Travel as a risk factor for uncomplicated Plasmodium falciparum malaria in the highlands of western Kenya.

In the 1980s, highland malaria returned to the tea estates of western Kenya after an absence of nearly a generation. In order to determine the importance of travel for the spread of malaria in this region, we prospectively collected blood films and travel, demographic and geographic information on well persons and outpatients on tea estates near the western rim of the Rift Valley. Risk factors for malaria asexual parasitaemia included: tribal/ethnic group, home province and home district malaria endemicity. Travel away from the Kericho tea estates within the previous two months showed an odds ratio (OR) for parasitaemia of 1.59 for well persons and 2.38 for outpatients. Sexual stages of malaria parasites (gametocytes) had an OR of 3.14 (well persons) and 2.22 (outpatients) for those who had travelled. Increased risk of malaria parasitaemia with travel was concentrated in children aged <5 years. An increase in population gametocytaemia is possibly due to increased chloroquine resistance and suppressed infections contracted outside of the tea estates.

Different approaches to modeling the cost-effectiveness of schistosomiasis control.

The limited economic resources available for health care in developing countries necessitates the involvement of cost analysis in the planning of any control intervention. A number of studies have undertaken cost-effectiveness analysis of schistosomiasis control, and the methodologies utilized in both cost and effectiveness evaluation are discussed. In attempting to relate cost to effectiveness, most studies have utilized static models expressing effectiveness in terms of coverage (drug delivery) or cure rate (infection prevalence reduction). These immediate output measures do not consider the long-term impact of control nor the effect on disease. An alternative approach is to use a model of the transmission dynamics of the parasite to permit evaluation of the long-term impact of control. An example of a population dynamic approach to cost-effectiveness analysis that can assess the impact of treatment on infection and disease due to the intestinal nematodes is presented to illustrate the potential of this approach in modeling the cost-effectiveness of schistosomiasis control.

The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa.

The paucity of precise information on the burden of malaria among pregnant women has hampered effective lobbying for the inclusion of preventative strategies against malaria in Safe Motherhood Initiatives. This article reviews the evidence on the coincidental risks of malaria and anemia in Africa and attempts to estimate the probable burden of malaria-related severe anemia in this susceptible group. Twenty-six studies on hemoglobin levels in all-parity pregnant women throughout this region could be matched with a malaria parasite ratio in children < 15 yr old (a measure of the intensity of transmission). In areas with no malaria, the mean hemoglobin levels were markedly higher than those found in areas with stable malaria transmission, though changes with increasing intensity of transmission were unclear. Eighteen studies from areas with stable malaria transmission in sub-Saharan Africa suggested that the median prevalence of severe anemia in all-parity pregnant women is approximately 8.2%. Assuming that 26% of these cases are due to malaria, it is suggested that as many as 400,000 pregnant women may have developed severe anemia as a result of infection with malaria in sub-Saharan Africa in 1995.

Dynamic models of schistosomiasis morbidity.

Previous attempts to assess the health impact of schistosomiasis control programs on community morbidity have been limited by a lack of a theoretical framework that describes the dynamic relationships between infection and morbidity. In this paper, a model of schistosomal morbidity is developed and parameterized. Morbidity is divided into that due to current heavy infection, and early and late stages of chronic disease. The model was parameterized using data showing resolution of disease after treatment, correlations between prevalence of disease and intensity of infection and using age-morbidity profiles. The fitted parameters suggest that early manifestations of disease such as hepatomegaly in Schistosoma mansoni and S. japonicum infections would resolve relatively quickly following treatment whereas later forms of disease such as liver fibrosis resolve very slowly or not at all. Similar general conclusions were obtained with data on early and late forms of urinary tract morbidity in S. haematobium.

Estimating prevalence of community morbidity due to intestinal helminths: prevalence of infection as an indicator of the prevalence of disease.

The rational design of helminth control programmes for endemic areas requires that the limited resources be focused on the communities in greatest need. The process of locality-targetting would be facilitated by a simple, inexpensive method of assessing morbidity at the community level. This paper describes how a simple model of the distribution of infection in human populations can use infection prevalence data to predict the proportion of heavy, and potentially clinically significant, infections in a community. Analysis of observed data for Ascaris lumbricoides indicates that the risk of clinical ascariasis increases non-linearly with the prevalence of infection. The predicted prevalence of morbidity is low up to approximately 60% prevalence of infection, but increases very rapidly thereafter. Analyses of data for Trichuris trichiura, Schistosoma mansoni, S. haematobium and the hookworms suggests qualitatively similar patterns. The application of the model in predicting resource requirements for control is illustrated using infection prevalence data for A. lumbricoides in Brazil.

Malaria in pregnancy as an indirect cause of infant mortality in sub-Saharan Africa.

Although randomized controlled trials of interventions to reduce malaria in pregnancy have demonstrated an increase in the birthweight of the newborn in primigravidae, the subsequent impact on infant mortality in all-parities has not been assessed. The aim of this paper was to model the possible impact of placental malarial infection on infant mortality through reduced birthweight. An extensive literature search was undertaken to define a series of parameters describing the associations between placental infection, birthweight and premature mortality in sub-Saharan Africa. It was shown that a baby is twice as likely to be born of low birthweight if the mother has an infected placenta at the time of delivery (all-parities: 23% vs 11%, primigravidae only: 32% vs 16%), and that the probability of premature mortality of African newborns in the first year of life is 3 times higher in babies of low birthweight than in those of normal birthweight (16% vs 4.6%). Assuming 25% of pregnant women in malaria-endemic areas of Africa harbour placental malarial infection, it is suggested that 5.7% of infant deaths in malarious areas could be an indirect cause of malaria in pregnancy. This would imply that, in 1997, malaria in pregnancy could have been responsible for around 3700 infant deaths under the diverse epidemiological conditions in Kenya. Placental infection with Plasmodium falciparum appears to have a more significant role in infant survival in Africa than has been previously assumed. This may explain the high reduction in infant mortality rates from interventions aimed at reducing transmission, over and above that expected from a decline in direct malaria-specific mortality alone.

Cost analysis of schistosomiasis.

Cost analysis of schistosomiasis is important both in assessing the economic impact of the disease and in identifying the most cost-effective approaches to control. Economic impact has been examined both within and without the health sector, but there is a lack of measurement of the effects of disease, or the threat of disease, on patterns of production and community development. The cost-effectiveness of control approaches has been examined empirically and by using static models. Future analyses require a stronger epidemiological basis incorporating realistic demography and the temporal dynamics of reinfection, and assessment of outcomes in terms of disease rather than infection.

A population dynamic approach to the cost-effectiveness analysis of mass anthelmintic treatment: effects of treatment frequency on Ascaris infection.

This study examines the cost-effectiveness of different frequencies of mass chemotherapy in reducing helminth infection and morbidity at the community level. The cost-effectiveness framework utilities a dynamic model of helminth transmission which permits the effectiveness of treatment to be expressed as some long-term reduction in infection and disease. Cost analysis is incorporated into this framework using an itemized cost menu and cost data from an actual control programme. The cost-effectiveness of mass treatment is investigated using epidemiological measures considered appropriate to Ascaris lumbricoides infection in both a high and low transmission area. The optimal strategy for control is shown to be dependent on the control objectives, the rate of transmission, and existing budget constraints. The analysis suggests that if the aim of control is to reduce morbidity due to ascariasis and mass treatment is the approach selected, then it is more cost-effective to intervene in a high transmission area than in a low transmission area, and that relatively long intervals between treatments offer the most cost-effective strategy.

Morbidity and mortality due to Ascaris-induced intestinal obstruction.

We examined epidemiological aspects of Ascaris-induced intestinal obstruction (AI-IO) through analysis of published reports on the subject. In 9 studies of > or = 100 patients admitted to hospital due to ascariasis, intestinal obstruction was the single most common complication and accounted for 38-87.5% of all complications (weighted mean 72%). The proportion of intestinal obstruction caused by ascariasis was identified in 14 studies from 7 countries with varying degrees of endemic ascariasis. Using relevant data on the duration of the study, the number of beds in the reporting hospital, and the number of hospital beds/1000 population in the area, the number of cases of AI-IO/year/1000 population was estimated from 11 studies. Both the proportion of AI-IO (range 0-0.71) and the number of cases of AI-IO/year/1000 population (range 0-0.25) were significantly related, in a non-linear manner, to the local prevalence of ascariasis (range 0.01-0.92). In 12 studies of > or = 30 patients with AI-IO, the case fatality rates ranged from 0 to 8.6% (weighted mean 5.7%). The mean age of patients with AI-IO was < or = 5 years in 6 of 7 studies in which age was specified.

Geohelminth infection of children from rural plantations and urban slums in Malaysia.

This study compares levels of geohelminth infection in children living in rural estates and urban slum areas of Malaysia. The statistical characteristics of geohelminth infection in 1499 children from birth up to 15 years of age, living in rural estates, were analysed according to age, sex and ethnic origin and compared with the same statistics for 1574 slum-dwelling children of similar age groups and ethnic origins. The prevalence and intensity of ascariasis and trichuriasis were significantly higher among children from the urban slums. Slum-dwelling ethnic Indians and Malays had higher levels of infection with Ascaris lumbricoides and Trichuris trichiura than their rural counterparts, but the infection status of the ethnic Chinese in the 2 areas was similar. Hookworm infection was similar in both areas, indicating that hookworm infection is neither necessarily nor solely a rural disease. These results suggest that urban slum children are at greater risk of ascariasis and trichuriasis than their rural counterparts.

Control of Ascaris infection by chemotherapy: which is the most cost-effective option?

Cost-effectiveness analysis is used to predict the optimal design of mass chemotherapy strategies in controlling Ascaris lumbricoides infection. The question of who to treat, how many to treat, and how often to treat are addressed using a population dynamic model of helminth transmission that assesses effectiveness in terms of disease reduction, combined with cost data from an actual control programme. Child-targeted treatment can be more cost-effective than population treatment in reducing the number of disease cases. The model also implies that, in the circumstances described here, enhancing coverage is a more cost-effective approach than increasing frequency of treatment.

The epidemiology of hookworm infection and its contribution to anaemia among pre-school children on the Kenyan coast.

Intestinal nematode infections are recognized as a major public health problem, and helminth control is currently being directed towards school-aged children who are known to harbour the heaviest infections and are most likely to suffer from associated morbidity. However, few data are available for the epidemiology of intestinal nematodes in pre-school children in Africa, and the contribution of hookworm infection to the aetiology and severity of anaemia among pre-school children remains poorly understood. This paper investigates the epidemiology of parasitic infections in 460 pre-school children who were part of a larger case-control study of severe malaria in Kilifi on the Kenyan coast. Almost one-third (28.7%) were infected with hookworm, 20.2% with Ascaris lumbricoides and 15.0% with Trichuris trichiura. Infection prevalence of each species rose with age, and the prevalence of heavy infection with hookworm and mean intensity of hookworm were markedly age-dependent. One-third (34.3%) of children had malaria. Overall, 76.3% of children were anaemic (haemoglobin < 110 g/L), with the prevalence decreasing with age. Anaemia was significantly worst in children with heavy hookworm infection (> 200 eggs per gram). This relationship held for all ages, both sexes, and was independent of socioeconomic factors. The application of attributable morbidity methods confirmed the contribution of hookworm infection to anaemia.

Desirable characteristics of a schistosomiasis vaccine: some implications of a cost-effectiveness analysis.

This paper investigates some of the characteristics which a vaccine for schistosomiasis would require to be more cost-effective than chemotherapy. The impact of a variety of possible vaccination scenarios are assessed in terms of the discounted years of heavy infection prevented in children, and the cost-effectiveness of these approaches are compared with annual mass treatment. The analyses demonstrate that the three critical parameters determining whether a vaccine would ever be more cost-effective than mass chemotherapy are price, duration of protection and efficacy. If the vaccine had sufficient duration of protection to be delivered through the regular childhood immunization programmes (EPI), it could be more cost-effective than annual chemotherapy. The necessary condition is that adding the vaccine to EPI must not cost more than $4.30 per person in excess of one round of chemotherapy. For a shorter duration of vaccine protection, the schistosomiasis vaccine could not exceed the cost (including delivery costs) of one round of annual chemotherapy by more than approximately $3.50.

The cost effectiveness of mass drug therapy for intestinal helminths.

This article reviews the principles involved in establishing the cost effectiveness of mass drug therapy for the major intestinal nematodes and the intestinal form of schistosomiasis, as well as the extent to which the available studies have provided definitive answers. For governments or agencies that have decided to introduce a control programme, there is considerable evidence about the comparative cost effectiveness of different types of delivery strategies. For example, mass treatment is more cost effective than selective treatment (treatment after individual screening) in high prevalence areas and at observed prices. Mass treatment targeted at known high risk groups, such as schoolchildren, for the major intestinal helminths (apart from hookworm) can be more cost effective than population-based mass treatment. However, this raises the question whether any form of mass anthelmintic chemotherapy is an efficient use of scare health resources in view of the competing demands for scarce public funds, and for the scarce resources of other funders of healthcare including donors, nongovernmental organisations and missions. Some evidence that it is an efficient use of resources is available; this article concludes by outlining the type of information that is required to strengthen the argument for mass therapy.

Estimation of intestinal nematode prevalence: influence of parasite mating patterns.

Prevalence of infection with intestinal helminths is usually assessed through stool examination. There are limitations in using this technique to measure infection status, since some infected individuals have no patent infection. The relationship between infection assessed by stool examination and actual infection prevalence is investigated for the three major nematode species--Ascaris lumbricoides, Trichuris trichiura and the hookworms--using a model which describes the presence of non-egg producing worm combinations. The analysis demonstrates that stool examination under-estimates the actual infection prevalence, and that the degree of under-estimation is dependent on the level of infection, the nematode species and the parasite sex ratio. These findings have implications for the validity of epidemiological surveys and the evaluation of control programmes.

Comparative cost-effectiveness of diagnostic tests for urinary schistosomiasis and the implications for school health programmes.

The use of self-reported schistosomiasis or blood in urine has received a great deal of interest as a cheap and simple technique for diagnosing individuals infected with Schistosoma haematobium and identifying schools with a high prevalence of infection. Although the answers to questions about the signs and symptoms of urinary schistosomiasis have been shown to be good markers of parasitological infection, a formal cost-effectiveness analysis of their performance in relation to urine filtration and parasitological examination (assumed to be the gold standard) is lacking. Using empirical data on the costs and effectiveness of these techniques in 15 schools in Tanzania, the cost for every correct diagnosis or for every infected child identified was assessed. Although self-reported schistosomiasis was shown to be three times more cost-effective than urine filtration in identifying infected individuals, it would have resulted in a third of the infected children being missed. Use of self-reported schistosomiasis first to identify high-risk schools for mass treatment and then to identify infected children in low-risk schools (for individual treatment) also appeared more cost-effective than urine filtration and would have resulted in only 8% of the infected children not being treated. The use of self-reported schistosomiasis or self-reported blood in urine should be continually supported as a simple, cheap and cost-effective tool for identifying schools at high-risk of schistosomiasis.

An investigation into the interaction between drug efficacy and drug price of praziquantel in determining the cost-effectiveness of school-targeted treatment for Schistosoma mansoni using a population dynamic model.

A population dynamic model of schistosome transmission was used to investigate the interaction between drug efficacy and drug price of different brands of praziquantel in determining the cost-effectiveness of school-targeted treatment for Schistosoma mansoni. In this analysis, costs were affected by coverage, drug price and distance travelled, and effectiveness by coverage and drug efficacy. Four effectiveness measures were assessed: the number of infection case-years prevented, heavy infection case-years prevented, hepatomegaly case-years prevented and fibrosis case-years prevented. The interactions between drug efficacy and drug price were complex. In particular, there was a highly nonlinear relationship between drug efficacy and cost-effectiveness, with drugs of low efficacy producing high and variable cost-effectiveness ratios, particularly when other programme costs related to distance travelled were high. The results suggest that given the current price range of praziquantel, a drug with less than a 50% chance of killing the worms is not to be recommended. This has important practical implications for the widespread use of praziquantel, since most international agencies procure praziquantel purely on the basis of price. There is clearly a need for studies which evaluate the efficacy of new brands of praziquantel, and more credence should be given to the use of high efficacy brands, not only in terms of maximizing the cost-effectiveness of the intervention programme, but also in delaying the onset of drug resistance.

Schools for health: Focus on health, education and the school-age child.

Mortality in children under five years old has been dramatically reduced through successful programmes of immunization and control of diarrhoeal diseases. UNICEF estimates that some 90% of children in developing regions now survive to reach school age. These survivors face new and continuing threats to their health, which can affect their physical development and may also prevent them taking full advantage of their only opportunity for formal education. The physical and mental growth of the 1000 million school-age children today will influence how the world is shaped for coming generations. Yet the health problems of this age group have received little attention. Recognizing the importance of this age group, a workshop funded by the Edna McConnell Clark Foundation was held 10-13 November 1994 in Fort Mitchell, Kentucky, USA, to review what is known about the health of school-age children, what is or can be done to improve their health, and what steps must be taken to find ways to improve the health and educational achievement of this important segment of the world's population. Don Bundy and Helen Guyatt here report on the workshop, which had three major conclusions: (1) the school-age children of developing countries face health problems that remain neglected and poorly understood; (2) an important research need is to develop simpler means of monitoring the health status of school-age children and evaluating the impact of public health interventions in this age group; and (3) two strategies are available to address this public health problem. The first is to develop further and test programmes that appear, from available evidence and pilot studies, to offer effective means of improving the health of this age group at reasonable cost, and to be sustainable; and the second is, over a longer term, to develop the capacity within countries to assess the health problems of school-age children and devise cost-effective strategies to address these problems. This report attempts, in brief form, to survey what is known about the health status of school-age children, to discuss the possible benefits to health and learning that accrue from health interventions, and to suggest some avenues currently available for both research and application.

Human behaviour, cost-effectiveness analysis and research and development priorities: the case of a schistosomiasis vaccine.

Cost-effectiveness analysis has been widely used in the health sector to guide decisions about where scarce resources aimed at disease prevention or control should be invested. It has rarely been used to guide decisions about what type of health research should be funded. In addition, the validity of the behavioural assumptions underlying the economic analysis is rarely considered explicitly. This paper explores the use of cost-effectiveness analysis to set priorities for research using the development of a schistosomiasis vaccine as an example. It then explicitly considers behavioural factors which might affect the accuracy of the calculations. A 'product profile' for the new technology is derived which can be used by developers as a target to aim at. To ensure that the vaccine would be more cost-effective than the currently preferred option for the control of schistosomiasis, chemotherapy based on praziquantel, researchers need a vaccine which has sufficient duration of protection to be delivered as part of the regular childhood immunization programme me. The cost of adding it to existing vaccination schedules should not be more than US$4.30 per child in excess of the cost of one round of chemotherapy. It should, ideally, have an efficacy over 80%. These results, however, depend on a number of cultural and behavioural factors which are often ignored in cost-effectiveness studies. For example, low rates of school attendance would increase the cost of contacting children for a chemotherapy programme and increase the relative attractiveness of a vaccine. For chemotherapy to be effective, children also need to comply each year for a number of years. Falling rates of compliance over time would reduce the effectiveness of chemotherapy and increase the attractiveness of a vaccine. But on the other hand, even though a vaccine may still be more cost-effective than chemotherapy at relatively low levels of vaccine efficacy, if mothers perceived the vaccine to be ineffective and refused to bring their children for vaccination, the success of the entire childhood immunization programme could be threatened.