High Prevalence of Mansonella Species and Parasitic Coinfections in Gabon Calls for an End to the Neglect of Mansonella Research

(See the Major Article by Sandri et al, on pages 287–96.)

Mansonellosis counts among the most prevalent and most neglected human filariases. This vector-borne parasite infection with species-dependent geographical distribution is encountered in large parts of sub-Saharan Africa and parts of Latin America and the Caribbean islands. The ill-defined and often questioned pathogenicity of Mansonella spp infection contributes to inappropriately scarce research resource allocation. Deservedly asked questions not only on clinical, epidemiological, or phylogenetic aspects of Mansonella spp infection, but also its influence on parasitic coinfections, impact on coendemic disease control programs, and the efficacy of vaccinations remain unanswered. Basic understanding of mansonellosis has not yet been achieved. In 2015, a potential new species, provisionally called Mansonella sp “DEUX,” was reported in febrile children in Gabon [1]. Interestingly, the presence of the obligate intracellular bacteria Wolbachia, which constitutes an effective treatment target, is still controversial across and within Mansonella spp [2].

In this issue of The Journal of Infectious Diseases, Sandri and colleagues present comprehensive new data on the molecular epidemiology of Mansonella spp, including endosymbiotic Wolbachia and parasitic coinfections, and link these to demographic and clinical data. Furthermore, Sandri et al provide molecular analyses on Mansonella species identification and illustrate their report with the first micrographs of the potential new species Mansonella sp “DEUX.”

In their cross-sectional study comprising pediatric, adult, and elderly individuals from a semiurban and rural population of Gabon, the researchers found molecular evidence of filarial infection in 48% of the 834 individuals. Impressively, the leading filarial parasite was the potential new species Mansonella sp “DEUX,” which was detected in 35%; Loa loa and Mansonella perstans were detected in 33% and 10%, respectively. The authors thereby provide the first population-based prevalence of the potential new species Mansonella sp “DEUX” in a Central African region, which remarkably exceeded the prevalence of M. perstans. Being adult/elderly or male and living in rural areas increased the risk of mansonellosis. This finding is in line with previous investigations [3] and indicates the close interaction of the human host with the transmitting vectors. Interestingly, epidemiological evaluations of the last decades showed wide variations of prevalence of M. perstans [3], which may be explained by highly focal distribution patterns of mansonellosis, but also methodological differences as supported by the research by Sandri et al.

Importantly, the spectrum of clinical symptoms and signs remains ill-defined for Mansonella infections. In this study, the most commonly reported symptom was fever, but axillary temperatures ≥38°C were only recorded in a minority of infected individuals and not associated with Mansonella sp “DEUX” infection, in contrast to the report by Mourembou et al [1]. Without the appreciation of pathogenicity and symptomatology of mansonellosis, indications for treating mansonellosis will remain unclear, especially in endemic settings where reinfection is common and current treatment regimens are unsatisfactory.

Remarkable too was the high prevalence of blood-borne coinfections detected by Sandri et al. More than a quarter (27%) of the population was infected with at least 2 filarial parasites, and most (81%) filarial species–positive individuals of all age groups were coinfected with 1–3 Plasmodium spp. Individuals with Mansonella sp “DEUX” infection had a higher risk of being concomitantly infected with L. loa and/or M. perstans. Disentangling the interparasite and parasite–host interactions underlying such multiple coinfections constitutes an interdisciplinary challenge, and its likely complexity underlines the possible implications of parasitic control programs on coendemic parasites.

Sandri et al for the first time report on the presence of endosymbiotic Wolbachia in the potential new species Mansonella sp “DEUX” in Gabon. The authors found Wolbachia in a third of Mansonella sp “DEUX”–monoinfected samples. This inconsistent detection of Wolbachia in Mansonella sp “DEUX” infection is in line with the previously reported inconsistent detection of Wolbachia in M. perstans using conventional polymerase chain reaction (PCR) compared to real-time quantitative PCR in the current study [2]. Whether Wolbachia is an essential endosymbiont for Mansonella spp or whether nondetection of Wolbachia in some Mansonella spp is due to methodological constraints remain open questions. Efficacy of antibiotic treatment targeting Wolbachia in microfilaremic patients with M. perstans infection leading to significant microfilarial depletion [4, 5], however, implies that Wolbachia is an obligatory endosymbiont.

A unique contribution of Sandri et al is the observation that M. perstans and Mansonella sp “DEUX” do not show distinctive features in microscopy and that previously published species-specific PCR primers of M. perstans were unlikely to detect Mansonella sp “DEUX.” In epidemiological studies relying on microscopy, Mansonella sp “DEUX” has thus most likely been reported as M. perstans, and the overall prevalence of mansonellosis underestimated as molecular studies, including the present study, show significantly higher prevalence. In studies that relied exclusively on molecular diagnostics, the use of PCR for M. perstans might also have led to a lower detection of mansonellosis by missing detection of Mansonella sp “DEUX.” More broadly, this observation highlights the benefits of a multimodal testing approach, that is, the combination of microscopy with molecular analyses of different genetic loci.

By confirming the presence and abundance of a potential new Mansonella spp with inconsistent presence of endosymbiotic Wolbachia, revealing a high load of mansonellosis and parasitic coinfections across all age groups in the population, and reporting again the absence of a clearly associated clinical presentation, Sandri et al not only provide valuable new data on mansonellosis in Gabon, Central Africa, but also emphasize the many unanswered questions surrounding mansonellosis. The recently published mitochondrial DNA of M. perstans hopefully constitutes the start to more genome-wide analyses [6] and a better understanding of Mansonella spp biology. The questioned clinical importance of mansonellosis does not justify the neglect of clinical research on Mansonella spp infection. On the contrary, the open questions on the pathogenicity of Mansonella spp warrant scientific dedication, all the more so with the growing understanding of the widespread distribution of Mansonella spp in endemic regions as acknowledged by Sandri et al. Well-designed epidemiological and clinical trials are needed to reveal the clinical implications of Mansonella spp infection and provide an informed basis for management and control strategies.

Notes

Financial support. S. B. is currently a participant in the Berlin Institute of Health–Charité Clinician Scientist Program funded by Charité–Universitätsmedizin Berlin and the Berlin Institute of Health.

Potential conflicts of interest. All authors: No reported conflicts of interest.

Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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