We propose that our patient was bitten by a sandfly in Malta and injected with Leishmania promastigotes. She initially developed localised disease, modified by ongoing immunosuppression, resulting in loss of immune control and then progressed to visceral infection. This is an unusual sequence of events in that patients usually develop either cutaneous leishmaniasis or visceral leishmaniasis depending on the infecting strain and host immunity. L donovani can cause both cutaneous and visceral disease.
Leishmaniasis is endemic in 88 countries and infects 12 million people worldwide causing 57 000 deaths every year.
2 Geographical distribution is expanding under the twin pressures of urbanisation and migration. Cutaneous leishmaniasis causes 75% of the 2 million new cases annually; however, visceral leishmaniasis is far more severe with an untreated mortality of almost 100%.
L donovani (Asia and Africa) and
L infantum (Southern Europe and South America) cause 500 000 cases of visceral leishmaniasis annually.
The infecting vector is the female phlebotomus sandfly and features include fever, cough, hepatosplenomegaly and lymphadenopathy. Recognised risk factors include HIV, malnutrition, transplantation and haematological neoplasia. Liposomal amphotericin is the gold standard for treatment of visceral leishmaniasis and cure rates of 98% have been demonstrated in immunocompetent patients.
3 Visceral leishmaniasis has been reported in three other cases involving adalimumab all in rheumatoid arthritis patients.
4–6The organism is an obligate intracellular protozoon, which replicates in macrophages. Adalimumab is a humanised IgG1 monoclonal antibody directed against the cytokine TNFα. Its action directly impairs the T helper type one response needed to control the disease as supported by the association of infliximab with a variety of opportunistic infections ranging from leprosy to
Pneumocystis jirovecii.
7The role of TNFα has been well-established in controlling tissue granuloma formation and cytokine-induced macrophage activation.
8 Patients with active leishmaniasis exhibit a lower frequency of TNFα monocytes, associated with higher levels of IL-10, suggesting a mechanism for individual susceptibility.
9 TNF-deficient mice exhibit absent early granulomatous reactions with widespread tissue inflammation and hepatic necrosis.
10 Key features in mice with persistent tuberculosis are the lack of an organised granulomatous response suggesting TNFα has a key role in signalling appropriate immune cells and maintaining granuloma structure.
11Monoclonal antibody treatment against TNFα is successfully used in disorders ranging from psoriasis to rheumatoid arthritis. Over 27 0000 patients worldwide have been treated with adalimumab. Use will only increase and the need for informed clinical surveillance among a wide variety of physicians will need to be enhanced accordingly. The risks associated with these drugs require careful assessment prior to use, advice to the patient on avoiding vector exposure and close clinical follow-up of the patient with a high index of suspicion for reported symptoms.
Learning points- Increasing use of biologics in a variety of specialties is likely to lead to a rise in the number of hitherto unusual opportunistic infections.
- Monoclonal antibodies to TNFα abrogate the normal T cell response to a wide variety of pathogens.
- With particular reference to diseases not normally associated with developed nations, a careful travel history and liaison with infectious diseases is important.
- Patients in living in endemic areas are at particular risk; however, this case highlights the limited nature of exposure sufficient to cause infection.
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