Improving malaria surveillance in inner city London: is there a need for targeted intervention?

Malaria in south east London is under-notified, and a previous local study has described how available data can underestimate the incidence. An active surveillance system was established and data on malaria cases diagnosed between the 1st January and 31st December 2000 were gathered from local laboratories, the Malaria Reference Laboratory (MRL) and a neighbouring health authority. In total 320 cases were identified in local residents (42.33 per 100,000). Of these 320, 293 were laboratory confirmed (38.75 per 100,000) and there were 47 notifications on clinical suspicion. Only 6.8% (20) laboratory-confirmed cases were formally notified. Males of African descent aged 25-39 years who travelled to West Africa were most affected, and 92.5% of the cases were of P. falciparum infection. The surveillance programme confirmed that formal malaria notifications are unreliable. The most important group of residents for targeted health intervention are members of ethnic minority groups, born in endemic areas and travelling to their countries of origin to visit family or friends.     

Can pharmacogenomics improve malaria drug policy?

Coordinated global efforts to prevent and control malaria have been a tour-de-force for public health, but success appears to have reached a plateau in many parts of the world. While this is a multifaceted problem, policy strategies have largely ignored genetic variations in humans as a factor that influences both selection and dosing of antimalarial drugs. This includes attempts to decrease toxicity, increase effectiveness and reduce the development of drug resistance, thereby lowering health care costs. We review the potential hurdles to developing and implementing pharmacogenetic-guided policies at a national or regional scale for the treatment of uncomplicated falciparum malaria. We also consider current knowledge on some component drugs of artemisinin combination therapies and ways to increase our understanding of host genetics, with the goal of guiding policy decisions for drug selection.     

Do untreated bednets protect against malaria?

Bednets are thought to offer little, if any, protection against malaria, unless treated with insecticide. There is also concern that the use of untreated nets will cause people sleeping without nets to receive more mosquito bites, and thus increase the malaria risk for other community members. Regular retreatment of nets is therefore viewed as critical for malaria control. However, despite good uptake of nets, many control programmes in Africa have reported low re-treatment rates. We investigated whether untreated bednets had any protective benefit (in October and November 1996) in The Gambia where nets, although widely used, are mostly untreated. Cross-sectional prevalence surveys were carried out in 48 villages and the risk of malaria parasitaemia was compared in young children sleeping with or without nets. Use of an untreated bednet in good condition was associated with a significantly lower prevalence of Plasmodium falciparum infection (51% protection [95% CI 34-64%], P < 0.001). This finding was only partly explained by differences in wealth between households, and children in the poorest households benefited most from sleeping under an untreated net (62% protection [14-83%], P = 0.018). There was no evidence that mosquitoes were diverted to feed on children sleeping without nets. These findings suggest that an untreated net, provided it is in relatively good condition, can protect against malaria. Control programmes should target the poorest households as they may have the most to gain from using nets.     

Intensity of malaria transmission,antimalarial-drug use and resistance in Uganda: what is the relationship between these three factors?

We studied (in 1998 and 1999) some factors that may be linked to the spread of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance in 7 discrete communities in Uganda. Exposure to malaria infection was measured by parasitological surveys in children aged 1-9 years, drug use by community surveys and drug resistance by in-vivo tests on children aged 6-59 months with clinical malaria. CQ use was inversely related to parasite prevalence (r = -0.85, P = 0.01). CQ and SP treatment failure rates varied significantly according to parasite prevalence (P = 0.001 and 0.04 respectively). The highest CQ (42.4%, 43.8%) and SP (12.5%, 14.8%) treatment failure rates were observed in sites characterized by high parasite prevalence. Using areas with medium parasite prevalence as reference, the relative risk (RR) for CQ treatment failure was 3.2 (95% CI 1.6-6.4) in high parasite prevalence sites and 3.1 (95% CI 1.2-7.7) in low parasite prevalence sites. The RR for SP treatment failure was also higher in sites with high parasite prevalence but low in those with low parasite prevalence. According to our findings, drug resistance seems to spread faster in higher transmission areas, regardless of drug pressure. In low transmission areas, drug pressure seems to be the critical factor. A decrease in transmission coupled with rational use of drugs may delay the spread of resistance.     

Impact of El Niño and malaria on birthweight in two areas of Tanzania with different malaria transmission patterns

BACKGROUND: Malaria infection increases low birthweight especially in primigravidae. Malaria epidemics occur when weather conditions favour this vector borne disease. Forecasting using the El Ni?o Southern Oscillation (ENSO) may assist in anticipating epidemics and reducing the impact of a disease which is an important cause of low birthweight. The aim of the present study was to determine the impact of the malaria epidemic in East Africa during 1997-1998 on birthweights in two different areas of Tanzania and to explore ESNO's potential for forecasting low birthweight risk in pregnant women. METHOD: A retrospective analysis of birthweight differences between primigravidae and multigravidae in relation to malaria cases and rainfall for two different areas of Tanzania: Kagera, which experiences severe outbreaks of malaria, and Morogoro which is holoendemic. Birthweight and parity data and malaria admissions were collected over a 10-year period from two district hospitals in these locations. RESULTS: The risk of delivering a low birthweight baby in the first pregnancy increases approximately 5 months following a malaria epidemic. An epidemic of marked reduced birthweight in primigravidae compared with multigravidae occurred, related to the ENSO of 1997-1998. In Kagera this birthweight difference and the risk of low birthweight were significantly lower compared with Morogoro, except after the ENSO when the two areas had similar differences. No significant interaction was noted between secundigravidae and any of the risk periods. The results indicate that the pressure of malaria is much greater on pregnant women, especially primigravidae, living in the Morogoro location. CONCLUSIONS: Surveillance of birthweight differences between primigravidae and multigravidae is a useful indicator of malaria exposure.     

Do bednets reduce malaria transmission by exophagic mosquitoes?

The impact of bednet coverage on malaria prevalence in a suburb of S?o Tomé was monitored, by passive case detection, over a three-year period (1997-1999), when bednet use increased from 20 to 74%. Malaria parasites were detected in 1651 (41.6%) of the 3967 slides taken during the study. All four human malaria parasites were seen, with Plasmodium falciparum being the predominant species (94.9% of positive slides). Prevalence of malaria among residents decreased, particularly in 1-4 year olds. In addition, there was a concomitant decrease in prevalence also among non-net users, suggesting a mass effect on transmission, even though the only vector in the area is largely exophagic and zoophilic.     

Clinical research on malaria: what for the future?

Malaria still remains one of the main public health problems in the world. In spite of early and numerous clinical trials, the situation seems to have been worsening in the last ten years. Malaria clinical research involves several levels: Several meta-analyses have been performed on this topic (in particular, the Cochrane Database Library has published studies on malaria prevention during pregnancy, management of clinical malaria attacks, vaccine trials or impregnated bed net trials). All these studies show the uneven quality of trials (only 10% to 50% can be kept in the analysis for methodological reasons), which seldom lead to similar conclusions. Besides, as resistances of both parasites and vectors to drugs or insecticides are regularly increasing, trials have to be repeated and new molecules have to be found and evaluated. Finally, practical application of such interventions may be difficult, due to the heterogeneity of epidemiological situations and the poverty of target populations. Various initiatives aiming to develop malaria clinical research have recently been launched. Donators are public or international (Global Fund, Roll Back Malaria Initiative, NIH, EDCTP programme), as well as private (Bill & Melinda Gates Foundation). These substantial funds should enhance the research of new antimalarial drugs and large-scale, adequately designed trials. However, to make sure these trials really benefit to populations exposed to the disease, ethical principles should be co-elaborated with developing countries, within collaborative networks between laboratories from industrialized and developing countries.     

Combination therapy for malaria in Africa: hype or hope?

The development of resistance to drugs poses one of the greatest threats to malaria control. In Africa, the efficacy of readily affordable antimalarial drugs is declining rapidly, while highly efficacious drugs tend to be too expensive. Cost-effective strategies are needed to extend the useful life spans of antimalarial drugs. Observations in South-East Asia on combination therapy with artemisinin derivatives and mefloquine indicate that the development of resistance to both components is slowed down. This suggests the possibility of a solution to the problem of drug resistance in Africa, where, however, there are major obstacles in the way of deploying combination therapy effectively. The rates of transmission are relatively high, a large proportion of asymptomatic infection occurs in semi-immune persons, the use of drugs is frequently inappropriate and ill-informed, there is a general lack of laboratory diagnoses, and public health systems in sub-Saharan Africa are generally weak. Furthermore, the cost of combination therapy is comparatively high. We review combination therapy as used in South-East Asia and outline the problems that have to be overcome in order to adopt it successfully in sub-Saharan Africa.     

Averting a malaria disaster in Africa--where does the buck stop?

The serious threat posed by the spread of drug-resistant malaria in Africa has been widely acknowledged. Chloroquine resistance is now almost universal, and resistance to the successor drug, sulfadoxine-pyrimethamine (SP), is growing rapidly. Combination therapy has been suggested as being an available and potentially lasting solution to this impending crisis. However, the current cost of combination therapy, and especially that of artemisinin combination therapy (ACT), is potentially a serious drawback, even if a significant part of its cost is passed on to the end-user. If the question of cost is not successfully addressed this could lead to adverse results from the deployment of combination therapy as first-line treatment. These adverse effects range from an increase in potentially fatal delays in infected individuals presenting to medical services, to exclusion of the poorest malaria sufferers from receiving treatment altogether. Urgent steps are needed to reduce the cost of combination therapy to the end-user in a sustainable way if it is to be usable, and some possible approaches are discussed.