Tropical Diseases: An Overview of Major Diseases Occurring in the Americas

The Trypanosomatidae family is composed by protozoan parasites responsible for causing a variety of human and non-human diseases, of varying gravities, in both new and old worlds. The distribution and adaptation of the trypanosomatids in tropical and subtropical countries, as well as the usual habitats of vectors commonly favour contamination of poor neglected populations, despite the increasing expansion to peri-urban and urban areas, thus reaching other social and economic realities. Illnesses like leishmaniasis and American trypanosomiasis (or Chagas disease) share the fact that both have a great diversity of reservoirs associated to the cycle of the parasites, which include synanthropic mammalians and the Homo sapiens itself. Therefore, to an efficient epidemiological control, the continuous search for new human cases, as well as the monitoring and controlling of infected animals is fundamental. The laboratorial techniques routinely used for detection of these diseases may vary from simple parasitological analysis to cutting-edge molecular technology. Due to its easiness and diagnostic sensitivity, the immunology/serology is broadly applied in the laboratories and also in field, even with its limitations. The molecular biology and its tools are emerging as sensitive and specific alternative strategies for the trypanosomiasis diagnosis, but some challenges still remain, especially concerning the standardization of protocols and the establishment of gold-standard procedures. New serological and molecular methods arise annually aiming to overlap deficiencies that may reduce the feasibility for applying in routine and in epidemiological researches. In this chapter, the past and current diagnostic situation of leishmaniases, Chagas disease and Human African trypanosomiasis (HAT) or “sleeping sickness” will be described, highlighting the technological advances and the difficulties to be faced for the next years, mainly regarding the applicability for public health.

Trypanosomatids parasites are causative agents of important neglected tropical diseases, such as leishmaniasis and Chagas disease. In the absence of an effective and safe vaccine, the main strategies currently available for the control of these diseases are chemotherapy whit drugs limited by their cost, toxicity, long time of treatment, and by emergence of resistant parasites. Therefore, in silico methods have arisen in the last years as powerful tools to optimize the search for new drugs and targets and for potential antigens for vaccines. In this context, the aim of this chapter is to provide the reader with important tools in use for drug design, particularly for molecular docking and epitope prediction for vaccines, in order to make useful to put this concepts and approaches in practice. All these tools should be applied in the fight against trypanosomatids.

The control of diseases caused by trypanosomatids, such as those caused by Leishmania spp. and Trypanosoma cruzi, is focused on the use of drugs to treat infected patients, which are limited by their high cost, high toxicity and safety concerns, in the absence of an effective and safe vaccine for use in humans. Therefore, new strategies for vaccines have emerged in the last years and better perspectives for the future are expected. In this context, the aim of this chapter is to discuss the past, present and future of vaccines against Leishmania spp. and Trypanosoma cruzi. In addition, we indicate important aspects for the development of anti-trypanosomatids vaccines.

Leishmaniasis and trypanosomiasis are challenges among neglected tropical diseases. They usually affect marginal and poor populations and have the potential of becoming lethal. Current treatment for both diseases is based on chemotherapy, with the drug of choice being pentavalent antimonials for leishmaniasis, while for Chagas disease the two nitro-heterocyclic drugs, Benznidazole and Nifurtimox are recommended. The limited number, low efficacy, and side effects of conventional anti-Leishmania and anti-Trypanosomal drugs and the resistance developed by parasites are the major factors responsible for the growth in mortality rates. Currently there is an urgent need to develop effective, safe, cost-effective drugs, and new treatment schemes, as well as vaccines. As a result, international health organizations, universities, foundations, and pharmaceutical corporations are working together to support analysis and development of new strategies for controlling these diseases.

Schistosomiasis is considered a neglected tropical disease and remains a major public health problem throughout the tropics and subtropics with significant socioeconomic impact. More than 200 million people are infected worldwide. Within schistosomiasis, the specie Schistosoma mansoni is a major cause of this parasitic disease in developing countries and has been associated with high morbidity and mortality during both acute and chronic phases of infection. For the diagnosis of schistosomiasis mansoni, the gold standard is used for the detection of parasite eggs in stools. However, in patients with low parasite infection burdens, the direct detection of eggs is difficult owing to its low sensitivity. For this reason, serological tests are used to detect secreted S. mansoni antigens or antibodies produced to combat adult worm or soluble egg antigens. However, these assays are unable to differentiate between the different phases, which is necessary to follow up the evolution of the disease and chemotherapy efficacy. Research into other diagnostic tests has shown ways of overcoming the problems inherent to antibody detection and parasitological techniques in moderately to marginally endemic areas. Other techniques, such as polymerase chain reaction assays, have been considered as methods for the diagnosis of S. mansoni infections in different samples: stool, serum and urine. In this chapter, imaging methods are used not for the diagnosis of schistosomiasis as a disease, but for the diagnosis of morbidity, identifying the changes caused by Schistosoma mansoni infection in the human organism.

Fungi are responsible for approximately 10% of nosocomial infections, with Candida spp. being the most prevalent etiological agent. Immunocompromised individuals are more susceptible to fungal infections. An early determination of the etiology of the infection is extremely important for these patients because it provides valuable information for choosing the best therapeutic scheme and may increase the chances of recovery. Due to the low sensitivity of direct examination, the determination of the etiology of a fungal infection often requires culture of biological specimens for isolation and identification of the disease causative agent. Blood culture is not effective for diagnosis of invasive fungal infections, even when serial specimens are analyzed. Serological identification of fungal cell wall proteins (galactomannan, mannan, β-glucan) are considered the first line diagnosis of invasive fungal infections; however, it has low sensitivity because the antigens are rapidly removed from the bloodstream. Molecular biology diagnostic methods have been developed as an alternative for the - detection of fungal infections that are difficult or impossible to detect by conventional microbiological and serological methods. In this chapter, we provide an up-to-date review of nosocomial fungal infections, focusing on the occurrence, etiology, risk factors, clinics, as well as the conventional and molecular methods of diagnosis. We also discuss the use of molecular markers for the detection of fungal infection.

The virulence pattern and the difficulties encountered in the diagnosis and treatment of many bacterial infections have turned its dissemination a serious problem of public health. It is essential, for an effective antimicrobial therapy, to have a precise and early diagnosis, thereby decreasing the risk of severe and fatal cases. However, many difficulties are found in conventional bacteriological diagnostic techniques due to several factors: loss of bacterial viability, delay in bacterial cultivation and the antibiotic therapy prior to the exam. The molecular biology methods are valuable tools, especially in the case of serious infectious diseases. These technologies have the ability to detect infectious agents with greater sensitivity and specificity without the need of viable parasites in the biological sample, such as the polymerase chain reaction (PCR) and its variations, the DNA microarray technology and proteomics analyzes. Some of these methods are already available in laboratories, especially those in the private network. However, the interpretation of the results requires differing and deep levels of knowledge, imposing the need for training human resources in order to get a wider dissemination and exploitation. This chapter describes the characteristics, pathogenicity, epidemiology and methods of laboratory diagnosis of significant bacterial infections and the achievements in molecular biology, which may be part of future routine diagnostic tests and thus, contribute to the prevention and control of infectious processes.

Geohelminths infections are a group of nematodes worms that are transmitted to human by ingestion of eggs or larvae penetration after contact with contaminated soil. The main species that infect people are the Ascaris lumbricoides, Trichuris trichiura, Necator americanus and Ancylostoma duodenale. Geohelminth infection has been shown to have a significant impact in modulates others pathologies. These parasites might enhance the survival modulating the immune response of their host inducing a regulatory response. This chapter is a review of the recent literature about the host immune response against geohelminths and the potential effect of these infections on non-parasite immune response.

Malaria remains a major health problem with 0.58 million of deaths in 2013. Malaria pathogenesis involves complex molecular interactions between parasite and host that lead to a wide variety of clinical symptoms. Among people living in endemic regions, only a fraction of infected people develops severe disease such as cerebral malaria, severe anemia and respiratory distress. This inter-individual variability may be explained by the parasite genetic diversity and the host genetic susceptibility. Children are susceptible to malaria disease and death until they develop an adaptive immunity after multiple exposures to parasite during their childhood. Several host genetic factors that may alter this immune response have already been identified. However, the molecular aspects are not fully understood and a major challenge is to identify these factors to progress in the understanding of the pathophysiological mechanisms and to propose new therapeutic strategies.

Several strategies to combat the impact of malaria infection are used with certain success. Those efforts resulted in a 25% reduction in the incidence and a 42% reduction of global mortality. Nevertheless, malaria still causes 584,000 deaths worldwide. The epidemiological situation of the area and the risks of malaria reintroduction in non-endemic areas are decisive factors for the control and diagnosis. The resilience of mosquito infection should be considered in the programs’ strategies for malaria control. An integrative approach focused on diagnosis and prophylaxis is needed to achieve a better control. Regarding diagnosis, the blood smear exam is the golden standard diagnosis for malaria; although blood smear has its advantages, it needs the expertise of a microscopist and can produce false negative results in low parasitemia situations. Molecular diagnosis methods have permitted an increase in sensitivity and specificity of Plasmodium detection. The major approach used was the parasite DNA amplification by PCR, allowing the species-specific parasites’ detection. Recently, detection of Plasmodium falciparum employing the LAMP method or biosensors has brought a perspective of lower cost and sensitive malaria diagnosis tests. Besides, molecular biology techniques are versatile tools to detect malarial resistance and studies aiming to characterize Plasmodium genetic markers of resistance and treatment failure are necessary at individual and population levels. Among the approaches to control malaria, vaccine development still poses an attractive idea. The improvements achieved on the diagnosis and vaccine fields represent a fundamental move for effective malaria control. Herein we discuss recent advances and obstacles on diagnosis and vaccine approaches developed for the control of malaria infection.

Dengue is a viral disease of leading public health impact worldwide. Transmitted by bites from infected Aedes spp. mosquitos, dengue virus (DENV) infections cause a wide range of clinical manifestations, including asymptomatic infection, dengue fever (DF), and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The pathogenesis of its most severe form, DHF/DSS, is not fully understood. With no licensed vaccine or specific antiviral therapy available, dengue prevention depends heavily on vector control efforts, which have proven difficult. Molecular and immunological tools have been indispensable to the development of DENV vaccine candidates, the identification of immunological correlates of protection, the early detection of disease prognosis and a better understanding of dengue pathogenesis. This chapter reviews the efforts, challenges and recent progress in the field towards dengue treatment and prevention.

Hepatitis A virus (HAV) infection is the most frequent cause of viral hepatitis worldwide. HAV belongs to the Picornaviridae family in the genus Hepatovirus. The genome of HAV is a positive-sense single-stranded RNA that is approximately 7.5 kb in length. In fact, HAV is classified into six genotypes: three isolated from humans (I–III) and three of simian origin (IV–VI). Worldwide, genotype I is the most prevalent, particularly subgenotype IA. A diagnosis of hepatitis A can be performed by detection of anti-HAV IgM and IgG antibodies by enzyme immunoassay or HAV RNA detection by nested-PCR. Hepatitis A is transmitted principally via the fecal-oral route, including person-to-person contact and the ingestion of water or food that is contaminated by the feces of infected individuals. HAV infection is usually selflimited and benign, with no symptoms, but a severe form of the disease, fulminant hepatitis, affects approximately 1% of the patients who are hospitalized for hepatitis A. In Latin America, several seroprevalence studies have demonstrated an epidemiological shift in HAV infection from high towards intermediate endemicity levels. In Brazil, a large number of children under five years of age (74.1-90%) have been found to be susceptible to HAV infection in 3 capitals of the North, Midwest and Southeast region of Brazil. There is no specific treatment for hepatitis A. Therapy should be supportive and aimed at maintaining an adequate nutritional balance.

The most effective measure for the control of hepatitis A virus (HAV) infection is to prevent fecal contamination of the hands, food and water. One preventive measure is the administration of immunoglobulin (IG) within 2 weeks after HAV exposure, which leads to effective protection in 85% of infected individuals. Currently, there are two main types of hepatitis A vaccine: live attenuated virus and inactivated virus vaccines. Live attenuated virus vaccines are weakly immunogenic when administered orally or parenterally, only one injection is administered, and they are licensed in China and Russia. Inactivated vaccines employ purified, formalininactivated, whole viruses that are produced in cell culture, are highly immunogenic and protect against both infection and disease. Inactivated vaccines can be monovalent or combination (HAV-HBV vaccine or HAV-typhoid vaccine). Monovalent vaccination regimens include two doses at an interval of 6 to 18 months between injections, with the first administered at 12 months of age. Nearly 100% of immunocompetent patients present immunity one month after receiving the recommended two doses, and adequate antibody levels could persist for 25 years or longer in adults and for 14 years or longer in children. The CDC recommends HAV vaccination according to the prevalence and incidence of hepatitis A. Some countries have introduced the HAV vaccine in childhood immunization calendars, leading to a decrease in the incidence of HAV. In Brazil, a single dose of HAV vaccine is recommended for children at 12-23 months of age by the health care system immunization program.

The hepatitis B virus is a hepatotropic agent belongs to the hepadnaviridae family. He is responsible for 350 million infections worldwide and is estimated two billion people have been infected. However, after implementation of universal HBV vaccination in infants occurred to decrease prevalence in many parts of the world. Their transmission occurs by cuts in skin and mucosa, unprotected sex and parenterally, sharing needles and syringes, tattoos, piercings, dental or surgical procedures.

Viral hepatitis are the major cause of liver transplants in the world - especially for hepatitis C (HCV) disorder that now affects over 185 million people in every continent. Initially known as hepatitis non-A non-B HCV was elucidated in 1989 as an etiologic agent. Since then HCV infection acquired special importance among the causes of liver disease particularly among HIV patients on antiretroviral therapy which presents significant morbidity and mortality from liver disease. The natural history of HCV is characterized by a silent evolution often the disease is diagnosed decades after the infection and usually in advanced stage. Hepatitis C has an important impact on global public health accounting for approximately 350,000 deaths per year.

Tuberculosis is a major public health problem in many regions of the world, accounting for up to 2 million deaths per year. The main causative agent of tuberculosis is Mycobacterium tuberculosis, which usually infects the lungs, causing symptoms such as fever, cough and chest pain. After infection, the bacilli can be cleared by a healthy immune system or, on the other hand, the infection may lead to latent tuberculosis or progress to active pulmonary tuberculosis. Moreover, in certain situations, such as cases of immunocompromised patients, these bacilli can spread through the lymphatic or hematogenous route to more distant organs, leading to extrapulmonary tuberculosis. Approximately 30% of the population worldwide has latent tuberculosis and 5 to 10% of individuals infected with M. tuberculosis progress to active tuberculosis disease. Although tuberculosis is a curable disease, some factors have been associated with the morbidity and mortality of global tuberculosis, including inadequate detection, increased abandonment rate of anti-TB treatment, co-infection with human immunodeficiency virus, increased drug resistance and inefficiency of the BCG vaccine in preventing the disease in adolescents and adults. New tools are therefore urgently needed to control tuberculosis. Knowledge of the molecular characteristics, immune response and pathogenesis of M. tuberculosis are essential for the development of new approaches to diagnosis, drugs and vaccines to assist in the clinical management and control of the disease. This first chapter on tuberculosis describes the epidemiological, immunological and clinical aspects of the disease, as well as the microbiologic and molecular characteristics of M. tuberculosis.

Tuberculosis (TB), which is one of the infectious diseases with highest mortality in the world, remains the second most common cause of death. More than 30% of the worldwide population has latent infection caused by Mycobacterium tuberculosis (Mtb). This large number of Mtb infected people hinders worldwide control of TB. Diagnosis of TB is a challenge because the clinical signs and symptoms are nonspecific and radiological tests are non-sensitive and/or unspecific. Sputum smear microscopy is the most common laboratorial diagnostic test used to confirm TB, but it has low sensitivity, varying from 30% to 60%. Culture in solid medium is considered the gold standard method for the diagnosis of TB, but the results can take up to 8 weeks. There is therefore a need to develop a fast and more accurate diagnostic test for TB. There are some alternative diagnostic tests for TB using immunological and molecular technologies. Studies which evaluated the performance of molecular biology tests indicate that the diagnostic methods for TB are improving and resulting in rapid detection of Kock’s bacilli directly from biological samples. Molecular biology based methods can detect the DNA of M. tuberculosis and also the genes which cause resistance to drugs and they could detect MDR-TB early. However, in paucibacillary forms of disease, as pulmonary TB with smear-negative, extrapulmonary TB, childhood TB and immune-compromised patients, the most molecular tests are unable to diagnose the disease. In latent TB infection (LTBI), the tuberculin skin test (TST), an old test used, remains the method for detecting the infection, but has some limitations. Recently, the development of in vivo T-cell-based interferon-gamma release assays (IGRAs), which are more specific to M. tuberculosis than the TST, is currently being proposed to diagnose LTBI. However, early detection of M. tuberculosis by antigen or antibody is difficult. There are some serological assays, using specific antigens to detect circling antibodies in development to increase their sensitivity. These tests are generally simple, rapid and not too expensive compared to molecular tools. Some studies have shown that serological diagnosis methods varygreatly in accuracy. Because of this, advances in immunological and molecular diagnosis tests must be made to increase the accuracy of detection of pulmonary and extrapulmonary TB and latent TB infection, mainly in regions with high prevalence of this disease. The early detection of TB enables the initiation of specific treatment and helps to break the transmission chain. However, new immunological and molecular tools still need validation in order to be implemented in national TB control programs. This chapter reviews and discusses new molecular and immunological diagnostic tests for TB and the recent advances in TB detection.

The introduction of antibiotics for the treatment of tuberculosis (TB) represented a major advance in the fight against the disease. Drug treatment is fundamental for controlling TB, promoting the cure of the patients and breaking the chain of transmission, when the anti-tuberculosis drug regimen is followed completely and correctly. Currently, the therapy of tuberculosis is performed with first-line antituberculosis drugs and some second-line drugs. However, the increased incidence of multidrug-resistant tuberculosis strains, and the association of HIV infection for tuberculosis patients, increase the problems associated with the currently available treatment of TB. The development of new anti-tuberculosis drugs with new mechanisms of action that allows shorter treatments and more effective, less toxic, with fewer side effects, is urgently required. In this chapter, we describe the current treatment regimens for tuberculosis, together with a description of the major antituberculosis drugs, their toxicity properties and pharmacological, still presenting new substances which are in advanced stages of clinical phase.

Tuberculosis remains a public health problem in many regions of the world. It has been a major cause of morbidity and mortality. Currently, Mycobacterium bovis bacillus Calmette Guerin (BCG) is the only vaccine which is used to control the spread of M. tuberculosis infection in humans. However, this vaccine provides a limited protection against tuberculosis in children. In endemic regions, BCG could not protect adolescents and adults against M. tuberculosis infection nor prevent evolution to active disease. Therefore, the development of new vaccines to increase the efficacy of vaccination against tuberculosis is urgently required. Currently, there are several preclinical and clinical studies of vaccine candidates. The spectrum of candidates includes multiple types of subunit vaccines, mycobacteria’s whole cell or extracts vaccines, live attenuated mutants, vaccines based on delivery by viral vehicles and new forms of recombinant BCG itself. This chapter reviews the efficacy and failure of the BCG, and vaccine candidates under clinical development in humans, including those developed to replace BCG (prime vaccines), to improve immunity promoted by BCG (prime-boost vaccines), and to decrease the time of chemotherapy (immunotherapeutic vaccines).

Bioinformatics is an interdisciplinary field that combines elements of the areas of biological sciences and computing, which has become fundamental in health science research. Bioinformatics is based on the development and application of computational tools to extract knowledge from biological data and to solve real-world problems in human health, which contributes to the diagnosis and control of infectious diseases. Much of the biological information is obtained through comparison of genomic sequences. Currently Next-Generation-Sequencing provides a wide genetic database which overcomes Sanger sequencing. Nitrogenous bases are identified by signals emitted for each fragment of DNA strand that it occurs through large massive reactions. In this context, sequence alignment methods are relevant. Evolutionary and functional patterns could be extracted from multiple sequence alignments, which could point to molecular markers, receptors, or targets that could be important to develop control measures of several diseases. Bioinformatics could also be applied in proteomic and transcriptomic studies, increasing the knowledge at the molecular biology level of protozoa and transmission vectors. Therefore, Bioinformatics tools are relevant to gather information about Neglected Tropical Diseases, and so, novel control methods could be tested and developed.