key: cord-292604-x9amm87g authors: Rupali, Priscilla title: Introduction to Tropical Medicine date: 2019-03-31 journal: Infectious Disease Clinics of North America DOI: 10.1016/j.idc.2018.10.011 sha: doc_id: 292604 cord_uid: x9amm87g Tropical medicine deals with infectious and noninfectious diseases geographically located between the tropics of Cancer and Capricorn. It encompasses diseases that result from poverty, poor sanitation, infrastructure, and inadequate health resources. Lack of availability of clean water and food made with unhygienic practices add to the morbidity of these diseases. The tropics are reeling under the onslaught of climate change, deforestation, and air, water, and soil pollution, which worsens an already fragile health system. This article provides an overview of the definition, classification, geophysical problems, syndromic approach to common tropical infections, diagnostic challenges in the tropics, and access to medicines. Introduction to Tropical spanned many decades in China, Hong Kong, and Taiwan (then called Formosa). He eventually came back to London where he lectured on tropical diseases at the St. George's hospital. He then became the chief medical officer to the Colonial Office. At this point he used his considerable influence to found a school for tropical medicine at the Albert Dock Seamen's Hospital. The London School of Hygiene and Tropical Medicine was formally inaugurated on October 2, 1899. He eventually went on to become the first president of the Royal Society of Tropical Medicine and Hygiene in 1907. He also made numerous contributions to parasitology, such as (1) the establishment of mosquito as the intermediate host of Wuchereria bancrofti, the causative agent of filariasis; (2) proposed the mosquito-malaria theory, which eventually spurred Sir Ronald Ross to discover that a mosquito was the definitive host for malaria; and (3) the discovery of a new species of Schistosoma (Schistosoma mansoni) and a new parasite, Spirometra or Sparganum mansoni and Spirometra mansonoides. A species of mosquito Mansonia spp and a filarial worm Mansonella spp were so named to honor him. He is hence known as the "Father of Tropical medicine." The tropics are regions of the earth that lie on either side of the equator between the tropics of Cancer and Capricorn (Fig. 1) . The tropics include parts of Central and South America, Australia, Africa, India, and Oceania. The tropics account for 36% of the Earth's landmass, and are home to a third of the world's people. 1 The tropics are warm throughout the year with temperatures ranging from 25 C to 28 C (77 F-82 F) because they are close to the equator with direct sunlight most of the year. However, rainfall does vary remarkably from one area to another with the Amazon basin recording a high rainfall and North Africa being an arid area recording little to no rainfall most of the year. These climatic conditions often influence the flora, fauna, and insect wildlife in these areas. Tropical regions are dominated by equatorial climates with a mean temperature greater than 18 C, and arid zones are characterized by general lack of water, which Rupali harms plant and animal life. They host 80% of the world's biodiversity. Environmental factors include the following: Climate: Climate change has a wide-ranging impact on habitats, species distribution, human health, agriculture, sea levels, and the frequency/intensity of extreme weather events. Changing rainfall patterns and increased temperatures have also led to increase in vector borne diseases, such as dengue and malaria, because of increased vector distributions and decreased vector and parasite incubation periods. Air pollution: Among the tropical regions, Southeast Asia reported the greatest increase in CO2 emissions leading to a decreased air quality followed by South Asia and South America, which has significantly impacted the climate and led to higher weather-related mortality and morbidity, infectious disease rates, and respiratory illnesses. Land degradation: Although land productivity has gone up because of increased livestock and cereal production, land degradation caused by poor agricultural practices and deforestation has led to altered ecosystems and has not changed the fact that more people in the tropics experience undernourishment compared with the rest of the world. Water scarcity: The tropics have more than 54% of the world's renewable water sources, yet more than half of these areas are considered vulnerable to water stress because of the inequality of water distribution, with Southeast Asia having the highest pollution discharge in the world. Overexploitation of wild marine food resources has led to the coral reef systems to be at high or medium risk of damage. Biodiversity: Tropical biodiversity is being threatened across all taxonomic groups with a rapid loss of primary forests. Protection and maintenance of these fragile ecosystems will have a long-term impact on human health and requires cooperation at global, regional, and international levels. Health is defined by the World Health Organization (WHO) as a "state of complete physical, mental and social well-being not merely the absence of disease or infirmity." However, there are many social determinants of health that affect a person's disease burden or longevity and these are often underemphasized or overlooked because the impact is often unmeasurable. Climate and other environmental factors and such social factors as poverty, overcrowding, undernutrition, and limited access to appropriate health care coupled with the lack of education and poor governance contribute to a higher prevalence of communicable and noncommunicable diseases. According to the State of Tropics report 2014, 2 globally extreme poverty has declined by almost 50% since the 1980s but almost two-thirds of the poorest people in the world continue to live in the tropics. Poverty reduction has taken place mostly in Southeast Asia and Central America coupled with a rapid increase in urbanization in these areas. The urbanization rate in the tropics has increased disproportionately to almost 45% by 2010, in turn giving rise to large populations of slum dwellers as compared with the temperate regions, which in turn brings with it diseases of hygiene and sanitation. About 40% of the world's population and 55% of children younger than age 5 also live in the tropics. By 2050, this is expected to increase to 50% and 60%, respectively. Between 1950 and 2010, the life expectancy in the tropics increased by 22.8 years to 64.4 years and infant mortality reduced by 36%. Despite these enormous strides in the improvement of mortality, 6.9 million children younger than age 5 died in 2011, of which 99% were in low-and low-middle-income countries. Infectious agents and toxins are transmitted through water, soil, food, vectors, plants, and animals. Freshwater constitutes only 2.5% of the total water resources on the planet. Of this only 0.3% is available as surface water, whereas the rest is in polar ice sheets, snow cover, and underground aquifers. Water scarcity is defined as less than 2000 cubic meters of water available per person per year. In the tropics the number of nations with water scarcity has tripled since 1962. This scarcity is most acute in South Asia, where 90% of the population is considered vulnerable, followed by North Africa and the Middle East at 62%. Statistics gathered by United Nations show that 900 million people lack access to safe drinking water and 2500 million live without appropriate sanitation. Hence access to safe water and sanitation were recognized as human rights in 2010 by the United Nations General assembly. Waterborne or water-related diseases 3 encompass illnesses resulting from indirect and direct exposure to water. The four main routes of transmission include (1) waterborne, (2) water washed, (3) water based/insect vector, and (4) water related. These diseases are transmitted through the direct drinking of water contaminated with pathogenic microorganisms. Contamination of drinking water often occurs through fecal contamination, caused by poor sewage disposal and improper sanitation. If contamination levels are high, the young, the old, and the immunocompromised are at significant risk of diarrheal diseases and some others. Some of the pathogenic organisms and diseases they cause are as follows: These are also known as water-scarce diseases, which thrive in water scarcity and poor sanitation. This depends more on water quantity than quality. a. Soil-transmitted helminths: Diseases of poor sanitation transmitted through contaminated soil. Most prevalent helminths include Ascaris spp, Trichuris trichura, Ancylostoma duodenale, or Necator Americanus. b. Acute respiratory infections: They are responsible for 19% of the total child deaths every year and good hygienic practices including hand washing with soap can significantly reduce the transmission of acute respiratory infections. c. Skin and eye diseases: Scabies, impetigo, trachoma, yaws, conjunctivitis, and skin ulcers. d. Fleas, ticks, and lice: Typhus, scabies, relapsing fever. These are infections caused by parasitic pathogens found in aquatic host organisms. Humans become infected either through skin penetration (schistosomiasis) or by ingesting the infective forms (dracunculiasis [ingestion of larvae in crustacean], paragonimiasis [metacercariae ingested in crab or crayfish], clonorchiasis [metacercariae ingested in fish]). These are diseases caused by the insect vectors breeding in and around water bodies. Malaria is one of the water-related diseases endemic in 117 countries with 3.2 billion people at risk. About 59% cases occur in Africa, 38% in Asia, and 3% in Americas. Mosquito-borne diseases include malaria, yellow fever, dengue fever, and filariasis. Fly-borne diseases include onchocerciasis and loiasis. Foodborne illnesses are defined by the WHO as diseases of infectious or toxic nature caused by the consumption of contaminated food or water. They are classified into two broad groups: intoxication and infection. Intoxication is caused by ingestion of toxin produced by pathogens, whereas infection is caused by ingestion of food containing viable pathogens. Intoxication is also possible by eating animals that have consumed toxin-producing organisms. Foodborne diseases result in considerable morbidity and mortality, and contribute to significant costs in tropical countries. Many of these are caused by bacteria, viruses, parasites, chemicals, and prions through contaminated food. The WHO estimates from 1990 to 2012 data that 582 million cases were caused by contaminated food resulting in 25.2 million DALYs (Disease adjusted life years). 4, 5 Norovirus is a leading cause of foodborne illness (125 million) followed by Campylobacter spp with 96 million cases. In addition, nontyphoidal Salmonella diarrheal and invasive infections result in a high burden of 4.07 million DALYs in the African region followed by the Southeast Asian region in children less than 5 years. The main pathogens of foodborne illnesses are bacteria (66%), viruses (4%), chemicals (26%), and parasites (4%). Bacteria cause 66% of the foodborne illnesses and botulism, Clostridium perfringens gastroenteritis, E coli infection, salmonellosis, and staphylococcal food poisoning. The most common clinical symptoms are diarrhea, vomiting, abdominal cramps, headache, and nausea. Foodborne parasitic diseases excluding enteric protozoa cause an estimated 23.2 million cases and 45,927 deaths annually resulting in an estimated 6.64 million DALYs. 5 Among these foodborne ascariasis and toxoplasmosis were common Tropical Health contributing to 12.3 and 10.3 million cases respectively. Human cysticercosis with 2.78 million, foodborne trematodiasis with 2.02 million, and toxoplasmosis with 825,000 DALYs resulted in a high burden of disease. Foodborne enteric protozoa resulted in an additional 67.2 million illnesses. Clinically foodborne pathogens can cause diarrhea, intoxications, and invasive enteric diseases. Bacteria producing acute diarrheas include Campylobacter, Salmonella spp, Shigella spp, Staphylococcus aureus, nontyphoidal Salmonella, enteropathogenic E coli, and V cholerae. 6 Bacteria causing intoxications include Clostridium botulinum, C perfringens, Bacillus cereus, and enterotoxigenic E coli. Bacteria causing chronic diarrheas include Brucella spp, Listeria spp, and Mycobacterium tuberculosis in immunocompetent hosts and nontuberculous mycobacteria in immunocompromised hosts. Most of the burden of foodborne illness caused by viruses is transmitted by poor hygienic practices either during food handling or food production. 7 They are transmitted by the fecal-oral route infecting their host after ingestion, followed by invasion of cells in the epithelial lining of the gut and replication at the same site or elsewhere in the body. Norovirus and hepatitis A are considered priority pathogens by the WHO and FAO (Food and Agriculture Organization of United Nations). Increasingly hepatitis E is a pathogen that is assuming increasing importance. Zoonotic food borne viruses Severe acute respiratory syndrome, monkey pox, and Nipah virus have been transmitted through various food-related incidents. Numerous parasites are transmitted by food including protozoa and helminths. However, some of these can also be transmitted by water, soil, or person to person contact. A wide variety of helminthic roundworms, tapeworms, and flukes are transmitted in foods, such as undercooked fish; crabs and mollusks; meat; raw aquatic plants, such as watercress; and raw vegetables contaminated by human feces. Cryptosporidium spp, Giardia intestinalis, Cyclospora cayetenensis, and Toxoplasma gondii Trichinella spp and Anisakis spp Tapeworms Diphyllobothrium spp and Taenia spp Insecticides used in crops, alcoholic beverages containing methanol, poisonous plants (eg, mushrooms, raw cassava roots), oysters, mussels, and clams (which ingest dinoflagellates producing saxitoxin), large reef fish (which ingest marine algae producing ciguatera toxin), finfish spoiled by bacteria leading to scombroid poisoning, and ingestion of puffer fish containing tetrodotoxin all can contribute to significant morbidity. Vector-borne diseases impose heavy economic and health burdens leaving many people who survive the infection permanently debilitated, disfigured, maimed, or blind. Vectors thrive in conditions where housing is poor, water is unsafe, and environment is contaminated with filth exacting their toll on the poor in developing countries ( Table 1) . Malaria is the vector-borne disease that causes the largest amount of morbidity and mortality. Dengue, yellow fever, and Zika are diseases that cause large outbreaks paralyzing health systems and contributing to considerable social and economic disruption. Onchocerciasis causes blindness, chikungunya severe arthritis, Japanese encephalitis permanent neurologic damage, Chagas heart failure and early death, and schistosomiasis poor nutritional status and school performance. Insect bites can cause problems and are venomous or nonvenomous. Venomous insects attack as a defense mechanism injecting painful toxic venom through their stings. Nonvenomous insects bite to feed on the blood of mammals (http://www. traveldoctor.co.uk/stings.htm). 8 Snakes are common in rural areas of tropical countries. Snakebites are a serious occupational hazard for agricultural laborers and fishermen. Generally, the two main families with maximum morbidity and mortality include Viperidae and Elapidae. Snakebites have now been included as a neglected tropical disease with one of the highest rates of mortality as demonstrated by the million deaths study. About 16% of cancers worldwide are caused by infectious agents in the developing world, and the most important cause after tobacco. If infections are controlled up to 1 in 10 cancers in the developing world can be prevented. Human papilloma virus is the most common infectious agent, followed by hepatitis B and Epstein-Barr virus contributing to cancers worldwide. Protein energy malnutrition and micronutrient deficiencies of vitamins and minerals are common in tropical countries and these often contribute to delayed childhood growth and poor child health indices. Although universal immunization and nutrient supplementation at child care centers through mid-day meal schemes have played a major role in mitigating this problem, these are often encountered in many poverty-stricken or famine-ridden countries. Tropical diseases are classified as communicable and noncommunicable diseases. Communicable diseases by definition include diseases that are transmitted to humans and in turn are further classified as those caused by bacteria, viruses, protozoa, parasites, and fungi. Noncommunicable diseases are diseases caused by genetic and lifestyle factors, such as cancers, cardiovascular diseases, diabetes, and chronic respiratory diseases. In addition, snakebites, scorpion stings, and marine and terrestrial envenomations are also management dilemmas. It is important to note that because of constraints of poverty in the tropics, often unsafe food practices are condoned leading to high morbidity among individuals. Air and water pollution can lead to a myriad of respiratory, gastrointestinal, skin, and neurologic disorders along with serving as carriers of infectious pathogens. Although it is impossible to list all the causative pathogens of disease in the tropics, a syndromic approach and a region-wise probability of common tropical diseases is most helpful when dealing with a patient in the tropics or even a returned traveler. Each area of the world is unique and endemic for specific tropical diseases. There is now through the Geosentinel network a large amount of data about the causes of fever in travelers in contrast with data from the tropical regions. Studies that are available use inconsistent definitions about "acute undifferentiated febrile illnesses" and diagnoses are not often confirmed. Fever in the tropics is often syndromic and in the absence of appropriate and accurate diagnostics, common diseases are vastly overdiagnosed, such as malaria in Africa and typhoid fever in South Asia. The advent of rapid diagnostic testing has led to the recognition of other important causes of acute febrile illnesses in the tropics ( Table 2) . Neurologic diseases in the tropics, although rare, are a cause of considerable morbidity and mortality. A history of travel including geographic locale and activities indulged in, possible exposures encountered, vaccines, prophylaxis and protective measures taken, along with the immune status of the host could help determine the etiologic organism of a particular neurologic syndrome. The neurologic syndromes are divided into global and focal syndromes ( Table 3) . Skin lesions are a common problem in the tropics and they could be a primary problem or secondary to an underlying systemic condition. It is important to focus on infections that are treatable, transmissible, and have a high morbidity or mortality. The history must include details of previous travel, previous skin lesions, activities indulged in, immune status of the host, vaccinations, and prophylaxis. Exposures to fresh or sea water, animals, arthropods, plants, breaks in skin including tattoos, sexual activities, and Although tropics are often considered exotic locations skin problems can often be from cosmopolitan causes. Sunburn, scabies, and prickly heat are common and chronic skin problems, such as atopic dermatitis, may exacerbate in a tropical environment. Tropical biodiversity also results in a wide variety of plants and hence hypersensitivity to plants, plant products, and drugs may also occur. It is important not to forget mundane causes, such as pyoderma and folliculitis. Because skin manifestations are myriad a syndromic approach does help to narrow down a definite diagnosis ( Table 4 ). Diarrhea as a syndrome in the tropics has been described as "Montezuma's revenge" and "Delhi belly" because of the associated morbidity. It also is the second most important cause of child deaths younger than the age of 5 years contributing to almost 500,000. In the Global Burden of Disease Study 9 diarrhea was a leading cause of death among all ages contributing to 1.31 million deaths. Most of the deaths in children and adults were attributable to Rotavirus, Shigella spp, and Salmonella spp. However, deaths on the whole have been reduced by 20.8% from 2005 to 2015. In the Global Enteric Multicenter Study 10 done in children younger than age 5, interventions to reduce deaths should be directed against five pathogens: stable enterotoxigenic E coli, enteropathogenic E coli, Cryptosporidium spp, Rotavirus, and Shigella spp. Different clinical syndromes of diarrhea have been defined, each reflecting different etiology and pathogenesis. These are briefly described in Tables 5 and 6 . Various challenges exist in the diagnosis of tropical infections. The challenges are multiple and are divided as discussed next. The burden of disease and the kind of setting where the disease is being diagnosed often determines the need of an appropriate diagnostic test. In a high-prevalence, low-resource setting a test that is low cost, point of care, requiring little technical expertise, with a high positive predictive value is required. In contrast in a lowprevalence, low-resource setting, additional tests may need to be performed to confirm the diagnosis. Subclinical and asymptomatic manifestations of a tropical disease may also make it difficult for a diagnostic test to distinguish between clinical disease and the former. In addition, if a test is serology-based in an endemic setting it may be difficult to establish causality for the clinical manifestations of the disease if baseline antibody titers is high. Although there are obvious infrastructural and financial challenges in low-resource settings there are also impediments with the lack of trained laboratory staff and quality assurance of available laboratory diagnostics. In addition, an ideal laboratory test needs to be rapid, point of care, requiring minimal technical expertise, following norms The WHO constitution dictates, "All people share the right to the highest attainable standard of health." Huge advances are being made toward internationally agreed global health targets, some of which include a reduction in child mortality by 50% between 1990 and 2013 and a 48% decline in AIDS related deaths since the peak of the HIV/AIDS epidemic in 2005 with at least half the infected people being able to access antiretroviral therapy. Many international agencies, such as the WHO and UNAID (Joint United Nations Programme on HIV/AIDS), pharmaceutical companies and Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator and the Global Antibiotic Research and Development Partnership have incessantly campaigned for increased access to medicines leading to an achievement of many of the health-related millennium development goals. 11 Controlling, eliminating, and eradicating neglected tropical diseases has been a major focus for the WHO since 2003 as it moved away from specific diseases to the health needs of poor communities. Over the years many disease conditions that were believed to require a concerted effort by the WHO were included. These were identified as follows ( Table 7 ) 12 This has led the WHO to adopt five major strategies to combat these diseases: Veterinary public health at the human animal interface: An integrated human and animal health approach is required for such diseases as cysticercosis, echinococcosis, and rabies, which involve vertebrate hosts. 5. Provision of safe water, sanitation and hygiene: Better sanitation and improved safe water supply coupled with vector control is being looked at for long-term economic growth and food production. Tropical medicine is an amalgamation of infectious and noninfectious diseases and deals with many important issues, such as water, hygiene, and sanitation, which is out of reach for many low-and middle-income tropical countries. As a result, the health indices for these countries often suffer necessitating global and local public health interventions. Research, development, global support, and funding along with access to major health interventions has empowered many of these countries to overcome the challenges faced by them while combating tropical diseases. Water and waterborne diseases: a review World Health Organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases, 2010: a data synthesis World Health Organization estimates of the global and regional disease burden of 11 foodborne parasitic diseases, 2010: a data synthesis A review on major food borne bacterial illnesses Improving food safety through a one health approach Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study Access to Medicine index 2018 -methodology report Accelerating work to overcome the global impact of neglected tropical diseases. A roadmap for implementation. Available at: www.who.int/neglected_ diseases/en A review of the global epidemiology of scrub typhus World malaria map Global morbidity and mortality of leptospirosis: a systematic review Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with riskfactor adjustment