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Jamison DT, Feachem RG, Makgoba MW, et al., editors. Disease and Mortality in Sub-Saharan Africa. 2nd edition. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2006.

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Disease and Mortality in Sub-Saharan Africa. 2nd edition.

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Chapter 12Vaccine-Preventable Diseases

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Vaccines have been frequently cited as one of the most equitable low-cost, high-impact public health measures, saving millions of lives annually when programs are implemented on the national level. Over the last 40 years, the use of smallpox, measles, diphtheria, tetanus, pertussis, and poliomyelitis vaccines have eradicated smallpox and eliminated disease in those populations that have achieved and sustained programs with high implementation rates. Although there are numerous licensed vaccines that could potentially benefit the African population, only those routinely used and potential vaccines with broad application on the horizon are covered in this chapter.

History of Vaccination in Africa

The eradication of smallpox was an outstanding display of concerted global action in a war against microbial invaders. The progress in expanding poliomyelitis and measles vaccination efforts and their elimination from many regions further demonstrates that vaccines are among the most powerful public health tools. National vaccination programs, which grew out of the smallpox eradication initiative, have developed in many countries through the administrative, technical, and financial support of the United Nations Children's Fund (UNICEF), the World Health Organization (WHO), and many bilateral or multilateral partner agencies (figure 12.1) (WHO and UNICEF 1996). In its 1993 World Development Report, the World Bank classified vaccination as one of the most cost-effective public health interventions (World Bank 1993). In addition, vaccination programs have been cited as providing one of the most equitable of public health programs, providing protection to the entire population when successfully implemented.

Figure 12.1

Figure 12.1

Percentage of Target Population in Africa Vaccinated, by Vaccine Type, 1980–2002 Source: WHO 2003.

The WHO created the Expanded Program on Immunization (EPI) in 1974 as a means to continue the great success that had been achieved earlier with the eradication of smallpox. At that time less than 5 percent of the world's children in the developing world were receiving immunizations. The six diseases chosen to be tackled under this new initiative were tuberculosis, diphtheria, tetanus, pertussis, polio, and measles. It was not until 1988 that the WHO recommended that yellow fever vaccine be added to the national immunization programs of those countries with endemic disease (WHO and UNICEF 1996). Later, in 1992, the World Health Assembly recommended hepatitis B vaccination for all infants. Most recently the WHO has recommended that the Haemophilus influenzae type B (Hib) conjugate vaccines be implemented into national immunization programs unless epidemiological evidence exists of low disease burden, lack of benefit, or overwhelming obstacles to implementation (WHO 2006).

The Vaccine-preventable Disease Burden

The WHO-estimated disease burdens from vaccine-preventable diseases are shown for 2002 by incidence of death and disability-adjusted life years (DALYS) in table 12.1. As the WHO does not necessarily classify disease based on what may be prevented by a specific vaccine, the table includes those syndromes that may be partially mitigated by vaccines (for example, acute lower respiratory tract infection, meningitis, or conditions associated with hepatitis B infections).

Table 12.1. WHO-Estimated Deaths and DALYs from Vaccine-Preventable Diseases, 2002 (thousands).

Table 12.1

WHO-Estimated Deaths and DALYs from Vaccine-Preventable Diseases, 2002 (thousands).

As most vaccine-preventable diseases are underreported in many countries, estimates of disease burden are made by a variety of methodologies that account for the susceptible fraction of the population, as calculated from natural immunity from presumed historical infections, historical immunization coverage rates, and vaccine effectiveness. Disease burden estimates also integrate rates of infectivity, specific sequelae, and local case fatality. Life expectancies on a national level can help to account for causes of competing mortality, allowing the assessment of health outcomes as deaths, years of life lost, or other measures (for example, DALYs). Estimates of disease burden have evolved over the years from simplistic models incorporating reported rates of disease and a reporting efficiency profile to the more complex Susceptible-Infected-Removed (SIR)–type models that can additionally account for local population-based coverage data and other deterministic data, such as socioeconomic factors and characteristics of the heterogeneity of populations throughout the region. Models are based on numerous assumptions, and their degree of accuracy is only as good as the data that support the many assumptions. Although disease burden is frequently indicated as point estimates, it is more appropriate to indicate the burden by a range of values to reflect uncertainty, sometimes by an order of magnitude or more for certain diseases.

Polio

Poliovirus is most often transmitted fecal-orally among persons living in unsanitary and crowded conditions. Acute infections are caused by any one of three serotypes of poliovirus that initially replicate in the gastrointestinal tract. Exposure to poliovirus predominantly results in asymptomatic infections. It has been estimated that 24 percent of infections result in minor illness characterized by a few days of varying symptoms, including fever, malaise, drowsiness, headache, nausea, vomiting, constipation, and sore throat (Gelfand et al. 1957). In fewer cases (4 percent), infection leads to nonparalytic polio or aseptic meningitis, which manifests as fever, vomiting, malaise, and sore throat; meningeal irritation occurs one to two days later, characterized by soreness and stiffness of the neck, back, limbs, and severe headache (Horstmann 1955). These symptoms can last up to 10 days, but recovery is usually rapid and complete. Paralytic polio, which affects less than 1 percent of those infected, is the most serious manifestation of the disease (Sabin 1951). This form of the disease presents initially as a minor fever with rapid progression to paralysis within a matter of days. Paralysis may affect the major muscles involved in respiration and therefore cause death if there is no appropriate rapid intervention.

Global efforts toward polio eradication have included vaccination campaigns and active surveillance. The annual incidence of paralytic polio was reduced from an estimated 350,000 in 1988 to about 1,000 from 2001 to 2004 (WHO 2004). Africa and South Asia are the last regions in the world where poliomyelitis is still endemic. False accusations of tainted vaccines by local leaders have led to a local resurgence of poliomyelitis cases and consequent spread to other parts of Africa (Heymann and Aylward 2004).

Two different poliomyelitis vaccines are currently used to protect against disease. Oral poliovirus vaccine (OPV) is a live attenuated vaccine containing all three serotypes of the poliovirus and induces protection as high as 95 percent in individuals who receive three doses. Additional booster doses are necessary to achieve nearly 100 percent protection. Currently the WHO recommends that OPV be given at birth, 6, 10, and 14 weeks in polio endemic or recently endemic countries (Sutter and Kew 2004). In many developed countries this vaccine is now delivered in a series of national or subnational campaigns several times a year. The majority of developing countries throughout the world rely on OPV for vaccinating their population, a combined birth cohort of 127 million people (Sutter and Kew 2004).

Because OPV is a live viral vaccine that can revert to a transmissible pathogenic virus, recipients or those in contact with them can be at increased risk of vaccine-associated paralytic poliomyelitis (VAPP) due to shedding of live virus into the environment. VAPP occurs in less than one person per 3.3 million doses administered (Sutter and Kew 2004). Viral shedding can be chronic and occur for years. Recent polio outbreaks have been blamed on continuous transmission of polioviruses derived from vaccine strains, most notably in areas with low immunization coverage rates (Kew et al. 2004). An assumption of the WHO eradication program is that countries would be able to stop vaccination after wild poliovirus ceases transmission; however, the possible threat of a resurgence because of the continued likely circulation of oral poliovirus vaccine would seriously challenge that strategy (Miller, Barrett, and Henderson 2006).

Inactivated poliovirus vaccine (IPV) is another vaccine, composed of three types of inactivated polioviruses. When IPV is administered to infants as the primary vaccine, the first two or three doses should be administered in the first six months of life, followed by a booster during the second year. It is also recommended that, when feasible, a second booster be given to children before they enter school. IPV efficacy rates have been estimated between 80 and 90 percent against paralytic polio (Plotkin and Vidor 2004). An increasing number of countries are transitioning from OPV to IPV because of the risk intolerance associated with vaccine-derived paralysis. Financial and operational barriers currently prevent many developing countries from doing the same, although costs and the ease of IPV use through combination vaccines may allow their greater use in the future.

Measles

Measles is an acute, highly infectious viral disease that is transmitted from person to person through large respiratory droplets. In the absence of vaccination, measles is estimated to infect virtually the entire population with the exception of isolated communities (Black 1976). Most children born to immune mothers are protected from the virus for the first six months of their lives from acquired maternal antibodies. More than 90 percent of infections are associated with clinical disease, which includes a range of symptoms, including fever, rhinorrhea, cough, and conjunctivitis. A rash commonly appears within three to four days after onset. Complications associated with measles include pneumonia, diarrhea, encephalitis, and blindness. The case-fatality rates in recent years have been estimated at 0.1 to 3 percent in many developing nations (Strebel, Papania, and Halsey 2004).

The number of deaths due to measles has been a subject of considerable controversy for the past several years, mostly because of the inability to specify accurately the cause of death in children afflicted with measles and other, similar conditions. Many models have been constructed that demonstrate a substantial reduction of measles deaths from the long-stated global number of 1 million deaths per year reported by the WHO prior to 1997. Large-scale urban and nationwide vaccination campaigns over the last few years have reduced measles mortality to 250,000–500,000 deaths per year, most of which still occur in Sub-Saharan Africa. Measles can coexist with several comorbid conditions that can cause death, so attribution to any one cause is somewhat arbitrary, rendering specific accounting difficult. It is likely, however, that recent implementation of mass vaccination campaigns throughout many regions, and in areas previously associated with high mortality, has dramatically reduced deaths due to measles. However, given the high transmission rate of measles virus, this reduction in mortality could only be maintained with continuous high coverage. Measles mortality can be estimated from the susceptibility profile of the population based on historical immunization coverage rates and natural immunity (Miller 2000). Transmission can be blocked if population-based immunity exceeds approximately 93 percent, limiting cases only to importations. Control in many urban parts of Africa may be difficult, given that transmission is higher in densely populated environments with low levels of hygiene (Miller 2000).

The measles vaccine is a live attenuated vaccine that can be administered by itself, combined with rubella vaccine, or with mumps and rubella vaccines. Nearly 95 percent of children vaccinated with at least one combination of the vaccine develop immunity. Most individuals who fail to develop immunity with one dose will do so upon receiving a second dose. Vaccination is believed to induce lifelong immunity. The first dose should be given on or after the first birthday. A second dose is given to children when they are about four to six years old but can be given as soon as one month after the first dose. Adverse reactions following immunization, such as fever, rash, or lowered platelet counts, have been observed in 5 to 15 percent of vaccine recipients. Many developing countries are now delivering measles vaccines in campaign style, similar to that used to deliver poliovirus vaccination.

Measles vaccination rates are sensitive indicators of functional public health systems. One to two doses of a US$0.14 vaccine could prevent a disease that practically affects 100 percent of the population with an approximate case-fatality rate of 3 to 6 percent in Sub-Saharan Africa. Given that measles vaccine is one of the most cost-effective and low-cost health interventions, low coverage rates of the vaccine in the 1990s is indicative of the poor state of public health infrastructures in various Sub-Saharan Africa populations (figure 12.2).

Figure 12.2

Figure 12.2

Immunization Coverage with Measles-Containing Vaccines, 2003 (percent) Source: WHO and UNICEF 2003.

Diphtheria-Tetanus-Pertussis

Diphtheria, tetanus, and pertussis are frequently cited together given that these three diseases are frequently controlled with a single vaccine. Each of these diseases will be covered in turn.

Diphtheria

Diphtheria is caused by toxin-producing strains of the bacterium Corynebacterium diphtheriae, which can be transmitted from person to person via respiratory droplets. The bacterium often affects the tonsils, pharynx, nasal mucosa, inner ear, vagina, or skin. Respiratory diphtheria presents as a sore throat often accompanying a mild fever. Death can result from severe cases in which swelling from pharyngeal and tracheal exudates obstruct the airway. Myocarditis and neuritis are two other complications associated with respiratory diphtheria. Cutaneous diphtheria presents as skin lesions and causes far fewer complications and deaths among those infected.

Estimates of the burden of diphtheria in Africa are unreliable, given the low number of diagnosed or reported cases. In The Gambia, an annual incidence rate of six cases per 1,000 persons under the age of five years was reported (Heyworth and Ropp 1973). Incidence data in Africa is limited to case series and hospital-based surveillance studies, where underreporting is likely, given that diphtheria is frequently reported as nonspecific upper respiratory infections (Rodrigues 1991).

The EPI has traditionally recommended three doses of the combined diphtheria-tetanus-pertussis (DTP) vaccine in the first year of life (in conjunction with polio vaccine). Most developed countries give subsequent booster doses in childhood and diphtheria-tetanus boosters in adulthood. There is growing concern that adolescents and adult populations are becoming more susceptible to diphtheria because repeated doses of diphtheria toxoid are needed to maintain immunity in these populations. Once a child is immunized, the immunity wanes relatively rapidly without exposure to natural C. diphtheriae (Galazka and Robertson 1996; Galazka, Robertson, and Oblapenko 1995; Geldermalsen and Wenning 1993). However, in Africa, the need for boosters is offset by the natural immunity provided by the presence of C. diphtheriae in skin ulcers as well as asymptomatic carriage in the throat, which spreads the organism throughout the population. Carrier rates in Africa have been estimated to be as high as 9.3 percent in children in the general population (Geldermalsen and Wenning 1993).

The risk of diphtheria epidemics is heightened among communities with an immunity gap in adults and a large number of susceptible children and adolescents (Galazka and Robertson 1996). As a means of controlling potential diphtheria outbreaks, immunization coverage rates should be increased among at-risk groups, cases should be promptly detected and managed, and close contacts should be recognized quickly to prevent secondary infections (Galazka, Robertson, and Oblapenko 1995). For these reasons effective vaccine and surveillance must be maintained in Sub-Saharan Africa in order to keep the prevalence of diphtheria at relatively low levels and to prevent possible epidemics. In addition, the use of booster doses should be considered, especially as immunity wanes in those populations with increasing hygiene and the consequent decrease to natural reexposure.

Pertussis

Pertussis, or whooping cough, is a highly contagious disease caused by the bacterium Bordetella pertussis, which is transmitted through respiratory excretions. Pertussis is characterized as spasms (paroxysms) of coughing followed by inspiratory "whooping." The paroxysms can vary in length and severity but may become so severe, especially among infants, that respiration is compromised, resulting in hypoxia. In some cases this can cause neurological damage. Pneumonia can also be a complication of pertussis infection. In a study conducted in Canada, pneumonia occurred in 2 percent of patients younger than 30 years old and in 5 to 9 percent of older participants (De Serres et al. 2000). Severe coughing in older persons can cause serious complications, ranging from rib fractures to pneumo-thorax, inguinal hernia, and herniated lumbar disks (De Serres et al. 2000; Postels-Multani et al. 1995).

In more developed countries transmission from adults to young infants is common. Girls tend to have higher incidence rates of the disease than boys (Dragsted et al. 2004; Mahieu et al. 1978; Preziosi et al. 2002). Pertussis is highly contagious in its early stages and has a secondary attack rate in other household members as high as 90 percent (Rodrigues 1991). Reported incidence rates of pertussis in Senegal prior to any immunization campaigns were estimated to be 183 per 1,000 child-years at risk under age five years, with a 2.8 percent case-fatality rate (Preziosi 2002). Similar studies have shown incidence rates in Africa to be nearly 1,000 per 100,000 inhabitants (Galazka 1992).

Each year there are an estimated 20 million to 40 million cases of pertussis and another 200,000 to 400,000 deaths attributed to the disease, 90 percent of which occur in the developing world (WHO 1999b). The WHO believes that only 1 to 2 percent of cases are reported worldwide. Pertussis diagnosis is difficult for several reasons. Paroxysms among adults are less severe and often misdiagnosed as other respiratory illnesses. Misdiagnosis is common in areas without adequately trained personnel or technology. In a study of 3,096 patients, B. pertussis was found in 496 individuals; 208 (42 percent) were diagnosed by polymerase chain reaction (PCR) alone, whereas 17 (3 percent) were diagnosed by culture alone (Dragsted et al. 2004). Rapid diagnosis of pertussis using PCR techniques together with serological assays can enhance diagnosis as well as surveillance of pertussis (Fry et al. 2004). Clinical diagnosis of pertussis by a trained physician has also proved to be a reliable diagnostic tool (Granstrom, Wretlind, and Granstrom 1991) and is often characterized by a cough that lasts at least 14 days (Patriarca et al. 1988). These are important implications when considering diagnosis of pertussis in remote areas with limited laboratory resources and few trained health professionals.

The incidence rate of pertussis has declined drastically over the past half-century primarily because of the administration of the inactivated whole-cell pertussis vaccines. Due to neurological reactions associated with the whole-cell vaccines, new acellular vaccines have been developed. Either of these vaccines is usually administered with the diphtheria and tetanus toxoids (TTs). The whole-cell vaccine is cheaper than the acellular vaccine and is produced in many developing countries (WHO 1999b). A herd effect of vaccination not only protects immunized infants but decreases transmission rates to protect unvaccinated infants (Miller and Gay 1997). The introduction of pertussis vaccines through the EPI in Senegal has resulted in steady and dramatic decreases in the incidence of the disease, especially among infants under six months old (Preziosi et al. 2002).

Tetanus

Tetanus is the only EPI vaccine-preventable disease that is not communicable but acquired through environmental contamination. The bacterium Clostridium tetani, which can grow in dirty flesh wounds, produces a neurotoxin causing convulsions and eventual death. Neonatal tetanus (NNT), the most common form of tetanus in the developing world, is the result of contamination of the umbilical stump either by the use of nonsterile instruments after delivery or the application of animal dung to the cut cord, a custom in many cultures, especially among groups in Sub-Saharan Africa (Elmore-Meegan et al. 2001). Symptoms can appear 3 to 14 days after birth following a period of normal feeding. Infected infants will gradually lose the ability to nurse properly followed by a period of convulsions, which increase in intensity and frequency. Mortality rates of infants can range from 25 to 90 percent with care, 95 percent without (http://www.who. int/vaccines/en/neotetanus.shtml).

NNT, which causes an estimated 450,000 infant deaths, is defined as tetanus in the first month of life. Another 40,000 maternal deaths are estimated to occur from tetanus acquired during delivery (WHO 1999a). NNT remains a global problem, but the greatest burden occurs in Africa (table 12.1) (Anita-Obong, Young, and Effiong 1993; Stanfield and Galazka 1984; WHO 1999c, 2001b). Nearly 90 percent of the global burden from NNT is from 28 countries. Of these, 16 are located in Africa (Angola, Burkina Faso, Cameroon, Chad, Côte d'Ivoire, Democratic Republic of Congo, Ethiopia, Ghana, Guinea-Bissau, Liberia, Mali, Mauritania, Mozambique, Niger, Nigeria, and Senegal). Additionally, 11 of the 12 countries reporting NNT mortality rates greater than 5 per 1,000 live births are in Africa (WHO 1999c).

The WHO estimates that approximately 3 percent of NNT cases are reported each year; this figure includes those reported from countries considered to have well-developed surveillance systems (WHO 1999b). Because death may occur within the first week of birth, it often is unreported in official mortality records and therefore is referred to as "the silent killer" (CVI 1994). Community surveys conducted in various states of Nigeria between 1990 and 1993 found that mortality rates from NNT ranged between 9 and 20 per 1,000 live births (Babaniyi and Parakoyi 1991). It was estimated in 1999 that nearly 46,000 cases of NNT occurred in Nigeria, representing 36 percent of all the NNT cases in the African region, although only 1,529 of the cases were actually reported. This problem of underreporting has serious implications for the control of the disease.

The World Health Assembly in 1989 set the goal for elimination (defined as incidence of less than 1 case per 1,000 live births) of NNT by 1995. This date was later delayed until 2005 because of operational constraints from the expanded scope of including maternal tetanus. By 1999 only 104 of the 161 developing countries in the world had eliminated neonatal tetanus. Sixteen of the 57 nations that have yet to reach this target are located in the African region (figure 12.3) (Idema et al. 2002). Included in this plan for elimination is the use of TT to protect pregnant women and the use of supplemental immunization activities, clean birthing practices, and active surveillance systems for women of childbearing age (WHO 2001b).

Figure 12.3

Figure 12.3

Maternal and Neonatal Tetanus Elimination Status, 2002 Source: WHO and UNICEF 2003.

DTP Vaccines

Inactivated diphtheria and TTs can be combined with whole-cell or acellular pertussis vaccines, such as DTwP or DTaP, respectively, and administered as a single injection. In most of Africa, the national EPI schedule of vaccination is at 6, 10, and 14 weeks of life. Although most developed countries administer booster doses, this does not routinely occur in Africa. Pertussis vaccine efficacy is 70 to 90 percent of fully vaccinated children (Edwards and Decker 2004); however, continuous protection requires booster doses. Three doses of tetanus or diphtheria toxoids are associated with greater than 95 percent protection against disease (Cherry and Harrison 2004; Feigin, Stechenberg, and Hertel 2004; Wharton and Vitek 2004); however, periodic boosting is necessary to ensure lifelong protection. DTP vaccine has been associated with adverse effects, such as local swelling and tenderness, fever, febrile seizures, anaphylaxis, hyporesponsive episodes, and encephalopathy (Edwards and Decker 2004). The more expensive acellular pertussis vaccines have greatly reduced these reactions.

The TT, given to immunize pregnant women to prevent neonatal and maternal tetanus, induces antibodies that can be passed from the mother to the fetus. In addition to being an effective vaccine, it is relatively cheap at about US$0.07 per dose (CVI 1994). Studies have shown that when 80 percent of women in an area have been vaccinated against tetanus with two doses, the level of seroprotection coupled with health education is adequate to eliminate tetanus (CVI 1994).

Some of the lowest coverage rates of TT are found in Africa. The EPI coverage rates among pregnant women with two doses had stagnated between 30 and 40 percent in most African nations by 1999. One of the objectives of the EPI is to increase coverage of three doses of DTP vaccine to 80 percent in all districts in the region. It is estimated that 53 percent of children under the age of one living in Sub-Saharan Africa have received three doses of the DTP vaccine (figure 12.4) (World Bank 2003).

Figure 12.4

Figure 12.4

Global and Regional Immunization Coverage, Three Doses DTP, 1980–2001 Source: WHO and UNICEF 2003.

Tuberculosis

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. Transmitted through respiratory droplets, tuberculosis is highly contagious, with studies showing a 25 to 50 percent infection rate of those in close contact with infected individuals (Smith and Starke 2004). TB presents clinically with a wide range of symptoms, depending upon the age of the individual. Infants and adolescents are most likely to have significant clinical manifestations compared with older children. Most infants will present with a nonproductive cough, shortness of breath, and low grade fever. Other common symptoms include night sweats, malaise, irritability, fatigue, and weight loss. TB is often misdiagnosed as other illnesses, such as bronchitis, until it progresses to more advanced stages. TB can also present as meningitis in infants or cause a chronic infectious process almost anywhere throughout the body. The time between preclinical infection and the onset of disease can be several weeks to many decades. Adults who are able to suppress acute infections often carry the bacterium latently, which results in reactivation of the disease later in life. Accurate diagnosis of TB is a critical component for better understanding the burden of disease as well as the effectiveness of interventions. In resource-poor areas of the world in which mycobacterial cultures and radiography are not accessible, microscopy is most commonly used to identify the organism and thus diagnose the disease.

TB is blamed for nearly 2 million to 3 million deaths annually, and it is believed that another 8 million people are infected with the bacterium each year. Nearly one-third of the world's population is currently infected with TB (WHO 2001a). In much of the world the TB incidence rates continue to grow, especially in Sub-Saharan Africa, despite the widespread use of the bacille Calmette-Guérin (BCG) vaccine (Cantwell and Binkin 1996). In Africa, coinfections of human immunodeficiency virus (HIV) and TB have led to increases in the incidence rate of TB by approximately 20 percent (Smith and Starke 2004).

BCG is a live attenuated bacterial vaccine most commonly administered intradermally at birth to prevent tuberculosis. The effectiveness of the BCG vaccine against TB has been debated, with a range estimated from 0 to 80 percent (Fine 2001). Most proponents claim that it is effective against TB meningitis, but it is not commonly believed to prevent TB in adults nor its transmission. The real impact of BCG may have been confounded by many other improvements in public health that could have contributed to the decrease in disease burden associated with tuberculosis (Smith and Starke 2004).

Yellow Fever

Yellow fever is an acute viral infection transmitted by mosquito, primarily the Aedes aegypti. Symptoms of the infection can vary, making diagnosis difficult and leading to the underestimation of morbidity (Monath 2004). After an incubation period of three to six days, onset of symptoms—rigors, headache, nausea, joint pain, jaundice, and myalgia—is rapid. In approximately 15 to 20 percent of cases, severe disease causes multiple organ failure.

Yellow fever is endemic to parts of South America as well as Sub-Saharan Africa in areas bordering jungles (figure 12.5). Between 1986 and 1995, reported incidence of yellow fever dramatically increased from previous reporting intervals, likely because of cessation of vaccinations. In Africa alone, 22,952 cases were reported, accounting for 89 percent of the total global cases during that period (Monath 2004). A case-fatality rate of 23 percent (5,357 deaths) was reported throughout Africa.

Figure 12.5

Figure 12.5

Epidemics of Yellow Fever in Africa Reported to the WHO, 1980–2003 Source: WHO 2003.

The yellow fever vaccine is a live attenuated viral vaccine recommended for anyone nine years or older living or traveling to endemic regions of South America and Africa. A single dose of the vaccine has shown to be effective for 30 to 35 years and most likely for the duration of the vaccine recipient's life (Monath 2004). Adverse effects from the vaccine have ranged from mild symptoms of headache, malaise, or low-grade fever to rare, more serious complications.

Hepatitis B

Many viral agents cause hepatitis; vaccine can counteract two of them—hepatitis A virus (HAV) and hepatitis B virus (HBV). Although a licensed vaccine against HAV is used in developed countries, it is currently not considered to be cost-effective for Africa. HBV, transmitted through blood-borne infections, sexually, or from mother to infant, can potentially cause more severe illness, including fulminant hepatitis, cirrhosis, and liver cancer. Persons infected as infants have a 70 to 90 percent chance of becoming a chronic carrier of the virus and can then either infect other persons or develop severe sequelae at a later stage in life.

National serosurveys for antibodies and antigenic markers for carrier states of HBV are available for almost all nations at various stages of resolutions due to blood-banking practices. The overall carriage rate for Sub-Saharan Africa is 12 percent. These data allow for estimations of disease burden based on a certain percentage of chronically infected persons progressing to hepatoma, fulminant hepatitis, or cirrhosis at later stages of life (Miller and McCann 2000). For Sub-Saharan Africa, this would translate into more than 500,000 deaths per year in each birth cohort at a mean age of 40 to 45 years. As life expectancy in Sub-Saharan Africa is currently declining from the HIV epidemic, actual death from hepatitis is likely to be lower.

Three doses of HBV vaccine, the first given at birth, could effectively prevent a child from becoming infected and from becoming a chronic carrier of the virus. Vaccine effectiveness is approximately 95 percent with three doses. Therefore, HBV vaccine could exert a powerful herd effect on the population by eliminating the long latency period during which persons could be infectious to others. Despite the benefits of implementing HBV into national vaccination campaigns, a minority of African nations are doing so (figure 12.6). The WHO endorses several immunization schedules so that HBV vaccine can be administered with other vaccines. The vaccine does not have any known serious effects and can be combined with other vaccines, including DTP and Hib.

Figure 12.6

Figure 12.6

African Nations Using Hepatitis B Vaccine in a National Infant Immunization Campaign, 2002 Source: WHO 2003.

As HBV is transmitted in a way similar to that of HIV, the uptake and use of this vaccine is a good proxy for the potential use of vaccines against HIV and the acquired immune deficiency syndrome (AIDS).

Haemophilus Influenzae type B

Hib is a bacterium transmitted through respiratory excretions and may be carried in the nasopharynx of about 15 percent of nonimmunized children (WHO 1998). The most common forms of invasive disease are meningitis, epiglottitis, pneumonia, arthritis, and cellulitis. Epiglottitis is characterized by swelling of the epiglottis, the tissue in the throat covering the larynx. The disease burden of Hib is highest among children between four and eighteen months, rarely occurring in infants younger than three months and after the age of six years. Hib meningitis could cause severe mental retardation in patients who recover from the acute form of the disease.

As it is difficult to culture this organism, disease burden estimates are made through a variety of modeling studies integrating data from geographic representational populations and similar socioeconomic stratification (Miller 1998; Miller and McCann 2000). In a Hib vaccine trial in The Gambia (Mulholland et al. 1997), the vaccinated group had 21 percent fewer occurrences of severe pneumonia than the control group, indicating that up to 21 percent of cases of severe pneumonia may be due to this organism. Extrapolation to the rest of the region would indicate that this vaccine could potentially prevent 90,000 to 123,000 deaths due to bacterial pneumonia or meningitis.

Since 1988, safe and effective vaccines have been developed to prevent Hib. A conjugate vaccine can be coadministered with DTP, IPV, and HBV vaccine. A full course of vaccine confers more than 95 percent protection against invasive Hib disease and results in a herd effect (Wenger and Ward 2004). This vaccine may be given in combination with DTP. In countries that have introduced a three- to four-dose regimen, Hib disease has almost been eliminated. The relatively high cost of the Hib vaccine has hindered many low-income countries from integrating the vaccine into routine vaccine schedules. Research has been conducted to explain quantitatively the benefits of adding Hib to national immunization programs in order to assist policy makers in endemic countries. It has been estimated that from 257,000 to 317,000 deaths could be averted each year through the routine use of Hib vaccine (Miller and McCann 2000). Although Hib vaccination would be a cost-effective intervention in low-income countries, its use in Africa has been limited.

Meningococcal Disease

Neisseria meningitides is a bacterium that causes meningitis, frequently with devastating neurological sequelae (Heymann et al. 1998; Merlin et al. 1996) and a death rate often exceeding 30 percent, even with optimal treatment (Campagne et al. 1999). Infections have also resulted in limb loss. Given its acute sporadic onset and devastating impact on young healthy individuals, mostly less than 30 years of age, meningococcal disease is one of the most feared infectious diseases. Although meningococcal disease is rare in infants up to three months of age, the incidence gradually increases to a peak at about one year of age and declines thereafter.

Although there are five serogroups (A, B, C, Y, and W135), serogroup A has caused annual epidemics in the African meningitis belt, an area stretching from Senegal to Ethiopia (Greenwood 1987; Greenwood et al. 1984; Lapeyssonnie 1963). Annual incidence rates in this portion of the African continent have exceeded 1,000 cases per 100,000 population in some instances (Granoff, Feavers, and Borrow 2004). In 1996 the largest recorded meningitis outbreak occurred in Africa, resulting in more than 250,000 cases and 25,000 deaths (Tikhomirov, Santamaria, and Esteves 1997).

A polysaccharide vaccine containing polysaccharides from serotypes A, C, Y, and W135 that is approximately 85 percent effective has been licensed but has been used only in response to outbreaks triggered by a weekly incidence of 10 to 15 cases per 100,000 persons in a geographically defined region. Frequently, surveillance and logistical difficulties to timely identification of outbreaks and delivery of vaccines in these instances have had a limited impact on epidemics. The 1996 outbreak and the continuous suboptimal implementation of emergency immunization campaigns led to a reevaluation of meningococcal disease-prevention strategies in this area (Miller and Shahab 2005). Robbins and colleagues (1997) called for immediate mass immunization, followed by a routine immunization program of four doses of polysaccharide vaccine given during the first five years of life. Others (WHO 1997) have suggested routine immunization of schoolchildren or improvement of the implementation of the current strategy of emergency response with mass immunization. To date, these vaccines are not used routinely in Sub-Saharan Africa. A conjugate meningococcal serogroup A vaccine currently being developed could routinely be administered to infants in Africa (LaForce 2004).

Future Vaccines

Parallel to the successful delivery of vaccines, great advances have been made in the field of vaccine development. Since the 1985 U.S. Institute of Medicine report established priorities for vaccine development (IOM 1986), many new vaccines with the potential to dramatically reduce morbidity and mortality have been developed. Within the last 20 years new safe and effective vaccines have been developed and licensed to protect populations against HBV and Hib. Great research strides in immunology have begun to pay dividends with the more recent licensure of rotavirus vaccines against diarrhea, human papillomavirus vaccine against genital warts and possible cervical cancer, and Streptococcus pneumoniae (SP) vaccine against pneumonia. Although these vaccines are currently licensed, they are presently not routinely used in Africa.

Vaccination Programs

The WHO objectives of the EPI in Africa are to strengthen the delivery of sustainable immunization services and to accelerate efforts to achieve polio eradication, measles control, neonatal tetanus elimination, and yellow fever control. Country strategic plans are prepared for the district level, with the goal of administering three doses of DTP to at least 80 percent of the target population in all districts and ensure increasing government funding for the EPI. EPI programs are strengthening health systems throughout Africa as well as implementing the use of new vaccines and technologies.

Prior to the implementation of immunization programs, vaccine-preventable diseases were highly endemic throughout Sub-Saharan Africa. During the 1990s the global immunization coverage exceeded 70 percent (figure 12.1); however, reported rates between regions and nations had great disparities. In Sub-Saharan Africa, reported immunization rates peaked in 1990 at 55 percent and remained steady throughout the decade. Immunization rates have decreased over the last 10 years in many low-income countries, particularly in Sub-Saharan Africa. For example, vaccination rates of all three doses of DTP (DTP3) in the Central African Republic decreased from 82 percent in 1990 to 29 percent in 2000. Similarly, the coverage rates with three doses of DTP vaccine dropped in the Democratic Republic of Congo from 79 percent in 1990 to 33 percent in 2000. These declines have been attributed to civil unrest and lack of political will among the national governments. As a result, millions of children have been left unvaccinated and vulnerable to disease.

The success of vaccination programs applied at the global level has had few parallels in public health. Immunizations remain one of the most cost-effective health interventions to prevent death and disability caused by infectious diseases. Despite great strides forward in vaccination development and administration throughout parts of the world, many countries, usually the poorest, struggle with vaccinating their children. This gap in immunization coverage results from many compounding problems, such as low political commitment on behalf of national and local governments, weak health service delivery systems, civil unrest, and underfunding and poor management. These problems are further compounded by relatively low levels of research and development of new vaccines to combat the predominant diseases in the developing world.

There are many possible reasons why routine vaccination has declined in Africa. Over the past decade, the budget of the WHO vaccine program has been heavily skewed toward the Poliomyelitis Eradication Initiative. Although this has led to high coverage rates against poliomyelitis virus, it likely has strained other vaccination services (Taylor, Cutts, and Taylor 1997). Additionally, throughout the 1990s, donors and the United Nations Children's Fund (UNICEF) emphasized that countries should pay for vaccine out of their own national budget rather than finance the cost through donors. The push toward self-reliance was made with good intentions, but fixed budgets within national economies may have simply moved funds from vaccine administration to vaccine purchase, with resultant declines in services.

An additional deterrent to vaccination adherence in much of the world is the threat of unsafe injections. It has been estimated that nearly 8 billion to 12 billion injections are administered in various health care settings throughout the world each year; 50 percent of these injections are believed to be unsafe and pose the risk of transmitting hepatitis, HIV, and other blood-borne pathogens (Miller and Pisani 1999). In many circumstances, especially in developing countries, disposable syringes are used multiple times, which increases the risk of disease transmission. Immunization rates drop dramatically when unsafe injection practices are publicized, whether they even are a part of vaccine campaigns.

Recognizing these factors, the WHO has recently been promoting the expansion and performance monitoring of services to local levels, with the goal of reaching routine coverage of at least 80 percent. This may rectify the maldistribution of vaccine delivery services within countries to increase the equity of benefits, especially to the populations on the margins, those likely to have the greatest disease burden.

Adoption of New Vaccines

The traditional EPI-targeted program has been challenged by the development of new vaccines that promise to reduce the disease burden further if they can be adopted into national programs. Since the development of national vaccine programs, there has been a widening gap in the number of vaccines used in developing and developed countries (figure 12.7).

Figure 12.7

Figure 12.7

Number of Childhood Vaccines Routinely Used in Developing and Established-Market Countrie Source: WHO and UNICEF 2003.

The use of these vaccines within already existing vaccine delivery infrastructures would greatly increase the armamentarium against infectious and even cancer-causing agents. However, despite the availability of these public health tools, countries have been slow to adopt them. For example, despite the World Health Assembly's recommendation to add HBV vaccine to all member nations' vaccination programs by 1997 (WHA 1992), less than one-half the global infant birth cohort receives this vaccine. Likewise, many African countries have yet to adopt the highly efficacious Hib vaccine. Given the array of new vaccines on the horizon, and potential vaccines against HIV, malaria, and tuberculosis, what is the likelihood of their adoption, especially in those countries that have the highest mortality from those diseases?

Factors such as national infrastructure to deliver vaccines and the cost of novel vaccines relative to national income in addition to an inadequate appreciation of the disease burden have prevented the adoption of newer vaccines. The Global Alliance for Vaccines and Immunizations (GAVI) has sought to address some of these factors through the creation of vaccine purchase funds and the direct allocation of financial resources to strengthen infrastructures at the local level. It is still too early to judge the success of these tactics and sustainability in the most resource-constrained areas such as Africa. Development agencies will have limited influence on per capita gross domestic product, but they can work with manufacturers to influence the vaccine cost to the country (either by offering financial support for vaccine purchase or guaranteeing volume purchase to lower vaccine prices) and strengthen vaccination services.

Vaccination: Problems and Barriers

The barriers to vaccine adoption are presumed to be multiple. If there is poor recognition of disease burden and costs, insufficient finances, or an ineffective vaccine delivery system, the introduction of a new vaccine is unlikely. However, methodological analyses can help focus deliberations and assist countries to overcome hurdles such as these. Demonstration of a country's disease burden as well as its associated economic burden may encourage the appropriate allocation of financial resources by clarifying the value of prevention through vaccination.

Economics has frequently been sited as a barrier to the use of newer vaccines. To address this, an analysis of the health and economic implications of new vaccine introduction was conducted to help national policy makers (Miller and McCann 2000). Disease burden, vaccine program costs, and the potential reduction of disease from vaccination were assessed for four vaccines that have not been adopted in many countries.

Without vaccination, HBV, Hib, SP, and rotavirus contribute to more than 1 million deaths in each successive birth cohort in Africa (Miller and McCann 2000). Routine scheduled use of HBV, Hib, SP, and rotavirus vaccines could potentially prevent most of these deaths (table 12.2). Incorporation of these vaccines into routine vaccination programs was estimated to cost between US$29 and US$150 per life year saved (Miller and McCann 2000). Based on these evaluations, HBV and Hib should be considered for integration into all national immunization programs. SP and rotavirus vaccines, with the given assumptions, would also be cost-effective. Proactive analysis of the epidemiologic and economic impact of these vaccines can hasten their introduction into national vaccination schedules.

Table 12.2. Potential Deaths Averted by HBV, Hib, Rotavirus, and SP Vaccine Implementation.

Table 12.2

Potential Deaths Averted by HBV, Hib, Rotavirus, and SP Vaccine Implementation.

Financial Implications, GAVI, and the Vaccine Fund

GAVI is a public-private partnership devoted to the promotion and strengthening of vaccine programs in low-income countries. Through the Vaccine Fund, which is the funding arm of GAVI, financial resources are provided for eligible countries to purchase vaccines and to fund the operational costs of managing immunization campaigns. GAVI provides funding to national governments based on national income (countries with gross national income per capita below US$1,000). Approximately half of the 75 countries eligible for funding through GAVI are located in Sub-Saharan Africa. In order for an eligible country to receive funding it must demonstrate that a well-functioning national mechanism is in place to coordinate immunization activities among the various partners within the country. The immunization program must have received a comprehensive assessment by GAVI-designated technical agencies during the previous three years, a multiyear immunization plan must be complete, and finally a strategy for improving the safety of injections must be demonstrated. Currently the GAVI's Vaccine Fund is providing financial support to governments in order to improve health services; distribute safe injection materials; and acquire the HBV, Hib, and yellow fever vaccines.

In an attempt to ensure the sustainability of immunization campaigns, GAVI requires countries that receive funding to create financial sustainability plans. Financial sustainability of immunization campaigns is vital in order to reach any long-term immunization goals. These financial sustainability plans are meant to be long-term plans that can improve the countries' immunization programs and serve as a foundation to expand support from other sources, namely, their own national budgets.

Initiatives by bilateral partner and health agencies emphasize the need for nations to strengthen health system infrastructures and assume responsibility for the provision of basic services, including childhood immunizations. Concurrent with these structural changes within nations are pricing and technology changes in vaccines. The six basic EPI vaccines are currently estimated to cost approximately US$0.50 per capita. New vaccines are appreciably more costly than traditional vaccines but far less expensive than the treatment costs of the diseases they prevent. The poorer developing countries, which often have the greatest disease burden, may be inclined to reject the adoption of these vaccines without full recognition of their true value.

A determination of the value of prevented disease is not a panacea for a shortage of financial resources. However, it can support the more efficient allocation of limited resources. Indeed, many new financial resources, most notably from the World Bank and the Bill & Melinda Gates Foundation, are expanding the number of potential resources available to help finance vaccination activities. There is concurrently an expanded role for medical associations on the national, regional, and global level to highlight the value of prevention through use of some of the best tools in public health.

Conclusion

Traditional vaccines are among the most cost-effective interventions there are and can potentially be used to achieve several Millennium Development Goals; however, continuous vaccination must be sustainable.

In many parts of Africa, vaccine infrastructure has been suboptimal, especially for routine vaccination. Immunization campaigns versus routine services appear to be dominating given logistical and operational hurdles in Sub-Saharan Africa

In Africa, new vaccines have been slow to be adopted into national EPI programs; likely reasons have been the lack of support for routine delivery throughout the continent. Logistical and operational factors are probable barriers that require substantial continuous investments in human capital, equipment, and financing.

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Copyright © 2006, The International Bank for Reconstruction and Development/The World Bank.
Bookshelf ID: NBK2284PMID: 21290645

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