BackgroundVitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery.MethodsTwo hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student’s t-test and Chi2 tests.ResultsAfter 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg) + 3.75, (3.16 – 4.34) versus + 2.61 (95% CI 1.99 – 3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘Deficient’ 25-hydroxyvitamin D serum levels (p 0.021).ConclusionsSupplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline ‘Deficient’ serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB.Trial registrationClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov

Background: In April 2019, an HIV screening camp for all ages was established in response to a report of an unusually large number of paediatric HIV diagnoses in Larkana, Pakistan. A cross-sectional study to understand the clinical profile of children who registered for HIV care was performed. Methods: Age-and sex-stratified HIV prevalence among individuals screened was estimated. Data on children who registered for HIV care including clinical history, HIV disease stage, Hepatitis B and C status and CD4 count was abstracted from clinical records and analysed using percentages and chi square tests. Findings: Between April-July 2019, 31,239 individuals underwent HIV testing of whom 930 tested HIV-positive. Of these, 763 (82•0%) were aged <16 years. Estimated HIV prevalence was 3.0% overall; 7.4% (283/3803) in children aged 0-2 years, 5.9% (321/5412) in children aged 3-5 years, and 1•3% (148/11251) in adults aged 16-49 years. Of the 591 children who registered for HIV care, 80.9% (478/591) were ≤5 years, 64•1% (379/591) were male and 53•4% (315/590) had a weight-forage Z-score <-3. Hepatitis B surface antigen and Hepatitis C antibody positivity was 8•4% (48/574) and 2•6% (15/574) respectively. Of children whose mothers tested for HIV, only 39/371 (10•5%) had HIV-positive mothers. Most children (89•2%, 404/453) reported multiple previous injections and 40/453 (8•8%) reported blood transfusions. Interpretation: This is an unprecedented HIV outbreak among children in Pakistan: a 54% increase in paediatric HIV diagnoses over the past 13 years. Epidemiological and molecular studies to understand the full extent of the outbreak and its drivers are needed to guide HIV control strategies.

BackgroundCrimean Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection that presents significant risk of nosocomial transmission to healthcare workers.AimEvaluation of CCHF infection prevention and control (IP&C) practices in healthcare facilities that routinely manage CCHF cases in Eurasia.MethodsA cross-sectional CCHF IP&C survey was designed and distributed to CCHF centers in 10 endemic Eurasian countries in 2016.ResultsTwenty-three responses were received from centers in Turkey, Pakistan, Russia, Georgia, Kosovo, Bulgaria, Oman, Iran, India and Kazakhstan. All units had dedicated isolation rooms for CCHF, with cohorting of confirmed cases in 15/23 centers and cohorting of suspect and confirmed cases in 9/23 centers. There was adequate personal protective equipment (PPE) in 22/23 facilities, with 21/23 facilities reporting routine use of PPE for CCHF patients. Adequate staffing levels to provide care reported in 14/23 locations. All centers reported having a high risk CCHFV nosocomial exposure in last five years, with 5 centers reporting more than 5 exposures. Education was provided annually in most centers (13/23), with additional training requested in PPE use (11/23), PPE donning/doffing (12/23), environmental disinfection (12/23) and waste management (14/23).ConclusionsStaff and patient safety must be improved and healthcare associated CCHF exposure and transmission eliminated. Improvements are recommended in isolation capacity in healthcare facilities, use of PPE and maintenance of adequate staffing levels. We recommend further audit of IP&C practice at individual units in endemic areas, as part of national quality assurance programs.

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IntroductionInvasive aspergillosis is a serious complication in immunocompromised patients. It is an opportunistic disease, which predominantly occurs in the lungs, although dissemination to virtually any organ is possible. Invasive aspergillosis in an immunocompetent patient with extension to the mediastinum has rarely been reported. Here, we present the case of a patient with no apparent immunodeficiency state, who presented with Aspergillus endocarditis and fulminant invasive aspergillosis with extensive involvement of the mediastinal structures, which ultimately was responsible for her death. To the best of our knowledge, this is the first reported case in the literature on fulminant invasive mediastinal aspergillosis with extension to the pulmonary vasculature and concomitant Aspergillus endocarditis in an apparently immunocompetent patient without pre-existing lung disease.Case presentationOur patient was a previously healthy 47-year-old Asian woman, who presented to our emergency room with severe progressive shortness of breath of one month’s duration, associated with orthopnea and unstable vital signs.ConclusionInvasive aspergillosis has been described in the presence of pulmonary disease, such as chronic obstructive pulmonary disorder, and one case has been reported in a patient without preexistent disease, but none of these have been fatal. Our case is therefore the first reported case of its kind. Our case shows that fulminant aspergillosis can occur in an immunocompetent host and can be fatal. We conclude that invasive aspergillosis should not be excluded from the differential diagnosis on the basis of immunocompetency.

Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Baluchistan province, Pakistan. Sporadic outbreaks of CCHF occur throughout the year especially in individuals in contact with infected livestock. Nosocomial transmission remains a risk due to difficulties in the diagnosis of CCHF and limited availability of facilities for the isolation of suspected patients. Rapid diagnosis of CCHF virus infection is required for early management of the disease and to prevent transmission. This study describes the case of a 43-year-old surgeon who contracted CCHF during a surgical procedure in Quetta, Baluchistan and who was transferred to a tertiary care facility at the Aga Khan University Hospital, Karachi within 1 week of contracting the infection. Diagnosis of CCHF was made using a rapid real-time reverse transcription polymerase chain reaction (RT-PCR) assay for CCHF viral RNA. The patient had chronic hepatitis B and hepatitis D infection for which he had previously received a liver transplant. He proceeded to develop classic hemorrhagic manifestations and succumbed to the infection 14 days post-onset of disease. There was no further nosocomial transmission of the CCHF during the hospital treatment of the surgeon. Early diagnosis of CCHF enables rapid engagement of appropriate isolation, barrier nursing and infection control measures thus preventing nosocomial transmission of the virus.

In Pakistan, HIV has converted from outbreak to concentrated epidemic and has also bridged into the low-risk population. The HIV epidemic in Pakistan mainly comprises subtype A. Here, we present the first case and genetic analysis of a circulating recombinant form 56_cpx in a Pakistani HIV-infected patient. Genetic analysis of the sequence indicated that Pakistani 56_cpx sequence had more drug resistance mutation than the other 56_cpx sequences available in the database.

The Muir-Torre syndrome of sebaceous neoplasms of the skin, with or without keratoacanthomas, and multiple low-grade visceral malignancies with prolonged survival is a rare disorder. Colonic polyps are frequently present, and the syndrome appears to be familial. We report 2 unrelated patients with the Muir-Torre syndrome. Each case exhibited sebaceous adenomas. Gastrointestinal findings included colonic adenocarcinomas and a tubulovillous adenoma. Although an unusual disease, the Muir-Torre syndrome requires recognition because these patients are at risk for multiple primary malignancies and may have family members also at risk.