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Objective: This work aimed to assess the impact of COVID-19 on healthcare supply in sub-Saharan Africa except South Africa. Method: A search through PubMed® between April 2020 and August 2022 selected 135 articles. The impact of COVID-19 was assessed on comparisons with the months prior to the onset of COVID-19 or an identical season in previous years. Results: The decline of health services, associated with a reduction in their quality, and the closure of specialized health units have been reported. Many control programs and public health interventions have been interrupted, with the risk of an increase of the corresponding diseases. Social disorganization has generated mental health issues among the population, including health personnel. The impact was heterogeneous in space and time. The main causes were attributed to containment measures (transport restrictions, trade closures) and the lack of human and material resources. The increase in costs, in addition to the impoverishment of the population, and the fear of being contaminated or stigmatized have discouraged patients from going to health centres. The studies mention the gradual return to normal after the first epidemic wave and the resilience of the healthcare system. Conclusion: Several articles make recommendations aimed at reducing the impact of future epidemics: support for community workers, training of health workers and reorganization of services to improve the reception and care of patients, technological innovations (use of telephones, drones, etc.) and better information monitoring.
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INTRODUCTION: Secondary infection is a frequent complication after bites by Bothrops atroxin French Guiana or B. lanceolatus in Martinique. Knowledge of the bacteria present in snake mouths is a valuable aid for determining probabilistic antibiotherapy after Bothrops bite. The objectives of this study were to describe the cultivable bacteria of the oral microbiota of the specimens of B. atrox and B. lanceolatus kept in captivity, and to study their susceptibility to antibiotics. METHODS: Fifteen B. atrox and 15 B. lanceolatus were sampled. Bacterial cultures were performed and each morphotype on plates was identified using MALDI-TOF mass spectrometry. Antibiotic susceptibility was studied using the agar disk diffusion method, with possible determination of the MICs. RESULTS: One hundred and twenty-two isolates were identified: 52 isolates and 13 species in B. atrox, 70 isolates and 23 species in B. lanceolatus. The main species were Providencia rettgeri, Morganella morganii, Pseudomonas aeruginosa, Staphylococcus xylosus, and Paeniclostridium sordellii (only in B. lanceolatus mouths). For B. atrox, 96% of isolates were susceptible to piperacillin/tazobactam, cefepime, imipenem and meropenem, 94% to ciprofloxacin and 76% to cefotaxime and ceftriaxone. For B. lanceolatus, 97% of isolates were susceptible to meropenem, 96% to cefepime, 93% to imipenem and piperacillin/tazobactam, 80% to ciprofloxacin, and 75% to cefotaxime and ceftriaxone. Many isolates were resistant towards amoxicillin/clavulanate. CONCLUSION: Among currently recommended antibiotics, cefepime and piperacillin/tazobactam seem more suitable than cefotaxime or ceftriaxone in the event of a Bothrops bite. Ciprofloxacin may also be considered for B. atrox.
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The following study aims at assessing the ophidian diversity of the Lama Forest, a classified area, situated in the South of Benin. One can distinguish three types of habitat according to the degree of human activity: the remaining dense forest at the centre, the intermediate plantation area, and finally the area around the edge which has been entirely subjected to human habitation. Each day for two weeks we have been working on various plots of study (by day), patrolled along transect routes (by night), and installed a trap in the central area. As a result, we were able to observe 32 snake specimens, 24 of which we captured. Nearly all were able to be identified, and have been classified into 13 genera and 17 species.
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Biodiversidade , Serpentes , Animais , Benin , Ecossistema , Geografia , Humanos , Projetos Piloto , Densidade Demográfica , Serpentes/fisiologia , ÁrvoresRESUMO
An open, pragmatic, phase IV clinical trial was undertaken to measure tolerance and assess the effectiveness of Antivipmyn® Africa, antivenom composed of lyophilized F(ab')(2) fragments of immunoglobulin G in field conditions. The study was conducted at the Institut Pasteur of Guinea (IPG) from August 2009 to February 2010. Two hundred twenty-eight victims of snakebites presented at the processing center of the IPG during this period, including one hundred fifty (65.8%) envenomations, mostly young men. One hundred twenty-four of them (82.7%) suffered from viper envenomations and 26 (17.3%) from elapid ones. All patients were treated by intravenous Antivipmyn® Africa, averaging 1.4 (± 1.0) vials, more in patients with neurotoxic envenomation than others (P < 10(-5)). Four patients (2.7%), showing cobralike envenomation, died shortly after their arrival at the IPG despite the administration of the antivenom. Ten patients showed mild side effects (rash or pruritus), out of which 5 (3.3%) were probably due to treatment. This study confirms the efficacy and safety of Antivipmyn® Africa.
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Antivenenos/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antivenenos/efeitos adversos , Criança , Pré-Escolar , Diagnóstico Tardio/estatística & dados numéricos , Feminino , Guiné/epidemiologia , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Lactente , Masculino , Pessoa de Meia-Idade , Mordeduras de Serpentes/diagnóstico , Mordeduras de Serpentes/epidemiologia , Venenos de Serpentes/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
The authors present a summary of the proceedings and the recommendations of the Fourth International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, held from 25 to 29 April 2011 in Dakar. After a two-day workshop for Senegalese health personnel on the most relevant aspects of the management of envenomations, about 270 participants met to share their experiences in the field. Nearly a hundred oral and poster presentations were made on the epidemiology of snakebites and scorpion stings in Africa, the composition and action of venoms and the manufacture and use of antivenoms. The last day was devoted to an institutional debate involving experts, representatives of national health authorities and concerned professionals (physicians, pharmacists, nurses and traditional healers) as well as members of the pharmaceutical industry to discuss and elaborate a set of recommendations. It was agreed that it is necessary to improve knowledge of the epidemiological situation by case reporting. Quality control of antivenoms and procedures for their registration at the level of national health authorities should aim at improving the distribution of safe and effective antivenoms in peripheral health centers for the better assessment of victims. It was also recommended that adequate training should be provided for health personnel in all aspects of medical management of envenomations. Equitable distribution of funding and the establishment of a network of African experts were also discussed in the conference.
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Congressos como Assunto , Picadas de Escorpião , Escorpiões , Mordeduras de Serpentes , África/epidemiologia , Animais , Antivenenos/uso terapêutico , Mordeduras e Picadas/epidemiologia , Mordeduras e Picadas/terapia , Humanos , Cooperação Internacional , Guias de Prática Clínica como Assunto , Picadas de Escorpião/epidemiologia , Picadas de Escorpião/terapia , Venenos de Escorpião/imunologia , Escorpiões/anatomia & histologia , Escorpiões/imunologia , Senegal/epidemiologia , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/terapia , Venenos de Serpentes/imunologia , Serpentes/anatomia & histologia , Serpentes/imunologiaRESUMO
BACKGROUND: Anemia during pregnancy is a serious public health problem. Control requires identification of the underlying etiology. The objective of this study carried out in conjunction with revision of the national policy for the protection of pregnant women in Benin was to determine the prevalence and etiology of anemia. METHODS: From October 2006 to April 2007, 300 pregnant women were examined at two maternities in Ouidah, Benin. Sociodemographic and environmental characteristics, dietary data, behavioral practices, and history of malaria infection during pregnancy were collected. Blood and stool samples were tested for the presence of malaria parasites and intestinal worms respectively. Hemoglobin and ferritinemia levels were also determined. RESULTS: The prevalence of anemia (Hb < 11 g/dL) was 65.7% while that of malaria and intestinal worms was 4.3% and 8% respectively. Iron deficiency was not found. A borderline significant correlation was found between helminthiasis and anemia. No correlation was found between anemia and malaria. These findings indicate that kits progressively introduced by the health system during the study period provided relatively effective care. CONCLUSION: This study demonstrates a high prevalence of moderate anemia during pregnancy and suggests that it is mainly due to intestinal helminthiasis. These findings underline the importance of preventive antihelminthic treatment during pregnancy.
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Anemia/epidemiologia , Anemia/etiologia , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/etiologia , Anemia/terapia , Benin/epidemiologia , Feminino , Política de Saúde , Humanos , Gravidez , Complicações Hematológicas na Gravidez/terapia , PrevalênciaRESUMO
The number of papers regarding envenoming is increasing but they often miss information and presentation to assess the needs for proper management. The author suggests some criteria to make data more informative and makes recommendations to improve the presentation of the method and results used for the study, and build argued discussion.
Le nombre d'articles concernant les envenimations s'accroît, mais ils y manquent encore trop souvent les informations et la présentation nécessaires à l'évaluation des besoins pour une prise en charge appropriée. L'auteur propose quelques critères pour rendre les données plus informatives et fait des recommandations pour améliorer la présentation de la méthode et des résultats, et construire une discussion argumentée.
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Picadas de Escorpião/diagnóstico , Mordeduras de Serpentes/diagnóstico , Humanos , Picadas de Escorpião/epidemiologia , Mordeduras de Serpentes/epidemiologiaRESUMO
The importance of congenital transmission of Chagas' disease increases with its emergence in communities infected with Trypanosoma cruzi, but where vector transmission has never existed or is fully controlled through vector control campaigns. In both endemic and non-endemic areas, the rates of mother-to-child transmission (MTCT) could be the same, by 5%, generating a constant source of new cases of the disease. Risk factors for vertical transmission are not fully elucidated, but the effectiveness of the adaptive immune response and the genetic susceptibility of both the mother and the child are suspected. Besides the risk of miscarriage or premature birth, neonatal infection by T. cruzi causes an acute form of Chagas disease, which may be accompanied by a severe infectious syndrome that can causes death if not treated early. This form of the disease is a real public health priority because it is frequent, severe, identifiable and curable. Indeed, almost all newborns diagnosed and treated before the end of their first year of life will be definitely cured. In all non-endemic areas, detection of cases of congenital Chagas disease is hampered by a very low prevalence of the disease in the general population of pregnant women, the lack of symptoms in most infected women and the disregard of these problems from health personnel in charge of monitoring pregnancy. Secondary prevention firstly consists in identifying infected women (with history of exposure and positive serology for Chagas disease) and secondly to look for the parasite in newborns from infected mothers. No primary prevention is indeed possible during pregnancy, since the only two drugs are toxic and possibly teratogenic. However, after birth, treatment could be offered to all infected women in order to prevent late complications of the disease and to make an attempt at breaking the chain of MTCT in future pregnancies.
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Doença de Chagas/congênito , Doença de Chagas/epidemiologia , Animais , Doença de Chagas/transmissão , Feminino , Humanos , Incidência , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , México/epidemiologia , Gravidez , População Rural , América do Sul/epidemiologia , Trypanosoma cruziRESUMO
A demographic survey site has been implemented in Niakhar rural zone in Senegal since the 1960s and many epidemiological and demographic studies have been conducted in this context. In this Sahelo-Sudanese area, malaria transmission is mesoendemic and mainly seasonal. In health care facilities, malaria real burden is poorly known as malaria diagnosis only relies on patients' clinical signs. The aim of our study was to measure the reliability of malaria diagnosis in these health centres by performing a parasitological confirmation of presumptive malaria cases and by assessing the validity of diagnosis according to child's age. A cross-sectional study was conducted in August-December 2006 (rainy season) and in February-June 2007 (dry season) in three health care facilities of the area (2 public centres and one private dispensary). Children aged 1 to 14 years old and accompanied by an adult were included. Two thick blood smears were carried out for each patient. A total of 474 children were included; among them 208 (43.9%) had a positive blood smear. Among the 335 (70.7%) presumptive malaria cases, 182 (54.3%) were confirmed by thick smear. Sensitivity specificity positive and negative predictive values were respectively 87.5%, 42.6%, 55.3% and 80.7%. Clinical signs which were predictive of confirmed malaria were vomiting and body temperature > or =38 degrees C. Clinical diagnosis performances decreased significantly during the dry season and in children under the age of two. The proportion of true malaria cases (54.3%) confirms the results of previous studies described in literature and shows a consistency for the last twenty years. Malaria is the main diagnosis attributed to patients by health care agents, regardless of the child's age or the season, whereas thick smear results are predominantly negative among children aged less than 2 and during dry season. A better knowledge of malaria morbidity in these health care facilities is an asset for setting up further epidemiological studies in this area and implementing interventions aiming at improving patients' care.
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Serviços de Saúde da Criança/normas , Malária/diagnóstico , Serviços de Saúde Rural/normas , Adolescente , Adulto , Criança , Serviços de Saúde da Criança/estatística & dados numéricos , Demografia , Humanos , Lactente , Malária/epidemiologia , Serviços de Saúde Rural/estatística & dados numéricos , População Rural/estatística & dados numéricos , Senegal/epidemiologia , Sensibilidade e EspecificidadeRESUMO
Verbal autopsy (VA) is a technique designed for reliable determination of the cause of death by interviewing the entourage of the deceased. When conducted rigorously using a standardized questionnaire, VA can establish the most probable diagnosis. Data obtained by VA can be suitable for demographic or epidemiologic purposes. The VA technique depends on the exact purpose for which the data will be used.
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Autopsia/métodos , Coleta de Dados/métodos , Países em Desenvolvimento , HumanosRESUMO
PURPOSE: The aim of the study was to determine the accuracy of a rapid diagnostic test in confirming presumptive malaria diagnosis in a rural zone of Senegal. Thick blood smear was used as the reference technique for comparison. METHOHDOLOGY: Testing was conducted on children between the ages of 1 and 14 years at three health care facilities located in the Niakhar are from August 2006 to June 2007. If malaria was suspected by the nurse based on clinical findings, two thick smears and one rapid diagnostic test (Core Malaria Pf) were performed. Blood slides were stained in Niakhar and read in Dakar. RESULTS: A total of 474 patients were examined. Three-fourths (75%) of these patients were seen during the rainy season. Malaria was suspected in 335 patients (71%). Rapid tests and thick smears were obtained in 330 of these patients with positive results in 194 (59%) and 180 (55%) respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the rapid test were 96%, 87%, 90% and 95% respectively. CONCLUSION: Our data show that the rapid diagnostic test used in this study exhibits good sensitivity and positive predictive value. Despite its cost this test could be helpful in confirming malaria diagnosis in outlying health care facilities without the necessary resources to perform blood smears. Confirmation is necessary to avoid unwarranted prescription of malaria treatment due to inaccurate clinical diagnosis
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Malária/diagnóstico , Kit de Reagentes para Diagnóstico , Serviços de Saúde Rural , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Valor Preditivo dos Testes , População Rural , Senegal , Sensibilidade e EspecificidadeRESUMO
The scorpionism is an actual public health problem in several parts of the world because, either incidence, or severity of envenomations is high and managed with difficulty by health services, or for these two reasons at the same time. The treatment of scorpion envenomation is complex and controversial, in particular regarding the utility of the antivenoms and symptomatic treatments that must be associated. The authors reviewed the literature of last 30 years to discuss the epidemiologic importance of scorpionism and to point out the principal therapeutic or preventive measures. According to the most recent studies, seven areas were identified as at risk: north-Saharan Africa, Sahelian Africa, South Africa, Near and Middle-East, South India, Mexico and South Latin America, east of the Andes. These involve 2.3 billion at risk population. The annual number of scorpion stings exceeds 1.2 million leading to more than 3250 deaths (0.27%). Although adults are more often concerned, children experience more severe envenomations and among them, mortality is higher. Improvement of therapeutic management would reduce the lethality very significantly.
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Antivenenos/uso terapêutico , Saúde Global , Picadas de Escorpião/epidemiologia , Venenos de Escorpião/efeitos adversos , Escorpiões , Adolescente , Adulto , Animais , Criança , Humanos , Incidência , Picadas de Escorpião/diagnóstico , Picadas de Escorpião/terapia , Venenos de Escorpião/químicaRESUMO
The authors carried out a 1-year study of a population of pregnant women delivering at Bermejo hospital, South Bolivia. In this area, vectorial transmission of Trypanosoma cruzi is negligible and women infect themselves during displacements in close endemic areas. The prevalence of T. cruzi in 508 pregnant women, diagnosed by several serological tests, was 33.9%. In eight infants, we observed T. cruzi in the umbilical cord (congenital transmission rate of 5.2%). The means of birth weights, lengths and hemoglobin rates were similar in the children from both seronegative and seropositive women, and in children infected or not by T. cruzi. This study could confirm a less severity of the congenital disease of Chagas in the absence of re-infestation of the mother during pregnancy. Serological screening of pregnant women by rapid diagnostic tests and examination of babies born from seropositive mothers by microhematocrit method at birth is a suitable strategy to detect and prevent congenital Chagas disease in non-endemic areas.
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Doença de Chagas/diagnóstico , Doença de Chagas/fisiopatologia , Doenças do Recém-Nascido/parasitologia , Trypanosoma cruzi/isolamento & purificação , Adolescente , Adulto , Animais , Bolívia/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Gravidez , Prevalência , Testes Sorológicos , Cordão Umbilical/parasitologiaRESUMO
BACKGROUND: Currently, the control of urinary schistosomiasis is mostly based on mass treatment. Characterization of Schistosoma haematobium transmission could lead to adding new methods to the control strategy. METHODS: We carried out malacological and cercariometrical surveys in irrigated perimeters of the Niger River valley. A semi-monthly follow-up was performed in three main sites of human-water contact in a village located at the border of the irrigated perimeter. Bulinids were collected during 20 min; after identification based on the shell morphology, their parasites were characterized by isoelectrofocalisation. The cercariometrical technique by differential filtration was used to evaluate the density of cercariae in every site with two 20-litre samples of water collected at various periods of the day (9, 12, 15 and 18 h). RESULTS: In the arm of the river, the cercariometry never showed cercariae whereas only some Bulinus truncatus, all negative, were collected. In the channels, B. truncatus and B. globosus were observed and highest density was found during the dry season. Only B. truncatus was naturally infested. Homozygote BB phenotype (characteristic of S. haematobium) was observed in all positive molluscs. Using cercariometry, more than two third of cercariae were collected at 3:00 PM. CONCLUSION: Transmission of S. haematobium was primarily focused in the irrigating channels during the dry hot season at the beginning of afternoon. These results should lead to improve the output of S. haematobium control methods within irrigated areas.
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Rios/parasitologia , Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/transmissão , Agricultura , Animais , Humanos , Níger , Abastecimento de ÁguaRESUMO
Preventive trials (to prevent from infection) or prophylaxis trials (to avoid consequences of the disease) differ from other clinical trials as they apply to healthy subjects or subjects considering themselves as such: the latter do not ask for intervention even less for trial. Moreover, it is generally an experiment which aims at validating a public health intervention, the individual character of which could appear as secondary regarding the collective interest. It concerns many tools or methods: preventive or prophylactic vaccines and drugs, condoms, impregnated bed nets, etc. The field of implementation of preventive trials is large and covers routine immunization (EPI), large-scale control or eradication of endemic diseases or epidemics, for which the concept of individual risk is generally better understood. Preventive trials imply ethical obligations (high individual or collective benefits and absence of risks as there is no immediate therapeutic compensation), methodological adaptations (because the number of subjects is considerably larger than for therapeutic trials) and a sensitive valorization towards a large population who is not asking for the recommended intervention. As regard the benefits, it is also necessary to consider the costs in comparison with the expected efficacy The methodological constraints are important because the demonstration of both safety and efficacy requires a very large number of subjects to validate the product. It is often necessary to use indirect or substitutive markers and indicators (title of protective antibodies rather than definite clinical protection) which need a preliminary validation. Before carrying out a preventive or prophylactic trial, it is advisable to specify the objectives in order to assess the real profits and absence of risks during the trial and after the implementation of the tested product. Preventive trials require a phase of technological transfer to guarantee the application of the validated tools for the benefit of the population at stake. In this respect, if trials for prevention are now well codified both on ethical and methodological aspects, trials for prophylaxis (filariasis with ivermectin, schistosomiasis with praziquantel, malaria with intermittent "preventive" treatment or HIV with antiretroviral treatment, for example) still remain a difficult issue at both ethical and methodological levels.
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Ensaios Clínicos como Assunto/ética , Experimentação Humana/ética , Medicina Preventiva/ética , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Experimentação Humana/normas , Humanos , Doença Iatrogênica/prevenção & controle , Medicina Preventiva/métodos , Medicina Preventiva/normas , Sujeitos da Pesquisa , Medição de RiscoAssuntos
Sociedades Científicas/organização & administração , Toxicologia/organização & administração , Peçonhas , Academias e Institutos/organização & administração , Academias e Institutos/tendências , África , Pesquisa Biomédica/organização & administração , Congressos como Assunto , Europa (Continente) , Humanos , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/mortalidade , Mordeduras de Serpentes/terapia , Toxicologia/tendências , Peçonhas/classificaçãoRESUMO
We studied some biochemical, toxic and immunological characteristics of the venoms of Bothrops atrox, Bothrops brazili and Lachesis muta, Viperidae responsible for most of the bites of venomous snakes in French Guiana. Chromatographic (HPLC) and electrophoretical profiles (SDS-PAGE), lethal, hemorrhagic, defibrinogenating, coagulant, thrombin like, proteolytic, fibrino(geno)lytic and phospholipase activities were studied. In addition, the neutralization of some toxic activities conferred by four antivenins was compared. The chromatographic and electrophoretic profiles were different for the three venoms, showing differences between Bothrops and L. muta venoms. In general, bothropic venoms showed the highest toxic and enzymatic activities, while the venom of L. muta showed the lowest lethal, hemorrhagic and coagulant activities. The enzymes of bothropic venoms responsible for gelatinolytic activity were around 50-90 kDa. All the venoms were able to hydrolyze a and beta chains of the fibrinogen, showing different patterns of degradation. Although all the antivenoms tested were effective to various degrees in neutralizing the venom of B. brazili and B. atrox, neutralization of L. muta venom was significantly better achieved using the antivenom including this venom in its immunogenic mixture. For the neutralization of L. muta venom, homologous or polyvalent antivenoms that include the "bushmaster" venom in their immunogenic mixture should be preferred.
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Antivenenos/uso terapêutico , Venenos de Serpentes/classificação , Venenos de Serpentes/toxicidade , Animais , Mordeduras e Picadas/tratamento farmacológico , Mordeduras e Picadas/epidemiologia , Venenos de Crotalídeos/toxicidade , Guiana Francesa/epidemiologia , Humanos , Testes de Neutralização , Venenos de Víboras/toxicidadeRESUMO
The 3rd International Conference on Envenomations was held in Brazzaville from 15 to 17 November; 2007. At this meeting, updating of epidemiological and treatment information on envenomations in Africa were presented. A round table concluded the conference drawing contributors' main recommendations. One of these recommendation pointed out the need to treat the problem of envenimations at a regional level by creating a group of experts in charge of considering the priorities as well as identifying relevant strategies of management, ensuring the plea and finding the financing.
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Antivenenos/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , África , Congressos como Assunto , Países em Desenvolvimento , Humanos , Fatores de Risco , Mordeduras de Serpentes/epidemiologiaRESUMO
The incidence of scorpion stings and spider bites is high in Latin America. This is particularly true for Mexico, part of Amazonia, and southern and eastern Brazil. Centruroides and Tityus scorpion stings present a real danger for humans, especially children. Envenomation results in intense pain, neurological signs, and cardiorespiratory manifestations that can lead to death by acute pulmonary edema or heart failure. In the event of confirmed envenomation, antivenin must be administered as soon as possible in association with symptomatic treatment and, if necessary, cardiorespiratory resuscitation. Spider bites are a less frequent and severe. Envenomation by Loxosceles is extremely painful and necrotizing. Severe visceral complications can develop. An effective antivenim has recently become available for local and systemic envenomation. Envenomation by Latrodectus leads to neurological symptoms that can also be treated with antivenom. Envenomation by other spiders is less frequent and generally harmless.