The Broader Economic Value of School Feeding Programs in Low- and Middle-Income Countries: Estimating the Multi-Sectoral Returns to Public Health, Human Capital, Social Protection, and the Local Economy.

Introduction: Globally, there are 370 million children receiving school meals every day. Coverage is least in low-income countries, where the need is greatest and where program costs are viewed as high in comparison with the benefits to public health alone. Here we explore the policy implications of including the returns of school feeding to other sectors in an economic analysis. Methods: We develop an economic evaluation methodology to estimate the costs and benefits of school feeding programs across four sectors: health and nutrition; education; social protection; and the local agricultural economy. We then apply this multi-sectoral benefit-cost analytical framework to school feeding programs in 14 countries (Botswana, Brazil, Cape Verde, Chile, Côte d'Ivoire, Ecuador, Ghana, India, Kenya, Mali, Mexico, Namibia, Nigeria, and South Africa) for which input data are readily available. Results: Across the 14 countries, we estimate that 190 million schoolchildren benefit from school feeding programs, with total program budgets reaching USD11 billion per year. Estimated annual human capital returns are USD180 billion: USD24 billion from health and nutrition gains, and USD156 billion from education. In addition, school feeding programs offer annual social protection benefits of USD7 billion and gains to local agricultural economies worth USD23 billion. Conclusions: This multi-sectoral analysis suggests that the overall benefits of school feeding are several times greater than the returns to public health alone, and that the overall benefit-cost ratio of school feeding programs could vary between 7 and 35, with particular sensitivity to the value of local wages. The scale of the findings suggests that school feeding programs are potentially much more cost-beneficial when viewed from the perspective of their multi-sectoral returns, and that it would be worthwhile following up with more detailed analyses at the national level to enhance the precision of these estimates.

Assays to detect beta-tubulin codon 200 polymorphism in Trichuris trichiura and Ascaris lumbricoides.

BACKGROUND: The soil-transmitted helminths (STH) Ascaris lumbricoides and Trichuris trichiura are gastrointestinal parasites causing many disabilities to humans, particularly children. The benzimidazole (BZ) drugs, albendazole (ALB) and mebendazole (MBZ), are commonly used for mass treatment for STH. Unfortunately, there is concern that increased use of anthelmintics could select for resistant populations of these human parasites. In veterinary parasites, and lately in filarial nematodes, a single amino acid substitution from phenylalanine to tyrosine, known to be associated with benzimidazole resistance, has been found in parasite beta-tubulin at position 200. We have developed pyrosequencer assays for codon 200 (TTC or TAC) in A. lumbricoides and T. trichiura to screen for this single nucleotide polymorphism (SNP). METHOD AND FINDINGS: Pyrosequencing assays were developed and evaluated for detecting the TTC or TAC SNP at codon 200 in beta-tubulin in A. lumbricoides and T. trichiura. Genomic DNA from individual worms, eggs isolated from individual adult worms or from fecal samples with known treatment history and origin, were sequenced at beta-tubulin by pyrosequencing, and genotypes were confirmed by conventional sequencing. The assays were applied to adult worms from a benzimidazole-naïve population in Kenya. Following this, these assays were applied to individual worms and pooled eggs from people in East Africa (Uganda and Zanzibar) and Central America (Panama) where mass anthelmintic drug programs had been implemented. All A. lumbricoides samples were TTC. However, we found 0.4% homozygous TAC/TAC in T. trichiura worms from non-treated people in Kenya, and 63% of T. trichiura egg pools from treated people in Panama contained only TAC. CONCLUSION: Although the codon 200 TAC SNP was not found in any of the A. lumbricoides samples analyzed, a rapid genotyping assay has been developed that can be used to examine larger populations of this parasite and to monitor for possible benzimidazole resistance development. The TAC SNP at codon 200, associated with benzimidazole resistance in other nematodes, does occur in T. trichiura, and a rapid assay has been developed to allow populations of this parasite to be monitored for the frequency of this SNP. Sample sizes were small, anthelmintic efficacy was not assessed, and treated and non-treated samples were from different locations, so these frequencies cannot be extrapolated to other populations of T. trichiura or to a conclusion about resistance to treatment. The occurrence of the TAC SNP at codon 200 of beta-tubulin in T. trichiura may explain why benzimidazole anthelmintics are not always highly effective against this species of STH. These assays will be useful in assessing appropriate treatment in areas of high T. trichiura prevalence and in monitoring for possible resistance development in these STH.

Parasitic infection with Trichuris trichiura influences plasma levels of soluble HLA class I

High levels of sHLA-I(soluble HLA class 1) have been correlated with rejection episodes in solid organ transport recipients and with graft versus host disease in bone marrow recipients. Studies of human infection with parasitic worms of the gut have suggested that certain individuals may be genetically predisposed to intense infection. In this study, the influence of parasitic helminth infection on levels of sHLA-I in plasma was investigated in 155 HLA typed individuals from St. Lucia exposed to the gut parasite Trichuris trichiura. The results confirmed previous findings showing increased levels of sHLA-I in HLA-A9, and in this case HLA-A23 postive individuals. However, HLA-A9 positive individuals with high worm burden had significantly lower levels of sHLA-I in their plasma compared with HLA-A9 positive subjects with low worm burden. These results suggest that the intensity of T. trichiuria infection infection influences the ability of HLA-A9 positive subjects to maintain high levels of sHLA-I. (AU)

Antigenic variability in trichuris trichiura populations

The present study examines antigenic variability for the human whipworm Trichuris trichiura. Recognition by IgG of somatic antigens of individual worms collected from 3 intensely infected children from Jamaica, West Indies has been investigated by immunoblotting. When probed with 1 plasma sample, significant differences in recognition of 2 selected antigens among worm populations and between male and female worms was observed. In addition, there was evidence for antigenic variability within worm populations at the individual worm level. Such variations may have considerable implications for the development of immunity to parasitic nematodes.(AU)

Short report: long-term serum antibody isotype responses to Strongyloides stercoralis filariform antigens in eight patients treated with ivermectin

The enzyme-linked immunosorbant assay was used to investigate long term changes in serum immunoglobulin G1 (IgG1), IgG4, IgE, and IgA against Strongyloides stercoralis phosphate-buffered saline-soluble filariform larval antigens in eight Jamaican patients treated with ivermectin. Patients were followed for periods of between 170 and 542 days. Based on repeated formalin-ether concentration and agar plate culture, all patients were found to be uninfected up to 18 months following chemotherapy. Generally, all antibody isotype levels decreased following treatment, although there was considerable heterogeneity among patients. In a single patient with hyperinfection, the decrease in IgG4 was marginal and may represent a treatment failure. Reduction in serum antibody isotype responses to S. stercoralis following treatment may be used to assess the effectiveness of ivermectin in treating endemic strongyloides (AU)

Treatment of patients infected with Strongyloides stercoralis using ivermectin: assessment of efficacy and safety - abstract

Infections with Strongyloides stercoralis are often refractory to thiabendazole therapy in certain patients. Ivermectin is being used increasingly for treatment of uncomplicated infections; however, possible immunopathological changes associated with drug-induced release of antigens as observed with use of the drug in filariasis has not been studied in strongyloidiasis. In this study we used the enzyme linked immunosorbant assay (ELISA) technique to examine the profiles of S. stercoralis-specific IgG4, IgE and IgA against saline soluble filariform extracts in 8 patients treated for the parasite. All patients were found to be negative for the parasite by stool examination following treatment. Isotype levels fell in concert following treatment although there was considerable heterogeneity among patients. Levels remained low following treatment response but were still measurable for up to eighteen months post-treatment. There appeared to be no rapid release of parasite antigens following treatment. One patient exhibited a transient increase in levels of IgA after which there was a decline in this and all other isotypes. The single patient with proven chronic infection and a history of gastrointestinal symptoms exhibited almost ablated IgG1, IgE and IgA responses prior to treatment but had a significant IgG4 response which remained high following treatment. The reduction in antibody levels post-treatment may be used as confirmation of parasitological cure. The study showed that there was no rapid release of S. stercoralis antigens as seen in filarial infections and that Ivermectin is safe and effective against the parasite (AU)

Serum isotype responses in patients infected with Strongyloides stercoralis following treatment with ivermectin - abstract

Infections with Strongyloides stercoralis occur worldwide and can cause significant morbidity and mortality in man. They are often refractory to conventional chemotherapy especially in immunocompromised individuals. Recent studies have shown that Ivermectin is a safe and effective drug for use in uncomplicated infections. In this study, the profiles of parasite-specific IgG1, IgG4, IgE and IgA against a PBS soluble S. stercoralis filariform extract following treatment with ivermectin were investigated using the enzyme-linked immunosorbant assay (ELISA) technique. A series of 8 patients with parasitologically proven strongyloidiasis were treated with ivermectin and followed up for periods of 5 to 18 months. The predominant isotype found in the sera of patients from this series was IgG. High levels of IgG1 were recorded in young individuals while IgG4 was predominant in older persons. Levels of all isotypes declined following treatment and remained low up to eighteen months. Furthermore, no parasitological evidence of S. stercoralis infection was found after treatment, using agar plate and formalin-ether concentration methods. The reduction in antibody levels of post-treatment may be used as an indicator of adequate treatment and also demonstrate that patients are not exposed to drug-induced antigens following treatment. The study of S. stercoralis specific isotype profile will be useful in immuno-epidemiological studies in communities (AU)

Age-prevalence and household clustering of Strongyloides stercoralis infection in Jamaica

The epidemiology of Strongyloides stercoralis was studied in families of clinical (reference) cases and their neighbours at endemic foci in Jamaica. Thirteen foci were studied based on the place of residence of a reference case. For each household of a reference case, the 4 most proximal neighbourhood households (spatial controls) were included in the study. Out of 312 persons contacted 244 were followed up using questionaires, stool examimation and serology. Prevalence of infection based on based on stool examination was 3.5 percent and on ELISA 24.2 percent. Prevalence increased with age but was not related to gender. Reference cases were significantly older than the general study population. The prevalence of infection based on both serology and stool examination was significantly higher in referecne than in neighbouring households (the reference cases, themselves, were not included in the analysis). Furthermore, prevalence of infection was highest among persons who shared a bedroom with a reference case and decreased significantly with increasing spatial separation. This is indicative of close contact transmission which has not been previously shown for a geohelminth, but which is common among microparasites.(AU)

The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regimes (AU)

Strongyloides stercoralis: characterization of immunodiagnostic larval antigens

Forty-one-, 31-, and 28-kDa proteins of strongyloides stercoralis filariform larvae have previously been demonstrated to be sensitively and specifically recognized by serum IgG in individuals with strongyloidiasis. Characteristics of these proteins, their immunodominant epitopes, and reactive antibodies are described here. The proteins are soluble is aqueous as well as detergent extracts. The immunodominant epitopes are present in S. stercoralis but not in S. cebus or S. ratti. Epitopes on the three proteins are not shared, as determined by cross-absorption of serum with each of the size components on nitrocellulose. In most sera from strongyloidiasis patients there was reactivity to each of the proteins by IgG1 and IgG4, but reactivity by IgG2 or IgG3 was detectable only in a minority. A rabbit antiserum raised to a 41-kDa size fraction of S. stercoralis larvae reacted against a doublet of 41-kDa which was distinct from the immunodiagnostic 41-kDa protein.(AU)

Prospective evaluation of enzyme-linked immunosorbent assay and immunoblot methods for the diagnosis of endemic Strongyloides stercoralis infection

Recently described enzyme-linked immunosorbent assay (ELISA) and immunoblot methods for the detection of serum IgG against Strongyloides stercoralis larval antigens were prospectively evaluated for the diagnosis of endemic strongyloidiasis. A modification of the ELISA involved preincubation of sera with Onchocerca gutturosa phosphate-buffered saline-soluble extract to remove cross-reactivity with other helminths. The sensitivity of the ELISA increased from 80 percent and 85 percent following preincubation. Similarly, there was an increase in specifity from 94 percent to 97 percent. The IgG recognition of 41-, 31-, and 28-kD filariform larval components showed sensitivities of 100 percent, 85 percent and 65 percent, respectively. Both the ELISA following incubation of sera with O. gutturosa extract and serum IgG reactivity to a 41-kD larval component using immunoblotting are sensitive and specific techniques for diagnosing endemic strongyloidiasis.(AU)

Age-prevalence profile and household clustering of cases of strongyloides infection at endemic foci at Jamaica - abstract

Strongyloides sterocalis infections were examined in families of clinical cases and also in those of their most proximal neighbours. Thirteen clinical cases in Kingston, Jamaica led to the identification of thirteen endemic foci. In addition to the clinical cases, 299 persons were contacted using questionnaires, stool examination and serology. Two hundred and thirty-one persons were fully compliant. The stool prevalence of S.sterocalis was 3.5 percent, while that based on ELISA was 24.2 percent (not including the 13 clinical cases). Both estimates of infection prevalence were significantly higher in the households of the clinical cases compared with the neighbours. The clinical cases were significantly older than the general study population. Furthermore, prevalence was highest among persons who shared a bedroom with a clinical case and decreased with spatial separation. These data strongly suggest that human strongyloides is a close-contact infection. This is likely to be facilitated by the direct phase of the parasite's life cycle and has significant implications for control of infections in endemic areas (AU)_

Serum IgG reactivity with 41-, 31- and 28-kDa larval proteins of Strongyloides stercoralis in individuals with strongyloidiasis

Proteins from a deoxycholate-soluble extract of Strongyloides stercoralis infective larvae were separated by SDS-PAGE, blotting onto nitrocellulose paper, and reacted with sera from individuals with confirmed S. stercoralis infections (n = 100), suspectedS. stercoralis infections in whom no larvae could be detected (n = 27), and other nematode infections (40 with Wuchereria bancrofti, 20 with Onchocerca volvulus, 20 with Necator americanus, and 20 with mixed Ascaris lumbricoides and Trichuris trichiura infections). Immunodominant proteins of approximately 41, 31, and 28 kDa were recongnized by IgG in 91 percent, 88 percent and 90 percent respectively, of sera from those with confirmed strongyloidiasis; in 100 percent, 100 percent, and 93 percent of sera from those with suspected strongyloidiasis; and in 9 percent, 12 percent and 14 percent of sera from those infected with other nematodes. IgG reactivity to each of these proteins was a more specific means of immunodiagnosis than the currently use indirect ELISA; the methods were equally sensitive.(AU)

The age of infection with varicella-zoster virus in St. Lucia, West Indies

Sera from an age-stratified sample of 1810 people from the Caribbean island of St. Lucia were tested for antibodies against varicella-zoster virus. The results indicate that very few infections occur in childhood which agrees with clinical survey data from other tropical countries, but contrasts with the observed high case rate in children in temperate countries. The alternative hypothesis which may explain these results are discussed, and it is suggested that high ambient tempertaures interfere with the transmission of the virus. Irrespective of the cause the pattern of varicella incidence observed has important implications for any vaccination policy adopted in tropical countries (AU)

Prospective evaluation of an ELISA and Western Blot for the diagnosis of endemic strongyloides stercoralis infection - abstract

Strongyloides stercoralis is the most serious intestinal nematode infecting humans in the Caribbean. The parasite is, however, difficult to diagnose using standard laboratory techniques, especially in sub-clinical cases. An ELISA, using PBS extracts of filariform larvae as antigen, and a Western Blot method were evaluated in the Jamaican community. Sensitivity and specificity of the ELISA were 73 per cent and 93 per cent (n=135) respectively. Pre-incubation of sera with Onchocerca gutterosa (Filariata) antigen increased sensitivity and specificity of the ELISA to 82 per cent and 97 per cent, respectively. Similarly, The Western Blot which was based on IgG recognition of proteins of 41kD and one of 31kD or 28kD detected 82 per cent of infected individuals and 97 per cent of true negatives. There was no notable cross-reactivity by either ELISA or Western Blot with Ascaris, Trichuris or hookworm, also common to the Region. ELISA proved to be a sensitive and specific test for diagnosing S. stercoralis infection in Jamaica. Western Blotting had no significant merits over those of ELISA although it confirmed the presence of 3 immunodominant bands which may play a role in future immunodiagnosis. Furthermore, it adds to the battery of sensitive serological tests available to clinicians who have to decide on the infection status of potential S. stercoralis patients who are about to receive immuno-suppressive therapy (AU)