000 new cases of leprosy each year, mostly in India, Brazil, and Myanmar (the former Burma). Between 2 and 3 million people are disabled by leprosy, which is curable by multi-drug therapy. Several species of filarial helminths, transmitted by mosquitoes, cause lymphatic filariasis, which can progress to debilitating elephantiasis.

What can be done to lessen the disease burden of the developing world?

Effective public health control measures and clinical treatments exist for most of the diseases discussed above. The relatively high cost of many of these measures and treatments precludes their use in many developing countries, which have per capita incomes of $500 or less (as compared to $23,000 in the U.S.). The governments of these countries spend as little as $4 or $5 per capita on health care (as compared to $1,300 per capita government spending on health in the U.S.) Moreover much of this $4 or $5 per capita may be spent on a modern hospital and medical school in the capital, with little money for health care getting to the rural poor. A large part of the cost of health care in these countries is borne by United Nations agencies such as WHO, UNICEF, and the World Bank, by the foreign aid agencies of individual developed countries, and by non-governmental agencies such as church-sponsored missions, relief organizations, and volunteer-assisted health care groups.

In order for governments and health agencies to best allocate limited resources for health care, it is important to know the cost-effectiveness of available disease control measures and treatments. The World Bank published a lengthy study entitled Disease Control Priorities in Developing Countries in 1993. On the basis of the best available evidence, the authors of this study calculated the cost per DALY saved for a variety of public health and clinical interventions. Public health interventions are directed at large groups of people (populations) and include: (1) educational campaigns designed to change health behaviors; (2) control of environmental health hazards; (3) immunizations; (4) mass chemoprophylaxis; (5) mass screening and referral. Clinical interventions are treatments given to individual sick patients. As one might expect, most of the interventions with the lowest cost per DALY saved fall in the public health realm, but a fair number of clinical interventions turn out to be very cost effective. Seven of the 21 most effective interventions ($25 or less per DALY saved) are clinical in nature, as is one of the six in the $25 to $75 range. Table 4 lists all the interventions with an estimated cost per DALY saved of $25 or less. Table 5 lists interventions with an estimated cost per DALY saved of $25 to $75.

Tables 4 and 5include only those interventions that have been studied for the major diseases. Cost effective interventions exist for many of the less common diseases encountered in the developing world. Also some of the interventions listed in Table 4 have multiple effects. For example, breastfeeding improves nutrition, enhances the infant's immunity, prevents infection (especially diarrheal diseases), and protects the mother's health by helping to postpone the next pregnancy. Several public health measures that have multiple effects were not analyzed for cost effectiveness in the World Bank study, but may be worthy of consideration in certain countries. These include: provision of clean water and sanitation; provision of soap; vector control; family planning services; establishment or reduction of motor vehicle speed limits.