Diagnostic Challenges in Gastrointestinal Infections and Yellow Fever

Travelling for business and pleasure is a small proportion of the total movement of people. Modern transport modes allow more goods and people to travel around the world at a faster pace; they also open up the airways to the transcontinental movement of vectors for infectious diseases. While travelling, people carry their genetic profile, immunological sequelae from previous illnesses, cultural preferences, traditions, and patterns of behaviour. They are also accompanied by microbes, animals and other biological lives.

The range of infectious diseases present at a certain time, and in a certain region has increased, with the travel possibilities' increasing, from one country to another, and more between continents. Transiting through different geographical areas, in a short time (as with long-distance flights), may increase the risk of contamination with foreign etiological agents. Cities are becoming important centres for the transmission of infectious diseases due to international travel and migration, as shown by recent pandemics. Several factors contribute to infectious disease emergence. Others commonly listed include microbial adaptation and change, demographics and behaviour, changes in the environment, technology and economic development, deterioration of public health and surveillance programs, and international travel and trade.

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Many tropical diseases have a polymorphic clinical feature, making diagnostic difficulties, especially for clinicians from the countries outside tropical areas. In developing and developed countries, doctors in urban settings need to be aware of developments in infectious diseases. Upon travel, an ill traveller’s diagnosis must analyse exposure specifics, including visited destinations, activities, ingestion of infected food or drink, contact with insects, livestock, freshwater, or blood and body fluids, and other possible exposures. Information on the geographic dissemination of infectious disease is significant in creating the differential diagnosis and testing in like manner. Empirical intervention is often important when there is a strong possibility of a certain condition and confirmatory lab tests are delayed or unavailable, especially for infections which are rapidly progressive or prolonged testing duration.

The common clinical picture usually shows like acute gastroenteritis, with a sudden or insidious onset, immediately after or after a period of time from returning to the country of origin. At the first contact with the health system, it is important to identify the patient's journey, with detailed information on particular aspects of the trip. Failure in the identification of the epidemiological link may lead to delayed diagnosis and treatment, possible with increasing risks of complications for the patient.

In the geographical area of ​​Romania, Rotavirus, Salmonella species, Shigella species, Clostridium difficile, Escherichia Coli or Giardia lamblia are the most common etiological agents of gastrointestinal infections. [1, 2, 3] Several tropical infectious diseases, such as amebiasis, malaria, leishmaniasis, dracunculiasis, schistosomiasis, brucellosis, leptospirosis, dengue fever, yellow fever, and viral haemorrhagic fever, can have a digestive onset, requiring increased attention from the clinician.

Amebiasis has a worldwide distribution, prevalent in Central and South America, Africa, and Asia, being produced by trophozoites of Entamoeba histolytica. Clinical manifestations can appear up to 4 months from contact with contaminated food or objects. In about 90% of cases, the disease may evolve asymptotic, self-limiting, with recurrences. The rest of the patients may have different severity clinical forms such as acute colitis (bloody diarrhoea, fever, abdominal pain), severe colitis (fulminant, abscesses), and chronic form (ameboma, and inflammatory bowel disease). The etiological diagnosis is based on microscopic identification of cysts and trophozoites in the stool of the patients, specific antibodies, and antigens detection. Malaria is produced by infection with Plasmodium species, by the bite of Anopheles mosquito, being recognized as the second case of death by infections in Africa. According to the European Centre for Disease Prevention and Control (ECDC), Romania, in 2018, confirmed and reported 18 cases of malaria. [4] The disease is endemic in sub-Saharan Africa and South Asia, has an incubation period between 8-25 days, with a clinical picture dominated by cyclical fever. The following manifestations insomnia, weakness, arthralgias, myalgias, diarrhoea, abdominal pain, headache, and hepatosplenomegaly can be associated with the fever in case of acute malaria. Classical clinical triad present in malaria consists of fever, splenomegaly, and anaemia. The microscopic examination of thin or thick blood smears, the detection of the parasite nucleic acid by real-time polymerase chain reaction assay, the identification of the plasmodium antigen by immunochromatography are specific tests used for the patients suspected to having malaria.

Leishmaniasis is a neglected tropical disease, protozoan vector-borne infection, whose transmission is through the bite of an infected female sandfly (Phlebotomine species). It is present in environments ranging from tropical forests in South and Central America to desert areas in West Asia, including North of Africa with cutaneous leishmaniasis which is the most common form, mucocutaneous, and visceral leishmaniasis, the last one being the most severe form of the diseases. The period of incubation varies widely from a few weeks to several months after the initial bite depending on the species. The wide spectrum of clinical manifestations in visceral leishmaniasis includes fever, anorexia, abdominal pain, emesis, diarrhoea, and hepatosplenomegaly. Diagnostic findings are based on skin biopsy, tissue culture, and presence of antibodies.

Dracunculiasis, also known as Guinea worm disease, being the largest problem today, existing in rural areas of South Sudan, Chad, Ethiopia, and Mali, which relies on water supplies that are contaminated. Clinical symptoms can take up to a year to appear, which can include painful blister centred on the worm, usually localised often in the lower extremity, fever, nausea, vomiting, and local lymphadenopathy.

Schistosomiasis is a disease caused by parasitic worms (Genus Schistosoma), also known as bilharzia, which is endemic to tropical and subtropical areas and listed as one of the neglected tropical diseases. With an incubation period of about 2-8 weeks, the acute clinical picture presented by flu-like syndrome, nausea, vomiting, abdominal pain, bloody diarrhoea, hepatosplenomegaly, and lymphadenopathy. Laboratory findings include direct detection of eggs by microscopic examination or of the parasite's nucleic acid in patients stool and urine, and serological tests for identifying the specific antibodies for the cases returned from endemic areas but without eggs demonstrated in faecal or urine samples.

Brucellosis is a zoonosis caused by four different species of Brucella. It is assessed as a major infectious disease in the Caribbean, the Middle East, Eastern Europe, Asia, and Africa. According to ECDC, 1 case of brucellosis was reported by Romania, in 2018. [4] The incubation period is 2 weeks to 5 months. General brucellosis signs are almost always vague and flu-like with gastrointestinal symptoms such as dyspepsia, diarrhoea, constipation, vomiting, abdominal pain, hepatic abscesses. However, the clinical picture is dominated by fever, with undetected aetiology through routine laboratory investigations. The diagnosis of brucellosis, although easy to confirm based on serological tests, often requires a period of time of up to one year, due to the presence of a polymorphic, sometimes oligosymptomatic, clinical picture.

Leptospirosis is a global zoonotic infection with a high prevalence in Caribbean and Pacific islands, Central and South America, Southeast Asia, predominantly during the rainy period, caused by pathogenic spirochetes of genus Leptospira. In 2018, 51 cases of leptospirosis were confirmed in Romania. [4] Usually, the incubation period is 1-2 weeks. It presents itself with a wide range of clinical symptoms, which could be easily mistaken for other diseases, including flu-like syndrome, nausea, vomiting, diarrhoea, rash, dry cough, jaundice, hepatomegaly and splenomegaly, oliguria/anuria, haemorrhages, with the involvement of multiple organs. Suspicion occurs in case of association between digestive, liver, kidney manifestations with fever, and myalgia. Confirmation requires the determination of specific antibodies.

Dengue fever, a global arboviral infection spread by the mosquito genus Aedes (A) (primarily A. aegypti, but also A. albopictus, and A. polynesiensis), a mosquito found in the world's tropical and subtropical regions, also involved in spreading Zika virus disease, yellow fever, and Chikungunya. About 40% of the world’s population, approx. 3 billion people live in regions with a dengue threat. [5] More than 100 countries are affected by dengue resulting in up to 22,000 deaths per annum globally. [6] In 2018, Romania reported 4 cases of dengue fever, all travel-associated. [4] With incubation of 3-14 days 50-80% patients are asymptomatic during the period of illness. [7] Classic dengue fever (breakbone fever) is distinguished by high-grade fever, severe cephalgia, myalgia, arthralgia, retro-orbital pain, abdominal pain or tenderness with persistent vomiting, and hepatomegaly. The diagnosis is supported by the combination of thrombocytopenia, leukopenia, modifications of the liver function tests and serological tests for dengue virus.

Yellow fever virus etiologically belongs to Family Flaviviridae, which causes acute viral disease transmitted by A. aegypti, and Haemagogus mosquitoes. The name's 'yellow' refers to jaundice that affects most patients. In tropical regions of Africa and Central and South America, the virus is endemic. In 2018, one case of yellow fever was reported by Romania. [4] Severe cases can have a mortality rate of up to 50%. [8, 9] With an incubation period of 3-6 days, clinical manifestations in the secondary phase which generally affects liver and kidney with fever, vomiting, abdominal pain, jaundice, dark urine, haemorrhage, and even shock. Yellow fever, especially during early stages, is difficult to diagnose, which can be confused with diseases like leptospirosis, fulminant forms of viral hepatitis, or even severe malaria. Confirmation of the diagnosis requires the detection of the virus by identifying viral ribonucleic acid (RNA), specific antigen or immunoglobulins M.

Viral haemorrhagic fever (VHF) is often referred to characterise a severe multiple organ syndrome. Etiologically, four particular RNA viral families (Arenaviridae, Bunyaviridae, Filovirdiae, and Flaviviridae) lead to VHF. The viruses that cause VHFs are spread across much of the globe. Haemorrhagic viruses are considered as potential biological warfare agents. Initially, clinical symptoms include fever, cephalgia, myalgia, arthralgia, and chills, which can lead to massive haemorrhages, shock, or even acute multiple organ dysfunction. Paraclinical parameters show an increase in liver enzymes and decrease in albumin levels. The coagulation panel shows an increase in prothrombin time and a decrease in fibrinogen. Paraclinical manifestations pose a risk in differential diagnosis with diseases like disseminated intravascular coagulation, malaria, haemolytic uremic syndrome to name some. Although confirming the diagnosis requires detection of viral RNA, viral antigens, or specific antibodies, the clinician must recognize them quickly before laboratory results because these diseases require strict isolation measures and biosafety level 4 laboratory facilities.

The early medical challenge is to include the possibility of tropical infectious diseases that are not common in the area in the differential diagnosis. Not only the characterisation of the symptoms but also the detection of infectious diseases based on a profound history of the patient but also reacting quickly can enormously help the clinicians. Taking into account the epidemiological sense of this problem is of paramount importance. Concerning human mobility, several specific aspects must be considered such as undiagnosed atypical and subclinical types or since patients do not recognize them or are treated as intercurrent diseases, but serious latent infections may develop.

As the travelling around the world will continue so will the microbes continue to evolve? The emergence of new infections will continue, and the distribution, severity and frequency of identified infections will change too. Travel will continue to be an important factor in the emergence of diseases. Analysis and surveillance will map and direct actions on the global movement and evolution of microbes. Integration of multidisciplinary knowledge and skills — social, biological, and physical sciences are required.

References:

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