Hiv and Global Health in a Pandemic Era

Four broad themes run through this year's N'Galy-Mann lecture: clinical medicine, HIV, health security, and global health. Three patterns of disease characterized medicine in East Africa at the time that AIDS was first described in the United States: diseases of poverty, mainly infectious;non-communicable diseases with differing international epidemiology;and classic tropical diseases restricted in distribution by ecologic needs of parasites and vectors. Limited resources did not prevent the practice of good medicine under adverse circumstances, nor application of basic principles of research. The recognition of a second AIDS virus (HIV-2) in West Africa in the mid-late 1980s required applied research to assess implications and potential global impact of this novel infection. CDC established a second collaborative research site in sub-Saharan Africa, Projet RETRO-CI, in Abidjan, Cote d'Ivoire (the first was Projet SIDA in the Democratic Republic of Congo, where N'Galy and Mann made seminal contributions). Controversy around HIV-2 diagnosis, transmission, and pathogenicity was slowly resolved through West African research showing HIV-2 was an AIDS-causing pathogen, slower than HIV-1 in its progression, and less transmissible until late in the course of infection. Mother-to-child transmission was exceptionally rare. Claims that HIV-2 protected against HIV-1 were not substantiated. Projet RETRO-CI clarified the spectrum of HIVassociated disease and the dominant role of tuberculosis. Placebo-controlled trials demonstrated efficacy of short-course zidovudine for prevention of perinatal transmission of HIV-1, and of cotrimoxazole prophylaxis in reducing hospitalization and mortality in persons with HIV. Global health today is dominated by discourse around health security. The West African and Congolese Ebola epidemics since 2014 aroused strong declarations, yet the world was poorly prepared to address the pandemic of COVID-19. Health in the world has changed substantially since AIDS emerged. As 2030, the year for delivery on the Sustainable Development Goals, approaches, development assistance for health remains essential to address traditional, unfinished commitments yet does not match today's global burden of disease. CROI attendees are encouraged to remember colleagues lost to COVID-19 and other challenges;to assess priorities in today's global health, including relating to HIV;and to reflect on what issues? N'Galy and Mann would focus on today.

Tropical infections as occupational diseases among young volunteers in social projects.

PURPOSE: The trend of volunteering overseas has increased tremendously over the last decade. Volunteers often go to regions where they are exposed to the risk of tropical infections like malaria, dengue, typhoid fever and schistosomiasis. Health assessments have shown a high occurrence of tropical infections among young volunteers. Such tropical infections are notifiable in Germany, as they are covered by a separate branch of the social insurance system. However, there is still limited data on systematical improvement of medical prevention and health care for volunteers. METHODS: This retrospective study included 457 cases with a diagnosis for a tropical infection or typhoid fever from January 2016 to December 2019. Data sets were anonymised and then analysed with descriptive statistics first. Cases of volunteers sent abroad by "Weltwärts" were compared to cases of aid workers sent to non-industrial countries. RESULTS: A high occurrence of tropical infections as occupational diseases has been shown for volunteers compared to other (mostly older) aid workers being sent to tropical regions. The risk of acquiring a tropical infection was significantly higher in Africa compared to other tropical regions. Cases of malaria were reported significantly more often among the group of volunteers than among aid workers during the period under review. Medical check-ups after travel were rare among volunteers. CONCLUSIONS: Data imply a disproportionate risk for malaria in Africa with a higher risk of acquiring malaria tropica in Sub-Saharan regions. Region-specific risks need to be addressed in training seminars in order to raise awareness among young volunteers before travel. Medical examinations after travel should be mandatory and specific to a particular region.

Epidemics of Neglect

The COVID-19 pandemic has exposed multiple fault lines in the performances of health services at every level – from community to national to global – in ensuring universal, equitable access to preventive and curative care. Tragically, this has been to the detriment of those who have suffered and died not only from COVID-19, but also from the myriad other ailments affecting people around the world. Of those, we wish to highlight here some key categories of diseases that have caused a greater burden of illness and deaths as a consequence of the policies and political decisions made in relation to the COVID-19 pandemic. In our view, these should be considered epidemics or, more accurately, syndemics – the clustering and interactions of two or more diseases or health conditions and socio-environmental factors – of neglect.

Travel-associated melioidosis: a narrative review.

BACKGROUND: Melioidosis, caused by Burkholderia pseudomallei, may be considered a neglected tropical disease that remains underdiagnosed in many geographical areas. Travellers can act as the sentinels of disease activity, and data from imported cases may help complete the global map of melioidosis. METHODS: A literature search for imported melioidosis for the period 2016-22 was performed in PubMed and Google Scholar. RESULTS: In total, 137 reports of melioidosis associated with travel were identified. The majority were males (71%) and associated with exposure in Asia (77%) (mainly Thailand, 41%, and India, 9%). A minority acquired the infection in the Americas-Caribbean area (6%), Africa (5%) and Oceania (2%). The most frequent comorbidity was diabetes mellitus (25%) followed by underlying pulmonary, liver or renal disease (8, 5 and 3%, respectively). Alcohol/tobacco use were noted for seven and six patients, respectively (5%). Five patients (4%) had associated non-human immunodeficiency virus (HIV)-related immunosuppression, and three patients (2%) had HIV infection. One patient (0.8%) had concomitant coronavirus disease 19. A proportion (27%) had no underlying diseases. The most frequent clinical presentations included pneumonia (35%), sepsis (30%) and skin/soft tissue infections (14%). Most developed symptoms <1 week after return (55%), and 29% developed symptoms >12 weeks after. Ceftazidime and meropenem were the main treatments used during the intensive intravenous phase (52 and 41% of patients, respectively) and the majority (82%) received co-trimoxazole alone/combination, for the eradication phase. Most patients had a favourable outcome/survived (87%). The search also retrieved cases in imported animals or cases secondary to imported commercial products. CONCLUSIONS: As post-pandemic travel soars, health professionals should be aware of the possibility of imported melioidosis with its diverse presentations. Currently, no licensed vaccine is available, so prevention in travellers should focus on protective measures (avoiding contact with soil/stagnant water in endemic areas). Biological samples from suspected cases require processing in biosafety level 3 facilities.

Use of mobile tele-dermatology in managing cutaneous leishmaniasis from a remote district of Nepal during the COVID 19 pandemic: A case series.

With the invent of smart phones, tele-dermatology has become a cheap and cost-effective medium to provide medical services to rural population. Its usefulness is more prominently noted during the COVID 19 pandemic and much more in countries with difficult terrain with limited specialist health providers. Cutaneous leishmaniasis (CL) is a neglected tropical disease which may cause significant disability if treatment is delayed. Here, we discuss three cases of CL from a remote district by use of tele-dermatology during the pandemic lockdown.

A review of nutrition in neuropathic pain of leprosy.

Leprosy is a neglected tropical disease (NTD) that continues to burden low- and middle-income countries (LMICs), despite being eliminated as a public health concern by the World Health Organization (WHO) in 2000. The causative agents, Mycobacterium leprae and Mycobacterium lepromatosis, affect nearly 200,000 individuals globally each year, with over 19,000 new cases detected in the Americas in 2020 alone. Canada has experienced an increasing incidence of leprosy, due to rising levels of travel and migration from endemic areas, reaching over 37,000 individuals with leprosy by the end of 2020. Patients experience a spectrum of signs and symptoms including hypopigmented cutaneous macules alongside peripheral neuropathy including peripheral neuropathic pain (PNP) and disabling sensory neuropathies. Despite the development of effective and curative therapeutics via multidrug therapy (MDT), many barriers to treatment adherence and effective immunological control of the pathogen challenge the care of patients with leprosy. Socioeconomic barriers, such as disability-related social stigma and often undiagnosed nutritional deficiencies, have resulted in heightened disease severity. PNP therapeutics are associated with significant side effects and remain ineffective as the majority of individuals will not experience a greater than 30% reduction of symptoms. Nutrient supplementation is known to be instrumental in reducing host oxidative stress, strengthening the immune system and mitigating comorbidities. Likewise, dietary lifestyle interventions known to be physiologically beneficial have recently emerged as powerful tools conferring neuroprotective effects, potentially mitigating PNP severity. However, a significant knowledge gap concerning the effect of adequate nutrition on host immunological control of leprosy and PNP severity exists. Further evaluation of this relationship will provide key insight into the pathogenesis of leprosy, strengthening the current body of literature.

Visceral leishmaniasis in the COVID-19 pandemic era.

Visceral l eishmaniasis (VL), also known as kala-azar, had once been targeted for elimination in 2020, which now has been shifted to 2030. The year 2020 was also the year in which the world was gripped by the coronavirus disease 2019 (COVID-19) pandemic. This review sheds light on the impact of COVID-19 on VL elimination programmes and the increasing incidences of COVID-19/VL cases. Lockdowns were imposed worldwide that led to the suspension of surveys, active case finding and mass drug administration, which are important activities to manage neglected tropical diseases. Healthcare machinery was redirected to control the pandemic and acute resource shortages were seen. Budget cuts from funding agencies and donors also came as a severe blow. Priority changes for manufacturers of drugs and diagnostic kits have also exacerbated the situation. Cases where patients were co-infected with VL and COVID-19 were reported across various settings and in people of various age groups, posing unprecedented challenges in diagnosis and treatment. Concerted efforts from all stakeholders are required to understand and deal with the impact that this pandemic has had on VL.

Impact of digital transformation on tropical health / Impacto de la transformación digital en la salud tropical

La Transformación Digital (TD) es todo un proceso que busca optimizar la relación usuario­organización, mejorando así los procesos y el desempeño. Con la llegada de la pandemia COVID-19 a principios del año 2020, cuando fue necesario acelerar la inclusión de las Tecnologías de Información y Comunicación (TIC) para continuar ofreciendo los servicios sanitarios, se constituye el sistema peruano de TD como un sistema funcional; con normas, principios y procedimientos; y con técnicas e instrumentos para ordenar las actividades del sector público y con miras a su optimización. Se planteó una investigación de carácter descriptivo para conocer el impacto de la transformación digital en la salud tropical del Perú. Para ello se determinaron el impacto en la gestión de datos, gobernanza, e intercambio de conocimiento e innovación digital de 4 enfermedades metaxénicas y 3 zoonóticas seleccionadas a partir del análisis de los distintos componentes de la sala virtual de situación de salud del Centro Nacional de Epidemiología, Prevención y Control de Enfermedades del Perú. Los datos fueron analizados bajo el Sistema de Información para la Salud (IS4H) de la OPS que permitió valorar la interoperabilidad de los procesos relacionados con la categorización de estas nosologías. Para todos los factores evaluados: gestión de datos, innovación, gestión y gobernanza y gestión e intercambio de conocimiento, los resultados, en general, estuvieron alrededor de la media (3 puntos, en una escala del 1 al 5), siendo el valor más alto (3,3 puntos) para la gestión y gobernanza, y el valor más bajo (2,7 puntos) para la innovación. Se necesita un enfoque más holístico en la salud pública para asegurarse de que se proporcione una respuesta eficaz frente a las enfermedades tropicales. Si los sistemas de salud se colocan en el medio de la acción, esto permitiría tener mayores posibilidades de hacer frente a estas enfermedades mediante el uso adecuado de las herramientas modernas que logren complementar el enfoque tradiciona(AU)

Digital Transformation (TD) is a whole process that seeks to optimize the user-organization relationship, thus improving processes and performance. With the arrival of the COVID-19 pandemic at the beginning of 2020, when it was necessary to accelerate the inclusion of Information and Communication Technologies (ICT) to continue offering health services, the Peruvian DT system was established as a functional system; with norms, principles and procedures; and with techniques and instruments to order the activities of the public sector and with a view to their optimization. A descriptive investigation was proposed to know the impact of digital transformation on tropical health in Peru. For this, the impact on data management, governance, and exchange of knowledge and digital innovation of 4 metaxenic and 3 zoonotic diseases selected from the analysis of the different components of the virtual health situation room of Centro Nacional de Epidemiología, Prevención y Control de Enfermedades of Peru. The data were analyzed under PAHO's Information System for Health (IS4H), which made it possible to assess the interoperability of the processes related to the categorization of these nosologies. For all the factors evaluated: data management, innovation, management and governance, and knowledge management and exchange, the results, in general, were around the average (3 points, on a scale from 1 to 5), with the highest value being highest (3.3 points) for management and governance, and the lowest value (2.7 points) for innovation. A more holistic approach to public health is needed to ensure that an effective response to tropical diseases is provided. If health systems are placed in the middle of the action, this would allow them to have greater possibilities of dealing with these diseases through the appropriate use of modern tools that manage to complement the traditional approach(AU)

Monkeypox awareness, knowledge, and attitude among undergraduate preclinical and clinical students at a Malaysian dental school: An emerging outbreak during the COVID-19 era

Objective: To evaluate the awareness, knowledge, and attitude on monkeypox viral infection among preclinical and clinical dental students in Malaysia. Methods: A cross-sectional study was conducted among 229 preclinical and clinical dental students via an online self-reported questionnaire. The questionnaire included 3 items on awareness, 15 items on knowledge, 9 items on attitude and 2 open-ended questions. Data were presented as frequencies and percentages. Chi-square test was used to compare knowledge and awareness scores between preclinical and clinical dental students and content analysis was performed for open-ended responses. Results: Preclinical and clinical dental students were aware of the existence of monkeypox (89.5% and 94.4%, respectively), that the disease emerged in non-endemic countries (81.0% and 87.1%, respectively) and that it was declared a public health emergency of international concern by the World Health Organization (73.3% and 79.0%, respectively). Clinical dental students' overall knowledge level was significantly higher than preclinical dental students (P=0.014). Both preclinical (95.2%) and clinical (96.8%) dental students demonstrated positive attitudes toward monkeypox with no significant difference (P=0.736) noted between them. Three themes emerged from the open-ended questions: (1) reimplementation of nationwide lockdown, (2) impact on the economy and health, and (3) disruption to the educational system. Students also anticipated their face-to-face learning to be reduced should there be a new outbreak. Conclusions: Both preclinical and clinical dental students showed comparable awareness and attitudes, while the latter demonstrated greater satisfactory knowledge toward the re-emergence of monkeypox during the COVID-19 pandemic. Nonetheless, efforts to improve dental students' understanding of this alarming outbreak are required, to safeguard their health and minimise transmission.

Evaluation of prognostic markers in patient infected with SARSCoV-2

Objectives: Prognostic markers used to measure the disease progression and patient outcome regardless of treatment in COVID-19. We aim to analyze and evaluate the prognostic markers for early identification of severe patients. Materials and Methods: During a 3-month period (November 2020 to January 2021), a total of 165 patients attending Sukraraj Tropical and Infectious Disease Hospital with laboratory-confirmed COVID-19 were enrolled and divided into non-severe and severe groups. The demographic data, underlying co-morbidities and laboratory findings were analyzed. Correlation, Regression analysis and ROC curve was performed to determine the risk factors and cut-off values for critically ill patients were speculated. Results: Disease severity was significantly associated with age (r = 0.359, p<0.001), RBC (r = -0.163, p = 0.037), AEC (r = -0.300, p<0.001), ALC (r = -0.239, p<0.001), ANC (r = 0.228, p<0.001), NLR (r = 0.336, p<0.001), PLR (r = 0.286, p<0.001), glucose (r = 0.155, p = 0.046), urea (r = 0.282, p<0.001), creatinine (r = 0.194, p = 0.012), AST (r = 0.169, p = 0.030), ferritin (r = 0.359, p<0.001) and CRP. Whereas Increasing age (AOR = 3.611), positive CRP (AOR = 2.930), high ferritin (AOR = 2.754), decreased AEC (AOR = 3.415) was found to be independent risk factors for COVID-19 severity. Similarly, ROC (Receiver Operating Characteristics) curve analysis showed age (AUC = 0.724), NLR (AUC = 0.710), PLR (AUC = 0.678), ferritin (AUC = 0.735), AEC (AUC = 0.661) can be used to monitor the disease severity. Conclusion: Our study revealed severe COVID-19 is associated with increased markers of innate immune response such as neutrophil count, NLR, CRP and serum ferritin;decreased markers of adaptive immune response such as lymphocyte and increased markers of major organ damage including AST, urea, and creatinine compared to COVID-19.

What about infection in travellers, migrants and refugees

Several factors have been linked to emerging infectious diseases including new agents (coronaviruses, zika virus), extension of geographical areas (schistosomiasis, dengue, West Nile, zika virus), increase in incidence (HIV, tuberculosis) and travel/migration (Chagas disease, cysticercosis). According to the World Migration Report 2020, the number of international migrants reached 272 million globally in 2019, and nearly two-thirds were labour migrants. Epidemiological evidence about infectious diseases and neuroinfection among travellers, migrants and refugees will be reviewed. Traveller's diarrhoea, dengue fever and other tropical diseases are reported in travellers. Re-emergence of infections in Europe includes chikungunya, dengue and malaria. Migration of asymptomatic people spread American trypanosomiasis in non-endemic areas and cases have been reported in Europe, Japan, and North-America. Neurocysticercosis is a common cause of seizures among South American migrants in USA. Migrants may be asymptomatic carriers (Chagas, HTLV-1). The involvement of CNS may occur in viral infections (HIV, HTLV-1, dengue, zika), malaria, schistosomiasis (myeloradiculopathy), Chagas disease (encephalitis, stroke), etc. Refugees may be at slightly higher risk of infectious diseases including tuberculosis, HIV, hepatitis and schistosomiasis. Systematic reviews have found that tuberculosis and hepatitis B and C prevalence is higher among migrants arriving in Europe, and the prevalence of antimicrobial resistance and infections was higher in refugees and asylum seekers than in other migrant groups. Infectious diseases in migrants may be explained by a higher prevalence in migrants' countries of origin, barriers to health care in host/transit countries, and poor living conditions. These factors are especially relevant in vulnerable populations (refugees, documented migrants).

American Society of Tropical Medicine and Hygiene, 70th Annual Meeting. Virtual - November 17-21, 2021

The 70th annual meeting of the American Society of Tropical Medicine and Hygiene was kicked off by Dr. Tedros Ghebreyesus, the Director-General of the World Health Organization (WHO). The virtual gathering format included plenary sessions, science and clinical sessions, E-poster sessions, and an exhibit hall featuring the latest products and services for tropical diseases and global health. This report provides highlights from the oral and poster sessions, focusing on developments in the treatment of tropical diseases.

Challenges and Promises for Obtaining New Antiprotozoal Drugs: What’s Going Wrong?

Infections by protozoa can cause some of the most serious human diseases, particularly in tropical regions. However, the number of available drugs used to treat such diseases tends to be limited with relatively high toxicity, and the vast majority of such drugs were developed in the 1920s to 1970s. The development of antiprotozoal drugs has been hindered owing in part to: (1) the highly complicated life cycles of such organisms and their ability to avoid innate immune defences;(2) challenges associated with culturing such organisms particularly in different phases of their growth and amplification;and (3) a lack of investment in biomedical research aimed at developing treatments for tropical diseases that do not tend to affect more affluent countries. Indeed, only three new drugs have entered into clinical trials in recent times, highlighting the tremendous gap in knowledge that should be bridged to more effectively treat protozoal infections.

Development of a Modified mRNA-Based Vaccine for Lassa Virus

Lassa virus (LASV) is a highly prevalent pathogen in West Africa, including Sierra Leone, Liberia, Guinea and Nigeria. The virus causes 100,000 to 300,000 infections per year, which lead to approximately 5,000 deaths annually. Lassa fever is currently on the WHO R and D Blueprint list of epidemic threats needing urgent R and D action, and therefore there is an unmet need for an effective LASV vaccine, especially one that prevents Service Members from becoming ill from epidemic disease exposure during operational deployments. The innovative vaccine technology used in this funded project was developed based on mRNA modified by incorporation of pseudouridin, which dramatically minimizes the indiscriminate activation of innate immune sensing and increases translation by an order of magnitude. This revolutionary technology was used by Moderna Therapeutics, the partner in this project, for the development of highly effective vaccines against influenza virus, rabies, HIV, Zika virus and SARS-CoV-2;the influenza and SARS-CoV-2 vaccines have been tested recently in clinical trials. Dr. Bukreyev and Moderna have designed and tested two Ebola virus modified mRNA-based vaccines encapsulated in lipid nanoparticles (LNP), which induced neutralizing antibodies in immunized guinea pigs and completely prevented death and disease caused by Ebola virus challenge