Procalcitonin is elevated in severe malaria and is a promising biomarker of severe malaria and multi-organ dysfunction: A cross-sectional study and meta-analysis.

BACKGROUND: Elevated procalcitonin (PCT) has been reported in bacterial infection and is positively associated with the severity of the disease. Patients with severe Plasmodium falciparum malaria also display higher procalcitonin levels compared to those with non-severe disease, indicating a possible role for bacterial infection in severe disease, however this observation remained variable in different study population. Furthermore, the significance of PCT in different clinical categories of severe malaria has not been evaluated so far. METHODS: A total of 74 P. falciparum-infected subjects were enrolled in the study comprising of 55 cases complicated malaria [cerebral malaria- 14; non-cerebral severe malaria- 21; multi-organ dysfunction- 20] and 19 uncomplicated cases. Serum levels of PCT were quantified by fluorescence immunoassay. For meta-analysis, the literature search was performed in different databases, and all relevant articles were screened, and eligible reports were identified based on predefined inclusion and exclusion criteria. The meta-analysis was performed by comprehensive meta-analysis software V3 and MedCalc 20.218. RESULTS: Patients with severe P. falciparum malaria had significantly higher PCT levels compared to uncomplicated cases (p = 0.01). Analysis of PCT in different categories of patients with severe malaria revealed significantly elevated PCT in multi-organ dysfunctions compared to those with uncomplicated malaria (p = 0.004) and cerebral malaria (p = 0.05). Interestingly the receiver operating characteristics curve analysis showed procalcitonin as a promising biomarker for differentiating severe malaria (AUC: 0.697, p = 0.01) and multi-organ dysfunction (AUC: 0.704, p = 0.007) from uncomplicated malaria and other clinical categories of falciparum malaria, respectively. Furthermore, meta-analysis also revealed an elevated procalcitonin in severe malaria and it could be an important biomarker in the management of severe disease. CONCLUSIONS: PCT is elevated in P. falciparum-infected patients and could be a good biomarker for diagnosis of severe malaria and multi-organ dysfunction. It can help in the management of severe disease with additional treatment options.

The role of MBL, PCT, CRP, neutrophil-lymphocyte ratio, and platelet lymphocyte ratio in differentiating infections from flares in lupus.

BACKGROUND: The distinction between infection and flare in systemic lupus erythematosus (SLE) has always been a dilemma for clinicians as the clinical and biochemical profiles overlap. The present study evaluated affordable biomarkers to distinguish infection from flare in an SLE cohort in a tertiary care center in eastern India. METHODS: One hundred and fifty-two SLE patients were clinically evaluated and enrolled in the present study. Hematological, immunological, and biochemical profiles and various biomarkers such as C reactive protein (CRP), procalcitonin (PCT), and Mannose-binding lectin (MBL) were quantified. RESULTS: One hundred and fifty-two patients (152) were enrolled in the present study and all had SLEDAI scores of more than 4. From which 70 had infection, and the common infections were urinary tract infection (34.28%) followed by pneumonia (27.14%). Neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) were significantly elevated in SLE with infections (NLR: 5.84 ± 2.47; CRP: 30.56 ± 41.63) than those with flare (NLR: 3.87 ± 2.62; CRP: 8.73 ± 9.53). The receiver operating characteristic curve (ROC) analysis revealed CRP, PLR, and NLR as important markers for predicting infections (CRP: AUC = 0.682, p = 0.0001; PLR: AUC = 0.668, p = 0.0008; NLR: AUC = 0.742, p < 0.0001). The MBL and PCT levels were comparable among SLE flare and those with infections. CONCLUSIONS: NLR and CRP levels are affordable biomarkers to distinguish infections from flares in SLE. MBL and PCT could not differentiate flare from an infection. Key Points • Biomarkers for the differentiation of infection and flare in SLE are limited. • NLR, PLR, and CRP are promising biomarkers to enable differentiation. • PCT and MBL are not ideal biomarkers to differentiate infection from flare.

CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study.

BACKGROUND: Cluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (-159 C > T) with susceptibility to SLE or disease severity needs to be defined. METHODS: Two hundred female SLE patients diagnosed on systemic lupus international collaborating clinics (SLICC) classification criteria and age, sex, matched healthy controls were enrolled in the present study. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: Prevalence of mutant genotypes (CT and TT) and minor allele (T) of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT: P < 0.0001; OR = 3.26, TT:P < 0.0001; OR = 3.39; T:P = 0.0009, OR = 1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P = 0.0002, OR = 8.07; T: P = 0.001, OR = 1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLE disease activity index-2K (SLEDAI-2K) scores and 24 hours proteinuria. CONCLUSION: CD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.

TNF-α promoter polymorphisms (G-238A and G-308A) are associated with susceptibility to Systemic Lupus Erythematosus (SLE) and P. falciparum malaria: a study in malaria endemic area.

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine associated with autoimmune and infectious diseases. Importance of TNF-α in P. falciparum malaria and systemic lupus erythematosus (SLE) have been demonstrated. However, association of functional promoter variants with SLE and malaria is lacking in malaria endemic population. A total of 204 female SLE patients and 224 age and sex matched healthy controls were enrolled in the study. Three hundred fourteen P. falciparum infected patients with different clinical phenotypes were included. TNF-α polymorphisms (G-238A & G-308A) were genotyped by PCR-RFLP. Plasma levels of TNF-α was quantified by ELISA. Heterozygous mutants and minor alleles of TNF-α (G-238A and G-308A) polymorphisms were significantly higher in SLE patients compared to healthy controls and associated with development of lupus nephritis. In addition, both promoter variants were associated with severe P. falciparum malaria. SLE patients demonstrated higher levels of plasma TNF-α compared to healthy controls. TNF-α (G-238A and G-308A) variants were associated with higher plasma TNF-α. In conclusion, TNF-α (G-238A & G-308A) variants are associated with higher plasma TNF-α levels in SLE patients residing in malaria endemic areas and could be a contributing factor in the development of SLE and susceptibility to severe P. falciparum malaria.

Cytokine Signature Associated with Disease Severity in Dengue.

Dengue is the most rapidly spreading viral disease transmitted by the bite of infected Aedes mosquitos. The pathogenesis of dengue is still unclear; although host immune responses and virus serotypes have been proposed to contribute to disease severity. In this study, we examined the circulating dengue virus (DENV) and measured plasma levels of inflammatory mediators. Ninety-eight patients during a dengue outbreak in eastern India in 2016 were included in the study. The presence of DENV was demonstrated by detecting NS1 antigen; IgM capture ELISA and serotypes were discriminated by type-specific RT-PCR and/or sequencing. Plasma samples were assayed for 41-plex cytokine/chemokines using multiplex Luminex assay. Eighty-five (87%) samples were positive by NS1/IgM capture ELISA/RT-PCR. All four serotypes of DENV were detected in this outbreak, with DENV-2 as the predominant type, seen in 55% of cases. Mixed infections were seen in 39% of subjects. Among the host inflammatory biomarkers, GM-CSF, IFN-γ, IL-10, IL-15, IL-8, MCP-1, IL-6, MIP-1ß, and TNF-α levels were significantly increased in dengue with and without warning signs, in severe dengue patients in comparison to healthy controls. Four cytokines IFN-γ, GM-CSF, IL-10, and MIP-1ß correlated significantly with disease severity and could serve as potential predictor for disease severity. Information on the host biomarkers and the dengue serotype may help guide in optimizing effective intervention strategies.

Care-seeking pathways, care challenges, and coping experiences of rural women living with rheumatoid arthritis in Odisha, India.

AIM: The aim of the study was to explore the care-seeking pathway of rural women living with rheumatoid arthritis (RA) and attending a tertiary health-care facility in Odisha, India. BACKGROUND: RA is the third leading chronic health condition and causes severe pain and immense psychosocial stress. The prevalence of RA is three to four times higher in women than in men. Furthermore, in India, women delay care seeking due to the prevailing sociocultural norms. Women report more severe symptoms and greater disability; however, there is a lack of information on their care-seeking pathways. METHOD: We conducted 113 in-depth interviews among RA patients those who visited specialists at the outpatients' Department of Rheumatology, SCB Medical College Hospital, a tertiary care hospital in Cuttack, Odisha, India. The grounded theory approaches were used for data analysis. FINDINGS: The key findings included physical pain and psychosocial stress in relation to RA, cultural issues in relation to RA, mapping of the health-care providers for RA, the first point of cares and changes in care-seeking pathways, the perceived challenge for seeking health-care, and coping strategies of patients and social supports. This study explored that the RA patients seek care from multiple providers - untrained, trained and specialist without any gatekeeping. However, the primary health centers were the first point of care for maximum patients due to accessibility and affordability. Furthermore, follow-up care is significant to prevent complication among RA patients; the primary health centers are the gateway for keeping RA patients. Hence, the availability of RA trained providers at primary health center including interprofessional care, such as physiotherapy providers, and proper referral system is essential to convalesce care-seeking pathways.

Association between vitamin D receptor polymorphisms and systemic lupus erythematosus in an Indian cohort.

AIM: Systemic lupus erythematosus (SLE) is an autoimmune disorder with various clinical manifestations. Susceptibility to development of SLE has been linked to several factors, such as genetic, environmental and hormonal. Vitamin D appears to have a regulatory role on disease manifestation and activity. Vitamin D exerts its effect through vitamin D receptors (VDR). Several studies have demonstrated an association between VDR polymorphisms and susceptibility to SLE in different populations, although the results are still inconclusive. In the present study, we investigated the association of VDR polymorphisms with SLE in a cohort of patients from Odisha, India. METHODS: Female SLE patients (n = 331) who fulfilled the revised American College of Rheumatology classification criteria were enrolled along with 282 healthy controls from similar geographical areas. VDR polymorphisms (BsmI, ApaI, TaqI and FokI) were typed by polymerase chain reaction followed by restriction fragment length polymorphism. Plasma level of 25-OH vitamin D was quantified by enzyme-linked immunosorbent assay. RESULTS: Prevalence of FokI (Ff) and TaqI (Tt) heterozygotes were significantly higher in SLE patients compared to healthy controls (Ff: P < 0.0001, odds ratio [OR] = 2.80, 95%CI = 1.99-3.95; Tt: P < 0.0001, OR = 2.07, 95%CI = 1.49-2.89). Furthermore, the minor alleles of FokI (f) and TaqI (t) polymorphisms were also more frequent in SLE patients than healthy controls (f: P < 0.0001, OR = 1.96, 95%CI = 1.52-2.52; t: P = 0.0002, OR = 1.60, 95%CI = 1.25-2.09). CONCLUSIONS: FokI and TaqI variants are significantly associated with SLE in an eastern Indian cohort. The cause-effect relationship can be assessed from the combined analyses of VDR polymorphism, plasma vitamin D levels and clinical manifestations.

A Comparison of the Intracerebral Hemorrhage Score and the Acute Physiology and Chronic Health Evaluation II Score for 30-Day Mortality Prediction in Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The intracerebral hemorrhage (ICH) score is well established as a reliable prognostic score in ICH, whereas recently, Acute Physiology and Chronic Health Evaluation II (APACHE II) has been observed to have a better discrimination in predicting mortality in primary pontine hemorrhage. Further, physiological parameters of APACHE II have been associated with outcome in ICH. This study is the first to observe a direct comparison between APACHE II and ICH scores in predicting 30-day mortality in spontaneous intracerebral hemorrhage (SICH). MATERIALS AND METHODS: This study was a prospective observational study where we compared the receiver operating characteristic (ROCs) of baseline ICH and APACHE II scores in patients with SICH for predicting 30-day mortality outcome. RESULTS: We observed that both APACHE II and ICH scores were good for predicting 30-day mortality with both having an area under the ROC curve of more than .8 (.831 [95% confidence interval {CI}, .740-.922; P <.001] and .892 [95% CI, .757-.932; P <.001], respectively). However, the ICH score was better discriminative (area under the curve AUC, .892 versus .831; P = .040) and better calibrated (P = .037 versus P = .089, Hosmer-Lemeshow goodness-of-fit test for logistic regression) for the same. Both APACHE II and ICH scores had a sensitivity of 87% at cutoff values of 19 and 3, respectively; however, the ICH score had a better specificity (90% versus 76.5%). CONCLUSION: The ICH score was observed to have a better discrimination and calibration for predicting 30-day mortality in SICH.

Transcriptomic meta-analysis reveals up-regulation of gene expression functional in osteoclast differentiation in human septic shock.

Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. This was followed by pathway-level analysis using three different algorithms (ORA, GSEA, SPIA). The identified up-regulated pathway, Osteoclast differentiation pathway (hsa04380) was validated in two independent cohorts. Of the pathway, 25 key genes were selected that serve as an expression signature of Septic Shock.

CR1 exon variants are associated with lowered CR1 expression and increased susceptibility to SLE in a Plasmodium falciparum endemic population.

BACKGROUND: Complement receptor 1 (CR1) plays an important role in immune complex clearance by opsonisation and possibly protects subjects from development of autoantibodies. Lower CR1 expression has been associated with susceptibility to systemic lupus erythematosus (SLE). In contrast, subjects displaying lower CR1 expression are protected against severe manifestations of falciparum malaria. This study is the first of its kind to investigate the association of CR1 variants with development of SLE in a P. falciparum endemic population from Odisha, India. METHODS: CR1 polymorphisms (intron 27 (A>T), exon 22 (A>G) and exon 33 (G>C)) were typed by PCR and restriction length polymorphism in 297 cases of female patients with SLE and 300 age-matched and sex-matched healthy controls from malaria endemic areas in Odisha, India. CR1 expression on monocytes was quantified by flow cytometry. RESULTS: The homozygous mutants of CR1 exon 22 (GG) and exon 33 (GG) and their minor alleles were associated with susceptibility to SLE. Furthermore, patients with SLE who harboured the GG genotype of the exon 33 polymorphism had a 3.12-fold higher chance of developing lupus nephritis. CR1 exon (22 and 33) variants were associated with lowered CR1 expression on monocytes in patients with SLE and in healthy controls. Patients with lupus nephritis showed significantly diminished CR1 expression than those without renal involvement (p=0.01). CONCLUSIONS: The results of the present study demonstrate that common CR1 exon variants are associated with diminished CR1 expression on monocytes and increased susceptibility to development of SLE and lupus nephritis in a malaria endemic area.

Host metabolic responses to Plasmodium falciparum infections evaluated by 1H NMR metabolomics.

The human malarial parasite Plasmodium falciparum causes the most severe forms of malarial infections, which include cerebral malaria and various organ dysfunctions amongst adults in India. So far no dependable clinical descriptor is available that can distinguish cerebral malaria from other symptomatically similar diseases such as sepsis and encephalitis. This study aims at evaluating the differential metabolic features of plasma samples from P. falciparum patients with varying severities, and patients suffering from symptomatically similar diseases. 1H Nuclear Magnetic Resonance (NMR) based metabolic profiling of the plasma of the infected individuals and the control population was performed. The differences in the plasma profiles were evaluated through multivariate statistical analyses. The results suggest malaria-specific elevation of plasma lipoproteins. Such an increase was absent in control populations. In addition, cerebral malaria patients exhibited a decrease in plasma glycoproteins; such a reduction was not observed in malarial patients without cerebral symptoms. The data presented here indicates that the metabolism and/or transport of the plasma lipids is specifically perturbed by malarial infections. The differential perturbation of the plasma glycoprotein levels in cerebral malaria patients may have important implications in the diagnosis of cerebral malaria.

Heterozygous mutants of TIRAP (S180L) polymorphism protect adult patients with Plasmodium falciparum infection against severe disease and mortality.

Toll-interleukin-1 receptor domain containing adapter protein (TIRAP) plays a crucial role in TLR2 and TLR4 signaling pathways. Glycosylphospatidylinositol (GPI), considered a toxin molecule of Plasmodium falciparum, interacts with TLR2 and 4 to induce an immune inflammatory response. A single nucleotide polymorphism at coding region of TIRAP (S180L) has been reported to influence TLRs signaling. In the present study, we investigated the association of TIRAP (S180L) polymorphism with susceptibility/resistance to severe P. falciparum malaria in a cohort of adult patients from India. TIRAP S180L polymorphism was typed in 347 cases of severe malaria (SM), 232 uncomplicated malaria and 150 healthy controls. Plasma levels of TNF-α was quantified by ELISA. Heterozygous mutation (S/L) conferred significant protection against MOD (multi organ dysfunction), NCSM (non-cerebral severe malaria) as well as mortality. Interestingly, homozygous mutants (L/L) had 16 fold higher susceptibility to death. TIRAP mutants (S/L and L/L) were associated with significantly higher plasma TNF-α levels compared to wild type (S/S). The results of the present study demonstrate that TIRAP S180L heterozygous mutation may protect patients against severe malaria and mortality.

Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens.

Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens.

MBL-2 polymorphisms (codon 54 and Y-221X) and low MBL levels are associated with susceptibility to multi organ dysfunction in P. falciparum malaria in Odisha, India.

BACKGROUND: Mannose binding lectin, a plasma protein protects host from virus, bacteria, and parasites. Deficiency in MBL levels has been associated with susceptibility to various infectious diseases including P. falciparum malaria. Common MBL polymorphisms in promoter and coding regions are associated with decrease in plasma MBL levels or production of deformed MBL, respectively. In the present study, we hypothesized that MBL2 variants and plasma MBL levels could be associated with different clinical phenotypes of severe P. falciparum malaria. METHODS: A hospital based study was conducted in eastern Odisha, India which is endemic to P. falciparum malaria. Common MBL-2 polymorphisms (codon 54, H-550L, and Y-221X) were typed in 336 cases of severe malaria (SM) [94 cerebral malaria (CM), 120 multi-organ dysfunction (MOD), 122 non-cerebral severe malaria (NCSM)] and 131 un-complicated malaria patients (UM). Plasma MBL levels were quantified by ELISA. RESULTS: Severe malaria patients displayed lower plasma levels of MBL compared to uncomplicated falciparum malaria. Furthermore, on categorization of severe malaria patients into various subtypes, plasma MBL levels were very low in MOD patients compared to other categories. Higher frequency of AB genotype and allele B was observed in MOD compared to UM (AB genotype: P = 0.006; B allele: P = 0.008). In addition, prevalence of YX genotype of MBL Y-221X polymorphism was also statistically more frequent in MOD case than UM (P = 0.009). CONCLUSIONS: The observations of the present study reveal that MBL-2 polymorphisms (codon 54 and Y-221X) and lower plasma MBL levels are associated with increased susceptibility to multi organ dysfunctions in P. falciparum malaria.

Vitamin D levels in Indian systemic lupus erythematosus patients: association with disease activity index and interferon alpha.

INTRODUCTION: Low levels of vitamin D have been associated with several autoimmune disorders including multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus (SLE). The major source of vitamin D is sunlight but exposure of SLE patients to UV rays has been shown to exacerbate disease pathology. Studies in various populations have shown an association between low vitamin D levels and higher SLE disease activity. METHODS: We enrolled 129 patients who fulfilled American College of Rheumatology criteria in the study. There were 79 treatment-naïve cases and 50 patients who were under treatment for underlying SLE. There were 100 healthy subjects from similar geographical areas included as controls. Plasma 25-OH vitamin D3 and interferon (IFN)-α levels were quantified by enzyme-linked immunosorbent assay (ELISA). The gene expression level of IFN-α was determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Plasma 25-OH vitamin D3 significantly correlated in an inverse manner with systemic lupus erythematosus disease activity index (SLEDAI) scores (P <0.0001, r = -0.42), anti-dsDNA (P <0.0001, r = -0.39), plasma IFN-α (P <0.0001, r = -0.43) and levels of IFN-α gene expression (P = 0.0009, r = -0.45). Further, plasma levels of IFN-α positively correlated with gene expression of IFN-α (P <0.0001, r = 0.84). Treatment-naïve SLE patients displayed significantly higher plasma levels of IFN-α compared to patients under treatment (P <0.001) and controls (P <0.001). CONCLUSIONS: These results suggest an important role of vitamin D in regulating disease activity in SLE patients and the need to supplement vitamin D in their treatment.

TLR-9 promoter polymorphisms (T-1237C and T-1486C) are not associated with systemic lupus erythematosus: a case control study and meta-analysis.

Toll like receptors (TLRs) are essential molecules implicated in both innate and adaptive immune response. Polymorphisms in TLR gene have been associated with various infectious diseases and autoimmune disorders. Role of TLR9 has been elegantly demonstrated in both human systemic lupus erythematosus (SLE) and mice model of lupus. In the present study we investigated association of TLR-9 promoter polymorphisms (T-1237C and T-1486C) with susceptibility/resistance to SLE in an Eastern Indian state which is endemic to parasitic diseases. 210 Female SLE patients who fulfilled the American College of Rheumatology criteria were enrolled along with matched healthy controls from Odisha, India. TLR-9 polymorphisms (T-1237C and T-1486C) were typed by polymerase chain reaction followed by restriction fragment length polymorphism. For meta-analysis, relevant literatures were searched from PubMed database and comprehensive meta-analysis V2 software was employed for analysis. Allele and genotype frequency of TLR-9 promoter polymorphisms (T-1237C and T-1486C) were comparable among SLE patients and controls. Further, meta-analysis of earlier reports and present study did not reveal a significant association of TLR-9 (T-1237C and T-1486C) polymorphisms with SLE. Data from the present study suggest that TLR-9 promoter polymorphisms are not associated with susceptibility to SLE in an area endemic to parasitic diseases.

Decreased prevalence of sepsis but not mild or severe P. falciparum malaria is associated with pre-existing filarial infection.

BACKGROUND: Enhanced inflammatory host responses have been attributed as the cellular basis for development of severe malaria as well as sepsis. In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype. This suggests that successful control of filariasis by employing mass drug administration, could potentially contribute to an increase in incidence of sepsis and cerebral malaria in human communities. A case control study was undertaken to address this critical and urgent issue. METHODS: Eighty-nine patients with sepsis and one hundred and ninety-six patients with P. falciparum malaria all originating from Odisha, were tested for prevalence of circulating filarial antigens - a quantitative marker of active filarial infection. Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25high T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients. RESULTS: Prevalence of filarial antigenemia was significantly less in sepsis patients as compared to controls suggesting that pre-existing filariasis could influence development of sepsis. On the other hand, levels of circulating filarial antigen were comparable in severe malaria cases and healthy controls suggesting that development of severe malaria is independent of pre-existing W. bancrofti infections. Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+ CD25high cells were comparable in malaria patients with or without filarial infections. CONCLUSIONS: These observations imply that successful control of filariasis could have adverse consequences on public health by increasing the incidence of sepsis, while the incidence of severe malaria may not adversely increase as a consequence of elimination of filariasis.