Infectious and Communicable Diseases
Infectious diseases account for less than 2 percent of deaths in high-income countries, but are responsible for 21 percent of deaths in low-and middle-income countries. Infectious diseases reveal a glaring difference in health status between rich and poor countries precisely because cost-effective interventions are available to prevent and treat so many of them.
"Infectious diseases account for less than 2 percent of deaths in high-income countries, but21 percent of deaths in low- and middle-income countries."
Infectious diseases pose a range of challenges. Some are transmitted directly from one person to another, others through contact with insects or other animals. The human body's immune system readily resists some, whereas others, including auto-immune diseases, attack and weaken the immune system itself. Some present visible and obvious symptoms in a short time, while others are harbored for years before becoming active. Infectious diseases also vary in their virulence, infectiousness, and duration, and the infectious agents of some develop resistance to medications more rapidly than others.
Three communicable diseases, HIV/AIDS, TB, and malaria, account for about 10 percent of the deaths in low- and middle-income countries. Looking at just these three diseases suggests the immense variety of infectious diseases and demonstrates why strategies for dealing with them must be so different. HIV/AIDS is transmitted primarily through sexual contact, TB through inhaling infectious droplets in the air, and malaria exclusively from mosquito bites. HIV/AIDS attacks the body's immune system, while TB primarily attacks the lungs and malaria impairs the bloodstream and can attack the brain, liver, and other organs. Untreated HIV/AIDS is almost invariably lethal, and TB and malaria can also be fatal.
"HIV/AIDS, TB, and malaria, account for about 10 percent of the deaths in low- and middle-income countries."
Another 10 percent of deaths in low- and middle-income countries are attributed to other diseases caused by infectious or communicable agents. For many of these diseases, such as pertussis, tetanus, and diphtheria, vaccines are available and universal coverage is practicable. Nevertheless, millions of children remain unvaccinated and consequently risk illness or death. Infections also cause diarrheal diseases that lead to needless deaths when children are not given proper treatment and die from dehydration.
HIV/Aids
HIV has spread worldwide in a short time, but is disproportionately concentrated in low-income countries.1 In 2004, some 2.9 million deaths attributed to AIDS occurred in the low- and middle-income countries, compared with an estimated 22,000 in the high-income countries. Sub-Saharan Africa is the region most affected by the epidemic. With only 10 percent of the world's population, it nonetheless accounts for 66 percent of all HIV cases and more than 75 percent of AIDS-related deaths. Countries in East Asia and the Pacific do not have prevalence rates as high as those in Sub-Saharan Africa, but their populations are large and prevalence is rising. In 2004, approximately 505,000 AIDS-related deaths occurred in this region, representing about 17 percent of all AIDS-related deaths.
"In 2004, some 2.9 million deaths attributed to AIDS occurred in the low- and middle-income countries, compared with an estimated 22,000 in the high-income countries."
When the disease was first identified in the early 1980s, most of those living with HIV/AIDS were men. The proportion of women affected by the epidemic has steadily grown: by 2004, women and girls accounted for nearly 50 percent of all people living with HIV/AIDS, and in Sub-Saharan Africa, women and girls represent 57 percent of those infected.
HIV is transmitted primarily through sexual intercourse, which accounts for approximately 80 percent of all infections. HIV is also transmitted via exposure to infected blood and from mother to child during childbirth or breastfeeding. Efforts to reverse the epidemic are founded on preventive strategies. For sexual transmission and exposure to infected blood, such measures include educating people about infection and how it is transmitted, encouraging condom use and decreased sexual contact with concurrent partners, screening blood that will be used for transfusions, establishing needle exchanges for injecting drug users, and promoting universal access to clean needles in health care settings. Antiretroviral drugs can be used to halt mother-to-child transmission (MTCT) during birth; perinatal transmission can also be reduced by limiting the duration of breastfeeding and preventing mixed feeding. Epidemic control strategies must also include treatment regimens using antiretroviral therapy (ART), which can extend lives and improve the quality of life for people living with AIDS.
In spite of these efforts, global attempts have not proved sufficient to control the spread of the pandemic or to extend the lives of the majority of those infected. The desired level of success has not yet been achieved for several reasons. Most people who could benefit from available control strategies (including treatment) do not have access to them. Modeling of the epidemic has determined that existing interventions could prevent 63 percent of all infections projected to occur between 2002 and 2010. However, as of now, fewer than one in five people at high risk of infection had access to the most basic prevention services, including condoms, AIDS education, MTCT prevention, voluntary counseling and testing (VCT), and harm reduction programs. Furthermore, care for those infected with HIV has historically been limited in developing country settings, and coverage of ART has been unavailable to most people living in resource-scare countries (notable exceptions include Argentina, Brazil, and Mexico). In short, national programs have lacked the means to undertake a comprehensive approach to HIV/AIDS.
"existing interventions could prevent 63 percent of all infections projected to occur between 2002 and 2010."
Another enormous barrier to developing appropriate control strategies is lack of data about how to best implement packages of existing interventions at appropriate scale to maximize the effect of care interventions and to protect the human rights of people affected by the epidemic. During the past decade, governments and NGOs have accumulated limited but valuable experience with preventive and treatment strategies in a wide range of settings, making it possible to identify and emulate general principles of success. Nevertheless, the epidemic has continued to spread, but much less quickly in countries—including Brazil, Mexico, Senegal, Thailand, and Uganda—where national policies have taken the AIDS epidemic seriously and implemented national programs to control the disease (see box 4.1 and box 4.2). These successful programs had several features in common, including high-level political leadership, active engagement of civil society and religious leaders, population-based programs designed to change social norms, condom promotion, surveillance and control of sexually transmitted infections (STIs), programs to combat stigma and discrimination, and interventions targeting key "bridge" populations.
[Box 4.2]
the epidemic has continued to spread, but much less quickly in countrieswhere national policies have taken the AIDS epidemic seriously"
Perhaps the greatest challenge to effective global control of HIV/AIDS, however, is the lack of reliable evidence to guide the selection of prevention and care interventions for specific areas or populations. In the same way that global policy makers increasingly recognize the need for rigorous evaluation of development programs to ensure their success and eliminate waste, the need for reliable scientific evaluations of AIDS control programs is equally paramount for the same reasons. Lack of data on both the effectiveness and the cost of interventions to guide informed policy-making means that the current allocation of resources for HIV/AIDS prevention is seldom evidence-based.
Nevertheless, in spite of the paucity of rigorous data on effectiveness and costs of various control strategies, action is required. Guidelines have been developed for selecting appropriate prevention and treatment strategies based on the epidemiological profile of a country (the characterization of individual epidemics, based on the prevalence of infection in particular key populations, such as sex workers, men who have sex with men, or intravenous drug users, and in the general population) and the unique political, cultural, and economic context.
These categories are listed in table 4.1, "Epidemic Profiles" (with the generalized epidemic category further subdivided into low and high categories). These categories can be used to develop prevention guidelines.
[Table .]
"where the prevalence of HIV infection is low, prompt, effective action is still imperative.
In countries where the prevalence of HIV infection is low, prompt, effective action is still imperative. Data collection is critical to evaluate the progress of the epidemic and guide public policy. Mapping key populations to learn about behaviors associated with infection and tracking the infection rate can provide valuable information for taking appropriate and timely actions. Basic knowledge about how HIV is transmitted and how to obtain and use condoms should be conveyed through limited mass media campaigns and school programs. Such information, education, and communication (IEC) activities should respond to prevailing attitudes toward sexual activity, as these will shape how people perceive educational materials. Public policies should also ensure that condoms are readily available through existing channels, such as pharmacies, clinics, and food stores. In addition, health facilities should screen all blood products to be used for transfusions and use sterile needles for all injections, because the rate of virus transmission through such means is high. Furthermore, because the infection spreads so rapidly among intravenous drug users, prevention programs are needed for this key population even where the infection is relatively unknown.
In countries with a concentrated epidemic, additional measures are needed. Programs aimed at preventing transmission among key populations at especially high risk of contracting or transmitting infection are of particular importance, including VCT for individuals and peer-based programs that educate individuals at risk, promote safe behaviors, and distribute condoms. Screening and treatment for STIs should be promoted, and pregnant women who fit a high-risk profile should be offered HIV screening and treatment, both to benefit them and to reduce the likelihood of mother-to-child transmission.
In a generalized low-level epidemic, such as in Tanzania, the emphasis on targeted interventions must be maintained or even strengthened, but interventions for broader populations must also be aggressively implemented. These prevention priorities should include surveillance of STIs, risk behaviors, and HIV infections in the entire population, with a particular focus on young people; extension of mass media IEC beyond basic education; routine voluntary and confidential HIV testing and STI screening and treatment promoted beyond key populations; subsidized and social marketing of condoms and strengthened distribution to ensure universal access; offering of HIV screening to all pregnant women; and broadening of peer approaches and targeted IEC to include all populations with higher rates of STIs and risk behavior.
"a generalized high-level epidemicis a national emergency that calls for the most vigorous possible public action."
In a generalized high-level epidemic, such as in Botswana and Zimbabwe, the epidemic is a national emergency that calls for the most vigorous possible public action. Routine HIV testing and STI screening and treatment should be promoted universally. Innovative mass strategies for reaching large numbers of people with information, screening, and condoms should be developed—for example, at workplaces, transit venues, political rallies, schools and universities, and military camps, and via youth brigades, workers' unions, and farmers' movements. Free distribution of condoms in all possible venues is imperative. VCT should be promoted for all couples initiating sexual relations. The poverty, education and social status of women, important factors in all epidemics, should be overriding concerns. Priority action should be taken to alter gender norms and reduce the economic, social, and legal restrictions on girls and women.
In addition to these preventive strategies, appropriate strategies for care and treatment are needed. Researchers have developed new therapies for treating HIV/AIDS, some of them easier to administer and less toxic than their predecessors. Treatment is also becoming a reality for many living in resource-constrained countries as the prices of antiretro-viral drugs have dropped significantly because of international negotiations with and political pressure on drug companies, the manufacture of generics, and changes to international trade policy to allow compulsory licensing of pharmaceutical products in cases of emergency and to ease importation of generics. As ART becomes more widely available, HIV resistance to a number of antiretroviral drug regimes has emerged, frequently requiring patients to switch from first-line to second-line drugs that are more costly and have more problematic side effects.
"The lives of people infected with HIV/AIDS can also be greatly improved and prolonged through psychosocial support, treatment of opportunistic infections, ART, and palliative care"
The lives of people infected with HIV/AIDS can also be greatly improved and prolonged through psychosocial support, treatment of opportunistic infections, ART, and palliative care, which includes not only end of life and pain control, but also the psychological, social and spiritual problems of patients and their families. End-of-life care can be provided in numerous settings, ranging from hospitals and hospices to individuals' homes. Many inexpensive measures to treat pain,2 diarrhea, nausea, and skin conditions3 in infected individuals are available and can improve patients' quality of life. Micronutrient supplements, which only cost US$15 a year, can increase body weight, reduce HIV viral load, improve CD4 counts, and reduce opportunistic infections in infected individuals. Despite the wide range of interventions to treat symptoms in people living with HIV/AIDS and their low cost, the need for palliative care for such people is far from being met.
Mass education campaigns can reduce the stigma of HIV infection and enable individuals to remain involved in their communities. Direct psychosocial support can also make a substantial difference. Studies in South Africa and Thailand have demonstrated that access to mental health services and counseling contribute significantly to patients' quality of life and, in some cases, was even associated with reduced mortality.
Diagnosing, treating, and managing life-threatening opportunistic infections (OIs) remains one of the most important aspects of caring for patients with HIV. When HIV begins to weaken patients' immune systems, which tends to occur five to seven years after infection, bacteria, fungi, viruses, and even cancers that would otherwise be held in check become active and damaging. Some infections such as pneumonia, tuberculosis4 and oral and esophageal candidiasis are relatively easy to diagnose and cost-effective to treat, while others, such as cytomegalovirus, and Mycobacterium avium complex, are difficult to diagnose and costly to treat. In the latter case, ART, which reduces the viral load of HIV, thereby improving the immune system, may be more cost-effective than treating the actual infection. Certain OIs are cost-effective to prevent, and simple prophylaxis, such as co-trimoxazole to prevent Pneumocystis jiroveci pneumonia, positively influences survival. However, prophylaxis of OIs is underused in low- and middle-income countries, and unfortunately the benefit is short-lived, as it does not halt the relentless erosion of the immune system in infected individuals. The only way to halt the progression of disease in these individuals is to interrupt viral replication through ART.
The prospects for treating people infected with HIV with antiretro-viral drugs in low- and middle-income countries have improved, but ART continues to be a costly and complex challenge. The cost of ART in some developing countries has fallen from US$15,000 per year per patient to less than US$150 per year. This lower price brings it within reach of many middle-income countries, but is still a substantial burden for low-income countries, where annual public health expenditures are often less than US$20 per person per year. WHO and the Joint United Nations Programme on HIV/AIDS estimate that only about 7 percent of the nearly 6 million people in need of treatment receive it and that the number of people requiring ART increases by 8,000 each day.
DCP2 (chapter 18) describes the various regimens available for first-line treatment of HIV/AIDS when drug resistance is not encountered and for second- or third-line therapies when resistance is encountered. The preferred first-line medications in developing countries are dictated by differential efficacy of a number of combinations, as well as pricing and patent concerns. Nearly all highly active ART has some side effects, ranging from the fairly simple to treat (for example, anemia, with iron supplementation) to the more complex (lipodystropy and cardiovascular disease).
To achieve the full benefit of ART, adherence must be nearly perfect (in excess of 90 percent); in cases of suboptimal adherence, resistance can develop in as little as two weeks. Experiences with ART in Haiti and Uganda have shown that programs to implement directly-observed treatment can achieve high drug adherence rates in low-income countries, sometimes higher than in wealthy countries. Nevertheless, high adherence cannot be taken for granted, as studies in India, Mexico, and Senegal have shown poor adherence rates, demonstrating the need for more research on effective intervention to increase adherence.
Confronting the HIV epidemic requires appreciation of the myriad interconnections between technology, economics, politics, and behavior. When political leaders and celebrities endorse public campaigns to raise awareness and normalize public discussion of HIV, then technical and behavioral approaches gain wider acceptance. When technical developments make screening more accurate, cheaper, and easier, then voluntary counseling and testing can be better targeted and more effective. When generic competition reduces the cost of drugs, when international assistance is available for their purchase, and when social programs encourage adherence to drug regimes, then ART becomes more cost-effective and financially feasible.
"Much more research is needed on the cost-effectiveness of interventions to combat HIV/AIDS"
Much more research is needed on the cost-effectiveness of interventions to combat HIV/AIDS, and figures in DCP2 chapter 18 should be interpreted with the recognition that interventions and their costs are changing rapidly. DCP2 chapter 2 reports that diagnosing and treating STIs cost about US$57 per DALY averted, while blood and needle safety programs cost about US$84 per DALY averted. Treatment of OIs costs about US$150 per DALY averted and preventing and treating coinfection with TB costs about US$120 per DALY averted. The cost-effectiveness of ART is difficult to estimate, because it depends on the price of drugs, the prevalence of drug-resistant strains, the costs of diagnostics, and the effectiveness of the health system in delivering the drugs appropriately. While ART is not likely to be as cost-effective as these other interventions, treatment is an important component of an overall national strategy to combat and control HIV and cannot be ignored. Whether it can be effectively extended in hard-hit low-income countries is a major test for the affected countries themselves and for the international community.
"Although preventing HIV/AIDS is often more cost-effective than treating it, decisions for allocating public funds are complicated by interactions between prevention and treatment."
The greatest research challenges in care and treatment for developing countries do not revolve around new drug development but rather around how to adapt care and treatment strategies to low-income, low-technology, low-human resource capacity settings in ways that maximize adherence; minimize toxicity, monitoring, and cost; and maximize the prolongation of high-quality life from ART—all without damaging the existing and often fragile health care infrastructures.
The synergy between prevention and treatment must be considered when struggling to allocate limited resources. Although preventing HIV/AIDS is often more cost-effective than treating it, decisions for allocating public funds are complicated by interactions between prevention and treatment. Making treatment available can remove some of the stigma and fear associated with AIDS and make those who are currently infected easier to contact and counsel so as to prevent future transmission. Treatment may also decrease infectiousness. However, there are concerns that the availability of treatment may reduce inhibitions and lead to increased risky behavior (as has been documented in the United States, Canada, and Europe). Poor adherence to treatment may also encourage drug resistance, while increased longevity as a result of treatment could expose more partners. The net effect of the interaction of prevention and treatment is likely to differ from one country to the next, and further study and monitoring of the interrelationships are imperative.
Controlling HIV/AIDS requires strategies and policies that address both prevention and treatment with limited resources. Much has been learned about the disease itself, the specific interventions and strategies, the interaction of prevention and treatment, and the larger contextual interconnections. DCP2 presents the accumulated experience and evaluations conducted to date that permit policy makers to select appropriate strategies.
Tuberculosis
TB remains the second largest cause of death from an infectious agent in the world, even though drugs to cure the disease have been available for 50 years.5 TB is high on the international public health agenda because of this enormous burden, because of the increase in TB cases associated with HIV infection and drug resistance, and because the internationally recommended TB control strategy known as DOTS has come to be recognized as one of the most cost-effective of all health interventions.
The resurgence of TB in high-income countries in the 1980s surprised public health officials, but effective public responses halted its spread and reduced the incidence in Western and Central Europe, Latin America and the Caribbean, and the Middle East and North Africa. TB has continued to spread and kill, however, wherever social conditions have deteriorated, public health measures are weak, and HIV/AIDS is prevalent. Thus the incidence of TB has been increasing in Eastern Europe, primarily in the former Soviet republics, since the political upheavals at the end of the 1980s and in Sub-Saharan Africa since the mid 1980s. By 2003, an estimated 8.8 million new cases of TB worldwide occurred annually. The highest incidence rate, 345 per 100,000 population per year, is in Sub-Saharan Africa, but the most populous countries of Asia—Bangladesh, China, India, Indonesia, and Pakistan—account for half of the world's cases of TB. Epidemiologists estimate that these upward trends can be reversed if 70 percent of cases are detected and 85 percent of those detected are cured. Reaching this target is necessary if the internationally sanctioned MDG of halving prevalence and death rates by 2015 is to be achieved.6
Interventions for controlling TB include preventing infection by means of vaccination, treating latent infections, and treating active disease. About 80 percent of infants worldwide currently receive a live attenuated vaccine, Bacille Calmette-Guerin (BCG). While the vaccine is protective against meningitis and miliary TB in children, it has low efficacy against pulmonary TB in adults.Vaccination is still cost-effective in places with a high incidence, but is often discontinued in low-incidence countries, because the risk of infection is low and the immune response to the vaccine makes tuberculin skin tests less effective for disease surveillance purposes.
Identifying and treating active cases is currently the primary and most effective measure to control TB. The cornerstone of this approach is the DOTS strategy. DOTS entails diagnosis with a positive sputum sample, short-course treatment with effective case management, regular drug supplies, and systematic monitoring to evaluate outcomes for every patient. Effective case management includes regular supervision by a health worker or community volunteer to assure that the patient is actually taking the medication. The additional cost of monitoring patients and ensuring their adherence to the drug regimen even after symptoms have stopped has proven cost-effective because of its impact on cure rates, consequently both slowing the epidemic and limiting the development of drug resistance.
In all regions except Europe and Central Asia, DOTS costs between US$5 and US$50 per DALY averted. Under certain circumstances, DOTS can save money as well as prevent new cases and deaths. Treating people who have multidrug-resistant strains or are also infected with HIV/AIDS is less cost-effective, because treatment costs are higher and both efficacy and expected benefits are lower. Nevertheless, treating patients with multidrug-resistant TB costs relatively little for the likely gains in healthy life, typically less than US$400 per DALY averted. Treating people with latent infections, that is, people who are infected with TB but are not symptomatic, is the least cost-effective, at US$5,500 to US$26,000 per DALY averted, when TB is endemic (relatively stable) and HIV prevalence is low. However, during a TB epidemic among HIV-infected individuals, providing treatment for latent infection among those who have not yet developed active disease could cost less than US$100 per DALY averted in low-income countries. BCG vaccination is also cost-effective at US$40 to US$170 per DALY averted.
Research could provide a better range of interventions in the future, whether by improving the DOTS approach; tightening the link between private providers, who in many settings are the first to see TB patients, and the public sector; improving the understanding of risk factors; refining diagnostics; or actively seeking cases. Developing a low-cost vaccine that would be more effective than BCG in protecting adults against pulmonary TB would revolutionize the control of TB by shifting the emphasis from treatment to prevention. Until that time, DOTS or other treatment regimens will play the central role.
Success in controlling TB is closely related to the capacity of local health systems to maintain an effective system for identifying cases, beginning treatment, and assuring adherence. The cost is not unmanageable at the global level. In 2005, the high-burden countries that account for about 80 percent of global cases spent only US$1.2 billion, of which about US$200 million came from international donors. Continued international financial assistance is critical to ensuring that TB control can be maintained in the world's poorest countries, where the challenge of TB control is aligned with the challenge of building and implementing effective public health programs.
Malaria
Malaria is directly responsible for about 2 percent of all deaths in the world each year (an estimated 1.2 million deaths) and almost 3 percent of global DALYs.7 In Sub-Saharan Africa, malaria accounts for a large share of the disease burden, causing about 9 percent of all deaths and 10 percent of all DALYs. The share in other regions is much lower, approximately 1 percent, but still accounts for a significant number of deaths and disabilities.
More than 3 billion people live in areas where malaria is present. Many countries outside Africa have successfully controlled the disease through a combination of preventive measures and treatment strategies. For those countries most afflicted by malaria, the implementation of such programs has been obstructed by the emergence and spread of drug-resistant strains of the parasite and of the vectors and hindered by the weakness of public health infrastructure.
Four species of malaria parasites infect human beings. Plasmodium vivax and P. falciparum are the most common, and the latter is the most dangerous. Virtually all deaths are caused by P. falciparum, which predominates in Haiti, Papua New Guinea, and Sub-Saharan Africa. P. vivax is more common in Central America and South Asia. The parasite is carried by mosquitoes, whose ability to reproduce and spread the parasite is strongly influenced by climate. Infestations occur when people are bitten by mosquitoes carrying the parasite. The incidence rate therefore depends on the number of bites per person that transmit the parasite, or the entomological inoculation rate. This ranges from less than 1 bite per person per year in Latin America and Southeast Asia to more than 300 in parts of tropical Africa (figure 4.1).
[Figure
4.1]
Correctly treated, uncomplicated malaria has a mortality rate of only 0.1 percent. When the disease is left untreated and affects vital organs, mortality rises steeply. Coma may occur, in which case the likelihood of death is about 20 percent in adults and 15 percent in children. Cerebral malaria can lead to convulsions, neurological damage, and death. Malaria infections also lead to anemia that can be mild, moderate, or severe.
In addition, malaria has a significant impact on other health conditions. Women contracting malaria during pregnancy are more likely to develop anemia and bear children with low birthweight who are then at greater risk of disease, disability, or even death. About 3.7 percent of maternal deaths, or 5,300 deaths per year, are the result of malaria-related conditions. Estimates show that between 190,000 and 934,000 children die each year when malaria contributes to the development of anemia. Being ill with malaria has a variety of other consequences. One study in Africa estimated that 13 to 15 percent of school absenteeism was due to malaria in children (Holding and Kitsao-Wekulo 2004). Studies in The Gambia and Kenya showed that children who were protected by insecticide-treated bednets grew faster than those left unprotected.
Drug use and vector controls are the main antimalaria strategies and interventions for controlling malaria. Others aim at killing mosquitoes, preventing bites, blocking the development of the disease, or treating the disease itself. Environmental methods to kill the mosquitoes that spread malaria include eliminating breeding sites and spraying insecticides. Other efforts to kill mosquitoes or prevent bites include indoor residual spraying and the use of insecticide-treated bednets. A range of drugs work prophylactically and are taken by travelers to malaria-ridden areas and pregnant women. Finding drugs to treat the disease has become more of a challenge because of the emergence of drug-resistant strains of malaria globally.
The effectiveness and feasibility of some interventions depend heavily on whether malarial transmission is unstable (low, erratic, or focal) or stable (frequent, intense, and year round). Where malarial transmission is unstable, protective immunity is not acquired. Where malarial transmission is stable, survivors develop some immunity, and by adulthood, malarial infections are commonly asymptomatic.
In areas with unstable transmission, focused programs that eliminate breeding sites through judicious use of insecticides or through changes in construction practices may be feasible and effective, while in areas with stable transmission, identifying and controlling all potential breeding sites is generally infeasible. In unstable transmission areas, prophylaxis for pregnant women or intermittent preventive therapy will be most effective only during localized temporary epidemics. In stable transmission areas, however, more general use of intermittent preventive therapy can be extremely effective.
Many places have successfully used insecticide-treated nets (ITNs) to reduce transmission. ITNs have been associated with reductions in child mortality by 18 percent and reductions in malarial episodes by as much as 50 percent in different parts of Africa. The impact of ITNs is related not only to the technical effectiveness of the nets and the duration and efficacy of the insecticide used, but to the social and cultural acceptance of their use and to their affordability. China, Tanzania, and Vietnam have successfully promoted the use of ITNs and achieved substantial control of malaria in many places. Strategies to encourage ITN use have included social marketing in Kenya and Malawi; assisted commercial sector development in Mali, Senegal, and Tanzania; free generalized distribution in Togo; and vouchers for highly subsidized ITNs distributed to pregnant women in Tanzania.
Treatment programs have traditionally relied on relatively inexpensive drugs, principally chloroquine. The key to success is timely detection and treatment. In South Africa, where 83 percent of the population live within 10 kilometers of a health clinic, health professionals play a central role. In countries like Burkina Faso, Ethiopia, and Uganda, where health clinics are much less accessible, reducing mortality and morbidity through treatment has required training mothers and community health workers to dispense treatment based on presumptive diagnoses.
In many areas, strains of the parasite resistant to chloroquine and sulfadoxine-pyrimethamine are now common. Fortunately, researchers have developed a new array of drugs, including artemisinin combination therapy (ACT), which costs more than traditional first-line drugs but is cost-effective in areas where drug-resistant strains are highly prevalent.
Health education and counseling are also significant for controlling malaria. They improve the timeliness of treatment by helping people identify the disease and seek appropriate care. They also promote better and more regular use of ITNs and encourage re-treatment of nets with insecticide as required. In addition, they further improve adherence to treatments, thereby reducing transmission of the parasite and the development of drug resistance.
Most of the malarial interventions available are quite cost-effective. Almost all of them cost less than US$150 per DALY averted and many of them can be implemented at a cost of less than US$10 per DALY. DCP2 estimates that ITNs cost between US$11 and US$17 per DALY averted, depending on the type of insecticide and the frequency of retreatments required; indoor residual spraying costs between US$5 and US$18 per DALY averted; and intermittent preventive treatment for pregnant women costs US$13 to US$35 per DALY averted.
Among drug treatments, chloroquine remains the most cost-effective treatment as long as chloroquine resistance is less than about 35 percent. When the prevalence of resistance increases beyond this level, ACT becomes more cost-effective. Sulfadoxine-pyrimethamine can be more cost-effective than chloroquine and ACT, but sulfadoxine-pyrimethamine resistance appears to emerge fairly quickly, and ACT is more cost-effective than sulfadoxine-pyrimethamine when sulfadoxine-pyrimethamine-resistance surpasses approximately 12 percent.
While malaria interventions are cost-effective, their feasibility depends on the availability of financial resources and health infrastructure and local epidemiological conditions. The total cost of a program to promote ITN use for children is about US$2.80 per capita per year, and a program for indoor residual spraying would cost about US$4 per capita per year. While these costs may seem low by many standards, they are prohibitive for countries where malaria is endemic, because the entire public budgets for all health expenditures in such countries range between US$2 and US$10 per capita per year. Breaking the financial constraints for these cost-effective programs requires substantial external assistance.
Research for a vaccine against malaria has long been under way, and should be further encouraged, but developing such a vaccine will require many more years. In the meantime, research is also needed to improve patient care, including easier, cheaper home management and evaluation of alternative delivery systems; prevention, such as intermittent treatment and increased ITN use; technologies, such as insecticides and antiparasitic effector molecules using genomics; and field evaluations of transgenic methods for interrupting malaria transmission.
Such research into new forms of intervention, together with the implementation of known and cost-effective prevention and treatment strategies, will permit successful control of this disease. Since the greatest burden of malaria is concentrated in countries where high transmission rates are combined with limited resources and weak health systems, control of malaria also undoubtedly requires expanded international assistance.
Vaccine-Preventable Diseases
Illnesses for which relatively inexpensive and highly effective vaccines are available account for a significant portion of the disease burden in developing countries.8 DCP2 (chapter 20) discusses TB, diphtheria, tetanus, pertussis, polio, measles, rubella, Hib, hepatitis B, yellow fever, meningococcal disease, and Japanese encephalitis. Vaccines are also available or are being developed for two causes of diarrheal disease: rotavirus and cholera (DCP2, chapter 19).
Vaccine-preventable diseases are quite varied. Some vaccine-preventable diseases are bacterial and others are viral; some are found primarily in human beings, while others readily thrive in other species as well; some have high fatality rates, while others are debilitating; some are concentrated in particular regions, while others are widespread; and some are spread through respiratory contact, while others are transmitted through insect bites or contact with infected fecal matter or blood. Despite this variability, vaccine-preventable diseases generally share two important characteristics: people can be infected without signs or symptoms (with the exception of tetanus) and vaccine-induced immunity is generally lifelong (with the exception of pertussis).
Countries that immunize a large share of their populations against these illnesses have eliminated most of the mortality and morbidity associated with them. Regions with lower vaccination coverage continue to have thousands of deaths that would be relatively easy to avert. In 2001, seven vaccine-preventable diseases—measles, hepatitis B, Hib, pertussis, tetanus, yellow fever, and diphtheria—caused more than 2.3 million deaths, primarily in Africa and Asia. Some 80 percent of all deaths from yellow fever occur in Africa, as do 59 percent of deaths from measles, 58 percent of deaths from pertussis, and 41 percent of deaths from tetanus. East Asia and the Pacific faces the largest burden of deaths from hepatitis B and its associated conditions and accounts for 62 percent of all such deaths. South Asia also has high mortality from these diseases, especially tetanus and measles.
In recent decades, a number of global initiatives have sought to expand the coverage of vaccines. Since 1974, WHO's Expanded Program on Immunization (EPI) has provided guidance and support for expanding coverage by standardizing immunization schedules,promoting safe injection technologies, improving the stocking and availability of vaccines, and protecting vaccines' potency through cold chain management. Its Reaching Every District strategy aims at having 80 percent of children in each country receive three doses of diphtheria-pertussis-tetanus vaccine. In 2000, international agencies, bilateral donors, private foundations, NGOs, and pharmaceutical companies collaborated in launching the Global Alliance for Vaccines and Immunization (GAVI). Since that time, GAVI has raised more than US$1.3 billion to strengthen immunization systems; introduce new or underutilized vaccines, such as those for Hib, hepatitis B, and yellow fever; and support safe injection practices. In addition, major research efforts are aimed at developing new vaccines and delivery methods.
Once a vaccine is available, the most important aspect of designing immunization programs is organizing the logistics of vaccinating people. In most developing countries, children are brought to fixed health facilities to receive injections or to take oral vaccines. A substantial number of vaccines are also delivered through outreach, that is, mobile strategies in which health care workers travel to homes and villages. Immunization campaigns that focus on specific antigens are another approach. The most famous immunization campaigns have focused on smallpox, which was declared completely eradicated in 1980, and polio, which is now found in only a handful of countries (DCP2, chapter 8).
Vaccination is generally very cost-effective. In the best of cases, vaccines are relatively inexpensive and a single dose leads to lifetime immunity. Whenever such an intervention is available for a widespread and potentially fatal infection, it is likely to be cost-effective.
The mix of delivery strategies, the price of key inputs (the vaccine itself plus labor, transportation, and cold storage), and the overall scale of the program all affect costs. Recurrent costs represent some 80 percent of the costs associated with delivering vaccines through fixed health facilities and 92 percent of the costs of immunization campaigns. The cost per fully immunized child for the six original EPI vaccines—TB, diphtheria, pertussis, tetanus, polio, and measles—is approximately US$20. Investigators estimate that the incremental cost of replacing oral polio vaccine with injectable polio vaccine and adding new antigens for hepatitis B, yellow fever, Hib, measles, rubella, Japanese encephalitis, and meningoccocal disease to existing programs is between US$1 and US$16 per person.
Cost-effectiveness is influenced not only by differences in prices and strategies but also by existing levels of immunization coverage. The cost per death averted from successfully vaccinating children against the six original EPI diseases is US$205 per death averted in South Asia and Sub-Saharan Africa, and US$3,540 per death averted in Europe and Central Asia, with the relatively high coverage rates in the latter region being largely responsible for the difference. Nevertheless, even at US$3,450 per death averted, vaccination is still highly cost-effective in Europe and Central Asia and compares favorably with many other uses of public money.
Future progress in controlling vaccine-preventable diseases depends on addressing financial and logistical constraints in low-income countries. Even though immunization programs are relatively inexpensive, the financial resources of many low-income countries are so constrained that even inexpensive programs account for substantial shares of available funding. On average, immunization programs account for 6 percent of government health expenditures in developing countries. However, among the world's lowest-income countries, expanding the coverage of traditional antigens, introducing new vaccines, and improving vaccine quality and safety could consume as much as 20 percent of a government's health budget in the absence of substantial foreign assistance.
The financial burden may be reduced through research and development into vaccines that require fewer doses and are cheaper to produce, easier to transport and store, and safer to administer. The development of new delivery strategies could also make a substantial difference to universalizing immunization coverage in low-income countries.
"even though children in developing countries still experience an average of 3.2 episodes of diarrhea each year, the number of deaths appears to have fallen significantly from an estimated 4 million to 6 million deaths in 1979 to an average of 2.6 million per year in the 1990s"
Diarrheal Diseases
Diarrheal disease is one of the top five preventable killers of children under five years old in developing countries.9 It is most dangerous for the young, with about 90 percent of deaths from diarrhea occurring in small children. However, even though children in developing countries still experience an average of 3.2 episodes of diarrhea each year, the number of deaths appears to have fallen significantly from an estimated 4 million to 6 million deaths in 1979 to an average of 2.6 million per year in the 1990s, with the bulk of the improvement attributable to effective public health interventions (see, for example, the discussion on using ORT in the Arab Republic of Egypt in DCP2, chapter 8).
Dozens of viruses, bacteria, protozoa, and helminths cause diarrheal disease. Some of these agents rely almost exclusively on human hosts, whereas others also infect animals. They are generally acquired through fecaloral transmission, often through the ingestion of contaminated water or unwashed foods. Infection by such agents causes severe bouts of diarrhea, compromises the body's immune system, weakens its ability to draw nourishment from food, and can lead to serious and rapid dehydration. Severe watery acute diarrhea, caused mostly by rotavirus, enterotoxigenic Escherichia coli, and vibrio cholerae, causes rapid dehydration and can lead to death. Persistent diarrhea is associated with malnutrition, and even though it accounts for a relatively small share of diarrheal cases, it is three times more likely to be fatal than watery diarrhea. Bloody diarrhea is often associated with intestinal damage and nutritional deterioration, some dehydration, and fevers.
The strategies for reducing the burden of diarrheal disease have not changed substantially since the first edition of Disease Control Priorities in Developing Countries (Jamison and others 1993) with the exception of some advances in vaccine technologies. Better and more hygienic feeding practices, immunization, improved water and sanitation, and better case management are the major interventions available for preventing and treating diarrheal disease.
Better and more hygienic feeding starts with programs that promote exclusive breastfeeding during a child's first six months of life. This reduces the likelihood that a child will ingest contaminated food or water during infancy and strengthens the child's immune system through the ingestion of beneficial elements in the mother's milk. Such programs include hospital policies that encourage breastfeeding, counseling and education from peers and health workers, mass media and community education campaigns, and mothers' support groups.10
Better feeding practices once a child is six months old can also be encouraged and effective. Some 800,000 lives per year could be saved by more hygienic food storage and preparation and by promoting education, providing good nutrition, and ensuring adequate weight gain. Researchers have also shown that vitamin A and zinc supplementation have beneficial effects on diarrhea: both are associated with reducing the frequency of severe diarrhea, and zinc supplementation also reduces the incidence of diarrhea.
"Some 800,000 lives per year could be saved by more hygienic food storage and preparation and by promoting education, providing good nutrition, and ensuring adequate weight gain."
Rotavirus immunization could prevent some 440,000 deaths per year from this common infection. Developing a safe and effective vaccine for cholera has also proven difficult, and it can usually be controlled through effective public health programs. Only Vietnam routinely deploys cholera vaccine. Other countries have decided that ORT is so inexpensive and so effective in preventing deaths from cholera that the costs and risks of immunization are not worthwhile. Measles compromises the immune system and can thereby lead to acute diarrhea. By reducing the occurrence of measles, vaccines could reduce 6 to 26 percent of diarrheal deaths among children under five.
Another way to reduce diarrheal disease is by providing clean water and sanitation, because estimates indicate that contaminated water causes 90 percent of diarrheal cases among children. Nevertheless, DCP2 (chapter 41, p. 778), notes that "domestic hygiene—particularly food and hand hygiene—is the principal determinant of endemic diarrheal disease rates and not drinking water quality." Rather than quality, the quantity, continuity, and convenience of water services is what reduces the incidence of diarrhea by encouraging more hygienic behavior with regard to personal care and food preparation.
Investment infrastructure for water and sanitation can be expensive relative to other preventive measures and case treatment. Nevertheless, water service has many health benefits beyond reducing diarrheal disease. When water service is associated with better personal hygiene, it interrupts the transmission of skin and eye infections such as trachoma from one person to the next; reduces the incidence of water-based illnesses such as schistosomiasis and guinea worm; and reduces exposure to water-related insect vectors responsible for dengue, malaria, and trypanosomiasis.
The most important benefit people popularly associate with water and sanitation services is greater convenience other than the effects on health. The savings in time and labor can be substantial, given that women and children in particular spend an average of more than an hour each day in rural East Africa and more than two hours each day in several Asian countries obtaining and hauling water. Surveys also show that people in developing countries value improved sanitation less for health reasons than for reasons of comfort, prestige, and safety.
"women and childrenspend an average of more than an hour each day in rural East Africa and more than two hours each day in several Asian countries obtaining and hauling water."
In public policy debates, the health benefits of water and sanitation can best be viewed as an additional benefit conferred by water and sanitation investments that are justified for other reasons. Public health policy still has a role to play in regulating water quality, but public health authorities may be justified in expanding their regulatory authority to consider the quantity and continuity of water service given services' important influence on hygienic behaviors that reduce the incidence of disease.
When diarrhea prevention fails, simple and low-cost techniques are available for managing most cases. ORT, which consists of the oral administration of fluids containing simple salts and sugars, is inexpensive, can be administered by family members with limited training, and is highly effective at reducing the severity of many diarrheal diseases and averting death. After its introduction in the 1980s, many countries rapidly expanded the use of ORT to reach 33 percent of children with diarrhea in the Philippines, 35 percent in Brazil, 50 percent in Egypt, and 81 percent in Mexico. Zinc supplementation for children with diarrheal disease also helps reduce the severity of the illness. For bloody diarrhea, treatment with antimicrobial drugs is indicated, but as with so many other diseases, resistance to first-line antimicrobials is spreading and making these drugs less effective.
"where basic water and sanitation are not available, hygiene is poor, and ORT is not widely used, public health interventions aimed at preventing diarrheal diseases are extremely cost-effective."
In places where basic water and sanitation are not available, hygiene is poor, and ORT is not widely used, public health interventions aimed at preventing diarrheal diseases are extremely cost-effective. Promoting exclusive breastfeeding, measles immunization, ORT, and hygiene costs less than US$5 per DALY averted; promoting better sanitation through public policy costs about US$11 per DALY averted; investing in and maintaining hand pumps for water costs about US$94 per DALY averted; house connections for potable water cost about US$223 per DALY averted; and construction and promotion of basic sanitation facilities costs more than US$270 per DALY averted (DCP2, chapter 41).
Factors that encourage the transmission and development of diarrheal diseases are prevalent among people living in poverty. Impoverished people are more likely to be undernourished, to lack clean water and sanitary means of disposing of human waste, to cohabit with animals that harbor and transmit human pathogens, and to lack access to proper means of food storage such as refrigeration. Nevertheless, progress against diarrheal diseases can be made despite poverty. Effective programs can encourage such healthful behaviors as exclusive breastfeeding and personal hygiene; improve environmental conditions through the provision of safe water and sanitation; and train caregivers to recognize symptoms, especially of the more dangerous forms of diarrhea, and apply relatively simple treatments.
"progress against diarrheal diseases can be made despite poverty."
