Abstract This overview aimed to describe the situation of healthcare access in sub-Saharan Africa, excluding South Africa, during the COVID-19 pandemic. A PubMed® search from March 31, 2020, to August 15, 2022, selected 116 articles. Healthcare access and consequences of COVID-19 were assessed based on comparisons with months before its onset or an identical season in previous years. A general reduction of healthcare delivery, associated with the decline of care quality, and closure of many specialty services were reported. The impact was heterogeneous in space and time, with an increase in urban areas at the beginning of the pandemic (March-June 2020). The return to normalcy was gradual from the 3rd quarter of 2020 until the end of 2021. The impact of COVID-19 on the health system and its use was attributed to (a) conjunctural factors resulting from government actions to mitigate the spread of the epidemic (containment, transportation restrictions, closures of businesses, and places of entertainment or worship); (b) structural factors related to the disruption of public and private facilities and institutions, in particular, the health system; and (c) individual factors linked to the increase in costs, impoverishment of the population, and fear of contamination or stigmatization, which discouraged patients from going to health centers. They have caused considerable socio-economic damage. Several studies emphasized some adaptability of the healthcare offer and resilience of the healthcare system, despite its unpreparedness, which explained a return to normal activities as early as 2022 while the COVID-19 epidemic persisted. There appears to be a strong disproportion between the moderate incidence and severity of COVID-19 in sub-Saharan Africa, and the dramatic impact on healthcare access. Several articles make recommendations for lowering the socioeconomic consequences of future epidemics to ensure better management of health issues. subSaharan sub Saharan Africa COVID19 COVID 19 COVID-1 PubMed 31 15 11 years delivery quality reported time MarchJune June 2020. . 2020) rd 202 2021 (a containment, containment (containment restrictions businesses worship worship) b (b institutions particular c (c costs population stigmatization centers socio economic damage unpreparedness persisted issues COVID1 1 COVID- 3 20 2

Abstract Background: Acute kidney injury (AKI) is a frequent complication of snakebite envenomation, which is still little known in sub-Saharan Africa. This study aims to describe the clinical, biological and ultrasonographic aspects of AKI following severe snakebite envenomation managed in the intensive care unit. Method: A prospective observational survey was performed in Benin over a period of 18 months. All patients suffering severe snakebite envenomation (SBE) were included. The diagnosis of AKI was made using the KDIGO criteria. Kidney ultrasound exam was performed in all patients to assess internal bleeding and morphological and structural abnormalities of the kidneys. Results: Fifty-one cases of severe SBE were included. All patients presented inflammatory syndrome and showed abnormal WBCT whereas bleeding was found in 46 of them (90%). The median time to hospital presentation was three days. The majority of patients were male (M/F sex ratio = 1.55) and the median age was 26. Sixteen patients (31%) showed AKI according to the KDIGO criteria. Severe AKI (KDIGO stage 2 and 3) was observed in three patients, including one stage 2 and two stage 3. Kidney ultrasound revealed three cases of kidney capsular hematoma (6%), two cases of kidney hypertrophy (3%), three cases of kidney injury (4%), two stage 1 KDIGO and one stage 2 KDIGO. Only one patient benefited from hemodialysis. All patients showing AKI recovered without sequels. The median duration of hospital stays was four days. Seven patients died (14%) including four among the 16 AKI patients. Antivenom has been administered to 41 patients (80%). The comparison between patients without and with AKI did not show any significant difference except gender (p = 10-2). Conclusion: AKI is a common complication of severe snakebite envenomation. Resulting from inflammatory and hemorrhagic disorders, AKI may prove to be a short-term life-threatening factor.

Abstract Traditional medicine plays an important role in the daily lives of people living in rural parts of Ethiopia. Despite the fact that Ethiopia has a long history of using traditional medicinal plants as an alternative medicine source, there is no checklist compiling these plants used for snakebite treatment. This review collected and compiled available knowledge on and practical usage of such plants in the country. A literature review on medicinal plants used to treat snakebites was conducted from 67 journal articles, PhD dissertation and MSc theses available online. Data that summarize scientific and folk names, administration methods, plant portion used for treatment and method of preparation of recipes were organized and analyzed based on citation frequency. The summarized results revealed the presence of 184 plant species distributed among 67 families that were cited for treating snakebite in Ethiopia. In this literature search, no single study was entirely dedicated to the study of traditional medicinal plants used for the treatment of snakebite in Ethiopia. Most of the species listed as a snakebite remedy were shrubs and climbers (44%) followed by herbs (33%) and trees (23%). Fabaceae was the most predominant family with the greatest number of species, followed by Solanaceae and Vitaceae. Remedies are mainly prepared from roots and leaves, through decoctions, infusions, powders and juices. Most remedies were administered orally (69%). The six most frequently mentioned therapeutically important plants were Nicotiana tabacum, Solanum incanum, Carissa spinanrum, Calpurnia aurea, Croton macrostachyus and Cynodon dactylon. Authors reviewed the vegetal substances involved in snakebite management and their action mode. In addition to screening the biologically active ingredients and pharmacological activities of these plant materials, future studies are needed to emphasize the conservation and cultivation of important medicinal plants of the country.

Abstract Snakebite is a critical public health issue in tropical countries, particularly in Africa, where 20% of snakebites globally occur. In 2017, the WHO added snakebite envenoming to the category A of neglected tropical diseases. In 2019, thanks to broad institutional and international NGO support, including strong mobilization of African experts and governments, WHO launched a strategy for prevention and control of snakebite envenoming with more ambitious goals. In sub-Saharan Africa, accessibility of antivenoms and symptomatic, adjuvant or replacement therapy is a priority. Several antivenoms are available but their evaluation has not been properly carried out and they remain expensive. To date, there are no manufacturers of antivenom in sub-Saharan Africa (except in South Africa), which requires their importation from other continents. The lack of experience in antivenom choice and its use by health authorities, health personnel and population largely explains the shortage in sub-Saharan Africa. The deficiency of epidemiological data does not allow the implementation of appropriate and efficient care. It is crucial to strengthen the health system which does not have the necessary means for emergency management in general and envenoming in particular. Providing peripheral health centers with antivenoms would decrease complications and deaths. The motivation of communities at risk, identified through the epidemiological data, would be to reduce the delay in consultation that is detrimental to the efficiency of treatment. Partnerships need to be coordinated to optimize resources from international institutions, particularly African ones, and share the burden of treatment costs among all stakeholders. We propose here a project of progressive implementation of antivenom manufacturing in sub-Saharan Africa. The various steps, from the supply of appropriate venoms to the production of purified specific antibodies and vial filling, would be financed by international, regional and local funding promoting technology transfer from current manufacturers compensated by interest on the sale of antivenoms.

Abstract Background The whole blood clotting test (WBCT) is a simple test of coagulation that is often used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in sub-Saharan Africa. WBCT requires only a clean glass tube and several milliliters of venous blood and is ideal for use in poorly equipped health centers throughout the rural areas where 95% of snakebites occur. However, questions surrounding the accuracy and reliability of the test remain unanswered due to variations in testing conditions and a lack of comparative research with which to validate them. This is the first study to evaluate WBCT results at both 20-min (WBCT20) and 30-min (WBCT30) reading times in the same group of snakebite patients. Methods In order to define the best reading time, the authors compared the results of serial WBCT evaluation at both 20 and 30 min after collection in 23 patients treated for snake envenomation in Bembèrèkè, northern Benin. Results WBCT results were identical at both reading times in patients without coagulopathy or when coagulation was restored permanently following a single dose of antivenom. Out of 17 patients with coagulopathy, 14 showed discrepancies between WBCT20 and WBCT30 results in at least one pair of serial evaluations. These could be completely contradictory results (e.g. normal clot at WBCT20 and no clot at WBCT30) or a marked difference in the quality of the clot (e.g. no clotting activity at WBCT20 and an unstable partial clot at WBCT30). WBCT discrepancies were encountered most frequently in three situations: initial normalization of hemostasis following antivenom therapy, detection of a secondary resumption of coagulopathy, or final restoration of hemostasis after a secondary resumption had occurred. Conclusions This study suggests that the WBCT is robust and that a sequential reading should improve the diagnosis and monitoring of venom-induced coagulopathies. It also indicates the possibility of discrepancies in the sensitivity of WBCT20 and WBCT30 for detecting the resolution or reoccurrence of coagulopathy and identifies how these findings, if confirmed, may be used to increase the efficacy and efficiency of antivenom treatment in the field.

Abstract Yellow fever was transported during the slave trade in the 15th and 16th centuries from Africa to the Americas where the virus encountered favorable ecological conditions that allowed creation of a sustainable sylvatic cycle. Despite effective vector control and immunization programs for nearly a century, yellow fever epidemics reemerged in many Latin American countries, particularly Brazil. The emergence or reemergence of vector-borne diseases encompasses many intricate factors. Yellow fever outbreaks occur if at least three conditions are fulfilled: the introduction of the virus into a non-immune human community, presence of competent and anthropophilic vectors and insufficiency of prevention and/or adequate management of the growing outbreak. On the other hand, two weapons are available to constrain yellow fever: vector control and immunization. In contrast, yellow fever is absent from Asia and the Pacific despite the presence of the vector and the susceptibility of human populations to the virus. Based on a review of the global history of yellow fever and its epidemiology, the authors deliver some recommendations for improving the prevention of epidemics.

Abstract Background Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. Methods In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. Results This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research – CONEP) and sanitation (National Health Surveillance Agency – ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. Conclusions This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.

Abstract: On June 9th, 2017 WHO categorized snakebite envenomation into the Category A of the Neglected Tropical Diseases. This new situation will allow access to new funding, paving the way for wider and deeper researches. It should also expand the accessibility of antivenoms. Let us hope that it also leads to cooperation among stakeholders, aiming at improving the management of snakebites in developing countries.

Abstract Background In Africa, snakebite envenomations are frequently complicated by life-threatening hemorrhagic syndromes. The authors of the present study conducted a prospective analysis at the University Hospital of Parakou (north of Benin) for seven months (January 1 to July 31, 2014) to assess the contribution of ultrasonography to the diagnosis of internal bleedings and management of envenomation. Methods An ultrasound examination was performed in all patients with clinical envenomation regardless of its severity. The study involved 32 patients admitted to the ICU of the University Hospital of Parakou. Results The average age was 27 ± 13.9 years. The main signs of severity were: prolongation of clotting time (88 %), severe anemia (41 %), clinical hemorrhage (47 %), and shock (19 %). The ultrasound imaging showed internal hemorrhage in 18 patients (56 %). There were hematomas (22 %), hemoperitoneum (13 %) or a combination of both (22 %). The occurrence of internal bleeding and hemoperitoneum were mainly related to the delay of hospital presentation (p = 0.007) and the existence of external bleeding (p = 0.04). Thirty patients (94 %) received antivenom. Case fatality rate was 3.1 %. Conclusion Ultrasonography may help in diagnosing internal bleeding, even in patients that did not show external hemorrhages, and evaluating its importance. As a consequence, the management of snakebite victims may be significantly improved.

Abstract Background Although considered a public health issue in Senegal, the actual incidence and mortality from snakebite are not known. In the present study, an epidemiological survey was carried out in Kédougou region, southeastern Senegal, where envenomations, particularly by Echisocellatus, are frequent and severe. Methods Three sources of data were used: records from health centers and reports by health professionals; traditional healers; and household surveys. Results The annual incidence and mortality provided by health centers were 24.4 envenomations and 0.24 deaths per 100,000 population, respectively. The annual incidence recorded by traditional healers was 250 bites per 100,000 inhabitants, but the number of deaths was unknown. Finally, the household surveys reported an annual incidence of 92.8 bites per 100,000 inhabitants and an annual mortality rate of 2.2 deaths per 100,000 inhabitants. The differences in incidence and mortality between the different methods were explained by significant bias, resulting in particular from the complex patient's healthcare-seeking behavior. The incidence provided by health records should be used to specify the immediate quantitative requirements of antivenoms and places where they should be available first. Conclusion Mandatory reporting of cases would improve the management of envenomation by simplifying epidemiological surveys. Patients' preference for traditional medicine should prompt health authorities to urge traditional healers to refer patients to health centers according to defined clinical criteria (mainly edema and bleeding or neurotoxic symptoms). Finally, household surveys were likely to reflect the actual epidemiological situation. Poison Control Center of Senegal should continue its work to sensitize stakeholders and train health staff.

Abstract During the 6th International Conference on Envenomation by Snakebites and Scorpion Stings in Africa held in Abidjan, from 1 to 5 June 2015, the measures for the management of envenomation were discussed and new recommendations were adopted by the participants. The high incidence and severity of this affliction were confirmed by several studies conducted in African countries. The poor availability of antivenom, particularly because of the cost, was also highlighted. Some experiences have been reported, mainly those regarding the financial support of antivenom in Burkina Faso (more than 90 %) and Togo (up to 60 %) or the mandatory reporting of cases in Cameroon. Key recommendations concerned: improvement of epidemiological information based on case collection; training of health workers in the management of envenomation; policy to promote the use of effective and safe antivenom; and antivenom funding by sharing its costs with stakeholders in order to improve antivenom accessibility for low-income patients.

Abstract Background Snakebites cause considerable death and injury throughout the globe, particularly in tropical regions, and pose an important yet neglected threat to public health. In 2008, the Centre Anti Poison et de Parmacovigilance du Maroc (CAPM) started to set up a specific strategy for the control of snakebites that was formalized in 2012. The aim of the present study is to describe and update the epidemiological characteristics of snakebites notified to CAPM between 2009 and 2013. Methods This retrospective five-year study included all cases of snakebites notified to CAPM by mail or phone. Results During the study period, 873 snakebite cases were reported to CAPM, an average incidence of 2.65 cases per 100,000 inhabitants with 218 cases each year. The highest incidence was found in Tangier-Tetouan region with 357 cases (40.9 %) followed by Souss Massa Draa region with 128 cases (14.6 %). The average age of patients was 26.8 ± 17.2 years. The male to female sex ratio was 1.67:1 and 77 % of cases occurred in rural areas. The bites occurred mainly in spring (44 %) followed by summer (42 %). Snake species was identified in 54 cases (6.2 %): colubrids represented 31 % (n = 18) and vipers 67 % (n = 36), mainly Daboia mauritanica, Bitis arietans and Cerastes cerastes. In 311 cases (35.6 %), the patients showed viper syndrome. Thrombocytopenia was observed in 23.5 % of viper syndrome cases, whereas, compartment syndrome was observed in 7.6 % patients. FAV-Afrique® was administered in 41 patients (5 %). In patients treated with antivenom, 38 patients recovered and three died. Twenty-seven deaths were reported (3.9 %). Conclusion Despite specific efforts to better understand the epidemiology of snakebites in Morocco (incidence, severity, snake species involved), it remains underestimated. Therefore, further work is still necessary to ensure accessibility of appropriate antivenom against venomous species and to improve the management of envenomation in Morocco.

Background Better treatments are urgently needed for the management of Ebola virus epidemics in Equatorial Africa. Methods We conducted a systematic review of the literature on the use of passive immunotherapy for the treatment or prevention of Ebola virus disease. We placed findings from this review into the context of passive immunotherapy currently used for venom-induced disease, and recent improvements in manufacturing of polyvalent antivenom products. Results Passive immunotherapy appears to be one of the most promising specific treatments for Ebola. However, its potential has been incompletely evaluated, considering the overall experience and recent improvement of immunotherapy. Development and use of heterologous serum derivatives could protect people exposed to Ebola viruses with reasonable cost and logistics. Conclusion Hyperimmune equine IgG fragments and purified polyclonal whole IgG deserve further consideration as treatment for exposure to the Ebola virus.

<title>Abstract</title><sec><title>Background:</title><p>Envenomation remains a neglected public health issue in most tropical countries. A better understanding of the epidemiology of bites and stings by venomous animals should facilitate their prevention and management. This study aimed to explore the benefits that could be derived from the compulsory notification of cases as it is now routinely practiced in Brazil.</p></sec><sec><title>Methods:</title><p>The Brazilian Notifiable Diseases Information System (SINAN) was consulted online for the 2001-2012 period on all envenomations by venomous terrestrial animals. We studied the incidence, severity, number of deaths, gender, season of accident and time between the accident and hospital consultation.</p></sec><sec><title>Results:</title><p>In total, 1,192,667 accidents and 2,664 deaths from terrestrial venomous animals (snakes, scorpions, spiders, bees and caterpillars) were reported in Brazil during these 12 years, the circumstances of which are detailed in this study. Most envenomations and deaths were caused by snakebites and scorpion stings. However, incidence and mortality showed high regional variations. During this period, the steady and parallel increase of the cases from all the species resulted from several factors including the human population increase, gradual improvement of data collection system and, probably, environmental and socioeconomic factors affecting in a different way the incidence of envenomation by each zoological group and by region.</p></sec><sec><title>Conclusion:</title><p>Mandatory reporting of cases appears to be a useful tool to improve the management of envenomations. However, local studies should be continued to account for the variability of accident circumstances and refine measures necessary for their management.</p></sec>

The tremendous outbreak of Ebola virus disease occurring in West Africa since the end of 2013 surprises by its remoteness from previous epidemics and dramatic extent. This review aims to describe the 27 manifestations of Ebola virus that arose after its discovery in 1976. It provides an update on research on the ecology of Ebola viruses, modes of contamination and human transmission of the disease that are mainly linked to close contact with an infected animal or a patient suffering from the disease. The recommendations to contain the epidemic and challenges to achieve it are reminded.