[Efficacy is good, impact is great]. / L'efficacité c'est bien, l'impact c'est top!

This article summarizes the different stages of research for the development of medical interventions and their specific characteristics in terms of design, population, resources, importance of results and scientific interest. The emphasis is focused on the two final stages of development, the effectiveness and the impact. An example from our own experience is given to illustrate the reduction of the effect of an intervention against malaria in young children at different stages of the development of the intervention, and the parallel decrease of the recognition by the scientific community of the importance of these results.

Towards a comprehensive simulation model of malaria epidemiology and control.

Planning of the control of Plasmodium falciparum malaria leads to a need for models of malaria epidemiology that provide realistic quantitative prediction of likely epidemiological outcomes of a wide range of control strategies. Predictions of the effects of control often ignore medium- and long-term dynamics. The complexities of the Plasmodium life-cycle, and of within-host dynamics, limit the applicability of conventional deterministic malaria models. We use individual-based stochastic simulations of malaria epidemiology to predict the impacts of interventions on infection, morbidity, mortality, health services use and costs. Individual infections are simulated by stochastic series of parasite densities, and naturally acquired immunity acts by reducing densities. Morbidity and mortality risks, and infectiousness to vectors, depend on parasite densities. The simulated infections are nested within simulations of individuals in human populations, and linked to models of interventions and health systems. We use numerous field datasets to optimise parameter estimates. By using a volunteer computing system we obtain the enormous computational power required for model fitting, sensitivity analysis, and exploration of many different intervention strategies. The project thus provides a general platform for comparing, fitting, and evaluating different model structures, and for quantitative prediction of effects of different interventions and integrated control programmes.

Cost-sharing strategies combining targeted public subsidies with private-sector delivery achieve high bednet coverage and reduced malaria transmission in Kilombero Valley, southern Tanzania.

BACKGROUND: Cost-sharing schemes incorporating modest targeted subsidies have promoted insecticide-treated nets (ITNs) for malaria prevention in the Kilombero Valley, southern Tanzania, since 1996. Here we evaluate resulting changes in bednet coverage and malaria transmission. METHODS: Bednets were sold through local agents at fixed prices representing a 34% subsidy relative to full delivery cost. A further targeted subsidy of 15% was provided to vulnerable groups through discount vouchers delivered through antenatal clinics and regular immunizations. Continuous entomological surveys (2,376 trap nights) were conducted from October 2001 to September 2003 in 25 randomly-selected population clusters of a demographic surveillance system which monitored net coverage. RESULTS: Mean net usage of 75% (11,982/16,086) across all age groups was achieved but now-obsolete technologies available at the time resulted in low insecticide treatment rates. Malaria transmission remained intense but was substantially reduced: Compared with an exceptionally high historical mean EIR of 1481, even non-users of nets were protected (EIR [fold reduction] = 349 infectious bites per person per year [x4]), while the average resident (244 [x6]), users of typical nets (210 [x7]) and users of insecticidal nets (105 [x14]) enjoyed increasing benefits. CONCLUSION: Despite low net treatment levels, community-level protection was equivalent to the personal protection of an ITN. Greater gains for net users and non-users are predicted if more expensive long-lasting ITN technologies can be similarly promoted with correspondingly augmented subsidies. Cost sharing strategies represent an important option for national programmes lacking adequate financing to fully subsidize comprehensive ITN coverage.

Spatial effects of the social marketing of insecticide-treated nets on malaria morbidity.

Randomized controlled trials have shown that insecticide-treated nets (ITNs) have an impact on both malaria morbidity and mortality. Uniformly high coverage of ITNs characterized these trials and this resulted in some protection of nearby non-users of ITNs. We have now assessed the coverage, distribution pattern and resultant spatial effects in one village in Tanzania where ITNs were distributed in a social marketing programme. The prevalence of parasitaemia, mild anaemia (Hb <11 g/dl) and moderate/severe anaemia (Hb <8 g/dl) in children under five was assessed cross-sectionally. Data on ownership of ITNs were collected and inhabitants' houses were mapped. One year after the start of the social marketing programme, 52% of the children were using a net which had been treated at least once. The ITNs were rather homogeneously distributed throughout the village at an average density of about 118 ITNs per thousand population. There was no evidence of a pattern in the distribution of parasitaemia and anaemia cases, but children living in areas of moderately high ITN coverage were about half as likely to have moderate/severe anaemia (OR 0.5, 95% CI: 0.2, 0.9) and had lower prevalence of splenomegaly, irrespective of their net use. No protective effects of coverage were found for prevalence of mild anaemia nor for parasitaemia. The use of untreated nets had neither coverage nor short distance effects. More efforts should be made to ensure high coverage in ITNs programmes to achieve maximum benefit.

Planning a family: priorities and concerns in rural Tanzania.

A fertility survey using qualitative and quantitative techniques described a high fertility setting (TFR 5.8) in southern Tanzania where family planning use was 16%. Current use was influenced by rising parity, educational level, age of last born child, breastfeeding status, a preference for longer than the mean birth interval (32 months), not being related to the household head, and living in a house with a tin roof. Three principal concerns amongst women were outlined from the findings. First, that there is a large unmet need for family planning services in the area particularly among teenagers for whom it is associated with induced abortion. Second, that family planning is being used predominantly for spacing but fears associated with it often curtail effective use. Third, that service provision is perceived to be lacking in two main areas--regularity of supply, and addressing rumours and fears associated with family planning. Reproductive health interventions in the area should ultimately be more widespread and, in particular, abortion is highlighted as an urgent issue for further research. The potential for a fast and positive impact is high, given the simplicity of the perceived needs of women from this study.

Relationships between the outcome of Plasmodium falciparum infection and the intensity of transmission in Africa.

Establishing the relationship between transmission intensity and health outcomes is crucial for the planning of long-term malaria control programs. Unfortunately this is fraught with methodologic difficulties. In this report, we address some of these problems by considering some important parameters that have previously been ignored. One important consideration is that the incidence of infection for Plasmodium falciparum malaria is much lower than entomologic inoculation rates (EIRs), especially at higher transmission levels. Moreover, biting rates of malaria vectors per host depend on his or her biomass and thus age. We propose an algorithm for estimating human infection rates from the EIR with allowance for these two factors. We then re-analyzed 1) data on EIR and age-specific incidence of clinical malaria in two villages in Senegal and 2) a survey of infant and child mortality rates across Africa. In each case, we review analyses of incidence in relation to the EIR and carry out a new analysis of morbidity and mortality rates in relation to the estimated incidence of infection (h). Reduction in malaria transmission may result in a shift of acute malaria attacks to older ages, and thus have little impact on life-time risk of clinical attacks. However, our analysis of the Senegalese data indicates that the peak incidence rate of disease relative to infection rates is in the youngest age groups in both the villages of Dielmo (EIR = 200 infectious bites per year) and Ndiop (EIR = 20). This suggests that simple models of acquired clinical immunity can explain age-incidence profiles better when incidence is expressed in relation to h, than when expressed in relation to the EIR. Relationships of malaria transmission intensity (in endemic areas) with overall mortality are very different from those with acute morbidity. Infant mortality rates (IMRs) decrease substantially when the EIR is reduced, probably largely because of prevention of indirect mortality. However, we were are not yet able to draw strong conclusions about the shape of relationships between the IMR and h because many of the available data points have similar values of h. The effects of transmission reduction on mortality rates in older age groups are also uncertain. However, it is clear that reduction of exposure during infancy is not reflected in increased mortality at older ages.

Field issues related to effectiveness of insecticide-treated nets in Tanzania.

Insecticide-treated nets (ITNs) impregnated with pyrethroid insecticides have become one of the most promising interventions to prevent malaria in highly endemic areas. Despite the large body of experience documenting their health impact and the best way to distribute them, some key practical issues remain unresolved. For example, the duration of effective life of a net under field conditions is unknown. The most important factor affecting net effectiveness is the issue of regular re-treatment with insecticide. Washing is also an important determinant of insecticide longevity in the field. Trials were undertaken to provide some essential field information on ITNs within the site of an extended ITN programme in the Morogoro region of Tanzania. It was found that 45% of all nets were in bad condition (defined as more than seven large holes). It is concluded that an effective 'life' for polyester nets is 2-3 years. Further, two-thirds of the 20% of nets that were reported as having been re-treated within the last 12 months had less than 5 mg/m(2) of insecticide. According to the World Health Organization this is insufficient to be effective. People reported that they washed their nets four to seven times per year, usually with soap. Observations showed that such washing does not harm the nets and that the wash-water was unlikely to have an impact on the environment. Finally, bioassays were carried out with Anopheles gambiae on polyester netting with 0.5, 2, 5, 10 and 30 mg/m(2) of deltamethrin, alphacypermethrin and lambdacyhalothrin to assess the effectiveness of pyrethroids. The results confirmed that even with low insecticide concentrations, nets can still provide partial protection.

Insecticide-treated bed nets and curtains for preventing malaria.

BACKGROUND: Malaria is an important cause of illness and death in many parts of the world, especially in sub-Saharan Africa. There has been a renewed emphasis on preventive measures at community and individual levels. Insecticide-treated nets (ITNs) are the most prominent malaria preventive measure for large-scale deployment in highly endemic areas. OBJECTIVES: To assess the impact of insecticide-treated bed nets or curtains on mortality, malarial illness (life-threatening and mild), malaria parasitaemia, anaemia, and spleen rates. SEARCH STRATEGY: I searched the Cochrane Infectious Diseases Group trials register (January 2003), CENTRAL (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to October 2003), EMBASE (1974 to November 2002), LILACS (1982 to January 2003), and reference lists of reviews, books, and trials. I handsearched journals, contacted researchers, funding agencies, and net and insecticide manufacturers. SELECTION CRITERIA: Individual and cluster randomized controlled trials of insecticide-treated bed nets or curtains compared to nets without insecticide or no nets. Trials including only pregnant women were excluded. DATA COLLECTION AND ANALYSIS: The reviewer and two independent assessors reviewed trials for inclusion. The reviewer assessed trial methodological quality and extracted and analysed data. MAIN RESULTS: Fourteen cluster randomized and eight individually randomized controlled trials met the inclusion criteria. Five trials measured child mortality: ITNs provided 17% protective efficacy (PE) compared to no nets (relative rate 0.83, 95% confidence interval (CI) 0.76 to 0.90), and 23% PE compared to untreated nets (relative rate 0.77, 95% CI 0.63 to 0.95). About 5.5 lives (95% CI 3.39 to 7.67) can be saved each year for every 1000 children protected with ITNs. In areas with stable malaria, ITNs reduced the incidence of uncomplicated malarial episodes in areas of stable malaria by 50% compared to no nets, and 39% compared to untreated nets; and in areas of unstable malaria: by 62% for compared to no nets and 43% compared to untreated nets for Plasmodium falciparum episodes, and by 52% compared to no nets and 11% compared to untreated nets for P. vivax episodes. When compared to no nets and in areas of stable malaria, ITNs also had an impact on severe malaria (45% PE, 95% CI 20 to 63), parasite prevalence (13% PE), high parasitaemia (29% PE), splenomegaly (30% PE), and their use improved the average haemoglobin level in children by 1.7% packed cell volume. REVIEWERS' CONCLUSIONS: ITNs are highly effective in reducing childhood mortality and morbidity from malaria. Widespread access to ITNs is currently being advocated by Roll Back Malaria, but universal deployment will require major financial, technical, and operational inputs.

Spatial patterns of infant mortality in Mali: the effect of malaria endemicity.

A spatial analysis was carried out to identify factors related to geographic differences in infant mortality risk in Mali by linking data from two spatially structured databases: the Demographic and Health Surveys of 1995-1996 and the Mapping Malaria Risk in Africa database for Mali. Socioeconomic factors measured directly at the individual level and site-specific malaria prevalence predicted for the Demographic and Health Surveys' locations by a spatial model fitted to the Mapping Malaria Risk in Africa database were examined as possible risk factors. The analysis was carried out by fitting a Bayesian hierarchical geostatistical logistic model to infant mortality risk, by Markov chain Monte Carlo simulation. It confirmed that mother's education, birth order and interval, infant's sex, residence, and mother's age at infant's birth had a strong impact on infant mortality risk in Mali. The residual spatial pattern of infant mortality showed a clear relation to well-known foci of malaria transmission, especially the inland delta of the Niger River. No effect of estimated parasite prevalence could be demonstrated. Possible explanations include confounding by unmeasured covariates and sparsity of the source malaria data. Spatial statistical models of malaria prevalence are useful for indicating approximate levels of endemicity over wide areas and, hence, for guiding intervention strategies. However, at points very remote from those sampled, it is important to consider prediction error.

An estimation of the entomological inoculation rate for Ifakara: a semi-urban area in a region of intense malaria transmission in Tanzania.

An entomological study on vectors of malaria and their relative contribution to Plasmodium falciparum transmission in the semi-urban area of Ifakara, south-eastern Tanzania, was conducted. A total of 32 houses were randomly sampled from the area and light trap catches (LTC) performed in one room in each house every 2 weeks for 1 year. A total of 147 448 mosquitoes were caught from 789 LTC; 26 134 Anopheles gambiae s.l., 615 A. funestus, 718 other anophelines and 119 981 culicines. More than 60% of the total A. gambiae s.l. were found in five (0.6%) LTCs, with a maximum of 5889 caught in a single trap. Of 505 A. gambiae s.l. speciated by polymerase chain reaction, 91.5% were found to be A. arabiensis. Plasmodium falciparum sporozoite enzyme-linked immunosorbent assay tests were performed on 10 108 anopheles mosquitoes and 39 (0.38%) were positive. Entomological inoculation rate (EIR) estimates were generated using a standard method and an alternative method that allows the calculation of confidence intervals based on a negative binomial distribution of sporozoite positive mosquitoes. Overall EIR estimates were similar; 31 vs. 29 [95% confidence interval (CI): 19, 44] infectious bites per annum, respectively. The EIR ranged from 4 (95% CI: 1, 17) in the cool season to 108 (95% CI: 69, 170) in the wet season and from 54 (95% CI: 30, 97) in the east of the town to 15 (95% CI: 8, 30) in the town centre. These estimates show large variations over short distances in time and space. They are all markedly lower than those reported from nearby rural areas and for other parts of Tanzania.

The contribution of health-care services to a sound and sustainable malaria-control policy.

HIV and AIDS, tuberculosis, and malaria, besides presenting a large mortality and morbidity burden in developing countries, are also responsible for poor economic development. In the past international agencies devoted resources and efforts to control malaria and other diseases without taking into account health-system performance and sustainability. Even assuming that the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM)--a recent international initiative--would provide the necessary funds, a poorly performing health-care system will not be able to use these funds optimally. Moreover, even if all interventions are cost-effective, their impact on mortality and morbidity will only be marginal if access to proper care is not guaranteed. It is the responsibility of scientists and health managers to highlight to donor agencies the importance of an accessible and well functioning health-care system at all levels for the control of specific diseases.

Species-specific field testing of Entamoeba spp. in an area of high endemicity.

Entamoeba histolytica has been separated in recent years into 2 morphologically identical species: the apathogenic E. dispar and the pathogenic E. histolytica, only the latter being pathogenic. Although various laboratory techniques allow discrimination between the 2 species there is a lack of field data about the suitability of available diagnostic tests for use in epidemiological studies and few epidemiological studies using species-specific diagnosis have been performed at community level in endemic areas, especially in sub-Saharan Africa. We conducted a repeated cross-sectional study of 967 schoolchildren in central Côte d'Ivoire to compare and evaluate light microscopy, 2 different antigen detection assays, and one polymerase chain reaction (PCR) assay. Microscopy and a non-specific antigen capture Entamoeba enzyme-linked immunosorbent assay (ELISA) were used for the primary screening of all children (time t0). The prevalence of the E. histolytica/E. dispar species complex at t0 was 18.8% by single microscopical examination and 31.4% using the non-specific ELISA. Approximately 2 months after the initial screening, fresh stool specimens were collected on 2 consecutive days (t1 and t2) from (i) all the children who were positive by microscopy at t0 (n = 182) and (ii) 155 randomly selected children who were negative at the primary screening. These samples were tested with a second antigen detection ELISA specific for E. histolytica (n = 238) and with a species-specific PCR assay (n = 193). The second and third examinations (t1 and t2) revealed an additional 43 infections with the species complex E. histolytica/E. dispar, so that the cumulative microscopical prevalence for t1 and t2 was 27.7%. The overall prevalence of E. histolytica by species-specific ELISA antigen detection was low (0.83%), while the prevalence of E. dispar was 15%. When analysing only microscopically positive samples by PCR (n = 129), the ratio E. histolytica: E. dispar was very low (1:46), suggesting that the vast majority of Entamoeba infections in this area were apathogenic. Both species-specific tests performed well but the ELISA was easier to use for large-scale field screening.

Anaemia during pregnancy in southern Tanzania.

Anaemia in pregnancy is associated with maternal morbidity and mortality and is a risk factor for low birth-weight. Of 507 pregnant women recruited in a community, cross-sectional study in southern Tanzania, 11% were severely anaemic (<8 g haemoglobin/dl). High malarial parasitaemia [odds ratio (OR)=2.3] and iron deficiency (OR=2.4) were independent determinants of anaemia. Never having been married (OR=2.9) was the most important socio-economic predictor of severe anaemia. A subject recruited in the late dry season was six times more likely to be severely anaemic than a subject recruited in the early dry season. Compared with the women who were not identified as severely anaemic, the women with severe anaemia were more likely to present at mother-and-child-health (MCH) clinics early in the pregnancy, to seek medical attention beyond the MCH clinics, and to report concerns about their own health. Pregnancy-related food taboos in the study area principally restrict the consumption of fish and meat. Effective anti-malaria and iron-supplementation interventions are available but are not currently in place; improvements in the mechanisms for the delivery of such interventions are urgently required. Additionally, opportunities for contacting the target groups beyond the clinic environment need to be developed.

Usefulness of a dispensary-based case-control study for assessing morbidity impact of a treated net programme.

BACKGROUND: Case-control studies have been proposed as an appropriate tool for health impact evaluation of insecticide-treated nets (ITN) programmes. METHODS: A dispensary-based case-control study was carried out in one village in Tanzania. Each case of fever and parasitaemia in a child under 5 years was paired with one community and one dispensary control without fever and parasitaemia. Cases and controls were compared with regard to ITN ownership and other factors assessed by a questionnaire. A cross-sectional survey of factors associated with parasitaemia, including ITN use, was carried out during the study. Dispensary attendance rates of the study children were calculated using passive case detection data. RESULTS: Cases and dispensary controls had higher dispensary attendance rates compared to community controls and children with nets attended more for most of the illness events. A comparison of cases and community controls showed a strong and statistically significant association between untreated net use and being a case (odds ratio [OR] = 2.1, 95% CI : 1.3-3.4). For those with ITN there was a smaller and weaker association between risk of being a case and ITN use (OR =1.4, 95% CI : 0.9-2.2). Comparison of cases and dispensary controls showed no association between untreated or treated nets and the risk of being a case (for treated nets OR = 0.9, 95% CI : 0.5-1.4 and for untreated nets OR = 1.2, 95% CI : 0.7-2.0). These results are contrary to those from the cross-sectional assessment, where children with ITN had a lower prevalence of parasitaemia than those with no nets (OR = 0.5, 95% CI : 0.3-0.9), and also contrary to other assessments of the health impact of ITN in this population. CONCLUSIONS: The positive association between mild malaria and net ownership is counter-intuitive and best explained by attendance bias, since children with nets attended more frequently for all curative and preventive services at the dispensary than those without nets. Dispensary-based case-control studies may not be appropriate for assessing impact of treated nets on clinical malaria, while cross-sectional surveys might represent an attractive alternative.

Reinfection with Schistosoma haematobium following school-based chemotherapy with praziquantel in four highly endemic villages in Côte d'Ivoire.

We present the comparative evaluation of school-based chemotherapy with praziquantel on Schistosoma haematobium reinfection patterns, 6, 12, 18 and 24 months after systematic treatment of schoolchildren in four villages of south-central Côte d'Ivoire. At baseline, very high S. haematobium infection prevalences of 88-94% were found in Taabo Village, located adjacent to a large man-made lake, and in Batera and Bodo, where small dams were constructed. In Assinzé, a village with no man-made environmental alterations, the baseline infection prevalence was significantly lower (67%). The parasitological cure rate, assessed 4 weeks after praziquantel administration in the village with the highest prevalence and intensity of infection, was high (82%), and showed a clear association with infection intensity prior to treatment. Six months after chemotherapy, significant reductions in the prevalence and intensity of infection were observed in all villages. However, infection prevalence was again high in Taabo Village (63%) and in Batera (49%). Different patterns of reinfection occurred in the four villages: rapid reinfection in Taabo Village to reach almost baseline infection prevalence 12 months post-treatment; slow but gradual increase in the prevalence and intensity of infection in Bodo; marked increase in prevalence and intensity of infection during the second year of the follow-up in Assinzé; and prevalence and intensity of infection that remained almost constant between 6 and 24 months post-treatment in Batera. Our study confirms that S. haematobium reinfection patterns largely depend on the local epidemiological setting, which is of central importance to tailoring treatment strategies that are well adapted to these different settings.

Introducing insecticide-treated nets in the Kilombero Valley, Tanzania: the relevance of local knowledge and practice for an information, education and communication (IEC) campaign.

Since 1997 the WHO has been recommending an integrative strategy to combat malaria including new medicines, vaccines, improvements of health care systems and insecticide-treated nets (ITNs). After successful controlled trials with ITNs in the past decade, large-scale interventions and research now focus on operational issues of distribution and financing. In developing a social marketing approach in the Kilombero Valley in south-east Tanzania in 1996, a combination of qualitative and quantitative methods was employed to investigate local knowledge and practice relating to malaria. The findings show that the biomedical concept of malaria overlaps with several local illness concepts, one of which is called malaria and refers to mild malaria. Most respondents linked malaria to mosquitoes (76%) and already used mosquito nets (52%). But local understandings of severe malaria differed from the biomedical concept and were not linked to mosquitoes or malaria. A social marketing strategy to promote ITNs was developed on the basis of these findings, which reinforced public health messages and linked them with nets and insecticide. Although we did not directly evaluate the impact of promotional activities, the sharp rise in ownership and use of ITNs by the population (from 10 to > 50%) suggests that they contributed significantly to the success of the programme. Local knowledge and practice is highly relevant for social marketing strategies of ITNs.

Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania.

BACKGROUND: Insecticide-treated nets have proven efficacy as a malaria-control tool in Africa. However, the transition from efficacy to effectiveness cannot be taken for granted. We assessed coverage and the effect on child survival of a large-scale social marketing programme for insecticide-treated nets in two rural districts of southern Tanzania with high perennial malaria transmission. METHODS: Socially marketed insecticide-treated nets were introduced step-wise over a 2-year period from May, 1997, in a population of 480000 people. Cross-sectional coverage surveys were done at baseline and after 1, 2, and 3 years. A demographic surveillance system (DSS) was set up in an area of 60000 people to record population, births, and deaths. Within the DSS area, the effect of insecticide-treated nets on child survival was assessed by a case-control approach. Cases were deaths in children aged between 1 month and 4 years. Four controls for each case were chosen from the DSS database. Use of insecticide-treated nets and potential confounding factors were assessed by questionnaire. Individual effectiveness estimates from the case-control study were combined with coverage to estimate community effectiveness. FINDINGS: Insecticide-treated net coverage of infants in the DSS area rose from less than 10% at baseline to more than 50% 3 years later. Insecticide-treated nets were associated with a 27% increase in survival in children aged 1 month to 4 years (95% CI 3-45). Coverage in such children was higher in areas with longer access to the programme. The modest average coverage achieved by 1999 in the two districts (18% in children younger than 5 years) suggests that insecticide-treated nets prevented 1 in 20 child deaths at that time. INTERPRETATION: Social marketing of insecticide-treated nets has great potential for effective malaria control in rural African settings.

Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel.

There is evidence that faecal egg counts of Schistosoma mansoni vary considerably from day to day, which results in poor sensitivity of single stool readings. Intra-specimen variation of S. mansoni egg counts may also be considerable, but has previously been considered as the less important component. We quantified the relative contribution of these two sources of variation among 96 schoolchildren from an area in Cjte d'Ivoire highly endemic for S. mansoni. Stool specimens were collected over 5 consecutive days, and 5 egg-counts were made in each specimen by the Kato-Katz technique. The point prevalence of the first sample was 42.7% and the cumulative prevalence after the maximum sampling effort was 88.5%. Using generalized linear mixed models we found that the presence of S. mansoni eggs in a stool sample varied much more between days than within specimens, indicating that stool sample examination over multiple days is required for accurate prevalence estimates. However, using the same approach, we found that among infected children intra-specimen variation in egg counts was 4.3 times higher than day-to-day variation. After praziquantel administration, day-to-day variation was more important than before, since most infections were very light and thus likely to be missed altogether by stool examination on a single day. We conclude that diagnostic sensitivity in high transmission areas is maximized by making several stool readings on several days, but examining 1 stool specimen several times can make reasonable estimates of infection intensity.

Child mortality and malaria transmission intensity in Africa.

The desirability of controlling malaria transmission in the areas of highest endemicity of Plasmodium falciparum has long been debated. Most recently, it has been claimed that rates of malaria morbidity are no higher in areas of very high transmission in Africa than they are in places with lower inoculation rates. We now review the literature on the relationship of morbidity and mortality to malaria transmission intensity, and have linked published child mortality and malaria transmission rates to examine how age-specific mortality actually varies with the inoculation rate of P. falciparum.

Impact on malaria morbidity of a programme supplying insecticide treated nets in children aged under 2 years in Tanzania: community cross sectional study.

OBJECTIVE: To assess the impact of a social marketing programme for distributing nets treated with insecticide on malarial parasitaemia and anaemia in very young children in an area of high malaria transmission. DESIGN: Community cross sectional study. Annual, cross sectional data were collected at the beginning of the social marketing campaign (1997) and the subsequent two years. Net ownership and other risk and confounding factors were assessed with a questionnaire. Blood samples were taken from the children to assess prevalence of parasitaemia and haemoglobin levels. SETTING: 18 villages in the Kilombero and Ulanga districts of southwestern Tanzania. PARTICIPANTS: A random sample of children aged under 2 years. MAIN OUTCOME MEASURES: The presence of any parasitaemia in the peripheral blood sample and the presence of anaemia (classified as a haemoglobin level of <80 g/l). RESULTS: Ownership of nets increased rapidly (treated or not treated nets: from 58% to 83%; treated nets: from 10% to 61%). The mean haemoglobin level rose from 80 g/l to 89 g/l in the study children in the successive surveys. Overall, the prevalence of anaemia in the study population decreased from 49% to 26% in the two years studied. Treated nets had a protective efficacy of 62% (95% confidence interval 38% to 77%) on the prevalence of parasitaemia and of 63% (27% to 82%) on anaemia. CONCLUSIONS: These results show that nets treated with insecticide have a substantial impact on morbidity when distributed in a public health setting.