Neurological Syndromes and the Traveller: an Approach to Differential Diagnosis

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2003.034330 on 20 February 2004. Downloaded from NEUROLOGICAL SYNDROMES AND THE TRAVELLER: AN APPROACH i2 TO DIFFERENTIAL DIAGNOSIS J N Day, D G Lalloo

J Neurol Neurosurg Psychiatry 2004;75(Suppl I):i2–i9. doi: 10.1136/nip.2003.034330

n 2001 there were 58 million overseas trips made by UK residents, and over 22 million people visited the UK from abroad. As the relative cost of air travel falls, holidays in exotic destinations Ihave become easier and therefore more common. Travel to such places can be associated with particular health risks, not only through exposure to indigenous pathogens but also through changes in behaviour when released from one’s normal day to day schedule—for example, use of alcohol and illicit drugs, ‘‘adventure holidays’’, transport, and sex. This article will focus on infectious agents that a neurologist may need to consider when asked to see an adult who has recently arrived from abroad. The emphasis will be on developing a logical approach to establishing a differential diagnosis rather than on an exhaustive list of all the potential weird and wonderful infectious agents or on the detailed specifics of treatment.

c THE PATIENT’S HISTORY

Detailed history taking is the key to establishing the diagnosis in infectious diseases. The first task is to define the syndrome with which the patient presents, and then to define the particular exposure, or risk, that the patient has faced. This must involve a detailed travel history—some illnesses, such as African trypanosomiasis, occur in small well defined geographical areas within a country’s borders (Fig 1). The differential diagnosis that this generates can then be further refined copyright. through knowledge of the incubation period of the suspected diseases. For example, a feverish illness developing on the third day after arrival in West Africa could not be due to malaria, because the minimum incubation period for this infection is one week. Of course, many infections can present with non-specific features leading to a wide variety of different syndromes, or have poorly defined or widely variable incubation periods and thus need to be considered in the differential diagnosis for many patients. Such diseases include those well known to physicians throughout history—tuberculosis, typhoid, malaria, and syphilis can all present in a wide variety of ways and often need to be included in the differential diagnosis. HIV will no doubt take its place in history alongside them. A carefully taken and wide ranging history will usually allow one to narrow the differential. Remember that many travellers travel frequently to different regions of the world and their presenting illness may result from exposure that occurred two or three trips http://jnnp.bmj.com/ previously—detailed travel histories are crucial. There are also an increasing number of immunocompromised individuals who are travelling abroad; this group in particular are at risk of exotic infections. This article is based around table 1, which classifies illnesses according to the syndrome with which they may commonly present, and describes the geographical origins of those illnesses along with their incubation periods, plus any other particular activity that might put the traveller at risk. It is not exhaustive. We have attempted to divide organisms that cause meningoencephalitis on September 25, 2021 by guest. Protected according to whether they produce a predominantly meningitic or encephalitic syndrome. Some pathogens will inevitably occur in both groups. Incubation periods are presented as ranges during which most cases of that disease will present. For some pathogens such as malaria, the minimum incubation period is well described (through knowledge gained from using malaria as a treatment for neurosyphilis). For other organisms such as helminths, it is more difficult to be precise. See end of article for authors’ Characteristic features of different syndromes will be described in the text, but unfortunately, affiliations particularly early in infection, such signs and symptoms may not be obvious. Infectious agents ______that are well recognised causes of disease in the UK will not be discussed in detail (for example, Correspondence to: herpes simplex). It is important to remember that a patient who has just spent two weeks in Dr J N Day, Oxford University Outer Mongolia may have acquired their fever and neurological syndrome in the UK the weekend Clinical Research Unit, The Hospital for Tropical Diseases, before departure. Not all fevers in returning travellers are caused by the overseas travel! 190 Ben Ham Tu, Quan 5, Ho Three infections are notable for their ability to cause many different syndromes, their high Chi Minh City, VietNam; mortality, and the availability of curative or dramatically disease modifying treatment if [email protected] ______diagnosed and treated early. They are malaria, typhoid, and HIV infection.

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Table 1 Predominant syndromes and possible causes with incubation periods and geographical distributions

Predominant syndrome Cause Incubation period Geographical location Specific risk Notes

Non-specific Parasitic Malaria P falciparum 7 days to 1 year Worldwide tropics Risk highest in West Africa. History of mosquito bites is unreliable. Painless (Plasmodium spp) Spread by female mosquitoes and non-irritant. Only P falciparum causes neurological illness P vivax 14 days–2 years Worldwide tropics P ovale 14 days–2 years Mainly Africa P malariae 14 days–?years Africa Bacterial Typhoid 3–56 days (average 10–20) Worldwide Poor sanitation Imported cases usually from South Asia Viral HIV 7–28 days Worldwide Sexual contact, injecting drug use 95% patients seropositive at 6 months Encephalitis Viral Enteroviruses 3–8 days Worldwide Recent epidemics Taiwan Herpes viruses HSV Highly variable Worldwide Can also cause meningitis Varicella zoster 13–21 days Worldwide Usually a cerebellar encephalitis B virus 2–10 days Macaque bites Prophylactic acyclovir recommended Arboviruses JEV 5–15 days SE Asia Seasonal peaks in transmission Mosquito borne WEE 5–15 days Western USA, South America EEE 5–15 days Eastern USA VEE 2–6 days South America SLE 5–15 days USA WNV 3–12 days America, North Africa, SE Asia, ?UK/Europe MVE 5–15 days South Australia TBE 7–14 days Central, Northern Europe, Asia Tick borne Rabies 3 days–many years Rare in developed countries Animal bites/scratches Incubation period ,90 days in 85% cases Bacterial Louse borne typhus 7–14 days Worldwide Disease of poverty and destitution; Human louse rare in tourists, aid workers possibly at risk Rocky mountain spotted 2–14 days USA, Canada, Mexico, South Can occur in urban environments Tick borne fever America Brucellosis 5–60 days Middle East, South America, Unpasteurised dairy produce, Meningitis and encephalitis can arise as a Northern Ireland contact with farm animals result of brucellosis. CSF shows predominant lymphocytosis, raised protein, and normal glucose Secondary syphilis 6–14 weeks Sexual contact Prominent and distinctive rash Parasitic African trypanosomiasis T b gambiense: months/ Disease occurs in Africa in Travel to rural areas e.g. Safari Spread by tsetse flies. Seek expert help. If years. T b rhodesiense: isolated pockets suspected may be necessary to start treatment weeks before lumbar puncture Meningitis Viral EV71, echo, coxsackie 3–8 days Worldwide Polio 7–14 days Eradicated from the Americas Almost(!) eradicated Mumps 12–25 days Worldwide Adults Meningitis can occur in the absence of parotitis EBV 35–45 days Worldwide Young adults CMV 3–8 weeks Worldwide LCV 6–13 days Animal handlers, the poor Infection from rodent droppings HIV 7–28 days Bacterial Meningococcus Hours–days Worldwide, but especially Sub-Haj pilgrims Outbreaks common in pilgrims returning to Saharan Africa, Middle East UK Pneumococcus Worldwide Note: penicillin resistance common in some countries (e.g. Spain, South www.jnnp.com Africa) Haemophilus influenzae Streptococcus suis China, VietNam Contact with pigs Listeriosis Unpasteurised dairy products Leptospirosis 2–26 days Watersports Brucellosis As before

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2003.034330 on 20 February 2004. Downloaded from from Downloaded 2004. February 20 on 10.1136/jnnp.2003.034330 as published first Psychiatry: Neurosurg Neurol J http://jnnp.bmj.com/ on September 25, 2021 by guest. Protected by Protected guest. by 2021 25, September on i4 www.jnnp.com Table 1 (continuted)

Predominant syndrome Cause Incubation period Geographical location Specific risk Notes

Lyme disease (stage 2) Weeks to months North America, Europe Hiking/camping 15% of patients affected Syphilis As before Tuberculosis (TB) Usually represents Insidious onset Good outcome depends upon prompt reactivation of latent disease diagnosis and treatment Fungal Cryptococcosis Weeks Depends upon variety Not clearly defined Disease can occur in the immunocompetent in the tropics Blastomycosis Not determined USA, Canada, Africa, India, Possibly associated with Usually evidence of skin or respiratory Middle East river banks involvement Histoplasmosis Days to weeks Worldwide excluding Europe Associated with bat and bird Different disease syndromes depending on droppings region Coccidiomycosis 10–30 days Semi-desert areas of the New Initial flu-like symptoms Associated with erythema nodosum. CSF World findings similar to TB(M) Parasitic—causes of Schistosomiasis Weeks to months, Africa, South America, SE Tropical fresh water contact Extremely common in sub-Saharan Africa eosinophilic meningitis sometimes years Asia, China Gnathostomiasis SE Asia, Pacific Basin Gastronomes Raw and pickled fish, shellfish, amphibian ingestion Angiostrongyliasis Sparganosis Widespread in Americas and Frog and snake ingestion tropics Cysticercosis (Taenia Central, South America, Asia, Swine/measley pork All but eradicated from industrialised solium, pork tapeworm) Africa countries Strongyloidiasis Worldwide Poor sanitation As part of hypereosinophilic syndrome Fits Bacterial Tetanus 3–21 days Worldwide Tetanic spasms may mimic seizures TB meningitis As for TB(M) Cerebral abscess Onset usually 1–4 weeks Parasitic Cysticercosis See above As before Most common cause of fits worldwide Schistosomiasis See above As before Hydatid disease Worldwide Communities with close exposure Especially Middle East to dogs Amoebic brain abscess Weeks to months Worldwide Poor sanitation Can be single or multiple Drugs Mefloquine, chloroquine Chloroquine, mefloquine, ciprofloxacin and ciprofloxacin are contraindicated in patients with epilepsy Paralysis Viral Rabies As above As before May be more common after ‘‘Paralytic’’ or ‘‘dumb’’ rabies contact with bats Polio 7–14 days See above Japanese encephalitis 5–15 days Produces a syndrome similar to polio in 5% of cases Enteroviruses Coxsackie, echoviruses, EV70, EV71

Bacterial Tetanus 3–21 days Worldwide History of injury in only 50% PRACTICE IN NEUROLOGY Botulism 12–72 hours Rare in developed world Usually food borne but can result from wound infection Post-infectious Guillain-Barre´syndrome Associated with campylobacter, EBV, echovirus, VZV, HIV, and infection Ectoparasites Tick bites 5–6 days All continents Hikers/campers, etc Usually resolves rapidly with tick removal Algae Paralytic shellfish 30 mins to 6 hours Latitudes 30˚–35˚ Nto Seafood lovers Dinoflagellate toxins concentrated through poisoning, ciguateratoxin 30˚–30˚ S food chain poisoning

CMV, cytomegalovirus; CSF, cerebrospinal fluid; EBV, Epstein Barr virus; EV71, enterovirus 71; HIV, human immunodeficiency virus; HSV, herpes simplex virus; JEV, Japanese encephalitis virus; LCV, lymphocytic choriomeningitis virus; MVE,

Murray Valley encephalitis; SLE, St Louis encephalitis; TBE, tick borne encephalitis; TB(M), tuberculosis (meningitis); WEE, EEE, VEE, western, eastern and Venezuelan encephalitis viruses; WNV, West Nile virus.

Table 2 World Health Organization definition of severe malaria (1990, revised 2000)

System Complication

Central nervous 1990: Unrousable coma not attributable to any other cause in a patient with falciparum system (cerebral malaria. Coma persists for at least 1 hour after a generalised convulsion. Coma defined by malaria) Glasgow coma score (or Blantyre coma score in children) 2000: Any impairment of consciousness Repeated generalised convulsions (.2 in 24 hours) i5 Haematological Severe anaemia (haemoglobin ,5 g/dl or normochromic normocytic with haematocrit ,15%) Spontaneous bleeding from gums, nose, gastrointestinal tract or laboratory evidence of DIC

Renal Renal failure: urine output ,400 ml in 24 hours with serum creatinine .265 mmol/l Macroscopic haemoglobinuria

Metabolic Hypoglycaemia (blood glucose ,2.2 mg/dl) Acidaemia (arterial or capillary pH ,7.35)

Cardiovascular/ Circulatory collapse or shock (systolic blood pressure ,70 mmHg respiratory Pulmonary oedema or ARDS

Other Prostration—i.e. inability of a child to sit (2000) Hyperparasitaemia .4% (2000)

Presence of any of the complications above defines severe malaria.

MALARIA Cerebral malaria This is the first diagnosis to exclude in any patient returning Cerebral malaria is the most obvious feature of severe from an endemic region with a fever. Mosquito bites are malaria and is strictly defined as unrousable coma, but in often unnoticeable, and chemoprophylaxis and bite avoid- practice any impairment of conscious level should be ance measures cannot provide 100% protection. The expected considered concerning. It is uniformly fatal in the absence standard of investigation to exclude malaria is at least three of treatment and the overall mortality of treated cerebral negative malaria blood smears each taken 24 hours apart. malaria is around 20% in adults. The prodromal illness There are a number of new rapid malaria detection tests usually lasts a few days, but can be much shorter in chil- available which are highly sensitive and specific. dren. However, it is possible to have lethal malaria infection copyright. Malaria is caused by protozoan parasites of the genus with no impairment of consciousness until death. Many Plasmodium, spread by female anopheline mosquitoes, which neurological symptoms and signs have been described in require a blood meal for egg development. Four distinct severe malaria, including meningism, fits, focal neurological species infect man (table 1). Between 1–3 million people die signs, and oculogyric crisis. However, these are rare, and from malaria each year. Most of these deaths occur in the most common manifestation is that of a symmetrical children, or in non-immune adults—those living outside encephalopathy with no focal neurological signs. Careful areas with high transmission—and are almost exclusively examination of eye movements should be performed to due to infection with Plasmodium falciparum. In areas of high exclude subtle seizure activity. A number of abnormalities on transmission, immunity develops which does not prevent fundoscopy have been described, including cotton wool spots, infection, but limits the severity of disease. This immunity is haemorrhages, and papilloedema (less common in adults). strain specific and is rapidly lost when a person leaves a Gaze may be divergent but cranial nerve lesions are unusual. http://jnnp.bmj.com/ hyperendemic region. Clinically, malaria is divided according Tone and reflexes may be increased, normal or depressed, to whether it is ‘‘uncomplicated’’ or ‘‘severe’’. The features of and abdominal reflexes are often absent. There may be uncomplicated malaria are common to all four infecting decorticate or decerebrate posturing and opisthotonus. Deep species. The syndrome consists of a prodromal period of coma, extensor posturing, seizure activity, respiratory dis- lassitude, headache, muscle aches and vague abdominal pain, tress, hypoglycaemia, hyperlactataemia, and a high parasite followed 2–8 hours later with fever: similar symptoms to the load . 4% (that is, more than 4% of all red blood cells common cold or flu. Rigors may occur. With prompt parasitised) are poor prognostic signs. on September 25, 2021 by guest. Protected presentation and treatment it is unusual to see the classical Laboratory findings in severe malaria can include a patterns of two (ovale and vivax) or three (malariae) day normocytic normochromic anaemia, thrombocytopenia, nor- intermittent fevers developing. Hepatosplenomegaly and mal or low white cell count, and evidence of disseminated anaemia may develop as the infection progresses and intravascular coagulation. Hypoglycaemia occurs as a direct pronounced diarrhoea, constipation, and even a dry cough consequence of infection or as a side effect of intravenous may occur. quinine treatment, and should be excluded in an unconscious The neurologist is more likely to be involved in the care of patient or anyone that deteriorates following admission. patients with severe or complicated malaria, which is always Hyponatraemia, raised urea and creatinine values, and raised due to P falciparum. Severe malaria is defined according to blood lactate may occur. Lumbar puncture may reveal World Health Organization (WHO) criteria, last updated in elevated pressure in children, but is usually normal in adults. 2000 (see table 2). Neurologists may also be involved in The cerebrospinal fluid (CSF) is usually normal in cerebral the care of patients with the post-malaria neurological malaria but there may be an elevated protein or mild syndromes—relatively rare conditions where neurological lymphocytosis. CSF lactate may be raised and glucose may symptoms develop after successful parasite clearance. be slightly low.

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Figure 1 Active foci of African trypanosomiasis (copyright A Stich, Medical Mission Institute, Wu¨rzburg).

Treatment from the Chinese Sweet Wormwood plant, will soon be It is important to exclude hypoglycaemia and underlying licensed in the UK and may be used more frequently in the seizure activity in any unconscious patient with malaria. In future. This ancient remedy has excellent efficacy and few the last 10 years there has been a dramatic increase in side effects, and in endemic regions may also reduce the incidence and global spread of drug resistance and in transmission by killing the sexual stages of the parasite. many parts of the world P falciparum is now completely Treatment of cerebral malaria is a medical emergency and resistant to chloroquine. Treatment options are therefore specialist advice should be sought. limited and the mainstay of treatment for severe malaria in Fits are common in cerebral malaria, particularly in the UK is intravenous infusion of quinine followed by a children. Phenobarbitone reduces fits in cerebral malaria, copyright. second drug, usually doxycycline. The most important side but trials in Kenya demonstrated an increase in mortality in effect of quinine is hypoglycaemia, but tinnitus, deafness, children receiving a single prophylactic injection. This may and nausea (cinchonism), and rarely cardiac arrhythmias, have been related to respiratory depression. The safety of can occur. It is likely that the artemisin derivatives, derived other anticonvulsants such as phenytoin in the setting of

Figure 2 Culinary sources of causes of eosinophilic meningitis (copyright JN Day). http://jnnp.bmj.com/ on September 25, 2021 by guest. Protected

www.jnnp.com NEUROLOGY IN PRACTICE J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2003.034330 on 20 February 2004. Downloaded from severe malaria has not been determined. Corticosteroids are infection made in the UK in 2002. Over half of these were in not beneficial in the treatment of cerebral malaria. heterosexuals, many having acquired their infection in sub- Saharan Africa. The many different presenting syndromes Post-malaria neurological syndromes can be caused by HIV itself, or by opportunistic infection as a Up to 3% of adults and 20% of children have a persistent result of immunosuppression in established HIV infection. neurological deficit after cerebral malaria. In children this Doctors with an interest in infectious diseases are often asked appears to be related to the length of coma, profound when HIV should be considered in the differential diagnosis; i7 anaemia, and prolonged seizures. Deficits include hemipar- the answer is usually ‘‘all the time’’. Encephalopathy esis, cortical blindness, tremor and isolated cranial nerve complicates 6% of all HIV seroconversion illnesses, and a palsies. Post-malaria neurological syndromes (PMNS) have further 6% will develop neuropathy as part of primary been described in patients who appear to have recovered infection. There is a clear benefit from starting anti-retroviral from their malarial illness but develop a new neurological therapy before there is severe immunosuppression (CD4 syndrome a few days or weeks after becoming aparasitaemic. ( 200 cells/ml); and there may be a benefit in treating acute These problems can include acute confusional states, seroconversion syndromes in preserving HIV-specific cyto- psychosis, generalised convulsions, tremor, or ataxia. PMNS toxic T cell responses, so it is vitally important to diagnose is a relatively rare condition and usually follows severe HIV infection if present. Other neurological syndromes malaria, but can follow uncomplicated disease and has been described as part of primary HIV infection include: retro- associated with the use of mefloquine, although it can occur orbital pain increased with eye movement, myelopathy, in patients who have been treated with other drugs. This has brachial neuritis, facial palsy, cauda equina, and Guillan- led to the recommendation that mefloquine should not be Barre syndromes. used in the treatment of cerebral malaria unless there is no alternative available. The symptoms are distressing but ENCEPHALITIS generally short lived (ranging from a few hours to 10 days). Arboviruses There is also a syndrome of cerebellar ataxia occurring after There are many arthropod borne viruses capable of causing malaria with symptoms continuing for a few weeks. Mostly encephalitis. Incubation periods and particular geographical these are self-limiting conditions that may have an auto- risks are given in table 1. Arboviruses are major causes of immune post-infectious aetiology. There is no trial evidence encephalitis worldwide, but Japanese encephalitis (JE) virus of benefit from treatment with corticosteroids. is probably responsible for more cases of acute encephalitis than all the other arboviruses combined. JE virus appears to TYPHOID be expanding outward from southern China and Southeast Typhoid is a systemic infection characterised by high fever, Asia and is reaching Russia, the Philippines, Pakistan, and copyright. headache, and clouding of consciousness. It is caused by Australia. Depending upon the climate, disease can be Salmonella typhi. Salmonella paratyphi can cause a similar transmitted seasonally or year round. Most cases are although usually less severe syndrome, and has a shorter asymptomatic, but of those with clinically apparent disease incubation period. Up to 300 cases of typhoid are imported to 30% will die and 50% will be left with neurological deficit. the UK each year, the majority originating from South Asia. Treatment is supportive, but an effective vaccine is available. The mortality of untreated typhoid is around 20%. With West Nile virus is also increasing its geographical range. appropriate treatment this falls to less than 1%. The duration Originally confined to Africa and the Middle East, it has of illness is usually about four weeks. Despite common caused sporadic cases in humans and horses in Europe since misconceptions, diarrhoea occurs in only about 40% of people the 1960s, and a Romanian outbreak in 1996 affected 400 with typhoid; 20% have normal bowel habit and 40% are adults with 17 deaths. The virus was detected for the first constipated. An initial high fever, headache, malaise, and time in the USA in New York in 1999 (resulting in 62 deaths). http://jnnp.bmj.com/ occasionally dry cough may be followed by abdominal There is evidence of seropositivity among British birds, but no distension, splenomegaly, and rose spots (difficult to see in dark skinned patients) in the second week. Untreated, the evidence of disease in the UK yet. A vaccine for tick borne patient may develop a pronounced confusional state and encephalitis is available for hikers/campers travelling to complications occur: these include intestinal perforation or Scandinavia and central Europe. abscess formation in sites such as the heart, bones, joints, pleural space, or gall bladder. Sudden and massive intestinal Enteroviruses haemorrhage may be life threatening. Meningitis or cerebral Polio is the most notable enterovirus to cause neurological on September 25, 2021 by guest. Protected abscess may occur. Typhoid may present to the neurologist disease. It appears to have been eradicated from the early in the disease because of an acute confusional state or Americas, and the WHO anticipates global eradication by fits. Later and rarer neurological complications include 2005. There were 2000 cases worldwide last year compared transverse myelitis, polyneuropathy, cranial mononeuropa- with 350 000 in 1988. Other enteroviruses cause seasonal thy, and demyelinating leucoencephalopathy. meningitis and meningoencephalitis, often in children. There Diagnosis is made through isolation of the organism from was a large outbreak of enterovirus 71 infection in children in blood, stool, urine or bone marrow cultures, and treatment is Taiwan in 1998, in which there were a large number of with quinolone antibiotics guided by antibiotic sensitivity neurological complications with a death rate approaching testing and knowledge of the resistance patterns in the 20%. Patients typically had myoclonus, ataxia, and cranial country where the infection was acquired. nerve involvement. Currently treatment is supportive, but pleconaril is a new anti-enteroviral drug currently under- HIV going evaluation. Japanese encephalitis (and other flavi- Travellers are at increased risk of all sexually transmitted viruses such as West Nile virus, tick borne encephalitis) can infections. There were over 4200 new diagnoses of HIV present with a syndrome clinically very similar to polio.

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RABIES sion is more rapid in EASS, death occurring within a few Rabies is universally fatal once symptoms become apparent. weeks compared with months to years in WASS. Infection is caused by viruses of the genus Lyssavirus, usually following a bite from a warm blooded animal. Different East African sleeping sickness animals have different susceptibilities to infection—foxes The first stage of disease develops 5–15 days after the and coyotes appear most susceptible, while the opossum infective bite. There may be a chancre at the site of the bite, i8 seems relatively protected. Most human cases are caused by but this painful, well circumscribed papule is often not seen dog bites, but infection can result from apparently trivial in Africans. Local lymphadenopathy may develop, and fever contact with bats and other animals. European bat lyssa accompanies the waves of parasitaemia. Invasion of the viruses, which are closely related to the rabies virus, can central nervous system leads to the second stage of disease— cause a rabies-like illness in humans; a bat handler died in a progressive chronic meningoencephalitis leading to death Scotland in 2002. Volunteer and licensed bat handlers should 6–9 months after the initial bite. Drowsiness is the prominent be vaccinated against rabies. feature—focal neurological signs are less common than in Following a bite or scratch (or perhaps inhalation of bat WASS. respiratory secretions), there is a variable incubation period, usually between 20–90 days, before the development of West African sleeping sickness prodromal symptoms. An incubation period of 19 years has Incubation is 2–3 weeks, but chancres are uncommon. There been reported. Forty per cent of patients describe itching or is usually an irregular fever, but other symptoms may be parasthesiae at the healed injury site, and constitutional absent. Winterbottom’s sign (enlarged posterior cervical symptoms include fever, headache, myalgia, and gastro- lymph nodes) is seen in up to 85% of patients. The intestinal upset. Over the next few days, progression to one of asymptomatic period that follows may last for several years two syndromes—furious or paralytic rabies—occurs. The and parasites may be difficult to find within the blood. Signs former is most common and is characterised by hydrophobic of second stage (central nervous system) infection include spasms, excitation, aggression, and hallucinations inter- motor problems, speech disturbance, or a syndrome resem- spersed with periods of calm. There may be opisthotonus bling parkinsonism. Patients may suffer personality changes and generalised convulsions, arrhythmias, respiratory dis- or psychosis; change in sleep patterns precede apathy, coma, turbance, cranial nerve lesions, and autonomic dysfunction. and death. Most neurological signs reverse with treatment. Eventually there is coma, paralysis, and death. Paralytic rabies is characteristic of bat transmitted rabies. Following Diagnosis and treatment of sleeping sickness the prodrome, there is paraesthesia and ascending flaccid Expert help should be enlisted in the diagnosis and treatment paralysis starting from the injury site. There is loss of tendon of sleeping sickness. Diagnosis is made through demonstra- copyright. and plantar reflexes, but sensation is intact. Death occurs tion of parasites in the blood or lymph node aspirates. Blood after 1–3 weeks. concentration methods improve detection of parasites and Treatment consists of good wound toilet and post-exposure immunological tests are available for the diagnosis of WASS. immunoglobulin and post-exposure vaccination for those Treatment depends upon stage of disease. CSF should always suffering animal bites or scratches. This is extremely effective be examined for parasites, although one or two doses of if given before the development of clinical disease. For treatment are normally given before lumbar puncture to clear established disease, treatment consists of symptom control parasites from the blood and prevent inadvertent inoculation through sedation. Although admission to intensive care can into the CSF. A CSF leucocyte count of . 5 cells/ml is extend life for weeks and sometimes months, treatment with considered evidence of second stage disease, whether or not hyperimmune serum and antiviral drugs has not been parasites are seen. effective and death is inevitable. In wealthy countries rabies The treatment for sleeping sickness has significant toxic http://jnnp.bmj.com/ vaccine is produced from cell culture lines. In less wealthy effects. First stage WASS can be treated with pentamidine. countries it is sometimes derived from neural tissue, and Suramin is used for EASS. Second stage WASS is treated with there is a risk of a post-vaccinal encephalomyelitis which has eflornithine, while EASS is treated with melarsoprol, which similar symptoms to paralytic rabies. The incubation period is causes an encephalopathic syndrome with 50% mortality in two weeks to two months. Conventional treatment includes 10% of patients. corticosteroids. A fifth of cases are fatal, but if recovery occurs it is usually complete. HERPES B VIRUS This simian herpes virus is enzootic in macaques, with 80– on September 25, 2021 by guest. Protected AFRICAN TRYPANOSOMIASIS 90% of macaques being infected. It is the equivalent of herpes Human African trypanosomiasis (sleeping sickness) is caused simplex virus in humans, causing life long infection with by subspecies of the protozoan Trypanosoma brucei—Tb intermittent viral shedding, and is the only simian herpes gambiense (West African sleeping sickness, WASS) and Tb virus known to cause infection in humans. Macaque handlers rhodesiense (East African sleeping sickness, EASS). There has and travellers who are bitten or scratched by monkeys are at been a notable increase in the prevalence of this disease since risk, although human infection is rare. Incubation period in the 1980s, and WHO estimates up to 600 000 people are humans is typically 2–10 days, but intervals of up to 10 years currently infected. There have been clusters of infection of between exposure and illness may represent reactivation of EASS among tourists visiting game parks. The disease is latent infection. A herpetiform rash may develop at the site of universally fatal if untreated and occurs in localised pockets. a bite or scratch, accompanied by fever and malaise. An It is spread by the painful bite of the Tsetse fly. EASS and ascending paralysis develops over the following 1–2 weeks, WASS differ in their epidemiology and clinical presentation. which then leads to a pan-encephalitis. Diagnosis can be EASS is a zoonosis, with cattle forming the main reservoir. made by polymerase chain reaction (PCR) of CSF. Mortality Humans are the major reservoir in WASS. Disease progres- is high at around 60%. Therapeutic experience is limited but

www.jnnp.com NEUROLOGY IN PRACTICE J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2003.034330 on 20 February 2004. Downloaded from intravenous acyclovir is recommended, as is post-exposure paralysis, and respiratory arrest. Some patients are reported acyclovir prophylaxis for those suffering bites or scratches. to suffer reversed perception of hot and cold. The neurological symptoms may persist for many years. CRYPTOCOCCAL MENINGITIS Cryptococcus neoformans has achieved prominence as the MEDICATION AND VACCINATIONS second leading cause of death in HIV positive patients Neurological illnesses may occur as a result of pre-travel worldwide. In the tropics, particularly northern Australia and vaccinations or a side effect of antimalarial drugs. Rarely i9 Papua New Guinea, there is a variety of C neoformans that Japanese B encephalitis vaccination has been associated with affects the immunocompetent (C neoformans var gattii). There encephalomyelitis (around 1 in 10 000), although the risk is commonly concomitant pulmonary disease. In the envir- may have been overstated. Many people taking a number of onment it is found in close association with the eucalyptus anti-malarial drugs report mild neuropsychiatric side effects. tree, and koala bears are also affected. Treatment is similar to Mefloquine may cause dizziness, vertigo, and fits, and very treatment for HIV associated disease, although there may be rarely may be associated with severe neuropsychiatric effects. a role for steroids. Permanent neurological deficit, particularly blindness, is common and the mortality rate is high. SUMMARY EOSINOPHILIC MENINGITIS Despite the large number of exotic infecting agents that may There are many causes of this syndrome. In travellers to cause neurological syndromes, the returning traveller is more Africa, schistosomiasis is the most common helminth likely to be infected with an organism that is well known to infection encountered. Very rarely, an eosinophilic meningitis the temperate physician. Meningitis will most likely be due to may result from the presence of ectopic eggs; this requires organisms indigenous to the UK, encephalitis will most likely prolonged infection and a relatively heavy worm burden, and be due to herpes simplex virus. The two most commonly is therefore rare in the tourist. Ectopic deposition of eggs in imported life threatening tropical infections are malaria and schistosomiasis can also cause spinal syndromes. typhoid, and these illnesses should be excluded quickly in all The risk of eosinophilic meningitis is greater for the patients. Detailed history taking, particularly regarding traveller to Southeast Asia, where the justifiably famous travel, activities while away, sexual history and immunisa- cuisine may include raw or pickled snails, amphibian, or tion history helps to narrow the differential diagnosis. A snakes (fig 2). The cautious take a phrase book into the methodical approach and basic knowledge of incubation restaurants. It is relatively easy to kill the worms with periods can help to limit unnecessary investigation. antiparasitic drugs. However, the physical damage caused by the infection may result in severe neurological deficit...... Steroids are recommended as adjuvant treatment. copyright. Authors’ affiliations TICK PARALYSIS J N Day, Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, VietNam Both hard (Ixodidae) and soft (Argasidae) ticks have been D G Lalloo, Clinical Research Group, Liverpool School of Tropical implicated in tick paralysis, due to a neurotoxin contained Medicine, Liverpool, UK within tick saliva that causes pre-synaptic neuromuscular block and decreased nerve conduction velocity. Most cases occur in North America and Australia, and the mortality is REFERENCES 10%. The syndrome, which is of a progressive ascending 1 Cook GC, Zumla A, eds. Manson’s tropical diseases, 21st ed. Saunders 2003, lower motor neurone paralysis, develops 5–6 days after the Elsevier Science Ltd, Edinburgh, UK. tick has been embedded. Over the next few days bulbar and c The standard tropical diseases text. 2 Newton PN, Angus BJ, Chierakul W, et al. Randomized comparison of respiratory paralysis will develop. There may be vomiting. The http://jnnp.bmj.com/ artesunate and quinine in the treatment of severe falciparum malaria. Clin attached tick is usually not obvious, and may be in a body Infect Dis 2003;37:7–16. fold or on the scalp. There may be more then one tick 3 Nguyen TH, Day NP, Ly VC, et al. Post-malaria neurological syndrome. Lancet 19965;348:917–21. attached so the whole body should be carefully examined. c Important paper describing this syndrome and the association with Symptoms usually resolve rapidly with tick removal. mefloquine treatment. 4 Crawley J, Waruiru C, Mithwani S, et al. Effect of phenobarbital on seizure Antitoxin is available in Australia. frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study. Lancet 2000;355:701–6. SHELLFISH/CIGUATERA TOXIN POISONING c Seminal paper demonstrating increased mortality in children with Various toxin producing dinoflagellates (algae) can become severe malaria given prophylactic phenobarbital. on September 25, 2021 by guest. Protected 5 Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging concentrated in the food chain and result in poisoning when pathogens [review]. Lancet 2002;359:507–13. eaten. Paralytic shellfish poisoning results from eating 6 World Health Organization. http://www.who.int/health_topics/malaria/ en/. bivalve molluscs such as clams, oysters, and scallops. Onset c WHO malaria site detailing epidemiology, ‘‘Roll Back Malaria’’ is rapid (within 30 minutes) and includes peri-oral anaes- campaign, definitions, and treatment. thesia, gastrointestinal symptoms, ataxia, and paralysis 7 Legros D, Ollivier G, Gastellu-Etchegorry M, et al. Treatment of human African trypanosomiasis – present situation and needs for research and rapidly progressing to respiratory arrest in 8% of cases. development [review]. Lancet Infect Dis 2002;2:437–40. Ciguateratoxin poisoning results from eating carnivorous fish c Good description of currently available treatment and future research objectives. such as snappers and barracuda. Incubation period is 8 Solomon T. Recent advances in Japanese encephalitis [review]. J Neurovirol minutes to 30 hours after ingestion. Again gastrointestinal 2003;9:274–83. 9 Shakir R, Newman P, Poser C, eds. Tropical neurology. Philadelphia: symptoms may be present, which accompany a wide variety Saunders, 1995. of neurological symptoms including ataxia, vertigo, flaccid c A good summary of neurological problems associated with the tropics.