Tropical Medicine and Infectious Disease — Open Access Journal

Crimean–Congo hemorrhagic fever virus (CCHFV) infection is identified in the 2018 World Health Organization Research and Development Blueprint and the National Institute of Allergy and Infectious Diseases (NIH/NIAID) priority A list due to its high risk to public health and national security. Tick-borne CCHFV is widespread, found in Europe, Asia, Africa, the Middle East, and the Indian subcontinent. It circulates between ticks and several vertebrate hosts without causing overt disease, and thus can be present in areas without being noticed by the public. As a result, the potential for zoonotic spillover from ticks and animals to humans is high. In contrast to other emerging viruses, human-to-human transmission of CCHFV is typically limited; therefore, prevention of spillover events should be prioritized when considering countermeasures. Several factors in the transmission dynamics of CCHFV, including a complex transmission cycle that involves both ticks and vertebrate hosts, lend themselves to a One Health approach for the prevention and control of the disease that are often overlooked by current strategies. Here, we examine critical focus areas to help mitigate CCHFV spillover, including surveillance, risk assessment, and risk reduction strategies concentrated on humans, animals, and ticks; highlight gaps in knowledge; and discuss considerations for a more sustainable One Health approach to disease control. Full article

COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic. The disease continues to pose a major therapeutic challenge. Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS). Cytokine release syndrome (or “cytokine storm”) is likely to be a contributing factor to ARDS in many patients. Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release. We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress. The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm. We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status. The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc). The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days. We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation. Ultimately, the patient was downgraded from the ICU and discharged within days. We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support. This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19. Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality—the cytokine storm. This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality. Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19. Full article

Background: Cholera remains a major global health problem, causing high output diarrhea leading to severe dehydration and shock in developing countries. We aimed to determine whether vasoactive intestinal polypeptide (VIP), the mediator of pancreatic cholera syndrome, has a role in the pathophysiology of human cholera. Methods: We conducted a prospective observational study of cholera cases hospitalized with severe dehydration. Plasma and stool water levels of VIP were measured just after admission, after complete rehydration (3–4 h), at 24 h post-rehydration and at discharge after diarrhea ceased. Results: In total, 23 cholera patients were examined between January and August 2018. The geometric mean of stool VIP (sVIP) and plasma VIP (pVIP) on admission were 207.67 and 8.34 pmol/L, respectively. pVIP values were all within the normal range (</= 30 pcmol/L); however, sVIP levels were very high at all timepoints, though less so just after rehydration. In multivariable GEE models, after adjustment for covariates, sVIP levels were significantly associated with duration of hospitalization (p = 0.026), total stool volume (p = 0.023) as well as stool output in the first 24 h (p = 0.013). Conclusions: The data suggest that VIP, which is released by intestinal nerves, may play an important role in human choleragenesis, and inhibitors of intestinal VIP merit testing for potential therapeutic benefits. Full article

Background: A survey was conducted among Rohingya refugees to assess their overall health literacy and health status. Methods: A questionnaire was developed to conduct face to face interviews among Rohingya refugees in Cox’s Bazar, Bangladesh in November–December 2017. Families were selected using convenience sampling from four large refugee camps. Results: Primary respondents aged 10–90 (median 32) years, 56% male, representing 1634 families were interviewed and provided data of themselves and 6268 additional family members, 4163 (66.4%) of whom were children aged <18 years. Of all, only 736 (45%) primary respondents knew how to appropriately treat diarrhoea, 882 (54%) relied on unqualified village “doctors” for treatment, 547 (33.5%) reported a family member suffering injuries in the previous six months, with 8% (42/547) of injuries fatal. One hundred and ninety two (11.8%) primary respondents also reported deaths within their family in the preceding 12 months, with the majority (70% [134/192]) occurring in males, and 44% (85/192) of all deaths were claimed to be homicidal. Conclusion: This survey highlights overall poor health literacy, limited access to qualified health care, and a high rate of injuries and assaults among Rohingyas. However, these data come from an anecdotal survey that excluded some sensitive but important questions. Full article

Extrapulmonary drug-resistant tuberculosis (DR-EPTB) poses a formidable diagnostic and therapeutic challenge.Besides associated with high morbidity, it is a major financial burden for the patient and the health system. In spite of this, it has often been neglected as it does not “pose” a visible public health threat. We study clinical profiles, treatment outcomes, and factors associated with unfavourable outcomes among DR-EPTB patients under programmatic settings in New Delhi, India, and evaluate how this could impact TB elimination. A retrospective analysis of all DR-EPTB patients registered at three nodal DR-TB centres in Delhi in 2016 was carried out. Of the 1261 DR-TB patients registered, 203 (16%) were DR-EPTB, with lymph nodes (118, 58%) being the most common site, followed by bone (69, 34%). Nearly 29% (n = 58) experienced adverse drug reactions with severe vomiting (26, 13 %), joint pain (21, 10%) and behavioral disorder (15, 7%). History of previous TB treatment was observed in a majority of the cases (87.7%). Nearly one-third of DR-EPTB cases (33%) had unfavourable treatment outcomes, with loss-to-follow-up (n = 40, 58%) or death (n = 14, 20%) being the most common unfavourable outcomes. In the adjusted analysis, weight band 31–50 kilograms (aRR = 1.8, 1.2–3.4) and h/o previous TB (aRR = 2.1, 1.1–4.8) were mainly associated with unfavourable outcomes. TB elimination efforts need to focus on all forms of TB, including DR-EPTB, leaving no one behind, in order to realise the dream of ending TB. Full article

Hepatitis B virus (HBV) infection is a serious problem and earlier studies in Papua New Guinea have reported a high prevalence of hepatitis B virus infection. These studies were undertaken using insensitive tests and before an expanded immunization program. The current HBV status is therefore uncertain. A retrospective study to investigate the HBV status was carried out using blood donor data at Nonga General Hospital, East New Britain Province, Papua New Guinea, from January 2003 to December 2018. Additional data for Human Immunodeficiency Virus, syphilis and hepatitis C virus were also collected. Data were analysed using NCSS statistical software. The mean hepatitis B antigen (HBsAg) sero-prevalence was 21% for the period of study and showed a downward trend over the period of the study, which may reflect the effect of the extended immunization program. HBsAg prevalence in male donors (23%) was significantly higher than females (16%). Donors living in Pomio district had a significantly lower proportion of sero-positive HBsAg donors (7%) than Gazelle (22%), Kokopo (22%) and Rabaul (20%), which was attributed to this district’s geographical isolation. Ethnically, Pomios donors (8%) had significantly lower HBsAg prevalence than the Taulils, (29%), Bainings (21%) and Tolais (21%). Fifteen to nineteen year olds (23%) were the predominant age group affected, and vertical or perinatal transmission was probably the primary transmission route. Our findings call for greater awareness on the part of public policy makers and should be considered when planning future public health campaigns. Full article

Background: This study aimed to identify the prevalence of diabetes mellitus (DM) and tuberculosis (TB) among household contacts of index TB patients in Yangon, Myanmar. Method: Household contacts were approached at their home. Chest X-ray and capillary blood glucose tests were offered based on World Health Organization and American Diabetes Association guidelines. Crude prevalence and odds ratios of DM and TB among household contacts of TB patients with and without DM were calculated. Results: The overall prevalence of DM and TB among household contacts were (14.0%, 95% CI: 10.6–18.4) and (5%, 95% CI: 3.2–7.6), respectively. More than 25% of DM cases and almost 95% of TB cases among household contacts were newly diagnosed. Almost 64% of known DM cases among household contacts had poor glycaemic control. The risk of getting DM among household contacts of TB patients with DM was significantly higher (OR—2.13, 95% CI: 1.10–4.12) than those of TB patients without DM. There was no difference in prevalence of TB among household contacts of TB patients with and without DM. Conclusion: Significant proportions of the undetected and uncontrolled DM among household contacts of index TB patients indicate a strong need for DM screening and intervention in this TB–DM dual high-risk population. Full article

Chagas disease, caused by a Trypanosona cruzi infection, is one of the main causes of heart failure in Latin America. It was originally a health problem endemic to South America, predominantly affecting residents of poor rural areas. With globalization and increasing migratory flows from these areas to large cities, the immigration of T. cruzi chronically-infected people to developed, non-endemic countries has occurred. This issue has emerged as an important consideration for heart transplant professionals. Currently, Chagas patients with end-stage heart failure may need a heart transplantation (HTx). This implies that in post-transplant immunosuppression therapy to avoid rejection in the recipient, there is the possibility of T. cruzi infection reactivation, increasing the morbidity and mortality rates. The management of heart transplant recipients due to Chagas disease requires awareness for early recognition and parasitic treatment of T. cruzi infection reactivation. This issue poses challenges for heart transplant professionals, especially regarding the differential diagnosis between rejection and reactivation episodes. The aim of this review is to discuss the complexity of the Chagas disease reactivation phenomenon in patients submitted to HTx for end-stage chagasic cardiomyopathy. Full article

Anthropic changes on the edges of the tropical forests may facilitate the emergence of new viruses from the sylvatic environment and the simultaneous circulation of sylvatic and urban viruses in the human population. In this study, we investigated the presence of arboviruses (arthropod-borne viruses) in the sera of 354 patients, sampled from February 2014 to October 2018 in Sinop city. We sequenced the complete genomes of one chikungunya virus (CHIKV)-positive and one out of the 33 Mayaro virus (MAYV)-positive samples. The CHIKV genome obtained here belongs to the East/Central/South African (ECSA) genotype and the MAYV genome belongs to the L genotype. These genomes clustered with other viral strains from different Brazilian states, but the CHIKV strain circulating in Sinop did not cluster with other genomes from the Mato Grosso state, suggesting that at least two independent introductions of this virus occurred in Mato Grosso. Interestingly, the arrival of CHIKV in Sinop seems to not have caused a surge in human cases in the following years, as observed in the rest of the state, suggesting that cross immunity from MAYV infection might be protecting the population from CHIKV infection. These findings reinforce the need for continued genomic surveillance in order to evaluate how simultaneously circulating alphaviruses infecting the human population will unfold. Full article

The epidemic strain of Venezuelan equine encephalitis virus (VEE) 1B invaded south Texas in 1971. The success of the eventual containment and control of the virus invasion was the early recognition and immediate detection, cooperation, coordination, and participation among multiple federal agencies. There were 4739 wild vertebrate animals trapped on a ranch in the area with only 1 VEE virus isolation from a Virgina opossum (Didelphis virginiana). A large number of mosquitoes were also collected on the ranch and tested, resulting in 240 VEE virus isolations. Virus isolations were obtained from 58% of the 33 equines tested. Wild vertebrates did not play a significant role in the outbreak. Full article

Malaria is one of the leading causes of death worldwide. According to the World Health Organization’s (WHO’s) world malaria report for 2018, there were 228 million cases and 405,000 deaths worldwide. This paper reviews and highlights the importance of accurate, sensitive and affordable diagnostic methods in the fight against malaria. The PubMed online database was used to search for publications that examined the different diagnostic tests for malaria. Currently used diagnostic methods include microscopy, rapid diagnostic tests (RDT), and polymerase chain reaction (PCR). Upcoming methods were identified as loop-mediated isothermal amplification (LAMP), nucleic acid sequence-based amplification (NASBA), isothermal thermophilic helicase-dependent amplification (tHDA), saliva-based test for nucleic-acid amplification, saliva-based test for Plasmodium protein detection, urine malaria test (UMT), and transdermal hemozoin detection. RDT, despite its increasing false negative, is still the most feasible diagnostic test because it is easy to use, fast, and does not need expensive equipment. Noninvasive tests that do not require a blood sample, but use saliva or urine, are some of the recent tests under development that have the potential to aid malaria control and elimination. Emerging resistance to anti-malaria drugs and to insecticides used against vectors continues to thwart progress in controlling malaria. Therefore, future innovation will be required to enable the application of more sensitive and affordable methods in resource-limited settings. Full article

The progress towards ending tuberculosis (TB) by 2035 is less than expected in 11 high TB burden countries in the World Health Organization South-East Asia and Western Pacific regions. Along with enhancing measures aimed at achieving universal access to quality-assured diagnosis, treatment and prevention services, massive efforts are needed to mitigate the prevalence of health-related risk factors, preferably through broader actions on the determinants of the “exposure-infection-disease-adverse outcome” spectrum. The aim of this manuscript is to describe the major socio-economic determinants of TB and to discuss how there are opportunities to address these determinants in an englobing manner under the United Nations Sustainable Development Goals (SDGs) framework. The national TB programs must identify stakeholders working on the other SDGs, develop mechanisms to collaborate with them and facilitate action on social-economic determinants in high TB burden geographical areas. Research (to determine the optimal mechanisms and impact of such collaborations) must be an integral part of this effort. We call upon stakeholders involved in achieving the SDGs and End TB targets to recognize that all goals are highly interlinked, and they need to combine and complement each other’s efforts to end TB and the determinants behind this disease. Full article

Q fever and rickettsial diseases occur throughout the world and appear to be emergent zoonoses in Chile. The diagnosis of these diseases is currently uncommon in Chile, as their clinical presentations are non-specific and appropriate diagnostic laboratory assays are of limited availability. During a recent outbreak of undiagnosed human atypical pneumonia, we serologically investigated a series of 357 cases from three regions of southern Chile. The aim was to identify those caused by Coxiella burnetii and/or Rickettsia spp. Serological analysis was performed by ELISA and an immunofluorescence assay (IFA) for acute and convalescence sera of patients. Our results, including data from two international reference laboratories, demonstrate that 71 (20%) of the cases were Q fever, and 44 (15%) were a likely rickettsial infection, although the rickettsial species could not be confirmed by serology. This study is the first report of endemic Q fever and rickettsial disease affecting humans in Chile. Full article

Tuberculosis (TB), the leading single infectious diseases killer globally, is driven by poverty. Conversely, having TB worsens impoverishment. During TB illness, lost income and out-of-pocket costs can become “catastrophic”, leading patients to abandon treatment, develop drug-resistance, and die. WHO’s 2015 End TB Strategy recommends eliminating catastrophic costs and providing socioeconomic support for TB-affected people. However, there is negligible evidence to guide the design and implementation of such socioeconomic support, especially in low-income, TB-endemic countries. A national, multi-sectoral workshop was held in Kathmandu, Nepal, on the 11th and 12th September 2019, to develop a shortlist of feasible, locally appropriate socioeconomic support interventions for TB-affected households in Nepal, a low-income country with significant TB burden. The workshop brought together key stakeholders in Nepal including from the Ministry of Health and Population, Department of Health Services, Provincial Health Directorate, Health Offices, National TB Program (NTP); and TB/Leprosy Officers, healthcare workers, community health volunteers, TB-affected people, and external development partners (EDP). During the workshop, participants reviewed current Nepal NTP data and strategy, discussed the preliminary results of a mixed-methods study of the socioeconomic determinants and consequences of TB in Nepal, described existing and potential socioeconomic interventions for TB-affected households in Nepal, and selected the most promising interventions for future randomized controlled trial evaluations in Nepal. This report describes the activities, outcomes, and recommendations from the workshop. Full article

The diagnosis of Zika virus infection is complicated and includes testing for nucleic acids and IgM and IgG antibodies, depending on the stage of infection. Zika IgG is an important marker of infection after the acute stage; however, IgG assays can lack specificity due to the similarities between Zika and other flaviviruses. In this study, the diagnostic sensitivity and specificity of the Elecsys^® Zika IgG assay were assessed in 496 samples from Zika endemic regions, and specificity only was assessed in 1685 blood screening and diagnostic samples from Zika non-endemic regions. Cross-reactivity was also assessed against a panel of 202 potentially cross-reacting samples. The performance of the Elecsys^® Zika IgG assay was compared with the anti-Zika virus ELISA IgG. In the samples from the Zika endemic regions, the Elecsys^® Zika IgG assay had 92.88% (95% confidence interval 89.42–95.48) sensitivity and 100% specificity and in the samples from Europe the Elecsys^® Zika IgG assay specificity was ≥99.62%. The Elecsys^® Zika IgG assay was highly specific in samples from both prevalent and non-endemic regions. Full article

Mosquito-borne viruses will continue to emerge and generate a significant public health burden around the globe. Here, we provide a longitudinal perspective on how the emergence of mosquito-borne viruses in the Americas has triggered reactionary funding by sponsored agencies, stimulating a number of publications, innovative development of traps, and augmented capacity. We discuss the return on investment (ROI) from the oscillation in federal funding that influences demand for surveillance and control traps and leads to innovation and research productivity. Full article

To detect Post-kala-azar leishmaniasis (PKDL) cases, several molecular methods with promising diagnostic efficacy have been developed that involve complicated and expensive DNA extraction methods, thus limiting their application in resource-poor settings. As an alternative, we evaluated two rapid DNA extraction methods and determined their impact on the detection of the parasite DNA using our newly developed recombinase polymerase amplification (RPA) assay. Skin samples were collected from suspected PKDL cases following their diagnosis through national guidelines. The extracted DNA from three skin biopsy samples using three different extraction methods was subjected to RPA and qPCR. The qPCR and RPA assays exhibited highest sensitivities when reference DNA extraction method using Qiagen (Q) kit was followed. In contrast, the sensitivity of the RPA assay dropped to 76.7% and 63.3%, respectively, when the boil & spin (B&S) and SpeedXtract (SE) rapid extraction methods were performed. Despite this compromised sensitivity, the B&S-RPA technique yielded an excellent agreement with both Q-qPCR (k = 0.828) and Q-RPA (k = 0.831) techniques. As expected, the reference DNA extraction method was found to be superior in terms of diagnostic efficacy. Finally, to apply the rapid DNA extraction methods in resource-constrained settings, further methodological refinement is warranted to improve DNA yield and purity through rigorous experiments. Full article