The American Journal of Tropical Medicine and Hygiene - Current Issue

Fifteen years of investment in malaria control on Bioko Island, Equatorial Guinea (EG), dramatically reduced malaria-associated morbidity and mortality, but the impact has plateaued. To progress toward elimination, EG is investing in the development of a malaria vaccine. We assessed the unique public–private partnership that has had such a significant impact on malaria on Bioko Island and now added a major effort on malaria vaccine development. As part of a $79M commitment, the EG government (75%) and three American energy companies (25%) have invested since 2012 greater than $55M in the Equatoguinean Malaria Vaccine Initiative (EGMVI) to support clinical development of Sanaria® PfSPZ vaccines (Sanaria Inc., Rockville, MD). In turn, the vaccine development program is building human capital and physical capacity. The EGMVI established regulatory and ethical oversight to ensure compliance with the International Conference on Harmonization and Good Clinical Practices for the first importation of investigational product, ethical approval, and conduct of a clinical trial in Equatoguinean history. The EGMVI has completed three vaccine trials in EG, two vaccine trials in Tanzania, and a malaria incidence study, and initiated preparations for a 2,100-volunteer clinical trial. Personnel are training for advanced degrees abroad and have been trained in Good Clinical Practices and protocol-specific methods. A new facility has established the foundation for a national research institute. Biomedical research and development within this visionary, ambitious public–private partnership is fostering major improvements in EG. The EGMVI plans to use a PfSPZ Vaccine alongside standard malaria control interventions to eliminate Pf malaria from Bioko, becoming a potential model for elimination campaigns elsewhere.

The COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a β-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia. Scientists have warned for decades that such sarbecoviruses are poised to emerge again and again, identified risk factors, and argued for enhanced pandemic prevention and control efforts. Unfortunately, few such preventive actions were taken resulting in the latest coronavirus emergence detected in late 2019 which quickly spread pandemically. The risk of similar coronavirus outbreaks in the future remains high. In addition to controlling the COVID-19 pandemic, we must undertake vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself.

The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.

Use of medical masks is a key strategy for COVID-19 prevention among healthcare workers. Unfortunately, there are global shortages of this essential commodity, and many have resulted in inappropriate usage to conserve supply. This article highlights the likely benefits of face mask containers in promoting safe, appropriate, and extended use of medical masks by healthcare workers in settings where a sustainable supply of medical masks may be limited.

In the United States, Chagas disease is diagnosed in less than 1% of the estimated > 300,000 people who have the disease. However, the actual prevalence remains unknown, and these estimates may be wide of the mark (too high or too low). The greater part of those living with the disease acquired the infection in an endemic region of Latin America, but autochthonous transmission in the United States is increasingly being described. These cases are considered rare, and the transmission routes are largely unknown. Although triatomines or “kissing bugs” harbor Trypanosoma cruzi in North America, most autochthonous cases are presumed rather than confirmed exposures to naturally infected kissing bugs. Public knowledge of Chagas is growing, and efforts are underway to provide greater awareness, but what are the risk factors for human transmission of Chagas disease in the United States?

Nine criteria regarding the infectious agent, mode of transmission, portal of entry, route of spread, target organs, target cells, pathologic lesions, incubation period, and modifiable spectrum of disease and outcomes appropriate to the intended experimental purpose are described. To provide context for each criterion, mouse models of two vector-borne zoonotic infectious diseases, scrub typhus and dengue, are summarized. Application of the criteria indicates that intravenous inoculation of Orientia tsutsugamushi into inbred mice is the best current model for life-threatening scrub typhus, and intradermal inoculation accurately models sublethal human scrub typhus, whereas the immunocompromised mouse models of dengue provide disease outcomes most closely associated with human dengue. In addition to addressing basic questions of immune and pathogenic mechanisms, mouse models are useful for preclinical testing of experimental vaccines and therapeutics. The nine criteria serve as guidelines to evaluate and compare models of vector-borne infectious diseases.

Gene drive technologies represent powerful tools to develop vector control strategies that will complement the current approaches to mitigate arthropod-borne infectious diseases. The characteristics of gene drive technologies have raised additional concerns to those for standard genetically engineered organisms. This generates a need for adaptive governance that has not been met yet because of the rapid rate of progress in gene drive research. For the eventual release of gene drive insects into wild populations, an international governance network would be helpful in guiding scientists, stakeholders, public opinion, and affected communities in its use. We examined the current institutions and governing bodies among various continents that could have an impact on gene drive governance or the potential to adapt to its future use. Possible governance strategies also are proposed that seek to bridge gaps and promote an ethically sound policy framework. Ideally, governance strategies should be developed before or at the same pace as gene drive research to anticipate field releases and maximize their impact as a public health tool. However, this is not likely to happen as it takes years to develop global accords, and some countries may choose to move ahead independently on the new technology.

Quality of care is essential for improving health outcomes, but heterogeneity in theoretical frameworks and metrics can limit studies’ generalizability and comparability. This research aimed to compare definitions of care quality across research articles that incorporate data from Service Provision Assessment (SPA) surveys. Following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we used a keyword search in PubMed. Each author reviewed abstracts, then full texts, for inclusion criteria, and peer-reviewed publications of empirical analysis using SPA data. The search yielded 3,250 unique abstracts, and 34 publications were included in the final analysis. We extracted details on the SPA dataset(s) used, theoretical framework applied, and how care quality was operationalized. The 34 included articles used SPA data from 14 surveys in nine countries (all in sub-Saharan Africa plus Haiti). One-third of these articles (n = 13) included no theoretical or conceptual framework for care quality. Among those articles referencing a framework, the most common was the Donabedian model (n = 7). Studies operationalized quality constructs in extremely different ways. Few articles included outcomes as a quality construct, and the operationalization of structure varied widely. A key asset of SPA surveys, owing to the standardized structure and use of harmonized data collection instruments, is the potential for cross-survey comparisons. However, this is limited by the lack of a common framework for measuring and reporting quality in the existing literature using SPA data. Service Provision Assessment surveys offer unique and valuable insights, and a common framework and approach would substantially strengthen the body of knowledge on quality of care in low-resource settings.

The COVID-19 pandemic has proved to be an enormous challenge to the health of the world population with tremendous consequences for the world economy. New knowledge about COVID-19 is being acquired continuously. Although the main manifestation of COVID-19 is SARS, dysfunction in other organs has been described in the last months. Neurological aspects of COVID-19 are still an underreported subject. However, a plethora of previous studies has shown that human CoVs might be neurotropic, neuroinvasive, and neurovirulent, highlighting the importance of this knowledge by physicians. Besides, several neurological manifestations had been described as complications of two other previous outbreaks of CoV diseases (SARS ad Middle East respiratory syndrome). Therefore, we should be watchful, searching for early evidence of neurological insults and promoting clinical protocols to investigate them. Our objectives are to review the potential neuropathogenesis of this new CoV and the neurological profile of COVID-19 patients described so far.

A 1-year population-based prospective study was launched in Seychelles, a country with one of the highest human incidence of leptospirosis worldwide, to describe the characteristic features of the epidemiology of the disease and highlight the most prominent risk factors. Diagnosis was based on the IgM enzyme-linked immunosorbent assay, microscopic agglutination test, and real-time PCR. A standardized questionnaire was administered to 219 patients aged ≥ 13 years consulting for acute febrile illness. The high incidence of leptospirosis in Seychelles was confirmed. The disease was particularly severe, as the case fatality rate was 11.8%. Leptospirosis was positively associated in univariate analysis with socio-professional and clinical variables including gardening/farming, oliguria, jaundice, conjunctivitis, history of hepatitis C virus infection, anemia, thrombocytopenia, and/or biological renal failure. Epidemiological analyses of the questionnaires highlighted a link of the disease with living in houses (versus apartment), the presence of animals around and in houses, gardening, and misuse of personal protective equipment. Multivariate analyses indicated that being a farmer/landscaper and having cattle and cats around the home are the most significant drivers of leptospirosis. Biological features most associated with leptospirosis were thrombocytopenia, leukocytosis, high values for renal function tests, and elevated total bilirubin. We report changes in behavior and exposure compared with data collected on leptospirosis 25 years ago, with indication that healthcare development has lowered case fatality. Continuous health education campaigns are recommended as well as further studies to clarify the epidemiology of human leptospirosis, especially the role of domestic animals.

For the last decade, the New Jersey (NJ) Department of Health has reported between 42 and 144 new cases each year of “spotted fever group rickettsiosis” (SFGR), a statistic that reflects uncertainty regarding which rickettsial agents (Proteobacteria: Rickettsiaceae: Rickettsia) are infecting NJ residents. To identify the Rickettsia circulating in NJ ticks, we used a combination of conventional and real time PCR approaches to screen 560 Dermacentor variabilis Say and 245 Amblyomma americanum L. obtained from a 1-day state-wide surveillance in May 2018 and an additional 394 D. variabilis collected across NJ in 2013–2018. We found zero D. variabilis infected with Rickettsia rickettsii, the agent of Rocky Mountain spotted fever and, on average, 1.3% infected with presumed nonpathogenic Rickettsia montanensis. We also found zero A. americanum infected with R. rickettsii, and 20% infected with Rickettsia amblyommatis, a prevalence somewhat lower than in more southern states. Overall, we conclude that it is unlikely that R. rickettsii vectored by D. variabilis is a primary cause of SFGR cases in NJ and discuss our findings in the context of known facts and current limitations. We conclude that understanding the causes of SFGR east of the Mississippi will require collaboration among medical doctors, public health authorities, and medical entomologists to follow up presumptive human cases of SFGR with detailed histories of exposure, species-specific molecular assays, and active surveillance of putative vectors and the pathogens they may carry.