Browsing by Author "Guy Mollett"

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Detection of Immunoglobulin G1 against rK39 Improves Monitoring of Treatment Outcomes in Visceral Leishmaniasis
(Oxford University Press, 2019) Guy Mollett; Bruno C. Bremer Hinckel; Tapan Bhattacharyya; Tegwen Marlais; Om Prakash Singh; Pascal Mertens; Andrew K. Falconar; Sayda El-Safi; Shyam Sundar; Michael A. Miles
Background: Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a fatal, neglected tropical disease that is targeted for elimination in India, Nepal, and Bangladesh. Improved diagnostic tests are required for early case detection and for monitoring the outcomes of treatments. Previous investigations using Leishmania lysate antigen demonstrated that the immunoglobulin (Ig) G1 response is a potential indicator of a patient's clinical status after chemotherapy. Methods: IgG1 or IgG enzyme-linked immunosorbent assays (ELISAs) with rK39 or lysate antigens and novel IgG1 rK39 rapid diagnostic tests (RDTs) were assessed with Indian VL serum samples from the following clinical groups: paired pre-and postchemotherapy (deemed cured); relapsed; other infectious diseases; and endemic, healthy controls. Results: With paired pre-and post-treatment samples (n = 37 pairs), ELISAs with rK39-and IgG1-specific conjugates gave a far more discriminative decrease in post-treatment antibody responses when compared to IgG (P <. 0001). Novel IgG1 rK39 RDTs provided strong evidence for decreased IgG1 responses in patients who had successful treatment (P <. 0001). Furthermore, both IgG1 rK39 RDTs (n = 38) and ELISAs showed a highly significant difference in test outcomes between cured patients and those who relapsed (n = 23; P <. 0001). RDTs were more sensitive than corresponding ELISAs. Conclusions: We present strong evidence for the use of IgG1 in monitoring treatment outcomes in VL, and the first use of an IgG1-based RDT using the rK39 antigen for the discrimination of post-treatment cure versus relapse in VL. Such an RDT may have a significant role in monitoring patients and in targeted control and elimination of this devastating disease. © 2018 The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
Male predominance in reported visceral leishmaniasis cases: Nature or nurture? A comparison of population-based with health facility-reported data
(Public Library of Science, 2020) Kristien Cloots; Sakib Burza; Paritosh Malaviya; Epco Hasker; Sangeeta Kansal; Guy Mollett; Jaya Chakravarty; Nurpur Roy; Bibek Kumar Lal; Suman Rijal; Shyam Sundar; Marleen Boelaert
Background Bangladesh, India, and Nepal aim for the elimination of Visceral Leishmaniasis (VL), a sys-temic parasitic infectious disease, as a public health problem by 2020. For decades, male patients have comprised the majority of reported VL cases in this region. By comparing this reported VL sex ratio to the one observed in population-based studies conducted in the Indian subcontinent, we tested the working hypothesis that mainly socio-cultural gender differences in healthcare-seeking behavior explain this gender imbalance. Methodology/Principal findings We compared the observed sex ratio of male versus female among all VL cases reported by the health system in Nepal and in the two most endemic states in India with that observed in population-based cohort studies in India and Nepal. Also, we assessed male sex as a poten-tial risk factor for seroprevalence at baseline, seroconversion, and VL incidence in the same population-based data. The male/female ratio among VL cases reported by the health systems was 1.40 (95% CI 1.37–1.43). In the population cohort data, the age-and study site-adjusted male to female risk ratio was 1.27 (95% CI 1.08–1.51). Also, males had a 19% higher chance of being seropositive at baseline in the population surveys (RR 1.19; 95% CI 1.11–1.27), while we observed no significant difference in seroconversion rate between both sexes at the DAT cut-off titer defined as the primary endpoint. Conclusions/Significance Our population-based data show that male sex is a risk factor for VL, and not only as a socio-cultural determinant. Biological sex-related differences likely play an important role in the pathogenesis of this disease. © 2020 Cloots et al.