This book evolved from the editors strong belief that the information and new developments that were evolving from the rapidly growing field of genomics and that are happening primarily in the develop
Species of the genera Trypanosoma and Leishmania are protozoan parasites responsible for a series of neglected tropical diseases. The people most affected by these parasites are the poorest living in tropical and subtropical regions of the world. Two subspecies of Trypanosoma brucei, T. b. gambiense and T. b. rhodesiense, are the causative agents of human African trypanosomiasis or sleeping sickness. Millions of people living in 36 sub-Saharan countries are at risk of acquiring the disease.(WHO 2010a) Due to increased control over the last decade, the number of reported cases has declined to under 10,000 in 2009 for the first time in 50 years (WHO 2010a). For chemotherapy, only four drugs (suramin, pentamidine, melarsoprol and eflornithine), of which three were developed >60 years ago, and one drug combination therapy (eflornithine/nifurtimox) are available (WHO 2010a; Steverding 2010). In addition, all drugs have major drawbacks including poor efficacy, significant toxicity, need for parental administration and drug resistance (Fairlamb 2003; Matovu et al. 2001; Delespaux and de Koning 2007).
Since the nine genes of a bacteriophage were first sequenced in 1977 (Sanger et al. 1977), genomics research has transformed the study of genetics and has stimulated the emergence of an ever-lengthening list of new research specializations, including computational genomics, bioinformatics, metagenomics, pharmacogenomics, structural genomics, and more. The much-heralded publication of the human genome in Nature (Feb. 15, 2001) and Science (Feb. 16, 2001) marked not only a major advancement of knowledge but also a fundamental change in how biological research is done (Butler 2001). It has been noted that “When historians look back at this turning of the millennium, they will note that the major scientific breakthrough of the era was the characterization in ultimate detail of the genetic instructions that make a human being” (Collins and Jegalian 1999).
Africa currently faces several opportunities and challenges in terms of genomics research. The continent harbors the richest biodiversity to provide fertile ground for harnessing genomics. On the other hand, it bears the heaviest burden of human diseases (both infectious and chronic) and the effects of climate change, pests, and diseases on native crops and livestock. In spite of the challenges, genomics research and the associated products stand to significantly benefit the region. By adopting genomics research, African researchers can tap into the rich continental diversity, embrace personalized medicine as well as establish crops and livestock breeds with desirable traits. These benefits will not come at an easy cost but the continent has an opportunity to learn from middle-income countries such as Mexico and Brazil that embraced the genomic revolution in a timely fashion. Hence the region should search for homegrown solutions, foster mutually beneficial collaboration, and invest substantially in genomics research.
Despite the steady decline in the global prevalence of leprosy, over 250,000 cases still appear every year, mostly in developing countries. Genomics showed that Mycobacterium leprae, the causative agent of the disease, represents an extreme case of reductive evolution since its 3.27-Mb chromosome has ∼1,300 pseudogenes. This formidable human pathogen cannot be cultured on artificial media, thus limiting our understanding of the disease pathogenesis, transmission, and control. There exists very little genetic variation among M. leprae strains, and the seven sequenced genomes exhibit over 99.995% identity, despite being from diverse geographic origins. The decrease in case numbers will negatively impact clinical expertise toward accurately diagnosing and treating leprosy, making it very important that efficient diagnostic and genotyping tools become available. The genomics of M. leprae has provided useful insights into its enigmatic biology and has helped develop promising immunological and nucleic-acid-based tools for more efficient and sensitive diagnosis. Comparative genomics of various M. leprae strains has been useful in developing robust and reliable molecular epidemiological tools to monitor the transmission dynamics of the disease, and efficient molecular drug susceptibility tests have been developed and implemented. In order to reduce the new case detection rate and disease transmission, further efforts are required to develop field-applicable, cost-effective tools which could diagnose all forms of leprosy at an early stage and be used in resource-limited settings.
Malaria is a disease caused by parasites from genus Plasmodium, a member of the Apicomplexan family. Apicomplexans are unique in that they are the only fully parasitic large clade on the tree of life. It is thought that every type of mammal, bird, and reptile is parasitized by at least one species of Plasmodium (Morrison 2009). Five Plasmodium species infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi, which until recently was thought to infect only nonhuman primates (Cox-Singh et al. 2008). P. falciparum and P. vivax are the most prevalent species, and P. falciparum is responsible for most cases of severe malaria and death. A key feature of Apicomplexans is that these eukaryotic organisms exist mainly in a haploid state with most having only a brief obligatory diploid phase. Another difference is the apicoplast, a plastid believed to have originated from the phagocytosis of a chloroplast-containing microorganism (Waller and McFadden 2005).
In recent decades, many infectious diseases have significantly increased in incidence and/or geographic range, in some cases impacting heavily on human, animal or plant populations. Some of these 'emerging infectious diseases' are associated with pathogens that have appeared in populations for the first time as a result of cross-species transmission (e.g. human immunodeficiency virus—acquired immunodeficiency syndrome (HIV-AIDS), severe acute respiratory syndrome (SARS)), while others were previously known but are rapidly increasing in incidence or geographic range as a result of underlying epidemiological changes (e.g. multi-drug resistant Staphylococcus aureus (MRSA) infection, dengue, West Nile encephalitis, foot and mouth disease, cassava mosaic disease). The latter include prominent diseases as tuberculosis, malaria and yellow fever that were once on the decline but are now 're-emerging diseases'.
Effective chemotherapy for tuberculosis (TB) was developed and evolved during the late 1940s through the early 1970s. For many years, isoniazid (INH) and para-aminosalicylic acid (PAS) for 18–24 months with streptomycin during the initial several months were standard therapy (Fox 1968; Indian Council of Medical Research 1963). This regimen was replaced by a 9-month regimen of INH and rifampin (RIF) supplemented with either ethambutol or streptomycin during the initial 2 months (Fox and Mitchison 1975; British Thoracic and Tuberculosis Association 1976). It was later found that the length of therapy could be decreased to 6 months with the addition of pyrazinamide (PZA) during the initial 2 months of therapy with INH and RIF (Singapore Tuberculosis Service/British Medical Research Council 1991; British Thoracic Association 1981). The recent emergence of multidrug-resistant (MDR – resistance to at least INH and RIF) and extensively drug-resistant (XDR – resistance to INH and RIF plus resistance to a fluoroquinolone and one or more of the injectable drugs: kanamycin, amikacin, and capreomycin) strains of TB has increased the need to discover and develop new and improved therapies for this disease. The so-called second-line TB drugs are less effective than the primary agents, and a higher incidence of adverse reactions occurs with their use. Therapy for MDRTB usually consists of a quinolone (e.g., moxifloxacin) and three to four other agents including an injectable drug. Options for treatment of XDRTB are often quite limited particularly in resource-poor settings.
Vibrio cholerae, a bacterium autochthonous to the aquatic environment and introduced into the human intestine through contaminated water or food, is the etiological agent of the acute secretory diarrheal disease described as cholera. The pathogen has a free-living planktonic existence in aquatic bodies and has the ability to transmit into humans and cause disease. The process of completing an annual cycle in the environment and the transmission from contaminated water or food to humans is described as the ecology and epidemiology of the pathogen. This species contains a wide variety of both pathogenic and nonpathogenic strains. At the subspecies level, the organism is classified into more than 200 serogroups (Li et al. 2002). The differentiation of V. cholerae into serogroups is based on the differences in the sugar composition and therefore antigenicity of the heat-stable surface somatic “O” antigen. Only strains of serogroups O1 and O139 that produce cholera toxin defined as toxigenic strains have been recognized as agents of sporadic, endemic, epidemic, and pandemic cholera (Fig. 3.1) (Kaper et al. 1995; Sack et al. 2004). Most other serogroups of V. cholerae are not pathogenic or rarely cause local outbreaks, or mild gastroenteritis. V. cholerae strains belonging to serogroup O1 are further differentiated into two biotypes, classical and El Tor. The differentiation into biotypes is based on a combination of phenotypic, biochemical, and genetic traits, that include susceptibility to polymixin B, hemagglutination of chicken erythrocytes, hemolysis of sheep erythrocytes, the Voges–Proskauer test, susceptibility to phages, and nucleotide sequences of specific genes (Kaper et al. 1995). The other serogroups of V. cholerae, collectively called non-O1, non-O139, are not associated with epidemics and are ubiquitously distributed in the aquatic environment (Faruque et al. 1998).
Brazil is a megabiodiverse country with approximately 20% of the total number of described species on the planet (Mittermeier et al. 2004). It has the largest tropical forest cover (>6 million km2, corresponding to approximately 30 times the area of the United Kingdom or approx. 20 times the area of Germany) and one of the largest marine realms (>4 million km2) of the planet. The diversity of biomes (e.g., the Amazon and Atlantic Forests, Southern Plains or Pampas, Cerrado (a savanna-like vegetation), Pantanal (wetlands), Caatinga, coral reefs, oceanic islands, mangroves, salt marshes, coastal environments, and deep sea; (IBGE 2004)) allows for the diversification of a variety of life forms. Between 1999 and 2009, more than 1,200 new species of plants and vertebrates were discovered only in the Amazon region, corresponding to one new discovery every 3 days (WWF 2010). There is indeed a considerable amount of literature on the biodiversity of plants and animals in Brazil. Their diversity is used as a basic parameter in the implementation of management actions on priority areas for conservation and protection (Myers et al. 2000). Studies on the microbial diversity are comparatively much scarcer. For instance, only recently the microbial diversity of Amazon and Cerrado soils and the marine realm have been studied in a systematic way. The aim of this chapter was to establish an overview on the microbial diversity studies (N = 150) carried out in Brazil mainly in the last 5 years, including taxonomic studies based on cultured microorganisms and culture-independent studies based on molecular fingerprints and 16S rRNA clone libraries. The chapter focuses mainly on prokaryotes with environmental (e.g., coral holobionts), agricultural (e.g., crop promoting), and biotechnological importance (e.g., bioremediation).
Approximately 46% and 32% of deaths among children under five globally occur in sub-Saharan Africa and South Asia, respectively. Over 80% of the 4.2 million child deaths in Africa are caused by infectious diseases, sharply contrasted to Europe where 39% of the 0.15 million child deaths are attributable to infectious diseases (Fig. 5.1) (Black et al. 2010). Hence, despite the remarkable public health advancements in hygiene, sanitation, antimicrobial drugs and vaccine strategies of the twenty-first century, the burden of infectious diseases remains unacceptably high in the developing world.
The need for new and useful compounds and biological processes to provide assistance and relief in all aspects of the human condition is ever growing. Drug resistance in bacteria, the appearance of life-threatening viruses, and a tremendous increase in the incidence of fungal and drug-resistant bacterial infections in the world’s population, each only underscores our inadequacy to cope with these medical problems. Added to this are enormous difficulties in raising enough food on certain areas of the earth to support local human populations. Environmental degradation, loss of biodiversity, and spoilage of land and water also add to problems facing mankind. In addition, there is the need for bio-derived fuels to supplant the ever-growing demand for petroleum and petroleum products.
The contrast between applications of genetic testing in the developed and developing worlds is startling. In the United States, people pay to have their DNA tested for such trivial traits as earwax consistency and odor sensitivities, as well as phenotypes easily evaluated with a glance in the mirror, such as hair color, curl, and thickness; eye color; and freckles. In the developing world, testing for most single-gene disorders, let alone for trivial traits, takes a backseat to dealing with infectious diseases, with their high prevalence, morbidity and mortality, and the rapid pace of the pathology compared to that of the inherited diseases.
