Requests for malaria prevention advice to Public Health England, Malaria Reference Laboratory: a retrospective observational study.

BACKGROUND: The Malaria Reference Laboratory (MRL) provides a specialist advisory service for complex queries from healthcare professionals. This study was conducted to examine the types of queries that general practitioners and nurses ask around malaria prophylaxis, to identify issues which are not obvious from existing easily available sources. METHODS: We reviewed all the faxed requests received over a period of 6 months at the MRL. RESULTS: There were a total of 608 queries (104 concerning children) relating to 450 travellers. 98% of requests were from general practice (GP or practice nurse). The most common enquiries were about travellers to multiple destinations (95/529, 17.96%), prolonged duration of travel (70/529, 13.23%), the immunosuppressed (38/529, 7.18%), potential drug interactions (69/529, 13.04%), pregnancy and conception (36, 6.81%). 79/529 queries related to patients with multiple conditions requiring expert advice from the MRL. 27% of the enquiries could have been answered by consulting the UK malaria prophylaxis guidelines available on the MRL site. CONCLUSION: Most queries where practitioners requested help were not easily answered with existing guidelines. Pregnancy and epilepsy are areas where guidance needs strengthening. Difficulties for practitioners were multifactorial, it would be difficult to address all scenarios in guidelines without making them unwieldy

Mortality associated with cysticercosis in a historical cohort from Britain

BACKGROUND: The burden of premature mortality associated with human cysticercosis is largely ignored mainly due to poor record-keeping in Taenia solium endemic regions. OBJECTIVE: To document mortality and survival characteristics of an historical cohort with cysticercosis. METHODS: The years of onset of symptoms and death untill 1957 were extracted from published reports of a British military cohort (n=450) examined in London in the early twentieth century. Data were entered into a Kaplan Meier survival analysis with the presence (or absence) of clinical manifestations as independent variables, which were then fitted into a Cox proportional hazards model to determine their significance. RESULTS: Cysticercosis was responsible for 24 (52.2%) of 46 deaths in the first 15 years of follow-up in comparison to 7 (19.4%) of 36 deaths in the 20-40 years of follow-up period. In the univariate and Cox analyses, intracranial hypertension (hazard ratio [HR]: 8.26; CI: 4.71, 14.49), ocular cysticercosis (HR: 6.60; CI: 3.04, 14.33), and mental disorder (HR: 3.98; CI: 2.22, 7.13) but not epilepsy (HR: 0.66; CI: 0.20, 2.18) were associated with mortality. Over half of all deaths in the first 15 years of follow-up were attributed to cysticercosis. CONCLUSIONS: Several deaths occurred early after acquiring cysticercotic infection. Intracranial hypertension, ocular cysticercosis, and mental disorder but not epilepsy were predictors of mortality in this cohort

Gametocyte carriage in Plasmodium falciparum-infected travellers.

BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease

Hyperreactive Malarial Splenomegaly Syndrome--Can the Diagnostic Criteria Be Improved?

Hyperreactive Malarial Splenomegaly Syndrome (HMSS) was described and defined before sensitive tests for malaria were available. We present a series of seven individuals who were referred to our clinics with possible HMSS. Chronic malaria was demonstrated in those successfully treated but not in those who failed to respond to therapy. This observation suggests that the newer molecular malaria assays have a role to play in the identification of individuals who are likely to respond to treatment for HMSS in non-endemic regions

Gnathostomiasis: An Emerging Imported Disease

As the scope of international travel expands, an increasing number of travelers are coming into contact with helminthic parasites rarely seen outside the tropics. As a result, the occurrence of Gnathostoma spinigerum infection leading to the clinical syndrome gnathostomiasis is increasing. In areas where Gnathostoma is not endemic, few clinicians are familiar with this disease. To highlight this underdiagnosed parasitic infection, we describe a case series of patients with gnathostomiasis who were treated during a 12-month period at the Hospital for Tropical Diseases, London

Visceral Leishmaniasis in Traveler to Guyana Caused by Leishmania siamensis, London, UK.

The parasite Leishmania siamensis is a zoonotic agent of leishmaniasis; infection in animals has been documented in Europe and the United States. Reported authochthonous human infections have been limited to Thailand. We report a case of human visceral Leishmania siamensis infection acquired in Guyana, suggesting colonization in South America

Epidemiology of imported cutaneous leishmaniasis at the Hospital for Tropical Diseases, London, United Kingdom: use of polymerase chain reaction to identify the species.

This study reviewed all patients diagnosed with imported cutaneous leishmaniasis (CL) at the Hospital for Tropical Diseases in London, United Kingdom, over an 11-year period. Diagnostic and epidemiologic information was collected prospectively for all patients with imported CL to this hospital during 1998-2009. A total of 223 patients were given a diagnosis of CL. Ninety patients were diagnosed with Old World CL, which was caused most commonly by Leishmania donovani complex (n = 20). A total of 71% were tourists to the Mediterranean region, 36% were migrants or visiting friends and relatives, and 17% were soldiers. One hundred thirty-three patients were given a diagnosis of New World CL. The Leishmania subgenus Viannia caused 97 of these cases; 44% of these were in backpackers and 29% were in soldiers. Polymerase chain reaction was more sensitive and faster for detecting Leishmania DNA (86% for Old World CL and 96% for New World CL) than culture. This is the largest study of imported leishmaniasis, and demonstrates that tourists to the Mediterranean and backpackers in Central and South America are at risk for this disease

Clinical Features of Imported Loiasis: A Case Series from the Hospital for Tropical Diseases, London.

We retrospectively analyzed the background, clinical features, and treatment response of 50 cases of imported loiasis who presented between 2000 and 2014 to the Hospital for Tropical Diseases (HTD), London, United Kingdom. Of them, 29 were migrants from, and 21 were visitors to, countries where the disease is endemic. Clinical features differed between these groups. Migrants experienced fewer Calabar swellings (odds ratio [OR] = 0.12), more eye worm (OR = 3.4), more microfilaremia (OR = 3.5), lower filarial antibody levels, and lower eosinophil counts (P 3,000 microfilariae/mL and all those with an elevated C-reactive protein (CRP) (≥ 5 mg/L) before treatment had reactions (P = 0.10 and P = 0.01, respectively). These data suggest that monotherapy with DEC may not be the optimal treatment for patients with loiasis, particularly for those with a high microfilarial load

Culture-adapted Plasmodium falciparum isolates from UK travellers: in vitro drug sensitivity, clonality and drug resistance markers.

BACKGROUND: The screening of lead compounds against in vitro parasite cultures is an essential step in the development of novel anti-malarial drugs, but currently relies on laboratory parasite lines established in vitro during the last century. This study sought to establish in continuous culture a series of recent Plasmodium falciparum isolates to represent the current parasite populations in Africa, all of which are now exposed to artemisinin combination therapy. METHODS: Pre-treatment P. falciparum isolates were obtained in EDTA, and placed into continuous culture after sampling of DNA. One post-treatment blood sample was also collected for each donor to monitor parasite clonality during clearance in vivo. IC₅₀ estimates were obtained for 11 anti-malarial compounds for each established parasite line, clonal multiplicity measured in vivo and in vitro, and polymorphic sites implicated in parasite sensitivity to drugs were investigated at the pfmdr1, pfcrt, pfdhfr, pfdhps and pfap2mu loci before and after treatment, and in the cultured lines. RESULTS: Plasmodium falciparum isolates from seven malaria patients with recent travel to three West African and two East African countries were successfully established in long-term culture. One of these, HL1211, was from a patient with recrudescent parasitaemia 14 days after a full course of artemether-lumefantrine. All established culture lines were shown to be polyclonal, reflecting the in vivo isolates from which they were derived, and at least two lines reliably produce gametocytes in vitro. Two lines displayed high chloroquine IC₅₀ estimates, and carried the CVIET haplotype at codons 72-76, whereas the remaining five lines carried the CVMNK haplotype and were sensitive in vitro. All were sensitive to the endoperoxides dihydroartemisinin and OZ277, but IC₅₀ estimates for lumefantrine varied, with the least sensitive parasites carrying pfmdr1 alleles encoding Asn at codon 86. CONCLUSIONS: This study describes the establishment in continuous culture, in vitro drug sensitivity testing and molecular characterization of a series of multiclonal P. falciparum isolates taken directly from UK malaria patients following recent travel to various malaria-endemic countries in Africa. These "HL" isolates are available as an open resource for studies of drug response, antigenic diversity and other aspects of parasite biology

Malaria

Migrant Health: Infectious diseases in non-UK born populations in the UK An update to the baseline report- 2011