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.

Use of intermittent presumptive treatment and insecticide treated bed nets by pregnant women in four Kenyan districts.

The roll back malaria (RBM) movement promotes the use of insecticide-treated bednets (ITNs) and intermittent presumptive treatment (IPT) of malaria infection as preventive measures against the adverse effects of malaria among pregnant women in Africa. To determine the use of these preventive measures we undertook a community-based survey of recently pregnant women randomly selected from communities in four districts of Kenya in December 2001. Of the 1814 women surveyed, only 5% had slept under an ITN. More than half of the 13% of women using a bednet (treated or untreated) had bought their nets from shops or markets. Women from rural areas used bednets less than urban women (11% vs. 27%; P < 0.001), and 41% of the bednets used by rural women had been obtained free of charge from a research project in Bondo or a nationwide UNICEF donation through antenatal clinics (ANCs). Despite 96% of ANC providers being aware of IPT with sulphadoxine-pyrimethamine (SP), only 5% of women interviewed had received two or more doses of SP as a presumptive treatment. The coverage of pregnant women with at least one dose of IPT with SP was 14%, though a similar percentage also had received at least a single dose as a curative treatment. The coverage of nationally recommended strategies to prevent malaria during pregnancy during 2001 was low across the diverse malaria ecology of Kenya. Rapid expansion of access to these services is required to meet international and national targets by the year 2005. The scaling up of malaria prevention programmes through ANC services should be possible with 74% of women visiting ANCs at least twice in all four districts. Issues of commodity supply and service costs to clients will be the greatest impediments to reaching RBM targets.

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.

A comparative cost analysis of insecticide-treated nets and indoor residual spraying in highland Kenya.

The relative cost of indoor residual house-spraying (IRS) versus insecticide-treated bednets (ITNs) forms part of decisions regarding selective malaria prevention. This paper presents a cost comparison of these two approaches as recently implemented by Merlin, a UK emergency relief organization funded through international donor support and working in the highland districts of Gucha and Kisii in Kenya. The financial costs (cash expenditures) and the economic costs (including the opportunity costs of using existing staff and volunteers, and an annualized cost for capital items) were assessed. The financial cost for IRS was US dollars 0.86 per person protected, compared with 4.21 dollars for ITNs (reducing to 3.42 dollars to the provider assuming cost recovery). The economic cost per person protected for IRS was 0.88 dollars, compared with 2.34 dollars for ITNs. The costs for ITNs were sensitive to the number of nets sold per community group ('efficiency'), as the delivery costs constituted upwards of 40% of the total cost. However, even marked increases in efficiency of these groups could not reduce the costs of ITNs to that comparable with IRS, except if more than one cycle of IRS was needed. The implications of predicted reductions in the cost of insecticide for both IRS and ITNs are also explored. The provision of itemized cost data allows predictions to be made on changes in the design of these programmes. Under almost all design scenarios, IRS would appear to be a more cost-efficient means of vector control in the Kenyan highlands.

Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania.

OBJECTIVE: To determine the impact of deworming on anaemia as part of a large-scale school-based anthelmintic treatment programme in the Tanga Region of the United Republic of Tanzania. METHODS: Both the reduction in the prevalence of anaemia and the cost per case prevented were taken into consideration. Cross-sectional studies involved parasitological examination and anaemia evaluation before and at 10 months and 15 months after schoolchildren were dewormed. FINDINGS: Baseline studies indicated that the prevalence of anaemia (haemoglobin < 110 g/l) was high (54%) among schoolchildren, particularly those with high intensities of hookworm and schistosomiasis. Attributable fraction analysis suggested that hookworm and schistosomiasis were responsible for 6% and 15% of anaemia cases, respectively. Fifteen months after deworming with albendazole and praziquantel the prevalence of anaemia was reduced by a quarter and that of moderate-to-severe anaemia (haemoglobin <90 g/l) was reduced by nearly a half. The delivery of these anthelmintics through the school system was achieved at the relatively low cost of US$ 1 per treated child. The cost per anaemia case prevented by deworming schoolchildren was in the range US$ 6-8, depending on the haemoglobin threshold used. CONCLUSIONS: The results suggested that deworming programmes should be included in public health strategies for the control of anaemia in schoolchildren where there are high prevalences of hookworm and schistosomiasis.

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.

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.

A population dynamic approach to evaluating the impact of school attendance on the unit cost and effectiveness of school-based schistosomiasis chemotherapy programmes.

This paper presents a first attempt at modelling the possible cost and effectiveness of reaching non-enrolled children through school-based programmes using empirical data from Egypt. A sex/school-attendance/age-structured population dynamic model was used to predict trends in infection and early disease. Four treatment delivery strategies were compared: school-based (coverage of 85 %) and school-aged targeted (coverage of 25, 50 and 85 %). The school-aged targeted strategies also included the school-based programme. For each alternative strategy, the maximum unit cost was calculated to obtain a cost-effectiveness ratio equal or smaller to the one obtained with the school-based programme (unit cost of US$ 0.60). The analysis showed that, for S. mansoni in Lower Egypt, a programme where only 85% of children attending school were treated would still prevent 77 % of the early disease cases prevented with a programme where 85 % of all school-age children were treated. However, using the school-aged targeted strategy, from US $ 0.06 to US $ 1.03 extra unit costs could be spent to reach non-enrolled children and still be more cost-effective. Treating non-enrolled children is an important consideration in maximizing the effectiveness of treatment programmes while maintaining a cost-effectiveness comparable to school-based delivery.

Sex-dependent neutralizing humoral response to Schistosoma mansoni 28GST antigen in infected human populations.

The reduction of Schistosoma fecundity observed after experimental vaccination with the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) antigen has been related to the inhibition of glutathione S-transferase (GST) enzymatic activity by specific antibody. The humoral immune response to the protective antigen Sm28GST and to the epitopes involved in the enzymatic site (amino acid ¿aa sequences 10-43 and 190-211) was evaluated in infected individuals before chemotherapy treatment. The capacity of the serum samples to inhibit GST enzymatic activity was assessed. Specific IgG3 response was predominant in the male population with a low intensity of infection and was associated with maximal GST inhibition. In contrast, the neutralizing activity of serum samples from women with a low intensity of infection was correlated with high specific IgA response specifically directed toward the 190-211 epitope. These results strongly support the hypothesis that GST-neutralizing IgG3 and IgA isotypes are sex dependent. The relationship of this specific acquired immune response with the level of intensity of infection is discussed.

Estimating the number of helminthic infections in the Republic of Cameroon from data on infection prevalence in schoolchildren.

INTRODUCTION: The prevalence of infection with helminths is markedly dependent on age, yet estimates of the total number of infections are typically based on data only from school-aged children. Such estimates, although useful for advocacy, provide inadequate information for planning control programmes and for quantifying the burden of disease. Using readily available data on the prevalence of infection in schoolchildren, the relation between the prevalence of infection in school-aged children and prevalence in the wider community can be adequately described using species-specific models. This paper explores the reliability of this approach to predict the prevalence infection in the community and provides a model for estimating the total number of people infected in the Republic of Cameroon. METHODS: Using data on the prevalence of helminthic infection in school-aged children in Cameroon, the prevalence of infection in pre-school children and adults was estimated from species-specific linear and logistic regression models developed previously. The model predictions were then used to estimate the number of people infected in each district in each age group in Cameroon. RESULTS: For Cameroon, if only the prevalence of infection in schoolchildren is used, the number of people infected with each helminthic species will be overestimated by up to 32% when compared with the estimates provided by the species-specific models. The calculation of confidence intervals supports the statistical reliability of the model since a narrow range of parameter estimates is evident. Furthermore, this work suggests that estimation of national prevalence of infection and the number infected will be enhanced if data are stratified by age; this model represents a useful planning tool for obtaining more accurate estimates. Estimates based on data aggregated from three geographical levels (district, regional, and national) show that summarizing prevalence data at the national level will result in biases of up to 19%. Such biases reflect differences in the geographical distribution for the prevalence of each species. DISCUSSION: Developing more accurate estimates requires a better understanding of the differences in the spatial heterogeneity of each species and also better methods of incorporating this information when making estimates.

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.

Malaria epidemiology and economics: the effect of delayed immune acquisition on the cost-effectiveness of insecticide-treated bednets.

An understanding of the epidemiology of a disease is central in evaluating the health impact and cost-effectiveness of control interventions. The epidemiology of life-threatening malaria is receiving renewed interest, with concerns that the implementation of preventive measures such as insecticide-treated bednets (ITNs) while protecting young children might in fact increase the risks of mortality and morbidity in older ages by delaying the acquisition of functional immunity. This paper aims to illustrate how a combined approach of epidemiology and economics can be used to (i) explore the long-term impact of changes in epidemiological profiles, and (ii) identify those variables that are critical in determining whether an intervention will be an efficient use of resources. The key parameters for determining effectiveness are the protective efficacy of ITNs (reduction in all-cause mortality), the malaria attributable mortality and the increased malaria-specific mortality risk due to delays in the acquisition of functional immunity. In particular, the analysis demonstrates that delayed immune acquisition is not a problem per se, but that the critical issue is whether it occurs immediately following the implementation of an ITN programme or whether it builds up slowly over time. In the 'worst case' scenario where ITNs immediately increase malaria-specific mortality due to reduced immunity, the intervention might actually cost lives. In other words, it might be better to not use ITNs. On the other hand, if reduced immunity takes two years to develop, ITNs would still fall into the category of excellent value for money compared to other health interventions, saving a year of life (YLL) at a cost of between US$25-30. These types of calculations are important in identifying the parameters which field researchers should be seeking to measure to address the important question of the net impact of delaying the acquisition of immunity through preventive control measures.

Can prevalence of infection in school-aged children be used as an index for assessing community prevalence?

Community data on the prevalence of helminth infections is important for guiding health policy, but expensive to collect. As a result most surveys focus on school-aged children, frequently using schools as a sentinel population. Since there already exists a vast amount of data on infection levels in school-aged children, but limited community-based data, we undertook a literature search on age-stratified infection data for intestinal nematode infections and schistosomiasis in Africa, to investigate whether estimates of the prevalence of infection in school-aged children could provide an index for determining community prevalence. The observed data on prevalence of infection in infants, school-aged children and adults were fitted using linear and logistic regression models which take into account variation in sample prevalences. Despite the wide variation in study sites, the observed relationship between community prevalence and school-aged prevalence was remarkably consistent for each parasite species. The prevalence of infection in school-aged children alone was shown to be higher than the predicted prevalence in the community, but the degree of overestimation was dependent on the parasite species and the level of infection. The results suggest that the prevalence of infection in school-aged children could provide a cost-effective predictive tool which can be used at a district/national level to identify target areas for control and to evaluate the numbers at risk of infection.

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.

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.

Worm burden in intestinal obstruction caused by Ascaris lumbricoides.

Examination of 24 case reports suggests the worm burden in those presenting to hospital with intestinal obstruction is > 60 and is about tenfold higher in fatal cases.