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Microbiological Diagnosis of Parasitic Diseases
Published in Nancy Khardori, Bench to Bedside, 2018
Xenodiagnosis is another method for recovery of parasites which involves use of an arthropod host. For example, reduviid bugs may be used in the diagnosis of Chagas’ disease. Here, the reduviid bugs are allowed to feed on the blood of a patient with suspicion of this parasitic infection. After 1-2 months, the arthropod’s feces is examined for the developmental stages of Trypanosoma cruzi (Maekelt 1964). This process is continued for a period of 3 months before reporting the specimen as negative. Xenodiagnosis is very rarely used for diagnostic purposes.
Chagas’ Disease
Published in F. Y. Liew, Vaccination Strategies of Tropical Diseases, 2017
Differential centrifugation of an epimastigote homogenate prepared in the Ribi apparatus yielded a microsomal-rich and a cell sap fraction that Ruiz et al.85 tested in mice for immunoprotective activity. The salient finding in this case was that even without challenge, many of the mice immunized with these fractions presented myocarditis, and mice injected with the cell sap produced anomalous electrocardiographic patterns. Circulating parasites were not detected in these animals by xenodiagnosis. However, the number of insects used and the frequency of testing were not described in the paper. These are critical factors impinging on the success of xenodiagnosis because parasites are not always detectable in reduviid bugs fed on infected blood.88 The humoral immunity of mice immunized with flagellar T. cruzi antigens was reported separately.89 Goncalves da Costa and Lagrande90 injected 106 BCG organisms s.c. into one of the hind footpads of specific pathogen-free OF mice. Three weeks later, the animals received a purified flagellar fraction from T. cruzi epimastigotes (CL isolate) into the same footpad. A challenge dose of 104 cell-culture- derived trypomastigotes was administered s.c. into the other hind footpad 6 d later. The immunization regimen caused the parasitemia levels to be slightly lower than those of nonimmunized controls and prevented mortality during the 36-d observation period. Immunization with the flagellar fraction alone did not afford significant protection but BCG enhanced by itself host resistance against the challenge. A protective effect was also seen in mice given an intravenous injection of cyclophosphamide at 200 mg/kg body weight 2 d before immunization. Although the cyclophosphamide treatment was intended to reduce the level of suppressor cell activity, its real consequences are difficult to evaluate.
Nifurtimox
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
There are no published large, well-designed randomized controlled trials on the use of nifurtimox in the treatment of acute-phase Chagas disease. A number of prospective and retrospective trials were performed in the 1960s and 1970s to evaluate the use of nifurtimox for this indication. However, the variable size and quality of these studies, as well as inconsistent case definitions, the nonstandard and often insensitive methods used for parasitologic and clinical evaluations of response to therapy, and variations in the duration and nature of post-therapy surveillance (including significant numbers of patients lost to follow-up) make interpretation of these studies difficult. Nonetheless, most studies have demonstrated a significantly greater rate of parasitologic response in nifurtimox-treated patients than in those receiving placebo. For example, in an Argentinian study, 550 children and adults with acute Chagas disease were treated with nifurtimox for 120 days (15 mg/kg/day in children, 7–10 mg/kg/day in adults) and outcomes compared with 55 patients who received placebo. Eighty-one percent of patients treated with nifurtimox tested seronegative for T. cruzi antibodies 2 years after completion of therapy, compared with 0% in the placebo group. All 55 patients with negative T. cruzi serology following therapy had a negative xenodiagnostic test, compared with five of nine who remained seropositive following therapy (Cerisola et al., 1970). Similarly, a multicenter study of nifurtimox (< 10 years, 15–20 mg/kg/day for 90 days; 11–16 years, 12.5–15 mg/kg/day for 90 days; > 17 years, 8–10 mg/kg/day for 120 days) in acute Chagas disease demonstrated that the mean duration of parasitemia (defined as disappearance of parasitemia as determined by microscopic examination of blood films, but not xenodiagnosis) was significantly shorter in patients receiving nifurtimox (41 vs. 80 days); 81% of nifurtimox-treated patients either did not develop anti-T cruzi antibodies or became seronegative following institution of therapy, whereas 100% of placebo-treated patients remained seropositive (Wegner and Rohwedder, 1972a). In addition, in a later study, the time to resolution of clinical manifestations of acute Chagas disease (e.g. fever, tachycardia, oculoganglionic syndrome, chagoma, and localized edema) was shorter in nifurtimox-treated patients (Wegner and Rohwedder, 1972a). However, in a study of 13 patients with acute Chagas disease that used the same treatment regimen as the Argentinian study, less than 50% of subjects became xenodiagnosis-negative after treatment (Rassi and Ferreira, 1971). This is in keeping with the findings of in vitro studies that suggest that response to nifurtimox may be variable depending on the geographical location and/or the strain of T. cruzi (see above under 2b, Emerging resistance and cross-resistance).
Clinical and pharmacological profile of benznidazole for treatment of Chagas disease
Published in Expert Review of Clinical Pharmacology, 2018
Jadel Müller Kratz, Facundo Garcia Bournissen, Colin J. Forsyth, Sergio Sosa-Estani
Clinical R&D for benznidazole (and CD more generally) has been hampered by a lack of investment. Only one large-scale, multicentric, randomized trial has taken place in the last half century [64]. Another challenge involves the difficulty of measuring treatment success during the chronic phase. Detection of the parasite (or parasite DNA) is a probable indication of treatment failure. Early studies relied on xenodiagnosis, while more recently polymerase chain reaction (PCR) has been employed. Negative serology is an effective proxy for parasitological cure in acute, congenital, and early chronic cases. However, in adult patients with chronic CD, it can take over 20 years following treatment to revert to negative serology [12]. There is an urgent need for development of a reliable test of cure to advance research and facilitate treatment.
Laboratory diagnosis of Lyme borreliosis: Current state of the art and future perspectives
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Benedikt Lohr, Volker Fingerle, Douglas E. Norris, Klaus-Peter Hunfeld
Currently, five different direct diagnostic tactics are used in the microbiological laboratory: (i) culture, (ii) nucleic acid-based methods, (iii) microscopic detection methods, (iv) direct detection of B. burgdorferi s.l.-specific proteins, and (v) xenodiagnosis. Of these, only culture and xenodiagnoses of B. burgdorferi s.l. detect viable organisms, and undoubtedly these offer the best confirmation of active infection in patients [2,3]. Bacterial culture has been increasingly used by researchers on both sides of the Atlantic, and the availability of cultured organisms has made investigations on the structural, molecular, antigenic, and pathogenetic properties of the different species of the B. burgdorferi s.l. complex possible [2,3].
Why hasn’t there been more progress in new Chagas disease drug discovery?
Published in Expert Opinion on Drug Discovery, 2020
Alane Beatriz Vermelho, Giseli Capaci Rodrigues, Claudiu T. Supuran
Nowadays the main criterion to establish treatment success (parasitological cure) is to reverse the conventional serology from positive to negative status in association with the negative results of parasitological tests (xenodiagnosis and/or hemoculture) [43,44]. Xenodiagnosis and hemoculture are difficult and expensive techniques that require special laboratory biosecurity and have a strong tendency to yield positive results in only a small proportion of serologically positive patients. All these factors limit their usefulness in diagnosis and/or in monitoring drug efficacy [6].