Immunohistochemical diagnosis of human infectious diseases: a review.

BACKGROUND: Immunohistochemistry (IHC) using monoclonal and polyclonal antibodies is a useful diagnostic method for detecting pathogen antigens in fixed tissues, complementing the direct diagnosis of infectious diseases by PCR and culture on fresh tissues. It was first implemented in a seminal publication by Albert Coons in 1941. MAIN BODY: Of 14,198 publications retrieved from the PubMed, Google, Google Scholar and Science Direct databases up to December 2021, 230 were selected for a review of IHC techniques, protocols and results. The methodological evolutions of IHC and its application to the diagnosis of infectious diseases, more specifically lice-borne diseases, sexually transmitted diseases and skin infections, were critically examined. A total of 59 different pathogens have been detected once in 22 different tissues and organs; and yet non-cultured, fastidious and intracellular pathogens accounted for the vast majority of pathogens detected by IHC. Auto-IHC, incorporating patient serum as the primary antibody, applied to diseased heart valves surgically collected from blood culture-negative endocarditis patients, detected unidentified Gram-positive cocci and microorganisms which were subsequently identified as Coxiella burnetii, Bartonella quintana, Bartonella henselae and Tropheryma whipplei. The application of IHC to ancient tissues dated between the ends of the Ptolemaic period to over 70 years ago, have also contributed to paleomicrobiology diagnoses. CONCLUSION: IHC plays an important role in diagnostic of infectious diseases in tissue samples. Paleo-auto-IHC derived from auto-IHC, is under development for detecting non-identified pathogens from ancient specimens.

Differential word expression analyses highlight plague dynamics during the second pandemic.

Research on the second plague pandemic that swept over Europe from the fourteenth to nineteenth centuries mainly relies on the exegesis of contemporary texts and is prone to interpretive bias. By leveraging certain bioinformatic tools routinely used in biology, we developed a quantitative lexicography of 32 texts describing two major plague outbreaks, using contemporary plague-unrelated texts as negative controls. Nested, network and category analyses of a 207-word pan-lexicome, comprising overrepresented terms in plague-related texts, indicated that 'buboes' and 'carbuncles' are words that were significantly associated with the plague and signalled an ectoparasite-borne plague. Moreover, plague-related words were associated with the terms 'merchandise', 'movable', 'tatters', 'bed' and 'clothes'. Analysing ancient texts using the method reported in this paper can certify plague-related historical records and indicate the particularities of each plague outbreak, which can inform on the potential sources for the causative Yersinia pestis.

Malaria in Europe: A Historical Perspective.

Endemic malaria, which claimed 229 million new cases and 409,000 deaths in 2019 mainly in Africa, was eradicated from Europe by the mid-20th century. Historical descriptions of intermittent tertian and quartan fever reported in texts of Hippocrates in Greece and Celsus in Italy suggest malaria. A few paleomicrobiology investigations have confirmed the presence of malarial parasite Plasmodium falciparum in 1st, 2nd, and 5th century infected individuals in diverse regions of Italy, and Plasmodium sp. later in Bavaria. The causative Plasmodium pathogens, discovered in the 19th century in Algeria, were controversially used as therapeutic agents in the European pharmacopeia more than two centuries after effective quinine-based treatments had been introduced in Europe. How Europe managed to eradicate malaria and what the history of malaria was in Europe are of medical interest, and this review traces research pathways for a renewed understanding of malaria eradication in Europe through combined historical and paleomicrobiological investigations.

Paleomicrobiology of the human digestive tract: A review.

The microbiota is a hot topic of research in medical microbiology, boosted by culturomics and metagenomics, with unanticipated knowledge outputs in physiology and pathology. Knowledge of the microbiota in ancient populations may therefore be of prime interest in understanding factors shaping the coevolution of the microbiota and populations. Studies on ancient human microbiomes can help us understand how the community of microorganisms presents in the oral cavity and the gut was shaped during the evolution of our species and what environmental, social or cultural changes may have changed it. This review cumulates and summarizes the discoveries in the field of the ancient human microbiota, focusing on the remains used as samples and techniques used to handle and analyze them.

The role of louse-transmitted diseases in historical plague pandemics.

The rodent-murine ectoparasite-human model of plague transmission does not correspond with historical details around plague pandemics in Europe. New analysis of ancient genomes reveal that Yersinia pestis was unable to be transmitted by rat fleas until around 4000 Before Present, which challenges the rodent-murine ectoparasite-human model of plague transmission and historical details around plague pandemics in Europe. In this Review, we summarise data regarding Y pestis transmission by human lice in the context of genomic evolution and co-transmission of other major epidemic deadly pathogens throughout human history, with the aim of broadening our view of plague transmission. Experimental models support the efficiency of human lice as plague vectors through infected faeces, which suggest that Y pestis could be a louse-borne disease, similar to Borrelia recurrentis, Rickettsia prowazekii, and Bartonella quintana. Studies have shown that louse-borne outbreaks often involve multiple pathogens, and several cases of co-transmission of Y pestis and B quintana have been reported. Furthermore, an exclusive louse-borne bacterium, namely B recurrentis, was found to be circulating in northern Europe during the second plague pandemic (14th-18th century). Current data make it possible to attribute large historical pandemics to multiple bacteria, and suggests that human lice probably played a preponderant role in the interhuman transmission of plague and pathogen co-transmission during previous large epidemics, including plague pandemics.

Five millennia of Bartonella quintana bacteraemia.

During the two World Wars, Bartonella quintana was responsible for trench fever and is now recognised as an agent of re-emerging infection. Many reports have indicated widespread B. quintana exposure since the 1990s. In order to evaluate its prevalence in ancient populations, we used real-time PCR to detect B. quintana DNA in 400 teeth collected from 145 individuals dating from the 1st to 19th centuries in nine archaeological sites, with the presence of negative controls. Fisher's exact test was used to compare the prevalence of B. quintana in civil and military populations. B. quintana DNA was confirmed in a total of 28/145 (19.3%) individuals, comprising 78 citizens and 67 soldiers, 20.1% and 17.9% of which were positive for B. quintana bacteraemia, respectively. This study analysed previous studies on these ancient samples and showed that the presence of B. quintana infection followed the course of time in human history; a total of 14/15 sites from five European countries had a positive prevalence. The positive rate in soldiers was higher than those of civilians, with 20% and 18.8%, respectively, in the 18th and 19th centuries, but the difference in frequency was not significant. These results confirmed the role of dental pulp in diagnosing B. quintana bacteraemia in ancient populations and showed the incidence of B. quintana in both civilians and soldiers.

An outbreak of relapsing fever unmasked by microbial paleoserology, 16th century, France.

OBJECTIVES: Depicting past epidemics currently relies on DNA-based detection of pathogens, an approach limited to pathogens with well-preserved DNA sequences. We used paleoserology as a complementary approach detecting specific antibodies under a mini line-blot format including positive and negative control antigens. METHODS: Mini line blot assay incorporated skim milk as negative control, Staphylococcus aureus as positive control, and antigens prepared from lice-borne pathogens Rickettsia prowazekii, Borrelia recurrentis, Bartonella quintana, and Yersinia pestis. Paleoserums were extracted from rehydrated dental pulp recovered from buried individuals. Mini line blots observed with the naked eye, were quantified using a scanner and appropriate software. Paleoserology was applied to the indirect detection of lice-borne pathogens in seven skeletons exhumed from a 16th-17th century suspected military burial site (Auxi-le-Château); and 14 civils exhumed from a 5th-13th century burial site (Saint-Mont). Direct detection of pathogens was performed using quantitative real-time PCR. RESULTS: In Auxi-le-Château, paleoserology yielded 7/7 interpretable paleoserums including 7/7 positives for B. recurrentis including one also positive for B. quintana. In Saint-Mont, paleoserology yielded 8/14 interpretable paleoserums and none reacted against any of the four pathogens. Antibodies against R. prowazekii and Y. pestis were not detected. The seroprevalence was significantly higher in the military burial site of Auxi-le-Château than in the civil burial site of Saint-Mont. Real-time PCR detection of B. quintana yielded 5/21 positive (3 at Saint-Mont and 2 at Auxi-le-Château) whereas B. recurrentis was not detected. CONCLUSIONS: Paleoserology unmasked an outbreak of relapsing B. recurrentis fever in one 16th - 17th century military garrison, missed by real-time PCR. Paleoserology offers a new tool for investigating past epidemics, in complement to DNA sequence-based approaches.

Soil salinity and aridity specify plague foci in the United States of America.

Plague is a deadly zoonosis that periodically reemerges as small outbreaks in geographically limited foci where the causative agent Yersinia pestis may reside in soil. We analyzed a dataset of 1.005 carefully documented plague cases that were georeferenced over 113 years in peer-reviewed literature in the contiguous United States. Plotting outbreaks by counties defined as plague foci on geographical maps, we observed a significant co-localization of plague outbreaks with high soil salinity measured by an electric conductivity of >4 dS/ m-1 and aridity measured by an aridity index <0.5. Thus, we identified aridity and soil salinity as significantly associated with ecological risk factors for relapsing plague in the contiguous United States. These results reveal two evolutive parameters that are partially associated with anthropic activities, complicating the epidemiology of plague in the contiguous United States. Exploiting aridity and soil salinity data may help in the surveillance of evolving plague foci in the contiguous United States.

Paleoproteomics of the Dental Pulp: The plague paradigm.

Chemical decomposition and fragmentation may limit the detection of ancient host and microbial DNA while some proteins can be detected for extended periods of time. We applied paleoproteomics on 300-year-old dental pulp specimens recovered from 16 individuals in two archeological funeral sites in France, comprising one documented plague site and one documented plague-negative site. The dental pulp paleoproteome of the 16 teeth comprised 439 peptides representative of 30 proteins of human origin and 211 peptides representative of 27 proteins of non-human origin. Human proteins consisted of conjunctive tissue and blood proteins including IgA immunoglobulins. Four peptides were indicative of three presumable Yersinia pestis proteins detected in 3/8 dental pulp specimens from the plague-positive site but not in the eight dental pulp specimens collected in the plague-negative site. Paleoproteomics applied to the dental pulp is a new and innovative approach to screen ancient individuals for the detection of blood-borne pathogens and host inflammatory response.