Unusual case of non-resolving necrotizing pneumonia: a last resort measure for cure.

Abstract To our knowledge, this is an unusual case of a community-acquired pneumonia (CAP) with sepsis secondary to Streptococcus pneumoniae that required lung resection for a non-resolving consolidation. A 74 year old previously healthy woman, presented with acute fever, chills and pleuritic chest pain in Emergency Department (ED). A diagnosis of CAP was established with a Pneumonia Severity Index CURB-65 score of 5/5. In the ER, she was promptly and appropriately managed with antibiotics and aggressive supportive therapy. She remained on ten days of intravenous antibiotics. However, 48 hours post antibiotic course, she returned to ER with fever and signs of sepsis. Despite timely and appropriate management, the consolidated lobe remained the focus of sepsis for over four weeks. The patient recovered after the offending lobe was resected. Histopathology of the lung tissue revealed acute and chronic inflammation. However, no malignancy, bacterial infection or broncho-pleural fistula was found. Eighteen months post-surgery, the patient remains well

Rabies post-exposure prophylaxis: A systematic review on abridged vaccination schedules and the effect of changing administration routes during a single course

International audienceRabies is a fatal zoonotic disease preventable through timely and adequate post-exposure prophylaxis (PEP) to potentially exposed persons i.e. wound washing and antisepsis, a series of intradermal (ID) or intramuscular (IM) rabies vaccinations, and rabies immunoglobulin in WHO category III exposures. The 2010 WHO position on rabies vaccines recommended PEP schedules requiring up to 5 clinic visits over the course of approximately one month. Abridged schedules with less doses have potential to save costs, increase patient compliance, and thereby improve equitable access to life-saving PEP for at-risk populations. We systematically reviewed new evidence since that considered for the 2010 position paper to evaluate (i) the immunogenicity and effectiveness of PEP schedules of reduced dose and duration; (ii) new evidence on effective PEP protocols for special populations; and (iii) the effect of changing routes of administration (ID or IM) during a single course of PEP. Our search identified a total of 14 relevant studies. The identified studies supported a reduction in dose or duration of rabies PEP schedules. The 1-week, 2-site ID PEP schedule was found to be most advantageous, as it was safe, immunogenic, supported by clinical outcome data and involved the least direct costs (i.e. cost of vaccine) compared to other schedules. To supplement this evidence, as yet unpublished additional data were reviewed to support the strength of the recommendations.Evidence suggests that changes in the rabies vaccine product and/or the route of administration during PEP is possible. Few studies have evaluated PEP schedules in persons with suspect or confirmed rabies exposures. Gaps exist in understanding the safety and immunogenicity of novel PEP schedules in special populations such as infants and immunocompromised individuals. Available data indicate that administering rabies vaccines during pregnancy is safe and effective

Raised levels of IFN-gamma and IL-13 are associated with pre-diabetes amongst newly diagnosed patients with tuberculosis

Objective: To investigate pre-diabetes and diabetes in newly-diagnosed tuberculosis patients and to assess the association of serum cytokine levels with diabetes status. Methods: The cross-sectional study was conducted at Indus Hospital and The Aga Khan University Hospital, Karachi from May to November 2015, and included patients of either gender aged 18 years or more with a confirmed diagnosis of tuberculosis who were either newly diagnosed or had received up to 1 month of anti-tuberculosis therapy were included. Patients were enrolled from among those presenting to the clinics at Indus Hospital, Karachi, and the Department of Medicine, Aga Khan University Hospital (AKUH), Karachi. The patients were tested for glycosylated haemoglobin and random blood glucose. Diabetes was defined as HbA1c \u3e6.5%; pre-diabetes as HbA1c=5.7-6.4%; and normoglycaemic as HbA1c \u3c5.7%. Serum cytokines were investigated using the Bio-plex 27, Bio-Rad assay. SPSS version 19.0 was used for data analysis. Results: Of the 211 subjects, 110(52%) were females and 101(48%) were males. The overall median age of the sample was 26 years, and 100(47.3%) subjects were underweight. Of the total, 24(11.4%) had diabetes and 45(21.3%) had pre-diabetes. Of the diabetics, only 7(29%) knew their status prior to screening. Interferon-gamma and interleukin-13 were significantly different among tuberculosis patients with diabetes, pre-diabetes and normoglycaemia (p\u3c0.05). Glycosylated haemoglobin levels showed a significant correlation with interferon-gamma levels. Conclusions: Raised interleukin-13 and interferon-gamma levels in newly-diagnosed tuberculosis patients with pre-diabetes

Geographic variation in access to dog-bite care in Pakistan and risk of dog-bite exposure in Karachi: prospective surveillance using a low-cost mobile phone system

Background: Dog-bites and rabies are under-reported in developing countries such as Pakistan and there is a poor understanding of the disease burden. We prospectively collected data utilizing mobile phones for dog-bite and rabies surveillance across nine emergency rooms (ER) in Pakistan, recording patient health-seeking behaviors, access to care and analyzed spatial distribution of cases from Karachi. Methodology and Principal: Findings A total of 6212 dog-bite cases were identified over two years starting in February 2009 with largest number reported from Karachi (59.7%), followed by Peshawar (13.1%) and Hyderabad (11.4%). Severity of dog-bites was assessed using the WHO classification. Forty percent of patients had Category I (least severe) bites, 28.1% had Category II bites and 31.9% had Category III (most severe bites). Patients visiting a large public hospital ER in Karachi were least likely to seek immediate healthcare at non-medical facilities (Odds Ratio = 0.20, 95% CI 0.17–0.23, p-value<0.01), and had shorter mean travel time to emergency rooms, adjusted for age and gender (32.78 min, 95% CI 31.82–33.78, p-value<0.01) than patients visiting hospitals in smaller cities. Spatial analysis of dog-bites in Karachi suggested clustering of cases (Moran's I = 0.02, p value<0.01), and increased risk of exposure in particular around Korangi and Malir that are adjacent to the city's largest abattoir in Landhi. The direct cost of operating the mHealth surveillance system was USD 7.15 per dog-bite case reported, or approximately USD 44,408 over two years. Conclusions: Our findings suggest significant differences in access to care and health-seeking behaviors in Pakistan following dog-bites. The distribution of cases in Karachi was suggestive of clustering of cases that could guide targeted disease-control efforts in the city. Mobile phone technologies for health (mHealth) allowed for the operation of a national-level disease reporting and surveillance system at a low cost.publishedVersio

One health for neglected tropical diseases

The forthcoming World Health Organization road map for neglected tropical diseases (NTDs) 2021–2030 recognises the complexity surrounding control and elimination of these 20 diseases of poverty. It emphasises the need for a paradigm shift from disease-specific interventions to holistic cross-cutting approaches coordinating with adjacent disciplines. The One Health approach exemplifies this shift, extending beyond a conventional model of zoonotic disease control to consider the interactions of human and animal health systems within their shared environment and the wider social and economic context. This approach can also promote sustainability and resilience within these systems. To achieve the global ambition on NTD elimination and control, political will, along with contextualised innovative scientific strategies, is required.http://trstmh.oxfordjournals.orghj2021Veterinary Tropical Disease

Developing local guidelines for management of sepsis in adults: sepsis guidelines for Pakistan (SGP)

Background: The purpose of developing ‘Sepsis Guidelines for Pakistan’ (SGP) is to provide clinicians practicing in local hospitals with a framework to aid timely recognition and management of adult patients in sepsis by adopting evidence-based recommendations of Surviving Sepsis Campaign (SSC) tailored to available resources. These recommendations are not meant to replace the SSC Guidelines. Methodology: SGP is an initiative of Pakistan Society of Critical Care Medicine (PSCCM). Four key decision points to be addressed in the guidelines were identified by a thirteen member multidisciplinary committee i.e., grading the hospitals in the country, recognition of sepsis and associated organ dysfunction, essential interventions to manage sepsis, and general measures for provision of a comprehensive care to patients in sepsis according to the level of education and training of healthcare providers and facilities and resources available in different levels of hospitals. The draft was presented at the 3rd Sepsis Symposium held on 13th September, 2014 in Karachi. The final document was approved by a panel of experts from across the country, representatives of relevant societies and Global Sepsis Alliance (GSA). Recommendations: Hospitals are divided into basic, intermediate and tertiary depending on the availability of diagnostic facilities and training of the medical personnel. Modified definitions of sepsis, severe sepsis, and septic shock are used given the lack of facilities to diagnose sepsis according to international definitionsand criteria in Pakistan. Essential interventions include fluid resuscitation, vasopressors to support the circulation, maintaining oxygen saturation ≥ 90% with oxygen, non-invasive ventilation or mechanical ventilation with lung protective strategies, prompt administration of antibiotics as recommended by the Medical Microbiology & Infectious Diseases Society of Pakistan (MMIDSP) and early source control. It is recommended to avoid starvation, keep an upper blood glucose ≤180 mg/dL, use daily pharmacoprophylaxis against venous thromboembolism (VTE), use stress ulcer prophylaxis, target haemoglobin of 7-9 g/dl in the absence of ischaemic heart disease, avoid sodium bicarbonate therapy as long as pH \u3e 7.20, avoid fresh frozen plasma in the absence of bleeding, transfuse platelets if indicated, not use intravenous immunoglobulins and avoid neuromuscular blocking agents (NMBAs) in the absence of ARDS, target specific titration endpoints when continuous or intermittent sedation is required in mechanically ventilated patients and use continuous renal replacement therapy (CRRT) to facilitate management of fluid balance in hemodynamically unstable septic patients in tertiary care centers. In addition a comprehensive, meticulous and multidisciplinary general care is required to improve outcome of sepsis by reinforcing hand hygiene and other infection control measures, adequate monitoring and documentation tailored to the available resources. Goals of care and prognosis should be discussed with patients and families early and either shifting the patient to a hospital with better facilities or limiting or withdrawing therapy in case of poor prognosis should be considered

Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus

BACKGROUND: Autonomic nervous system (ANS) dysfunction is present in up to one third of patients with tetanus. The prognostic value of ANS dysfunction is known in severe tetanus but its value is not well established in mild to moderate tetanus. METHODS: Medical records of all patients admitted with tetanus at two academic tertiary care centers in Karachi, Pakistan were reviewed. The demographic, clinical and laboratory data was recorded and analyzed. ANS dysfunction was defined as presence of labile or persistent hypertension or hypotension and sinus tachycardia, tachyarrythmia or bradycardia on EKG. Patients were divided into two groups based on presence of ANS dysfunction (ANS group and non ANS group). Tetanus severity was classified on the basis of Ablett criteria. RESULTS: Ninety six (64 males; 32 females) patients were admitted with the diagnosis over a period of 10 years. ANS group had 31 (32%) patients while non ANS group comprised of 65 (68%) patients. Both groups matched for age, gender, symptom severity, use of tetanus immunoglobulin and antibiotics. Twelve patients in ANS group had mild to moderate tetanus (Ablett I and II) and 19 patients had severe/very severe tetanus (Ablett III and IV). Fifteen (50%) patients in ANS group required ventilation as compared to 28 (45%) in non-ANS group (p = 0.09). Fourteen (47%) patients died in ANS group as compared to 10 (15%) in non ANS group (p= 0.002). Out of those 14 patients died in ANS group, six patients had mild to moderate tetanus and eight patients had severe/ very severe tetanus. Major cause of death was cardiac arrhythmias (13/14; 93%) in ANS group and respiratory arrest (7/10; 70%) in non ANS group. Ten (33%) patients had complete recovery in ANS group while in non ANS group 35(48%) patients had complete recovery (p= 0.05). CONCLUSIONS: ANS dysfunction was present in one third of our tetanus population. 40% patients with ANS dysfunction had only mild to moderate tetanus. ANS dysfunction, irrespective of the need of mechanical ventilation or severity of tetanus, predicted poor outcome

Expression of M. tuberculosis-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis

Background Appropriate immune activation of T cells and macrophages is central for the control of Mycobacterium tuberculosis infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules – 1 and 3 and CD4+CD25+FoxP3+T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB. M. tuberculosis -stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann–Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests. Results In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC. M. tuberculosis-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression in M. tuberculosis stimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017). Conclusions The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB