10 Travel‐related opportunistic infections

The PubMed database was searched under the following headings: HIV or AIDS and malaria, Malaria falciparum, leishmaniasis or Leishmania spp, Trypanosoma cruzi, American trypanosomiasis or Chagas disease, histoplasmosis, Histoplasma capsulatum, blastomycosis, Blastomyces dermatitidis, coccidioidomycosis, Coccidioides immitis, penicilliosis or Penicillium marneffei. According to figures from the Health Protection Agency, travel abroad by United Kingdom (UK) residents followed the international trend and continued to increase with an estimated 66.4 million visits overseas in 2005. More males than females travelled from the UK and were, on average, between 35 and 44 years of age. Around two-thirds of UK residents travelled for holidays in 2005, the majority to other countries in the European Union (EU). Since 2003, visits to tropical destinations have increased by 28% compared to a decrease of 0.2% for visits within the EU. The number of visits made to see friends and relatives continued to increase at a higher rate (23% since 2003). These figures are particularly relevant to travellers with HIV either involving those with the disposable income to travel or those visiting family overseas. People living with HIV are affected by the usual coughs and travel-associated diarrhoea, however, and this may interfere with their adherence to antiretroviral medication and so pose a greater problem. Anecdotally, patients may discontinue ART while travelling, bringing risks of seroconversion-like illness to others and opportunistic infections. Malaria is a protozoal infection transmitted in endemic areas by the bite of a female anopheles mosquito. There are five main species of parasite that can infect humans but Plasmodium falciparum is the most serious and can be rapidly fatal. Every year, 1500–2000 cases are reported to the Health Protection Agency (HPA) Malaria Reference Laboratory (MRL), and there are nine to 13 deaths in the UK [1]. Most of these are related to delay in diagnosis. In the UK the burden of falciparum malaria falls heavily on those of African and south Asian ethnicity. According to the Health Protection Agency the commonest reason for presenting with malaria in the UK is ‘visiting family from country of origin’ and migrants now living in the UK are often poorly compliant with malaria precautions, believing themselves not to be at risk of malaria [2]. However, immunity to malaria wanes quickly and this group of patients should be targeted for advice regarding avoiding mosquito bites and taking prophylactic antimalarials [1]. Evidence from South Africa suggests that people with HIV who are non-immune to malaria are at higher risk of severe disease or death from malaria [3,4]. Observational and prospective studies from Africa suggest that the likelihood of severe malaria and death is increased with HIV coinfection in areas of unstable malaria transmission [4]. The increased incidence of severe malaria is chiefly seen in individuals with CD4 T-cell counts <200/μL [3], but among individuals with no immunity to malaria there does not appear to be an increased incidence of parasitaemia per se [5]. In settings of year-round malaria transmission where most adults are semi-immune to malaria, the incidence of parasitaemia and clinical malaria are increased in individuals with HIV infection [5]. Malaria presents non-specifically with fever, headache, arthralgia, myalgia, diarrhoea and sometimes features of bacterial infection. Patients may be severely unwell and hypotensive, requiring intensive care unit (ICU) involvement early in the hospital admission. Other than severity there is no evidence that HIV serostatus modifies presentation. Complications of malaria include hyperparasitaemia, acute renal failure, hypoglycaemia, disseminated intravascular coagulopathy, lactic acidosis, fulminant hepatic failure and cerebral malaria [6]. Mortality is still around 20% with higher rates in HIV-seropositive individuals when treated in Africa. Controversy remains concerning the impact of malaria on mother-to-child transmission of HIV but HIV-seropositive women with malaria have an increased incidence of anaemia, infants with low birth weight, prematurity and infant mortality due to malarial parasites preferentially binding to the placenta [7]. Malaria should be diagnosed in the same way as in HIV-seronegative individuals, using a combination of thick and thin blood films with or without a rapid diagnostic (antigen) test in HIV-seropositive individuals (category IV recommendation). In practice, this involves considering the diagnosis in anyone with fever who has returned from an endemic area. Falciparum malaria usually presents within 3 months of their return but non-falciparum malaria may recrudesce many years after their return. There is little information on how HIV may modify this but partial immunity may delay the presentation of falciparum malaria. Malaria should be suspected in anyone returning from an endemic area, as the presentation, especially in the semi-immune person, is very variable. Diagnosis is made by a thick and thin blood film although highly sensitive and specific diagnostic dipsticks now exist [8–10]. Thick films (to diagnose malaria and estimate the percentage parasitaemia) and thin films (for speciation) should be collected on all patients (category IV recommendation) [6]. Rapid diagnostic tests for malaria antigens may be helpful if malaria is suspected but blood films are negative. In HIV-seronegative individuals they are less sensitive but are useful for laboratories with less experience in interpreting malaria blood films [6]. There is limited information on their performance in HIV-seropositive individuals. Current guidelines recommend that any patient considered to be at risk of viral haemorrhagic fever should have a malaria film done under category 3 conditions first [11]. Follow the World Health Organization guidelines [12]. Antiretroviral drug interactions are hypothetical except for that between efavirenz and amodiaquine, a combination which should be avoided. Non-severe falciparum malaria should be treated with oral artemether–lumefantrine or oral quinine followed by doxycycline, or with Malarone (atovaquone–proguanil) (category IV recommendation). Severe falciparum malaria (>2% parasitaemia ±organ dysfunction) should be treated initially with intravenous artesunate where available or with quinine by intravenous infusion with cardiac monitoring when artesunate cannot be administered. Individuals with severe malaria should be referred promptly to a specialist unit (category IV recommendation). The many potential antimalarial and antiretroviral drug interactions are summarized below (Table 10.1) [13]. However, most do not seem to be clinically problematic despite many drugs being metabolized via the same hepatic cytochrome pathway. The interactions are therefore largely hypothetical except for efavirenz and amodiaquine, which should not be co-administered. The choice of antimalarials is therefore determined by the species and severity of the malaria with similar considerations as for HIV-seronegative individuals [6]. Uncomplicated falciparum malaria should be treated with oral artemether–lumefantrine (Co-artem, Riamet). If the weight is >35 kg the treatment schedule is four tablets at 0, 8, 24, 36, 48 and 60 h. Alternatives are oral quinine (600 mg tid po for 7 days plus doxycycline 200 mg orally once a day for 5–7 days) or Malarone (atovaquone–proguanil) (four tablets daily orally for 3 days) if there are no complications. There is a potential interaction between ritonavir and quinine, which may result in increased quinine levels [14]. If individuals meet criteria for parenteral quinine, they should still receive a standard loading dose of quinine (see below) but protease inhibitors should be stopped until the patient is stable and able to take oral medications. There should also be increased vigilance for signs of quinine toxicity, including evidence of prolongation of the QT interval, and quinine dose reduction may be required if any signs of toxicity are noted. Non-nucleoside reverse transcriptase inhibitors (NNRTI) may decrease quinine levels and since quinine metabolism may be enhanced with malaria this may result in significant underdosing with standard doses of quinine [15,16]. NNRTI and quinine should ideally be avoided but if the patient is already on NNRTI and quinine must be prescribed, the dose of quinine may need to be titrated against the clinical response and the patient monitored carefully for signs of toxicity, such as abnormalities on cardiac monitoring. Concerns have been raised about the safety and efficacy of artemisinin-based combination treatments when combined with antiretroviral therapy [13]. Artesunate plus amodiaquine combinations have reduced efficacy, as compared to artemether plus lumefantrine (co-artemether), and when combined with efavirenz have been with and also suggest that lumefantrine is increased with to be with an The is but should be that lumefantrine in was and in many there are to recommend dose but increased vigilance is was that should be avoided in patients taking protease inhibitors due to drug More has that when with the under the and of artemether was reduced and that lumefantrine was without to levels this may suggest may be with and they may be considered as in the treatment of malaria information on the efficacy and toxicity of these combinations in HIV-seropositive individuals is required and must be that there is still limited experience of the of these in HIV-seropositive individuals in Severe or falciparum malaria is as cases with renal acidosis, or acute or hypoglycaemia, very low by as or disseminated intravascular [6]. should be treated with a parenteral which should also be in cases where the parasitaemia is or when the is to take oral these falciparum malaria is treated with intravenous artesunate at 0, daily to a combined with doxycycline 200 mg once a quinine dose by infusion for 48 until the is able to take oral is an Rapid should be made to a specialist (category IV recommendation). The loading dose of quinine should be if quinine or has been in the h. the and QT and can hypoglycaemia, so treatment must be while to a cardiac with of blood There is a potential for increased cardiac due to an interaction between quinine and The treatment of choice for non-falciparum malaria is a of oral (600 mg mg after mg daily for days) followed by days of mg orally once a mg once a to the is not required for [6]. Patients should be for to and the risk of Patients with can be with for but specialist advice should be HIV-seropositive individuals who travel to areas should be malaria and advice on how to mosquito bites as of a (category IV recommendation). HIV-seropositive travellers are at higher risk of severe malaria, and of malaria should be should receive the same travel advice concerning the of malaria as the HIV-seronegative the of malaria should be of and Diagnosis and treatment (see The advice regarding on the and and specialist advice is available from the Health and by the of Health for or for in may the risk of malaria, HIV-seropositive patients should still receive standard malaria and all the advice around of malaria. The main for are mg orally once Malarone (atovaquone–proguanil) once daily and doxycycline mg orally once mg once with 200 mg orally once are less now due to are to travel and continued for after return with the of Malarone (atovaquone–proguanil) which is days travel and continued for after return and which should be to if treatment to the to and to to an if to is in patients with a of including and cardiac with are in those with low those on travel and those with a of drug are particularly in adults and many therefore this in particularly if with a low or with a of drug In the of and specialist advice should be the of and the incidence of cardiac with Malarone is and and protease inhibitors may and levels although there are no to the dose of and their patients must for should be avoided in hepatic in those who cannot of a to and also in women and under the of Other areas of advice to include the of percentage than when after and of mosquito to is a group of by of the Leishmania that are transmitted by by drug In the most cases of leishmaniasis from the Africa or and leishmaniasis from or the leishmaniasis in HIV-seropositive individuals usually in those with CD4 counts below 200 Leishmania of which usually presents with features of fever and weight with most with or without with of the of the or usually on the or Most reported cases of in are of leishmaniasis may be with a of intravenous drug leishmaniasis but not presents in the same way as does in HIV-seronegative the features may be for other opportunistic infections. leishmaniasis may as does in individuals with a that to a but a of may and may be for or leishmaniasis in with HIV infection to be very in as which most leishmaniasis in However, any patient with a suspected on the should be seen by a leishmaniasis may be seen in cases in or South where the species have greater for Diagnosis of leishmaniasis or (category recommendation). is suspected but standard tests are with a tropical specialist is to on the and of tests in the of HIV infection (category IV recommendation) Diagnosis on or of diagnosis is most useful of Leishmania species may In the of standard diagnostic tests may be less sensitive and advice should be (category diagnosis may be made by or include this has the but should be by a in the as or is to with the tropical disease and taking those with may so should be with the diagnosis may be made on of or other tests include the test and to to The of may be reduced in coinfection due to low levels of in HIV-seropositive individuals or diagnosis may be made from a is to the with a to that are tests are not helpful in the diagnosis of for leishmaniasis should be with the tropical (category IV recommendation). is the treatment of choice for leishmaniasis (category recommendation). of leishmaniasis is with or intravenous (category recommendation). The treatment of choice for leishmaniasis in an HIV-seropositive is for doses on days 24, and is the available in the UK in European countries may be has also been for treatment of leishmaniasis of clinical studies has that treatment with is as but less than treatment with HIV-seropositive individuals have a rate after treatment for leishmaniasis of leishmaniasis is the standard of care in in the after treatment was or 3 may be while has also been for of leishmaniasis There is evidence to the of specific and this is with the tropical disease the of oral treatment when standard treatment however, the failure of this when is The of in combination with or followed by oral may be a when standard treatment but are can be made cases should be with the tropical leishmaniasis can be treated with of or on the species although there is limited experience of therapy in individuals with HIV infection. is with the tropical disease of leishmaniasis is not patients not taking at the of there is no specific evidence to when should be but suggests this should be as as the patient is stable on There are to and when to of recommend that can be stopped if leishmaniasis has been treated the patient is stable on and the CD4 T-cell has been for months However, is among patients with treatment and CD4 T-cell counts of leishmaniasis are with or including in the or leishmaniasis or There are also of leishmaniasis presenting as an after the of antiretroviral therapy There are with HIV medication and treatment for leishmaniasis and with an HIV is Chagas disease or American trypanosomiasis is by a which is a of the Trypanosoma is to and South and from in the to the of and in the is by also as in in areas There is that of Trypanosoma infection can disease in patients with including HIV-seropositive individuals who have or travelled to endemic main of disease in people with or are most in individuals with CD4 T-cell counts are the commonest presentation, of of Chagas disease in HIV-seropositive Patients can with features of a or are of fever, and signs and is the most presentation seen in a of often with is often and at but can with or failure Chagas disease may also the and or Chagas disease should be suspected in patients from the endemic areas of and South or with a of blood or intravenous drug with from these Diagnosis of Chagas disease a combination of and if available (category recommendation). individuals with HIV infection from an endemic should be with if be for disease (category IV recommendation) disease, studies similar to those for and with low tests are not diagnostic for from including thick or and after are usually may also in the diagnosis if other tests are there is often failure to to treatment for should in is that all HIV-seropositive people with risk for Chagas disease be for to to infection if should be in with a specialist tropical disease for and for Chagas disease should be with the tropical (category IV recommendation). is the treatment of choice for acute infection or of Chagas disease, with the (category recommendation). should be considered for individuals with HIV infection and (category recommendation) The treatment for acute infection or Chagas disease in HIV-seropositive patients is daily in doses for higher dose may be in acute daily in doses for days is considered an with is there is no evidence to the but the is to be by the same as other opportunistic and be by the and response to These drugs have and treatment should be by a specialist tropical disease individuals for cruzi, or individuals with disease, a of treatment with or as should be individuals with and to the risks and of treatment should be considered on a by Individuals not and to or to should be treatment with or is not usually required for individuals for if on but if the is not able to take are either to if the the or to the patient There is no for The is now considered to be Since clinical cases and are related to CD4 T-cell is that decrease the incidence of of has been with a of disease in those with disease of in HIV-seropositive individuals are Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides and Penicillium marneffei. of these is The of infection is via of for that are and can be many by disease, which is while those with disease and individuals with disseminated In the of these can be in HIV-seropositive individuals. is in and of the United the South and in the is in and Africa is in the of the United the and around the of the United and is in the of the United and in infection should be suspected in who has in an endemic area, although for travel to an endemic is can either or infection. Individuals with CD4 counts to HIV-seronegative individuals. may be if and fever with and on can with either infection or as a illness the most of infection was as acute disseminated infections. features of disseminated include fever, weight and and disseminated may be with disease signs include or and In many cases of disseminated disease signs and are for or although disease may be less with disease is but has been reported for and of are with disseminated may be with and Patients may with a and include or involvement of the disease may also with infection with to of individuals with AIDS disease in features of include and a of weight and fever without in the most often as disseminated or disease, and as an in the there has been of cases that are which are with a test or by an or on These cases are with an viral on and with a CD4 T-cell of In disseminated disease of are (category recommendation). and should be if disseminated disease is suspected (category recommendation). Diagnosis should be via and (category recommendation). should be to to the response to therapy in disseminated disease (category recommendation). diagnosis involves of the from or a which can take to for or of the on a or has a on In disseminated disease, of are and blood may also be diagnostic test for is available and is particularly useful in patients with disseminated disease or in with disease but is largely limited to a is in of cases with Patients with disseminated may have very levels Diagnosis of disease may be as and tests may all be negative. seem to be very useful to but are not disease should be treated initially as for HIV-seronegative individuals with for and for (category IV recommendation). severe disseminated infection should receive treatment with 3 (category for histoplasmosis, category IV for therapy therapy should be with in the of coccidioidomycosis, (category recommendation). treatment should be with the oral and monitoring should be to levels (category recommendation). or treatment is with 200 mg as the oral due to and with monitoring to levels due to between individuals an of and guidelines for HIV-seronegative individuals but for the less individuals who with this of disease (category IV recommendation). mg is the (category IV recommendation) 200 mg po a loading dose of 200 mg mg for 3 days) can also be for treatment of disseminated in HIV-seropositive individuals interactions between other and (Table in antiretroviral including ritonavir other can increase levels of other while modify the metabolism of If is required is to that have drug interactions and to drug monitoring to and antiretroviral including that from a with experience of these is required to these severe disseminated or for disseminated or for disseminated is usually for treatment for the first of at 3 for is the for severe disseminated in HIV-seropositive individuals, on the of a clinical which less toxicity and and greater clinical as compared to (category recommendation) exist for other disseminated with is to at 3 for followed by for for other (category IV recommendation). There is no evidence that higher doses of any treatment Patients to may be treated with intravenous for although have been little in severe disseminated disease (category IV recommendation). therapy for therapy for the should be with oral 200 mg po with drug monitoring as this the dose should be 200 mg with the of the (category recommendation) disease with to for followed by mg to than for at is there are clinical but severe disease is treated with 3 followed by with mg orally (category IV recommendation). recommend using with in the and mg orally should be in with or without when there is disease levels do not need to be and exist of the of and against such as and in settings where individuals not to and these have in against These may be considered in cases or and (category recommendation) therapy Severe disease or with may be treated with 60 mg for the first of for and related is not (category IV recommendation). can be if after of therapy there has been of for months and the CD4 is (category recommendation). is not for individuals with CD4 counts who in an endemic may be considered in cases with 200 mg which has been to the incidence of and of therapy for disseminated when therapy been for at been for at blood and below the of and the CD4 was years of no noted. is that can be stopped for other under similar conditions to those The to is however, of are seen with and not to be so treatment within of therapy (category IV recommendation). has been with in individuals include and There is less information with and although infection is a opportunistic infection in patients with HIV infection who in and was from and to be by with than the themselves of have been reported among to from countries the There is also an of infection in In the are the most affected The most clinical features of penicilliosis include fever, weight and patients with which a and These are often on the and disseminated infection is fatal. may and The diagnosis can be made by of from or other that of from the and other a on and which that the to a at a of these is other such as and may have similar clinical There are no available tests for this disease although can be in the should be treated with therapy for followed by 200 mg orally for and therapy 200 mg once a day (category IV recommendation). Penicillium is sensitive to In the treatment experience has been with intravenous per day for followed by oral 200 mg po for a has a response rate of to and is for other therapy with 3 for the first should be considered in the UK (category IV recommendation). has been as therapy in patients with HIV who have treatment of infection however, there are that may be when on ART and individuals have CD4 counts with may be considered for travellers to endemic areas with CD4 counts has been on studies in other and a in that 200 mg once a day orally be as to travellers to the endemic areas who have CD4 counts There is little information on the impact of on but in the incidence low in individuals Most cases of penicilliosis at very low CD4 counts where is by However, should be in all patients diagnosed with penicilliosis as as a clinical response is to treatment of There is little information on due to penicilliosis but as with other is a presentation.