The Infectious Etiology of Chronic Diseases Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary (2004) / Chapter Skim
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2 Endemic Infectious Diseases Linked to Chronic Diseases: Implications for Developing Countries
2 Endemic Infectious Diseases Linked to Chronic Diseases: Implications for Developing Countries
Pages 81-134
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From page 81... ...
The chronic impact of repeated malnourishing diarrheal illnesses is greater than that of acute deaths from enteric illness, which claims more than 6,000 children each day. Early diarrheal illnesses have significant long-term effects not only on physical fitness, but on growth, cognition, and school performance.
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From page 82... ...
Maureen Durkin discussed ostensibly preventable or controllable infections that are important causes of childhood cognitive disability, paralysis, epilepsy, blindness, and deafness in developing countries. These infections include congenital disorders, such as syphilis, rubella, and cytomegalovirus, as well as infections occurring during infancy and childhood, such as malaria, meningitis, Japanese viral encephalitis, measles, poliomyelitis, and trachoma.
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From page 83... ...
Center for Global Health, University of Virginia School of Medicine; and Federal University of Ceara, Fortaleza, Brazil The assessment of the global burden of diseases is increasingly important in recognizing and analyzing their importance as well as the priority of economic investments in their amelioration. In this perspective we recognize the quality of life or years lived with varying degrees of disability in addition to the quantity of life lost to premature mortality, as important outcomes or consequences of all diseases or conditions.
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From page 84... ...
Likewise, from placebo-controlled prospective studies of albendazole treatment of helminthic infections in Kenyan and Jamaican schoolchildren, intestinal helminths have been found to impair growth, fitness, and even cognitive function (Adams et al., 1994; Nokes et al., 1992a,b; Nokes and Bundy, 1992; Stephenson et al., 1993)
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From page 85... ...
For example, we are now learning that the 48 dehydrating, malnourishing diarrheal illnesses that often occur each year in the critically formative first two years of life may have profound, lasting consequences for impaired fitness, growth, cognitive development, and school performance several years later. Initial studies in Northeast Brazil show reduced fitness 4 to 6 years later associated with early childhood diarrhea, and specifically with cryptosporidial infections in the first 2 years of life, independent of respiratory illnesses, anthropometry, anemia, and intestinal helminths (Guerrant and Blackwood, 1999)
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From page 86... ...
47 years Guerrant et al., 1999 later (by 48.2 percent for median and Ndamba et al., 1993 high diarrhea burdens, respectively; for comparison, fitness scores improved 6.9 percent 4 months after albendazole treatment of schoolboys in Kenya and a 4.3 percent increase in HST scores correlated with a 16.6 percent increase in work productivity in sugarcane cutters in Zimbabwe Cognitive impairment Impaired cognitive function at 69 y.o. Guerrant et al., 1999 Early childhood diarrhea by McCarthy Draw-A-Design (02 y.o.)
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From page 87... ...
(TONI-III) scores at 610 y.o., when controlling for maternal education, breast feeding duration, and early helminthic infections; and WISC coding and digit span scores were lower in children who had one or more persistent diarrheal illnesses in their first 2 years of life.
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From page 88... ...
We conclude that the higher frontal lobe executive functioning impairment seen at 612 years old associated with diarrhea in the first 2 years of life, especially with impaired schooling, growth and cognition, suggest that early childhood diarrhea results in critical neurodevelopmental impairment that greatly magnifies the importance of ameliorating these diarrheal illnesses and their long-term consequences. These potential consequences of early childhood malnourishing and dehydrating diarrheal illnesses should not be a great surprise when one considers the importance of early childhood years in human brain development (Dobbing, 1985; 1990; Dobbing and Sands, 1985; Niehaus et al., 2002)
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From page 89... ...
The potential impact of these still common early childhood diarrheal illnesses on long-term development or disability only further adds to their morbidity costs. Refining DALYs for Diarrheal Disease As shown in the first row of Table 2-2, following the standard formulas with age-weighting and discounting at 3 percent, and all disability falling into the lowest class (weight of 0.096)
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From page 90... ...
Considered differently, for every 5 percent of children affected lifelong, DALYs increase by about 100 million; 25 percent of children affected would increase current DALY estimates by over six-fold; only 5 percent affected lifelong (or 10 percent affected for only 25 years) would more than double the total global diarrhea DALYs (Guerrant et al., 2002a)
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From page 91... ...
The American Journal of Tropical Medicine and Hygiene 61:707713. Guerrant RL.
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From page 92... ...
The American Journal of Tropical Medicine and Hygiene 66:590593. Nokes C and Bundy DA.
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From page 93... ...
. The range of risk factors for the development of epilepsy varies with age and geographic location (Sander, 2003)
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. Indeed, poor sanitation and malnutrition are risk factors for infections and these are common in low-income countries.
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. There is, however, no objective information on the relative distribution of risk factors or attributable risk for the epilepsies in the community in most of the world and this is an area that requires urgent research (Sander and Shorvon, 1996)
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From page 96... ...
Five to ten percent of survivors of acute bacterial meningitis will develop chronic epilepsy and this is usually associated with learning deficits and other neurological disabilities (Marks et al., 1992; Bittencourt et al., 1999; Oostenbrink et al., 2002)
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From page 97... ...
IMPLICATIONS FOR DEVELOPING COUNTRIES 97 falciparum malaria and may have severe consequences. Survivors are at high risk of neurological disabilities including epilepsy (Waruiru et al., 1996; Molyneux, 2000; Versteeg et al., 2003)
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From page 98... ...
Studies are urgently needed to elucidate the whole spectrum of attributable risk factors for epilepsy. More research is also needed to understand the molecular basis of all epilepsies particularly the ones caused by infectious agents.
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From page 99... ...
Infectious causes of developmental disabilities thus take a major and potentially unavoidable toll on the population health and economies of low-income countries today. This paper reviews some of the major infectious causes of develop
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From page 100... ...
The most severe outcomes generally result when conception occurs during the early stages of maternal syphilis infection. Outcomes are less severe when conception occurs during the latent state of maternal infection, and clinical manifestations of congenital syphilis are thought to be least severe when onset of maternal infection occurs during the third trimester of pregnancy (Wicher and Wicher, 2001)
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From page 101... ...
Congenital Rubella Congenial rubella leads to a range of adverse pregnancy outcomes or birth defects but only when maternal rubella virus infection occurs within the first 18 weeks of pregnancy. Outcomes include fetal death, spontaneous abortion, stillbirth, premature birth and, among surviving infants, sensorineural deafness, cataracts and other visual impairments, mental retardation, autistic features, cardiac defects, and increased susceptibility to juvenile diabetes and other chronic conditions (Peckham and Newell, 2001)
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From page 102... ...
. Mother-to-Child Transmission of HIV and Herpes Viruses This is an emerging cause of developmental disabilities in populations where high HIV prevalence among childbearing women is combined with lack of access to antenatal antiretroviral therapy and cesarean delivery, which in combination are highly effective in preventing vertical transmission of HIV (European Mode of Delivery Collaboration, 1999; International Perinatal HIV Group, 1999)
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From page 103... ...
Research is urgently needed on the role of maternal infections in the etiology of adverse perinatal outcomes; on the causal role of infections in developmental disabilities; and on the impact of infection treatment and control on the prevalence of neurodevelopmental disabilities in low-income countries. Infections During Infancy and Childhood Infections acquired during infancy and childhood that continue to cause developmental disabilities among children in low-income countries, where access to prophylaxis and treatment is often limited and delayed, include neonatal infections (Wolf et al., 1999; Durkin et al., 2000)
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From page 104... ...
The cost-effectiveness of malaria prophylaxis and treatment programs is well established in populations where malaria is endemic, even without accounting for the potential for long-term neurological deficits in children who survive cerebral malaria. Other parasitic diseases, such as intestinal helminthic diseases, also affect a large proportion of the world's child population and may adversely affect school performance and cognitive development (Dickson et al., 2000)
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From page 105... ...
. Measles Measles is an acute viral disease that is still a leading cause of death worldwide, largely because of its occurrence among children under age 5 in developing countries.
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From page 106... ...
Specific interventions should be tailored to local epidemiology and resources and needs, and should include vaccination programs with high coverage to prevent conditions such as congenital rubella, bacterial meningitis and poliomyelitis, development of laboratory facilities and networks to facilitate accurate diagnoses, and commitment of resources to prevent other infectious diseases, such as pediatric AIDS, malaria, neurocysticercosis, leprosy, viral encephalitis, and trachoma. Additional recommendations articulated in the Institute of Medicine report on
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From page 107... ...
5. Support research on factors that are crucial to understanding how to prevent developmental disabilities in low-income countries, such as the etiology and prevention of adverse perinatal outcomes and the impact of maternal education and alleviation of poverty on the prevention of infections resulting in developmental disabilities.
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From page 108... ...
1999. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1: a meta-analysis of 15 prospective cohort studies.
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From page 109... ...
2001. Maternal and congenital syphilis in Bolivia, 1996: prevalence and risk factors.
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From page 110... ...
An area is called endemic for HTLV-1 if 210 percent of the healthy adult population is infected. The islands of Kyushu and Okinawa, in southwestern Japan, are hyperendemic areas for HTLV-1, 15 percent of the healthy adult population carry the virus (Blattner, 1990)
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From page 111... ...
. HTLV-1-related disease in mothers may also be associated with the increased risk of transmission of the virus to their children, as suggested by a recent study which found that HTLV-1 is present in 43 percent of children born from mothers with strongyloidiasis, and 20 percent of children born from mothers with tropical spastic paraparesis (p < 0.01)
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From page 112... ...
Classical complications include lymphoproliferative disorders, such as Adult T-cell Leukemia/Lymphoma (ATLL) and autoimmune disorders (Tropical Spastic Paraparesis)
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Tropical Spastic Paraparesis The general term "tropical spastic paraparesis" (TSP) was introduced by Mani et al.
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From page 114... ...
. A combination of corticosteroids, antiretroviral drugs, and rehabilitation might considerably improve the quality of life of TSP patients -- particularly if treatment is started early in the course of the disease in those cases with rapid progression (Araujo et al., 1995)
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From page 115... ...
In a study in 6 hospitals in Lima, Peru, 23 patients were diagnosed with Norwegian scabies over 19 months. Seventy percent of patients were serologically confirmed to have HTLV1 infection; 9 percent were on long-term oral corticosteroid treatment; 1 patient had Down's syndrome; 2 patients were chronically malnourished; and 2 patients had no known risk factors for crusted scabies.
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From page 116... ...
is adversely affected by HIV infection. Similarly, in a Brazilian study, patients with TB and HTLV-1 exhibited a worse clinical course and a poorer prognosis than those without HTLV-1.
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From page 117... ...
1985. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis.
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From page 118... ...
American Journal of Tropical Medicine and Hygiene 60:146149. Gradilone A, Zani M, Barillari G, Modesti M, Agliano AM, Maiorano G, Ortona L, Frati L, Manzari V
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From page 119... ...
American Journal of Tropical Medicine and Hygiene 56:561 565.
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From page 120... ...
. As HCV-specific cellular immune responses are present in chronic infection, the other consideration is that the cytokine response may be qualitatively different in individuals with chronic infection as compared with acute resolved HCV.
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From page 121... ...
CD8 Response to HCV Infection The CD8+ T-cell response is thought to play a crucial role in the course of HCV infection. In humans and in chimpanzees, a strong and broadly directed HCV-specific CTL response has been associated with viral clearance during acute HCV infection.
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From page 122... ...
. Patients with concomitant HCV and schistosomiasis exhibit a unique clinical, virological, and histological pattern manifested by virus persistence with high HCV RNA titers, higher necroinflammatory and fibrosis scores in their liver biopsies and poor response to interferon therapy (Kamal et al., 2000a; Angelico et al., 1997; Pereira et al., 1995; Kamal et al., 2000b)
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From page 123... ...
. Immune responses during the first few months of acute HCV infection seem crucial for viral control, but the relationship of these responses to natural history is poorly characterized.
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From page 124... ...
The American Journal of Tropical Medicine and Hygiene 62:8899. Gerlach T, Diepolder H, Jung M, Gruner N, Schraut W, Zachoval R, Hoffman R, Schirren A, Santantonio T, Pape G
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From page 125... ...
The American Journal of Tropical Medicine and Hygiene 62:7379. He XS, Rehermann B, Lopez-Labrador FX, Boisvert J, Cheung R, Mumm J, Wedemeyer H, Berenguer M, Wright TL, Davis MM, Greenberg HB.
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From page 126... ...
Immune activation leads to up-regulation of viral co-receptors, decreased chemokine secretion, enhanced viral entry and integration, viral assembly and/or release of the viral particles, changes in the cytokine environment and various degrees of immune dysfunction, hyporesponsiveness, and apoptosis. Because all systemic and/or local concurrent infections cause various degrees of immune activation, it is very likely that they may enhance HIV infection, increase HIV replication and viral load, and even promote progression of the disease.
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From page 127... ...
A recent study conducted in western Kenya indicated that although a standard two-dose S/P regimen worked well in controlling peripheral parasitemia and placental malaria during pregnancy in HIV-negative women, it failed to prevent peripheral and placental parasitemia in HIV-infected women. Poor response to S/P antimalarial treatment was also reported in pregnant Malawian women with HIV-1 infection.
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From page 128... ...
. Cellular immune responses to malaria are seemingly also affected by HIV-1 infection.
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From page 129... ...
. Preliminary studies conducted with PBMC from HIV-positive individuals residing in western Kenya indicated that recall immune responses induced by soluble malarial antigens can increase HIV-1 replication (Xiao et al., unpublished observation)
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From page 130... ...
From a mechanistic point of view, however, a common thread that seems to tie this interaction together is immune activation induced by infectious agents prevalent in malaria-endemic areas. Therefore, removing risk factors of immune activation (i.e., co-infectious agents)
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1991. Antimalarial antibody in relation to seroreactivity for HIV infection in sera from blood donors.
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Fever associated with primary HIV infection masqueraded as malaria Likely outcome 1. Increased prevalence of peripheral malarial parasitema and placental malaria Mother 2.
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From page 133... ...
chemokine receptors Possible effect 1. Increased susceptibility of mononuclear cells to HIV infection 2.
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From page 134... ...
1994. Immunologic cross-reactivity between structural proteins of human T-cell lymphotropic virus type I and the blood stage of Plasmodium falciparum.
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