Non-endemic Areas Research Articles

Nasopharyngeal carcinoma: nationwide trends in subtype-specific incidence and survival over 3 decades in a non-endemic area

PurposeTo identify trends in incidence and survival of NPC, subdivided by EBV status and histopathological subtype, over a 30-year period in the Netherlands.MethodsAnonymized data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank (PALGA) for the period 1989–2018 were linked to identify and classify NPC cases.ResultsIncidence of NPC remained stable, with an annual percentage change (APC) of − 0.2. (95% CI − 0.9; 0.5). EBV testing became routine only in the last decade, the incidence of EBV-positive tumors remained stable over this period (APC 1.2, 95% CI − 1.3; 3.8). An increase in EBV-negative tumors (APC: 7.1, 95% CI 2.5; 11.9) and a decrease in untested tumors were found (APC: − 10.7, 95% CI − 15.7; − 5.7). The incidence of non-keratinizing, differentiated tumors increased (APC: 3.8, (95% CI 2.2; 5.5) while the incidence of other histological subtypes remained stable. Overall survival was better in patients diagnosed after 1998 (hazard ratio 0.8, 95% CI 0.6; 0.9). EBV status, histology, stage, and age were independently associated with relative excess risk of dying, but period of diagnosis was not.ConclusionTesting for EBV increased over time, and a stable incidence of EBV-positive NPC over the last 10 years. The rising incidence of non-keratinizing, differentiated NPC mirrors data from the US and suggests a shift in non-endemic regions.

Association between living in the endemic area and level of knowledge of visceral leishmaniasis

BackgroundIran is a country with a high prevalence of visceral leishmaniasis (VL) and seven endemic provinces. In this study, we tried to identify unobserved classes of knowledge among Iranians toward VL and assess the predictors of each latent class.MethodsThis cross-sectional study was conducted among randomly selected participants from endemic and non-endemic areas of VL in Iran in 2020 and 2021. The collected data included demographic characteristics and questions about knowledge, attitude, and practice toward VL. We performed latent class analysis using a procedure for latent class analysis (PROC LCA) in SAS to identify the class membership of knowledge of participants toward VL.ResultsFive latent classes were identified: very low (38.9%), low (15.5%), moderate (6.2%), high (14.1%), and very high (25.2%) knowledge about VL. Living in endemic areas significantly increased the odds of belonging to the low (adjusted OR (AOR = 7.23; 95% confidence interval (CI):4.52–11.58), high (AOR = 2.71; 95%CI: 1.73–4.23), and very high (AOR = 8.47; 95%CI: 5.78–12.41) classes compared to the very low class. Also, having academic education increased the odds of membership in the very high class (AOR = 2.36; 95%CI: 1.61–3.47) compared to the very low class.ConclusionThis study revealed that more than 50% of the participants fell into the latent classes of very low and low knowledge toward VL. Some educational workshops in the endemic areas could be effective in enhancing knowledge about VL.

Detection of Plasmodium spp. in asymptomatic blood donors by the new Brazilian NAT PLUS HIV/HBV/HCV/Malaria Bio-Manguinhos kit.

Transfusion-transmitted malaria (TTM) is a public health problem in endemic and nonendemic areas. The Brazilian Ministry of Health (MH) requested the development of a nucleic acid amplification test (NAT) for the detection of Plasmodium spp. in public blood centers to increase blood safety. The new Brazilian NAT kit named NAT PLUS HIV/HBV/HCV/Malaria Bio-Manguinhos was first implemented in HEMORIO, a public blood center in the city of Rio de Janeiro. Since October 1, 2022, this blood center has been testing all its blood donations for malaria in a pool of six plasma samples to detect Plasmodium spp. by real-time polymerase chain reaction (PCR). Since the implementation of the NAT PLUS platform until February 2023, HEMORIO has successfully received and tested 200,277 donations. The platform detected two asymptomatic donors in the city of Rio de Janeiro, which is a nonendemic region for malaria. Our analyses suggested a malaria from the Amazon region caused by Plasmodium vivax, in the first case, while an autochthonous transmission case by Plasmodium malariae was identified in the rural area of Rio de Janeiro state. The NAT PLUS platform detects Plasmodium spp. in plasma samples with sensitivity capable of detecting subpatent infections. This is the first time worldwide that a group developed and implemented molecular diagnosis for Plasmodium spp. to be used by public blood centers to avoid TTM.

Des-gamma-carboxy prothrombin (DCP) as a biomarker for treatment response in hepatocellular carcinoma.

547 Background: Causes of variable disease response to first-line treatment with atezolizumab/bevacizumab (atezo/bev) in hepatocellular carcinoma (HCC) patients remain unclear. Identifying tumor markers that predict treatment efficacy may help raise clinical suspicion for early disease progression. The role of des-gamma-carboxy prothrombin (DCP) is not well established in Hepatitis B Virus (HBV) non-endemic areas. This study aimed to investigate DCP as a predictive biomarker of atezo/bev treatment response in HCC patients. Methods: This single-center retrospective analysis evaluated DCP and radiographic response in HCC patients who received atezo/bev in the first-line setting. DCP was measured at the time of best response evaluation and compared to day one of atezo/bev initiation. Elevated DCP was defined by >=7.5 ng/mL. DCP response was defined as a decrease of >=50% at response assessment compared with baseline. Treatment response was evaluated based on imaging modalities including computed tomography and/or magnetic resonance imaging. Objective response rate (ORR) was defined as the percentage of patients with complete response (CR) and partial response (PR). Disease control rate (DCR) was defined as the percentage of patients with CR, PR, and stable disease (SD). No Response (NR) was defined as the percentage of patients with SD and PD. Comparisons of treatment effects were performed using two-tailed Fisher Exact Probability Test. Results: A total of 53 HCC patients treated with atezo/bev as first-line therapy were included. The best treatment responses according to radiographic evaluation were as follows: CR 3.8%, PR 22.6%, SD 52.8%, and PD 20.8%, respectively. Patients with DCP response had ORR of 69% (odds ratio, 15.75; 95% CI, 3.50-70.9; P=.0002) and DCR of 100% ( P=.047). Patients with >=50% increase in DCP at response evaluation compared to day one of treatment had ORR of 4.5% and NR of 95% ( P=.0035). On day one of treatment, 70% of patients had an elevated DCP. There was no difference between elevated DCP vs non-elevated DCP on day one of treatment and ORR. Conclusions: This study found that DCP has utility in predicting response to atezo/bev for HCC patients in HBV non-endemic areas. Further studies are needed to confirm findings and evaluate the prognostic implications of DCP in HBV non-endemic areas.

Subcutaneous dirofilariasis in a 25-year-old male patient in Belgium on ultrasonography: a case report

BackgroundSubcutaneous dirofilariasis is a parasitic zoonosis commonly described in Canidae but rarely seen in humans. Most physicians are unfamiliar with this disease, especially in nonendemic areas, which can lead to medication error and diagnostic and treatment delay. To the best of our knowledge, no previous case of subcutaneous dirofilariasis preoperatively diagnosed on ultrasound has been described in Western Europe.Case presentationA 25-year-old Belgian male patient presented with a subcutaneous nodule in the epigastric region. Ultrasound investigation showed a typical cystic lesion with an internal serpiginous structure with echogenic lines, and there was active twirling movement of this serpentine structure during investigation, pathognomonic for subcutaneous dirofilariasis. Surgical extirpation was performed, and the diagnosis was histopathologically confirmed.ConclusionSubcutaneous dirofilariasis has a characteristic appearance on ultrasound but is not well known in nonendemic areas, often leading to diagnostic delay and initial incorrect treatment. More knowledge of this disease and of its characteristic ultrasound appearance will hopefully lead to better patient care.

Diagnostic challenges of neurosarcoidosis in non-endemic areas.

Neurosarcoidosis (NS) is a challenging diagnosis, particularly when cases occur in low-prevalence, non-endemic geographic regions. In the United States, the highest incidence is in the Midwest and Northeast, compared to our Southwest location. While it is well known that NS may clinically and neuroradiographically mimic meningeal carcinomatosis, autoimmune or infectious pachymeningitis, neurosyphilis, or tuberculosis, diagnosis may be particularly challenging if systemic signs of sarcoidosis are lacking or unconfirmed or if dural-based masses are present. We reviewed our Colorado experience with NS cases, focusing our study on cases where NS represented the first histological confirmation of disease. A search of departmental databases was conducted with the search term "neurosarcoidosis" to identify cases 1-2008 to 12-2019, inclusive of the given case numbers. Patients were only included if their clinical and neuroimaging features were unusual and only when a biopsy of the central nervous system (CNS) represented the first confirmed diagnosis of sarcoidosis. A total of 17 cases were identified, of which the biopsy of the CNS was used for the initial confirmation of the disease in 9 of them. The most unusual findings were two patients with dural-based masses, one of which had pure NS as the cause of meningioma-like lesions and the second of which had coexistent meningioma and intimately admixed non-necrotizing granulomas of NS. NS with unusual features, especially in non-endemic areas, continues to yield diagnostic challenges for neurologists, neuroradiologists, and pathologists.

Amoebic colitis and liver abscess: A rare case of autochthonous invasive infection due to Entamoeba histolytica

We report an unusual and confirmed case of invasive amebiasis in a non-endemic area where the source of infection remains unknown. During her admission, the patient developed amebic colitis and extraintestinal liver abscess with a favorable outcome following the antiparasitic therapy.

Expecting the Unexpected: Schistosomial Appendicitis in Nonendemic Area

Abstract Background Schistosomiasis is a granulomatous disease prevalent in tropical and subtropical areas. Appendicitis secondary to schistosomiasis is a rarely encountered presentation, even in endemic areas. Most acute intestinal schistosomiasis presents with abdominal pain and bloody diarrhea. Other atypical clinical presentations include intestinal obstruction, peritonitis, and acute appendicitis. Case Description We report a case of a 37-year-old male from the Philippines who presented with the clinical picture of acute appendicitis and was treated with laparoscopic appendectomy. Pathological study revealed calcified Schistosomia japonicum's egg in a background of acute inflammation. Conclusion Worldwide increase in immigration and tourism resulted in an increased number of schistosomiasis in nonendemic areas. Considering this, we are faced with the uncommon etiology of acute appendicitis.

Disseminated Talaromyces marneffei infection associated with haemophagocytic syndrome in an HIV-negative patient in northern China: a case report

BackgroundTalaromyces marneffei is endemic to eastern India, Southeast Asia, and Guangdong and Guangxi provinces in China. It is common in immunocompromised individuals, especially in HIV-infected patients.Case presentationA 66-year-old male who had a history of hypertension and resided in Shandong Province (Northern China) was admitted for recurrent fever for one month. The patient had recurrent fever, multiple lymphadenopathies, hepatosplenomegaly, a back rash, and a progressive decrease in white blood cells and platelets. Talaromyces marneffei was isolated from peripheral blood and bone marrow after admission, and suspected fungal cells were found via lymph node pathology. The patient’s infection secondary to haemophagocytic syndrome continued to worsen despite antifungal, anti-inflammatory, and symptomatic treatment, leading to death due to multiple-organ failure.ConclusionAlthough rare, infection due to Talaromyces marneffei in HIV-negative patients has been increasing in recent years, and we should be vigilant about “new” infections in nonendemic areas.

The Laboratory Diagnosis of Malaria: A Focus on the Diagnostic Assays in Non-Endemic Areas.

Even if malaria is rare in Europe, it is a medical emergency and programs for its control should ensure both an early diagnosis and a prompt treatment within 24-48 h from the onset of the symptoms. The increasing number of imported malaria cases as well as the risk of the reintroduction of autochthonous cases encouraged laboratories in non-endemic countries to adopt diagnostic methods/algorithms. Microscopy remains the gold standard, but with limitations. Rapid diagnostic tests have greatly expanded the ability to diagnose malaria for rapid results due to simplicity and low cost, but they lack sensitivity and specificity. PCR-based assays provide more relevant information but need well-trained technicians. As reported in the World Health Organization Global Technical Strategy for Malaria 2016-2030, the development of point-of-care testing is important for the improvement of diagnosis with beneficial consequences for prompt/accurate treatment and for preventing the spread of the disease. Despite their limitations, diagnostic methods contribute to the decline of malaria mortality. Recently, evidence suggested that artificial intelligence could be utilized for assisting pathologists in malaria diagnosis.

An imported malaria case with repeated episodes of neurological syndromes resulting from different Plasmodium species

BackgroundImported cerebral malaria (CM) cases in non-endemic areas are often misdiagnosed, which delays treatment. Post-malaria neurological syndrome (PMNS) after recovery from severe malaria can also complicate diagnosis.CaseWe report an imported malaria case from West Africa with two sequential episodes with neurological syndromes within about a month. The first episode was diagnosed as CM with microscopy-positive Plasmodium falciparum infection. The second episode, occurring a month after the recovery from the first CM episode, was consistent with PMNS, since malaria parasites were not detected by microscopy in peripheral blood smears. However, this diagnosis was complicated by the detection of Plasmodium vivax in peripheral blood by PCR, suggesting a potential cause of the second episode by P. vivax.ConclusionThis study suggests that PMNS often occurs after severe falciparum malaria. Concurrent P. vivax infection with pathogenic biomass being predominantly extravascular further complicates accurate diagnosis.

Proposals for the early diagnosis of late-onset hereditary ATTR amyloidosis in ‍nonendemic areas in Japan

Late-onset hereditary ATTR (ATTRv) amyloidosis in nonendemic areas takes long periods of time to diagnose in many cases because the clinical symptoms are varied and nonspecific with the family history often unidentifiable. In recent years, disease-modifying therapies have been available for ATTRv amyloidosis, and early diagnosis is increasingly needed. The diagnosis of ATTRv amyloidosis usually requires histological confirmation of the amyloid deposition, although the amyloid detection rate largely depends on the experience, knowledge, and skill of the physician who performs the biopsy. It is important to consider ATTRv amyloidosis as a differential disease in idiopathic polyneuropathy. If ATTRv amyloidosis is strongly suspected, it is acceptable to perform TTR genetic testing prior to histological examination after a thorough differential diagnosis has been made.

Clinical Presentations of Melioidosis and Antibiogram of Burkholderia pseudomallei: An 8-year Study in a Tertiary Care Center, South India

Abstract Background: Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in tropical countries. In nonendemic areas, the disease is rarely suspected because of varying clinical presentations and only a few attempts are made to isolate the pathogen. Many cases are left underdiagnosed or underreported in geographical areas where the disease is not endemic. This study aimed to analyze the clinical presentations, comorbidities, and antibiotic susceptibility patterns in patients with melioidosis in a tertiary care center. Materials and Methods: A retrospective study was done on culture-confirmed melioidosis patients admitted to a tertiary care center, from January 2015 to December 2022. Relevant information on clinical presentations, mortality rate, comorbidities, and antibiogram was collected from hospital medical records. Results: A total of 73 culture-confirmed cases of melioidosis were included in the study. Common clinical presentations were pneumonia (n = 35, 47.9%), septicemia (n = 13, 17.8%), and deep abscesses (n = 9, 12.3%). The mortality rate from melioidosis was 15.1% (n = 11). No significant difference was found in the mortality rate between pneumonia and septicemia groups (P = 0.716). Diabetes mellitus (DM) was the major comorbidity detected (n = 56, 76.7%). Isolates were susceptible to ceftazidime (n = 71, 97.3%), meropenem (n = 71, 97.3%), and co-trimoxazole (n = 60, 82.2%). Conclusions: Common clinical presentations of melioidosis in our setting were pneumonia and septicemia. DM was the major comorbidity. Nearly one in six patients died. Ceftazidime and meropenem were the effective antibiotics. These findings may help physicians to make an early microbiological diagnosis which is essential to reduce mortality.

Wildlife as a Sentinel for Pathogen Introduction in Nonendemic Areas: First Detection of Leishmania tropica in Wildlife in Spain

Wildlife as a Sentinel for Pathogen Introduction in Nonendemic Areas: First Detection of <i>Leishmania tropica</i> in Wildlife in Spain

Human T-cell lymphotropic virus type 1-related uveitis, review about a case

Abstract Human T-cell lymphotropic virus type 1 (HTLV-1) is an endemic retrovirus associated with adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM-TSP), and HTLV-1 uveitis (HU). The latter may occur in association with HAM-TSP, more rarely along ATL, or as an isolated manifestation of the viral infection. The authors present a review of the literature on HU, illustrated by a clinical case. A literature search was performed in the MEDLINE database (PubMed) and included surveys completed until 2022. HU prevalence is increasing in nonendemic metropolitan areas due to migration, thus it is becoming an increasingly relevant agent in the differential diagnosis of patients with uveitis.

Diagnostic challenges in cutaneous leishmaniasis due to atypical Leishmania infantum: pathologists' insights from re-emergence zones.

Leishmaniasis, a parasitic infection affecting both humans and animals, is increasingly spreading across Mediterranean and European regions, largely driven by human migration and environmental changes. In countries like Türkiye and across Europe, which have seen large influxes of migrants, the incidence of cutaneous leishmaniasis (CL) is rising, with cases now appearing in cities where the disease was previously undocumented. In these previously non-endemic areas, physicians unfamiliar with the characteristic lesions may misdiagnose CL, particularly in cases with only cutaneous manifestations. This study aims to evaluate the impact of re-emerging CL on the routine diagnostic practices of pathologists in Türkiye, by retrospectively reviewing cases. We conducted a retrospective analysis of CL cases diagnosed between 2013 and 2022 at a single pathology center in Türkiye, covering multiple provinces. Twelve cases of CL were identified and analyzed based on clinical presentation, pre-diagnosis, histopathological findings, and molecular diagnostics. DNA extraction and PCR were performed on paraffin-embedded tissue samples to identify the Leishmania species involved. Out of the twelve CL cases reviewed, seven exhibited morphological findings strongly suggestive of CL (MFSS of CL), warranting further microbiological evaluation. All patients presented with non-healing skin lesions characterized by central ulceration, crater-like formations, or papulonodular lesions. Notably, CL was included in the clinical pre-diagnosis in only 58.3% of cases, while it was not considered in the remaining 41.7% of cases. Clinicians initially pre-diagnosed skin tumors in six cases (50%), four of which led to wide surgical excision. Histopathological examination in all cases revealed chronic or mixed (acute/chronic) inflammation, predominantly rich in histiocytes. To further investigate the role of Leishmania species in the pre-diagnosis, DNA extraction and PCR were performed on paraffin-embedded tissue samples, identifying L. infantum as the causative agent in 10 cases and L. major in two cases. Notably, L. infantum was the causative agent in all five cases initially misdiagnosed as skin tumors, which were also associated with a granulomatous type of chronic inflammation.

The use of recombinant K39, KMP11, and crude antigen-based indirect ELISA as a serological diagnostic tool and a measure of exposure for cutaneous leishmaniasis in Sri Lanka.

Cutaneous leishmaniasis (CL) in Sri Lanka is caused by Leishmania donovani, a parasite widely known to cause visceral leishmaniasis. Despite the fact that CL is not generally believed to elicit serological immune responses, recent studies show the presence of antibody responses against this atypical form of CL. This study assesses the potential of using recombinant K39 (rK39), KMP11, and crude parasite antigen-based indirect ELISAs as serological diagnostic tools and measures of exposure for CL in Sri Lanka. The study used serum samples from confirmed CL patients (n = 266) and apparently healthy individuals from endemic settings (n = 411). Serum samples from individuals residing in non-endemic areas were used as negative controls. In-house indirect ELISAs were optimized and validated for recombinant antigens. Previously validated crude parasite extract-based indirect ELISA was performed for comparison. The statistical analyses were performed using SPSS v26.0. The rK39 (sensitivity = 71.2%, specificity = 64%) and KMP11 (sensitivity = 79.2%, specificity = 71.4%) based indirect ELISA were shown to be less suitable for the diagnosis of CL, while crude parasite extract-based indirect ELISA (sensitivity = 82.4%, specificity = 85.7%) might be a better method of diagnosis. All 03 ELISAs seemed to be good methods as measures of exposure since correlations were observed between the seropositivity of all 03 ELISAs (rK39: p = 0.037, KMP11: p = 0.007, CrudeAg: p = 0.000) with provincial case incidences. The findings will be important in identifying the disease hotspots in order to design the control measures for CL induced by L. donovani in Sri Lanka.

Abrupt Increase in Detection of Locally Acquired West-Nile-Virus-Lineage-2-Mediated Neuroinvasive Disease in a Previously Non-Endemic Area of Southern Italy (2023).

West Nile virus (WNV) is a public health concern in Europe. Rising temperatures and the migration of potential vectors promote the spread of viruses to previously unaffected areas. In 2023, the Apulia region of Southern Italy experienced an unexpected increase in West Nile neuroinvasive disease (WNND); no such cases had been reported in the previous 10 years. Overall, eight autochthonous cases of WNV infection were identified between July and October 2023, six of which were WNND. All cases were male (median age, 73 years). Two of the cases were blood donors. All WNND cases were hospitalized and all recovered within a few weeks. Surveillance data showed that, in the Apulia region, WNV Lineage 2 was detected in humans, mosquitoes, and horses. Based on the number of WNND cases reported, we can assume that a high number of infections occurred during the summer period. Changes in the climate in the region over recent years could be considered among the main drivers of the rapid increase in WNV infections. Therefore, integrated surveillance should be strengthened to avoid the potential massive spread of WNV in Southern Italy. Moreover, the implementation of whole-genome sequencing of WNV strains, as well as seroepidemiological studies in the area, will facilitate a better understanding of circulation dynamics.

Imported malaria into Australia: surveillance insights and opportunities.

Malaria continues to pose a significant burden in endemic countries, many of which lack access to molecular surveillance. Insights from malaria cases in travellers returning to non-endemic areas can provide valuable data to inform endemic country programmes. To evaluate the potential for novel global insights into malaria, we examined epidemiological and molecular data from imported malaria cases to Australia. We analysed malaria cases reported in Australia from 2012 to 2022 using National Notifiable Disease Surveillance System data. Molecular data on imported malaria cases were obtained from literature searches. Between 2012 and 2022, 3204 malaria cases were reported in Australia. Most cases (69%) were male and 44% occurred in young adults aged 20-39years. Incidence rates initially declined between 2012 and 2015, then increased until 2019. During 2012-2019, the incidence in travellers ranged from 1.34 to 7.71 per 100 000 trips. Cases were primarily acquired in Sub-Saharan Africa (n = 1433; 45%), Oceania (n = 569; 18%) and Southern and Central Asia (n = 367; 12%). The most common countries of acquisition were Papua New Guinea (n = 474) and India (n = 277). Plasmodium falciparum accounted for 58% (1871/3204) of cases and was predominantly acquired in Sub-Saharan Africa, and Plasmodium vivax accounted for 32% (1016/3204), predominantly from Oceania and Asia. Molecular studies of imported malaria cases to Australia identified genetic mutations and deletions associated with drug resistance and false-negative rapid diagnostic test results, and led to the establishment of reference genomes for P. vivax and Plasmodium malariae. Our analysis highlights the continuing burden of imported malaria into Australia. Molecular studies have offered valuable insights into drug resistance and diagnostic limitations, and established reference genomes. Integrating molecular data into national surveillance systems could provide important infectious disease intelligence to optimize treatment guidelines for returning travellers and support endemic country surveillance programmes.

Identification and management of gastrointestinal manifestations of hereditary transthyretin amyloidosis: Recommendations from an Italian group of experts

Gastrointestinal manifestations are common across all hereditary transthyretin amyloidosis (ATTRv) genotypes. However, they are poorly specific, and their recognition as part of ATTRv is difficult, resulting in misdiagnosis with more common conditions. Moreover, delays in diagnosis occur because of fragmented knowledge, a shortage of centers of excellence and specialists dedicated to ATTRv management, and the scarce involvement of gastroenterologists in multidisciplinary teams. A group of Italian gastroenterologists with experience in the management of ATTRv took part in a project aimed at assessing the awareness of ATTRv among the community of Italian gastroenterologists through an online survey and providing education about practical aspects of ATTRv management. Survey results reported low participation, and very few patients with ATTRv were cared for by gastroenterologists. This highlights the need for greater attention to rare diseases in gastroenterology and emphasizes increasing awareness of ATTRv and diagnostic suspicion. Based on the experts' recommendations, a diagnosis of ATTRv should be suspected when at least one of the 'red flags' is detected. Subsequently, it is suggested to promptly ask for genetic testing and exclude a serum and urinary monoclonal protein, even before the detection of amyloid in biopsy samples, particularly in non-endemic areas.