Guidelines for the public health management of typhoid and paratyphoid in England: practice guidelines from the National Typhoid and Paratyphoid Reference Group.

OBJECTIVES: The Typhoid and Paratyphoid Reference Group (TPRG) was convened by the Health Protection Agency (HPA) and the Chartered Institute of Environmental Health (CIEH) to revise guidelines for public health management of enteric fever. This paper presents the new guidelines for England and their rationale. METHODS: Methods include literature reviews including grey literature such as audit data and case studies; analysis of enhanced surveillance data from England, Wales and Northern Ireland; review of clearance and screening schedules in use in other non-endemic areas; and expert consensus. RESULTS: The evidence and principles underpinning the new guidance are summarised. Significant changes from previous guidance include: • Algorithms to guide risk assessment and management, based on risk group and travel history; • Outline of investigation of non-travel cases; • Simplified microbiological clearance schedules for cases and contacts; • Targeted co-traveller screening and a "warn and inform" approach for contacts; • Management of convalescent and chronic carriers. CONCLUSIONS: The guidelines were launched in February 2012. Feedback has been positive: the guidelines are reported to be clear, systematic, practical and risk-based. An evaluation of the guidelines is outlined and will add to the evidence base. There is potential for simplification and consistency between international guidelines.

Knowledge, attitudes and health outcomes in HIV-infected travellers to the USA.

BACKGROUND: The USA bans entry to non-citizens unless they obtain a waiver visa. AIM: To establish how many people with HIV infection travelled to the USA, whether they were aware of the travel restriction, whether they travelled with a waiver visa and HIV inclusive medical insurance and how they managed with their antiretroviral medication (ARV). DESIGN: Collation of data from cross-sectional studies conducted independently at three different medical centres, Manchester, Brighton and London, using a structured self-completion questionnaire. RESULTS: The overall response rate was 66.6% (1113 respondents). 349 (31%) had travelled to the USA since testing HIV positive, of whom only 14.3% travelled with a waiver visa. 64% and 62% of the respondents at Manchester and Brighton were aware of the need of a waiver visa. 68.5% (212) were on ARV medication at the time of travel and, of these, 11.3% stopped their medication. Of those taking ARV medication, only 25% took a doctors' letter, 11.7% posted their medication in advance. Of those discontinuing treatment (n=27), 55.5% sought medical advice before stopping, 11 were on NNRTI-based regimen and one developed NNRTI-based mutation. Only 27% took up HIV inclusive medical insurance. Many patients reported negative practical and emotional experiences resulting from travel restrictions. CONCLUSION: The majority of HIV patients travel to the USA without the waiver visa, with nearly half doing so with insufficient planning and advice. A significant minority (11.3%) stop their medication in an unplanned manner, risking the development of drug resistance.

Malaria prophylaxis policy for travellers from Europe to the Indian Subcontinent.

Analysis of malaria imported into eight European countries from the Indian Sub-continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus statement on the use of chemoprophylaxis within TropNetEurop. The proportion of cases from the ISC in 2004 ranged from 1.4%-4.6% of total imported cases. Plasmodium falciparum cases reported from the eight countries was only 23 (13% of all cases from the region). Total malaria reports between 1999-2004 fell from 317 to 180. The risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed. The group recommended non-selective prescribing of chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should be dropped.

New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers.

BACKGROUND: Mucosal leishmaniasis (ML) is an important complication of new world cutaneous leishmaniasis (CL) caused by species of the Leishmania Viannia subgenus. Previous reports of ML among travellers to Latin America are few. AIMS: To determine the annual number of cases of CL due to L. Viannia species diagnosed at this institution and to correlate this with changing patterns of travel. Secondly, to document the clinical presentation, diagnosis, treatment and outcome of ML at this institution. DESIGN: Retrospective observational study. METHODS: Data were collected from a clinical database, laboratory records, patient case notes and an international passenger survey. RESULTS: Between 1995 and 2003, the annual number of cases of CL (total 79) steadily increased from 4 per year to 18 per year; the estimated number of travellers from the UK to Latin America increased 3.5-fold. Six cases of ML were diagnosed among British travellers in 1995 (1), 1997 (1) and 2002 (4). These infections were acquired in Bolivia (3), Colombia (2) and Belize (1). Nasopharyngeal symptoms developed 0-15 months after returning to the UK. Four patients had concurrent CL at diagnosis. Diagnosis of ML was delayed up to 6 months from the onset of symptoms. Mucosal biopsies from all 6 patients were PCR-positive for L. (Viannia) DNA; microscopy and culture were less sensitive. ML relapsed in one patient following treatment. DISCUSSION: Increasing travel to Latin America from the UK was associated with an increasing number of diagnoses of L. Viannia CL. ML is likely to emerge as a more frequently imported infection among such travellers. Familiarity with these diseases is important for prompt diagnosis and optimal management.

Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers.

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross-over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection. Pharmacokinetic parameters were derived from the main metabolite alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1)) and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life between both routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9 (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.

Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. OBJECTIVES: To present epidemiological and clinical data on imported P. vivax malaria collected at European level. MATERIAL AND METHODS: Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. RESULTS: Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41-158) versus 31 days (inter-quartile range 4-133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. CONCLUSIONS: TropNetEurop data can contribute to the harmonization of European treatment policies.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Descriptive study on the efficacy and safety of artesunate suppository in combination with other antimalarials in the treatment of severe malaria in Sudan.

Documentation on the efficacy of artesunate in Africa is limited, and no experience of artesunate use in Sudan is documented. Severe malaria in rural areas of Sudan, where facilities for the safe and effective use of parenteral quinine are lacking, is a frequent problem. Early treatment with artesunate suppositories would provide a simple method for use by unskilled staff and would be an alternative approach to treat malaria in settings with poor resources. We describe a hospital-based study of rectal artesunate in 100 adult patients with severe falciparum malaria with a dose derived from pharmacokinetic data (200 mg every 8 hours) over 3 days, which halted progression of severe disease and had a low fatality rate. The dosage schedule led to a rapid clinical response and reduced parasite clearance and fever subsidence times of (31.5 +/- 10.1 hours) and (31.4 +/- 11.1 hours). The sequential treatment of rectal artesunate with either doxycycline or pyrimethamine/sulfadoxine or mefloquine resulted in similar clinical cure rates of around 100%, and the combination of artesunate with either doxycycline or pyrimethamine/sulfadoxine was equally effective as mefloquine in preventing recrudescence. There were no significant adverse effects or signs of toxicity related to the treatment observed during the 28-day follow-up. The combination regimens could be used in areas where there is limited access to parenteral therapy for malaria.

Schistosomiasis prophylaxis in vivo using N,N-diethyl-m-toluamide (DEET).

Topical N,N-Diethyl-m-toluamide (DEET) was studied as a schistosomiasis prophylactic in vivo for the use of individuals with limited exposure. Fifteen subjects, on a 3-week expedition to Lake Malawi in September 2001, applied 50% DEET to their skin after exposure to lake water. No subjects developed evidence of a new infection at 3-month follow-up.

Knowledge of malaria, risk perception, and compliance with prophylaxis and personal and environmental preventive measures in travelers exiting Zimbabwe from Harare and Victoria Falls International airport.

BACKGROUND: Travel associated malaria is a major health risk for visitors to malaria endemic destinations. To examine the knowledge of malaria prevention, risk perception, current prophylactic behavior, and compliance with chemoprophylaxis and personal and environmental protection measures we conducted a study in a cohort of travelers exiting Zimbabwe from two international airports during a peak malaria transmission period. METHODS: Data were collected by pretested self-administered questionnaires from 595 adults in the departure lounges of Harare and Victoria Falls International airports. Excluded were children and travelers from the African continent. A multilingual research assistant supervised data collection. RESULTS: The majority of travelers obtained health advice prior to travel. Patterns of protective behavior and compliance with prophylaxis were inconsistent with a high perception of malaria threat and good knowledge. About 23% of travelers failed to use chemoprophylaxis during their visit. In the group of travelers who used chemoprophylaxis, 18% were noncompliant. Fifteen drug combinations were in use. Full compliance with medication plus use of personal preventive measures always was estimated as 13%. Forgetfulness was the main cause of noncompliance, followed by deliberate omission due to side effects. Of 57 travelers who reported side effects from current medication, over half used mefloquine. CONCLUSIONS: There is a need to examine how people process personal risk and communications about risk. We must recognize the competition between precautionary measures against malaria and other life demands that are imposed by travel, especially in young long stay travelers and persons visiting primarily for business purposes. Mediating a protective response will also depend on judgments about the effectiveness of the action, strengthening travelers intentions toward adherence, and increasing efficacy perception by individuals and their peers. Conflicts in prophylactic recommendations need to be resolved. As ecotourism develops in Zimbabwe and other malaria regions, stakeholders in this rapidly growing industry must be made aware of the important role they can play in protecting clients from malaria.

Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study.

Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers.

Pharmacopoeial quality of drugs supplied by Nigerian pharmacies.

BACKGROUND: The quality of medicines available in some less-developed countries is inadequate in terms of content of active ingredient. Reasons for the poor quality of drugs include widespread counterfeiting of medicines in less-developed countries, excessive decomposition of active ingredient as a result of high temperature and humidity, and poor quality assurance during the manufacture of medicinal products. Our aim was to investigate the quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria, and, in instances of poor quality, to ascertain the reason why. METHODS: We randomly collected 581 samples of 27 different drugs from 35 pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for drug content by validated chromatographic methods, and compared our results with pharmacopoeial requirements. FINDINGS: 279 (48%) samples did not comply with set pharmacopoeial limits, and this proportion was uniform for the various types of drugs tested. Although some preparations contained no active ingredient, most had amounts just outside the pharmacopoeial limits. We identified samples with both too much and too little active drug content. INTERPRETATION: The most probable cause of the poor quality of drugs is absence of adequate quality assurance during manufacture. Substandard drugs sold in the pharmacies of less-developed countries could contribute to global microbial resistance and therapeutic failure of infectious diseases.

Prevention and treatment of malaria in UK travellers.

With around 2500 new cases of malaria being reported each year and more than a million UK residents visiting malaria endemic countries, there has never been a greater need for effective prevention and treatment. The latest information on malaria management is outlined below.

Respiratory infections in the traveler.

The growth of travel of recent years has been unprecedented and presents new challenges to health professionals worldwide. More travelers of diverse backgrounds are visiting exotic locales rarely encountered before. This poses new risks to health, in addition to potentially aiding the spread of emerging respiratory infections. Travelers such as immunocompromised individuals and members of ethnic minorities are at significant risk for travel-related infections. Respiratory illnesses are some of the most common infections affecting human beings, yet little information has been published on them in relation to travel. Multidisciplinary approaches and collaboration across different sectors are needed to address the many issues involved in travel-related respiratory infections. This article discusses some of the topical issues of respiratory tract infections occurring in travelers.

Safety of iodine based water sterilization for travelers.

The recent report by Khan et al. of an unexpectedly high concentration of free iodine in water filters, which may have led to the high proportion of abnormal thyroid function tests in Peace Corps workers, is of concern for travel advisors when asked to recommend suitable means of water sterilization. Many travelers use iodine based filters and/or chemicals for purification of water when traveling in areas with contaminated water supplies and may therefore be at risk of excess iodine intake. Aside from iodine impregnated resin filtration systems, tetraglycine hydroperiodide tablets, tincture of iodine 2% and more commonly, chlorine-based proprietary products are widely used to sterilize water for drinking, and usually purchased by travelers without advice on how they should be used. A single tetraglycine hydroperiodide tablet in a liter of water releases 8 mg of iodine in comparison to the 10 mg/liter released from the iodinated resin pumps described by Khan et al. Although the instructions for using iodine tincture are imprecise, the normal recommendation is 5 drops per liter of water, increasing this to 12 drops where Giardia cysts may be present. The lower of the two doses would yield about 2 mg/liter of free iodine per liter depending on the pipette used, although, because of the potassium iodide present in the formulation, a total of 4 mg iodine would be available for absorption.

Self-testing for falciparum malaria with antigen-capture cards by travelers with symptoms of malaria.

Kits for self-diagnosis of malaria by travelers in remote areas have been advocated. Antigen-capture test cards work reliably in the laboratory, but there is limited data regarding self-testing by ill patients. One hundred and fifty-three symptomatic patients presenting for a malaria test attempted self-diagnosis using these kits. Nine percent failed to perform a valid test. Against blood-film proven malaria, specificity was 97% (95% confidence intervals [CI] 93-99%) and sensitivity 95% (95% CI 74-99%). Although these results are encouraging, technical problems need to be addressed and test sensitivity proven by additional field-testing before this technology can be marketed to travelers.