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Travel related infections. Emily Wood, MD September 29, 2013 Bar Harbor, Maine. Scope of the issue. International travel has increased by 50% over the past decade - 983 million tourist arrivals in 2011 Long-distance travel, especially to Asia and Africa, has increased disproportionately
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Travel related infections Emily Wood, MD September 29, 2013 Bar Harbor, Maine
Scope of the issue • International travel has increased by 50% over the past decade - 983 million tourist arrivals in 2011 • Long-distance travel, especially to Asia and Africa, has increased disproportionately • Travel frequency is also increasing for persons with comorbid conditions, those traveling for business, or those visiting friends and relatives Ann Intern Med. 2013;158:456-468
GeoSentinal data • Global sentinel surveillance network • 54 globally dispersed physician-based travel/tropical medicine clinics chosen for experience and training in travel and tropical medicine • 42,173 ill returned travelers 2007-2011 • GI (34%), fever (23.3%), rash (19.5%) • Asia (32.6%), sub-Saharan Africa (26.7%) • 40.5% had pre-travel visit Ann Intern Med. 2013;158:456-468
Outline of talk • Fever in returning travelers • Skin lesions in returning travelers • Systemic infections • Local infections • Diffuse • Nodular • Ulcers • Migratory • Arthopod bites
Malaria • Protozoan parasite transmitted to human RBCs by female anophelene mosquito bite • Plasmodium falciparum and P vivax are most common • P vivax and P ovale can persist or stay dormant in liver as hypnozoites • P falciparum can result in recrudescence, when parasites are incompletely eliminated and infection recurs weeks-months later
Malaria • 3.3 billion people live in areas at risk of malaria transmission in 109 countries and territories. • 35 countries (30 in sub-Saharan Africa and 5 in Asia) account for 98% of global malaria deaths. • WHO estimates that in 2008 malaria caused 190 - 311 million clinical episodes, and 708,000 - 1,003,000 deaths. • 89% of the malaria deaths worldwide occur in Africa. • Malaria is the 5th cause of death from infectious diseases worldwide (after respiratory infections, HIV/AIDS, diarrheal diseases, and tuberculosis). • Malaria is the 2nd leading cause of death from infectious diseases in Africa, after HIV/AIDS.
Malaria in the US – 2008 • 1,298 reports of cases of malaria with an onset of symptoms in 2008 among patients in the United States • One transfusion-related case, 1 congenital case, and 2 fatal cases. • Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 40.6%, 14.6%, 1.5%, and 1.4% of cases, respectively. • The first documented case of simian malaria, P. knowlesi, was reported in a U.S. traveler. • Eight (0.6%) of the 1,298 patients were infected by two or more species. • The infecting species was unreported or undetermined in 41.2% of cases. • Highest estimated relative case rates among those returning from West Africa. • A total of 508 U.S. civilians acquired malaria abroad; • among the 480 civilians for whom chemoprophylaxis information was known, 344 (71.7%) reported that they had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. MMWR Surveill Summ. 2010 Jun 25;59(7):1-15.
Clinical features • Patients asymptomatic from time of the original mosquito bite until approximately a week later • Typical incubation period usually between 8 – 17 days for P falciparum, P vivax, and P ovale and 18 - 40 days for P malariae. • Initial symptoms of malaria are nonspecific and similar to the symptoms of a minor systemic viral illness • fever, headache, fatigue, muscle and joint pain, nausea, and vomiting
Clinical features • Classic malaria paroxysm of chills and rigors, followed by fever spikes, followed by profuse sweating and fatigue • Paroxysms coincide with the synchronous rupture of blood schizonts and liberation of metabolic waste by-products into the bloodstream. • Can occur in 48-hour cycles (tertian malaria) in P falciparum, P vivax, and P ovale infections • 72-hour cycles (quartan malaria) in P malariae • Cyclic paroxysms suggestive of malaria but not always presents, especially early on.
Severe malaria Clinical Features Pathophysiology • Impaired consciousness/coma • Prostration or sit up with assistance • Convulsions • Deep breathing, respiratory distress (acidotic breathing) • Circulatory collapse/shock, systolic blood pressure <70 mm Hg • Jaundice • Hemoglobinuria • Abnormal spontaneous bleeding • Acute renal failure • Pulmonary edema (radiologic) • Parasitemia > 5% • Sequestration of erythrocytes with mature forms of the parasite in deepvascular beds of vital organs small infarcts, capillary leakage, and organ dysfunction • Anemia, thrombocytopenia • 10-20% fatality with treatment
Diagnosis • Light microscopy – standard tool • Allows for identification of infection species as well as quantification of parasitemia • Should be done every 6-12 hrs for 48 hrs before diagnosis ruled out • Drawbacks: labor intensive, time, consuming, requires training and expertise; less reliable for very low levels of parasitemia
Rapid diagnostic tests • Introduced in the 1990s • Use immunochromatographic lateral flow technology for antigen detection: a blood sample migrates across the surface of a nitrocellulose membrane by means of capillary action. The membrane contains stripes of antibodies specific for different epitopes of a target antigen (one of which is conjugated to an indicator), along with a control antibody specific for an indicator-labeled antibody complex • Antigen targets are malaria antigens conserved across all human malarias and antigens specific to individual Plasmodium species • HRP-2, PLDH, aldolase enzymes
P. falciparum sensitivity and specificity for this test are 95 percent and 94 percent, respectively; the P. vivax sensitivity and specificity are 69 percent and 100 percent.
Diagnosis and treatment: CDC guidelines CDC Malaria Hotline: (770) 488-7788 or (855) 856-4713, (770) 488-7100 after hours.
Dengue fever • Transmitted between people by mosquitoes Aedesaegyptiand A albopictus. • Symptoms usually begin 4-7 days after mosquito bite and last 3 to 10 days • Rarely transmitted by organ transplants or blood transfusions, and there is evidence of vertical transmission • Epidemics occur when there is a concurrence of large number of vector mosquitoes, a large number of people with no immunity to 1 of the 4 virus types (DENV 1-4) and the opportunity for contact.
Originated in monkeys and independently jumped to humans in Africa or Southeast Asia 100-800 years ago. • Dengue was minor, geographically restricted disease until the middle of the 20th century. • World War II—in particular the coincidental transport of Aedes mosquitoes around the world in cargo— thought to have played a crucial role in the dissemination • First documented in the 1950s during epidemics in Philippines and Thailand. • 1981 - large number of DHF cases began to appear in the Caribbean and Latin America
Epidemiology • Over 40% of the world's population at risk from dengue. • WHO currently estimates may be 50–100 million dengue infections worldwide every year. • Before 1970, only nine countries had experienced severe dengue epidemics. • The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. The American, South-east Asia and the Western Pacific regions are the most seriously affected. • Cases across the Americas, South-east Asia and Western Pacific have exceeded 1.2 million cases in 2008 and over 2.3 million in 2010. • In 2010, 1.6 million cases of dengue were reported in the Americas alone, of which 49,000 cases were severe dengue. http://www.who.int/mediacentre/factsheets/fs117/en/index.html
Clinical features • Incubation 3-14 days • Majority asymptomatic or fever plus rash • Classic dengue: fever, retro-orbital headache, musculoskeletal pain, rash • Leukopenia, thrombocytopenia • Diagnosis clinical; also serology, PCR
Dengue Hemorrhagic Fever (DHF) Dengue Shock Syndrome (DSS) • Acute immunopathologic disease that is usually seen in secondary infection, in 90% of cases, after exposure to heterologous DENV serotype • DHF: fever, positive tourniquet test, platelets < 100, hemoconcentration (>20% above normal) • Period of defervescence correlates with onset of hemorrhagic complications • DSS: DHF plus shock
Chikungunya fever • “Chikungunya”: derived from local language in Tanzania – “that which bends up” or “stooped walk”
Clinical manifestations – acute • Abrupt onset fever and malaise after an incubation period of 2-4 days (range 1 to 14). • Fever may be high grade (40ºC); usually lasts 3-5 days. • Polyarthralgias begin 2-5 days after onset of fever and commonly involves multiple joints (often 10 or more joint groups). Joints affected include hands, wrists, ankles; usually symmetric; distal > proximal joints. • Skin manifestations seen in 40 to 75 percent of patients – usually macular or maculopapular rash (appears > 3 days after onset, lasts 3-7 days). Usually on limbs and trunk (and spares the face, palms and soles) • Headache, myalgia, and GI symptoms can be seen. • On physical examination, can see periarticular edema or swelling, peripheral lymphadenopathy, conjunctivitis may be observed. • Lymphopenia, thrombocytopenia, elevated liver enzymes may be seen.
Clinical manifestations - persistent • Can have persistent rheumatologic signs and symptoms including arthritis/arthralgia, edematous polyarthritis of fingers and toes, morning pain and stiffness and severe tenosynovitis (especially of wrists, hands and ankles). • Occasionally, unusual joints (such as sternoclavicular or temperomandibular joints) involved. • New onset Raynaud phenomena 2-3 months after infection have been described in up to 20 percent of cases. • The duration of persistent symptoms is variable. • 47 patients with acute chikungunya fever followed in Marseilles, France, 82 percent had persistent joint symptoms. At one, three, and six months following acute illness, symptoms persisted in 88, 86, and 48 percent of patients, respectively; at 15 months, 4 percent remained symptomatic. • 88 patients in Reunion evaluated a mean of 18 months after confirmation of acute chikungunya infection, 63 percent reported persistent polyarthralgia.
Severe complications • In older reports, described as a self-limited illness, while severe complications and death have been reported in the more recent outbreaks - ? modulation in virus virulence, improved epidemiologic observation, or both. • Severe complications and death occur more often among patients older than 65 years and in those with underlying chronic medical problems. • Severe complications include respiratory failure, cardiovascular decompensation, myocarditis, acute hepatitis, renal failure and neurologic involvement. • Meningoencephalitis is the most common neurologic complication; can also see acute flaccid paralysis and Guillain Barre syndrome. • In Reunion, the estimated incidence of severe disease was 17 per 100,000 population.
Diagnosis • Serology is the primary tool for diagnosis in the clinical setting. • IgM anti-chikungunya virus antibodies present starting 5 days following onset of symptoms and persist for several weeks to 3 months. • IgG antibodies begin to appear about 2 weeks following onset of symptoms and persist for years. • In endemic areas chikungunya infection can be suspected based on characteristic clinical findings in outbreaks • Viral culture and RT-PCR of Chikungunya virus RNA can be useful for research purposes.
Treatment • Supportive care. • No antiviral agents have been shown to be effective in human infection • ribavirin and interferon-alpha appear to have in vitro activity against virus replication • ?CHIKV IVIG • No vaccine is available. • Patients receiving care in an area inhabited by mosquitoes competent to transmit chikungunya virus should be treated in screened, mosquito-free areas or under a bednet to avoid spread. JID 2009:200 (15 August)
Chikungunya vs. Dengue • Chikungunya and dengue virus infections have some common clinical symptoms and areas of geographic distribution • Can be difficult to distinguish in the setting of acute febrile illness with rash. • Polyarthralgia occurs in virtually all cases of chikungunya fever but is not typical of dengue fever (though dengue fever patients commonly have myalgias). • Leukopenia, neutropenia and thrombocytopenia significantly more common in patients diagnosed with dengue than chikungunya.
Surveillance Am. J. Trop. Med. Hyg., 76(1), 2007, pp. 184–186
Rashes in systemic infections: Rickettsial • Fever, headache, malaise within 1-2 weeks of infection • Maculopapular, vesicular, or petechial rash or an eschar at the site of tick bite • African tick bite fever • Southern Africa, tache noir • Mediterranean spotted fever • Northern Africa, rash, fever • Scrub typhus • Asia, can have lymphadenopathy, cough, hearing difficulties, and encephalitis
African trypanosomiasis • Transmitted through bite of tsetse fly • protozoan parasite Trypanosoma brucei (T. b. rhodesiense and T. b. gambiense) • Tsetse flies inhabit rural, densely vegetated areas; travelers to urban areas are not at risk. • T. b. rhodesiense: high fever, a chancre at the bite site, skin rash, headache, myalgia, thrombocytopenia, and CNS involvement within a month • T. b. gambiense: fever, headache, malaise, myalgia, facial edema, pruritus, lymphadenopathy, and weight loss, CNS infection in months- years
African trypanosomiasis PLoS Neglected Tropical Diseases, Nov 2011, Vol. 5 Issue 11, p1-9,
Swimmer’s itch • Cercarial dermatitis • Non-human schistosomes • Distribution of rash is limited to areas of the body immersed in water. • Itchy red papules, may become vesicular, develop hours to a day after exposure • Human schistosomes can also cause a rash
Seabathers itch • Salt water exposure • Jellyfish larvae release nematocysts, inject toxin • Distribution matches areas covered by bathing suit, etc. • Inflammatory papules, can become vesicular or pustular
Dirofilariasis • Mediterranean, but many parts of the world (US) • Dog heartworm • Can be transmitted to humans by mosquitoes • Cutaneous or pulmonary syndrome
Cysticercosis • Caused by larval state of pork tapeworm, T. solium. • Neurocysticercosis versus extra neural cysticercosis • Muscle or subcutaneous infection more common in patients from Asia, Africa
Leishmaniasis • Parasitic infection transmitted by sandfly to humans and other mammals • Many species, vary in geography, biology, vector • Three major clinical syndromes: • Cutaneous • Mucosal • Visceral
Leishmaniasis • Endemic in scattered foci in over 98 countries on 5 continents • Annual incidence of 0.7 to 1.2 million new cases per year. • 75% reported from 10 countries: Afghanistan, Algeria, Brazil, Colombia, Costa Rica, Ethiopia, Islamic Republic of Iran, North Sudan, Peru, and the Syrian Arab Republic Herwaldt BL, Stokes SL, Juranek DD. American cutaneous leishmaniasis in US travelers. Ann Intern Med 1993;118:779–84.
Cutaneous leishmaniasis • Returning travelers present with nonhealing cutaneous lesion • Incubation period of weeks to months • Papule nodule ulceration, often chronic, slowly progressive • Nodules, psoriasiform plaques, verrucous lesions, and sporotrichoid presentations can occur • Usually painless, rolled edge, can have satellite lesions
Leishmaniasis • Diagnosis • Scraping, aspiration, or biopsy of lesion • Histology, culture, PCR • CDC offers diagnostic services • Treatment • Many lesions resolve without treatment • Local versus systemic therapy • Cryotherapy, topical paromycin • Systemic azoles, miltefosine, sodium stibogluconate, amphotericin, pentamidine