A systematic review and meta-analysis of inflammatory biomarkers associated with malaria infection and disease severity.

Inflammatory biomarkers; C-reactive protein (CRP), Interleukin 6 (IL-6), and tumor necrosis factor- alpha (TNF-α) play a very crucial role in disease pathogenesis. Studies conducted earlier showed the associativity of these biomarkers with malaria severity. Meta-analysis of individual biomarkers was done in many studies, while in a few others, all these candidates were estimated, but the findings were inconclusive. Therefore, a systematic review and meta-analyses were performed to evaluate differences in biomarkers mentioned above in complicated and uncomplicated malaria patients. Studies focussed on CRP, IL-6, and TNF-α with quantitative data on complicated and uncomplicated malaria patients were searched on PubMed, Scopus, and Google Scholar. The quality of the studies selected for this review was checked following Newcastle-Ottawa Scale guidelines. The standard mean difference and confidence interval of biomarkers in the targeted groups were calculated using the random effects model. Egger's test and funnel plot asymmetry were performed to assess the publication bias. Thirteen studies that qualified the inclusion criteria were considered for this meta-analysis. CRP levels were higher in complicated malaria patients than uncomplicated ones (P < 0.00001, pooled SMD: 0.90 mg/L, 95 % CI: 0.51 to 1.30 mg/L, I2: 80 %, six studies). IL-6 levels were elevated in complicated cases (P < 0.00001, pooled SMD: 0.89 pg/ml, 95 % CI: 0.66 to 1.12, I2: 99 %, four studies) and TNF-α also showed an increase in severe complicated patients (P < 0.00001, pooled SMD: 1.18 pg/ml, 95 % CI: 1 to 1.36, I2: 99 %, six studies). In most of the included studies, CRP, IL-6, and TNF-α were higher in complicated malaria patients. Nevertheless, the results of a few studies were not convincing. Due to the lack of specificity in all individual biomarkers, none had adequate diagnostic accuracy. Considering the role of pro-inflammatory cytokines in the CRP activation pathway in malaria progression, the combination of these biomarkers should be used in monitoring the disease severity.

Biomarkers of disease severity in vivax malaria.

Severe complications have been observed and established for Plasmodium falciparum as well as P. vivax infections worldwide. Although P. vivax infection is not fully acknowledged as malignant malaria, recently life-threatening complications have been reported to occur in many studies. The recognition of biomarkers with excellent sensitivity and reliability plays a prime role in disease management. Acute inflammatory response and oxidative stress are observed in malaria due to the production of reactive oxygen species. Lipid and protein oxidative injuries are prospective biomarkers for disease severity owing to the damage caused by the parasite. We have tried to find out whether protein carbonylation (PC), lipid peroxidation (LPO) and superoxide dismutase (SOD) could suffice as a biomarker for severe vivax malaria or not. Blood samples were collected from the individuals attending Jawaharlal Nehru Medical College of Aligarh Muslim University during the wet season of malaria transmission. Microscopy and rapid diagnostic kits were used as a tool for malaria diagnosis. A total of 214 subjects were enrolled for the study: 30 febrile controls and 184 subjects with vivax malaria. Protein carbonylation and lipid peroxidation were found to be directly associated with parasite count and total antioxidant status (TAS). Increase in oxidative stress was also observed in severe vivax malaria patients. Levels of uric acid and bilirubin too were raised in complicated cases. Protein carbonylation was found to be a more reliable indicator of vivax malaria severity than lipid peroxidation.

Altered haematological parameters in children with malaria infection, a systematic review and meta-analysis.

OBJECTIVE: This study aimed to illustrate the effect of malaria infection on red blood cell parameters in children and evaluate the diagnostic relevance of haematological parameters in predicting malaria. METHODS: The studies were identified through databases like PubMed, Google Scholar, and Scopus to retrieve related articles. Fourteen studies were selected by literature search based on inclusion and exclusion criteria, and a meta-analysis on different red blood cell parameters was performed. RESULTS: Haematocrit, haemoglobin concentration, and RBC count show statistically significant findings with p values of (<0.00001), (p<0.00001) and (p=0.0004), respectively. Other parameters like MCV, MCH, and MCHC show statistically non-significant results with p values of 0.21, 0.36, and 0.63, respectively. CONCLUSION: Considering the above findings, the combination of haemoglobin concentration, haematocrit, and RBC counts could be used as reliable parameters to predict the presence of infection and included in the diagnostic strategy for malaria in children.

Towards digital diagnosis of malaria: How far have we reached?

The need for precise and early diagnosis of malaria and its distinction from other febrile illnesses is no doubt a prerequisite, primarily when standard rapid diagnostic tests (RDTs) cannot be totally relied upon. At the time of disease outbreaks, the pressure on hospital staff remains high and the chances of human error increase. Therefore, in the era of digitalisation of medicine as well as diagnostic approaches, various technologies such as artificial intelligence (AI) and machine learning (ML) should be deployed to further aid the diagnosis, especially in endemic and epidemic situations. Computational techniques are now more at the forefront than ever, and the interest in developing such efficient technologies is continuously increasing. A comprehensive understanding of these digital technologies is needed to maintain the scientific rigour in these attempts. This would enhance the implementation of these novel technologies for malaria diagnosis. This review highlights the progression, strengths, and limitations of various computing techniques so far employed to diagnose malaria.

Immunohistopathological changes in the placenta of malaria-infected women in unstable transmission setting of Aligarh.

INTRODUCTION: Pregnant women are more susceptible to malaria due to a combination of physiological and immunological changes. The infection may even affect the growth and survival of the foetus, which mainly occur when parasite enters the placenta. The sequestration of infected erythrocytes may trigger the host response, leading to placental inflammation and altered development, affecting the structure and nutrient transport of placenta. These factors collectively impair placental functions and affect foetal growth. METHODS: Pregnant women with peripheral parasitaemia for P. falciparum and P. vivax (20 each) were included in the present study, along with 15 age-matched uninfected healthy pregnant women. Placentae were analysed for the presence of local parasitaemia along with pathological lesions caused due to the parasite. Immunohistochemical staining for CD20, CD45 and CD68 cells was performed for examining the specific leucocytes in the intervillous space of the placenta. RESULTS: Of the 20 individuals with P. falciparum, only seven placentae showed parasitaemia, whereas individuals with P. vivax showed no placental infection. The pathological changes observed in the P. falciparum-infected placenta include syncytial knotting, excess fibrinoid deposition, syncytiotrophoblast necrosis, syncytial rupture, thickening of trophoblast basement membrane and increased collagen deposition. Immunohistochemical staining showed a significant increase in B cells (CD20), leucocytes (CD45) and monocytes and macrophages (CD68) in the P. falciparum-infected placenta (p < 0.0001). DISCUSSION: The result implies that P. falciparum is responsible for pathological alterations in placenta, affecting the nutrient transport across placenta and foetal growth. The immune cells also migrate to the placenta and accumulate in the intervillous space to show humoral and cell-mediated immunity against the parasite.

A micro-epidemiological report on the unstable transmission of malaria in Aligarh, India.

India contributes approximately 70% to the malaria burden of Southeast Asia. The transmission of disease in the country is generally hypoendemic, seasonal and unstable. Most researchers focus upon the hyperendemic malarious regions with stable malaria transmission. There is paucity of data regarding malaria transmission in hypoendemic regions, here we are presenting an epidemiological picture of clinical manifestations through a hospital-based survey in Aligarh, India, during 2016-18. Two thousand sixty-eight patients were diagnosed with malaria infection in Jawaharlal Nehru Medical College and Hospital (JNMCH), out of which 1104 were enrolled for clinical analysis. Ninety per cent of the cases were reported during July-November, and the rest in the dry season. A progressive increase in the prevalence rate was observed during the study period, i.e. 4.8, 7.57 and 8.7% in 2016, 2017 and 2018, respectively. Of the total cases, 75.77% had vivax malaria, while rest suffered from falciparum malaria. The risk of disease was significantly higher in the age group 0-15 years compared to all other age groups (p < .0001). The infection rate was higher in males (61%) compared to females (39%) p < .0001. Overall 8.6% of the patients had severe malaria who fulfilled the WHO criteria. The increasing rate of malaria infection during the study period and a considerable no. of severe vivax malaria cases warrant an efficient disease monitoring system, pointing towards the need to carry out micro-epidemiological studies in order to estimate the real burden of malaria in the country.

Differential status and significance of non-enzymatic antioxidants (reactive oxygen species scavengers) in malaria and dengue patients.

An imbalance in oxidants and antioxidants is observed during malaria and dengue infections which is associated with the production of reactive oxygen species (ROS) via haem degradation or immune activation, a contributing factor for disease pathogenesis. The levels of non-enzymatic antioxidants and total antioxidant status (TAS) in malaria and dengue patients were analysed and compared with healthy controls. Particular attention was paid to elevated levels of total bilirubin (TB) and uric acid (UA) during disease progression and haemolysis and noticed a significant increase in dengue patients (dengue>Pf>Pv>control). A highly significant difference was also observed between dengue and Pf patients (p < 0.0001) for these parameters. Glutathione levels were comparable in dengue and falciparum malaria but were significantly higher than that of vivax malaria patients. Ascorbate levels were significantly depleted in all the patient groups (p < 0.0001) and a negative correlation was established for TAS and ascorbate levels in dengue patients (r=-0.32). A good positive correlation was observed between TAS-UA and TAS-TB levels. Thus, these findings suggest that severe haemolysis, renal failure, and liver dysfunction have higher prominence in dengue patients during the simultaneous outbreak of the two arthropod-borne diseases. A differential status of non-enzymatic antioxidants was also observed during the different stages of dengue and malaria.

Discriminating Clinical and Biological Features in Malaria and Dengue Patients.

BACKGROUND: Malaria and dengue are the most widespread infectious diseases of tropical countries with an estimated 219 and 50 million cases globally. The aim of the proposed study was to find out discriminating clinical features of falciparum malaria and dengue. METHOD: Falciparum malaria was diagnosed by looking at the ring and gametocyte stages by microscopic examination in Giemsa stained slides. Dengue was diagnosed by ELISA for dengue-specific IgM and IgG. Liver enzymes (AST and ALT) and kidney markers (creatinine and urea) were estimated by standard biochemical techniques. RESULT: AST and ALT showed similar rise in both, severe malaria and dengue patients but it was much pronounced in dengue haemorrhagic fever where it attained 3-4 folds increase. Creatinine and urea showed higher levels in dengue compared to malaria. Thrombocytopenia (76.27%), convulsions (18.64%) and hepatic dysfunction (5.08%) were more prominent in dengue than that in malaria where these parameters were 50.89, 7.14 and 2.67%, respectively. Conversely, cases with anaemia, splenomegaly and jaundice were three times more in falciparum malaria. Acute renal failures and neurological sequelae were noticed in slightly higher number of dengue patients. CONCLUSION: Thrombocytopenia and hepatic dysfunction were more common in dengue, while anaemia, splenomegaly, jaundice and convulsions were more frequent in falciparum malaria. Neurological sequelae and cases of acute renal failure were almost equal in both the infections.