Infectious Disease-related Mortality Research Articles

Burden and trends of infectious disease mortality attributed to air pollution, unsafe water, sanitation, and hygiene, and non-optimal temperature globally and in different socio-demographic index regions

BackgroundEnvironmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019.MethodsThis observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019.ResultsIn 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature.ConclusionsOur study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Ocular toxicity of daily anti-tubercular treatment regimen: A prospective observational study

Context: India carries a significant burden of TB which is the commonest cause of infectious disease-related mortality. Anti-tubercular drugs can cause serious ocular toxic effects. Optical coherence tomography (OCT) can be used as a valuable tool in the quantitative analysis of anti-tubercular treatment (ATT)-induced toxic optic neuropathy. Aims: To study the changes in visual parameters in patients on ATT and to analyze the OCT changes in patients by taking measurements once before initiation of treatment and once during ongoing treatment (between three and six months). Settings and Design: Tertiary care center, Prospective observational study. Methods and Material: A prospective observational study was conducted in 140 eyes of 70 subjects undergoing ATT as per the latest RNTCP guidelines where the following determinants were examined, and the corresponding values were taken once before initiation of treatment and once during ongoing treatment (between three and six months) and results were analyzed. Around 90% of the subjects were examined at the end fourth month. Visual acuity was taken using the Log Mar chart, color vision using Ishihara’s chart, and slit lamp examination and fundus evaluation using a 90 D lens. OCT was done and average nasal, temporal, superior, and inferior quadrant retinal nerve fiber layer (RNFL) measurements were taken. Perimetry was also done; however, findings were not included in this study. Statistical Analysis Used: Frequency and percentage were applied to study the changes in visual parameters in patients on ATT. A paired t-test was applied for numerical variables to analyze the OCT changes in patients undergoing ATT. A P value < 0.05 was considered statistically significant. Results: Despite a near-normal appearance of the fundus on ophthalmoscopy, OCT clearly demonstrated and quantified the loss of retinal nerve fibers. Statistically significant RNFL thinning (P value < 0.001) was noted in the superior, temporal, and inferior quadrants and least in the nasal quadrant (P = 0.005). Significant deterioration in visual acuity was observed following three months of ATT (P = 0.001). Red-green color vision abnormalities were detected in 14 out of 140 eyes (10%). Conclusions: RNFL thickness was reduced on OCT. RNFL thickness quantification and assessment of other visual parameters especially color vision help in the early diagnosis of ocular toxic effects of ATT. Hence, awareness and active screening are imperative in preventing visual impairment and blindness.

Anti-tuberculosis treatment-induced hepatotoxicity in a post-operative setting

The most frequent cause of infectious disease-related mortality globally is tuberculosis (TB), a multisystemic disease with a wide range of presentations and symptoms. Around 12% of extrapulmonary TB cases and 1–3% of all TB cases are caused by abdominal TB. The issue of antituberculosis drug-induced liver injury (ATLI), which has long been a challenge in the management of TB infection, is one of increased significance. The major steps to reduce the occurrence of ATLI are to identify the possible risk factors of hepatotoxicity and to provide an appropriate weight-based anti-tuberculosis treatment (ATT). This case report clarifies the significance of appropriate weight-based dosing of ATT, particularly in a post-operative environment as evidenced in this instance where the patient experienced considerable post-operative weight loss.

Evaluation of the Relationship among Different Haemoglobin Genotypes, Calcium, and Membrane Potential in Patients with Malaria in FMC, Umuahia

Malaria is still a major contributor to the high rate of global infectious disease-related mortality and morbidity particularly in Nigeria. The aim of this study is to assess the relationship between various Hemoglobin Genotypes, Calcium, and Membrane Potential in malaria patients. Retrospective analysis of the results of the distribution of Malaria parasitemia among suspected cases of malaria, various Haemoglobin genotypes, Calcium and Membrane Potential were conducted in Federal Medical Centre (FMC) Umuahia, Abia State. Two hundred cases were examined by Giemsa staining method using thick film. Haemoglobin genotype determination was performed by Cellulose acetate electrophoresis. Obtained data were analyzed using One-Way ANOVA. Results: One hundred and seventy (85.0%) were positive for Malaria parasite. The prevalence was 92(54.1%) and 78(46.0%) for females and males respectively and at p<0.05, the result obtained from the statistics is considered significant. There are high prevalence of parasitemia in AA, 80(40.0%), with genotype SS recording the least with 30(15%). The age group 27-35 years had the highest occurrence of parasitemia with (44.1%) while the least was obtained in the age range 45-53 years with (2.4%). It was observed that the density of Malaria parasitemia was highest in the age group 27-35 years meaning that parasite density decreases with increasing age and the Haemoglobin genotype AA had the highest Malaria density. Also, the serum Calcium and Membrane Potential were significantly reduced in Sickle cell disease (HbSS) when compared to the HbAA and HbAS individuals. This signifies a low energy level in Sickle cell patients that can result in oxidative stress. This may probably indicate that serum Calcium and Membrane Potential are significantly reduced in Sickle cell patients compared with other Haemoglobin genotypes with Malaria.

Structure activity relationship of pyrazinoic acid analogs as potential antimycobacterial agents

Tuberculosis (TB) remains a leading cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a critical component of the first-line TB treatment regimen because of its sterilizing activity against non-replicating Mycobacterium tuberculosis (Mtb), but its mechanism of action has remained enigmatic. PZA is a prodrug converted by pyrazinamidase encoded by pncA within Mtb to the active moiety, pyrazinoic acid (POA) and PZA resistance is caused by loss-of-function mutations to pyrazinamidase. We have recently shown that POA induces targeted protein degradation of the enzyme PanD, a crucial component of the coenzyme A biosynthetic pathway essential in Mtb. Based on the newly identified mechanism of action of POA, along with the crystal structure of PanD bound to POA, we designed several POA analogs using structure for interpretation to improve potency and overcome PZA resistance. We prepared and tested ring and carboxylic acid bioisosteres as well as 3, 5, 6 substitutions on the ring to study the structure activity relationships of the POA scaffold. All the analogs were evaluated for their whole cell antimycobacterial activity, and a few representative molecules were evaluated for their binding affinity, towards PanD, through isothermal titration calorimetry. We report that analogs with ring and carboxylic acid bioisosteres did not significantly enhance the antimicrobial activity, whereas the alkylamino-group substitutions at the 3 and 5 position of POA were found to be up to 5 to 10–fold more potent than POA. Further development and mechanistic analysis of these analogs may lead to a next generation POA analog for treating TB.

Shorter versus longer durations of antibiotic treatment for patients with community-acquired pneumonia: a protocol for a systematic review and meta-analysis

IntroductionCommunity-acquired pneumonia (CAP), frequently encountered in both outpatient and inpatient settings, is the leading cause of infectious disease-related mortality. While equipoise regarding the optimal duration of antimicrobial therapy to treat...

Inhibiting glycolysis by targeting the enzyme PFKFB3 restricts macrophage anti-mycobacterial activity and neutrophil phagocytosis of Mycobacterium tuberculosis.

Abstract Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB), a leading cause of infectious disease-related mortality around the world. Myeloid cells are important in TB as Mtb host cells and anti-Mtb effector cells but the factors that differentiate these roles are not clearly defined. Immunometabolism is a driver of immune function and may be an important determinant of this interaction and represents a potential target for host-directed therapies against TB. To better understand how immunometabolism relates to TB, we incubated macrophages and neutrophils from Mtb-infected macaques with a panel of metabolic inhibitors and measured how this affected cellular responses to Mtb infection. Specifically, we targeted glycolysis, oxidative phosphorylation, and fatty acid oxidation and measured how this affected macrophage and neutrophil phagocytosis, macrophage control over Mtb viability and replication, and neutrophil production of extracellular traps. We found that targeting glycolysis by inhibiting PFKFB3, a rate-limiting enzyme in glycolysis, reduced macrophage anti-Mtb activity and neutrophil phagocytosis, while inhibition with the glucose analog 2-DG did not. In contrast, incubating cell-free mycobacteria with PFKFB3 inhibitors severely inhibited their growth, suggesting that these bacteria use different metabolic pathways in cells and culture to survive. Inhibiting oxidative phosphorylation with metformin or fatty acid oxidation with etomoxir did not change how macrophages or neutrophils responded to Mtb or affect mycobacterial growth in culture. These results indicate a role for immunometabolism in myeloid responses to Mtb and may inform efforts for development of metabolism-targeted therapies for TB. Supported by grants from NIH (R01AI134183)

Malaria and Associated Risk Factors in Awka, Awka South Local Government Area, Anambra State, Nigeria

Malaria is still a major contributor to high rate of the global infectious disease–related mortality and morbidity due to its marked effects and alteration on the haematological parameters of infected individuals. This study was conducted to determine the following: prevalence and intensity of malaria, the associated risk factors of in Awka metropolis from January to June 2021. A total of 1060 subjects were enrolled int the study. Prevalence of malaria parasites was determined using thick and thin films. A total 925 individuals were infected with malaria parasite giving a prevalence of 87.3%. Of the 925 individuals infected, 743(80.3%) had mild infection, 150 (16.2%) moderate infection. The study showed that more males (94.2%) were infected with the malaria parasite than females (80.6%). The highest prevalence of malaria (94.3%) occurred among those less than ten years old while the least prevalence (72.2%) was recorded among those more than sixty years old. The prevalence of malaria in relation to age was statistically significant (p<0.05). In relation to occupation, farmers recorded the highest prevalence of malaria (94.7%) while civil servants had the least prevalence (65.4%). Based on literacy level, the highest prevalence of malaria was recorded among those with primary education (96.8%) while those with tertiary education had the least prevalence (84.3%). On marital status, married ones had the highest prevalence of malaria (91.9%) while the singles had the least prevalence (80.1%). The high prevalence of malaria in Awka calls for intensive education and free supply of insecticide treated nets.

Defective expansion and function of memory like natural killer cells in HIV+ individuals with latent tuberculosis infection.

PurposeTuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development. NK cells have an important role in T cell independent immunity against TB, but the exact role of NK cell subsets in LTBI and HIV is not well characterized.MethodsIn this study, we compared the expansion and function of memory like NK cells from HIV-LTBI+ individuals and treatment naïve HIV+LTBI+ patients in response to Mtb antigens ESAT-6 and CFP-10.ResultsIn freshly isolated PBMCs, percentages of CD3-CD56+ NK cells were similar in HIV+LTBI+ patients and healthy HIV-LTBI+ individuals. However, percentages of CD3-CD56+CD16+ NK cells were higher in healthy HIV-LTBI+ individuals compared to HIV+LTBI+ patients. HIV infection also inhibited the expansion of memory like NK cells, production of IL-32α, IL-15 and IFN-γ in response to Mtb antigens in LTBI+ individuals.ConclusionWe studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-γ and granzyme B and increased CCL5 production. Our study highlights the effect of HIV and LTBI on modulation of NK cell activity to understand their role in development of interventions to prevent progression to TB in high risk individuals.

HIV/AIDS, hepatitis and tuberculosis-related mortality among incarcerated people: a global scoping review

PurposePeople in prison are at a higher risk of preventable mortality from infectious disease such as human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis B (HBV), hepatitis C (HCV) and tuberculosis (TB) than those in the community. The extent of infectious disease-related mortality within the prison setting remains unclear. The purpose of this paper was to collate available information on infectious disease-related mortality, including the number of deaths and calculate the person-time death rate.Design/methodology/approachThe authors searched databases between 1 January 2000 and 18 November 2020 for studies reporting HIV, HBV, HCV, TB and/or HIV/TB-related deaths among people in prison.FindingsThe authors identified 78 publications drawn from seven Joint United Nations Programme on HIV/AIDS’ regions encompassing 33 countries and reporting on 6,568 deaths in prison over a 20-year period. HIV/AIDS (n = 3,305) was associated with the highest number of deaths, followed by TB (n = 2,892), HCV (n = 189), HIV/TB (n = 173) and HBV (n = 9). Due to the limitations of the available published data, it was not possible to meta-analyse or in any other way synthesise the available evidence.Research limitations/implicationsTo inform targeted efforts to reduce mortality, there is a need for more, better quality data to understand infectious disease-related mortality in custodial settings. Increased investment in the prevention and management of infectious diseases in custodial settings, and in documenting infectious disease-related deaths in prison, is warranted and will yield public health benefits.Originality/valueTo the authors’ best knowledge, this is the first scoping review focussed on deaths due to these infections among people in prison internationally. The gaps identified form recommendations to improve the future collection and reporting of prison mortality data.

Diagnosing sputum smear negative pulmonary tuberculosis patients by transbronchial biopsy and bronchoalveolar lavage smear.

Pulmonary tuberculosis is one of the leading causes of infectious disease related mortality. Transbonchial biopsy and bronchoalveolar lavage smear obtained by bronchoscopy provides greater quantity of material for analysis, thus increases the chances of diagnosing the disease. Objectives: To diagnose sputum smear negative pulmonary tuberculosis patients by Transbronchial Biopsy and Bronchoalveolar smear keeping bronchoalvelar lavage culture as gold standard. To calculate and compare the diagnostic accuracy of transbronchial biopsy and bronchoalveolar lavage smear in sputum negative patients. Study Design: Cross-sectional validation study. Setting: Department of histopathology, Foundation University Medical College, Islamabad and Department of Pulmonology and Microbiology, Fauji Foundation Hospital, Rawalpindi. Period: From May 2016 to May 2017. Materials & Methods: It comprised 96 patients who underwent bronchoscopy. Transbronchial biopsy, bronchoalveolar lavage smear preparation and bronchoalveolar lavage culture was performed on specimens of all patients. Results: Out of 96 patients 22 (22.91%) patients were actually having tuberculosis whereas 74 (77%) had only clinical and radiological suspicion of tuberculosis. The mean age of patients was 43 years with a standard deviation of ±19.1 .The age range was 12-80 years. The sensitivity, specificity, positive predictive value, negative predictive value and true positives of transbronchial biopsy were 68.1%, 77%, 46.8%, 89% and15.62% while the values for bronchoalveolar lavage were 50%, 97.29%, 84.6%, 86.7% and 11.45% respectively. Thus, the diagnostic accuracy calculated for transbronchial biopsy and bronchoalveolar lavage was 75% and 13.54% respectively. Conclusions: Bronchoscopy should be done in all sputum negative tuberculosis patients having strong clinical and radiological suspicion to obtain transbronchial biopsy and bronchoalveolar lavage for timely diagnosis, treatment and prevention of disease transmission as well as to avoid empirical treatment and its side effects in patients having no tuberculosis. The diagnostic accuracy of transbronchial biopsy is almost 5 times more compared to bronchoalveolar lavage smear.

GC-MS analysis of raw and roasted seeds of Chrysophyllum albidum, a medicinal plant used for the treatment of tuberculosis

Tuberculosis is a multi-systematic disease with myriad presentations and manifestations and is the most common cause of infectious disease-related mortality worldwide. The disease is treated with the roasted cotyledonous part of Chrysophyllum albidum seeds by traditional practitioners in Ogun state, Nigeria. The phytoconstituents of the hexane fraction and the hexane extracts of the roasted seeds at 50o C, 100o C and 120o C were investigated using GC-MS analysis. The results showed the hexane fraction of the raw seeds contained 92.71 % by proportion of esters of long chain fatty acids. The hexane extract of roasted seeds (50o C) contained 68.69 % of long chain fatty acids, hexane extract of roasted seeds (100o C) contained74.54 % while the hexane extract of roasted seeds (120oC) contained 91.65 %.The traditional method of application of roasted seeds instead of raw seeds in treating tuberculosis enhances the availability of free fatty acids. The main fatty acids content at 120o C are Hexadecanoic acid and 9, 12-Octadecadienoic acid. Fatty acids had been reported to be toxic to Mycobacterium tuberculosis. Thus the efficacy of the treating of tuberculosis with the roasted seeds of Chrysophyllum albidum is due to the presence of hexadecanoic acid and 9,12-Octadecadienoic acid which could work together or work synergistically with other antimicrobial effectors to bring about macrophage-mediated killing of the pathogen.

A Case of Neurological Manifestations Accompanying Generalized Tuberculosis

Tuberculosis (TB), a multisystemic disease with variety presentations and manifestations, is the most common cause of infectious disease–related mortality worldwide [1]. A 23-year-old, male, is admitted to the Infectious diseases clinic “Mother Theresa” hospital in Tirana, after one year intermittent FUO and exudative pleural effusion treated first in Albania and then Italy. He had fever, back pain, muscular weakness, difficulty walking, urinary retention. In chest x ray radiological examination, CT scan of thorax and MRI of spinal cord are seen military form lesions, and vertebral destructions that raise suspicion of a possible pulmonary and extra pulmonary TB. The patient’s condition is randomly assigned to the beginning of antitubercular therapy (ATT), manifesting disturbance of conscience and coma. LCS results with 50 cells / mm3 and the CT scan of head detects hydrocephalus; funduscopia detected papilledema on 1st stage; which mean that the case is complicated with TB meningitis. The patient passes to the intensive care unit where ATT tapered cortisone, CNS diuretics and supportive therapy. After a week the patient comes out of the coma, begins his clinical improvement, but the neurological consequences of hydrocephaly and paraplegia become clearer. Two months later the patient was better clinically, walking with support .Peripheral neurological deficits persisted up to 10 months after leaving the hospital but with progressive improvement. The best ways to reduce mortality and morbidity associated with TBM are the timely diagnosis.

A first-in-human, randomized, double-blind, placebo-controlled, single and multiple ascending oral dose study to assess the safety, tolerability, and pharmacokinetics of BZF961 with and without ritonavir in healthy adult volunteers

Objective: Infection with hepatitis C virus is the leading indication for liver transplantation and most common cause of infectious disease-related mortality in the United States. BZF961 is a novel inhibitor of the hepatitis C virus NS3-4A protease.Methods: This sequential, three part exploratory first-in-human study investigated the safety and pharmacokinetics of single and multiple ascending oral doses of BZF961 in healthy subjects. The first two parts were randomized, double-blind, placebo-controlled, time-lagged, single and multiple ascending oral dose segments. The third part analyzed the effect of ritonavir on BZF961 pharmacokinetics.Results: BZF961 was generally safe and well-tolerated in single and multiple oral doses in healthy subjects. There were no deaths and no serious adverse events. The most common adverse events were nausea and other gastrointestinal symptoms. Co-administration of ritonavir with BZF961 was well tolerated and increased BZF961 exposure by up to 60-fold, as well as reduced the overall exposure variability.Conclusions: BZF961 was generally safe and well-tolerated and its exposure was boosted by the co-administration of ritonavir.

A Unique Case of Stroke and Upper Limb Paralysis in a Mid-18th Century Natural Mummy.

Despite its globally acknowledged importance in the clinical setting, the history of stroke has to date only been reconstructed through historical descriptions, whereas no clear palaeopathological evidence has ever been adduced. Here, a unique case of a naturally mummified body from the mid-18th century is shown to have a high degree of contracture of the upper left hand, whereas coeval documentary sources clearly indicate that the patient experienced a stroke in the last phase of his life that left him disabled. This example highlights how a combination of historical research and traditional palaeopathology can help in the reassessment of the presence of cerebrovascular diseases in the past. Stroke represents the second leading cause of death above age 60 globally and a leading cause of disability.1 By understanding its history and evolution, future preventive and therapeutic strategies may be improved. Cardiovascular diseases are complex entities caused by the interplay between genetics and environmental modulation, greatly increased in prevalence and incidence in Western societies on account of the drop in infectious disease–related mortality, longer life spans, and hypercaloric lifestyles.2 Historically, stroke was first described by Hippocrates (460–370 BC) who coined the term apoplexy and related an ischemic insult to a paralytic outcome, but a clear physiopathological understanding had to wait until the 17th-century discoveries of Johann Jacob Webpfer (1620–1695). In particular, the Swiss physician described the origins and terminations of the carotid and vertebral arteries at the arterial circle at the brain base. He also documented their occlusion and calcification and the fact that stroke could be provoked by a hemorrhage within the brain. This latter discovery proved to be a physiopathological turning point.3,4 Later in that century, the 1664 masterpiece Cerebri Anatome of Thomas Willis (1621–1675) further clarified cerebral vascular irroration, but it would be another …

Tuberculosis in a Portuguese Cohort

Background: Tuberculosis (TB) is a multisystemic disease and a leading cause of infectious disease-related mortality worldwide. Objectives: This study aims to characterize patients with TB in a portuguese cohort. Methods: Retrospective analysis of files pertaining inpatients with TB admitted between 1/2005 - 12/2014. Data were analysed using χ2 or Fisher exact test (p<0.005 = statistically significant) and odds ratio was calculated. Results: 222 cases were found: 128 patients had pulmonary involvement (PTB) and 100 extrapulmonary disease (ETB) (6 had overlapping disease), with men being mostly affected. The most common locations of ETB were lymphatic (27.0%), meningeal and osteoarticular (both 19.0%). The majority exhibited risk factors (64.0%, p<0.005). PTB was associated with smoking (p=0.000, OR=5.05) and contact with TB-infected person (p=0.002, OR=7.53). Human immunodeficiency virus (HIV) infection (p=0.000, OR=5.16) and age > 65 (p=0.005, OR=3.34) were associated with ETB. 48 patients were HIV-infected, with median CD4 count of 74.5 cells/μL (13-136), most cases occurring in the setting of new HIV diagnosis. HIV infection was statistically associated with disseminated (OR=12.64), pleural (OR=8.50), meningeal (OR=2.96) and lymphatic TB (OR=2.38). HIV negativity was associated with pulmonary (OR=4.08) and osteoarticular disease (OR=5.42). PTB was confirmed mainly by culture or PCR test plus smear (81.3%). ETB diagnosis was more complex. Clinical outcome was favourable (PTB 98.4%; ETB 94.0%). Eight patients died. Conclusions: TB remains an important healthcare issue in Portugal. Contact with TB-infected person and smoking (PTB) and HIV infection and age > 65 (ETB), were significant risk factors. HIV infection was associated with disseminated, pleural, meningeal and lymphatic disease.

Epidemiology of Infectious Disease-Related Death After Release from Prison, Washington State, United States, and Queensland, Australia: A Cohort Study.

People in prison may be at high risk for infectious diseases and have an elevated risk of death immediately after release compared with later; their risk of death is elevated for at least a decade after release. We compared rates, characteristics, and prison-related risk factors for infectious disease-related mortality among people released from prisons in Queensland, Australia, and Washington State, United States, regions with analogous available data. We analyzed data from retrospective cohort studies of people released from prison in Queensland (1997-2007, n=37,180) and Washington State (1999-2009, n=76,208) and linked identifiers from each cohort to its respective national death index. We estimated infectious disease-related mortality rates (deaths per person-years in community) and examined associations using Cox proportional hazard models. The most frequent infectious disease-related underlying cause of death after release from prison was pneumonia (43%, 23/54 deaths) in the Australian cohort and viral hepatitis (40%, 69/171 deaths) in the U.S. cohort. The infectious disease-related mortality rate was significantly higher in the U.S. cohort than in the Australian cohort (51.2 vs. 26.5 deaths per 100,000 person-years; incidence rate ratio = 1.93, 95% confidence interval 1.42, 2.62). In both cohorts, increasing age was strongly associated with mortality from infectious diseases. Differences in the epidemiology of infectious disease-related mortality among people released from prison may reflect differences in patterns of community health service delivery in each region. These findings highlight the importance of preventing and treating hepatitis C and other infectious diseases during the transition from prison to the community.

Novel targeting of the lepB gene using PCR with confronting two-pair primers for simultaneous detection of Mycobacterium tuberculosis complex and Mycobacterium bovis.

Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex (MTC), is the leading cause of infectious disease-related mortality worldwide. The standard method for TB diagnosis usually requires long periods of mycobacteria cultivation, leading to delayed diagnosis, inefficient treatment and widespread occurrence of the disease. Therefore, a rapid method for the detection and differentiation of MTC from other mycobacteria is essential for disease diagnosis. Here, we describe the potential of using the type I signal peptidase (lepB) gene as a novel target for TB diagnosis, based on confronting two-pair primers PCR (PCRCTPP) that can detect MTC and simultaneously differentiate M. bovis. The limit of detection of the developed technique was equivalent to 12–120 bacilli. PCR-CTPP was highly specific to only MTC and M. bovis, and no cross-reaction was detected in 27 DNA of the non-tuberculous mycobacterial and bacterial strains tested. Thirty-nine blinded clinical isolates and 72 sputum samples were used to validate the PCR-CTPP in comparison with the standard mycobacterial culture method. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PCR-CTPP were equal to 95, 100, 100 and 95 %, respectively, when tested with clinical isolates. Furthermore, upon testing with the sputum samples, the sensitivity, specificity, PPV and NPV were observed to be 84, 76, 90 and 67 %, respectively. Hence, this highly sensitive novel technique, which is rapid, easy to conduct and cost-effective, is a potential method for TB diagnosis and epidemiological studies, especially in resource-limited countries with a high TB burden.

Anti-Tubercular Treatment of Tuberculous Meningitis Cause Paradoxical Multiple Neurotuberculoma

Tuberculosis is the most common cause of infectious disease related mortality worldwide. Paradoxical reactions to antituberculous treatment have created difficulties in the management of extrapulmonary tuberculosis, particularly central nervous system tuberculosis. We report a three years baby with tuberculous meningitis, who was treated outside with anti-tuberculous drugs without steroid one month back and presented in our emergency as status epilepticus. This case emphasizes the importance of addition of steroid along with anti-tubercular drugs in the treatment of central nervous system tuberculosis. J Nepal Paediatr Soc 2014;34(3):236-238 DOI: http://dx.doi.org/10.3126/jnps.v34i3.10752

2D DIGE proteomic analysis of multidrug resistant and susceptible clinical Mycobacterium tuberculosis isolates

Tuberculosis (TB) is the leading cause of infectious disease related mortality worldwide. Infection of Mycobacterium tuberculosis (Mtb) leads to nearly 3 million deaths every year due to tuberculosis. Rifampicin and Isoniazid (RH) are the key drugs to being used for the treatment of tuberculosis. Reports in recent years indicate that the increasing emergence of resistance to these drugs. The resistance to these drugs severely affects options for effective treatment. The current vaccine for tuberculosis has variable protective efficacy and there is no commercially available serodiagnostic test for this disease with acceptable sensitivity and specificity for routine laboratory use, especially in case of multidrug resistance. In order to develop a new diagnostic tool for detection of Mtb, multidrug resistant Mtb as well and improve the tuberculosis vaccine, it is necessary to indentify novel antigenic candidates, especially in identification of multidrug resistant associated protein antigens. Here, we present a 2-D gel-based proteomic survey of the changes in RH resistant Mtb. The proteins extracted from RH resistant and susceptible Mtb clinical isolates were analyzed by two-dimensional differential in gel electrophoresis (2D-DIGE). Protein intensities of 41 spots were found to be regulated in RH resistant isolates. A total of 28 proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Twelve proteins of interest are NADH-dependent enoyl-[acyl-carrier-protein] reductase, 60 kDa chaperonin 2, Chaperone protein DnaK, 3-oxoacyl-(Acyl-carrier-protein0 reductase, Probable acetyl-CoA acyltransferase FadA2, two Acetyl/propionyl-CoA carboxylase, alpha subunit, Universal stress protein Rv1636/MT1672, Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, Glutamine synthetase 1 and two uncharacterized proteins (Rv2557 and Rv1505c).