Tropical Diseases Caused by Mosquitoes

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1		Abdullahi Umar Ibrahim	--	5020	2022-11-09 11:41:54	\|
2	format correction	Dean Liu	Meta information modification	5020	2022-11-10 04:47:09	\|

This entry is adapted from the peer-reviewed paper 10.3390/tropicalmed7100309

Tropical diseases (TDs) are among the leading cause of mortality and fatality globally. The emergence and reemergence of TDs continue to challenge healthcare system. Several tropical diseases such as yellow fever, tuberculosis, cholera, Ebola, HIV, rotavirus, dengue, and malaria outbreaks have led to endemics and epidemics around the world, resulting in millions of deaths. The increase in climate change, migration and urbanization, overcrowding, and other factors continue to increase the spread of TDs.

CRISPR electrochemistry biosensor

1. Introduction

The world is constantly facing the outbreak and reemergence of tropical diseases (TDs). The history of TDs dates back to ancient times, including the Roman and Egyptian empires. TDs are defined as diseases that are prevalent or indigenous to tropical and subtropical regions. Some of the most common TDs include malaria, cholera, yellow fever, dengue, Zika, etc. ^[1]^[2].

Mosquitoes are arthropods which are involved in the transmission of multiple pathogens, causing diseases that include dengue fever, chikungunya fever, malaria, filariasis, Japanese encephalitis, Zika, etc. TDs caused by mosquitoes have been associated with the mortality of humans every year. Therefore, mosquitoes are a major public health threat and thus can affect the economies of infected regions or countries. In the past few years, synthetic pesticides have been used to control mosquitoes. However, synthetic pesticides can cause contamination, kill many beneficial insects, and lead to the development of resistant-types after long-term use ^[3].

Advances in microscopy, molecular biology, biochemistry, diagnostic techniques, and treatment approaches in the 20th and 21st centuries have contributed to the understanding of the genetic contents of pathogens, biochemical reactions, and controlled such as susceptibility and resistance to drugs, vaccination of tropical diseases. The use of computer-aided techniques and other relevant technologies continue to aid experts in mapping regions of origins, predictions of spread, and creation of awareness using media outlets ^[2]^[4].

Early diagnosis of TDs is crucial for timely treatment, increasing patients’ survival rates, preventing further outbreaks, and minimizing the cost of diagnosis. Advances in science and technology continue to improve the accuracy, sensitivity, and specificity of diagnostic approaches. Currently, molecular testing and antibody-based approaches are regarded as the standard approaches for diagnosing TDs. Other techniques used by medical experts include imaging approaches (such as X-ray, CT scans, ultrasound), blood tests, microscopy, sputum tests, etc. These techniques have several limitations which include the need for sophisticated devices, the need for highly trained and skilled pathologists and medical laboratory technicians, the use of toxic chemical reagents, and a lack of POC diagnostics ^[4].

Genome editing technology is regarded as one solution that can be used to modify the genome of organisms and harness their mechanism as a form of biomimetic approach for accurate detection of diseases. The three most widely techniques employed for manipulating the genomes of different species, including mosquitoes, include Zinc-finger Nucleases (ZFNs) and Transcription Activator-like Effector Nucleases (TALENs). Advancement in molecular biology has led to the discovery of unique immune pathways utilized by bacteria to fight against viruses such as bacteriophages ^[5]^[6]. This immune response approach is termed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat). When viruses invade bacteria, they inject their nucleic acid (in the form of RNA or DNA) which hijack the bacterial DNA replication system, generating more viruses and subsequently destroying the bacterial cell. To prevent this type of invasion, bacteria utilize a three-step process that includes adaptation, expression (biogenesis or recognition), and interference to ensure immunity ^[7].

Since the first deployment of CRISPR/Cas9 for genome editing in 2012, many researchers have successfully applied this technique to accurately edit the genomes of a variety of organisms such as bacteria, yeast, plants, and animals including mosquitoes. CRISPR/Cas technology is cheaper, easy-to-use, and accurate compared to ZFNs and TALENs. Scientists biomimic this pathway by designing a synthetic RNA known as single guide RNA (SgRNA) which binds with the target (pathogen) nucleic acid (RNA in viruses and DNA in bacteria and parasites). The application of the CRISPR/Cas system has proven to be among the most, reliable, accurate, sensitive, specific, and fast methods for screening pathogens associated with TDs. CRISPR/Cas9 genome editing technology also enables the modification of the target genes of pests. This is especially useful in controlling vector-borne diseases caused by mosquitoes ^[3]^[6]^[8].

2. Tropical Diseases (TDs)

The study and classification of TDs became a hot topic during the era of exploration and colonialism by the British, American, Portuguese, Spanish, French, etc., who came in contact with these type of diseases in tropical regions. The study, diagnosis, and treatment of these diseases led to the establishment of tropical medicine. Increased research in this field has led scientists to understand the mode of transmission, vectors, and symptoms of these diseases during the 19th century. Moreover, pathogens such as viruses, bacteria, fungi, and parasites that are associated with TDs were identified, as well as vectors such as lice, mosquitoes, fleas, etc., and other TDs associated with food and water contamination ^[2]^[4].

Many TDs spread as a result of interactions and complex cycles of transmission between human primates and animals such as invertebrates (e.g., flies, mosquitoes, snails) and vertebrates (e.g., livestock, dogs, cats, bats, snakes, etc.). The widespread and reemergence of TDs depends on several factors including an increase in population or population growth, global warming, exploration, migration, deforestation, meteorological events such as flooding, urbanization, etc. However, a change in environmental conditions such as extreme weather conditions and variations in rainfall, temperature, and humidity have influenced the widespreadness of TDs compared to other factors. Variations of rainfall and temperature have both been associated with influencing pathogen and vector replication and reproduction, as well as vector metabolism, host distribution, and the selection of habitats for breeding ^[9].

2.1. Transmission of Tropical Diseases

In both tropical and temperate climate regions, numerous viral and bacterial diseases are spread via several routes including transmission from one person to another through coughing, sneezing (airborne disease), or sexual contact (sexually transmitted diseases). Example of airborne diseases include tuberculosis, measles, and respiratory syncytial virus. TDs can be also be transmitted through drinking contaminated water and food sources (also known as waterborne and foodborne diseases, respectively). The mechanism of transmission of the majority of these diseases depends on an intermediate carrier also known as a vector. These organisms or carriers harbor these pathogens from an infected person or animal (zoonotic) and transfer it to others. Most often, these pathogens undergo mutation or developmental changes within the carriers which make them more virulent and difficult for the human immune system to fight ^[9]^[10].

2.2. Classification of TDs

There are several ways in which TDs can be classified. However, the most common classifications are based on the type of pathogen (such as viruses, bacteria, parasites, etc.), vectors, or carriers (such as ticks, mosquitoes, flies, etc.), which are also termed as arthropod-borne diseases and also based on concern (neglected and non-neglected TDs) ^[2]^[4]. When these diseases are transmitted by arthropods (such as flies, ticks, or mosquitoes), they are termed arboviruses or arthropod-borne viruses ^[2].

2.2.1. Viruses

Virus-causing diseases are one of the most common and widely distributed pathogenic diseases in nature. Unlike bacteria that store their genetic content in the form of DNA, viruses store their genetic constituent in the form of RNA. They invade and hijack the host’s nucleic acid replication system which provides the necessary machinery to replicate new viral particles ^[11].

Dengue Virus (DENV)

Dengue fever is a disease caused by positive-stranded RNA containing the virus known as dengue virus, which is transmitted by a mosquito-borne flavivirus. Aedes aegypti mosquitoes are regarded as the main carriers of dengue virus and can transfer this virus during feeding on human primates (also known as Human-to-Mosquito Transmission). Moreover, medical experts also report the possibility of maternal transmission (from pregnant mothers to their babies). The most common acute symptoms of dengue fever include severe pain in the muscles, joints, ocular inflammation, headache, nausea, vomiting, rashes, swollen glands, etc. When this virus infects infants and children, it causes “dengue hemorrhagic fever” which leads to critical conditions such as shock (also known as “Dengue shock syndrome”) and circulatory system failure. Despite the prevalence of DENV around the world, there is no specific medication against the virus. However, doctors control the disease using medications to lower fever, relieve pain, prevent dehydration, manage bleeding, etc. ^[12].

In terms of epidemiology, DENV is found in many tropical and subtropical areas around the world and has been reported in more than 100 countries including Africa (Ivory Coast, Seychelles, Reunion Island, Cape Verde, etc.), Asia (Bangladesh, Afghanistan, China, Cambodia, Indonesia, India, Pakistan, Malaysia, etc.), America (Brazil, Peru, Ecuador, Nicaragua), and Australia. DENV has caused several endemics and epidemics around the world, with the incidence of the virus having recently increased due to human factors such as deforestation, massive urbanization, and global warming, which has expanded the regions inhabited by the Aedes mosquito vector. Approximately 400 million cases and more than 20 thousand deaths are reported almost every year, with more than 3 billion people at risk. The first outbreak of DENV dates back to 1779 in Indonesia and Egypt ^[13]. The disease was also recorded in North America in 1780 and it has reemerged over the years. In 2010, more than 1.5 million cases of DENV were reported in both South and North America. However, the largest number of infected cases was reported in 2016 in the United State of America (USA), with more than 2.38 million cases ^[14]. Several countries continue to report an increased number of cases daily, with Brazil having the highest number with more than 167 thousand as of March 2022.

Zika Virus (ZIKV)

ZIKV is another mosquito-borne disease that is predominant in several tropical and subtropical areas of West Africa, East Africa, South America, and Asia. The virus is a single-stranded positive-sense RNA virus that belongs to the “Flaviviridae” family. ZIKV shares numerous characteristics with other flaviviruses such as DENV, yellow fever virus, West Nile virus, and Japanese encephalitis. Aedes mosquitoes are regarded as the main carriers of ZIKV and can transfer this virus during feeding on human primates. During feeding, the virus is injected by mosquitoes which further replicates in dendric cells and is subsequently transported in the blood to other organs and tissues ^[15]^[16].

The virus can be acquired in the laboratory, through sexual intercourse or blood transfusions, or via the exchange of other bodily fluids such as breast milk, saliva, or the urine of an infected patient. The vector-borne transmission of the virus occurs in two cycles known as the sylvatic and urban cycles. The sylvatic cycle revolves around transmission of the virus by arboreal mosquitoes to non-human primates (NHPs), while the urban cycle revolves around transmission between human primates and urban mosquitoes. Scientists have also identified the virus antibodies in animal species such as goats, sheep, buffalo, lions, elephants, zebra, hippos, etc. The virus has been associated with Guillain-Barre syndrome in adults and microcephaly, arthrogryposis, ophthalmological defects, hearing defects, and cerebral malformations in children. The majority of infections caused by ZIKV are asymptomatic ^[16]^[17].

In terms of epidemiology, the virus was first isolated from the sentinel rhesus monkey in Uganda in 1947, while the first human isolation of the virus was reported in Nigeria in 1952. Since then, the disease has caused several epidemics and endemics around the world. Despite ZIKV having caused several health burdens, it was not until 2016 that the WHO declared it as a global health emergency due to the outbreak of the disease in South America. Just like many pathogenic tropical viruses, there is no specific antiviral drug or vaccine against ZIKV. Almost 100 thousand cases were reported in 2016, 609 in 2017, 1800 in 2018, and 15 cases in 2019 using EpiWATCH ^[18].

Yellow Fever Virus

Yellow fever virus is from the Flaviviridae family which causes yellow fever. It is related to Japanese encephalitis, St. Louis encephalitis, and West Nile virus. Yellow fever viruses are transmitted to people through a carrier known as Haemagogus or Aedes mosquitoes. These mosquitoes acquire the virus through feeding on infected animals or humans and transmit it to other primates. Thus, people infected by yellow fever virus through Aedes mosquitoes are referred to as being “viremic”. Yellow fever has three transmission cycles which include sylvatic (jungle), where the virus is transmitted by mosquitoes from NHPs, such as monkeys to humans visiting the jungle; savannah (intermediate), where the virus is transmitted from mosquitoes directly to humans (human to human); or from NHPs to humans. Urban transmission is initiated by viremic humans who have visited the savannah or jungle region and urban mosquitoes which feed on the infected person and transmit the disease to other humans ^[19]^[20].

Some of the mild symptoms associated with this disease include headache, fever, chills, back pains, weakness, fatigue, vomiting, and nausea. When left untreated, it can lead to critical or severe conditions such as liver, kidney, and heart failure or malfunctions, shock, jaundice (yellow skin), bleeding, etc. The mortality rate is high, as more than 50% of people infected with the virus die of the disease. There is no specific drug against yellow fever diseases; however, physicians prescribe medications that relieve pain, fever, and aches ^[21].

Unlike DENV that is prevalent in almost every continent, yellow fever is limited to Africa where it originated and has caused several epidemics in South Africa and other African countries such as the Democratic Republic of Congo (DRC) and Angola ^[20]. Several incidences of the disease have also been reported in Latin America, with more than 12 South American countries affected. Despite the fact that there are vaccines against the disease, the prevalence of the disease continues to spread, resulting in more than 70 thousand deaths per year. The increase incidence of the disease is associated with the widespread distribution of Aedes mosquitoes as a result of climate change ^[22]. Yellow fever has been recognized as a disease of significant public concern due to it pathology and high mortality rate in both human and NHPs. However, little is known about why the cases cease in some years and appear in other years, and what promotes the strong seasonal trends ^[21].

Rotavirus

Rotavirus is a pathogenic double-stranded RNA virus from the Reoviridae family. The name “Rota” is derived from the Latin word meaning “wheel”. Rotavirus is regarded as one of the most common pathogens that are detrimental in terms of pathology and is associated with causing watery diarrhea in children under 5 years of age. Other symptoms of the rotavirus-causing disease apart from severe dehydration include fever, nausea, vomiting, etc. Human primates are the reservoir of the disease which is found in the gastrointestinal tract and stool. The disease can be transmitted from person to person through fecal–oral routes (i.e., injecting infected food or water) and fomites (environmental surfaces contaminated by the stool of infected patients). The incidence of rotavirus is also reported in NHPs such as mammals, e.g., pigs ^[23]^[24].

The history of rotavirus dates back to the 1970s when several pediatricians and other medical experts embarked on studies to explore the causes of diarrhea in children as a result of striking mortality rates ranging from 3–12 million per year. Regions of high incidence include Bangladesh, Peru, and Guatemala which recorded more episodes of diarrhea cases. As a result of research using instruments such as electron microscopy and other biomedical instrumentation, scientists discovered several viral-causing diarrheas such as Norwalk agent and rotavirus (which appears to be a wheel-shaped virus), as well as other causing pathogens including different species of bacteria and parasites ^[23]^[24].

Globally, more than 2.7 million incidences are recorded and 600 thousand children die as a result of the virus annually, with the majority of deaths reported in India (i.e., with more than 100 thousand deaths yearly). Moreover, the majority of cases are reported in sub-Saharan Africa and South-East Asian countries. It is estimated that the disease leads to more than 500 thousand deaths in most of the underdeveloped countries. In the US, rotavirus is regarded as the most common cause of severe gastroenteritis in children ^[23]^[25].

Scientists over the years have developed vaccines against the virus, with the first developed in the USA in 1998 known as Roatshield, which was later withdrawn due to rare adverse effects. Currently, there are several vaccines used to treat rotavirus (such as Rotavac, Rotateq, Rotasil, Rotarix, etc.), in more than 100 countries around the world. The increase in vaccination has led to a decrease in incidence, hospitalization, and mortality among infants. Despite the massive level of vaccination, the disease continues to cause concern in many underdeveloped countries with low access to vaccines and quality medical care ^[24].

Human Immunodeficiency Virus

HIV/AIDS is one of the most common diseases that affects the immune system. It is caused by human immunodeficiency virus which belongs to the genus of viruses known as “lentiviruses”. In terms of its pathophysiology, HIV has been described to overcome or overpower the immune system’s T-cells known as CD4 helper cells, rendering the immune system susceptible to invasion from other pathogenic agents and cancers. As a result of the decline in response to foreign invaders by the immune system, HIV is accompanied by the term AIDS (Acquired Immune Deficiency Syndrome). The virus can be transmitted in several ways as a result of the exchange of bodily fluid such as blood, breast milk, vaginal secretions, and semen. The virus can also be transmitted from an infected pregnant mother to her baby. Some of the mild symptoms of the disease include fever, headache, sore throat, rashes, diarrhea, cough, swollen lymph glands, weight loss, etc. ^[26]^[27].

In terms of epidemiology, HIV is believed to originate from West Africa where it was transmitted to humans by a subspecies of chimpanzee. The disease is among the list of the most critical diseases that have emerged in the history of humanity. By 1996, the disease had already infected more than 13 million people within sub-Saharan Africa. The disease was declared epidemic in 1989 by the WHO as a result of an increase in the number of cases ^[28]. Despite major advances in diagnosis and treatment of HIV over the past two decades, it still remains a global concern. Currently, there is no specific drug against the virus. Even though there has been a decrease in the number of deaths cause by the virus, it is still prevalent in poor countries with substandard medical care systems. HIV has spread to almost every country and it was estimated that more than 37 million people were living with the virus in 2020 ^[29].

Ebola Virus

Ebola virus is one of the reemerging diseases causing severe health issues in African countries. It is formerly known as Ebola hemorrhagic fever. Symptoms of the disease cause by the virus include fever, hemorrhage, headache, and vomiting diarrhea. The mode of transmission of the disease is still unclear but medical experts believe the virus can be acquired as a result of direct contact with bodily fluid such as bloods and other secretions from infected patients as well as contact with surfaces contaminated with the virus. Scientists have categorized it as zoonosis and linked the disease with fruit bat and porcupines ^[30]^[31].

Ebola virus originated from two African countries, including the DRC and Congo, in 1976. The virus reemerged in West African countries, with early incidences in Liberia, Guinea, Sierra Leone, and Nigeria in 2014, and is regarded as the most serious health emergency crisis in the region. As of 2015, there had been more than 28 thousand reported cases and more than 11 thousand deaths. The average fatality rate of the disease is 50%; however, fatality rates in the past outbreak have varied between 25–90%. Even with advances in the diagnosis of the disease using advance technology, the outbreak of Ebola still remains intermittent and unpredictable. There have been more than 30 outbreaks of Ebola since 1976 ^[30]. The two recent outbreaks were reported in the DRC in 2018, with more than 3 thousand cases, and on 7 February 2021 ^[31]^[32].

2.2.2. Bacteria

Bacteria are among the most abundant and ubiquitous microbes in nature. Bacteria can be classified as either pathogenic or non-pathogenic (e.g., microbiomes). They can also be classified as Gram positive or Gram negative. Some of the pathogenic bacteria that cause diseases include Mycobacterium tuberculosis, Vibrio cholerae, Escherichia coli, etc. ^[33].

Tuberculosis (TB)

TB is one of the most common bacterial diseases caused by bacteria know as Mycobacterium tuberculosis. It was discovered in 1882 and its mode of transmission was first reported in 1909. It is a slender, rod-shaped microbe with length ranging from 1–10 mm and strict aerobes (i.e., needing oxygen to survive). Tuberculosis is an airborne disease that is transmitted from an infected patient to others via sneezing, coughing, talking, etc. Depending on the environment, the bacterial particles can remain suspended in the air for hours and thus can be transmitted as a result of coming in contact with surfaces contaminated with the bacilli ^[34].

The pathogenesis of the bacteria occurs in the lung’s alveoli where it causes pulmonary tuberculosis. A few weeks after exposure, a granuloma is formed as a result of the immune system response against the bacilli. When the bacteria spread to other tissues in the body it is termed as “systemic miliary tuberculosis”. Treatment of tuberculosis depends on the severity of the disease. Pulmonary tuberculosis is mostly treated using antibiotics. However, Mycobacterium tuberculosis is becoming resistant to drugs and thus has increased virulence ^[35].

TB still remain a global health issue despite the use of antibacterial drugs against the bacteria. As of 2015, there are more than 10 million people suffering from the disease, with 10% mainly children and 12% people suffering with HIV/AIDS. As of 2015, the number of deaths associated with TB was estimated to be around 2 million. In the last few years, cases of TB have declined marginally. Even though the disease has been controlled in many countries, it is still a health issue in many underdeveloped countries and continues to threaten to become an increasing burden due to both extensive drug resistance and multi-drug resistance ^[35].

Cholera

Cholera is another bacterial disease that is associated with diarrhea. It is caused by a Gram-negative bacterium with a coma-like shape known as Vibrio cholerae. Cholera can be transmitted through the fecal–oral route as a result of eating food or drinking water contaminated with the bacteria. When the bacterium enters a host cell, it secretes toxins which leads to symptoms such as diarrhea, vomiting, abdominal pain, and hypovolemic shock. Factors that increase the risk of the disease include lack of access to clean and sanitized water, people with O blood group, living in overcrowded societies, use of antihistamine and proton pump inhibitors, etc. ^[36]^[37].

Despite progress in research regarding the diagnosis and treatments of diseases, cholera continues to be a burden in many countries. In terms of outbreaks, scientists have identified two serotypes known as O1 and O139 which causes disease, while more than 190 serotypes are non-pathogenic. O1 has been associated with the most recent outbreaks in Bangladesh and Kerala, India. O139, on the other hand, has caused sporadic outbreaks in some regions within Asia ^[37]^[38]. Despite the fact that the majority of positive cases and deaths toll are underreported, it was estimated that there are more than 4 million cases of cholera yearly and more than 140 thousand deaths globally. The disease is found to be endemic in many countries within Asia and Africa, while cases have been reported in countries within the Caribbean, Middle East, and South and North America ^[38]^[39].

Escherichia coli

E. coli is another bacterium that causes bacteremia in some developed countries. The bacteria are found in the lower intestine of blooded animals. There have been several strains of E. coli identified and the majority do not cause infection, while a few are pathogenic and have been found to cause food poisoning and diarrhea. An example of this bacteria is the Shiga toxin-producing E. Coli O157:H7. This strain is an enterohemorrhagic type that causes diarrhea hemolytic-uremic syndrome and hemorrhagic colitis in humans. It is classified as both a food and water-borne disease that is transmitted via the fecal–oral route as a result of consuming uncooked meat and contaminated liquid, including raw meat and vegetables ^[40]. Pathogenic E. coli are known to cause travelers’ diarrhea and kidney problems. Common symptoms include abdominal cramp, vomiting, fever, and diarrhea. Outbreaks of this pathogenic bacteria have been reported in Japan, the USA, and Scotland ^[41].

2.2.3. Parasites

Parasites are group of organisms that live in or on another organism known as the host, at whose expense they obtain their nourishment while simultaneously infecting the host. Parasites can be classified as single-cell organisms (e.g., protists) and multi-cell organisms (e.g., helminths or worms). Parasites ranges from micro-size to macro-size organisms. Even though some parasites can be found intracellular, the majority live extracellular inside the host and are mostly found in the gut, blood, lymphatics, etc. Unlike bacteria and viruses that replicate inside host primates, parasites undergo complex developmental transformation within the host and can reproduce sexually and asexually. Examples of parasitic diseases and pathogens include Plasmodium (malaria), Trypanosoma (African sleeping sickness, Chagas disease), hookworm (ancylostomiasis), roundworms (Ascaris), tapeworm (Dipylidium caninum disease), Leishmania (Leishmaniasis or kala-azar), etc. ^[42].

Malaria

Malaria is the most common parasitic disease globally. It is cause by protists known as Plasmodium. There are different species of Plasmodium; however, Plasmodium falciparum is identified as the most virulent and the leading cause of death among Plasmodium species. Plasmodium is transmitted to human primates by anopheline mosquitoes during feeding. After injection of the parasites by the carrier, the infection cycle begins in the liver cells followed by the red blood cells where the parasites consume hemoglobin. The completion of the cycle ends in the erythrocytes, where the parasites divide and infect more red blood cells. The general symptoms of malaria include fever, weakness and fatigue, sweating, nausea, vomiting, diarrhea, headache, abdominal pain, etc. ^[43]^[44].

Malaria is more prevalent in sub-Saharan Africa countries, where there are widespread untreated water bodies. Malaria cases are estimated to be around 300 million with more than 1 million deaths every year. Malaria has also reemerged in countries that had been declared malaria-free. Outbreaks of malaria continue to be an issue in Africa, the Amazon region, and Asia. The WHO and other international organizations have launched several campaigns and projects to eradicate malaria globally but it still remains elusive. Factors associated with persistent malaria include resistance to insecticide and drugs, lack of adequate healthcare facilities and sanitation programs in underdeveloped countries, and lack of priority concern from international bodies ^[45]^[46].

Trypanosomiasis

Trypanosomiasis is another disease that is cause by species of the genus Trypanosoma. An example of trypanosomiasis is Chagas disease, also known as American trypanosomiasis that is cause by Trypanosoma cruzi. Unlike malaria, trypanosomiasis is transmitted by bugs which feed on infected feces and enter into human primates through the mouth, nose, skin, eyes, etc. Symptoms of this disease include inflammation or swelling of the lymph nodes and fever, while in critical conditions it can lead to cardiac malfunction, digestive disorders, and death ^[47].

Another common disease-causing trypanosomiasis is known as sleeping sickness or African trypanosomiasis, which is transmitted by tsetse flies (Glossina species). Species associated with this disease include Trypanosoma brucei rhodesiense, which is found in South and Eastern Africa, and Trypanosoma brucei gambiense, which is most common in Central Africa and West Africa. The common acute symptoms of African trypanosomiasis include weakness, dizziness, fever, and headache. In a critical condition, the disease can cause neurological disorders with symptoms such as delusions, hallucination, seizures, etc. ^[48]^[49]. Epidemics of sleeping sickness have caused concern in the past. However, as a result of intervention by both national and international organizations, the disease is well-controlled with cases of less than 600 reported in the DRC in 2020 ^[50].

Leishmaniasis

Leishmaniasis is a parasitic disease that is cause by protists known as the Leishmania genus. Scientists have identified about 20 species that causes disease to human primates and NHPs (i.e., mammals). An example of Leishmaniasis is Cutaneous Leishmaniasis, which is locally known as oriental sore, Delhi boil, or Baghdad ulcer. Another example is Visceral Leishmaniasis, which is locally known as kala-azar in India and refers to black sickness. In recent years, the number of cases has surged from less than a million to 1.2 million. Visceral Leishmaniasis is regarded as the most dangerous form of Leishmaniasis. Leishmania can be transmitted as a result of a bite from infected phlebotomine sandflies. This species is found within the macrophages and plays a crucial role in fighting against invading microorganisms in the host’s body ^[51]. The symptoms of Leishmaniasis include weight loss, increase pigmentation, fever, and swelling of the liver and spleen. Apart from humans, other reservoir hosts identified include dogs and rodents ^[51]^[52].

In terms of epidemiology, the disease is prevalent in both tropical and subtropical regions, with recent cases in Sudan and India. Few cases have been reported in the US and Southern Europe, while Australia and Antarctica are the only continents with no reported cases. According to the WHO, there are more than 10 million recorded cases with 300 million people at risk in more than 90 countries. The disease is predominant in rural settlements but can also be found in the outskirts of cities ^[53].

2.3. Neglected Tropical Disease (NTDs)

The last century has witnessed a decline in the incidence of and elimination of numerous TDs in the majority of developed countries. However, millions of people are still affected by these types of diseases, especially in underdeveloped countries which contribute to high mortality rates. These types of diseases are termed as NTDs. Example of NTDs include leprosy, Guinea worm disease, African sleeping sickness, rabies, Leishmaniasis, Schistosomiasis, Fascioliasis, dengue, Dracunculiasis, Onchocerciasis, Chagas disease, yaws, hookworm, trachoma, etc. ^[54].

The prevention and control of NTDs in underdeveloped countries are highly challenged by several factors such as the socioeconomic status of the regions, a lack of medical equipment, a lack of adequate response and concern from international organizations, a lack of awareness, etc. NTDs can be found in some regions located within Africa, Asia, and Latin America. The majority of NTDs are associated with rural areas and regions which lack access to hygienic food, clean water, and safe ways of waste disposal ^[32].

The primary ways of controlling or preventing NTDs include controlling the vectors or via massive drug administration. As carriers of pathogens, vectors play crucial role in disease pathways. Thus, controlling vectors such as black flies and mosquitoes that transmit disease as well as improving environmental hygiene and water sanitation are highly crucial for controlling and preventing NTDs. Consequently, massive drug administration is another effective way or intervention in eliminating NTDs. Diseases that can be eliminated using this intervention approach include trachoma, Onchocerciasis, Dracunculiasis, Schistosomiasis, lymphatic filariasis, and soil-transmitted helminths (hookworm or Ascaris) ^[55].

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