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Malaria Journal Aug 2023Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs.
METHODS
Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group.
RESULTS
Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) -0.68, 95% CI -1.26 to -0.10), memory (SMD -0.52, 95% CI -0.99 to -0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13-0.78).
CONCLUSION
Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection.
TRIAL REGISTRATION
This systematic review was registered under PROSPERO: CRD42020154777.
Topics: Child; Child, Preschool; Humans; Developing Countries; Cognition; Malaria, Cerebral; Africa South of the Sahara
PubMed: 37537555
DOI: 10.1186/s12936-023-04653-9 -
Scientific Reports Jan 2024Magnesium is associated with Plasmodium infections and malaria severity. This systematic review and meta-analysis was conducted to synthesize the link between Plasmodium... (Meta-Analysis)
Meta-Analysis
Magnesium is associated with Plasmodium infections and malaria severity. This systematic review and meta-analysis was conducted to synthesize the link between Plasmodium infections and magnesium levels for improved clinical guidance and therapeutic interventions in malaria-affected regions. A systematic literature search was conducted across multiple databases, including ProQuest, Scopus, Embase, Ovid, MEDLINE, PubMed, and Google Scholar. The risk of bias in the selected studies was assessed using the Joanna Briggs Institute critical appraisal tools. A thematic synthesis was employed to demonstrate the magnesium levels across selected studies, for analyzing and grouping based on geographic regions, age demographics, and clinical manifestations of malaria. Meta-analyses determined differences in magnesium levels between individuals with malaria, uninfected controls, and patients with different clinical severities of malaria. The effect sizes from individual studies were pooled using the random-effects model. Out of 2533 records identified, 13 studies were included in the review. The thematic synthesis revealed complex and varied results, with studies showing different magnesium levels in malaria patients across different geographies, age groups, and clinical presentations. The meta-analysis indicated elevated magnesium levels in malaria patients compared with uninfected controls (P < 0.01, Hedges' g: 1.94, 95% CI 0.86-3.03, I: 98.38%, 9 studies). No statistically significant difference was observed in magnesium levels between patients with severe and nonsevere malaria (P: 0.34, Hedges' g: 0.62, 95% CI - 0.64-1.88, I: 91.46%, 2 studies). A significant increase in magnesium levels was seen in patients with malaria who died compared with those who survived (P < 0.01, Hedges' g: 0.39, 95% CI 0.13-0.64, I: 3.39%, 3 studies). This systematic review and meta-analysis presented relationship between magnesium levels and malaria. While the meta-analysis indicated a general trend of increased magnesium levels in patients with malaria, the substantial heterogeneity and instability of the results hint toward a rich yet uncharted territory requiring more research depth. The intricate interplay between magnesium levels and malaria beckons a multidimensional approach in future studies.
Topics: Humans; Magnesium; Malaria
PubMed: 38228783
DOI: 10.1038/s41598-024-51718-z -
Transactions of the Royal Society of... Oct 2023Strongyloidiasis is a parasitosis representing a significant public health problem in tropical countries. It is often asymptomatic in immunocompetent individuals but its... (Meta-Analysis)
Meta-Analysis
Strongyloidiasis is a parasitosis representing a significant public health problem in tropical countries. It is often asymptomatic in immunocompetent individuals but its mortality rate increases to approximately 87% in severe forms of the disease. We conducted a systematic review, including case reports and case series, of Strongyloides hyperinfection and dissemination from 1998 to 2020 searching PubMed, EBSCO and SciELO. Cases that met the inclusion criteria of the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were analysed. Statistical analysis was performed using Fisher's exact test and Student's t-test and a Bonferroni correction for all the significant values. A total of 339 cases were included in this review. The mortality rate was 44.83%. The presence of infectious complications, septic shock and a lack of treatment were risk factors for a fatal outcome. Eosinophilia and ivermectin treatment were associated with an improved outcome.
Topics: Animals; Humans; Strongyloidiasis; Strongyloides stercoralis; Superinfection; Ivermectin
PubMed: 37300462
DOI: 10.1093/trstmh/trad032 -
PLoS Neglected Tropical Diseases Dec 2023Cutaneous (CL) and mucocutaneous leishmaniasis (MCL) are parasitic diseases caused by parasites of the genus leishmania leading to stigma caused by disfigurations. This...
BACKGROUND
Cutaneous (CL) and mucocutaneous leishmaniasis (MCL) are parasitic diseases caused by parasites of the genus leishmania leading to stigma caused by disfigurations. This study aimed to systematically review the dimensions, measurement methods, implications, and potential interventions done to reduce the CL- and MCL- associated stigma, synthesising the current evidence according to an accepted stigma framework.
METHODS
This systematic review followed the PRISMA guidelines and was registered in PROSPERO (ID- CRD42021274925). The eligibility criteria included primary articles discussing stigma associated with CL and MCL published in English, Spanish, or Portuguese up to January 2023. An electronic search was conducted in Medline, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library. The mixed methods appraisal tool (MMAT) was used for quality checking. A narrative synthesis was conducted to summarise the findings.
RESULTS
A total of 16 studies were included. The studies report the cognitive, affective, and behavioural reactions associated with public stigma. Cognitive reactions included misbeliefs about the disease transmission and treatment, and death. Affective reactions encompass emotions like disgust and shame, often triggered by the presence of scars. Behavioural reactions included avoidance, discrimination, rejection, mockery, and disruptions of interpersonal relationships. The review also highlights self-stigma manifestations, including enacted, internalised, and felt stigma. Enacted stigma manifested as barriers to forming proper interpersonal relationships, avoidance, isolation, and perceiving CL lesions/scars as marks of shame. Felt stigma led to experiences of marginalisation, rejection, mockery, disruptions of interpersonal relationships, the anticipation of discrimination, fear of social stigmatisation, and facing disgust. Internalised stigma affected self-identity and caused psychological distress.
CONCLUSIONS
There are various manifestations of stigma associated with CL and MCL. This review highlights the lack of knowledge on the structural stigma associated with CL, the lack of stigma interventions and the need for a unique stigma tool to measure stigma associated with CL and MCL.
Topics: Humans; Leishmaniasis, Mucocutaneous; Cicatrix; Social Stigma; Stereotyping; Fear; Leishmaniasis, Cutaneous
PubMed: 38153950
DOI: 10.1371/journal.pntd.0011818 -
PloS One 2024Toxoplasma gondii (T. gondii) is a worldwide distributed protozoan parasite which has infected a wide range of warm-blooded animals and humans. The most common form of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Toxoplasma gondii (T. gondii) is a worldwide distributed protozoan parasite which has infected a wide range of warm-blooded animals and humans. The most common form of T. gondii infection is asymptomatic (latent); nevertheless, latent toxoplasmosis can induce various alterations of sex hormones, especially testosterone, in infected humans and animals. On the other hand, testosterone is involved in behavioral traits and reproductive functions in both sexes. Hence, the purpose of this systematic review is to summarize the available evidence regarding the association between T. gondii infection and testosterone alteration.
METHODS
In the setting of a systematic review, an electronic search (any date to 10 January 2023) without language restrictions was performed using Science Direct, Web of Science, PubMed, Scopus, and Google Scholar. The PRISMA guidelines were followed. Following the initial search, a total of 12,306 titles and abstracts were screened initially; 12,281 were excluded due to the lack of eligibility criteria or duplication. Finally, 24 articles met the included criteria. A mean±standard deviation (SD) was calculated to assess the difference of testosterone between T. gondii positive and T. gondii negative humans. The possibility of publication bias was assessed using Egger's regression. P-value < 0.05 was considered statistically significant.
RESULTS
This systematic review identified 24 articles (18 studies in humans and six studies in animals). Most human studies (13 out of 19) reported an increased level of testosterone following latent toxoplasmosis in males, while three studies reported decreased levels and two studies reported an insignificant change. Eleven articles (seven datasets in males and seven datasets in females) were eligible to be included in the data synthesis. Based on the random-effects model, the pooled mean± SD of testosterone in T. gondii positive than T. gondii negative was increased by 0.73 and 0.55 units in males and females, respectively. The Egger's regression did not detect a statistically significant publication bias in males and females (p = value = 0.95 and 0.71), respectively. Three studies in male animals (rats, mice, and spotted hyenas) and two studies in female animals (mice and spotted hyenas) reported a decline in testosterone in infected compared with non-infected animals. While, one study in female rats reported no significant changes of testosterone in infected than non-infected animals. Moreover, two studies in male rats reported an increased level of testosterone in infected than non-infected animals.
CONCLUSIONS
This study provides new insights about the association between T. gondii infection and testosterone alteration and identifies relevant data gaps that can inform and encourage further studies. The consequence of increased testosterone levels following T. gondii infection could partly be associated with increased sexual behavior and sexual transmission of the parasite. On the other hand, declining testosterone levels following T. gondii infection may be associated with male reproductive impairments, which were observed in T. gondii-infected humans and animals. Furthermore, these findings suggest the great need for more epidemiological and experimental investigations in depth to understand the relationship between T. gondii infection and testosterone alteration alongside with future consequences of testosterone alteration.
Topics: Male; Humans; Female; Animals; Mice; Rats; Testosterone; Hyaenidae; Toxoplasmosis; Toxoplasma; Reproduction; Seroepidemiologic Studies
PubMed: 38568993
DOI: 10.1371/journal.pone.0297362 -
PloS One 2023Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis, therefore, was conducted to investigate the scientific evidence regarding the potential association between T. gondii infection and psychiatric disorders in Iran.
METHODS
We systematically reviewed articles from world-wide databases, including PubMed, Scopus, Science Direct, Web of Science, Google Scholar, and Iranian national databases up to July 30th, 2021. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included studies. The common odds ratio (OR) was estimated using inverse variance and a random-effects model. Heterogeneity was assessed using the χ2-based Cochrane test (Q) and the I2 index. Also, sensitivity analyses and publication bias were calculated. Moreover, subgroup analysis was performed based on the type of disorder and quality score of different eligible studies.
RESULTS
16 studies were included in this meta-analysis. Our meta-analyses found that the OR of the risk of anti- T. gondii IgG and IgM in psychiatric patients compared to the control group was 1.56 (95% CI; 1.23-1.99) and 1.76 (95% CI: 1.19-2.61), respectively. Subgroup analysis based on the type of disorder showed that the OR of the risk of anti- T. gondii IgG in Iranian schizophrenia patients and other psychiatric disorders compared to the control group were 1.50 (95% CI; 1.09-2.07) and 2.03 (95% CI: 1.14-3.60), respectively, which are statistically significant. Also, the OR of the risk of anti- T. gondii IgM in Iranian schizophrenia and depression patients compared to the control group was 1.54 (95% CI; 0.9-2.64) and 1.03 (95% CI: 0.2-5.24), respectively, which are not statistically significant. Additionally, subgroup analysis based on quality scores showed no significant influence on the results according to the moderate quality studies. However, this association was significant according to the high quality studies. The obtained results of Egger's test were 1.5 (95% CI; -0.62-3.73, P = 0.15) and 0.47 (95% CI; -0.82-1.76, P = 0.45), respectively, indicating publication bias. The significant results of the heterogeneity analysis confirmed a high level of heterogeneity in the IgG test (P = 0.000, I2 = 66.6%). However, no significant results from the test of heterogeneity were detected in the IgM test (P = 0.15, I2 = 27.5%). The results of the sensitivity analysis showed that the impact of each study on the meta-analysis was not significant on overall estimates.
CONCLUSIONS
Despite the limited number of studies, these outcomes supported a possible link between T. gondii infection and psychiatric disorders in Iran. However, more high-quality investigations are needed in the future.
Topics: Humans; Iran; Toxoplasmosis; Toxoplasma; Schizophrenia; Immunoglobulin G; Immunoglobulin M; Seroepidemiologic Studies
PubMed: 37552680
DOI: 10.1371/journal.pone.0284954 -
Nutrients Nov 2023Micronutrient insufficiency has been implicated in malaria pathogenesis. However, the role of copper in malaria remains inconclusive. This study aimed to investigate the... (Meta-Analysis)
Meta-Analysis
Micronutrient insufficiency has been implicated in malaria pathogenesis. However, the role of copper in malaria remains inconclusive. This study aimed to investigate the association between copper levels and malaria pathogenesis, providing a deeper understanding of copper's role in the disease. A systematic review was conducted following the registered protocol in PROSPERO (CRD42023439732). Multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, and Google Scholar, were searched for relevant studies reporting blood copper levels in patients with malaria. The Joanna Briggs Institute critical appraisal checklist was used for assessing methodological quality. Qualitative and quantitative syntheses were employed, organizing, and summarizing the findings of the included studies. To calculate the standardized mean difference (Hedge's g) and 95% confidence intervals (CIs), a random-effects model was used. After screening the databases, 16 studies were included. Most studies (52.9%) reported that individuals with malaria had significantly higher copper levels than uninfected controls. The meta-analysis, based on 16 studies, showed no significant difference in copper levels between patients with malaria and uninfected controls overall ( = 0.39; Hedges' g, 0.38; 95% CI, -0.48 to 1.25; , 98.73%). Subgroup analysis showed a significant difference in copper levels between patients with malaria and uninfected controls among studies conducted in Asia ( < 0.01; Hedges' g, 1.74; 95% CI, 1.04 to 2.44; , 90.88%; five studies) and studies employing plasma blood samples ( < 0.01; Hedges' g, 1.13; 95% CI, 0.60 to 2.07; , 93.11%; four studies). The qualitative synthesis of the reviewed studies suggests a complex relationship between copper levels and malaria. The meta-analysis results showed no significant difference in copper levels between patients with malaria and uninfected controls overall. However, subgroup analyses based on various factors, including continent and blood sample type, showed copper level variations. These findings highlight the need for further research to better understand the role of copper in malaria pathogenesis by considering geographical factors and the blood sample type used for copper level measurement.
Topics: Humans; Copper; Malaria; Asia
PubMed: 38004142
DOI: 10.3390/nu15224749 -
Current Medical Imaging Aug 2023Liesegang rings (LR) are concentric acellular lamellar structures, usually found in cystic and inflammatory tissues but can also be seen in neoplastic conditions. They...
INTRODUCTION
Liesegang rings (LR) are concentric acellular lamellar structures, usually found in cystic and inflammatory tissues but can also be seen in neoplastic conditions. They have been mistakenly interpreted as various structures like psammomatous calcification, parasites, and algae. This study has aimed to systematically review and summarize the existence of LRs in both non-neoplastic and neoplastic conditions of the kidney. The systematic search in PUBMED, PUBMED CENTRAL, and EMBASE databases along with Google Scholar was performed by using Kidney, Liesegang Rings, or Liesegang structure or pseudo parasitic structure in combination with the Boolean operators ''and'' as searching terms. Data were collected for demographic characteristics and histopathology diagnosis. The search function was limited to human subjects. Two reviewers independently performed the eligibility assessment and data extraction. Eligibility inclusion criteria were all publications in the English literature worldwide related to Liesegang rings in association with kidney's non-neoplastic and neoplastic conditions, regardless of the years of publication. Also included were those cases whose full articles were unavailable, but the abstract was well-described, fulfilling our inclusive criteria. Eligibility exclusion criteria included LRs found elsewhere in the body organs apart from the kidney and availability of full text in a different language, non-human, and duplicate article/case.
METHOD
After the exclusion of the articles as per the exclusion criteria, the total articles that fulfilled the inclusive criteria were reviewed. In addition, all the articles were further cross-referenced for additional articles. All published papers retrieved from this search were considered for this review. A total of 22 records (26 cases) were found with a diagnosis of LRs in the kidney to date. Some articles were published as case series. Accordingly, 26 patients were reported to have Liesegang rings associated with kidney neoplastic and non-neoplastic conditions, 12 were male and 14 were female. For one case the gender was not mentioned. LRs presented a higher frequency in individuals between the 4th and 5th decades of life. No single case was reported in infants and younger children. Regarding predisposing factors for LRs, cystic fluid contents were the most common underlying condition.
RESULT
In our practice, we encountered an unusual case of a 55-year-old female with a complaint of pain in the left upper quadrant of the abdomen. The ultrasound revealed nephrolithiasis and chronic kidney disease for which a nephrectomy was performed. On the histopathological examination, there was an incidental finding of Liesegang rings and a papillary adenoma along with features of chronic pyelonephritis. Our review will provide insight into LRs in different spectrums of kidney diseases.
CONCLUSION
This study represents the first available systematic review of the literature demonstrating LRs in the kidney. Although Liesegang rings have no great clinical significance, nonetheless, their presence in both tissue and cytological specimens should be kept in mind while dealing with different lesions of the kidney as they are good mimickers of many organic and inorganic substances, parasites, and malignancies.
PubMed: 37594156
DOI: 10.2174/1573405620666230817094600 -
Parasites & Vectors Aug 2023Bovine babesiosis, caused by different Babesia spp. such as B. bovis, B. bigemina, B. divergens, and B. major, is a global disease that poses a serious threat to... (Review)
Review
Bovine babesiosis, caused by different Babesia spp. such as B. bovis, B. bigemina, B. divergens, and B. major, is a global disease that poses a serious threat to livestock production. Babesia bovis infections are associated with severe disease and increased mortality in adult cattle, making it the most virulent agent of bovine babesiosis. Babesia bovis parasites undergo asexual reproduction within bovine red blood cells, followed by sexual reproduction within their tick vectors, which transmit the parasite transovarially. Current control methods, including therapeutic drugs (i.e., imidocarb) have been found to lead to drug resistance. Moreover, changing environmental factors add complexity to efficient parasite control. Understanding the fundamental biology, host immune responses, and host-parasite interactions of Babesia parasites is critical for developing next-generation vaccines to control acute disease and parasite transmission. This systematic review analyzed available research papers on vaccine development and the associated immune responses to B. bovis. We compiled and consolidated the reported vaccine strategies, considering the study design and rationale of each study, to provide a systematic review of knowledge and insights for further research. Thirteen studies published since 2014 (inclusive) represented various vaccine strategies developed against B. bovis such as subunit, live attenuated, and viral vector vaccines. Such strategies incorporated B. bovis proteins or whole live parasites with the latter providing the most effective prophylaxis against bovine babesiosis. Incorporating novel research approaches, such as "omics" will enhance our understanding of parasite vulnerabilities.
Topics: Animals; Cattle; Babesia bovis; Babesiosis; Cattle Diseases; Babesia; Vaccines
PubMed: 37563668
DOI: 10.1186/s13071-023-05885-z -
The Lancet. Infectious Diseases Feb 2024Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure.
METHODS
For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2-3 and between day 0 and days 5-7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680.
FINDINGS
Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2-3 were -0·6 g/dL (95% CI -0·7 to -0·5), -0·7 g/dL (-0·8 to -0·5), -0·6 g/dL (-0·7 to -0·4), and -0·5 g/dL (-0·7 to -0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2-3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias.
INTERPRETATION
Treatment of patients with G6PD activity of 30% or higher with 0·25-0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25-1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses.
FUNDING
Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.
Topics: Humans; Antimalarials; Artemether, Lumefantrine Drug Combination; Artesunate; Australia; Hemoglobins; Hemolysis; Malaria, Vivax; Plasmodium vivax; Primaquine; Prospective Studies; Retrospective Studies
PubMed: 37748497
DOI: 10.1016/S1473-3099(23)00431-0