Phylogenetic analysis reveals a new introduction of Yellow Fever virus in São Paulo State, Brazil, 2023.

Yellow Fever (YF) is a viral arbovirosis of Public Health importance. In Brazil, surveillance is focused mainly on detecting epizootic events of Platyrrhini. Herein, we compared the detection and phylogenetic analysis of YF virus in two neotropical primates (NTP), a Callithrix detected in the previous epidemic period (2016-2020), and a Callicebus nigrifons, showing a new introduction of YF in 2023. This paper illustrates the importance of joint actions of laboratory and field teams to ensure quick response to Public Health emergencies, such as the intensification of vaccination of susceptible human populations.

Ultimobranchial body cyst in an adult horse: clinical, histopathologic, and immunohistochemical features.

A 9-y-old Mangalarga Marchador gelding was referred to a veterinary hospital because of a swelling on the upper right side of the neck. Ultrasound examination revealed a multilocular structure adjacent to the thyroid gland with low echogenic content suggestive of fluid. The mass was removed surgically. Histologically, the cystic cavities in the surgical sample were filled with abundant eosinophilic secreta and lined by cuboidal, segmentally ciliated, columnar epithelium with interspersed goblet cells. Segmental crowding of the multilayered lining of the cyst was noted. Immunohistochemistry suggested the presence of both C cells and follicular cells, given the positivity of the immunomarkers calcitonin and TTF-1, respectively. The histogenesis of ultimobranchial cysts is uncertain. Based on clinical, histopathologic, and immunohistochemical identification, the cystic structure in this case is compatible with an ultimobranchial body cyst.

Naturally Acquired Rabies in White-Eared Opossum, Brazil.

Opossums are considered resistant to rabies. Nonhematophagous bats are reservoirs of rabies in urban areas of South America. We analyzed bats and opossums tested for rabies during 2021 in a highly urbanized city in Brazil to understand spillover in an urban setting. Wildlife surveillance is necessary to prevent rabies in humans and domestic animals.

A rare case of primary hepatic poorly differentiated leiomyosarcoma in a goat.

A 12-year-old Saanen goat presented with a history of hyporexia and sudden recumbency. Euthanasia was indicated due to suspicion of hepatic neoplasia associated with senility. Necropsy revealed generalized oedema and increased liver size and weight (33 × 38 × 17 cm and 10.6 kg, respectively), with a firm, multilobular mass. Fusiform to polygonal neoplastic cells, with marked pleomorphism, anisocytosis and anisokaryosis, were seen on histopathological examination of the hepatic mass. The neoplastic cells were immunohistochemically positive for alpha-smooth muscle actin and vimentin but immunonegative for pancytokeratin. The Ki-67 index was 18.8%. A poorly differentiated leiomyosarcoma was diagnosed on the basis of the gross, histopathological and immunohistochemical findings and should be included in the differential diagnosis of liver disease in goats.

Histopathologic and Immunohistochemical Assessment of Acute Respiratory Distress Syndrome (ARDS): Challenges and Complexities of Postmortem Diagnosis.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition due to acute lung injury (ALI), characterized by rapid-onset respiratory failure, leading to the clinical manifestations of poor lung compliance, severe hypoxemia, and dyspnea. ARDS/ALI has many causes, most commonly related to infections (sepsis, pneumonia), traumas, and multiple transfusions. The objective of this study is to assess the performance of postmortem anatomopathological examination in identifying etiological agents associated with ARDS or ALI in deceased patients from the State of São Paulo from 2017 to 2018. A retrospective cross-sectional study was performed based on the final outcome obtained by histopathology, histochemical, and immunohistochemical examination for ARDS/ALI differential diagnosis at the Pathology Center of the Adolfo Lutz Institute in São Paulo, Brazil. Of the 154 patients clinically diagnosed with ARDS or ALI, 57% tested positive for infectious agents, and the most frequent outcome was influenza A/H1N1 virus infection. In 43% of cases, no etiologic agent was identified. The opportunity to establish a diagnosis, identify particular infections, confirm a microbiological diagnosis, and uncover unanticipated etiologies is provided by postmortem pathologic analysis of ARDS. A molecular assessment could improve the diagnosis accuracy and lead to research into host responses and public health measures.

Canine distemper virus and canine adenovirus type 1 co-infection in a free-living hoary fox (Lycalopex vetulus) from Brazil.

The present case is the first description of a co-infection with canine distemper virus (CDV) and canine adenovirus type 1 (CAdV-1) in a free-living hoary fox pup from Brazil. The animal was found and rescued with poor body condition, dehydration, incoordination, ataxia, excessive vocalization, and "blue eyes" phenomenon. Despite the efforts, euthanasia was elected due to worsening clinical signs and poor prognosis. Pathologic examination revealed a mild, acute, random, necrotizing hepatitis, acute bronchopneumonia, hydrocephalus, corneal edema with epithelium degeneration, and acidophilic intracytoplasmatic inclusion bodies in different epithelial cells types with rare syncytial. Through immunohistochemistry, CDV antigen was observed in the tongue, trachea, lungs, liver, spleen, stomach, intestine and urinary bladder. Adenovirus antigen was identified in the nucleus of scattered hepatocytes. Polymerase chain reaction and sequencing demonstrated high similarity with CAdV-1 and wild-type strain of CDV close related to Brazilian viral lineages isolated from domestic dogs. Disease surveillance in wildlife animals is essential to assess possible conservation threats and consider the implementation of mitigation or control measures.

RBD and Spike DNA-Based Immunization in Rabbits Elicited IgG Avidity Maturation and High Neutralizing Antibody Responses against SARS-CoV-2.

Neutralizing antibodies (nAbs) are a critical part of coronavirus disease 2019 (COVID-19) research as they are used to gain insight into the immune response to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections. Among the technologies available for generating nAbs, DNA-based immunization methods are an alternative to conventional protocols. In this pilot study, we investigated whether DNA-based immunization by needle injection in rabbits was a viable approach to produce a functional antibody response. We demonstrated that three doses of DNA plasmid carrying the gene encoding the full-length spike protein (S) or the receptor binding domain (RBD) of SARS-CoV-2 induced a time-dependent increase in IgG antibody avidity maturation. Moreover, the IgG antibodies displayed high cross neutralization by live SARS-CoV-2 and pseudoviruses neutralization assays. Thus, we established a simple, low cost and feasible DNA-based immunization protocol in rabbits that elicited high IgG avidity maturation and nAbs production against SARS-CoV-2, highlighting the importance of DNA-based platforms for developing new immunization strategies against SARS-CoV-2 and future emerging epidemics.

Toxoplasmosis in a free-ranging hairy dwarf porcupine (Sphiggurus spinosus) with a potential novel genotype.

Toxoplasmosis is a zoonotic disease caused by the ubiquitous coccidia Toxoplasma gondii. Rodents play an important role in maintaining its life cycle, as they are one of the main diet sources for felids (wild and domestic), the unique definitive hosts. However, reports of toxoplasmosis in porcupines (Order Rodentia) are uncommon, with gaps concerning its pathophysiology. South America is the continent with the greatest genetic diversity of rodents and T. gondii. A free-ranging hairy dwarf porcupine was admitted to a wildlife rescue centre with a history of trauma. During rehabilitation, the animal presented neurological symptoms (sporadic episodes of hind limbs paresis) and died 5 months later. The main findings during necropsy were brain congestion and severe incisor overgrowth associated with maxillary perforation. The histopathological exam showed moderate encephalitis, with variable-sized round cysts, positive for PAS stain and immunohistochemistry for T. gondii. Additionally, two cysts were observed in the medulla of the adrenal gland. Molecular techniques were performed to characterize the parasite load by qPCR (Cq = 30) and the genotype by PCR-RFLP with 11 markers, which revealed a potential new genotype. This case adds to the body of knowledge in comparative pathology of Neotropical Rodentia and reports a new potential genotype circulating in South America.

Myeloid and histiocytic sarcomas in subantarctic fur seals Arctocephalus tropicalis, Brazil.

Histopathological and immunohistochemical methods were used to diagnose round cell tumors in 2 subantarctic fur seals Arctocephalus tropicalis with marked anemia. Although wild-born, both individuals were placed under human care while juveniles in a Brazilian aquarium. Both pinnipeds were PCR tested for herpesvirus, and 1 was infected with otariid gammaherpesvirus 5 (OtHV-5), previously described in a subantarctic fur seal stranded in Brazil. Although some gammaherpesviruses can cause sarcomas and other neoplasms, it was not possible to definitively associate OtHV-5 with the neoplasm. To our knowledge, these are the first neoplasm records in subantarctic fur seals.

CLINICO-PATHOLOGIC FINDINGS AND PATHOGEN SCREENING IN FUR SEALS (ARCTOCEPHALUS AUSTRALIS AND ARCTOCEPHALUS TROPICALIS) STRANDED IN SOUTHEASTERN BRAZIL, 2018.

Among pinnipeds, four Otariidae species (eared seals) have been reported as occasional or frequent vagrants along the coast of Brazil, mainly in the southern region. These animals usually arrive debilitated during winter and are directed to rehabilitation. Nevertheless, available information on sanitary aspects of stranded pinnipeds in Brazil is limited. Increased fur seal strandings (n=23) were recorded during the 2018 winter season in southeast Brazil (Iguape, Ilha Comprida, and Ilha do Cardoso, Sao Paulo State) compared to 2017 (n=2). Of these 23 fur seals, two were found dead and were in a good postmortem condition, and four died during rehabilitation and were subsequently necropsied. The remaining fur seals were not analyzed due to advanced decomposition (9/23) or successful rehabilitation (8/23). Herein, we report the antemortem hematology (n=4) and postmortem pathologic, parasitologic, and molecular analysis results as well as the most likely cause of stranding and/ or death (CSD) in five free-ranging juvenile South American fur seals (Arctocephalus australis) and one free-ranging juvenile subantarctic fur seal (Arctocephalus tropicalis). All animals were males, and all but one had poor body condition. Pathologic examinations revealed a variety of lesions, predominantly hemodynamic disturbances, endoparasitism, and inflammatory disease processes of suspected infectious nature. Molecular analyses detected gammaherpesvirus infections in two South American seals and one subantarctic fur seal, Sarcocystis sp. in one subantarctic fur seal, and Neospora spp. in two South American fur seals. All seals were PCR-negative for morbillivirus, flavivirus, and Toxoplasma gondii. The most likely CSDs were: starvation (2), aspiration pneumonia (1), asphyxia (1), predator attack (1), and presumed systemic infectious disease (1). These findings expand the geographic range of various pathogens of pinnipeds and may be of value to first responders, clinicians, and diagnosticians.

Novel gammaherpesvirus associated with primary gastric T-cell lymphoma in a free-ranging giant armadillo in Brazil.

The number of viral-associated neoplasms reported in wildlife has increased over the last decades, likely because of growing research efforts and a potentially greater burden of carcinogenic pathogens. Herein, we describe a primary gastric T-cell lymphoma in one free-ranging giant armadillo (Priodontes maximus) from Brazilian Pantanal infected by a novel gammaherpesvirus, proposed as Cingulatid gammaherpesvirus 1 (CiHV-1). By chromogenic in situ hybridisation against Epstein-Barr virus some neoplastic cells were labeled. Subsequently, a molecular screening was carried out to detect the occurrence of this pathogen in other giant armadillos in the same region. Overall, this novel virus was detected in 14.3% (3/21) of the tested giant armadillos. We suggest this herpesvirus, the first in Xenarthra, as a plausible aetiology of the neoplasm. The implications of CiHV-1 for this species are uncertain; while no outbreaks of disease have been recorded, the present study raises concerns. Further research is warranted to assess the real significance of CiHV-1 and its potential oncogenic role in this species.

Análise de algoritmo diagnóstico de febre amarela em amostras de primatas não humanos encaminhadas ao Centro de Patologia do Instituto Adolfo Lutz / Analysis of a diagnostic algorithm for yellow fever in primate samples non-humans sent to the Pathology Center of Instituto Adolfo Lutz

O Centro de Patologia do Instituto Adolfo Lutz (CPA-IAL) é credenciado pelo Ministério da Saúde como laboratório de referência macrorregional para a vigilância epidemiológica de febre amarela (FA) em seres humanos e primatas não humanos (PNH) do Brasil, atuando por meio de análise histopatológica e imuno-histoquímica (IHQ). Até o ano de 2018, ambos os exames eram aplicados a todas as amostras de PNH recebidas para a pesquisa de FA. Em 2019, implantou-se um algoritmo diagnóstico baseado na triagem pelas características histopatológicas observadas no tecido hepático, possibilitando a racionalização do uso da IHQ. Objetivo: Avaliar a aplicação do algoritmo diagnóstico comparado ao período que antecedeu sua implantação. Métodos: Estudo retrospectivo de relatórios anatomopatológicos de PNH emitidos, entre 2018 e 2019, no CPA-IAL para determinação de índices de performance diagnóstica do exame histopatológico na vigilância epidemiológica de febre amarela, avaliação da sensibilidade do exame imuno-histoquímico para amostras com autólise de moderada a avançada e comparação da mediana de tempo decorrido para emissão dos relatórios em cada período. Resultados: Não houve diferença estatisticamente significante na performance da detecção de FA por histologia e IHQ entre os períodos pré e pós algoritmo; houve importante redução na quantidade de exames IHQ solicitados e no tempo de liberação dos relatórios (p<0,0001). Conclusões: O algoritmo resultou em desempenho semelhante, redução do tempo de liberação oportuno para a vigilância epidemiológica do agravo e da quantidade de reações IHQ realizadas, portanto, apresentando-se adequado para o diagnóstico de febre amarela em PNH no CPA-IAL.

Novel alphaherpesvirus in a wild South American sea lion (Otaria byronia) with pulmonary tuberculosis.

In 2017, an adult male South American sea lion (Otaria byronia), presenting emaciation and a cervical abscess, stranded alive in Florianópolis, southern Brazil. The animal was directed to a rehabilitation center, dying a few days later. On necropsy, the main gross findings were necrotizing lymphadenitis of the right prescapular lymph node and nodular bronchopneumonia. A novel alphaherpesvirus, tentatively named Otariid alphaherpesvirus 1, was amplified in several tissue samples. No histopathologic findings associated with viral infection were observed. Additionally, pulmonary tuberculosis by Mycobacterium pinnipedii was diagnosed by histopathological, immunohistochemical, and molecular techniques. Several bacteria were cultured from antemortem and postmortem samples, including Proteus mirabilis from the cervical abscess and cardiac blood, and Escherichia coli from the cervical abscess and pericardial effusion. Flavivirus, morbillivirus, and Apicomplexa were not detected by molecular techniques. Herein, we report a novel alphaherpesvirus in a pinniped species of the family Otariidae. Although previously described in Southern Hemisphere pinniped species, including South American sea lions, there is limited information regarding M. pinnipedii impact over this group. Further research is required to determine the associated pathogenesis of this novel herpesvirus, and prevalence of Otariid alphaherpesvirus 1 and M. pinnipedii in the reproductive colonies.

Yellow Fever as Cause of Death of Titi Monkeys (Callicebus Spp.).

From 2016 to 2018, an epidemic wave of yellow fever (YF) occurred in Brazil, affecting a large number of Platyrrhini monkeys. Titi monkeys (Callicebus spp.) were severely affected yet pathological characterizations are lacking. This study characterized epizootic YF in 43 titi monkeys (Callicebus spp.) with respect to the microscopic lesions in liver, kidney, spleen, heart, brain, and lung, as well as the distribution of immunolabeling for YF virus antigen, and the flaviviral load in the liver. Of 43 titi monkeys examined, 18 (42%) were positive for yellow fever virus (YFV) by immunohistochemistry or reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Affected livers had consistent marked panlobular necrotizing hepatitis, lipidosis, and mild inflammation, with intense immunolabeling for YFV mainly in centrilobular hepatocytes (zone 1; P = .05). In the spleen, consistent findings were variable lymphoid depletion (10/11), lymphoid necrosis (lymphocytolysis; 4/11), and immunolabeling for YFV in histiocytic cells (3/16). The main finding in the kidney was multifocal acute necrosis of tubular epithelium (5/7) that was occasionally associated with intracytoplasmic immunolabeling for YFV (6/15). These data indicate that titi monkeys are susceptible to YFV infection, developing severe hepatic lesions and high viral loads, comparable to humans and Alouatta spp. Thus, Callicebus spp. may be reliable sentinels for YF surveillance.

Concurrent yellow fever and pulmonary aspergillosis due to Aspergillus fumigatus in a free-ranging howler monkey (Alouatta sp).

Herein, we describe a unique case of concomitant angioinvasive pulmonary aspergillosis due to Aspergillus fumigatus and yellow fever in a free-ranging howler monkey (Alouatta sp). Lung samples were negative for influenza viruses A and B.

Cytokine profile and parasite load in lymph nodes of dogs naturally infected with Leishmania infantum from distinct epidemiological scenarios in São Paulo State, Brazil.

Visceral leishmaniasis (VL) is an important zoonotic vector-borne disease and domestic dogs are considered the main domiciliary and peri-domiciliary reservoir of Leishmania (Leishmania) infantum in South America. Distinct eco-epidemiological scenarios associated to the prevalence of the disease, clusters of parasite genotypes and chemotypes of vectors population are described in Brazil, especially in the state of São Paulo (SP). In this context, the purpose of the present study is to evaluate the clinical signs, histopathological lesions, parasite load and cytokine profile by immunohistochemistry (IHC) in popliteal lymph nodes of canines naturally infected with L. infantum, from different municipalities of the state of SP. Eighty-three dogs with VL, 61 from northwest SP (NWSP) and 22 from southeast SP (SESP), were clinically classified in stage II, with no babesiosis and ehrlichiosis. Subcapsular inflammatory infiltration and histiocytosis were significantly higher in the SESP group (p = 0.0128; 0.0077, respectively). On the other hand, dogs from NWSP revealed 4.6-fold significantly higher parasite burden (p = 0.0004) and higher IHC scores of IL-1ß (p = 0.0275) and IL-4 (p = 0.0327) in the popliteal lymph node tissues, which may be associated with the susceptibility and progression of the disease in these dogs. Differences in immune response profile associated with higher parasite load in dogs can also contribute to explain the distinct eco-epidemiological patterns of VL in specific geographic regions.

Differential Yellow Fever Susceptibility in New World Nonhuman Primates, Comparison with Humans, and Implications for Surveillance.

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

Yellow fever surveillance challenge: Investigation of a marmoset non-autochthonous case.

Yellow fever (YF) surveillance in Brazil is focused mainly on the detection of epizootic events regarding New World non-human primates (NWNHP). We present a challenging case of a Callitrichidae (Callithrix spp) kept as a domiciliated pet that lived in the urban area of São Paulo municipality and was positive to YF virus by RT-qPCR and immunohistochemistry. After investigation, it was the first occurrence of non-autochthonous YF case of NWNHP described, with probable place of infection in the North shore of São Paulo state. This case illustrates the importance of coordinated laboratorial and field actions, and risks posed by transit of wildlife.

Genomic Surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.

High-risk Human Papillomavirus Testing for Triage of Women with Previous Cytological Abnormalities from the Vale do Ribeira Region.

OBJECTIVE: To evaluate the performance of the hybrid capture 2 (HC2) high-risk papillomavirus (hrHPV) assay and cytological test in women with previous abnormalities, to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN 2). METHODS: A cytological test and HC2 (Qiagen, Gaithersburg, Maryland, EUA) for hrHPV were conducted in 359 liquid-based (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) samples collected from women from the Vale do Ribeira Region, during July 2013 and September 2015 with previous cytology classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), and atypical glandular cells (AGC). The histopathological examination was conducted in 179 women. The performance evaluations were calculated using the "exact" Clopper-Pearson 95% confidence interval (CI) test by MEDCALC (Medcalc Software Ltd, Ostend, Belgium). RESULTS: The ≥ CIN 2 frequency was 11.7% (21/179). The HC2 for hrHPV and repeat cytology to detect ≥ CIN 2 obtained, respectively, a sensitivity of 90.5% (95%CI = 69.6-98.8) and 90.5%, (95%CI = 69.6-98.8), a specificity of 65.8% (95% CI = 57.9-73.2) and 43.7% (95%CI = 35.8-51.8), a positive predictive value of 26.0% (95% CI = 21.4-31.3) and 17.6%, (95%CI = 14.9-20.6), and a negative predictive value of 98.1% (95%CI = 93.3-99.5) and 97.2% (95% CI = 90.1-99.2). CONCLUSION: Hybrid capture 2 for hrHPV improves the performance of the detection of ≥ CIN 2, without compromising sensitivity, and provides a greater safety margin to return to the triennial screening of women undergoing follow-up due to previous abnormalities, without underlying ≥ CIN 2.

OBJETIVO: Avaliar o desempenho da captura híbrida 2 (CH2) para papilomavírus humano de alto risco (HPVar) e repetição do exame citopatológico em mulheres com anormalidades em citologia anterior, para detectar neoplasia intraepitelial cervical grau 2 ou pior (≥ NIC 2). MéTODOS: Foi realizado exame citopatológico e CH2 para HPVar (Qiagen, Gaithersburg, Maryland, EUA) em 359 amostras em meio líquido (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) coletadas de mulheres da região do Vale do Ribeira, durante julho de 2013 e setembro de 2015 com citologia anterior classificada como células escamosas atípicas de significado indeterminado (ASC-US), lesão intraepitelial de baixo grau (LSIL), células escamosas atípicas, não podendo excluir lesão de alto grau (ASC-H) e células glandulares atípicas (AGC). O exame histopatológico foi realizado em 179 mulheres. As avaliações de desempenho foram calculadas usando o teste de intervalo de confiança (IC) "exato" de Clopper-Pearson de 95% pelo software MEDCALC (Medcalc Software Ltd, Ostend, Bélgica). RESULTADOS: A frequência de ≥ NIC 2 foi 11,7% (21/179). A CH2 para o HPVar e a citologia de repetição para a detecção ≥ NIC 2 obteve, respectivamente, sensibilidade de 90.5% (IC 95% = 69,6­98,8) e 90,5% (IC 95% = 69,6­98,8), especificidade de 65,8% (IC 95% = 57,9­73,2) e 43,7%, (IC 95% = 35,8­51,8), valor preditivo positivo de 26,0% (IC 95% = 21,4­31,3) e 17,6%, (IC95% = 14,9­20,6), e valor preditivo negativo de 98,1% (IC 95% = 93,3­99,5) e 97,2%, (IC 95% = 90,1­99,2). CONCLUSãO: No geral, a CH2 para HPVar aprimora o desempenho para detecção de ≥ NIC 2, sem comprometer a sensibilidade e proporciona maior margem de segurança do retorno ao rastreio trienal de mulheres com anormalidades citológicas prévias, sem ≥ NIC 2 subjacente.