The latest medical research on Travel Medicine

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Global prevalence of polypharmacy among the COVID-19 patients: a comprehensive systematic review and meta-analysis of observational studies.

Tropical Medicine and International Health

Polypharmacy has traditionally been defined in various texts as the use of 5 or more chronic drugs, the use of inappropriate drugs, or drugs that are not clinically authorized. The aim of this study was to evaluate the prevalence of polypharmacy among the COVID-19 patients, and the side effects, by systematic review and meta-analysis.

This study was performed by systematic review method and in accordance with PRISMA 2020 criteria. The protocol in this work is registered in PROSPERO (CRD42021281552). Particular databases and repositories have been searched to identify and select relevant studies. The quality of articles was assessed based on the Newcastle-Ottawa Scale checklist. Heterogeneity of the studies was measured using the I2 test.

The results of meta-analysis showed that the prevalence of polypharmacy in 14 studies with a sample size of 189,870 patients with COVID-19 is 34.6% (95% CI: 29.6-40). Studies have shown that polypharmacy is associated with side effects, increased morbidity and mortality among patients with COVID-19. The results of meta-regression analysis reported that with increasing age of COVID-19 patients, the prevalence of polypharmacy increases (p < 0.05).

Polypharmacy is seen in many patients with COVID-19. Since there is no definitive cure for COVID-19, the multiplicity of drugs used to treat this disease can affect the severity of the disease and its side effects as a result of drug interactions. This highlights the importance of controlling and managing prescription drugs for patients with COVID-19.

Effect of Flight Connectivity on Introduction and Evolution of COVID-19 in Canadian Cities.

Journal of Travel Research

The COVID-19 pandemic has challenged health services and governments in Canada and around the world. Our research aims to evaluate the effect of domestic and international air travel patterns on the COVID-19 pandemic in Canadian provinces and territories.

Air travel data were obtained through licensed access to the 'BlueDot Intelligence Platform', BlueDot Inc. Daily provincial and territorial COVID-19 cases for Canada and global figures, including mortality, cases recovered, and population data were downloaded from public datasets. The effects of domestic and international air travel and passenger volume on the number of local and non-local infected people in each Canadian province and territory were evaluated with a semi-Markov model. Provinces and territories are grouped into large (>100 000 confirmed COVID-19 cases and > 1 000 000 inhabitants) and small jurisdictions (≤100 000 confirmed COVID-19 cases and ≤ 1 000 000 inhabitants).

Our results show a clear decline in passenger volumes from March 2020 due to public health policies, interventions, and other measures taken to limit or control the spread of COVID-19. As the measures were eased, some provinces and territories saw small increases in passenger volumes, although travel remained below pre-pandemic levels. During the early phase of disease introduction, the burden of illness is determined by the connectivity of jurisdictions. In provinces with a larger population and greater connectivity, the burden of illness is driven by case importation, although local transmission rapidly replaces imported cases as the most important driver of increasing new infections. In smaller jurisdictions, a steep increase in cases is seen after importation, leading to outbreaks within the community.

Historical travel volumes, combined with data on an emerging infection, are useful to understand the behaviour of an infectious agent in regions of Canada with different connectivity and population size. Historical travel information is important for public health planning and pandemic resource allocation.

Transcriptional response of individual Hawaiian Culex quinquefasciatus mosquitoes to the avian malaria parasite Plasmodium relictum.

Malaria Journal

Plasmodium parasites that cause bird malaria occur in all continents except Antarctica and are primarily transmitted by mosquitoes in the genus Culex. Culex quinquefasciatus, the mosquito vector of avian malaria in Hawai'i, became established in the islands in the 1820s. While the deadly effects of malaria on endemic bird species have been documented for many decades, vector-parasite interactions in avian malaria systems are relatively understudied.

To evaluate the gene expression response of mosquitoes exposed to a Plasmodium infection intensity known to occur naturally in Hawai'i, offspring of wild-collected Hawaiian Cx. quinquefasciatus were fed on a domestic canary infected with a fresh isolate of Plasmodium relictum GRW4 from a wild-caught Hawaiian honeycreeper. Control mosquitoes were fed on an uninfected canary. Transcriptomes of five infected and three uninfected individual mosquitoes were sequenced at each of three stages of the parasite life cycle: 24 h post feeding (hpf) during ookinete invasion; 5 days post feeding (dpf) when oocysts are developing; 10 dpf when sporozoites are released and invade the salivary glands.

Differential gene expression analyses showed that during ookinete invasion (24 hpf), genes related to oxidoreductase activity and galactose catabolism had lower expression levels in infected mosquitoes compared to controls. Oocyst development (5 dpf) was associated with reduced expression of a gene with a predicted innate immune function. At 10 dpf, infected mosquitoes had reduced expression levels of a serine protease inhibitor, and further studies should assess its role as a Plasmodium agonist in C. quinquefasciatus. Overall, the differential gene expression response of Hawaiian Culex exposed to a Plasmodium infection intensity known to occur naturally in Hawai'i was low, but more pronounced during ookinete invasion.

This is the first analysis of the transcriptional responses of vectors to malaria parasites in non-mammalian systems. Interestingly, few similarities were found between the response of Culex infected with a bird Plasmodium and those reported in Anopheles infected with human Plasmodium. The relatively small transcriptional changes observed in mosquito genes related to immune response and nutrient metabolism support conclusions of low fitness costs often documented in experimental challenges of Culex with avian Plasmodium.

Haematological profile of malaria patients with G6PD and PKLR variants (erythrocytic enzymopathies): a cross-sectional study in Thailand.

Malaria Journal

Glucose 6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PKLR) deficiencies are common causes of erythrocyte haemolysis in the presence of antimalarial drugs such as primaquine and tafenoquine. The present study aimed to elucidate such an association by thoroughly investigating the haematological indices in malaria patients with G6PD and PKLRR41Q variants.

Blood samples from 255 malaria patients from Thailand, Myanmar, Laos, and Cambodia were collected to determine haematological profile, G6PD enzyme activity and G6PD deficiency variants. The multivariate analysis was performed to investigate the association between anaemia and G6PD MahidolG487A, the most common mutation in this study.

The prevalence of G6PD deficiency was 11.1% (27/244) in males and 9.1% (1/11) in female. The MAFs of the G6PD MahidolG487A and PKLRR41Q variants were 7.1% and 2.6%, respectively. Compared with patients with wildtype G6PD after controlling for haemoglobinopathies, G6PD-deficient patients with hemizygous and homozygous G6PD MahidolG487A exhibited anaemia with low levels of haemoglobin (11.16 ± 2.65 g/dl, p = 0.041). These patients also exhibited high levels of reticulocytes (3.60%). The median value of G6PD activity before treatment (Day 0) was significantly lower than that of after treatment (Day 28) (5.51 ± 2.54 U/g Hb vs. 6.68 ± 2.45 U/g Hb; p < 0.001). Reticulocyte levels on Day 28 were significantly increased compared to that of on Day 0 (2.14 ± 0.92% vs 1.57 ± 1.06%; p < 0.001). PKLRR41Q had no correlation with anaemia in malaria patients. The risk of anaemia inpatients with G6PD MahidolG487A was higher than wildtype patients (OR = 3.48, CI% 1.24-9.75, p = 0.018). Univariate and multivariate analyses confirmed that G6PD MahidolG487A independently associated with anaemia (< 11 g/dl) after adjusted by age, gender, Plasmodium species, parasite density, PKLRR41Q, and haemoglobinopathies (p < 0.001).

This study revealed that malaria patients with G6PD MahidolG487A, but not with PKLRR41Q, had anaemia during infection. As a compensatory response to haemolytic anaemia after malaria infection, these patients generated more reticulocytes. The findings emphasize the effect of host genetic background on haemolytic anaemia and the importance of screening patients for erythrocyte enzymopathies and related mutations prior to anti-malarial therapy.

Prevalence and factors associated with COVID-19 vaccine acceptance among the general population in Asadabad, Iran: a cross-sectional study.

Tropical Medicine and International Health

Vaccination can be an essential protective measure against Coronavirus disease 2019 (COVID-19) if well received by the public. Various factors affect the acceptance or refusal of vaccines. Several waves of COVID-19 caused much death in Iran. This study aimed to evaluate the acceptance of the COVID-19 vaccine in the general population of Asadabad in 2021.

In this cross-sectional study, 650 people from the general population of Asadabad with a mean age of 34.6 (SD = 15.1) years were selected and included. In addition to socio-economic and demographic data, data were collected using the COVID-19 fear scale. Univariate and multiple logistic regression models were used to investigate the relationship between the tendency to get the COVID-19 vaccine (the dependent variable) and other variables.

About 42.3% of participants were reluctant to receive the available COVID-19 vaccines. After adjusting for several covariates, there was a significant relationship between willingness to get vaccinated and family history of COVID-19 infection (AOR = 1.86, 95% CI 1.06-3.27, p = 0.032), trust in healthcare workers (AOR = 2.07, 95% CI 1.13-3.79, p = 0.019), trust in existing vaccines (AOR = 3.94, 95% CI 2.15-7.23, p < 0.001), encouraging family members to get vaccinated (AOR = 7.6, 95% CI 4.12-14.01, p < 0.0001). Also, people infected with COVID-19 are less likely to accept vaccination (AOR = 0.55, 95% CI 0.33-0.93, p = 0.025). Also, a unit increase in the score of fear of getting the COVID-19 virus increased the odds of getting the COVID-19 vaccine by 6% (AOR = 1.06, 95% CI 1.02-1.10, p = 0.002).

The culture and context of different societies can affect the acceptance or refusal of the COVID-19 vaccine. Based on these characteristics and providing extensive education to the people, the health authorities in each community should build trust and better communicate all health information to clear any fear and remove all obstacles to increase willingness to get COVID-19 vaccination.

Genetic polymorphism of circumsporozoite protein of Plasmodium falciparum among Chinese migrant workers returning from Africa to Henan Province.

Malaria Journal

Plasmodium falciparum malaria is recognized as a major global public health problem. The malaria vaccine was important because the case fatality rate of falciparum malaria was high. Plasmodium falciparum circumsporozoite protein (PfCSP) is one of the potential vaccine candidates, but the genetic polymorphism of PfCSP raises concerns regarding the efficacy of the vaccine. This study aimed to investigate the genetic polymorphism of PfCSP and provide data for the improvement of PfCSP-based vaccine (RTS,S malaria vaccine).

Blood samples were collected from 287 Chinese migrant workers who were infected with P. falciparum and returning from Africa to Henan Province during 2016-2018. The Pfcsp genes were analysed to estimate the genetic diversity of this parasite.

The results showed that there were two mutations at the N-terminus of imported Pfcsp in Henan Province, including insertion amino acids (58.71%, 118/201) and A → G (38.81%, 78/201). The number of repeats of tetrapeptide motifs (NANP/NVDP/NPNP/NVDA) in the central repeat region ranged mainly from 39 to 42 (97.51%, 196/201). A total of 14 nonsynonymous amino acid changes were found at the C-terminus. The average nucleotide difference (K) of imported Pfcsp in Henan Province was 5.719, and the haplotype diversity (Hd) was 0.964 ± 0.004. The estimated value of dN-dS was 0.047, indicating that the region may be affected by positive natural selection. The minimum number of recombination events (Rm) of imported Pfcsp in Henan Province was close to that in Africa. The analysis of genetic differentiation showed that there may be moderate differentiation between East Africa and North Africa (Fst = 0.06484), and the levels of differentiation in the other regions were very small (Fst < 0.05).

The N-terminus of Pfcsp was relatively conserved, and the central repeat region and the Th2R and Th3R regions of the C-terminus were highly polymorphic. The gene polymorphism pattern among Chinese migrant workers returning from Africa to Henan Province was consistent with that in Africa. The geographical pattern of population differentiation and the evidence of natural selection and gene recombination suggested that the effect of polymorphism on the efficacy of PfCSP-based vaccines should be considered.

Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites.

Malaria Journal

Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines are the only candidate malaria vaccines that induce > 90% vaccine efficacy (VE) against controlled human malaria infection and the only malaria vaccines to have achieved reproducible VE against malaria in adults in Africa. The goal is to increase the impact and reduce the cost of PfSPZ vaccines by optimizing vaccine potency and manufacturing, which will benefit from identification of immunological responses contributing to protection in humans. Currently, there is no authentic animal challenge model for assessing P. falciparum malaria VE. Alternatively, Plasmodium knowlesi (Pk), which infects humans and non-human primates (NHPs) in nature, can be used to experimentally infect rhesus macaques (Macaca mulatta) to assess VE.

Sanaria has, therefore, produced purified, vialed, cryopreserved PkSPZ and conducted challenge studies in several naïve NHP cohorts. In the first cohort, groups of three rhesus macaques each received doses of 5 × 102, 2.5 × 103, 1.25 × 104 and 2.5 × 104 PkSPZ administered by direct venous inoculation. The infectivity of 1.5 × 103 PkSPZ cryopreserved with an altered method and of 1.5 × 103 PkSPZ cryopreserved for four years was tested in a second and third cohort of rhesus NHPs. The lastly, three pig-tailed macaques (Macaca nemestrina), a natural P. knowlesi host, were challenged with 2.5 × 103 PkSPZ cryopreserved six years earlier.

In the first cohort, all 12 animals developed P. knowlesi parasitaemia by thick blood smear, and the time to positivity (prepatent period) followed a non-linear 4-parameter logistic sigmoidal model with a median of 11, 10, 8, and 7 days, respectively (r2 = 1). PkSPZ cryopreserved using a modified rapid-scalable method infected rhesus with a pre-patent period of 10 days, as did PkSPZ cryopreserved four years prior to infection, similar to the control group. Cryopreserved PkSPZ infected pig-tailed macaques with median time to positivity by thin smear, of 11 days.

This study establishes the capacity to consistently infect NHPs with purified, vialed, cryopreserved PkSPZ, providing a foundation for future studies to probe protective immunological mechanisms elicited by PfSPZ vaccines that cannot be established in humans.

Possible clinical implications and future directions of managing bacterial biofilms in cutaneous leishmaniasis wounds.

Tropical Medicine and International Health

Cutaneous leishmaniasis (CL) lesions are chronic and result in disfiguring scars. The microbiological aspects of these wounds have not been systema...

Annual distributions of insecticide-treated nets to schoolchildren and other key populations to maintain higher ITN access than with mass campaigns: a modelling study for mainland Tanzania.

Malaria Journal

Since 2013, the National Malaria Control Programme in mainland Tanzania has deployed annual distributions of insecticide-treated nets (ITNs) through primary schools to maintain ITN access and use. This School Net Programme (SNP) is slated to be used throughout mainland Tanzania by 2023. This modelling study projects ITN access under different ITN distribution strategies and quantification approaches.

A stock and flow model with a Tanzania-specific ITN decay rate was used to calculate annual net crops for four different ITN distribution strategies, varying quantification approaches within each strategy. Annual nets-per-capita (NPC) was derived from net crop and a standardized population projection. Nonparametric conditional quartile functions for the proportion of the population with access to an ITN (ITN access) as a function of NPC were used to predict ITN access and its variability. The number of ITNs required under the varying quantification approaches for the period 2022-2030 was calculated.

Annual SNP quantified using a "population times 15%" approach maintained ITN access between 80 and 90%, when combined with reproductive and child health (RCH) ITN distribution, requiring 133.2 million ITNs. The same strategy quantified with "population times 22%" maintained ITN access at or above 90%, requiring 175.5 million ITNs. Under 5-year mass campaigns with RCH distribution for pregnant women and infants, ITN access reached 90% post-campaign and fell to 27-35% in the 4th year post-campaign, requiring 120.5 million ITNs over 8 years. 3-yearly mass campaigns with RCH reached 100% ITN access post-campaign and fell to 70% in the 3rd year post-campaign, requiring 154.4 million ITNs.

Given an ITN retention time in Tanzania of 2.15 years, the model predicts that mass campaigns conducted every 3 years in mainland Tanzania will not maintain ITN access at target levels of 80%, even with strong RCH channels. Mainland Tanzania can however expect to maintain ITN access at 80% or above by quantifying SNP using "population × 15%", in addition to RCH ITN delivery. This strategy requires 14% fewer ITNs than a 3-year campaign strategy while providing more consistent ITN coverage. Meeting the targets of 80% ITN use would require maintaining 90% ITN access, achievable using a "population times 22%" quantification approach for SNP.

An epidemiological analysis of imported malaria in Shanghai during a COVID-19 outbreak.

Malaria Journal

The goal of this study was to understand the epidemiological characteristics of imported malaria in Shanghai specifically during the epidemic period of novel corona-virus pneumonia (COVID-19), to provide a reference for preventing the transmission of imported malaria after this disease had been previously eliminated.

The data of malaria cases reported in Shanghai from 2020 to 2021 were obtained from the China Information System for Disease Control and Prevention (CISDCP) and the Information System for Parasitic Disease Control and Prevention (ISPDCP). The characteristics of demographic and epidemiological distribution, travel-related information, diagnosis information, regions of infection acquisition and disposal information of epidemic situation were analysed with descriptive statistics.

A total of 112 cases of malaria were reported in Shanghai from January 2020 to December 2021. There were 18 cases and 94 cases in 2020 and 2021, respectively, reaching the lowest and highest levels in the past 10 years. The incidence of malaria associated with seasons had an increasing trend (χ2 = 81.143, P < 0.05). These cases included Plasmodium falciparum (97, 86.61%), Plasmodium vivax (4, 3.57%), Plasmodium ovale (8, 7.14%) and Plasmodium malariae (3, 2.68%). The median age of patients with malaria was 38.0 years, the majority of these individuals were males (109, 97.32%), and most of them were labour personnel (93, 83.04%). Of the reported cases, 8 of these individuals (7.14%) reported experiencing malaria symptoms before their arrival in China after their stay overseas; 97 of these individuals (86.61%) reported experiencing symptoms within 14 days after their initial arrival from overseas; 15 of these individuals (13.39%) were diagnosed with 'severe malaria'; and 4 of these individuals (3.57%) were also diagnosed with COVID-19. All cases were imported from Africa, and there were no indigenous cases and deaths.

Due to the impact of COVID-19, the number of imported malaria cases in Shanghai had greatly increased; however, prevention and control measures for imported malaria could be implemented to prevent re-transmission of this condition. Considering that the number of individuals returning from overseas labour is likely to increase in the next few years, it is necessary to strengthen the surveillance of imported malaria and to review the protocol for potential epidemic situations. Together, these measures could support the maintation of free-malaria status in Shanghai.

Occurrence and anti-microbial susceptibility pattern of extended spectrum beta-lactamase producing Enterobacteriaceae in governmental hospitals wastewater in Addis Ababa, Ethiopia.

Tropical Medicine and International Health

Worldwide, come out and dissemination of extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae has been warning the efficacy of antibiotics to treat an infection. Hospital wastewaters were a reservoir of such kind of resistant bacteria. Currently, the predominant antibiotics used for the treatment of hospitalized patients infected by Gram-negative bacteria are the β-lactam antibiotics. Therefore, it is an important source to investigate the magnitude of ESBLs producing bacteria and their antimicrobial susceptibility pattern. This study aimed to determine the occurrence of ESBLs producing Enterobacteriaceae (ESBLs-pE) and their antibiotic susceptibility pattern in wastewater released from five governmental hospitals in Addis Ababa, Ethiopia.

A cross-sectional study was conducted from April 1 to May 31, 2020. A total of 100 wastewaters were collected from five governmental hospitals in Addis Ababa using a grap-sampling technique. All Enterobacteriaceae were screened for ESBLs production using cefotaxime and ceftazidime as per 29th CLSI guideline. Each screen positive for ESBLs production was confirmed by the combination disk method (CDT) and their antibiotic susceptibility pattern was done using the Kirby-Bauer disk diffusion method on Muller Hinton agar (MHA). Data were entered and summarized using SPSS version 20 software.

Of all Enterobacteriaceae, 48.3% were confirmed ESBLs-pE. The highest ratio of ESBLs-PE was observed in the adult ward (66.7%) and laundry unit effluent (58.8%). The highest ESBL producers were E. coli (21.8%) and K. pneumoniae (4.8%). The most elevated resistance level of ESBL producers were observed to cefotaxime (95.8%) and amoxicillin/clavunalate (93%). 64% of tested Enterobacteriaceae isolates were multi drug resistant (MDR).

Higher magnitude of MDR and ESBLs-pE were present in the hospital wastewater. The majority of them were in the adult ward and laundry unit effluents. The most frequent ESBLs-pE was among E.coli and K. pneumoniae. Hence, Consistent infection prevention and control procedures should be in practice at each ward/unit.

Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives.

Malaria Journal

The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property.

Here, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques.

The two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor.

This study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2.