Editor’s Choice Articles

Leptospirosis is one of the most widespread zoonotic diseases and can infect both humans and animals worldwide. The role of the cat as a susceptible host and potential environmental reservoir of Leptospira is still not well understood, due to the lack of obvious clinical signs associated with Leptospira spp. infection in this species. This study aims to describe the first European detection of Leptospira interrogans serogroup Australis ST 24 in a young outdoor cat with a severe comorbidity (feline panleukopenia virus). In addition, the results of a preliminary study conducted in 2014–2016 are presented (RC IZSVE 16/12), which reports an investigation of Leptospira exposure of outdoor cats in Northeast Italy by means of serological investigation and molecular evaluation of urine. The animals included in the survey are part of samples collected during active and passive surveillance (diagnostic samples). The study reported a seroprevalence of 10.5% among outdoor cats and the serogroups identified were Grippotyphosa, Icterohaemorrhagiae, Bratislava, Canicola and Ballum. Symptomatic cats reported high MAT titres (ranging from 1:800 to 1:1600) towards antigens belonging to the serovars Grippotyphosa (1:800), Bratislava (1:1600), Icterohaemorrhagiae (1:200) and Copenhageni (1:200–1:800). In one subject, urine tested positive for Leptospira PCR. Cats with high antibody titres for Leptospira and/or positivity on molecular test suffered from immunosuppressive comorbidities (feline immunodeficiency virus and feline leukaemia virus; feline herpesvirus and lymphoma; hyperthyroidism). The overall prevalence of serum antibodies against Leptospira found in free-ranging cats (10.53%, 95% CI: 4.35–16.70%) and the identification of L. interrogans ST 24 in a young cat with immunosuppressive disease (feline panleukopenia virus) suggest the possibility of natural resistance to clinical leptospirosis in healthy cats. In a One Health perspective, further studies are needed to better define the pathogenesis of leptospirosis in cats and their epidemiological role as environmental sentinels or possible carriers of pathogenic Leptospira. Full article

With increased focus on nontuberculous mycobacterial pulmonary disease (NTM-PD), and the improvement in detection methods, the global incidence continues to increase every year, but the diagnosis and treatment are difficult with a high misdiagnosis rate and poor curative effect. This study aimed to analyze the clinical indicators of different pathogenic NTM in the Yangtze River Delta. The study retrospectively analyzed the medical records of patients with NTM-PD, who resided in the Yangtze River Delta and were diagnosed using sputum or bronchial lavage fluid and hospitalized in Shanghai Pulmonary Hospital from March 2017 to February 2019. The clinical data of confirmed patients were collected. Among the 513 cases of NTM-PD, 482 cases were infected by four common bacteria: Mycobacterium intracellulare (224, 46.5%), M. abscessus (138, 28.6%), M. kansasii (84, 17.4%), and M. avium (36, 7.5%). The analysis found that different NTM strains have their corresponding positive and negative correlation factors (p < 0.05). M. intracellulare, M. abscessus, M. kansasii, and M. avium were the main pathogenic bacteria isolated from patients with NTM-PD in the Yangtze River Delta were. Different strains resulted in different clinical features, assisting in the early diagnosis and treatment of NTM-PD. Full article

Dengue is a mosquito-borne flaviviral serious febrile illness, most common in the tropical and subtropical regions including Pakistan. Vitamin D is a strong immunomodulator affecting both the innate and adaptive immune responses and plays a pivotal role in pathogen-defense mechanisms. There has been considerable interest in the possible role of vitamin D in dengue viral (DENV) infection. In the present prospective cross-sectional study, we assessed a possible association between serum vitamin D deficiency (VDD) and susceptibility towards severe dengue fever (DF) illness. Serum vitamin D levels were measured at the time of hospitalization in 97 patients diagnosed with dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) at Mayo Hospital, King Edward Medical University, Lahore, PK, from 16 November 2021 to 15 January 2022. In terms of disease severity, 37 (38.1%) patients were DF, 52 (53.6%) were DHF grade 1 and 2, and 8 (8.2%) were DSS. The results revealed that most patients (75 (77.3%)) were vitamin-D-deficient (i.e., serum level < 20 ng/mL), including 27 (73.0%) in DF, 41 (78.8%) in DHF grade 1 and 2, and 7 (87.5%) in DSS. The degree of VDD was somewhat higher in DSS patients as compared to DF and DHF grade 1 and 2 patients. Overall, serum vitamin D levels ranged from 4.2 to 109.7 ng/mL, and the median (IQR) was in the VDD range, i.e., 12.2 (9.1, 17.8) ng/mL. Our results suggest that there may be a possible association between VDD and susceptibility towards severe dengue illness. Hence, maintaining sufficient vitamin D levels in the body either through diet or supplementation may help provide adequate immune protection against severe dengue fever illness. Further research is warranted. Full article

Background: In recent decades, the increase in population movements has turned the focus to imported diseases. The COVID-19 pandemic has negatively impacted the access to health care systems, especially in highly vulnerable populations. We address the effects of the pandemic on the health screening of migrant unaccompanied minors (UM) in Spain. Method: Retrospective cross-sectional study including UM screened for imported diseases with a unified protocol at a pediatric reference unit for tropical and infectious diseases in Madrid, Spain. We compared the pre-pandemic (2018–2019) and post-pandemic periods (2020–2021). Results: A total of 192 minors were screened during the study period, with a drop in UM’s referral to our center in the post-pandemic years (140 in 2018–2019 vs. 52 in 2020–2021). Out of 192, 161 (83.9%) were diagnosed with at least one medical condition. The mean age was 16.8 years (SD 0.8) and 96.9% were males. Most cases were referred for a health exam; only 38% of children were symptomatic. Eosinophilia was present in 20.8%. The most common diagnosis were latent tuberculosis infection (LTBI) (72.9%), schistosomiasis (15.1%), toxocariasis (4.9%) and strongyloidiasis (4.9%). The prevalence of LTBI did not vary significantly (69.3% vs. 82.7%, p = 0.087). A total of 38% of the patients diagnosed with LTBI never started treatment or were lost to follow-up, as were two out of three patients with active pulmonary tuberculosis. Conclusions: In this series, the number of UM referred for health screening has dropped dramatically after the COVID pandemic, and two years after the beginning of the pandemic, access to care is still limited. Lost to follow-up rates are extremely high despite institutionalization. Specific resources, including multidisciplinary teams and accessible units are needed to improve diagnoses and linkage to care in this vulnerable population. Full article

High IL-10 levels are pivotal to parasite survival in visceral leishmaniasis (VL). Antigenic stimuli induce IL-10 expression and release of adenosine by CD39/CD73. Due their intrinsic ability to express IL-10 and produce adenosine from extracellular ATP, we evaluated the IL-10, CD39, and CD73 expression by Regulatory T cells (Treg) correlated with VL pathology. Using flow cytometry, Treg cells was analyzed in peripheral blood samples from VL patients (in the presence and absence of Leishmania infantum soluble antigen (SLA)) and healthy individuals (negative endemic control—NEC group), without any treatment. Additionally, IL-10 levels in leukocytes culture supernatant were measured in all groups by ELISA assay. VL patients presented more Treg frequency than NEC group, independently of stimulation. ELISA results demonstrated that SLA induced higher IL-10 expression in the VL group. However, the NEC group had a higher Treg IL-10⁺ compared to the VL group without stimulation and SLA restored the IL-10 in Treg. Additionally, an increase in Treg CD73⁺ in the VL group independently of stimuli compared to that in the NEC group was observed. We suggest that Treg are not the main source of IL-10, while the CD73 pathway may be an attempt to modulate the exacerbation of immune response in VL disease. Full article

The Lao People’s Democratic Republic is an endemic area of dengue, with cases reported in urban and rural areas every year. In this study, we indirectly evaluated the efficacy of a larvicide (SumiLarv^TM 2MR discs) that was used for vector control against Aedes mosquitoes. Villages in a rural area of Lao PDR were selected as study areas, non-intervention and intervention villages. At the intervention village, the larvicide was used to treat refillable water containers for 27 months (October 2017 to February 2020), while at the non-intervention villages were no treatment. The serum samples of villagers from both villages were randomized to collect in the pre-intervention and in post-intervention periods. An enzyme-linked immunosorbent assay (ELISA) was used to examine anti-dengue virus (DENV) IgG antibody levels in serum samples. Recombinant DENV serotype 2 non-structural protein1 was used as an antigen for the ELISA, the optical density (OD) values were analyzed for comparison. The results showed that the OD values decreased significantly (p < 0.01) between the pre-intervention and post-intervention periods at the intervention site. The treatment of water storage containers in rural areas with SumiLarv^TM 2MR discs may help to protect residents from Aedes mosquito bites, and hence, reduce DENV infections. Full article

The polyomaviruses that infect humans, JC virus (JCV) and BK virus (BKV), can establish persistent infections in the cells that make up the renal system, causing nephritis and BKV-associated nephropathy in up to 10% of renal transplant patients, and of these, 90% lose the graft and return for hemodialysis. This study aimed to determine the prevalence of polyomaviruses (PyV) in the population with chronic kidney disease (CKD), classified into three groups (conservative, dialysis, and transplanted) and a control group. Urine samples were collected from 290 individuals, including 202 patients with CKD and 88 from the control group. PyV screening was performed by PCR amplification of a fragment of the VP1 region, and the JCV and BKV species were distinguished through enzymatic digestion with the restriction endonuclease BamHI from the amplification of a TAg region. All amplification products were visualized on a 3% agarose gel. The prevalence of PyV infection was correlated with clinical-epidemiological variables using the chi-squared and Fisher’s exact tests. In the group with CKD, the prevalence of PyV was 30.2%, a higher rate being observed in conservative patients (36.66%; 22/60), followed by dialysis patients (30.48%; 25/82), and transplanted patients (20%; 12/60). In the control group, the prevalence was 46.59% (41/88). The differentiation between species revealed that JCV was present in 77.8% and BKV in 22.2% of the group with CKD. The prevalence of infection was higher in male patients (59.32%), whose most common pathology was systemic arterial hypertension (35.59%). In the group of transplanted patients, there was a statistically significant association between infection and the use of the immunosuppressant azathioprine (p = 0.015). The prevalence of PyV infection was higher in the control group than in the group with CKD, being predominant in males and in patients with systemic arterial hypertension. Full article

Due to the rapid evolution of the monkeypox virus, the means by which the monkeypox virus is spread is subject to change. Therefore, the present study aims to analyze the detection of the monkeypox virus according to the collection site of samples from confirmed monkeypox cases. A systematic literature review was performed using PubMed, Scopus, Web of Science, and Embase databases until 5 October 2022. A total of 1022 articles were retrieved using the search strategy. After removing duplicates (n = 566) and examining by title, abstract, and full text, 65 studies reporting monkeypox case reports were included with a detailed description of risk factors, sexually transmitted infections (STIs), site of monkeypox virus-positive specimens, location of skin lesions, and diagnostic test. A total of 4537 confirmed monkeypox cases have been reported, of which 98.72% of the cases were male with a mean age of 36 years, 95.72% had a sexual behavior of being men who have sex with men, and 28.1% had human immunodeficiency virus (HIV). The most frequent locations of lesions in patients diagnosed with monkeypox were: 42.85% on the genitalia and 37.1% in the perianal region. All confirmed monkeypox cases were diagnosed by reverse transcriptase polymerase chain reaction (RT-PCR), and the most frequent locations of samples collected for diagnosis that tested positive for monkeypox virus were: 91.85% from skin lesions, 20.81% from the oropharynx, 3.19% from blood, and 2.43% from seminal fluid. The disease course of the cases with monkeypox was asynchronous, with no severe complications, and most patients did not report specific treatment but simply followed a symptomatic treatment. Full article

Objectives: In COVID-19 patients, bacterial and fungal pulmonary coinfections, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, or Aspergillus, have been reported, but to our knowledge, no case has been reported due to Pasteurella multocida. Patients and methods: We describe three cases of Pasteurella multocida coinfections occurring during the 4th wave of COVID-19 in Martinique (French West Indies). Results: All three cases were fatal; thus, Pasteurella multocida has to be considered as a potentially severe coinfection agent. Conclusions: Alteration of the epithelial–endothelial barrier due to a SARS-CoV-2 infection probably promotes the expression of a Pasteurella infection. In addition, the SARS-CoV-2 infection induced immunosuppression, and an inflammatory cascade could explain the infection’s severity. The use of corticosteroids, which are part of the first-line therapeutic arsenal against COVID-19, may also promote the pathogenicity of this agent. Full article

Malaria is one of the deadliest tropical diseases, especially causing havoc in children under the age of five in Africa. Although the disease is treatable, the rapid development of drug resistant parasites against frontline drugs requires the search for novel antimalarials. In this study, we tested a series of organosulfur compounds from our internal library for their antiplasmodial effect against Plasmodium falciparum asexual and sexual blood stages. Some active compounds were also obtained in enantiomerically pure form and tested individually against asexual blood stages of the parasite to compare their activity. Out of the 23 tested compounds, 7 compounds (1, 2, 5, 9, 15, 16, and 17) exhibited high antimalarial activity, with IC₅₀ values in the range from 2.2 ± 0.64 to 5.2 ± 1.95 µM, while the other compounds showed moderate to very low activity. The most active compounds also exhibited high activity against the chloroquine-resistant strain, reduced gametocyte development and were not toxic to non-infected red blood cells and Hela cells, as well as the hematopoietic HEL cell line at concentrations below 50 µM. To determine if the enantiomers of the active compounds display different antimalarial activity, enantiomers of two of the active compounds were separated and their antimalarial activity compared. The results show a higher activity of the (–) enantiomers as compared to their (+) counterparts. Our combined data indicate that organosulfur compounds could be exploited as antimalarial drugs and enantiomers of the active compounds may represent a good starting point for the design of novel drugs to target malaria. Full article

Plasmodium knowlesi, a malaria parasite that occurs naturally in long-tailed macaques, pig-tailed macaques, and banded leaf monkeys, is currently regarded as the fifth of the human malaria parasites. We aimed to investigate genetic diversity based on the cytochrome c oxidase subunit I (COI) gene, detect Plasmodium parasites, and screen for the voltage-gated sodium channel (VGSC)-mutation-mediated knockdown resistance (kdr) of Anopheles mosquitoes in Ranong province, which is the most P. knowlesi-endemic area in Thailand. One hundred and fourteen Anopheles females belonging to eight species, including An. baimaii (21.05%), An. minimus s.s. (20.17%), An. epiroticus (19.30%), An. jamesii (19.30%), An. maculatus s.s. (13.16%), An. barbirostris A3 (5.26%), An. sawadwongporni (0.88%), and An. aconitus (0.88%), were caught in three geographical regions of Ranong province. None of the Anopheles mosquitoes sampled in this study were infected with Plasmodium parasites. Based on the sequence analysis of COI sequences, An. epiroticus had the highest level of nucleotide diversity (0.012), followed by An. minimus (0.011). In contrast, An. maculatus (0.002) had the lowest level of nucleotide diversity. The Fu’s Fs and Tajima’s D values of the Anopheles species in Ranong were all negative, except the Tajima’s D values of An. minimus (0.077). Screening of VGSC sequences showed no presence of the kdr mutation of Anopheles mosquitoes. Our results could be used to further select effective techniques for controlling Anopheles populations in Thailand’s most P. knowlesi-endemic area. Full article

In 2017–2019, Brazil recorded its most severe outbreak of yellow fever due to the spread of the virus (YFV) in the country’s southeast. Here, we investigated mosquito fauna and the spatial distribution of species in a primatology center in the Atlantic Forest bioregion in Rio de Janeiro state to evaluate the risk of YFV transmission in distinct environments. Fortnightly mosquito collections were performed from December 2018 to December 2019 at 12 sites along a disturbance gradient from a modified environment to 400 m inside the forest. We used ovitraps, BG-Sentinel, and protected human attraction (PHA). A total of 9349 mosquitoes of 21 species were collected. The collection method strongly influenced the captured fauna, with species such as Anopheles cruzii, Psorophora ferox, Runchomyia cerqueirai, Wyeomyia incaudata, Wy. theobaldi, Sabethes chloropterus, and Sa. albiprivus only collected via PHA. Collections with ovitraps resulted in low diversity and richness, with Haemagogus leucocelaenus and Hg. janthinomys/capricornii predominating. The diverse local fauna and the abundance and ubiquity of the latter species, which are the primary vectors of YFV, indicated that this area was highly vulnerable to arbovirus transmission, especially yellow fever, highlighting the need for improved surveillance and vaccination coverage in human and captive endangered non-human primates. Full article

Cancer and parasitic diseases, such as leishmaniasis and Chagas disease, share similarities that allow the co-development of new antiproliferative agents as a strategy to quickly track the discovery of new drugs. This strategy is especially interesting regarding tropical neglected diseases, for which chemotherapeutic alternatives are extremely outdated. We designed a series of (E)-3-aryl-5-(2-aryl-vinyl)-1,2,4-oxadiazoles based on the reported antiparasitic and anticancer activities of structurally related compounds. The synthesis of such compounds led to the development of a new, fast, and efficient strategy for the construction of a 1,2,4-oxadiazole ring on a silica-supported system under microwave irradiation. One hit compound (23) was identified during the in vitro evaluation against drug-sensitive and drug-resistant chronic myeloid leukemia cell lines (EC₅₀ values ranging from 5.5 to 13.2 µM), Trypanosoma cruzi amastigotes (EC₅₀ = 2.9 µM) and Leishmania amazonensis promastigotes (EC₅₀ = 12.2 µM) and amastigotes (EC₅₀ = 13.5 µM). In silico studies indicate a correlation between the in vitro activity and the interaction with tubulin at the colchicine binding site. Furthermore, ADMET in silico predictions indicate that the compounds possess a high druggability potential due to their physicochemical, pharmacokinetic, and toxicity profiles, and for hit 23, it was identified by multiple spectroscopic approaches that this compound binds with human serum albumin (HSA) via a spontaneous ground-state association with a moderate affinity driven by entropically and enthalpically energies into subdomain IIA (site I) without significantly perturbing the secondary content of the protein. Full article

Recent Japanese encephalitis virus (JEV) outbreaks in southeastern Australia have sparked interest into epidemiological factors surrounding the virus’ novel emergence in this region. Here, the geographic distribution of mosquito species known to be competent JEV vectors in the country was estimated by combining known mosquito occurrences and ecological drivers of distribution to reveal insights into communities at highest risk of infectious disease transmission. Species distribution models predicted that Culex annulirostris and Culex sitiens presence was mostly likely along Australia’s eastern and northern coastline, while Culex quinquefasciatus presence was estimated to be most likely near inland regions of southern Australia as well as coastal regions of Western Australia. While Culex annulirostris is considered the dominant JEV vector in Australia, our ecological niche models emphasise the need for further entomological surveillance and JEV research within Australia. Full article

Five species of Plasmodium cause malaria in humans and two of them, P. vivax and P. falciparum, pose the greatest threat. Rapid antigen detection tests (RADT) have been used for many years to diagnose and distinguish malaria caused by these two parasites. P. falciparum malaria can single-handedly be diagnosed using an RADT, which detects the unique P. falciparum specific histidine-rich protein 2 (HRP2). Unfortunately, there is no RADT that can single-handedly diagnose P. vivax malaria because no specific marker of this parasite has yet been described. Here, we report the discovery of a unique P. vivax protein (Vir14, NCBI Reference Sequence: XP_001612449.1) that has no sequence similarity with proteins of P. falciparum and no significant similarities with proteins of other species of Plasmodium. We propose that this protein could be an outstanding candidate molecule for the development of a promising RADT that can single-handedly and specifically diagnose P. vivax malaria. Full article

Tropical diseases (TDs) are among the leading cause of mortality and fatality globally. The emergence and reemergence of TDs continue to challenge healthcare system. Several tropical diseases such as yellow fever, tuberculosis, cholera, Ebola, HIV, rotavirus, dengue, and malaria outbreaks have led to endemics and epidemics around the world, resulting in millions of deaths. The increase in climate change, migration and urbanization, overcrowding, and other factors continue to increase the spread of TDs. More cases of TDs are recorded as a result of substandard health care systems and lack of access to clean water and food. Early diagnosis of these diseases is crucial for treatment and control. Despite the advancement and development of numerous diagnosis assays, the healthcare system is still hindered by many challenges which include low sensitivity, specificity, the need of trained pathologists, the use of chemicals and a lack of point of care (POC) diagnostic. In order to address these issues, scientists have adopted the use of CRISPR/Cas systems which are gene editing technologies that mimic bacterial immune pathways. Recent advances in CRISPR-based biotechnology have significantly expanded the development of biomolecular sensors for diagnosing diseases and understanding cellular signaling pathways. The CRISPR/Cas strategy plays an excellent role in the field of biosensors. The latest developments are evolving with the specific use of CRISPR, which aims for a fast and accurate sensor system. Thus, the aim of this review is to provide concise knowledge on TDs associated with mosquitoes in terms of pathology and epidemiology as well as background knowledge on CRISPR in prokaryotes and eukaryotes. Moreover, the study overviews the application of the CRISPR/Cas system for detection of TDs associated with mosquitoes. Full article

Under the Global Program to Eliminate Lymphatic Filariasis (LF) American Samoa conducted seven rounds of mass drug administration (MDA) between 2000 and 2006. Subsequently, the territory passed the WHO recommended school-based transmission assessment survey (TAS) in 2011/2012 (TAS-1) and 2015 (TAS-2) but failed in 2016, when both TAS-3 and a community survey found LF antigen prevalence above what it had been in previous surveys. This study aimed to identify potential environmental drivers of LF to refine future surveillance efforts to detect re-emergence and recurrence. Data on five LF infection markers: antigen, Wb123, Bm14 and Bm33 antibodies and microfilaraemia, were obtained from a population-wide serosurvey conducted in American Samoa in 2016. Spatially explicit data on environmental factors were derived from freely available sources. Separate multivariable Poisson regression models were developed for each infection marker to assess and quantify the associations between LF infection markers and environmental variables. Rangeland, tree cover and urban cover were consistently associated with a higher seroprevalence of LF-infection markers, but to varying magnitudes between landcover classes. High slope gradient, population density and crop cover had a negative association with the seroprevalence of LF infection markers. No association between rainfall and LF infection markers was detected, potentially due to the limited variation in rainfall across the island. This study demonstrated that seroprevalence of LF infection markers were more consistently associated with topographical environmental variables, such as gradient of the slope, rather than climatic variables, such as rainfall. These results provide the initial groundwork to support the detection of areas where LF transmission is more likely to occur, and inform LF elimination efforts through better understanding of the environmental drivers. Full article

Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose–response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21–39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed. Full article

Alveolar echinococcosis (AE) is a severe parasitic zoonosis caused by the larval stage of Echinococcus multilocularis. The identification of the antigens eliciting acquired immunity during infection is important for vaccine development against Echinococcus infection. Here, we identified that E. multilocularis calreticulin (EmCRT), a ubiquitous protein with a Ca²⁺-binding ability, could be recognized by the sera of mice infected with E. multilocularis. The native EmCRT was expressed on the surface of E. multilocularis larvae as well as in the secreted products of metacestode vesicles and protoscoleces (PSCs). The coding DNA for EmCRT was cloned from the mRNA of the E. multilocularis metacestode vesicles and a recombinant EmCRT protein (rEmCRT) was expressed in E. coli. Mice immunized with soluble rEmCRT formulated with Freund’s adjuvant (FA) produced a 43.16% larval vesicle weight reduction against the challenge of E. multilocularis PSCs compared to those that received the PBS control associated with a high titer of IgG, IgG1 and IgG2a antibody responses as well as high levels of Th1 cytokines (IFN-γ and IL-2) and Th2 cytokines (IL-4, IL-5 and IL-10), produced by splenocytes. Our results suggest that EmCRT is an immunodominant protein secreted by E. multilocularis larvae and a vaccine candidate that induces partial protective immunity in vaccinated mice against Echinococcus infection. Full article

Human African trypanosomiasis (HAT) is a neglected tropical disease that has not received much attention in Zambia and most of the countries in which it occurs. In this study, we assessed the adequacy of the healthcare delivery system in diagnosis and management of rHAT cases, the environmental factors associated with transmission, the population at risk and the geographical location of rHAT cases. Structured questionnaires, focus group discussions and key informant interviews were conducted among the affected communities and health workers. The study identified 64 cases of rHAT, of which 26 were identified through active surveillance and 38 through passive surveillance. We identified a significant association between knowledge of the vector for rHAT and knowledge of rHAT transmission (p < 0.028). In all four districts, late or poor diagnosis occurred due to a lack of qualified laboratory technicians and diagnostic equipment. This study reveals that the current Zambian healthcare system is not able to adequately handle rHAT cases. Targeted policies to improve staff training in rHAT disease detection and management are needed to ensure that sustainable elimination of this public health problem is achieved in line with global targets. Full article

Leptospirosis is a major zoonotic disease that has emerged worldwide, and numerous studies performed in affected countries have provided epidemiological knowledge of the disease. However, currently, there is inadequate knowledge of leptospirosis in the Middle East. Therefore, we grouped publications from various Middle Eastern countries to acquire a general knowledge of the epidemiological situation of leptospirosis and provide an initial description of the leptospiral relative risk and circulating serogroups. We conducted a detailed literature search of existing studies describing Leptospira prevalence and seroprevalence in Middle Eastern countries. The search was performed using online PubMed and ScienceDirect databases. One hundred and one articles were included in this review. Some countries, including Iran, Turkey, and Egypt, reported more publications compared to others, such as Lebanon, Kuwait, and Saudi Arabia. Frequently, the seroprevalence of leptospirosis varied considerably between and within countries. The prevalence of leptospirosis was comparable in most Middle Eastern countries; however, it varied between some countries. The methods of detection also varied among studies, with the microscopic agglutination test used most commonly. Some hosts were more recurrent compared with others. This review summarizes the epidemiological situation of Leptospira infection in the Middle East, reporting predominant serogroups—Sejroe, Grippotyphosa, Icterohaemorrhagiae, Autumnalis, and Pomona—that were identified in the most commonly tested hosts. Our findings emphasize the need to develop a deeper understanding of the epidemiology of Leptospira spp. and prioritize the disease as a public health problem in this region. To achieve this goal, increased awareness is critical, and more publications related to the topic and following a standardized approach are needed. Full article

Current knowledge on Leishmania infection after kidney transplantation (KT) is limited. In order to offer a comprehensive guide for the management of post-transplant Leishmaniasis, we performed a systematic review following the latest PRISMA Checklist and using PubMed, Scopus, and Embase as databases. No time restrictions were applied, including all English-edited articles on Leishmaniasis in KT recipients. Selected items were assessed for methodological quality using a modified Newcastle–Ottawa Scale. Given the nature and quality of the studies (case reports and retrospective uncontrolled case series), data could not be meta-analyzed. A descriptive summary was therefore provided. Eventually, we selected 70 studies, describing a total of 159 cases of Leishmaniasis. Most of the patients were adult, male, and Caucasian. Furthermore, they were frequently living or travelling to endemic regions. The onset of the disease was variable, but more often in the late transplant course. The clinical features were basically similar to those reported in the general population. However, a generalized delay in diagnosis and treatment could be detected. Bone marrow aspiration was the preferred diagnostic modality. The main treatment options included pentavalent antimonial and liposomal amphotericin B, both showing mixed results. Overall, the outcomes appeared as concerning, with several patients dying or losing their transplant. Full article

Aedes aegypti and Aedes albopictus are considered the most important vectors of arboviruses in the world. Aedes aegypti is the primary vector of dengue, urban yellow fever, chikungunya and zika in Brazil, and Ae. albopictus is considered a potential vector. Distribution patterns and the influence of climatic variables on the oviposition of Ae. aegypti and Ae. albopictus were evaluated in Morretes, a tourist city in the coastal area of Paraná State, Brazil, which has recently been experiencing cases of dengue fever. Eggs were collected using ovitraps over a period of one year (September 2017 to September 2018) and reared from hatching until the emergence of the adults. Both Aedes species were found in anthropized areas with a high human density index. Findings suggest that the monthly average temperature (LRT = 16.65, p = 0.001) had significant positive influences on the oviposition of the Aedes species. Considering the wide distribution of DENV around the Paraná coast and the presence of Ae. albopictus alongside Ae. aegypti, studies on natural arbovirus infection patterns and seasonality are recommended in the region. Full article

Hospital workers are at high risk of contact with COVID-19 patients. Currently, there is no evidence-based, comprehensive risk assessment tool for healthcare-related exposure; so, we aimed to identify independent factors related to COVID-19 infection in hospital workers following workplace exposure(s) and construct a risk prediction model. We analyzed the COVID-19 contact tracing dataset from 15 July to 31 December 2021 using multiple logistic regression analysis, considering exposure details, demographics, and vaccination history. Of 7146 included exposures to confirmed COVID-19 patients, 229 (4.2%) had subsequently tested positive via RT-PCR. Independent risk factors for a positive test were having symptoms (adjusted odds ratio 4.94, 95%CI 3.83–6.39), participating in an unprotected aerosol-generating procedure (aOR 2.87, 1.66–4.96), duration of exposure >15 min (aOR 2.52, 1.82–3.49), personnel who did not wear a mask (aOR 2.49, 1.75–3.54), exposure to aerodigestive secretion (aOR 1.5, 1.03–2.17), index patient not wearing a mask (aOR 1.44, 1.01–2.07), and exposure distance <1 m without eye protection (aOR 1.39, 1.02–1.89). High-potency vaccines and high levels of education protected against infection. A risk model and scoring system with good discrimination power were built. Having symptoms, unprotected exposure, lower education level, and receiving low potency vaccines increased the risk of laboratory-confirmed COVID-19 following healthcare-related exposure events. Full article

Background: The greatest challenges are imposed on the overall capacity of disease management when the cases reach the maximum in each wave of the pandemic. Methods: The cases and deaths for the four waves of COVID-19 in 119 countries and regions (CRs) were collected. We compared the mortality across CRs where populations experience different economic and healthcare disparities. Findings: Among 119 CRs, 117, 112, 111, and 55 have experienced 1, 2, 3, and 4 waves of COVID-19 disease, respectively. The average mortality rates at the disease turning point were 0.036, 0.019. 0.017, and 0.015 for the waves 1, 2, 3, and 4, respectively. Among 49 potential factors, income level, gross national income (GNI) per capita, and school enrollment are positively correlated with the mortality rates in the first wave, but negatively correlated with the rates of the rest of the waves. Their values for the first wave are 0.253, 0.346 and 0.385, respectively. The r value for waves 2, 3, and 4 are −0.310, −0.293, −0.234; −0.263, −0.284, −0.282; and −0.330, −0.394, −0.048, respectively. In high-income CRs, the mortality rates in waves 2 and 3 were 29% and 28% of that in wave 1; while in upper-middle-income CRs, the rates for waves 2 and 3 were 76% and 79% of that in wave 1. The rates in waves 2 and 3 for lower-middle-income countries were 88% and 89% of that in wave 1, and for low-income countries were 135% and 135%. Furthermore, comparison among the largest case numbers through all waves indicated that the mortalities in upper- and lower-middle-income countries is 65% more than that of the high-income countries. Interpretation: Conclusions from the first wave of the COVID-19 pandemic do not apply to the following waves. The clinical outcomes in developing countries become worse along with the expansion of the pandemic. Full article

Chagas disease, caused by the protozoa Trypanosoma cruzi, is an important yet neglected disease that represents a severe public health problem in the Americas. Although the alteration of natural habitats and climate change can favor the establishment of new transmission cycles for T. cruzi, the compound effect of human-modified landscapes and current climate change on the transmission dynamics of T. cruzi has until now received little attention. A better understanding of the relationship between these factors and T. cruzi presence is an important step towards finding ways to mitigate the future impact of this disease on human communities. Here, we assess how wild and domestic cycles of T. cruzi transmission are related to human-modified landscapes and climate conditions (LUCC-CC). Using a Bayesian datamining framework, we measured the correlations among the presence of T. cruzi transmission cycles (sylvatic, rural, and urban) and historical land use, land cover, and climate for the period 1985 to 2012. We then estimated the potential range changes of T. cruzi transmission cycles under future land-use and -cover change and climate change scenarios for 2050 and 2070 time-horizons, with respect to “green” (RCP 2.6), “business-as-usual” (RCP 4.5), and “worst-case” (RCP 8.5) scenarios, and four general circulation models. Our results show how sylvatic and domestic transmission cycles could have historically interacted through the potential exchange of wild triatomines (insect vectors of T. cruzi) and mammals carrying T. cruzi, due to the proximity of human settlements (urban and rural) to natural habitats. However, T. cruzi transmission cycles in recent times (i.e., 2011) have undergone a domiciliation process where several triatomines have colonized and adapted to human dwellings and domestic species (e.g., dogs and cats) that can be the main blood sources for these triatomines. Accordingly, Chagas disease could become an emerging health problem in urban areas. Projecting potential future range shifts of T. cruzi transmission cycles under LUCC-CC scenarios we found for RCP 2.6 no expansion of favourable conditions for the presence of T. cruzi transmission cycles. However, for RCP 4.5 and 8.5, a significant range expansion of T. cruzi could be expected. We conclude that if sustainable goals are reached by appropriate changes in socio-economic and development policies we can expect no increase in suitable habitats for T. cruzi transmission cycles. Full article

The COVID-19 pandemic has had a significant impact on all facets of life and has exacerbated many challenges faced by people living with tuberculosis (TB). This study aimed to assess the health-related quality of life (HRQoL) of TB patients in Guinea during the first wave of the COVID-19 pandemic. A mixed methods study was conducted using two validated tools to assess HRQoL and qualitative interviews among TB patients enrolled in treatment at 11 health centers in Conakry, Guinea. Logistic regression was used to identify factors associated with the deterioration of HRQoL. We included 439 participants in the study, among whom 44% and 31% experienced pain and anxiety, respectively. We found that an increase in the number of household size and the distance from participants’ residence to the health centers were significantly associated with lower HRQoL. Qualitative interviews highlighted nutritional and financial issues, which were exacerbated during the COVID-19 pandemic and beliefs that the Guinean Government’s assistance plan was insufficient. This study supports the implementation of specific relief plans for TB patients, which includes nutritional and psychological support, especially those whose movements are limited by travel restrictions, preventing access to TB care, reducing work opportunities and exacerbating financial needs and stress. Full article

(1) Background: There is a dearth of data on the levels and determinants of testing for drug-related infectious diseases among people who use drugs (PWUD). We assessed the proportions and determinants of testing for drug-related infectious diseases to inform ongoing interventions for PWUD. (2) Methods: A cross-sectional study involving 599 PWUD was conducted in Dar es Salaam and Tanga between January and February 2019. Data were collected through a researcher-administered questionnaire using handheld tablets. Logistic regression models were used to identify independent testing determinants for drug-related infectious diseases. (3) Results: A majority (98.0%) of participants were males, with a mean age of 36.8 (SD = 7.8) years. 75.0%, 40.6%, 38.6%, and 8.2% reported having ever tested for HIV, tuberculosis (TB), sexually transmitted infections (STIs), and viral hepatitis, respectively. The likelihood of HIV testing was higher among those living with someone (AOR = 2.18, 95% CI: 1.09–4.68) compared with those who were homeless and perceived treatment was appropriate (AOR = 2.18, 95% CI: 1.05–4.46), but was lower among those who experienced mild to moderate (AOR = 0.44, 95% CI: 0.21–0.95) and severe internalized stigma (AOR = 0.44, 95% CI: 0.22–0.94) compared with those reporting no internalized stigma, and among those who experienced financial difficulties resulting from spending on health care services (AOR = 0.60, 95% CI: 0.40–0.89). Perception of treatment appropriateness (AOR = 2.29, 96% CI: 1.10–5.06) and severe enacted stigma (AOR = 1.90, 95% CI: 1.06–3.42) were associated with increased odds of TB testing. The odds of STIs testing increased among those who were married (AOR = 2.31, 95% CI: 1.45–3.72) compared with those who were single and those who had experienced mild (AOR = 2.39, 95% CI: 1.28–4.53) or severe (AOR = 6.20, 95% CI: 1.99–23.83) sexual violence, compared with those who had not experienced sexual violence. However, the odds decreased among those who had been remanded in the past month (AOR = 0.64, 95% CI: 0.43–0.95) compared with those who were not remanded and among those who had financial difficulties resulting from spending on health care services (AOR = 0.66, 95% CI: 0.47–0.94). The likelihood of testing for viral hepatitis testing increased among those who had heard about the comprehensive HIV intervention package (CHIP) (AOR = 2.59, 95% CI: 1.40–4.94); however, it decreased among those who had financial difficulties resulting from spending on health care services (AOR = 0.48, 95% CI: 0.24–0.92). (4) Conclusions: Except for HIV, PWUD had undergone limited testing for drug-related infectious diseases. The study findings highlight some factors influencing testing for the selected infectious diseases investigated, which should be targeted for tailored interventions to improve diagnosis and treatment. Full article

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H₂O₂ equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H₂O₂ equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection. Full article

Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment is a limitation of using human surveys to provide an early indicator of the impact of mass drug administration (MDA), and MX may be more useful in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) in 35 primary sampling units (PSUs) in Samoa, and investigated associations between the presence of PCR-positive mosquitoes and Ag-positive humans. We observed a statistically significant decline in estimated mosquito infection prevalence post-MDA at the national level (from 0.9% to 0.3%, OR 0.4) but no change in human Ag prevalence during this time. Ag prevalence in 2019 was higher in randomly selected PSUs where PCR-positive pools were detected (1.4% in ages 5–9; 4.8% in ages ≥10), compared to those where PCR-positive pools were not detected (0.2% in ages 5–9; 3.2% in ages ≥10). Our study provides promising evidence for MX as a complement to human surveys in post-MDA surveillance. Full article

This study focuses on cardiovascular manifestation, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students aged 13–18 years from two schools, who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography, and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms. We enrolled 314 participants; of these, 13 participants were lost to follow-up, leaving 301 participants for analysis. The most common cardiovascular signs and symptoms were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). One participant could have more than one sign and/or symptom. Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular manifestations were found in 29.24% of patients, ranging from tachycardia or palpitation to myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. In conclusion, Cardiovascular manifestation in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myopericarditis. The clinical presentation of myopericarditis after vaccination was usually mild and temporary, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for cardiovascular side effects. Clinical Trial Registration: NCT05288231. Full article

The Northern Territory (NT) is a geographically remote region of northern and central Australia. Approximately a third of the population are First Nations Australians, many of whom live in remote regions. Due to the physical environment and climate, and scale of social inequity, the rates of many infectious diseases are the highest nationally. Molecular typing and genomic sequencing in research and public health have provided considerable new knowledge on the epidemiology of infectious diseases in the NT. We review the applications of genomic sequencing technology for molecular typing, identification of transmission clusters, phylogenomics, antimicrobial resistance prediction, and pathogen detection. We provide examples where these methodologies have been applied to infectious diseases in the NT and discuss the next steps in public health implementation of this technology. Full article

Hepatitis E virus (HEV) is a waterborne zoonotic disease that can result in a high fatality rate in pregnant women and infants. In 2018, a large HEV outbreak emerged in Chattogram, Bangladesh, resulting in 2800 cases and a significant public health response to mitigate the transmission. While the source of the outbreak remained poorly understood, authorities suggested that possible risk factors for HEV infection included contamination of water supply, exacerbated by concurrent severe flooding events in the community. A cross-sectional study was conducted to investigate the distribution and risk factors for HEV seroprevalence between January and December 2018 in the Chattogram city area. A total of 505 blood samples were collected from symptomatic patients of 10 hospitals who met the case definition for an HEV infection. Standard ELISA tests were performed in all patients to identify anti-HEV antibodies. The size and location of HEV seroprevalence clusters within Chattogram were investigated using SaTScan. We investigated the association between risk of HEV infection and individual and environmentally lagged risk factors using Bernoulli generalised linear regression models. Our results indicate an overall HEV seroprevalence of 35% with significant variation according to sex, source of drinking water, and boiling of drinking water. A positive cross-correlation was found between HEV exposure and precipitation, modified normalised difference water index (MNDWI), and normalised difference vegetation index (NDVI). Our model indicated that risk of infection was associated with sex, age, source of drinking water, boiling of water, increased precipitation, and increased MNDWI. The results from this study indicate that source and boiling of drinking water and increased precipitation were critical drivers of the 2018 HEV outbreak. The communities at highest risk identified in our analyses should be targeted for investments in safe water infrastructure to reduce the likelihood of future HEV outbreaks in Chattogram. Full article

Both directly and indirectly transmitted infectious diseases in humans are spatial-related. Spatial dimensions include: distances between susceptible humans and the environments shared by people, contaminated materials, and infectious animal species. Therefore, spatial concepts in managing and understanding emerging infectious diseases are crucial. Recently, due to the improvements in computing performance and statistical approaches, there are new possibilities regarding the visualization and analysis of disease spatial data. This review provides commonly used spatial or spatial-temporal approaches in managing infectious diseases. It covers four sections, namely: visualization, overall clustering, hot spot detection, and risk factor identification. The first three sections provide methods and epidemiological applications for both point data (i.e., individual data) and aggregate data (i.e., summaries of individual points). The last section focuses on the spatial regression methods adjusted for neighbour effects or spatial heterogeneity and their implementation. Understanding spatial-temporal variations in the spread of infectious diseases have three positive impacts on the management of diseases. These are: surveillance system improvements, the generation of hypotheses and approvals, and the establishment of prevention and control strategies. Notably, ethics and data quality have to be considered before applying spatial-temporal methods. Developing differential global positioning system methods and optimizing Bayesian estimations are future directions. Full article

Malaria infection during pregnancy is an important driver of maternal and neonatal health in endemic countries. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention at each scheduled antenatal care visit, starting at the second trimester, in areas of high and moderate transmission. However, the increased resistance to SP in some endemic areas challenges its effectiveness. Furthermore, SP is contraindicated in the first trimester of pregnancy and in HIV-infected women on co-trimoxazole prophylaxis due to potential drug–drug interactions. Thus, in recent last decades, several studies evaluated alternative drugs that could be used for IPTp. A comprehensive literature review was conducted to summarize the evidence on the efficacy and safety of antimalarial drugs being evaluated for IPTp. Chloroquine, amodiaquine, mefloquine and azithromycin as IPTp have proven to be worse tolerated than SP. Mefloquine was found to increase the risk of mother-to-child transmission of HIV. Dihydroartemisin-piperaquine currently constitutes the most promising IPTp drug alternative; it reduced the prevalence of malaria infection, and placental and clinical malaria in studies among HIV-uninfected women, and it is currently being tested in HIV-infected women. Research on effective antimalarial drugs that can be safely administered for prevention to pregnant women should be prioritized. Malaria prevention in the first trimester of gestation and tailored interventions for HIV-infected women remain key research gaps to be addressed. Full article

Monkeypox (MPX) has been regarded as a neglected tropic disease of Western and Central Africa since the early 70s. However, during May 2022, an unprecedent outbreak of MPX has involved most of European Countries, as well as North and South America. While the actual extent of this outbreak is being assessed by health authorities, we performed a pilot study on specific knowledge, attitudes, and practices (KAP) in a sample of Italian medical professionals (24–30 May 2022; 10,293 potential recipients), focusing on Occupational Physicians (OP), Public Health Professionals (PH), and General Practitioners (GP), i.e., medical professionals more likely involved in the early management of incident cases. More specifically, we inquired into their attitude on the use of variola vaccine in order to prevent MPX infection. From a total of 566 questionnaire (response rate of 5.5%), 163 participants were included in the final analyses. Knowledge status was quite unsatisfying, with substantial knowledge gaps on all aspect of MPX. In turn, analysis of risk perception suggested a substantial overlooking of MPX as a pathogen, particularly when compared to SARS-CoV-2, TB, HIV, and HBV. Overall, 58.6% of respondents were somehow favorable to implement variola vaccination in order to prevent MPX, and the main effectors of this attitude were identified in having been previously vaccinated against seasonal influenza (adjusted Odds Ratio [aOR] 6.443, 95% Confidence Interval [95%CI] 1.798–23.093), and being favorable to receive variola vaccine (aOR 21.416; 95%CI 7.290–62.914). In summary, the significant extent of knowledge gaps and the erratic risk perception, associated collectively stress the importance of appropriate information campaigns among first-line medical professionals. Full article

Integrated Vector Management (IVM) has yielded exemplary results in combating and preventing vector-borne diseases (VBDs) and their vectors. It’s success and positive outcomes depend on the sound planning, implementation, enforcement, and validation of the locally adapted vector control efforts from the involved national sectors and stakeholders. Nevertheless, current realities create several implications impeding IVM’s performance. Hence, there is a need to adjust local IVM plans to several factors, such as (i) the rapidly changing and unpredictable environmental conditions (i.e., climate change, shift on species distribution, invasive species—Anopheles stephensi, Aedes aegypti and Ae. albopictus); (ii) the environmental impacts from human activities (i.e., fossil fuel use, food sources, industry, land use, urbanization and deforestation); (iii) changes in human demographics and the international movement of people (travelers and forcibly displaced persons due to conflicts and severe weather) increasing the risk of contracting and transmitting vector-borne diseases and shifting humanitarian emergencies and societal demands; (iv) the SARS-CoV2 pandemic outbreak and the implication on national public health systems; (v) the continuous flow of technological advancements and newly acquired knowledge; (vi) the realization of the strong link between planetary health and public health. Addressing these factors in IVM can become difficult, taking into consideration the numerous involved sectors, stakeholders, and fields in the management of vectors and vector-borne diseases (VBD). This document proposes and discusses the aspects and steps of a holistic approach, referenced as the Circular Policy, for national and local IVM strategies to be effective and adaptable, capable of providing the optimum outcomes. Full article

We report the first pediatric disease in which the use of minimally invasive autopsy (MIA) confirmed severe dengue as the cause of death. During the COVID-19 pandemic, a previously healthy 10-year-old girl living in north-eastern Brazil presented fever, headache, diffuse abdominal pain, diarrhoea, and vomiting. On the fourth day, the clinical symptoms worsened and the patient died. An MIA was performed, and cores of brain, lungs, heart, liver, kidneys, and spleen were collected with 14G biopsy needles. Microscopic examination showed diffuse oedema and congestion, pulmonary intra-alveolar haemorrhage, small foci of midzonal necrosis in the liver, and tubular cell necrosis in the kidneys. Dengue virus RNA and NS1 antigen were detected in blood and cerebrospinal fluid samples. Clinical, pathological, and laboratory findings, in combination with the absence of other lesions and microorganisms, allowed concluding that the patient had died from complications of severe dengue. Full article

The prevention of malaria in travelers with the use of antimalarials often occurs in connection with international travel to areas of significant risk of infection. Although these travelers sometimes cause outbreaks in their malaria-free home countries, the cardinal objective of prescribed chemoprophylaxis is to protect the traveler from patent malaria during travel. Here we consider the chemoprophylaxis of domestic travelers from malaria-free but -receptive areas within malaria-endemic countries. The main objective in this setting is the protection of those areas from reintroduced malaria transmission. In order to better understand policy and practices in this regard, we surveyed malaria prevention and treatment guidelines of 36 malaria-endemic countries and 2 that have recently eliminated malaria (Sri Lanka, China) for recommendations regarding malaria chemoprophylaxis for domestic travel. Among them, just 8 provided specific and positive recommendations, 1 recommended without specific guidance, and 4 advised against the practice. Most nations (25/38; 66%) did not mention chemoprophylaxis for domestic travel, though many of those did offer guidance for international travel. The few positive recommendations for domestic travel were dominated by the suppressive prophylaxis options of daily doxycycline or atovaquone-proguanil or weekly mefloquine. The incomplete protection afforded by these strategies, along with impractical dosing in connection with the typically brief domestic travel, may in part explain the broad lack of policies and practices across malaria-endemic nations regarding chemoprophylaxis. Full article

The elimination of lymphatic filariasis (LF) is achieved through repeated mass drug administration (MDA) of anti-filarial medications, which interrupts transmission and prevents new infections. Accurate transmission assessments are critical to deciding when to stop MDA. Current methods for evaluating transmission may be insufficiently sensitive, resulting in post-MDA resurgence. We, therefore, evaluated potential diagnostic testing scenarios for post-MDA surveillance. Data were used from two surveys (a household cluster and a cohort) conducted in an area of Mandalay Region, Myanmar, with ongoing transmission following several rounds of MDA. First, age- and sex-adjusted seroprevalence were estimated for the area using the household survey. Next, three Bayesian networks were built from the combined datasets to compare antigens by immunochromatic testing (ICT) and/or Og4C3 enzyme-linked immunosorbent assay (ELISA) and antibody (Ab) detection methods (Wb123 or Bm14 Ab ELISA). The networks were checked for validity and then used to compare diagnostic testing scenarios. The adjusted prevalence from the household survey for antigen, Wb123 Ab and Bm14 Ab were 4.4% (95% CI 2.6–7.3%), 8.7% (5.96–12.5%) and 20.8% (16.0–26.6%), respectively. For the three networks, the True Skill Statistic and Area Under the Receiver Operating Characteristic Curve for antigen, Wb123 and Bm14 Ab were 0.79, 0.68 and 0.55; and 0.97, 0.92 and 0.80, respectively. In the Bayesian network analysis, a positive case was defined as testing positive to one or more infection markers. A missed result was therefore the probability of a positive case having a negative test result to an alternate marker. The probability of a positive case prior to any testing scenario was 17.4%, 16.8% and 26.6% for antigen, Wb123 Ab and Bm14 Ab, respectively. In the antigen-only testing scenario, the probability of a missed positive LF result was 5.2% for Wb123 and 15.6% for Bm14 Ab. The combination of antigen plus Bm14 Ab testing reduced the probability of missing a positive LF case as measured by Wb123 Ab to 0.88%. The combination of antigen plus Wb123 Ab was less successful and yielded an 11.5% probability of a missed positive result by Bm14 Ab testing. Across scenarios, there was a greater discordance between Bm14 and both antigen and Wb123 Ab in the 1–10 age group compared to older ages. These findings suggest that the addition of Bm14 Ab improves the sensitivity of LF testing for current or past infection. The combination of antigen plus Bm14 Ab should therefore be considered for inclusion in post-MDA surveillance to improve the sensitivity of transmission surveys and prevent the premature cessation of MDA. Full article

The COVID-19 pandemic and public health response to the pandemic has caused huge setbacks in the management of other infectious diseases. In the present study, we aimed to (i) assess the trends in numbers of samples from patients with influenza-like illness and severe acute respiratory syndrome tested for influenza and the number and proportion of cases detected from 2015–2021 and (ii) examine if there were changes during the COVID-19 period (2020–2021) compared to the pre-COVID-19 period (2015–2019) in three states of India. The median (IQR) number of samples tested per month during the pre-COVID-19 period was 653 (395–1245), compared to 27 (11–98) during the COVID-19 period (p value < 0.001). The median (IQR) number of influenza cases detected per month during the pre-COVID-19 period was 190 (113–372), compared to 29 (27–30) during the COVID-19 period (p value < 0.001). Interrupted time series analysis (adjusting for seasonality and testing charges) confirmed a significant reduction in the total number of samples tested and influenza cases detected during the COVID-19 period. However, there was no change in the influenza positivity rate between pre-COVID-19 (29%) and COVID-19 (30%) period. These findings suggest that COVID-19-related disruptions, poor health-seeking behavior, and overburdened health systems might have led to a reduction in reported influenza cases rather than a true reduction in disease transmission. Full article

Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain–Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8⁺T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host’s immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus’ ability to cross both the blood–brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host’s immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection. Full article

Rabies is a viral zoonosis that causes an estimated 59,000 preventable human fatalities every year. While more than 120 countries remain endemic for dog-mediated rabies, the burden is the highest in Africa and Asia where 99% of human rabies cases are caused by domestic dogs. One such rabies-endemic country is South Africa where an estimated 42 preventable human deaths occur every year. Although canine rabies had been well described for most of the provinces in South Africa, the epidemiology of rabies within the North West Province had not been well defined prior to this investigation. As such, the aim of this study was to use nucleotide sequence analyses to characterise the extant molecular epidemiology of rabies in the North West Province of South Africa—with specific focus on the interface between dogs and sylvatic species. To this end, Rabies lyssavirus isolates originating from the North West Province were subjected to molecular epidemiological analyses relying on the Bayesian Markov Chain Monte Carlo methodology on two distinct gene regions, viz. the G-L intergenic region and partial nucleoprotein gene. Our results provided strong evidence in support of an endemic cycle of canine rabies in the East of the province, and three independent endemic cycles of sylvatic rabies spread throughout the province. Furthermore, evidence of specific events of virus spill-over between co-habiting sylvatic species and domestic dogs was found. These results suggest that the elimination of canine-mediated rabies from the province will rely not only on eliminating the disease from the dog populations, but also from the co-habiting sylvatic populations using oral rabies vaccination campaigns. Full article

In Vietnam, the public health burden of rickettsial infections continues to be underestimated due to knowledge gaps in the epidemiology of these diseases. We conducted a systematic study among 27 hospitals from 26 provinces in eight ecological regions throughout Vietnam to investigate the prevalence, distribution, and clinical characteristics of rickettsial diseases. We recruited 1834 patients in the study from April 2018 to October 2019. The findings showed that rickettsial diseases were common among undifferentiated febrile patients, with 564 (30.8%) patients positive by qPCR for scrub typhus, murine typhus or spotted fever. Scrub typhus (484, 85.8%) was the most common rickettsial disease, followed by murine typhus (67, 11.9%) and spotted fever (10, 1.8%). Rickettsial diseases were widely distributed in all regions of Vietnam and presented with nonspecific clinical manifestations. Full article

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Until 2022, only six locally transmitted human JE cases had been reported in Australia; five in northern Queensland and one in the Northern Territory. Thus, JE was mainly considered to be a disease of travellers. On 4 March 2022, JE was declared a ‘Communicable Disease Incident of National Significance’ when a locally acquired human case was confirmed in southern Queensland. By 11 May 2022, 41 human JE cases had been notified in four states in Australia, in areas where JE has never been detected before. From this perspective, we discuss the potential reasons for the recent emergence of the JE virus in Australia in areas where JE has never been previously reported as well as the implications of and options for mass immunisation programs if the outbreak escalates in a JE virus-immunologically naïve population. Full article

Background: During the COVID-19 pandemic, distinguishing dengue from COVID-19 in endemic areas can be difficult, as both may present as undifferentiated febrile illness. COVID-19 cases may also present with false-positive dengue serology. Hospitalisation protocols for managing undifferentiated febrile illness are essential in mitigating the risk from both COVID-19 and dengue. Methods: At a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, from January 2020 to December 2021. Results: A total of 6103 cases of COVID-19 and 1251 cases of dengue were managed at our institution, comprising a total of 3.9% (6103/155,452) and 0.8% (1251/155,452) of admissions, respectively. A surge in dengue hospitalisations in mid-2020 corresponded closely with the imposition of a community-wide lockdown. A total of 23 cases of PCR-proven COVID-19 infection with positive dengue serology were identified, of whom only two were true co-infections; both had been appropriately isolated upon admission. Average length-of-stay for dengue cases initially admitted to isolation during the pandemic was 8.35 days (S.D. = 6.53), compared with 6.91 days (S.D. = 8.61) for cases admitted outside isolation (1.44 days, 95%CI = 0.58–2.30, p = 0.001). Pre-pandemic, only 1.6% (9/580) of dengue cases were admitted initially to isolation-areas; in contrast, during the pandemic period, 66.6% (833/1251) of dengue cases were initially admitted to isolation-areas while awaiting the results of SARS-CoV-2 testing. Conclusions: During successive COVID-19 pandemic waves in a dengue-endemic country, coinfection with dengue and COVID-19 was uncommon. Routine COVID-19 testing for febrile patients with viral prodromes mitigated the potential infection-prevention risk from COVID-19 cases, albeit with an increased length-of-stay for dengue hospitalizations admitted initially to isolation. Full article

(1) Background: Every year, 2.5 million neonates die, mostly in low- and middle-income countries (LMIC), in total disregard of their fundamental human rights. Many of these deaths are preventable. For decades, the leading causes of neonatal mortality (prematurity, perinatal hypoxia, and infection) have been known, so why does neonatal mortality fail to diminish effectively? A bottom-up understanding of neonatal morbi-mortality and neonatal rights is essential to achieve adequate progress, and so is increased visibility. (2) Methods: We performed an overview on the leading causes of neonatal morbi-mortality and analyzed the key interventions to reduce it with a bottom-up approach: from the clinician in the field to the policy maker. (3) Results and Conclusions: Overall, more than half of neonatal deaths in LMIC are avoidable through established and well-known cost-effective interventions, good quality antenatal and intrapartum care, neonatal resuscitation, thermal care, nasal CPAP, infection control and prevention, and antibiotic stewardship. Implementing these requires education and training, particularly at the bottom of the healthcare pyramid, and advocacy at the highest levels of government for health policies supporting better newborn care. Moreover, to plan and follow interventions, better-quality data are paramount. For healthcare developments and improvement, neonates must be acknowledged as humans entitled to rights and freedoms, as stipulated by international law. Most importantly, they deserve more respectful care. Full article

While chronic schistosomiasis is pathologically well defined, the acute form of the disease is less well understood. It is generally agreed that early lesions, such as lung nodules and bladder polyps, are reversible, which impedes identification of the time elapsed since exposure. The intermediate stage between the acute and the chronic forms of schistosomiasis requires further investigation, as does the clinical stage due to lesions remaining after treatment. With current schistosomiasis control efforts gradually progressing to elimination, there is a need to focus on post-transmission schistosomiasis, which not only refers to remaining lesions from previous infections, but also accounts for the potential presence of surviving worms after treatment. This issue is particularly salient for migrants from endemic to non-endemic countries and should be kept in mind for returning expatriates from schistosomiasis-endemic countries. Negative stool examination or urine filtration are generally taken as indicative of cure since rectoscopy for Schistosoma mansoni infection, or cystoscopy for S. haematobium infection, are rarely performed. However, pathology of affected organs may persist indefinitely, while potentially remaining live worms could produce additional pathology. Hence, post-transmission schistosomiasis can prevail for years after elimination of the disease, and thus, warrant further attention. Full article

Leishmaniasis is a parasitic, widespread, and neglected disease that affects more than 90 countries in the world. More than 20 Leishmania species cause different forms of leishmaniasis that range in severity from cutaneous lesions to systemic infection. The diversity of leishmaniasis forms is due to the species of parasite, vector, environmental and social factors, genetic background, nutritional status, as well as immunocompetence of the host. Here, we discuss the role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis, focusing on innate immune cells and Leishmania major interactions. Full article