Improving access to early treatment of malaria: a trial with primary school teachers as care providers.

The feasibility of improving access to early case detection and prompt and adequate management of acute episodes of malaria using school teachers was explored through an intervention trial in Ghana. Of all the 'fevers' diagnosed as presumptive malaria by the trained teachers, 93% met the case definition. However, a lower proportion (75%) of such correctly diagnosed cases were subsequently treated according to the treatment protocol provided. In a scaled up study, pre-packaging of the antimalarial drug improved the rate of adequate treatment to 97% of cases correctly diagnosed as presumptive malaria. Pre-packaging of chloroquine ensured a high level of user compliance (96.6%), even in the face of diminished supervision of the teachers. It is feasible for the health and education sectors to work in partnership to improve access to early case detection and adequate management of acute episodes of malaria.

Unit-dose packaged drugs for treating malaria.

BACKGROUND: Unit-dose packaging of antimalarial drugs may improve malaria cure by making it easier for patients to take their treatment correctly. OBJECTIVES: To summarize the effects of unit-dose packaged treatment on cure and treatment adherence in people with uncomplicated malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (November 2004), CENTRAL (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), LILACS (November 2004), conference proceedings, and reference lists of articles. We also contacted pharmaceutical companies, organizations, and researchers in the field. SELECTION CRITERIA: Randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and controlled before-and-after studies of unit-dose packaged drugs for treating uncomplicated malaria. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility and methodological quality, and extracted data for an intention to treat analysis, where possible. We combined binary data using relative risk (RR) and the fixed-effect model, and presented them with 95% confidence intervals (CI). We attempted to contact study authors for additional information. MAIN RESULTS: Three quasi-RCTs (895 participants) and one cluster-RCT (6 health facilities) met the inclusion criteria. Trials were of poor methodological quality, and none adequately assessed treatment failure. Unit-dose packaged drugs (in conjunction with prescriber training and patient information) appeared to be associated with higher participant-reported treatment adherence in all trials.A meta-analysis of two trials (596 participants) showed that participant-reported treatment adherence was higher with blister-packed tablets compared with tablets in paper envelopes (RR 1.18, 1.12 to 1.25). Two trials using tablets in sectioned polythene bags as the intervention also noted an increase in participant-reported treatment adherence: the cluster-RCT (6 clusters) compared it with tablets in paper envelopes, and the other trial compared it with syrup in bottles (RR 2.15, 1.76 to 2.61; 299 participants). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effect of unit-dose packaged antimalarial drugs on treatment failure. Unit-dose packaging supported by prescriber training and patient information appears to improve participant-reported treatment adherence, but these data come from trials with methodological limitations.

Impact of prepackaging antimalarial drugs on cost to patients and compliance with treatment.

OBJECTIVE: To examine the extent to which district health teams could reduce the burden of malaria, a continuing major cause of mortality and morbidity, in a situation where severe resource constraints existed and integrated care was provided. METHODS: Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy. FINDINGS: Compliance improved by approximately 20% in both adults and children. There were 50% reductions in cost to patients, waiting time at dispensaries and drug wastage at facilities. The intervention, which tended to improve both case and drug management at facilities, was well accepted by health staff and did not involve them in additional working time. CONCLUSION: The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance.

An epidemiological and ecological study of human alveolar echinococcosis transmission in south Gansu, China.

Human alveolar echinococcosis (AE) is usually a rare, highly pathogenic zoonotic disease, transmitted across the northern hemisphere between fox and rodent hosts. In China the first cases were described in 1965; however very few epidemiological studies have been undertaken since. Following identification in 1991 of a serious focus of human AE in south Gansu province, detailed village-based community and ecological studies were carried out between 1994 and 1997. Hepatic ultrasound mass screening with serological testing (five tests) identified 84/2482 new AE cases (3%). An overall prevalence of 4.1% (135/3331) was recorded for the area when previous cases were also included. Based on a seropositive result only, without an ultrasound scan indication, no additional AE cases were identified. Of the evolutive AE cases, 96% were seropositive in at least one test, while up 15-20% of individuals who exhibited hepatic calcified lesions and 12-15% exhibiting hepatic nodular lesions were seropositive for specific Em2 or Em18 antibodies. Village (n=31) human AE prevalence rates varied from 0 to 15.8%. Questionnaire analysis indicated that total number of dogs owned over a period was a risk factor (P<0.006), but not a history of red fox hunting (P>0.6). Rodent ecology studies revealed an association between density indices of voles (Microtus limnophilus) and village AE prevalence rates, on the one hand, and village landscape characterised by a ratio of scrub/grassland to total area above 50% (P<0.005). Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture. This in turn probably results in creation of optimal peri-domestic habitats for rodents that serve as intermediate host species (such as M. limnophilus) and subsequent development of a peri-domestic cycle involving dogs.

Incidence and management of malaria in two communities of different socio-economic level, in Accra, Ghana.

Two adjacent communities of differing socio-economic levels were selected, in Accra, Ghana, for the study of the home management of malaria. The youngest child in each selected household, each of which had a child aged < 5 years, was recruited for weekly follow-up, following informed consent. Malaria was the most common condition reported by the 'caregivers' (mothers of the subjects and others caring for the subjects) in each community, with 2.0 episodes of clinical malaria/child during the 9-month study. Most (89%) of the caregivers in the better-off community had been educated beyond primary-school level, but 55% of the caregivers in the poorer community had either received no formal education or only primary-school education. This difference was also reflected by the educational facilities provided to the children studied: 52% of the those in the better-off community attended nurseries, kindergartens or creches, compared with 8% of the children investigated in the poorer community. The proportion of caregivers who purchased drugs without prescription or used left-over drugs to treat clinical malaria in the children was higher in the poorer community (82% v. 53%), and a child from the poorer community was less likely to have been taken to a clinic or hospital to be treated for malaria than a child from the better-off community (27% v. 42%). During the follow-up period two children died, one from each community. Treatment of malaria in young children is likely to be less effective in the poorer community, where a lack of economic access to health services was demonstrated.

It all began with Ronald Ross: 100 years of malaria research and control in Sierra Leone (1899-1999).

It was in Sierra Leone, 100 years ago in 1899, that human malarial parasites were first observed in wild-caught Anopheles gambiae and An. funestus, the principal vectors of malaria in Africa. In the same year, Ronald Ross initiated the first antilarval measures for malaria control. This paper reviews 100 years of malaria field research and control in Sierra Leone, which became known as the 'White Man's Grave' in the 19th century largely because of the high malaria-related mortality amongst Europeans living there. The establishment of a field laboratory for the Liverpool School of Tropical Medicine in Freetown in 1920 made Sierra Leone the centre for malaria field research in Africa up to and during the Second World War. Eminent malariologists including Ronald Ross, Samuel Christophers, George Macdonald, Leonard Bruce-Chwatt, Brian Maegraith, Ian Macgregor, Brian Greenwood and Michael Service visited Sierra Leone for malaria-related activities. This review highlights the tremendous efforts made towards defining the epidemiological picture of the disease and the most effective means of combatting it. Malaria control in Sierra Leone, as in many other parts of the world, used to be based largely on mosquito eradication. However, experience gained over the past 100 years has shown that mosquito control is often not cost-effective in areas where the interruption of transmission cannot be sustained. Emphasis should now be on early diagnosis, treatment with effective antimalarials, and the selective use of preventive measures including vector control and insecticide-treated materials where they can be sustained.

Sensitivity in vitro of Plasmodium falciparum to three currently used antimalarial drugs on the western border of Thailand.

The sensitivity in vitro of Plasmodium falciparum to mefloquine, quinine and artemisinin was assessed in an area of multi-drug resistance on the Thai-Myanmar border, using the World Health Organization's microtest, based on schizont maturation inhibition. Participating individuals were exclusively those who had contracted their infections within Myanmar. A total of 34 successful tests were carried out for mefloquine and quinine, showing a marked decrease in sensitivity compared to previously published results. Ten artemisinin tests were successful, with many failures due to the poor storage stability of the test plates. The implications of the shelf-life of the artemisinin plates is discussed. These results contribute to setting a base line of sensitivity to artemisinin in vitro.

Transmission control and drug resistance in malaria: a crucial interaction.

Drug resistance is a major problem affecting progress on malaria control, while many current programmes are seeking to introduce impregnated bednets to reduce transmission and hence child mortality and morbidity. David Molyneux, Katherine Floyd, Guy Barnish and Eric Fèvre propose that more consideration should be given to the interaction between transmission control and the development of drug resistance, and that vector control as a means of reducing disease transmission is involved in reducing the rate of development, and the level, of resistance. Therefore, investment in vector control can have important benefits in reducing the future expenditure on drugs (as well as other costs, such as hospitalization, management of resistant cases and severe disease, drug development and household expenditure on malaria chemotherapy). Modelling the many parameters that impact on this complex relationship will better inform policy makers.

A comparison of three malaria diagnostic tests, under field conditions in North-west Thailand.

A hospital-based trial to compare the clinical diagnosis of malaria; microscopy, and a rapid diagnostic antigen capture detection dipstick (ParaSight-F) was conducted in North-west Thailand. 301 people who presented themselves at the hospital were selected. 204 (68%) were presumptively diagnosed as having malaria by the triage nurses; 64 (21.3%) were P. falciparum parasite positive, and 94 (32%) tested positive for P. falciparum with the ParaSight-F test strips. There was no association between hemoglobin levels (<10g/dl and > or = 10g/dl) and malaria, and although there was a good statistical association between temperature and malaria the specificity, sensitivity and positive predictive values were all low, indicating that temperature alone is a poor indicator of the disease. Based on the microscopy results, we found that a presumptive clinical diagnosis dramatically over-diagnosed malaria, and similarly there were a large number of false positives using the ParaSight-F test. We believe that many of the patients had received some form of malaria treatment prior to presentation at the hospital, and that the high number of false positives are explained by persistent antigenemia and the possibility of there being sequestered parasites following incomplete chemotherapy.

Malaria-treatment policies: when and how should they be changed?

There appears to be a large a gap in the literature between primary work on malaria control and policy on the one hand and the interpretation of such work in making real policy decisions on the other. The focus of the present review is policy formulation for treatment of uncomplicated falciparum malaria, rather than prophylaxis in travellers or the treatment of severe disease. The World Health Organization has formulated guidelines addressing the issue of changing from one recommended drug for treating malaria to another, but there does not appear to have been a comprehensive attempt to describe how and when such a decision on drug policy should be made. Issues of drug availability, both to countries and to communities within them, are discussed, as well as the acceptability of drug regimens and compliance with them. It emerges that the cost of treatment has a disproportionate influence on the decision-making process, and that the indirect costs of drug failure are often not considered properly. Brief mention is made of the indicators of overall disease burden. There is some discussion about the usefulness of one recently introduced economic indicator: the disability-adjusted life-year (DALY). Also examined are the difficulties that arise within the context of drug-policy changes, such as a regimen's appropriateness to all target groups, and the strong influence of the private sector on decision-making that affects its own financing. The consensus seems to be that a policy change is urgent when high-level resistance occurs in 40% or more of treated cases, when parasitological response is poor, and when the costs of treatment failures are higher than those of treatments with a newer drug. It also emerges that much remains to be done regarding co-operation between public and private sectors; considering the importance of private-sector provision of health care, this needs to be addressed.

Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1.

The development of an effective malaria vaccine depends upon identification of antigens that are targets of protective immune responses. An immunoepidemiologic approach has been used to investigate the relationship between antibody responses to a defined region of the major merozoite surface protein of Plasmodium falciparum (PfMSP-1 19) and resistance to clinical malaria in 2 populations of children from West Africa. After allowing for the confounding effects of age, antibodies to PfMSP-1 19 were shown the provide 40% protection against clinical malaria in children in Sierra Leone. In Gambian children, antibodies to one of the epidermal growth factor-like motifs of PfMSP-1 19 were strongly associated with resistance to both clinical malaria and high levels of parasitemia.

The late biting habit of parous Anopheles mosquitoes and pre-bedtime exposure of humans to infective female mosquitoes.

Using the all-night landing catch method (18:00-06:00) we showed, for Anopheles gambiae in Sierra Leone and A. punctulatus in Papua New Guinea, that parous females have a tendency to bite later than nulliparous ones. The biting habit of sporozoite-infected A. punctulatus was also investigated. The sporozoite rates for Plasmodium falciparum and P. vivax were 1.8 and 1.4% respectively, but only one (1.3%) of 76 females infected with P. falciparum was caught between 18:00 and 21:00. A significantly higher proportion (11.6%) of mosquitoes infected with P. vivax was caught in the same period. The late biting habit of mosquitoes infected with P. falciparum is discussed in relation to the differential biting habits of parous and nulliparous females. We conclude with a hypothesis that, in areas where Anopheles mosquitoes have a late-biting cycle and low parous rate, exposure to mosquitoes infected with P. falciparum during the pre-bedtime period (18:00-22:00) is very low. This hypothesis could explain why insecticide-treated bed nets protect children better in areas of seasonal transmission, where nulliparous females tend to predominate, than in areas of perennial transmission, where parous females are usually more numerous. The same hypothesis is compatible with the finding in Papua New Guinea that insecticide-impregnated bed nets are more protective against P. falciparum than against P. vivax malaria.

Vectorial capacity and entomological inoculation rates of Anopheles gambiae in a high rainfall forested area of southern Sierra Leone.

We report the first study of gonotrophic cycle duration, survival rates, pre-gravid rates, vectorial capacity and chromosomal polymorphism of Anopheles gambiae s.s. in Sierra Leone. In the village of Bayama in the Southern Province, An. gambiae was the only species found to be naturally infected with Plasmodium falciparum and it constituted 99.7% of 22,541 anopheline mosquitoes caught. Chromosomal studies revealed only An. gambiae s.s. out of 66 females examined for chromosomal polymorphism, 61 (92.4%) had the 2LA inversion in the standard arrangement. Other inversions observed in low frequencies included 2Rcu and 2Ru. We estimated a gonotrophic cycle length of three days and survival rate per gonotrophic cycle of 0.59 for this species. The mean daily survival rate of An. gambiae was 0.85 and the entomological inoculation rate was 1,235 infective bites/person/year. Blood-meal ELISA tests showed that the species was very anthropophagic and that there were an estimated 35.4 daily inoculations per infective case. The epidemiological significance of these entomological parameters is discussed in the light of parasitological results for nearby villages.

Malaria in a rural area of Sierra Leone. III. Vector ecology and disease transmission.

Studies were undertaken on the role of Anopheles gambiae and An. funestus in the transmission of malaria in four villages in a high-rainfall, forested area in the Bo district of southern Sierra Leone. Anopheles gambiae s.s., identified chromosomally as the Forest form, was the most important vector, with a mean annual sporozoite rate, based on ELISA, of 7.4%. Anopheles funestus, which was found in considerably lower numbers, was mainly a dry season vector, with an annual sporozoite rate of 11.4%. Despite these relatively high sporozoite rates, vector populations were at a low level, with approximate mean densities of only 1.0 An. gambiae and 0.1 An. funestus resting females per house room, and average biting rates of just 1.1 and 0.1 bites/person/night by these two species, respectively. In the rainy season, biting rates peaked at 9.5 An. gambiae bites/person/night and 1.0 An. funestus bites/person/night. Annual sporozoite inoculation rates by An. gambiae and An. funestus were 0.088 and 0.007 infective bites/person/night, respectively. ELISA showed that both species were highly anthropophagic. Exit-trap collections and outdoors searches showed that An. gambiae exhibited a considerable degree of exophily. Light traps inside houses caught nine anopheline species, whereas pyrethrum spray collections in houses caught only An. gambiae, An. funestus and An. hancocki.