Imported Diseases
The common diseases of travellers (Table 21.2) returning to temperate climates are malaria, acute gastroenteritis including typhoid, infectious hepatitis and worm infestation. Diarrhoea in returning travellers requires investigation for worms and parasites (especially Giardia and amoeba), but usually no organism is found and the symptoms settle spontaneously or with simple therapy. Other diseases common in the tropics but rarely seen in returning travellers include tuberculosis, schistosomiasis, hydatid disease, poliomyelitis, tetanus, cholera, leprosy and trypanosomiasis.
Table 21.2 Diseases of the Returning Traveller
| Incidence | Disease |
| Common | Malaria |
| Typhoid | |
| Diarrhoea often viral as pathogens rarely found but consider: | |
| Giardia lamblia and worms | |
| Amoebic colitis which must be distinguished from ulcerative colitis and Crohn’s disease | |
| Salmonella and | |
| Shigella infection | |
| Tropical sprue | |
| Infectious hepatitis | |
| Rare | Tuberculosis – usually not acute and more likely in Asian immigrants |
| Amoebic liver abscess | |
| Hydatid liver cyst | |
| Exceedingly rare | Rabies |
| Cholera | |
| Exotic viruses | |
| Lassa fever | |
| Marburg | |
| Ebola | |
Malaria
Malaria is a disease of the subtropics and where the anopheline mosquito is found. Transmission is via the mosquito, which carries infected blood from infected to uninfected humans. The mosquito lives chiefly between latitude 15° north and south and not more than 1,500 m (5,000 ft) above sea level.
Clinical Features
The patient presents with fever and rigors usually within 4 weeks of returning from or travelling through a malarial zone. Occasionally symptoms may not develop for 12 months or more. The patient has usually failed to take antimalarials regularly, not slept under mosquito nets or failed to continue prophylaxis for 6 weeks after returning. The fever may fit the pattern of tertian (a 3-day pattern with fever peaking every other day (Plasmodium vivax and P. ovale)), quartan (a 4-day pattern with fever peaking every third day) or subtertian (a non-specific febrile pattern (P. falciparum)). Diagnosis depends upon clinical awareness and then seeing the parasite in a blood film. In the UK, P. falciparum and P. vivax are most frequently seen in travellers from Africa and Asia. Malignant tertian malaria refers to P. falciparum which, very occasionally, produces high levels of parasitaemia (only P. falciparum gives red blood cell parasitaemia of > 1–2%), serious complications of cerebral malaria or acute haemolysis and renal failure (blackwater fever).
Prophylaxis
Prophylaxis is by a combination of mosquito control, sleeping under mosquito nets and specific prevention with proguanil (Paludrine) 200 mg/day, with chloroquine 300 mg twice weekly. For regions known to have chloroquine-resistant malaria, mefloquine, doxycycline and atovaquone-proguanil are used. Prophylaxis should be continued for 6 weeks after returning home.
NB Before advising travellers, check whether they are entering a malarial zone, and seek advice from the nearest centre for tropical diseases about the current recommended prophylaxis because drug resistance, particularly of P. falciparum malaria, is continually changing.
Treatment
See Table 21.3.
Table 21.3 Antimalarial Drugs
| Drug | Important side effects | Comments |
| Chloroquine | GI upset, headache, retinal damage and cataracts, rarely myelotoxicity, psychosis. Contraindicated in epilepsy.*Reduce dose in renal failure | Resistance is widespread, but confined to Plasmodium falciparum. Not active against dormant hepatic forms (hypnozoites) of Plasmodium vivax and Plasmodium ovale |
| Fansidar (pyrimethamine and sulphadoxine) | Skin rash, myelotoxicity | For eradication of Plasmodium falciparum infection |
| Maloprim (pyrimethamine and dapsone) | Skin rash, myelotoxicity | Prophylaxis only |
| Malarone (proguanil and atovaquone) | GI upset, mouth ulcers, insomnia, blood disorders, skin rash, hyponatraemia | Prophylaxis and treatment of uncomplicated Plasmodium falciparum |
| Mefloquine | Contraindicated in first trimester, breast-feeding, neurological disease, epilepsy* (including family history), liver disease, concurrent β-blocker therapy. | Prophylaxis and treatment of chloroquine-resistant Plasmodium falciparum malaria |
| Causes neuropsychiatric effects and Gl upset. Avoid pregnancy for 3 months after stopping treatment. | ||
| Treatment duration should not exceed 1 year | ||
| Primaquine | GI upset, haemolysis, particularly in G6PD deficiency | Eradication of dormant hepatic forms (hypnozoites) of Plasmodium vivax and Plasmodium ovale |
| Proguanil | GI upset, rarely mouth ulcers. | Prophylaxis only |
| Reduce dose in renal failure | ||
| Quinine | Tinnitus, hypoglycaemia, headaches, flushing, Gl upset, rash, myelotoxicity | Agent of choice for treatment of chloroquine-resistant or severe Plasmodium falciparum malaria |
| Riamet (artemether and lumefantrine) | GI upset, skin rash, arthralgia, myalgia, arrhythmias (QT prolongation) | Treatment of uncomplicated Plasmodium falciparum |
| GI, gastrointestinal; G6PD, glucose-6-phosphate dehydrogenase. | ||
| * Doxycycline is an alternative in patients with epilepsy. | ||
Acute Attacks
Patients with malaria should be given oral quinine (or Malarone or Riamet). Intravenous quinine is potentially dangerous because it may produce cardiac asystole but is used in those who are vomiting or too ill to take oral therapy. Exchange transfusion may be required in very ill patients with high parasitaemia – consider if levels above 10%. Some require full intensive care, including treatment of cerebral oedema, renal and liver failure and shock. Hypoglycaemia from a combination of liver failure and quinine-induced insulin secretion is easily overlooked; pulmonary oedema from fluid overload is common in those treated for shock.
After treatment of the acute attack, falciparum malaria is cleared with Fansidar or doxycycline, and vivax malaria with primaquine (check the glucose-6-phosphate dehydrogenase status first).
Typhoid
Clinical Features
Symptoms begin with malaise, headache, dry cough and vague abdominal pain, up to 21 days after returning from a typhoid area. Travellers to any area with poor sanitation are at risk and typhoid occasionally occurs in non-travellers. In the first week, fever is marked, with dry cough and constipation typical features. In the second week, the fever persists, the abdomen distends, diarrhoea may or may not occur and rose spots develop as crops of pale pink macules on the sides of the abdomen. Delirium and death may occur in untreated cases.
NB Symptoms of dry cough, constipation and fever should be sufficient to alert the clinician, particularly in returning holiday-makers.
Investigation
Leukopenia and neutropenia may or may not be present. Blood culture is mandatory if typhoid is suspected and culture of urine and stool should also be performed.
Treatment
Salmonella typhi responds to ciprofloxacin. Cefotaxime is also effective.
NB
- It is unnecessary to give antibiotics to patients who are clinically well but from whom S. typhi is grown from the stools. If these patients are given antibiotics, they are more likely to become chronic excretors of antibiotic-resistant S. typhi.
- Typhoid must be reported to the public health authorities.
- Excretors of S. typhi are not allowed to work in the food industry.
Dysentery
Bacillary Dysentery (Shigellosis)
Bacillary dysentery is caused by the genus Shigella. S. sonnei is the most common and occurs in outbreaks in close communities. It produces the most serious clinical form of the disease, including septicaemia. It is transmitted by faecal contamination of food and water and 2–4 days after ingestion produces acute diarrhoea, sometimes accompanied by abdominal colic, vomiting and tenesmus. If severe, there is rectal blood, mucus and pus. Asymptomatic carriage can occur.
The disease is prevented by good sanitation, clean water supplies and good personal hygiene. Infected patients should be isolated and rehydrated. Ciprofloxacin (or amoxicillin or trimethoprim if sensitive) are required if the patient is unwell, but antibiotics are not indicated for mild cases. The public health service must be informed and patients and close contacts should not handle food until the stool cultures are negative.
Shigella dysentery can be confused with Salmonella food poisoning, and amoebic and ulcerative colitis (p. 130).
Amoebic Dysentery
This is an infection of the colon by the protozoon Entamoeba histolytica. In the acute dysenteric form, the illness begins suddenly with fever, abdominal pain, nausea, vomiting and diarrhoea containing mucus and blood. More commonly, amoebic colitis presents less acutely with intermittent diarrhoea with or without abdominal pain, mucus and blood.
The major complications are hepatic abscesses and pericolic amoebomas which can be confused with colonic carcinoma. The diagnosis is made by finding trophozoites or cysts in fresh faeces, rectal mucus or rectal biopsy and supported by a positive complement fixation test.
Metronidazole is the treatment of choice for all invasive forms of amoebiasis, but abscesses may have to be drained if they do not resolve on drug therapy. Diloxanide is used to eradicate chronic amoebic cysts.
Cyst excretors should not handle food, and contacts should be screened. Acute amoebiasis can be confused with bacillary dysentery, Salmonella food poisoning and ulcerative colitis, and chronic infection with Giardia lamblia, tropical sprue, ulcerative colitis and diverticular disease (p. 139).
Giardiasis
Giardia lamblia is a flagellate protozoon which infects the small intestinal wall but not the blood. Viable cysts are ingested with contaminated food and may be excreted asymptomatically, or produce diarrhoea and steatorrhoea. The diagnosis is confirmed by the presence of trophozoites or cysts in stools or duodenal aspirates. Tinidazole and metronidazole are the drugs of choice.
Pyrexia of Unknown Origin
There are many definitions of pyrexia of unknown origin. In practice, the difficulty arises when the cause is unidentified after the clear clinical possibilities have been excluded and a basic set of tests performed. It is usually a hospital problem. A broad-spectrum antibiotic has commonly been given. The causes are listed in Table 21.4.
Table 21.4 Causes of Pyrexia of Unknown Origin (Mnemonic – IMAGINE)
| Infections | Bacterial. Bacillary endocarditis and septicaemia (including culture-negative) |
| *Collections of pus | |
| Subphrenic | |
| Intrahepatic | |
| Perirenal | |
| Pelvic | |
| Pleura | |
| Bone (osteomyelitis) | |
| Viral/rickettsial | |
| (including hepatitis B) | |
| Protozoal | |
| Malaria, amoeba, spirochaetes | |
| Specific | |
| Tuberculosis* (all sites), typhoid, Brucella, Lyme disease (Borrelia burgdorferi) | |
| Malignancy | Kidney and liver (primary and secondary) |
| PancreasMicrometastases, lymphoma (Hodgkin’s and non-Hodgkin’s), leukaemia | |
| Autoimmunediseases | *Systemic lupus erythematosus, polyarteritis nodosa, systemic vasculitis |
| Chronic active hepatitis | |
| Rheumatoid disease, Still’s disease (including adult Still’s disease, p. 295) | |
| Granulomas | Sarcoid |
| Crohn’s disease | |
| Iatrogenic | Drug fever |
| Nurses and doctors and all paramedicals, | Factitious fever |
| etc. | Consult exhaustive lists in big books, but remember that the cause is more often a rare manifestation of a common disease than a common manifestation of a rare disease |
| * Denotes a more likely cause of pyrexia of unknown origin; all are treatable and potentially curable. | |
Special Points in the History
- exposure to infection (meals away from home, febrile illness in household contacts, unpasturised milk or cheese, undercooked eggs and poultry).
- occupation: farmer, veterinary surgeon, sewer worker, forester (for Brucella, Leptospira, anthrax, cat-bite fever, Lyme disease).
- drug history, e.g. antibiotics, methyldopa, hydralazine, phenytoin, including non-prescribed preparations.
- travel (malaria, amoebiasis) and sexual history.
- pets, including dogs, cats and birds.
Special Points in Examination
NB Repeat regularly, e.g. on alternate days, if the fever persists.
- cardiovascular: murmurs, especially if changing, suggest infective endocarditis; tender temporal arteries; Dressler syndrome
- respiratory: crackles (crepitations or rales) for early pneumonia (e.g. Legionnaires’ disease); sinuses; consider recurrent pulmonary thromboembolic disease
- abdomen: palpable liver, gall bladder or spleen (with or without tenderness)
- musculoskeletal: muscle stiffness and tenderness of inflammatory diseases, e.g. polymyalgia rheumatica
- skin rashes (drugs, rose spots of typhoid): splinter haemorrhages; Osler’s nodes
- lymph nodes (all groups)
- check all orifices: mouth (teeth for apical abscesses), ears, perineum (anus and genitourinary tract)
Basic Screening Tests Already Performed (Check)
Most will need to be repeated until a diagnosis has been achieved.
- Haemoglobin: if anaemia is present and considerable, it is usually relevant. If iron-deficient and there is no overt blood loss, exclude gut malignancy.
- White blood cell (WBC) count: neutrophilia is associated with pyogenic infection and neoplasia, and neutropenia with viral infection. Lymphocytosis may suggest tubercle. Leukaemia and infectious mononucleosis are usually associated with abnormal peripheral counts and cell types (remember direct tests for infectious mononucleosis). Eosinophilia may suggest parasites or polyarteritis nodosa.
- Erythrocyte sedimentation rate: if over 100 mm/h, check for myeloma and consider polymyalgia rheumatica or underlying malignancy.
- Mid-stream urine: haematuria, possibly microscopic, occurs with bacterial endocarditis, renal carcinoma, polyarteritis nodosa and leptospirosis. WBCs in infection. Early morning urine for acid-fast bacillus (AFB). NB Glycosuria suggests infection somewhere.
- Chest X-ray: carcinoma (primary or secondary) in lungs, and bone metastases. Miliary shadowing in miliary tuberculosis and sarcoid. Hilar nodes in tuberculosis, lymphoma, sarcoid and carcinoma.
- Sputum for microorganisms, including AFB.
- Liver function tests (LFTs) for secondary or primary malignancy, abscess, biliary disease, hepatitis (p. 144).
- Infectious mononucleosis screening test, e.g. Monospot.
- Blood culture (× 3).
Further Tests Commonly Required as Determined by Clinical Leads
- viral, brucella, mycoplasma and coxiella antibody titres
- auto-antibody screen
- ultrasound or computed tomographic (CT) scan of abdomen for liver abscesses, and for secondaries, for renal tumours and abscesses, and for splenic enlargement, and of the pelvis for pelvic lesions
- echocardiography for vegetations
- CT scanning of chest for lymphadenopathy and infection
Invasive Procedures as Indicated
- temporal artery biopsy
- liver needle biopsy (tuberculosis, granulomas, neoplasm)
- muscle biopsy
Go back again and again to take a new history, to re-examine the relevant areas and to repeat selected investigations, especially those that might have been performed too early, i.e. before they could have become abnormal.
Other Imported Pathogens: Nematodes, Schistosomes
The worms listed in Table 21.5 are found worldwide and not uncommonly in travellers who live rough or enter areas of poor sanitation.
Table 21.5 Common Worms
| Worm | Major clinical features | Treatment |
| Threadworm | Anal itch | Piperazine |
| (Enterobius vermicularis) | Worm on stool | Thiabendazole (treat all household members to prevent reinfection) |
| Roundworm | Worm on stool | Piperazine |
| (Ascaris lumbricoides) | ||
| Hookworm | Nil. If severe infection, | Bephenium (Alcopar) |
| (Necator americanus: | iron-deficient anaemia; | Pyrantel |
| Ancylostoma duodenale) | malnutrition in children | Tetrachloroethylene |
| Eggs or worms in stools | ||
| Schistosoma | Fever and eosinophilia | Praziquantel (for both) |
| S. mansoni (spur on side) | Initially diarrhoea | |
| S. haematobium (spur on tail) | Haematuria |
Septicaemia
Common organisms are Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Enterococcus species. Common sources include intravenous catheters, genitourinary and respiratory tract, and intra-abdominal foci. Coagulase-negative staphylococci isolated from blood cultures may be contaminants and not clinically significant, but they are a common cause of hospital-acquired bacteraemia related to intravenous catheters.
Management
General measures include good nursing care and fluid and electrolyte balance, and in severe cases intensive therapy, including treatment of shock and renal failure.
The key management points are:
