The economic impact of project MARS (motivating adolescents to reduce sexual risk).

OBJECTIVE: The purpose of this study was to economically evaluate Project MARS (Motivating Adolescents to Reduce Sexual Risk; T. J. Callahan, E. A. Montanaro, R. E. Magnan, & A. D. Bryan, 2013, "Project MARS: Design of a multi-behavior intervention trial for justice-involved youth," Translational Behavioral Medicine, Vol. 3, pp. 122-130), an ongoing, randomized, sexual-risk-reduction intervention for justice-involved youth. We consider the effect of including viral STIs in the economic analysis, and explore the impact of the MARS intervention on the perceived cost of acquiring STIs to justice-involved youth. METHOD: 206 participants, ages 14 to 18, participated in a sexual-risk-reduction intervention that included screening and treatment for chlamydia and gonorrhea. A Bernoulli probability model was used to estimate averted STIs attributable to the MARS intervention. The economic benefit of averted STIs was monetized using the direct medical cost of treatment. In addition, we used a contingent valuation (willingness-to-pay) model to investigate the impact of the Project MARS on participants' perceived cost of acquiring an STI. RESULTS: Using the standard outcome domains typically used to evaluate STI interventions, Project MARS resulted in a reduction of $2.08 in direct medical costs for every $1 spent. When viral STIs were added to the economic model, a considerable increase in averted direct medical costs ($2.68 for every $1 spent) was found. Preliminary contingent valuation estimates suggest that participants' willingness-to-pay for averted STIs significantly increased after receiving the MARS intervention. CONCLUSION: From an economic perspective, Project MARS is a worthwhile program to adopt. Future attention should be given to the impact of behavioral interventions on viral infections.

Screening and treatment of chagas disease in organ transplant recipients in the United States: recommendations from the chagas in transplant working group.

Donor-derived transmission of Trypanosoma cruzi, the etiologic agent of Chagas disease, has emerged as an issue in the United States over the past 10 years. Acute T. cruzi infection causes substantial morbidity and mortality in the posttransplant setting if not recognized and treated early. We assembled a working group of transplant infectious disease specialists, laboratory medicine specialists, organ procurement organization representatives and epidemiologists with expertise in Chagas disease. Based on review of published and unpublished data, the working group prepared evidence-based recommendations for donor screening, and follow-up testing and treatment of recipients of organs from infected donors. We advise targeted T. cruzi screening of potential donors born in Mexico, Central America and South America. Programs can consider transplantation of kidneys and livers from T. cruzi-infected donors with informed consent from recipients. However, we recommend against heart transplantation from infected donors. For other organs, we recommend caution based on the anticipated degree of immunosuppression. Our recommendations stress the need for systematic monitoring of recipients by polymerase chain reaction, and microscopy of buffy coat and advance planning for immediate antitrypanosomal treatment if recipient infection is detected. Data on management and outcomes of all cases should be collected to inform future guidelines and to assist in coordination with public health authorities.

Enzyme enhanced solid-state fermentation of kenaf core fiber for storage and pretreatment.

Kenaf is an annual fiber crop adaptable to a wide range of climates and soil types. This study investigated the use of kenaf core fiber as a feedstock for enzyme-enhanced fermentation. Triplicate kenaf core fiber samples were treated with enzymes having cellulase:hemicellulase activity ratios of 0:1, 0.015:1, 0.45:1, and 2.54:1 at a rate of 5010 IU/kg dry matter hemicellulase activity, vacuum-sealed, and incubated at 37 degrees C for 21 d. Samples were analyzed for pH, water soluble carbohydrates, organic acids, and hemicellulose and cellulose concentrations. All treatments produced a pH less than 4.0, which is sufficient for stable storage. Treatments with 2.54:1 and 0.45:1 produced the highest water soluble carbohydrate and lactic acid concentrations. Enzymes with no or low cellulase activity produced results similar to the control. Utilizing enzyme mixtures with high cellulase activity is an effective pretreatment method for ensiled kenaf core fiber.

Application of an improved method for the recombinant k 39 enzyme-linked immunosorbent assay to detect visceral leishmaniasis disease and infection in Bangladesh.

Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement=0.970) and more reliable compared to the original method (kappa=0.587, P<0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kala-azar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.

Tracing the pathways of neotropical migratory shorebirds using stable isotopes: a pilot study.

We evaluated the potential use of stable isotopes to establish linkages between the wintering grounds and the breeding grounds of the Pectoral Sandpiper (Calidris melanotos), the White-rumped Sandpiper (Calidris fuscicollis), the Baird's Sandpiper (Calidris bairdii), and other Neotropical migratory shorebird species (e.g., Tringa spp.). These species molt their flight feathers on the wintering grounds and hence their flight feathers carry chemical signatures that are characteristic of their winter habitat. The objective of our pilot study was to assess the feasibility of identifying the winter origin of individual birds by: (1) collecting shorebird flight feathers from several widely separated Argentine sites and analyzing these for a suite of stable isotopes; and 2) analyzing the deuterium and 18O isotope data that were available from precipitation measurement stations in Argentina. Isotopic ratios (delta13C, delta15N and delta34S) of flight feathers were significantly different among three widely separated sites in Argentina during January 2001. In terms of relative importance in separating the sites, delta34S was most important, followed by delta15N, and then delta13C. In the complete discriminant analysis, the classification function correctly predicted group membership in 85% of the cases (jackknifed classification matrix). In a stepwise analysis delta13C was dropped from the solution, and site membership was correctly predicted in 92% of cases (jackknifed matrix). Analysis of precipitation data showed that both deltaD and delta18O were significantly related to both latitude and longitude on a countrywide scale (p < 0.001). Other variables, month, altitude, explained little additional variation in these isotope ratios. Several issues were identified that will likely constrain the degree of accuracy one can expect in predicting the geographic origin of birds from Argentina. There was unexplained variation in isotope ratios within and among the different wing feathers from individual birds. Such variation may indicate that birds are not faithful to a local site during their winter stay in Argentina. There was significant interannual variation in the deltaD and delta18O of precipitation. Hence, specific locations may not have a constant signature for some isotopes. Moreover, the fractionation that occurs in wetlands due to evaporation significantly skews local deltaD and delta18O values, which may undermine the strong large-scale gradients seen in the precipitation data. We are continuing the research with universities in Argentina with a focus on expanding the breadth of feather collection and attempting to resolve the identified issues.

Isotope variations in white-tailed kites from various habitats in California: possible limitations in assessing prey utilization and population dynamics.

White-tailed kite (Elanus leucurus) populations in the 1930s were close to extirpation in the United States. But by the 1940s, an upward trend towards recovery was apparent and continued to their current stable population levels. These dramatic fluctuations in kite numbers may have been related to changes in rodent prey populations due to the conversion of native habitats to agriculture. To address this question, we evaluated the use of stable isotope analysis in determining if a shift in diet could be isotopically differentiated in current and historic kite populations. We first compared delta13C, delta15N, and delta34S values from present-day kite flight feathers and prey fur samples from four locations in California. The total ranges of isotope values for kite and their rodent prey were similar within each site. Carbon isotope values ranged from -27.1 to -22.2 per thousand in Arcata, -26.1 to -16.9 per thousand in Davis, -27.0 to -15.0 per thousand in Cosumnes, and -28.2 to -11.6 per thousand in Santa Barbara. Nitrogen isotope values ranged from 3.2 to 15.7 per thousand in Arcata, 2.8 to 12.7 per thousand in Davis, 4.0 to 15.7 per thousand in Cosumnes, and 1.7 to 20.0 per thousand in Santa Barbara. Sulfur isotope values ranged from -7.8 to 12.4 per thousand in Arcata, -1.1 to 9.2 per thousand in Davis, 0.7 to 10.9 per thousand in Cosumnes, and -8.6 to 15.6 per thousand in Santa Barbara. Carbon, nitrogen, and sulfur isotope values at each site reflect typical trophic enrichments due to physiological processes. At each site, delta13C and delta15N values reflected the influence of a predominantly C3 or a mixed C3/C4 plant community. Sulfur isotope values reflect the influence of predominant marine or terrestrial sulfur sources at each site. However, variability in isotope values may limit the usefulness of such analyses for addressing prey utilization and population dynamics.

Hospital control and multidrug-resistant pulmonary tuberculosis in female patients, Lima, Peru.

We examined the prevalence of tuberculosis (TB), rate of multidrug-resistant (MDR) TB, and characteristics of TB on a female general medicine ward in Peru. Of 250 patients, 40 (16%) were positive by sputum culture and 27 (11%) by smear, and 8 (3%) had MDRTB. Thirteen (33%) of 40 culture-positive patients had not been suspected of having TB on admission. Six (46%) of 13 patients whose TB was unsuspected on admission had MDRTB, compared with 2 (7%) of 27 suspected cases (p = 0.009). Five (63%) of 8 MDRTB patients were smear positive and therefore highly infective. In developing countries, hospital control, a simple method of reducing the spread of MDRTB, is neglected.

Tracking Cryptosporidium parvum by sequence analysis of small double-stranded RNA.

We sequenced a 173-nucleotide fragment of the small double-stranded viruslike RNA of Cryptosporidium parvum isolates from 23 calves and 38 humans. Sequence diversity was detected at 17 sites. Isolates from the same outbreak had identical double-stranded RNA sequences, suggesting that this technique may be useful for tracking Cryptosporidium infection sources.

Identification of 5 types of Cryptosporidium parasites in children in Lima, Peru.

Cryptosporidium parvum is usually considered to be the pathogen responsible for human cryptosporidiosis. We genotyped Cryptosporidium in 132 stool specimens from 80 Peruvian children, representing 85 infection episodes, using techniques that differentiate Cryptosporidium species and C. parvum genotypes. Five types of Cryptosporidium were identified: C. parvum human (67), bovine (8), and dog (2) genotypes, C. meleagridis (7), and C. felis (1). Twenty-five (29%) of the 85 infection episodes were associated with diarrhea. There was no significant difference in age, antecedent stunting, percentage with diarrhea, or duration of diarrhea for episodes with human genotype, compared with those of zoonotic Cryptosporidium. Duration of oocyst shedding was longer for human genotype than for zoonotic Cryptosporidium (mean, 13.9 days and 6.4 days, respectively; P=.004). Serum samples from 8 children with C. meleagridis, C. felis, or C. parvum dog genotype were tested for anti-human immunodeficiency virus (HIV) type 1 antibodies; all were found to be negative. Contrary to common belief, novel Cryptosporidium species and C. parvum genotypes can infect HIV-negative children.

A multilocus genotypic analysis of Cryptosporidium meleagridis.

Cryptosporidium meleagridis is a common cause of cryptosporidiosis in birds. In addition, recent reports have described the parasite as an etiologic agent of cryptosporidiosis in both immunocompetent and immunocompromised humans. Therefore, it is important to genetically characterize isolates of C. meleagridis from different hosts and geographic areas, and to develop molecular tools to differentiate isolates from various hosts or areas. In this study, a total of 11 isolates of Cryptosporidium meleagridis from both human and avian hosts were examined at three genetic loci: the small-subunit rRNA, 60-kDa glycoprotein precursor, and 70-kDa heat shock protein genes. Two genotypes of C. meleagridis were seen at the small-subunit rRNA locus. These differed from each other by the presence or lack of a heterogeneous copy of the gene and an ATT repeat. The 60-kDa glycoprotein precursor gene divided these eleven isolates of C. meleagridis into six genotypes with high sequence diversity between groups. The highest genetic heterogeneity, however, was seen at the 70-kDa heat shock protein locus, and was primarily present at the 3' end of the gene. This heterogeneity separated eight isolates of C. meleagridis into six genotypes. These data could be useful in the development of molecular tools to promote understanding of the transmission of C. meleagridis in humans.

An outbreak of cryptosporidiosis linked to a foodhandler.

In September and October 1998, a cryptosporidiosis outbreak occurred on a Washington, DC, university campus. In a case-control study of 88 case patients and 67 control subjects, eating in 1 of 2 cafeterias was associated with diarrheal illness (P<.001). Morbidity was associated with eating dinner on 22 September (odds ratio, 8.1; 95% confidence interval, 3.4-19.5); weaker associations were found for 6 other meals. Cryptosporidium parvum was detected in stool specimens of 16 (70%) of 23 ill students and 2 of 4 ill employees. One ill foodhandler with laboratory-confirmed C. parvum prepared raw produce on 20-22 September. All 25 Cryptosporidium isolates submitted for DNA analysis, including 3 from the ill foodhandler, were genotype 1. This outbreak illustrates the potential for cryptosporidiosis to cause foodborne illness. Epidemiologic and molecular evidence indicate that an ill foodhandler was the likely outbreak source.

Use of the recombinant K39 dipstick test and the direct agglutination test in a setting endemic for visceral leishmaniasis in Nepal.

We evaluated the field use of two serologic tests for visceral leishmaniasis (VL), the direct agglutination test (DAT) and rK39 dipstick test, in the context of a case-control study. Most VL cases in Nepal are currently diagnosed on clinical grounds and with relatively non-specific tests such as the formol-gel test. Among 14 newly diagnosed VL patients with bone-marrow slides confirmed positive in two independent laboratories, the sensitivity of both tests was 100%. Among 113 controls with no personal or household history of VL, the specificity of the rK39 was 100% while that of the DAT was 93%. The rK39 was less expensive than DAT, and has the advantages of ease of use and obtaining results within minutes. The wider use of the rK39 dipstick test could improve the specificity of VL diagnosis in Nepal.

Factors associated with visceral leishmaniasis in Nepal: bed-net use is strongly protective.

Since 1980, visceral leishmaniasis (VL) has reemerged as a public health problem in lowland Nepal. We conducted a case-control study to identify risk factors. In univariate analyses among 84 cases and 105 controls, protective factors included sleeping on a bed or cot (Odds ratio [OR] 0.44, P < 0.01) and sleeping under a bed-net regularly (OR 0.23, P < 0.001) or in the warm months (OR 0.20, P < 0.001). The bed-nets in use in this region were commercially available and untreated with insecticide. Ownership of a cow or buffalo was protective (OR 0.34, P < 0.001), whereas dampness observed in the mud floor of the house was a strong risk factor (OR 4.0, P < 0.001). In multivariable models, bed-net usage, cow or buffalo ownership, and damp floors were significantly associated with altered risk. A program to increase bed-net usage could therefore decrease the incidence of VL in Nepal.

The contrasting epidemiology of Cyclospora and Cryptosporidium among outpatients in Guatemala.

We compared epidemiologic characteristics of Cryptosporidium and Cyclospora in surveillance data from outpatient departments in Guatemala. Routinely-submitted stool specimens were screened by microscopy. Age, sex, and symptom data were collected. Cyclospora was detected in 117 (2.1%) and Cryptosporidium in 67 (1.2%) of 5,520 specimens. The prevalence of Cyclospora peaked in the warmer months, while Cryptosporidium was most common in the rainy season. Both affected children more than adults, but Cryptosporidium affected children at a younger age than Cyclospora (median age 2 years versus 5 years; P < 0.001). Cyclospora showed a stronger association with diarrhea than Cryptosporidium, even when data were stratified by age. These contrasts may reflect differences in the relative importance of transmission modes, the frequency of exposure, and the development of immunity.

Epidemiologic studies of Cyclospora cayetanensis in Guatemala.

In 1996 and 1997, cyclosporiasis outbreaks in North America were linked to eating Guatemalan raspberries. We conducted a study in health-care facilities and among raspberry farm workers, as well as a case-control study, to assess risk factors for the disease in Guatemala. From April 6, 1997, to March 19, 1998, 126 (2.3%) of 5, 552 surveillance specimens tested positive for Cyclospora; prevalence peaked in June (6.7%). Infection was most common among children 1.5 to 9 years old and among persons with gastroenteritis. Among 182 raspberry farm workers and family members monitored from April 6 to May 29, six had Cyclospora infection. In the case-control analysis, 62 (91%) of 68 persons with Cyclospora infection reported drinking untreated water in the 2 weeks before illness, compared with 88 (73%) of 120 controls (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.4, 10.8 by univariate analysis). Other risk factors included water source, type of sewage drainage, ownership of chickens or other fowl, and contact with soil (among children younger than 2 years).

Human hydatidosis in the central Andes of Peru: evolution of the disease over 3 years.

To document the natural history of Echinococcus granulosus infection and response to treatment of human hydatidosis, we reexamined 28 of 37 subjects with E. granulosus infection diagnosed in an epidemiological study conducted in 1994. Twenty-six (70%) of those 37 subjects underwent abdominal ultrasonography, chest radiography, and enzyme-linked immunoelectrotransfer blot assay in 1997. Medical records from two additional individuals were reviewed. Eight patients had their cysts surgically removed during the 3-year follow-up interval; no surgical complications or recurrences occurred. Among eight patients with cystic disease not treated by surgery, four had cyst-growth ranging from 0.4 to 1.4 cm during the 3-year interval. One patient developed a new cyst and another's simple cyst became septate; two developed new calcifications. Of 12 seropositive subjects with no cysts present in 1994, 10 reverted to seronegative, a finding that suggests a significant proportion of seropositive subjects in echinococcus-endemic regions may have only transient infection without disease. When cysts do develop, their growth rates and time courses are highly variable; over the 3-year period, we observed growth, septation, degeneration, and calcification of cysts.

Magnitude of the disease burden from neurocysticercosis in a developing country.

Cysticercosis contributes to higher epilepsy rates in developing countries than in industrialized ones, yet no estimate exists for the associated burden of disease. We used epidemiological data on neurocysticercosis in Peru to calculate the burden of disease and applied our model to the other countries of Latin America where neurocysticercosis is endemic to determine a regional estimate. Analysis of 12 population-based community studies demonstrated that neurocysticercosis was endemic in highland areas and high jungles, with seroprevalences from 6% to 24%. In one community, the adult seizure disorder rate was 9.1% among seropositive persons versus 4. 6% among seronegative persons; we used this difference for estimates. On the basis of average prevalence rates in areas of endemicity of 6%-10%, we estimated that there are 23,512-39,186 symptomatic neurocysticercosis cases in Peru. In Latin America, an estimated 75 million persons live in areas where cysticercosis is endemic, and approximately 400,000 have symptomatic disease. Cysticercosis contributes substantially to neurological disease in Peru and in all of Latin America.

Assessment of potential indicators for protein-energy malnutrition in the algorithm for integrated management of childhood illness.

Potential indicators were assessed for the two classifications of protein-energy malnutrition in the guidelines for integrated management of childhood illness: severe malnutrition, which requires immediate referral to hospital, and very low weight, which calls for feeding assessment, nutritional counselling and follow-up. Children aged < 2 years require feeding assessment and counselling as a preventive intervention. For severe malnutrition, we examined 1202 children admitted to a Kenyan hospital for any association of the indicators with mortality within one month. Bipedal oedema indicating kwashiorkor, and two marasmus indicators (visible severe wasting and weight-for-height (WFH) Z-score of < -3) were associated with a significantly increased mortality risk (odds ratios, 3.1-3.9). Very low weight-for-age (WFA) (Z-score of < -4.4) was not associated with an increased risk of mortality. Because first-level health facilities generally lack length-boards, bipedal oedema and visible severe wasting were chosen as indicators of severe malnutrition. To assess potential WFA thresholds for the very low weight classification, our primary source of data came from 1785 Kenyan outpatient children, but we also examined data from surveys in Nepal, Bolivia, and Togo. We examined the performance of WFA at various thresholds to identify children with low WFH and, for children aged < or = 2 years, low height-for-age (HFA). Use of a WFA threshold Z-score of < -2 identified a considerable proportion of children (from 13% in Bolivia to 68% in Nepal) which, in most settings, would pose an enormous burden on the health facility. Among ill children in Kenya, a threshold WFA Z-score of < -3 had a sensitivity of 89-100% to detect children with WFH Z-scores of < -3, and, with an identification rate of 9%, would avoid overburdening the clinics. Potential modifications include use of a more restrictive cut-off in countries with high rates of stunting, or the elimination of the WFA screen in order to concentrate efforts on intervention for all children below the 2-year age cut-off. Key issues in every country include the capacity to provide counselling for many children and linkage to nutritional improvement programmes in the community.

PIP: Severe malnutrition and very low weight were assessed as potential indicators for the classification of protein-energy malnutrition in the guidelines for the integrated management of childhood illness. For severe malnutrition, the authors examined 1202 children under age 5 years admitted to a Kenyan hospital for any association of the indicators with mortality within 1 month. Bipedal oedema indicating kwashiorkor, and the marasmus indicators of visible severe wasting and a weight-for-height (WFH) Z score of less than -3 were associated with a significantly increased risk of mortality. Very low weight-for-age (WFA) was not associated with an increased risk of mortality. Bipedal edema and visible severe wasting were chosen as indicators of severe malnutrition since first-level health facilities typically lack length-boards. Data for 1785 Kenyan outpatient children as well as survey data from Nepal, Bolivia, and Togo were used in assessing potential WFA thresholds for the very low weight classification. Use of a WFA threshold Z-score of less than -2 identified from 13% of children in Bolivia to 68% in Nepal who would in most settings burden health facilities. Among sick children in Kenya, a threshold WFA Z-score of less than -3 was 89-100% sensitive in detecting children with WFH Z-scores of less than -3 and, with an identification rate of 9%, would not overburden health clinics. Potential modifications include the use of a more restrictive cutoff in countries with high rates of stunting or the elimination of the WFA screen in order to focus efforts upon intervention for all children under the 2-year age cutoff.