Succinyl-CoA Synthetase: New Antigen Candidate of Bartonella bacilliformis

Abstract

BackgroundBartonella bacilliformis is the causative agent of Carrion’s disease, a neglected illness with mortality rates of 40–85% in the absence of treatment. The lack of a diagnostic technique to overcome misdiagnosis and treat asymptomatic carriers is of note. This study aimed to identify new B. bacilliformis antigenic candidates that could lead to a new diagnostic tool able to be implemented in endemic rural areas.Methodology/Principal FindingsBlood (n = 198) and serum (n = 177) samples were collected in northern Peru. Clinical data were recorded. Specific 16S rRNA amplification by RT-PCR, IFA and ELISA for IgM/IgG with whole cells as antigens was done. Western blot analysis and N-terminal amino acid sequencing detected seroreactive proteins. ELISAs for IgM/IgG for the antigenic candidates were performed. Of the population 33.3% reported at least one symptom compatible with Carrion’s disease; 25.4% (IFA), 27.1% (ELISA-IgG), 33.9% (ELISA-IgM) and 38.9% (RT-PCR) of samples were positive. Four proteins were considered potential antigenic candidates, including two new antigenic candidates, succinyl-CoA synthetase subunit α (SCS-α) and succinyl-CoA synthetase subunit β (SCS-β). On Western blot both Pap31 and SCS-α interacted with IgM, while GroEL and SCS-β interacted with IgG. The presence of specific antibodies against the antigenic candidates varied from 34.5% (IgG against SCS-α) to 97.2% (IgM against Pap31).Conclusions/SignificanceRT-PCR and the high levels of positivity for specific ELISAs demonstrate high levels of B. bacilliformis exposure and asymptomatic carriers among inhabitants. The new antigens identified might be used as a new rapid diagnostic tool to diagnose acute Carrion’s disease and identify asymptomatic carriers.

Molecular Detection of Bartonella bacilliformis in Lutzomyia maranonensis in Cajamarca, Peru: A New Potential Vector of Carrion’s Disease in Peru?

“…3 There are around 40-50% of asymptomatic carriers in endemic areas who, in the absence of an animal reservoir, are considered the perpetuators of the disease. 5 Peru has endemic areas with approximately 1.7 million atrisk inhabitants. [1][2][3] Moreover, in the last few years, an expansion of this disease toward new areas has been reported.…”

Carrion's Disease: the Sound of Silence

“…Ellis et al reported a case-control study during an outbreak of acute bartonellosis in the Urubamba Valley (Cusco department) in 1998 (37), and more recently, Sánchez Clemente et al (28) described a 2003 outbreak in Caraz (an area of endemicity in the Ancash department). In 2013 to 2014, 428 cases were reported in the Piura department, with an outbreak in the Lalaquiz district (44,50,51). Finally, in 2016, 33% of the total number of cases were reported in Huanuco (52).…”

“…Thus, it was estimated that the negative net migration rate of Peruvian inhabitants to other countries in the period 1990 to 2012 was Ͼ2.5 million, with the number of Ecuadorian people living in other countries in 2008 also being around 2.5 million (http://www.migracionoea.org/index.php/es/parte-iii-informes-por-pais.html) (65). This and the high prevalence of carriers in areas of endemicity (50), together with the periodic visits of emigrants to related areas of endemicity and the possible long duration of asymptomatic infections (50,62), underline the undoubtable presence of asymptomatic carriers in countries where the disease is not endemic.…”

“…Indeed, one study described the isolation of B. bacilliformis from an individual who had visited Ecuador 3 years previously (62). Moreover, asymptomatic carriers have also been described in areas of endemicity (35,50,148,149). It is believed that these carriers perpetuate the disease and can introduce it into new areas, either within a stable setting with a vector in the area (as described in Colombia in the mid-1930s) or within an unstable setting in which no vector is present.…”

“…Indeed, Chamberlin and coworkers analyzed the prevalence of asymptomatic B. bacilliformis carriers in an area of endemicity by PCR and found that 0.5% were positive (35). More recently, a study including an area of endemicity (Huancabamba) and an postoutbreak area (Lalaquiz), both in the northern Peruvian department of Piura, showed that approximately half of the volunteers in the area of endemicity and about 40% of the individuals in the postoutbreak area had a positive result by quantitative real time-PCR (qPCR), demonstrating the high number of asymptomatic carriers in these zones (50). It is of concern that the positivity observed was near the qPCR detection limit, showing that the presence of bacteria in the blood may have been very low.…”