Tropical Medicine and Infectious Disease

Background: Motivated by a case finding of Mediterranean spotted fever (MSF) associated with atypical pneumonia and pleural effusion in which Rickettsia conorii subsp. israelensis was identified by molecular methods in the pleural fluid, we wanted to summarize the clinical presentations of rickettsiosis in Italy by systematic research and to make a systematic review of all the global cases of rickettsiosis associated with pleural effusion. Methods: For the literature search, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. We chose to select only the studies published in last 25 years and confirmed both with serological and molecular assays. Results: Human cases of rickettsiosis in Italy were reported in 48 papers describing 2831 patients with very different clinical presentations; the majority was MSF accounted to R. conorii and was reported in Sicily. Pleural effusion associated with infection with microorganisms belonging to Rickettsiales was described in 487 patients. It was rarely associated with microorganisms different from O. tsutsugamushi; also rarely, cases of scrub typhus were reported outside Southeast Asia and in the largest majority, the diagnosis was achieved with serology. Conclusions: MSF, especially when caused by R. conorii subsp. israelensis, may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis Full article

Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010–2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187–0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314–0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015–2019 (risk ratio [RR] 1.808, 95% CI 1.594–2.051) and even during 2020–2021 (RR 1.771, 95% CI 1.238–2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036–1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165–1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338–1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555–3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures. Full article

The number of people vaccinated against COVID-19 increases worldwide every day; however, it is important to study the risk of breakthrough infections in vaccinated individuals at high risk of exposure such as healthcare personnel (HCP). A systematic literature review (SLR) applying the PRISMA declaration and the PECOS format using the following entry terms was used: “Health Personnel OR Healthcare Worker OR Healthcare Provider OR Healthcare Personnel AND breakthrough OR infection after vaccine*”. The research was carried out utilizing the following databases: SCOPUS, PubMed, Embase, and Web of Sciences. An overall very low incidence of post-vaccination breakthrough infections was found, ranging from 0.011 to 0.001 (per 100 individuals at risk). Our findings further support the published high effectiveness rates of mRNA vaccines in preventing SARS-CoV-2 infections among fully vaccinated HCP. Additional studies are needed to define the duration of the vaccine-induced protection among HCP. Full article

Trypanosoma cruzi infection leads to Chagas disease (CD), a neglected tropical infection of significant public health importance in South and Central America and other, non-endemic, countries. Pregnant women and their children are of particular importance to screen as T. cruzi can be transmitted vertically. The objective of this study was to screen for T. cruzi infection among pregnant women from endemic areas seen at the Hospital General de Mexico for prenatal care, so that they and their children may be quickly connected to CD treatment. Pregnant women were recruited through the hospital prenatal clinic and screened for T. cruzi infection using a series of serological and molecular tests. Of 150 screened patients, mean age 26.8 (SD 6.4), 30 (20.0%) were positive by at least one diagnostic test. Of these, only nine (6%) were positive as determined by PCR. Diagnosis of chronic CD is difficult in endemic places like Mexico due to the limitations of current commercially available diagnostic tests. Further evaluation of diagnostic performance of various assays could improve current CD diagnostic algorithms and proper care management in these regions. Genetic variability in the parasite may also play a role in the differing assay performances seen in this study, and this may be a valuable avenue of further research. Full article

Rapid identification of patients likely to develop pulmonary complications in severe leptospirosis is crucial to prompt aggressive management and improve survival. The following article is a cohort study of leptospirosis patients admitted at the National Kidney and Transplant Institute (NKTI). Logistic regression was used to predict pulmonary complications and obtain a scoring tool. The Kaplan–Meir method was used to describe survival rates. Among 380 patients with severe leptospirosis and kidney failure, the overall mortality was 14%, with pulmonary hemorrhage as the most common cause. In total, there were 85 (22.4%) individuals who developed pulmonary complications, the majority (95.3%) were observed within three days of admission. Among the patients with pulmonary complications, 56.5% died. Patients placed on mechanical ventilation had an 82.1% mortality rate. Multivariate analyses showed that dyspnea (OR = 28.76, p < 0.0001), hemoptysis (OR = 20.73, p < 0.0001), diabetes (OR = 10.21, p < 0.0001), renal replacement therapy (RRT) requirement (OR = 6.25, p < 0.0001), thrombocytopenia (OR = 3.54, p < 0.0029), and oliguria/anuria (OR = 3.15, p < 0.0108) were significantly associated with pulmonary complications. A scoring index was developed termed THe-RADS score (Thrombocytopenia, Hemoptysis, RRT, Anuria, Diabetes, Shortness of breath). The odds of developing pulmonary complications were 13.90 times higher among patients with a score >2 (63% sensitivity, 88% specificity). Pulmonary complications in severe leptospirosis with kidney failure have high mortality and warrant timely and aggressive management. Full article

Quantitative real-time PCR and genomic sequencing have become mainstays for performing molecular detection of biological threat agents in the field. There are notional assessments of the benefits, disadvantages, and challenges that each of these technologies offers according to findings in the literature. However, direct comparison between these two technologies in the context of field-forward operations is lacking. Most market surveys, whether published in print form or provided online, are directed to product manufacturers who can address their respective specifications and operations. One method for comparing these technologies is surveying end-users who are best suited for discussing operational capabilities, as they have hands-on experience with state-of-the-art molecular detection platforms and protocols. These end-users include operators in military defense and first response, as well as various research scientists in the public sector such as government and service laboratories, private sector, and civil society such as academia and nonprofit organizations performing method development and executing these protocols in the field. Our objective was to initiate a survey specific to end-users and their feedback. We developed a questionnaire that asked respondents to (1) determine what technologies they currently use, (2) identify the settings where the technologies are used, whether lab-based or field-forward, and (3) rate the technologies according to a set list of criteria. Of particular interest are assessments of sensitivity, specificity, reproducibility, scalability, portability, and discovery power. This article summarizes the findings from the end-user perspective, highlighting technical and operational challenges. Full article

Managing substantial proximal and/or distal femoral bone defects is one of the biggest challenges in chronic hip periprosthetic joint infection. Most authors use two-stage arthroplasty with a temporary antibiotic-loaded cement spacer for the management of these patients. In this study, we show our experience with one-stage exchange arthroplasty in managing severe bone defects due to radiological-extensive proximal femoral osteomyelitis. Two patients were included in the study. They showed radiological-extensive proximal femoral osteomyelitis, and they were treated with one-stage exchange arthroplasty using megaprosthesis. Diffuse osteomyelitis was confirmed in both cases; in one case, the histology was compatible with osteomyelitis, and the other case had a positive culture identified in a bone sample. At a minimum of a four-year follow-up, the patients did not reveal any clinical, radiological or laboratory signs of infection. In conclusion, one-stage exchange arthroplasty and megaprosthesis is an option for the treatment of chronic hip periprosthetic joint infection associated with radiological-diffuse proximal femoral osteomyelitis. Full article

This paper discusses the contributions that One Health principles can make in improving global response to zoonotic infectious disease. We highlight some key benefits of taking a One Health approach to a range of complex infectious disease problems that have defied a more traditional sectoral approach, as well as public health policy and practice, where gaps in surveillance systems need to be addressed. The historical examples demonstrate the scope of One Health, partly from an Australian perspective, but also with an international flavour, and illustrate innovative approaches and outcomes with the types of collaborative partnerships that are required. Full article

(1) Background: This study aims to assess the magnitude of, and factors associated with, depression and anxiety among Vietnamese frontline hospital healthcare workers in the fourth wave of COVID-19; (2) Methods: A hospital based cross-sectional study was carried out within two weeks, October 2020, at a central COVID-19 treatment hospital. Depression and anxiety were measured with PHQ-9 and GAD-7, respectively. Bivariate and multivariate logistic regression analysis were applied to recognize variables related to depression and anxiety, respectively; (3) Results: Among 208 frontline hospital healthcare workers, overall prevalence of depressive symptoms, anxiety symptoms, and both symptoms of depression and anxiety was 38.94%, 25.48% and 24.04%, respectively, in healthcare workers. In a reduced model after using multivariate stepwise logistic regression, age (OR = 0.9, p = 0.001), marital status (OR = 7.84, p = 0.027), profession (OR = 0.39, p = 0.028), having experienced traumatic stress following a work event (OR = 46.24, p < 0.001), feeling at very high risk for COVID-19 (OR = 0.02, p < 0.04), and affected by workplace conditions (OR = 5.36, p < 0.001) were associated with the symptoms of depression. With regard to symptoms of anxiety, single status (OR: 12.18, p = 0.002), being medical technician (OR: 68.89, p < 0.001), alcohol use (OR: 6.83, p = 0.014), using pain relief medications (OR: 25.50, p = 0.047), having experienced traumatic stress following a family event (OR: 130.32, p = 0.001), having experienced traumatic stress following a work event (OR: 181.55, p = 0.002), reporting at very high risk for COVID-19 (OR: 29.64, p = 0.011), treating moderate (OR: 6.46, p = 0.038) and severe (OR: 18.96, p = 0.004) COVID-19 patients, and being significantly affected by the community (OR: 6.33, p = 0.003) were increased risk factors for the symptoms of anxiety. Meanwhile, those living with 4–5 people (OR: 0.15, p = 0.011), specializing in infectious disease (OR: 0.13, p = 0.044)/resuscitation and emergency medicine (OR: 0.04, p = 0.046), and having knowledge preparation before participating in COVID-19 (OR: 0.008, p = 0.014) were less associated with the symptoms of anxiety; (4) Conclusions: There was a relatively high prevalence among Vietnamese hospital healthcare workers exhibiting symptoms of depression and anxiety during the ongoing pandemic. Greater attention to training in psychological skills should be suggested for those belonging to a younger age group, being single/widowed/divorced, treating moderate and severe COVID-19 patients, feeling at very high risk for COVID-19, being significantly affected a lot the community or workplace conditions, or experiencing traumatic stress following a family/work event in the past week. Full article

Tungiasis is a cutaneous parasitosis caused by an embedded female sand flea. The distribution of cases can be spatially heterogeneous even in areas with similar risk profiles. This study assesses household and remotely sensed environmental factors that contribute to the geographic distribution of tungiasis cases in a rural area along the Southern Kenyan Coast. Data on household tungiasis case status, demographic and socioeconomic information, and geographic locations were recorded during regular survey activities of the Health and Demographic Surveillance System, mainly during 2011. Data were joined with other spatial data sources using latitude/longitude coordinates. Generalized additive models were used to predict and visualize spatial risks for tungiasis. The household-level prevalence of tungiasis was 3.4% (272/7925). There was a 1.1% (461/41,135) prevalence of infection among all participants. A significant spatial variability was observed in the unadjusted model (p-value < 0.001). The number of children per household, earthen floor, organic roof, elevation, aluminum content in the soil, and distance to the nearest animal reserve attenuated the odds ratios and partially explained the spatial variation of tungiasis. Spatial heterogeneity in tungiasis risk remained even after a factor adjustment. This suggests that there are possible unmeasured factors associated with the complex ecology of sand fleas that may contribute to the disease’s uneven distribution. Full article

The objective of this pilot malacological survey was to identify the snail intermediate hosts for Schistosoma haematobium in endemic rural and semi-urban areas of Gabon. Snails were collected, morphologically identified, and tested for infection by cercarial shedding. Released cercariae were morphologically identified using low-power light microscopy. A total of six species of snails were collected throughout the study area, with Bulinus truncatus, B. forskalii, and Potadoma spp. being the most predominant species collected. Only the Bulinus species were tested for infection by cercarial shedding, of which only B. truncatus shed cercariae. Some B. truncatus shed mammalian schistosome cercariae, while others shed Gymnocephalus cercariae. Our results indicate that B. truncatus appears to be a potential intermediate host of schistosomiasis in Gabon, where cases of S. haematobium, S. guineensis, and S. intercalatum infection are reported. However, it will be important to further understand the species diversity and transmission dynamics of schistosomes. Full article

The burden of AIDS-defining cancers has remained relatively steady for the past two decades, whilst the burden of non-AIDS-defining cancer has increased. Here, we conduct a study to describe mortality trends attributed to HIV-associated cancers in 31 countries. We extracted HIV-related cancer mortality data from 2001 to 2018 from the World Health Organization Mortality Database. We computed age-standardized death rates (ASDRs) per 100,000 population using the World Standard Population. Data were visualized using Locally Weighted Scatterplot Smoothing (LOWESS). Data for females were available for 25 countries. Overall, there has been a decrease in mortality attributed to HIV-associated cancers among most of the countries. In total, 18 out of 31 countries (58.0%) and 14 out of 25 countries (56.0%) showed decreases in male and female mortality, respectively. An increasing mortality trend was observed in many developing countries, such as Malaysia and Thailand, and some developed countries, such as the United Kingdom. Malaysia had the greatest increase in male mortality (+495.0%), and Canada had the greatest decrease (−88.5%). Thailand had the greatest increase in female mortality (+540.0%), and Germany had the greatest decrease (−86.0%). At the endpoint year, South Africa had the highest ASDRs for both males (16.8/100,000) and females (19.2/100,000). The lowest was in Japan for males (0.07/100,000) and Egypt for females (0.028/100,000). Full article

Myocarditis represents a potential complication of various infectious and noninfectious agents and a common diagnostic challenge for clinicians. Data regarding Campylobacter-associated myocarditis are limited. Here, a case of a 13-year-old female with Campylobacter jejuni gastroenteritis complicated by myocarditis is presented, followed by a literature review in order to retrieve information about Campylobacter-associated carditis in the pediatric population. A search on MEDLINE/PubMed yielded 7relevant cases in the last 20 years. Most of them (six/seven) were males and the mean age was 16.1 years. All patients presented with gastrointestinal symptoms followed in six/seven cases by chest pain within two to seven days. Campylobacter was isolated from stool cultures in six patients; abnormal electrocardiographic findings were detected in six; and abnormal echocardiographic findings in three of the cases. Five patients were treated with antibiotics. Full recovery was the clinical outcome in six patients, whereas one patient died. Concerning the nonspecific symptoms of patients with myocarditis, high clinical suspicion of this complication is necessary in cases where patients with a recent infection present with chest pain and elevated cardiac biomarkers. Full article

Nodding syndrome (NS) is a debilitating yet often neglected neurological disease affecting thousands of children in several sub-Saharan African countries. The cause of NS remains unknown, and effective treatment options are lacking. Moreover, knowledge regarding NS is scarce and is based on a limited number of publications, with no comprehensive overview published to date. Therefore, the aim of this scoping review was to summarise the current evidence and identify existing knowledge gaps in order to help clinicians, scientists, and policymakers develop guidelines for prioritising this severe condition. We searched the Medline (Ovid), Embase (Ovid), Scopus, and Global Health Library databases in accordance with the PRISMA extension for scoping review guidance and in accordance with the Joanna Briggs Institute guidelines and methodology for a scoping review, using keywords describing NS. We then extracted and presented the original data regarding the epidemiology, aetiology, pathophysiology, clinical features, diagnosis, management, and outcomes of NS, as well as community perceptions and the psychosocial and economic impact of NS. Out of 1470 identified articles, a total of 69 were included in this scoping review. Major gaps exist in understanding the aetiology and pathogenesis of NS. Future research is urgently needed not only to address these gaps, but also to study the treatment options, epidemiology, and psychosocial and economic impacts of NS. Innovative interventions and rehabilitation programmes designed to address the psychosocial and economic burdens associated with NS are also urgently needed. Full article

Cryptosporidium species are intestinal protozoan parasites that infect and cause diarrhoea in animals and humans. The current study was conducted to determine the prevalence and risk factors of Cryptosporidium infection among HIV-infected patients in the Central region of Ghana. In this cross-sectional study, four hundred eighteen documented HIV-infected participants from four health facilities that provide antiretroviral therapy (ART) services across the Central region of Ghana were selected by systematic random sampling. An enzyme-linked immunosorbent assay (CoproELISA^TM, Cryptosporidium Savyon^® Diagnostics Ltd., Ashdod, Israel) was used to detect Cryptosporidium antigens in stool samples obtained from participants. Information regarding participants’ sociodemographic characteristics and clinical symptoms as well as potential environmental and behavioral risk factors were collected using a structured questionnaire. Chi-square or Fisher’s exact tests were used to determine associations between Cryptosporidium infections and explanatory variables, while risk factors were assessed using multivariate logistic regression analysis. The overall prevalence of Cryptosporidium infection among HIV-infected participants in this study was 6.2% (95% CI: 3.90–8.54). Cryptosporidium was not significantly associated with any of the sociodemographic variables, patient clinical symptoms, and environmental factors. However, the prevalence of the parasite was significantly higher 25% (95% CI: 1.17–48.83; p = 0.013) among participants who did not always wash their hands before meals and those who did not always wash vegetables before eating them, 23.5% (95% CI: 1.05–46.01; p = 0.016). Multivariate logistic regression analysis showed that participants who used public water closet facilities were approximately 9 times more likely to become infected with the parasite than those who practised open defecation (OR: 8.83; 95% CI: 1.22–64.13; p = 0.031). In conclusion, Cryptosporidium is prevalent among HIV-infected patients in the Central region of Ghana. An important risk factor identified was the use of the public water closet toilet facility. More attention should be given to ensuring cleanliness at shared water closet facilities in addition to adequate disinfection of hands after using such facilities. Full article

Rabies transmitted by sylvatic populations has become an increasing concern in Brazil. A total of 113 participants with a history of contact with sylvatic populations were interviewed in 27 municipalities of Ceará State in northeast Brazil. Questionnaires included questions on knowledge, attitudes and practices (KAP) regarding sylvatic rabies. Most of the respondents (92%) knew about rabies and confirmed at least one species that transmitted the disease (79.6%). Of these respondents, 69% mentioned monkeys, and 67.2% mentioned dogs. However, 16% of the respondents listed an incorrect species. In general, knowledge on the symptoms and signs and on prevention measures was weak. The majority raised pets (93.8%), most commonly dogs and cats, and, of all the pets, 85.7% were claimed to be vaccinated against rabies. A total of 67.3% reported the appearance of free-living wild animals around their houses, mostly marmosets and wild canids; 18.3% reported that sylvatic populations had attacked animals or humans. Seventy-three percent had raised or still were raising wild animals as pets, mostly capuchin monkeys (79.5%) and marmosets (24.1%). This is the first KAP study on sylvatic rabies in Brazil. The data indicate important knowledge gaps and risk behavior within a high-risk population. There is a need for strengthening and improving sylvatic rabies surveillance and control, combined with the intensification of education and information campaigns. Full article

Scrub typhus is a neglected tropical disease predominantly occurring in Asia. The causative agent is a bacterium transmitted by the larval stage of mites found in rural vegetation in endemic regions. Cases of scrub typhus frequently present as acute undifferentiated febrile illness, and without early diagnosis and treatment, the disease can develop fatal complications. We retrospectively reviewed de-identified data from a 23-year-old woman who presented to an emergency department with complaints of worsening abdominal pain. On presentation, she appeared jaundiced and toxic-looking. Other positive findings on abdominal examination were a positive Murphey’s sign, abdominal guarding and hepatosplenomegaly. Magnetic resonance cholangiopancreatography demonstrated acalculous cholecystitis. Additional findings included eschar on the medial aspect of the left thigh with inguinal regional lymphadenopathy. Further, positive results were obtained for immunoglobulins M and G, confirming scrub typhus. The workup for other infectious causes of acute acalculous cholecystitis (AAC) detected antibodies against human herpesvirus 4 (Epstein–Barr virus), suggesting an alternative cause of AAC. Whether that represented re-activation of the Epstein–Barr virus could not be determined. As other reports have described acute acalculous cholecystitis in adult scrub typhus patients, we recommend doxycycline to treat acute acalculous cholecystitis in endemic regions while awaiting serological confirmation. Full article

Coccidioidomycosis (CM), caused by the dimorphic fungi Coccidioides immitis and C. posadasii, typically presents as acute or chronic pulmonary disease. However, disseminated disease occurs in about 1% of patients. Disseminated CM may affect multiple organ systems, including cutaneous, osteoarticular, and central nervous system sites. Here, we present a case of disseminated CM in a patient from a border city in Texas. The patient had a history of uncontrolled diabetes mellitus and was also taking an over-the-counter medication acquired in Mexico that contained a potent corticosteroid. The patient presented with seizures and was found to have a brain infarct, cavitary lung lesions, synovitis of the knee, multiple skin lesions, and chorioretinitis. The patient had a very high complement fixation titer for Coccidioides; fungal spherules were seen in a skin biopsy specimen, and Coccidioides grew in culture from a sample of synovial fluid and the skin biopsy specimen. This case illustrates the dissemination potential of Coccidioides, the danger of unregulated pharmaceuticals, the importance of thorough history taking, and recognizing risk factors that contribute to disseminated CM. Full article

India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP’s minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017–2019) and five implementing partner agencies (2013–2020), with summary national data on the state-wise ACF outcomes for 2018–2020 published in annual reports by the NTEP. The data revealed variations in the strategies used to map and screen vulnerable populations and the diagnostic algorithms used across the states and union territories. National data were unavailable to assess whether the NTEP indicators for the minimum proportions identified with presumptive TB among those screened (5%), those with presumptive TB undergoing diagnostic tests (>95%), the minimum sputum smear positivity rate (2% to 3%), those with negative sputum smears tested with chest X-rays or CBNAAT (>95%) and those diagnosed through ACF initiated on anti-TB treatment (>95%) were fulfilled. Only 30% (10/33) of the states in 2018, 23% (7/31) in 2019 and 21% (7/34) in 2020 met the NTEP expectation that 5% of those tested through ACF would be diagnosed with TB (all forms). The number needed to screen to diagnose one person with TB (NNS) was not included among the NTEP’s programme indicators. This rough indicator of the efficiency of ACF varied considerably across the states and union territories. The median NNS in 2018 was 2080 (interquartile range or IQR 517–4068). In 2019, the NNS was 2468 (IQR 1050–7924), and in 2020, the NNS was 906 (IQR 108–6550). The data consistently revealed that the states that tested a greater proportion of those screened during ACF and used chest X-rays or CBNAAT (or both) to diagnose TB had a higher diagnostic yield with a lower NNS. Many implementation challenges, related to health systems, healthcare provision and difficulties experienced by patients, were elicited. We suggest a series of strategic interventions addressing the implementation challenges and the six gaps identified in ACF outcomes and the expected indicators that could potentially improve the efficacy and effectiveness of community-based ACF in India. Full article