The near exclusive use of praziquantel (PZQ) for treatment of human schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. We measured susceptibility to PZQ of isolates of Schistosoma mansoni obtained from patients from Kisumu, Kenya continuously exposed to infection as a consequence of their occupations as car washers or sand harvesters. We used a) an in vitro assay with miracidia, b) an in vivo assay targeting adult worms in mice and c) an in vitro assay targeting adult schistosomes perfused from mice. In the miracidia assay, in which miracidia from human patients were exposed to PZQ in vitro, reduced susceptibility was associated with previous treatment of the patient with PZQ. One isolate (“KCW”) that was less susceptible to PZQ and had been derived from a patient who had never fully cured despite multiple treatments was studied further. In an in vivo assay of adult worms, the KCW isolate was significantly less susceptible to PZQ than two other isolates from natural infections in Kenya and two lab-reared strains of S. mansoni. The in vitro adult assay, based on measuring length changes of adults following exposure to and recovery from PZQ, confirmed that the KCW isolate was less susceptible to PZQ than the other isolates tested. A sub-isolate of KCW maintained separately and tested after three years was susceptible to PZQ, indicative that the trait of reduced sensitivity could be lost if selection was not maintained. Isolates of S. mansoni from some patients in Kisumu have lower susceptibility to PZQ, including one from a patient who was never fully cured after repeated rounds of treatment administered over several years. As use of PZQ continues, continued selection for worms with diminished susceptibility is possible, and the probability of emergence of resistance will increase as large reservoirs of untreated worms diminish. The potential for rapid emergence of resistance should be an important consideration of treatment programs. The emergence of drug resistant pathogens is a great challenge to the control of infectious diseases. Schistosomiasis is one of the world's greatest neglected tropical diseases, and it is primarily controlled with the drug praziquantel. This drug is often used by repeatedly treating patients to maintain reduced worm burdens, an ideal situation to encourage the evolution of resistant worms. Although drug based control programs are increasing, monitoring efforts for drug resistance remain rare. We measured drug susceptibility of schistosomes from a cohort of patients in Kenya who are enrolled in a longitudinal study in which they are repeatedly treated with praziquantel. We found that schistosomes from previously treated patients were significantly less susceptible than those that were not. Also, schistosomes derived from a single patient who had been treated with praziquantel 18 times showed marked resistance. Although the findings of this study indicated that reduced drug susceptibility occurs in this population of schistosomes, this trait does not seem to be spreading widely or creating clinical levels of resistance. We hypothesize that the trait remains at low frequency because of the large population of schistosomes that are not exposed to the drug and/or potential fitness costs associated with reduced susceptibility.

Summary: There is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas: immunopathogenesis, resistance to reinfection and diagnostics. It is clear that the bulk of, if not all, morbidity due to human schistosomiasis results from immune‐response‐based inflammation against eggs lodged in the body, either as regulated chronic inflammation or resulting in fibrotic lesions. However, the exact nature of these responses, the antigens to which they are mounted and the mechanisms of the critical regulatory responses are still being sorted out. It is also becoming apparent that protective immunity against schistosomula as they develop into adult worms develops slowly and is hastened by the dying of adult worms, either naturally or when they are killed by praziquantel. However, as with anti‐egg responses, the responsible immune mechanisms and inducing antigens are not clearly established, nor are any potential regulatory responses known. Finally, a wide variety of immune markers, both cellular and humoral, can be used to demonstrate exposure to schistosomes, and immunologic measurement of schistosome antigens can be used to detect, and thus diagnose, active infections. All three areas contribute to the public health response to human schistosome infections.

We evaluated a commercial point-of-care circulating cathodic antigen (POC-CCA) test for assessing Schistosoma mansoni infection prevalence in areas at risk. Overall, 4,405 school-age children in Cameroon, Côte d'Ivoire, Ethiopia, Kenya, and Uganda provided urine for POC-CCA testing and stool for Kato-Katz assays. By latent class analysis, one POC-CCA test was more sensitive (86% versus 62%) but less specific (72% versus ∼100%) than multiple Kato-Katz smears from one stool. However, only 1% of POC-CCA tests in a non-endemic area were false positives, suggesting the latent class analysis underestimated the POC-CCA specificity. Multivariable modeling estimated POC-CCA as significantly more sensitive than Kato-Katz at low infection intensities (< 100 eggs/gram stool). By linear regression, 72% prevalence among 9–12 year olds by POC-CCA corresponded to 50% prevalence by Kato-Katz, whereas 46% POC-CCA prevalence corresponded to 10% Kato-Katz prevalence. We conclude that one urine POC-CCA test can replace Kato-Katz testing for community-level S. mansoni prevalence mapping.

The inflammatory infiltrates in the heart lesions of chronic chagasic cardiomyopathy are composed predominantly of small lymphocytes with admixed macrophages, plasma cells, and segmented leukocytes. The phenotypes of the lymphoid cells in these infiltrates of human Chagas' disease have not been previously detailed. We used a panel of monoclonal and polyclonal antibodies to immunohistochemically characterize the inflammatory cells in frozen and fixed cardiac tissues from autopsied patients with severe chronic chagasic cardiomyopathy. In all cases, the inflammatory lesions were dominated by CD8+ lymphocytes, many of which expressed granzyme A. A few macrophage-like cells that expressed tumor necrosis factor-α were observed in each case. Relatively few natural killer cells or B lymphocytes were found in the lesions. These findings in human chagasic lesions are compatible with concepts that involve cytolysis and fibrosis, and new experimental findings that emphasize potential roles for CD8+ T cells in Chagas' disease.