Tropical Medicine and Infectious Disease

In Morocco, eight species of venomous snakes belonging to the Viperidae and Elapidae families are responsible for severe envenomation cases. The species from the Elapidae family is only represented by the medically relevant cobra Naja haje, which is widely distributed in North Africa. However, there is little information on the systemic effects of Moroccan cobra venom on vital organs due to regional variations. It has been demonstrated that the venom of Naja haje from Egypt causes hemorrhage, while the venom of the Moroccan cobra is neurotoxic and devoid of systemic bleeding. This variability is known to significantly influence treatment efficacy against Naja haje cobra bites in the Middle East. In this study, we examined the pathophysiological mechanisms responsible for the lethality induced by Naja haje venom, as well as the evaluation of the neutralizing capacity of two antivenoms; the monospecific antivenom made for Naja haje only and the antivenom marketed in the Middle East and North Africa. We first determined the toxicity of Naja haje venom by LD₅₀ test, then compared the neutralizing capacity of the two antivenoms studied by determining the ED₅₀. We also performed histological analysis on Swiss mice envenomed and treated with these antivenoms to observe signs of cobra venom envenomation and the degree of reduction of induced systemic alterations. The results showed significant differences between both antivenoms in terms of neutralization. The monospecific antivenom was four times more effective than the marketed antivenom. These results were confirmed by a histological study, which showed that monospecific antivenoms neutralized severe signs of mortality, such as congestion of blood vessels in the heart and kidneys, pulmonary and renal edema, cytoplasmic vacuolization of hepatocytes in the liver, and infiltration of inflammatory cells in the brain and spleen. However, the polyvalent antivenom failed to protect all severe lesions induced by Naja haje venom in mice. These findings highlight the negative impact of geographic variation on the effectiveness of conventional antivenom therapy and confirm the need for a specific Naja haje antivenom for the effective treatment of cobra envenomation in Morocco. Full article

The protoscolex (PSC) is generated by asexual reproduction at the larval stage of taeniid Echinococcus granulosus that causes cystic echinococcosis or hydatidosis, a worldwide zoonosis. The PSC is enveloped by a complex cellular syncytial tegument responsible for ionic movements and the hydroelectrolytic balance of the parasite. We recently reported on two electrical potentials in bovine lung protoscoleces (PSCs) that reflect differences in ionic movements between the parasite’s invaginated and evaginated developmental stages. Here, we explored the effect of temperature and ionic substitutions on the tegumental potentials of bovine lung PSCs of Echinococcus granulosus by microelectrode impalements. We observed that the transient peak potential was temperature-dependent, consistent with an active transport component in the invaginated state only. Further changes in the electrical potentials by high K⁺ depolarization, low external Ca²⁺, and addition of the diuretic amiloride are in agreement with the presence of a Ca²⁺-sensitive cation-selective electrodiffusional pathway in the outer surface of the parasite. Variations in electrical potential differences through the tegument provide an accessible and valuable parameter for studying ionic transport mechanisms and, therefore, potential targets for developing novel antiparasitic drugs. Full article

Morocco is one of the richest countries in biodiversity in the Mediterranean region, especially in its ophidian fauna. In total, there are eight species of venomous snakes, with seven belonging to the Viperidae family, responsible for 67.2% of severe envenomation cases in the country. Cerastes cerastes, Daboia mauritanica and Bitis arietans are considered among the most venomous vipers whose bites cause high levels of morbidity, disability or mortality. Despite their wide distribution in the kingdom, the incidence of these snakebites remains poorly understood and largely underestimated. Moreover, intraspecific variations in the venom composition significantly affect the effectiveness of antivenoms. Due to the unavailability of locally produced antivenoms, we evaluated the efficacy of Inoserp-MENA, the only available antivenom in Morocco, against C. cerastes, D. mauritanica and B. arietans. First, we conducted a comprehensive characterization of these venoms, including an LD₅₀ test to examine their toxicity and SDS-PAGE as a technique to analyze the enzymes responsible for biological activities, such as hemorrhagic and edematous activities and myotoxicity, which generate physiopathological effects in the skin, paws and muscles of envenomed mice. Then, we assessed the ability of Inoserp-MENA antivenom to neutralize the toxic activities of Moroccan vipers. Our results indicate that the venom of C. cerastes, D. mauritanica and B. arietans are toxic, causing severe alterations such as edema, myotoxicity, myonecrosis and significant hemorrhages with the formation of hemorrhagic foci. C. cerastes venom is more dangerous in terms of lethality and hemorrhages, while B. arietans venom is more edematous. The effects of C. cerastes venom were effectively neutralized, but Inoserp-MENA antivenom failed to protect mice against the toxic effects induced by B. arietans and D. mauritanica venom. The study reveals alarming shortcomings in the effectiveness of the current commercially available antivenom’s dosage and neutralization capabilities, highlighting the urgent need to develop a region-specific viper envenomation therapy. Full article

Chikungunya (CHIK) is a re-emerging viral infection endemic in tropical and subtropical areas. While the typical clinical presentation is an acute febrile syndrome, long-term articular complications and even death can occur. This review characterizes the global epidemiological and economic burden of chikungunya. The search included studies published from 2007 to 2022 in MEDLINE, Embase, LILACS, and SciELO for a thorough evaluation of the literature. Rayyan software was used for data analysis, and data were summarized descriptively and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventy-six publications were included. Chikungunya is widely distributed in the tropics, including Africa, Asia, South America, and Oceania/the Pacific Islands, and co-circulates with other simultaneous arboviruses such as DENV, ZIKV, and YFV. Chikungunya infection can lead to chronic articular manifestations with a significant impact on the quality of life in the long term. In addition, it generates absenteeism and economic and social losses and can cause fatal infections in vulnerable populations, mainly in high-risk patients with co-morbidities and at the extremes of age. Reported costs associated with CHIKV diseases are substantial and vary by region, age group, and public/private delivery of healthcare services. The chikungunya disease burden includes chronicity, severe infections, increased hospitalization risks, and associated mortality. The disease can impact the economy in several spheres, significantly affecting the health system and national economies. Understanding and measuring the full impact of this re-emerging disease is essential. Full article

Under-reporting of tuberculosis (TB) disease in children and adolescents is a significant global concern, as many children are missing from TB notification data. A systematic literature review was conducted to understand the global reporting gap of child and adolescent TB as well as current interventions to close this gap in Low- and Middle- Income Countries (LMIC). Our study found large and variable gaps in child and adolescent TB reporting, due to various factors. Interventions to close this gap exist but are limited. Future studies are necessary to improve global surveillance systems to improve TB care delivery for children and adolescents. Full article

Acute phase proteins have been used as tools for the diagnosis, monitoring, and prognosis of several diseases in domestic animals. However, the dynamics of these proteins in infection by Trypanosoma cruzi, the causative agent of Chagas disease in dogs, is still unknown. The aim of this study was to determine concentrations of acute phase proteins (C-reactive protein, haptoglobin, ferritin and paraoxonase-1) in dogs in a coastal town of Ecuador, with natural Trypanosoma cruzi infection with or without seroreactivity of Ehrlichia canis, Ehrlichia ewingii, Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi and Dirofilaria immitis. For the detection of Trypanosoma cruzi serum antibodies, two different antigen-based enzyme-linked immunosorbent assay tests were implemented. For the detection of seroreactivity of Ehrlichia canis, Ehrlichia ewingii, Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi and Dirofilaria immitis, an IDEXX SNAP^® 4Dx^® test was used. To determine the concentration of C-reactive protein and ferritin, an immunoturbidimetric assay was used; haptoglobin concentration was measured using a commercial colorimetric method validated in dogs; a spectrophotometric method was used to determine the serum concentration of paraoxonase-1. Results showed a reduction in the serum levels of paraoxonase-1 in Trypanosoma cruzi-seroreactive dogs, either with or without seroreactivity to other vector-borne diseases. A serum ferritin increment was observed in Trypanosoma cruzi-seroreactive dogs with seroreactivity to any other vector-borne diseases. Our findings suggest that paraoxonase-1 levels are reduced in Trypanosoma cruzi-seroreactive dogs without evident clinical signs of Chagas disease, despite their seroreactivity to the other vector-borne diseases studied. These findings could indicate an oxidative stress response in Trypanosoma cruzi-seroreactive dogs with no evident signs of inflammation. Full article

The pandemic situation of COVID-19, which affected almost the entire civilized world with its consequences, offered a unique opportunity for analysis of geographical space. In a relatively short period of time, the COVID-19 pandemic became a truly global event with consequences affecting all areas of life. Circumstances with COVID-19, which affected the territory of Slovakia and its regions, represent a sufficient premise for analysis three years after the registration of the first case in Slovakia. The study presents the results of a detailed spatiotemporal analysis of the course of registered cases of COVID-19 in six periods in Slovakia. The aim of the paper was to analyze the development of the number of people infected with the disease COVID-19 in Slovakia. At the level of the districts of Slovakia, using spatial autocorrelation, we identified spatial differences in the disease of COVID-19. Moran’s global autocorrelation index and Moran’s local index were used in the synthesis of knowledge. Spatial analysis of data on the number of infected in the form of spatial autocorrelation analysis was used as a practical sustainable approach to localizing statistically significant areas with high and low positivity. This manifested itself in the monitored area mainly in the form of positive spatial autocorrelation. The selection of data and methods used in this study together with the achieved and presented results can serve as a suitable tool to support decisions in further measures for the future. Full article

Chagas Disease (CD) is highly prevalent among the indigenous populations in the Sierra Nevada de Santa Marta, Colombia. Villages examined show prevalence rates ranging from 43.6% up to 67.4%. In the present study, associated medical conditions were assessed with a particular focus on ECG alterations. CD diagnosis was based on a rapid test, two different ELISAs, and a specific and highly sensitive Chagas real-time PCR. In both CD positive and CD negative patients, relations of the status and medical (physical examination-based, questionnaire-based) and/or electrocardiogram-based findings were investigated. As expected, CD-associated symptoms and complaints were predominantly found in CD-positive patients. Interestingly, ECG-findings were found to show the potential of leading to early CD diagnosis because ECG alterations were already seen in early stagechanges of the disease. In conclusion, although the observed ECG changes are unspecific, they should be considered as an indicator for a CD screening and, in case of positive results, an associated early treatment of the disease. Full article

Background: China was certified malaria-free by the World Health Organization on 30 June 2021. However, due to imported malaria, maintaining a malaria-free status in China is an ongoing challenge. There are critical gaps in the detection of imported malaria through the currently available tools, especially for non-falciparum malaria. In the study, a novel point-of-care Rapid Diagnostic Test designed for the detection of imported malaria infections was evaluated in the field. Methods: Suspected imported malaria cases reported from Guangxi and Anhui Provinces of China during 2018–2019 were enrolled to evaluate the novel RDTs. Diagnostic performance of the novel RDTs was evaluated based on its sensitivity, specificity, positive and negative predictive values, and Cohen’s kappa coefficient, using polymerase chain reaction as the gold standard. The Additive and absolute Net Reclassification Index were calculated to compare the diagnostic performance between the novel RDTs and Wondfo RDTs (control group). Results: A total of 602 samples were tested using the novel RDTs. Compared to the results of PCR, the novel RDTs presented sensitivity, specificity, PPV, NPV, and diagnostic accuracy rates of 78.37%, 95.05%, 94.70%, 79.59%, and 86.21%, respectively. Among the positive samples, the novel RDTs found 87.01%, 71.31%, 81.82%, and 61.54% of P. falciparum, P. ovale, P. vivax, and P. malariae, respectively. The ability to detect non-falciparum malaria did not differ significantly between the novel and Wondfo RDTs (control group). However, Wondfo RDTs can detect more P. falciparum cases than the novel RDTs (96.10% vs. 87.01%, p < 0.001). After the introduction of the novel RDTs, the value of the additive and absolute Net Reclassification Index is 1.83% and 1.33%, respectively. Conclusions: The novel RDTs demonstrated the ability to distinguish P. ovale and P. malariae from P. vivax which may help to improve the malaria post-elimination surveillance tools in China. Full article

Background: Schistosomiasis, due to S. mansoni, is prevalent in Rwanda. However, there is a paucity of information related to the abundance, species, distribution, and infectivity of Schistosoma intermediate host snails. Methods: Snails were collected from 71 sites, including lakeshores and wetlands. Snails obtained were morphologically identified, and cercariae were shed using standard procedures. Cercariae were molecularly characterized using PCR. GPS coordinates were used to generate geospatial maps of snail distribution that were overlaid with geospatial distribution of schistosomiasis among pre-school children in the same areas. Results: Overall, 3653 snails were morphologically classified as Bulinus spp. and 1449 as Biomphalaria spp. A total of 306 snails shed cercariae, 130 of which were confirmed as S. mansoni cercaria by PCR. There was no significant difference in the proportion of S. mansoni cercariae in wetlands compared to lakeshores. Conclusion: Rwandan water bodies harbor an important number of snails that shed S. mansoni cercariae. Furthermore, a strong spatial correlation was observed between the distribution of schistosomiasis in children and the spatial distribution of snail infectivity with S. mansoni. The presence of Bulinus spp. Suggests a potential risk of S. haematobium, although molecular analysis did not show any current transmission of this parasite. Full article

Contaminated fresh produce has been identified as a vehicle for human foodborne illness. The present study investigated the counts, antimicrobial resistance profile, and genome-based characterization of Escherichia coli in 11 different types of fresh salad vegetable products (n = 400) sampled from retailers in Abu Dhabi and Dubai in the United Arab Emirates. E. coli was detected in 30% of the tested fresh salad vegetable items, with 26.5% of the samples having an unsatisfactory level (≥100 CFU/g) of E. coli, notably arugula and spinach. The study also assessed the effect of the variability in sample conditions on E. coli counts and found, based on negative binominal regression analysis, that samples from local produce had a significantly higher (p-value < 0.001) E. coli count than imported samples. The analysis also indicated that fresh salad vegetables from the soil-less farming system (e.g., hydroponic and aeroponic) had significantly (p-value < 0.001) fewer E. coli than those from traditional produce farming. The study also examined the antimicrobial resistance in E. coli (n = 145) recovered from fresh salad vegetables and found that isolates exhibited the highest phenotypic resistance toward ampicillin (20.68%), tetracycline (20%), and trimethoprim-sulfamethoxazole (10.35%). A total of 20 (13.79%) of the 145 E. coli isolates exhibited a multidrug-resistant phenotype, all from locally sourced leafy salad vegetables. The study further characterized 18 of the 20 multidrug-resistant E. coli isolates using whole-genome sequencing and found that the isolates had varying numbers of virulence-related genes, ranging from 8 to 25 per isolate. The frequently observed genes likely involved in extra-intestinal infection were CsgA, FimH, iss, and afaA. The β-lactamases gene bla_CTX-M-15 was prevalent in 50% (9/18) of the E. coli isolates identified from leafy salad vegetable samples. The study highlights the potential risk of foodborne illness and the likely spread of antimicrobial resistance and resistance genes associated with consuming leafy salad vegetables and emphasizes the importance of proper food safety practices, including proper storage and handling of fresh produce. Full article

Background: COVID-19 caused devastating effects on global healthcare systems. The elderly and people with chronic comorbidities were at a particularly high risk of mortality and morbidity. However, the evidence on the association of COVID-19 severity with noncommunicable diseases (NCDs) in the African population is scarce. Objective: The aim is to estimate COVID-19 severity among African patients with hypertension, diabetes, and cardiovascular diseases (CVDs) and its implications for case management. Methods: We will adhere to the extension for Scoping Reviews of PRISMA (PRISMA-ScR). The following electronic databases will be searched: PubMed, Scopus, Web of Science, Embase, CINAHL, and Joanna Briggs Institute. The search will be conducted after the publication of this protocol. Two reviewers will extract data from articles published after March 2020 without language restrictions. A descriptive analysis of the important findings and a narrative synthesis of the results will serve as the basis for interpretation. Expected results and conclusions: This scoping review is expected to determine the odds of patients with chronic comorbidities to progress to severe stages of COVID-19. The review will generate an evidence-based and set foundation for recommendations toward the establishment of surveillance systems and referral guidelines for the management of NCDs in the face of COVID-19 and future pandemics. Full article

This study compared the clinical–parasitological profiles of gestational (GM), placental (PM), and congenital (CM) malaria in northwestern Colombia. A cross-sectional study with 829 pregnant women, 549 placentas, and 547 newborns was conducted. The frequency of GM was 35.8%, PM 20.9%, and CM 8.5%. P. vivax predominated in GM; in PM, the proportion of P. vivax and P. falciparum was similar; in CM, P. falciparum predominated. The main clinical findings were headache (49%), anemia (32%), fever (24%), and musculoskeletal pain (13%). The clinical manifestations were statistically higher in P. vivax infections. In submicroscopic GM (positive with qPCR and negative with thick blood smear), the frequency of anemia, sore throat, and a headache was statistically higher compared with pregnant women without malaria. GM, PM, and CM reduce birth weight and head circumference. In Colombia, this is the first research on the clinical characteristics of GM, PM, and CM; contrary to evidence from other countries, P. vivax and submicroscopic infections are associated with clinical outcomes. Full article

Antimicrobial resistance (AMR) is increasing and represents one of the greatest public health challenges of our time, accounting for considerable morbidity and mortality globally. A “One Health” surveillance strategy, which integrates data concerning the resistant organisms circulating in humans, animals, and the environment, is required to monitor this issue and enable effective interventions. The timely collection, processing, analysis, and reporting of AMR surveillance data are necessary for the effective delivery of the information generated from such surveillance. Nepal has greatly improved its surveillance activities through a network of human and animal health laboratories; however, the data reported by sentinel laboratories are often inconsistent, incomplete, and delayed, causing challenges in terms of data cleaning, standardization, and visualization on a national level. To overcome these issues, innovative methods and procedures have been adopted in Nepal, with the development and customization of digital tools that reduce the human time and effort spent on data cleaning and standardization, with concomitant improvements in the accuracy of data. These standardized data can be uploaded to the district health information system 2 (DHIS2) One Health AMR surveillance portal, enabling the generation of reports that will help decision-makers and policy planners to combat the global problem of AMR. Full article

Neuroinflammation is critical in developing and progressing neurological diseases. The underlying pro-inflammatory cytokine expression combined with additional mechanisms in the neuropathology, such as oxidative stress, brain–blood barrier damage, and endothelial dysfunction, could contribute to the susceptibility to developing severe COVID-19. The physiopathology of SARS-CoV-2 and other human coronaviruses (H-CoVs) has not been completely understood; however, they have all been linked to a disproportionated response of the immune system, particularly an exacerbated cytokine production and the dysregulation of total cell counts. In this article, based on the compilation of studies reported by our working group regarding COVID-19 and neurological diseases, we propose that the inflammation observed in the central nervous system, through a CSF analysis, could be conditioned by neurological disease(s) and enhanced by COVID-19. Therefore, it is necessary to determine the cytokine profile in different neurological disorders to propose adequate treatments and avoid severe forms of the disease in these patients. Full article

Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be used up. However, the evidence for DIC in malaria patients is still not clear, and small case series and retrospective studies have shown varying results. This meta-analysis was intended for the evaluation of the evidence of DIC among malaria patients using a meta-analysis approach. The protocol for the systematic review was registered at PROSPERO as CRD42023392194. Studies that investigated DIC in patients with malaria were searched in Ovid, Scopus, Embase, PubMed, and MEDLINE. The pooled proportion with 95% confidence intervals (CI) of DIC among malaria patients was estimated using a random-effects model. A total of 1837 articles were identified, and 38 articles were included in the meta-analysis. The overall proportion of DIC in malaria was 11.6% (95% CI: 8.9%–14.3%, I²: 93.2%, 38 studies). DIC in severe falciparum malaria and fatal malaria was 14.6% (95% CI: 5.0–24.3%, I²: 95.5%, 11 studies) and 82.2% (95% CI: 56.2–100%, I²: 87.3, 4 studies). The estimates of DIC among severe malaria patients who had multi-organ dysfunction with bleeding, cerebral malaria, acute renal failure, and ≥2 complications were 79.6% (95% CI: 67.1–88.2%, one study), 11.9% (95% CI: 7.9–17.6%, one study), 16.7% (95% CI: 10.2–23.3%, ten studies), and 4.8% (95% CI: 1.9–7.7%, nine studies), respectively. The proportion estimates of DIC among the patients with malaria depended on the Plasmodium species, clinical severity, and types of severe complications. The information from this study provided useful information to guide the management of malaria patients. Future studies are needed to investigate the association between Plasmodium infection and DIC and to understand the mechanism of malaria-induced DIC. Full article

Chagas disease is derived from the infection by the protozoan Trypanosoma cruzi. In many countries, benznidazole is the only drug approved for clinical use despite several side effects and the emergence of resistant parasite strains. In this context, our group has previously pointed out that two novel aminopyridine derivatives complexed with Cu²⁺, namely, cis-aquadichloro(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamino)copper (3a) and its glycosylated ligand cis-dichloro (N-{[4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)pheny]lmethyl}-2-pyridinemethamino)copper (3b), are effective against T. cruzi trypomastigote forms. With this result in mind, the present work aimed to investigate the effects of both compounds on trypomastigotes physiology and on the interaction process with host cells. Apart from loss of plasma membrane integrity, an increased generation of reactive oxygen species (ROS) and decreased mitochondrial metabolism were observed. Pretreatment of trypomastigotes with these metallodrugs inhibited the association index with LLC-MK₂ cells in a typical dose-dependent manner. Both compounds showed low toxicity on mammalian cells (CC₅₀ > 100 µM), and the IC₅₀ values calculated for intracellular amastigotes were determined as 14.4 µM for 3a and 27.1 µM for 3b. This set of results demonstrates the potential of these aminopyridines complexed with Cu²⁺ as promising candidates for further antitrypanosomal drug development. Full article

Decreasing global tuberculosis (TB) notifications indicate problems related to TB patient detection and treatment outcomes. Pharmaceutical care (PC) has potential roles in managing these issues. However, PC practices have not yet become widespread in the real world. This systematic scoping review aimed to identify and analyze the current literature on practical models of pharmaceutical care for improving tuberculosis patient detection and treatment outcomes. We then discussed the present challenges and future considerations for the successful implementation of PC services in TB. A systematic scoping review was performed to identify the practice models of PC in TB. Systematic searches and screening were used to identify relevant articles in the PubMed and Cochrane databases. We then discussed the challenges and recommendations for successful implementation using a framework to improve professional healthcare practice. Our analysis included 14 of 201 eligible articles. We identified that the focuses in the PC of TB are on increasing patient detection (four articles) and improving TB treatment outcomes (ten articles). Practices cover services in the community and hospital settings, such as screening and referring people with presumptive TB, tuberculin test services, collaborative practices for treatment completion, directly observed treatment, the solution of drug-related problems, reporting and managing adverse drug reactions, and medication adherence programs. Although PC services positively increase TB patient detection and treatment outcomes, hidden challenges in the actual practice are analyzed. Several factors should be comprehensively considered in successful implementation, such as guidelines, individual pharmacy personnel, patient, professional interaction, organizational capacity, regulation, incentive, and resource factors. Hence, a collaborative PC program that involves all related stakeholders should be considered to create successful and sustainable PC services in TB. Full article