Neglected etiologies of prolonged febrile illnesses in tropical and subtropical regions: A systematic review.

BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments. METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias. RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles. CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.

Snakebite envenoming at MSF: A decade of clinical challenges and antivenom access issues.

The medical humanitarian organization Médecins Sans Frontières (MSF) provides medical care in more than 70 countries and admits more than 7000 cases of snakebite in its facilities each year. We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects. The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.

Corrigendum to "Snakebite envenoming in humanitarian crises and migration: A scoping review and the Médecins Sans Frontières experience" [Toxicon: X 13 (March 2022) 100089].

[This corrects the article DOI: 10.1016/j.toxcx.2021.100089.].

[Newly arrived refugees suffer from infectious diseases, deficiencies and poor mental health].

Refugees arrive in Denmark by different paths and canals. In some municipalities all refugees are offered a systematic health assessment when they receive a residence permit. The conducted assessments in Copenhagen and Aarhus have resulted in five studies and this review sums up some of the important results. Vitamin-D deficiencies, anaemia, latent tuberculosis, and symptoms of PTSD are just some of the most frequent conditions seen in newly arrived refugees. A health assessment upon resettlement has several important purposes and should be offered to all newly arrived refugees in Denmark.

Snakebite envenoming in humanitarian crises and migration: A scoping review and the Médecins Sans Frontières experience.

Snakebite envenoming is a public health concern in many countries affected by humanitarian crises. Its magnitude was recognized internationally but associations between snakebite peaks and humanitarian crises were never clearly established or analysed. This scoping review searched any available evidence of this hypothesized association between snakebite types of crises, through PubMed/Medline by two researchers. The search also included hand searching, and reports from humanitarian organizations working in this area. The scoping review yielded 41 results. None described a robust epidemiological link or evidence of causality. There is an evidence gap regarding our research question. Several publications however point or hint towards the occurrence of snakebite outbreaks during conflict, displacement, floods, and migration of impoverished agricultural workers. Non-systematic screening yielded another 11 publications (52 in total). We found Médecins Sans Frontières routine reports showing that 6469 patients were admitted in 2019 throughout its projects in 17 countries. The impact of snakebite was the highest in four countries particularly affected by humanitarian crises, South Sudan, Ethiopia, Central African Republic, and Yemen, with some hospitals receiving more than 1000 annual admissions. Time correlations with conflict and events are shown in Figures. We found no published epidemiological data formally showing any associations between humanitarian crises and snakebite incidence. However, the search publications showing peaks during crises, and monitoring curves in four countries point towards an increased risk during humanitarian crises. We call for urgent population-based studies and surveillance. Stakeholders should consider upgrading snakebite care and antivenom supply during humanitarian crises in snakebite-endemic countries.

SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP.

Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30 × 109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post-SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated.

The Impact of Early-Life Exposures on Women's Reproductive Health in Adulthood.

PURPOSE OF REVIEW: To review the effects of early-life, preconception, and prior-generation exposures on reproductive health in women. RECENT FINDINGS: Women's early-life factors can affect reproductive health by contributing to health status or exposure level on entering pregnancy. Alternately, they can have permanent effects, regardless of later-life experience. Nutrition, social class, parental smoking, other adverse childhood experiences, environmental pollutants, infectious agents, and racism and discrimination all affect reproductive health, even if experienced in childhood or in utero. Possible transgenerational effects are now being investigated through three- or more-generation studies. These effects occur with mechanisms that may include direct exposure, behavioral, endocrine, inflammatory, and epigenetic pathways. SUMMARY: Pregnancy is increasingly understood in a life course perspective, but rigorously testing hypotheses on early-life effects is still difficult. In order to improve the health outcomes of all women, we need to expand our toolkit of methods and theory. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40471-021-00279-0.

Patterns of enrollment in a New Orleans women's substance use rehabilitation center.

BACKGROUND: Research has told us little about the demographics of individuals entering substance use programs in New Orleans, Louisiana, especially women accessing treatment programs. Considering that New Orleans is a predominantly Black city and both substance use treatment and research have historically left out Black patients, this study evaluates the age, race, insurance status, education level, and substance of choice for patients entering Grace House Rehabilitation Center, an all women nonprofit substance use treatment program in New Orleans, Louisiana. METHODS: Since 2013, Tulane School of Medicine students have held weekly primary care clinics at Grace House. This study used the clinic's patients' handwritten intake forms to collect demographic variables between 2013 and 2019. The study then evaluated the data using descriptive statistical analysis. RESULTS: The study analyzed 743 patient charts. We found that 78.4% of women admitted to Grace House were white (n = 627), and 14.5% of women were Black (n = 1160). The study excluded all other racial and ethnic groups due to the groups' small sample size. The average age at admittance was 34.7 years for both white and Black women; however, the average age for Black women was 42 years old. The 743 women studied reported the use of 1123 unique substances. While more than half of both populations used only one type of substance, Black women more commonly used only one substance. CONCLUSION: New Orleans is a predominantly Black community, yet young Black women are largely missing from the patient population that we studied. While multiple reasons exist for the lack of Black women in this population, Black substance-using women are clearly left out of the life-saving treatment that they deserve. The medical community must investigate further to make genuine, impactful changes to how substance use treatment is accessed by all minority groups, but especially Black women.

Health screening among children newly granted asylum in Denmark.

AIM: To describe the findings and recommendations of the general health assessment (GHA) of newly resettled refugee children in Denmark. METHODS: This cross-sectional study included children (aged <18 years) undergoing GHA from 2017 to 2019 at a university hospital Section of Immigrant Medicine. GHA was offered to all refugees newly resettled in the Municipality of Copenhagen. It comprised of a structured questionnaire, clinical examination, blood test and recommendations. RESULTS: In the study period, 107 children were eligible, 100 children had a GHA performed and of whom all were included in the study. Trauma was reported in 61% (n = 61/100) of children. The median duration of the asylum-seeking process was 18 months (IQR: 8-24), and the highest number of relocations was nine. Latent tuberculosis (n = 2/100 [2%]) was the only infectious disease diagnosed. Specific recommendations for follow-up were frequent and included referral to specialist departments (n = 26/100 [26%]), suggestions for family doctor (n = 96/100 [96%]) and for municipality (n = 62/100 [62%]). CONCLUSION: Self-reported trauma was frequent among 100 newly resettled refugee children. For most children, the asylum process was protracted and included several relocations. Specific follow-up recommendations were given to the vast majority. GHA may contribute to improving health, which could possibly support integration for the child and family.

Immune thrombocytopenia (ITP) World Impact Survey (iWISh): Patient and physician perceptions of diagnosis, signs and symptoms, and treatment.

Immune thrombocytopenia (ITP) is now well-known to reduce patients' health-related quality of life. However, data describing which signs and symptoms patients and physicians perceive as having the greatest impact are limited, as is understanding the full effects of ITP treatments. I-WISh (ITP World Impact Survey) was an exploratory, cross-sectional survey designed to establish the multifaceted impact of ITP, and its treatments, on patients' lives. It focused on perceptions of 1507 patients and 472 physicians from 13 countries regarding diagnostic pathway, frequency and severity of signs and symptoms, and treatment use. Twenty-two percent of patients experienced delayed diagnosis (caused by several factors), 73% of whom felt anxious as a result. Patients rated fatigue among the most frequent, severe symptom associated with ITP at diagnosis (58% most frequent; 73% most severe), although physicians assigned it lower priority (30%). Fatigue was one of the few symptoms persisting at survey completion (50% and 65%, respectively) and was the top symptom patients wanted resolved (46%). Participating physicians were experienced at treating ITP, thereby recognizing the need to limit corticosteroid use to newly-diagnosed or first-relapse patients and espoused increased use of thrombopoietin receptor agonists and anti-CD20 after relapse in patients with persistent/chronic disease. Patient and physicians were largely aligned on diagnosis, symptoms, and treatment use. I-WISh demonstrated that patients and physicians largely align on overall ITP symptom burden, with certain differences, for example, fatigue. Understanding the emotional and clinical toll of ITP on the patient will facilitate shared decision-management, setting and establishment of treatment goals and disease stage-appropriate treatment selection.

Poor Head Growth Is Associated with Later Mental Delay among Vietnamese Preterm Infants: A Follow-up Study.

BACKGROUND: Preterm infants in low- and middle-income countries are at high risk of poor physical growth, but their growth data are still scarce. OBJECTIVES: To describe the growth of Vietnamese preterm infants in the first 2 years, and to compare with references: World Health Organization (WHO) child growth standards, and healthy Southeast Asian (SEA) infants. Further, to assess the association between growth in the first year and neurodevelopment at 2 years corrected age (CA). METHODS: We conducted a cohort study to follow up preterm infants discharged from a neonatal intensive care unit for 2 years. Weight, length and head circumference (HC) were measured at 3, 12 and 24 months CA. Neurodevelopment was assessed using Bayley Scales of Infant and Toddler Development-3rd Edition at 24 months CA. RESULTS: Over 90% of the cohort showed catch-up weight at 3 months CA. Weight and length were comparable to healthy SEA but were lower than WHO standards. HC was significantly smaller than those of WHO standards with HC Z-scores steadily decreasing from -0.95 at 3 months CA to -1.50 at 24 months CA. Each one decrement of HC Z-score from 3 to 12 months CA was associated with nearly twice an increase in odds of mental delay at 24 months CA (odds ratio 1.89; 95% confidence interval 1.02-3.50). CONCLUSION: Vietnamese preterm infants exhibited early catch-up weight but poor head growth, which was associated with later delays in mental development. Our findings support the importance of HC measures in follow-up for preterm infants.

Immune thrombocytopenia (ITP) World Impact Survey (I-WISh): Impact of ITP on health-related quality of life.

Immune thrombocytopenia (ITP) has a substantial, multifaceted impact on patients' health-related quality of life (HRQoL). Data describing which aspects of ITP physicians and patients perceive as having the greatest impact are limited. The ITP World Impact Survey (I-WISh) was a cross-sectional survey, including 1507 patients and 472 physicians, to establish the impact of ITP on HRQoL and productivity from patient and physician perspectives. Patients reported that ITP reduced their energy levels (85% of patients), capacity to exercise (77%), and limited their ability to perform daily tasks (75%). Eighty percent of physicians reported that ITP symptoms reduced patient HRQoL, with 66% reporting ITP-related fatigue substantially reduced patient HRQoL. Patients believed ITP had a substantial impact on emotional well-being (49%) and 63% worried their condition would worsen. Because of ITP, 49% of patients had already reduced, or seriously considered reducing their working hours, and 29% had considered terminating their employment. Thirty-six percent of patients employed at the time of the survey felt ITP decreased their work productivity, while 51% of patients with high/very high symptom burden reported that ITP affected their productivity. Note, I-WISh demonstrated substantive impact of ITP on patients' HRQoL both directly for patients and from the viewpoint of their physicians. Patients reported reduced energy levels, expressed fears their condition might worsen, and those who worked experienced reduced productivity. Physicians should be aware not only of platelet counts and bleeding but also the multi-dimensional impact of ITP on patients' lives as an integral component of disease management.

Health status of refugees newly resettled in Denmark.

INTRODUCTION: The municipality of Copenhagen offers general health assessment (GHA) to all newly resettled refugees, conducted at the Section of Immigrant Medicine, Hvidovre Hospital. This study described their disease burden and sociodemographic characteristics. METHODS: In this cross-sectional study, all adult individuals assessed from 1 January 2017 to 30 January 2019 were included. Doctors performed the GHA, including a structured questionnaire, clinical examination and blood testing. RESULTS: In total, 160 refugees were included. Few suffered from communicable diseases (e.g., 1% hepatitis B virus) or other somatic diseases (4% diabetes Type 2). However, deficiencies such as vitamin D deficiency (76%), vitamin B12 deficiency (31%) and anaemia (12%) were frequent. The majority reported headache (54%) or other pain (53%). Furthermore, signs of post-traumatic stress disorder were frequent (33%) and significantly associated with experience of torture, prison and persecution. CONCLUSIONS: The population presented with pertinent health issues such as vitamin deficiencies, mental health issues and symptoms of pain. Few suffered from non-communicable or communicable diseases. Our results suggest that an offer of specialised services at municipality level for all newly resettled refugees may be beneficial. Furthermore, the study underlines the need for more research within the field of refugee health. FUNDING: None. TRIAL REGISTRATION: Ethical approval was obtained from the Capital Region of Denmark and the Danish Patient Safety Authority.

The health status of newly arrived asylum-seeking minors in Denmark: a nationwide register-based study.

OBJECTIVES: Asylum-seeking minors are known to be at increased risk of physical and mental diseases compared to both native children and adult asylum seekers. We present a nationwide register-based study based on the health assessment of 7210 newly arrived minors in Danish asylum centres from 1 January 2011 to 31 December 2015. METHODS: We describe socio-demographic characteristics, trauma history and symptoms of physical and mental health. To associate the reporting of traumatic events and signs of anxiety or depression, we performed logistic regression analysis. RESULTS: We found a high, albeit varying, prevalence of traumatic experiences, sleeping and eating problems, and head- and toothache. In the subgroup that was assessed for need of urgent support, more than two of every five minor scored above the threshold. In the subgroup examined by a doctor, one of every four had at least one abnormal finding. CONCLUSIONS: The prevalence of trauma and mental health symptoms and the association of the two were striking. Our findings underline that timely recognition and appropriate treatment of childhood traumas should be given high priority in the receiving communities.