EMILY WOOD, MD

SEPTEMBER 29, 2013BAR HARBOR, MAINE

Travel related infections

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 network54 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 travelersSkin lesions in returning travelers

Systemic infections Local infections

Diffuse Nodular Ulcers Migratory Arthopod bites

Fever

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.

Clinical FeaturesClinical Features PathophysiologyPathophysiology

• 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 deep vascular beds of vital organs small infarcts, capillary leakage, and organ dysfunction

• Anemia, thrombocytopenia

• 10-20% fatality with treatment

Severe malaria

P falciparum More likely to cause complicated malaria

P vivax More likely to cause uncomplicated malaria, can cause more severe illness

P ovale More likely to cause uncomplicated malariaLess likely to cause relapse than P vivax

P malariae More likely to cause uncomplicated malariaVery low level of parasitemiaCan have long latency period - up to years

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 1990sUse 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 Aedes aegypti and 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 daysMajority asymptomatic or

fever plus rashClassic dengue: fever, retro-

orbital headache, musculoskeletal pain, rash

Leukopenia, thrombocytopenia

Diagnosis clinical; also serology, PCR

Pictures

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

Diagnosis

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.

Skin lesions in the returning traveler

Surveillance

Am. J. Trop. Med. Hyg., 76(1), 2007, pp. 184–186

International Journal of Infectious Diseases (2008) 12, 593—602

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 dermatitisNon-human schistosomesDistribution 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 exposureJellyfish 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 heartwormCan 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 monthsPapule nodule ulceration, often

chronic, slowly progressiveNodules, 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

Cutaneous larva migrans

Human infection with non-human hookworms, usually dog or cat

Infection most common in tropical and subtropical countries of Southeast Asia, Africa, South America, Caribbean, and southeastern United States.

Larvae found on sandy beaches, in sand boxes, and under dwellings

Humans infected when filariform larvae in soil partially infect skin

Most frequently on lower extremities buttocks and

anogenital region, trunk, and upper extremities less often

Starts as pruritic papule and develops into elevated, serpiginous, reddish-brown lesions in 2-3 days

10% of cases vesiculobullous

Strongyloides

Skin lungs small intestine

Autoinfection can occur

EosinophiliaDuodenitisCoughHyperinfection

syndromeLarva currens – like

CLM, but larva track can progress 1 cm in 5 minutes http://www.stanford.edu/group/parasit

es/ParaSites2006/Strongylodiasis/epidemiology.html

Loaisis

Parasitic worm, Loa loa, transmitted by deerflies Breed in the high-canopied rain forest of West and

Central Africa

Eye infectionCalabar swellingsWorms can survive for > 10 years

Ganthostomiasis

Asia, MexicoUndercooked fish, poultryMigrating larvae cause

localized swellings that last 1-2 weeks and associated with edema, pain, itching, and erythema

Swelling can occur for months-years

Can migrate throughout body, including CNS, GI, GU, lungs, eye

Myiasis

Maggots of African tumbu fly or South/Central American botfly

Eggs hatch and larvae burrow into human skin

Patients present with persistent boils which exude serous fluid, can report sensations of movement or pain in skin

Close inspection reveals moving spiracles of larvae

Tungiasis

Tunga penetrans – tiny, parasitic flea found in W. Indies, S. and C. America, W. and E. Africa

Gravid female burrows into broken skin on contact and lives there for 2 weeks until eggs are ready to be shed.

Pale/white, annular blister-like papule with a central black punctum

Questions or comments?

References

Centers for Disease Control. Malaria treatment. Available at: http://www.cdc.gov/malaria/diagnosis_treatment/treatment.html. Accessibility verified 9/24/13.

Ansart S, Perez L, et al. Spectrum of dermatoses in 165 travelers returning from the tropics with skin diseases. Am. J. Trop. Med. Hyg. 2007; 76: 184-6.

Leder K, Torresi J, et al. GeoSentinal surveillance of illness in returned travelers, 2007-2011. Ann Intern Med. 2013: 158:456-468.

Wattal C, Goel N. Infectious disease emergencies in returning travelers. Med Clin N Am. 2012; 96: 1225-55.

Magill A. Cutaneous leishmaniasis in the returning traveler. Infec Dis Clin N Am. 2005; 19: 241-66.

Lederman E, Weld L, et al. Dermatologic conditions of the ill returned traveler: an analysis from the GeoSentinel Surveillance Network. Int J Infect Dis. 2008; 12: 593-602.

Morris-Jones R, Morris-Jones S. Travel-associated skin disease. Infec Dis Clin N Am. 2012; 26: 675-89.