David J. Bradley

Unhealthy landscapes: policy recommendations on land use change and infectious disease emergence

Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers’ objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.

Drawers of Water: Domestic Water Use in East Africa

This document which is a chapter reprinted from a book originally published in 1972 focuses on the total social costs of improvements on water supply for the prevention of infections. It notes that particular water-multiplied infections and diseases with water-related insect vectors are local problems and can best be overcome by particular local solutions. However some improvements are so costly that they are not feasible in certain environments and the health benefits from a given improvement will also vary with the environment. In this perspective seven model East African habitats are considered in detail; two are urban three are rural with dispersed settlement and two more are rural nucleated settlements. These models include urban high density low and medium density urban dispersed semiarid dispersed highland humid dispersed lowland humid nucleated semiarid and nucleated humid. Health costs are measured on an arbitrary centile scale and are conceived as aggregating the costs of morbidity mortality currently available treatment and economic loss.

Imported malaria and high risk groups: observational study using UK surveillance data 1987-2006

Objective To examine temporal, geographic, and sociodemographic trends in case reporting and case fatality of malaria in the United Kingdom. Setting National malaria reference laboratory surveillance data in the UK. Design Observational study using prospectively gathered surveillance data and data on destinations from the international passenger survey. Participants 39 300 cases of proved malaria in the UK between 1987 and 2006. Main outcome measures Plasmodium species; sociodemographic details (including age, sex, and country of birth and residence); mortality; destination, duration, and purpose of international travel; and use of chemoprophylaxis. Results Reported cases of imported malaria increased significantly over the 20 years of the study; an increasing proportion was attributable to Plasmodium falciparum (P falciparum/P vivax reporting ratio 1.3:1 in 1987-91 and 5.4:1 in 2002-6). P vivax reports declined from 3954 in 1987-91 to 1244 in 2002-6. Case fatality of reported P falciparum malaria did not change over this period (7.4 deaths per 1000 reported cases). Travellers visiting friends and relatives, usually in a country in Africa or Asia from which members of their family migrated, accounted for 13 215/20 488 (64.5%) of all malaria reported, and reports were geographically concentrated in areas where migrants from Africa and South Asia to the UK have settled. People travelling for this purpose were at significantly higher risk of malaria than other travellers and were less likely to report the use of any chemoprophylaxis (odds ratio of reported chemoprophylaxis use 0.23, 95% confidence interval 0.21 to 0.25). Conclusions Despite the availability of highly effective preventive measures, the preventable burden from falciparum malaria has steadily increased in the UK while vivax malaria has decreased. Provision of targeted and appropriately delivered preventive messages and services for travellers from migrant families visiting friends and relatives should be a priority.

Risk factors for mortality from imported falciparum malaria in the United Kingdom over 20 years: an observational study

Objectives To determine which travellers with malaria are at greatest risk of dying, highlighting factors which can be used to target health messages to travellers. Design Observational study based on 20 years of UK national data. Setting National register of malaria cases. Participants 25 054 patients notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and 2006. Main outcome measures Comparison between those with falciparum malaria who died and non-fatal cases, including age, reason for travel, country of birth, time of year diagnosed, malaria prophylaxis used. Results Mortality increased steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65 years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001 compared with 18–35 year olds. There were no deaths in the ≤5 year age group. Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to 13.3), P<0.001). Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds ratio 4.6 (3.1 to 9.9), P<0.001). Case fatality was particularly high from the Gambia. There was an inverse correlation in mortality between region of presentation and number of cases seen in the region (R2=0.72, P<0.001). Most delay in fatal cases was in seeking care. Conclusions Most travellers acquiring malaria are of African heritage visiting friends and relatives. In contrast the risks of dying from malaria once acquired are highest in the elderly, tourists, and those presenting in areas in which malaria is seldom seen. Doctors often do not think of these as high risk groups for malaria; for this reason they are important groups to target in pre-travel advice.

Consequences of helminth aggregation for the dynamics of schistosomiasis

The distribution of schistosome worms among their human hosts is not random but aggregated. The consequences of introducing aggregation into models of schistosomiasis transmission, especially that of Macdonald, are explored. There are two possibilities for aggregation, with the sexes distributed either independently or together. Both have profound though differing effects on the breakpoint concept, which is largely destroyed when the sexes are aggregated together, and Macdonalds epidemiological conclusions are not robust to variations from the Poisson distribution. The conclusion from his model that if schistosome densities in man are reduced appropriately the infection will spontaneously proceed to extinction even in the presence of conditions suitable for transmission, is also not therefore robust.

Malaria prophylaxis: guidelines for travellers from Britain. Malaria Reference Laboratory of the Public Health Laboratory Service, London.

Summary points Travellers to malarious areas must avoid mosquito bites, take chemoprophylaxis, and urgently seek early diagnosis and treatment for febrile illness The key to preventing malaria is avoiding infective mosquito bites by using repellents, covering up at night, and sleeping with bednets if mosquitos cannot be excluded from the room Appropriate chemoprophylaxis is essential when travelling to endemic areas—drug resistance is increasing in many areas so recommended regimens have changed Doses and choice of drug may have to be altered in those with concomitant illness Standby treatment may be given to those who will be unable to reach medical services for extended periods No prophylaxis is infallible so all fever and flu-like illnesses occurring within a year of returning from malarious regions need to be urgently investigated with malaria in mind

Survival of toxigenic Vibrio cholerae O1 with a common duckweed, Lemna minor, in artificial aquatic ecosystems

Cholera epidemics occur twice a year in Bangladesh. During epidemics, Vibrio cholerae O1 are isolated from patients, as well as from the surface water, but the bacteria disappear during inter-epidemic periods. Their reservoirs or sites of survival and multiplication during inter-epidemic period are still unknown. The present survival study in the laboratory explored the role of an aquatic plant, Lemna minor (duckweed), as a possible reservoir. L. minor was added to sea-salt solution at pH 8.5, containing V. cholerae. Survival of V. cholerae on L. minor, in water on which L. minor was floating, and in control water (without L. minor) was monitored at regular intervals. Survival of both environmental and clinical strains of V. cholerae was assessed by viable counts on thiosulphate-citrate-bile salt-sucrose agar. It was observed that both strains survived better on L. minor than in water on which L. minor was floating or in control water. It is suggested that plants may serve as an effective environmental reservoir for V. cholerae either through a non-specific association or by interaction with V. cholerae in commensal relationship.

The interpretation of intensity and aggregation data for infections of Schistosoma haematobium

The relationships between mean intensities of infection, the aggregation of infection among hosts, and host age are analysed using data from 2 large (> 3000 individuals) field studies of Schistosoma haematobium infection. The data show a convex relationship between mean intensity and age, a convex relationship between an inverse index of aggregation and age, and an age-dependent relationship between the mean and aggregation of infection intensity when levels of infection are high. These patterns are qualitatively compared with the output of mathematical models based on an immigration-death process (model I), and incorporating age-dependent changes in the distribution of exposure to infection as suggested by field data (model II), or reductions in the rate of infection as a function of either current (model III) or cumulative (model IV) parasite burdens, that is, density-dependent processes without or with memory, respectively. Models II and III were able to reproduce observed patterns, but model IV, which is a possible representation of acquired immunity, was not. These results are consistent with the following assumptions: (i) age-related patterns of aggregation can be generated without recourse to density-dependent processes; (ii) the epidemiological impact of density-dependent processes depends on whether these act with or without memory; and (iii) any acquired immunity to human S. haematobium infection may be significantly less than life-long.

The effect of chemoprophylaxis on the timing of onset of falciparum malaria

The association between chemoprophylaxis and delayed onset of falciparum malaria was investigated in a retrospective study of 477 nonimmune cases reported to the UK Malaria Reference Laboratory (MRL) who had used either mefloquine (n = 56), chloroquine‐proguanil (n = 90) or no chemoprophylaxis (n = 331). For holiday and short‐term travellers using mefloquine the time between arrival in the UK and diagnosis was found to be significantly longer than for chloroquine and proguanil (C‐P) users or for those who had not used prophylaxis at all (P < 0.004). This delay was primarily due to a later onset of symptoms. C‐P use was not associated with delay in onset of symptoms or diagnosis when compared to not using prophylaxis. Possible reasons for the findings are discussed. Mefloquine may continue to exert a partially suppressive effect on resistant strains of Plasmodium falciparum (Pf). That chloroquine with proguanil was not found to have such an effect may be due to poor compliance to proguanil or differences in the mode of action and range of parasite resistance to the two regimens. Differences in drug compliance may be one reason why only mefloquine users on holiday or short‐term journeys experienced delays to onset of disease. Drug compliance amongst cases of breakthrough malaria on chemoprophylaxis may be lower than is generally recognized. It is important for clinicians and travellers to be aware that the onset of falciparum malaria may be delayed by mefloquine prophylaxis.

Prophylaxis against malaria for travellers from the United Kingdom. Malaria Reference Laboratory and the Ross Institute.

To provide revised guidance on malaria prevention for the medical advisers of travellers from the United Kingdom going overseas to malarious areas, a committee of those most involved in giving advice and with specialist expertise in the United Kingdom agreed a policy document. There is a need for all travellers to be aware of the risk of malaria and to take measures to avoid being bitten by anopheline mosquitos, especially at night. Chemoprophylaxis is recommended also for most malarious areas. In view of the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and proguanil, mefloquine is added to the list of recommended drugs for more areas than in the past, and is the preferred chemoprophylactic for east and central Africa. Chloroquine with proguanil continues to be widely appropriate. Detailed recommendations are given for each country. Travellers out of reach of prompt medical assistance are advised to carry treatment doses of a standby drug: halofantrine, Fansidar, or quinine. The need for full compliance with any regimen is emphasised. No prophylaxis is totally effective. Malaria must be considered in the differential diagnosis of any fever in someone who has visited an endemic area within the past year.