Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients

Forty-seven bronchoalveolar lavage fluid samples from 16 human immunodeficiency virus (HIV)-infected patients were used to test the latency model of Pneumocystis infection in the human host. Identification of DNA sequence polymorphisms at 4 independent loci were used to genotype Pneumocystis jiroveci from the 35 samples that contained detectable P. jiroveci DNA. Eighteen of those 35 samples came from patients who did not have Pneumocystis pneumonia (PCP) and had confirmed alternative diagnoses. Seven patients had asymptomatic carriage of P. jiroveci over periods of less than or equal to9.5 months after an episode of PCP, and in all 7 cases, a change in genotype from that in the original episode of PCP was observed. The absence of P. jiroveci DNA in one-fourth of the 47 samples and the observed changes in genotype during asymptomatic carriage do not support the latency model of infection. Asymptomatic carriage in HIV-infected patients may play a role in transmission of P. jiroveci and may even supply a reservoir for future infections

Systematic review of the efficacy and safety of biological therapy for inflammatory conditions in HIV-infected individuals

Biologic therapies are injectable immunomodulatory agents directed against specific immune cell or chemical targets. They have transformed the lives of HIV-uninfected individuals with severe inflammatory conditions including psoriasis, rheumatoid arthritis, and ulcerative colitis. The perceived increased infection risk associated with these agents means that HIV-infected individuals have not been included in randomised control trials of these drugs. The literature for use of biologic therapies in HIV-infected populations is limited to case reports and case series. There are additional data on use of rituximab, a monoclonal antibody against B lymphocytes, in the setting of HIV-associated haematological malignancy. We performed a systematic review of efficacy and safety of biologic therapy for inflammatory conditions in HIV-infected individuals. Our systematic review identified 37 treatment episodes with six different biologic agents encompassing 10 different inflammatory conditions. Broadly, efficacy of the agents studied was comparable to reports from HIV-uninfected patients. Both infectious and non-infectious sequelae were also comparable with trial data from HIV-uninfected patients. HIV control, even for the minority of individuals not receiving anti-retroviral therapy (ART) at the time of biologic therapy, was not adversely affected. However, detail was limited concerning ART regimens and both immunological and virological parameters of follow-up. Overall available literature is of very low quality and likely subject to publication bias of successful cases. Firm conclusions are not possible regarding the efficacy and safety of biologic agents in HIV-infected individuals; however, there appear to be sufficient data to warrant inclusion of individuals with well-controlled HIV in future trial studies

Bronchiectasis and other chronic lung diseases in adolescents living with HIV.

: The incidence of pulmonary infections has declined dramatically with improved access to antiretroviral therapy (ART) and cotrimoxazole prophylaxis, but chronic lung disease (CLD) is an increasingly recognized but poorly understood complication in adolescents with perinatally acquired HIV. : There is a high prevalence of chronic respiratory symptoms, abnormal spirometry and chest radiographic abnormalities among HIV-infected adolescents in sub-Saharan Africa, wherein 90% of the world's HIV-infected children live. The incidence of lymphocytic interstitial pneumonitis, the most common cause of CLD in the pre-ART era, has declined with increased ART access. Small airways disease, particularly constrictive obliterative bronchiolitis and bronchiectasis, are emerging as leading causes of CLD among HIV-infected adolescents in low-income and middle-income countries. Asthma may be more common in high-income settings. Likely risk factors for CLD include recurrent pulmonary infections, air pollution, HIV-related immune dysfunction, and untreated HIV infection, particularly during critical stages of lung development. : Globally, the importance of HIV-associated CLD as a cause of morbidity and mortality is increasing, especially as survival has improved dramatically with ART and growing numbers of children living with HIV enter adolescence. Further research is urgently needed to elucidate the natural history and pathogenesis of CLD, and to determine optimal screening, diagnostic and treatment strategies.<br/

Approach to Fungal Infections in Human Immunodeficiency Virus-Infected Individuals Pneumocystis and Beyond

Many fungi cause pulmonary disease in HIV-infected patients. Major pathogens include Pneumocystis jirovecii, Cryptococcus neoformans, Aspergillus species, Histoplasma capsulatum, Coccidioides species, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Talaromyces marneffei, and Emmonsia species. Because symptoms are frequently non-specific, a high index of suspicion for fungal infection is required for diagnosis. Clinical manifestations of fungal infection in HIV-infected patients frequently depend on the degree of immunosuppression and the CD4 + TH cell count. Establishing definitive diagnosis is important because treatments differ. Primary and secondary prophylaxis depends on CD4+ TH cell counts as well as geographic location and local prevalence of disease

Burkitt non-Hodgkin lymphoma presenting with mental neuropathy ('numb chin' syndrome) in an HIV-positive patient

Mental nerve neuropathy is usually due to local trauma or dental causes, but may be a manifestation of malignancy. A patient with virologically controlled human immunodeficiency virus (HIV) infection presented with a 'numb chin' on the background of long-standing night sweats, malaise and weight loss, worsening respiratory symptoms, and lymphadenopathy. Burkitt non-Hodgkin lymphoma was diagnosed from histology of a lymph node. Imaging (magnetic resonance imaging and18fluorodeoxyglucose [FDG]-positron emission tomography-computed tomography [PET-CT]) showed abnormal intracranial enhancement of the right mandibular nerve and extensive18FDG-avid lymphadenopathy above and below the diaphragm, focal lesions in the spleen and within the right mandible. The patient received chemotherapy and remains in clinical and radiological remission seven years later. This case highlights the need for clinicians to maintain a high index of suspicion for underlying malignancy when an HIV-infected patient presents with new onset of a 'numb chin'. Additionally, it demonstrates the importance of functional18FDG-PET-CT and neuroimaging in order to identify site(s) of pathology

Resolving MISS conceptions and misconceptions: A geological approach to sedimentary surface textures generated by microbial and abiotic processes

The rock record contains a rich variety of sedimentary surface textures on siliciclastic sandstone, siltstone and mudstone bedding planes. In recent years, an increasing number of these textures have been attributed to surficial microbial mats at the time of deposition, resulting in their classification as microbially induced sedimentary structures, or MISS. Research into MISS has developed at a rapid rate, resulting in a number of misconceptions in the literature. Here, we attempt to rectify these MISS misunderstandings. The first part of this paper surveys the stratigraphic and environmental range of reported MISS, revealing that contrary to popular belief there are more reported MISS-bearing rock units of Phanerozoic than Precambrian age. Furthermore, MISS exhibit a pan-environmental and almost continuous record since the Archean. Claims for the stratigraphic restriction of MISS to intervals prior to the evolution of grazing organisms or after mass extinction events, as well as claims for the environmental restriction of MISS, appear to result from sampling bias. In the second part of the paper we suggest that raised awareness of MISS has come at the cost of a decreasing appreciation of abiotic processes that may create morphologically similar features. By introducing the umbrella term ‘sedimentary surface textures’, of which MISS are one subset, we suggest a practical methodology for classifying such structures in the geological record. We illustrate how elucidating the formative mechanisms of ancient sedimentary surface textures usually requires consideration of a suite of sedimentological evidence from surrounding strata. Resultant interpretations, microbial or non-microbial, should be couched within a reasonable degree of uncertainty. This approach recognizes that morphological similarity alone does not constitute scientific proof of a common origin, and reinstates a passive descriptive terminology for sedimentary surface textures that cannot be achieved with the current MISS lexicon. It is hoped that this new terminology will reduce the number of overly sensational and misleading claims of MISS occurrence, and permit the means to practically separate initial observation from interpretation. Furthermore, this methodology offers a scientific approach that appreciates the low likelihood of conclusively identifying microbial structures from visual appearance alone, informing the search for true MISS in Earth's geological record and potentially on other planetary bodies such as Mars.Instances of sedimentary surface textures in the field were identified coincidentally during multiple seasons of varied field investigations primarily funded for NSD by a variety of organisations including a George Frederic Matthew Research Grant from the New Brunswick Museum for 2012, and a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to MRG. AGL is supported by the Natural Environment Research Council [grant number NE/L011409/1].This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.earscirev.2016.01.00

HIV-Associated CD8 Encephalitis: A UK Case Series and Review of Histopathologically Confirmed Cases

HIV-associated CD8-encephalitis (HIV-CD8E) is a severe inflammatory disorder dominated by infiltration of the brain by CD8 T-lymphocytes. It occurs in people with HIV, typically when the virus is apparently well-controlled by antiretroviral treatment (ART). HIV-CD8E presents with symptoms and signs related to marked cerebral inflammation and swelling, and can lead to coma and death unless treated promptly with corticosteroids. Risk events such as intercurrent infection, antiretroviral therapy interruption, immune reconstitution inflammatory syndrome (IRIS) after starting ART, and concomitant associations such as cerebrospinal fluid (CSF) HIV viral escape have been identified, but the pathogenesis of the disorder is not known. We present the largest case series of HIV-CD8E to date (n = 23), representing histopathologically confirmed cases in the UK. We also summarize the global literature representing all previously published cases with histopathological confirmation (n = 30). A new variant of HIV-CD8E is described, occurring on a background of HIV encephalitis (HIVE).Together these series, totalling 53 patients, provide new insights. CSF HIV viral escape was a frequent finding in HIV-CD8E occurring in 68% of those with CSF available and tested; ART interruption and IRIS were important, both occurring in 27%. Black ethnicity appeared to be a key risk factor; all but two UK cases were African, as were the majority of the previously published cases in which ethnicity was stated. We discuss potential pathogenic mechanisms, but there is no unifying explanation over all the HIV-CD8E scenarios.

Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis

The coalescence of the HIV-1 and tuberculosis (TB) epidemics in Sub-Saharan Africa has had a significant and negative impact on global health. The availability of effective antimicrobial treatment for both HIV-1 (in the form of highly active antiretroviral therapy (HAART)) and TB (with antimycobacterial agents) has the potential to mitigate the associated morbidity and mortality. However, the use of both HAART and antimycobacterial therapy is associated with the development of inflammatory paradoxical syndromes after commencement of therapy. These include paradoxical reactions (PR) and immune reconstitution inflammatory syndromes (IRIS), conditions that complicate mycobacterial disease in HIV seronegative and seropositive individuals. Here, we discuss case definitions for PR and IRIS, and explore how advances in identifying the risk factors and immunopathogenesis ofthese conditions informs our understanding of their shared underlying pathogenesis. We propose that both PR and IRIS are characterized by the triggering of exaggerated inflammation in a setting of immunocompromise and antigen loading, via the reversal of immunosuppression by HAART and/or antimycobacterials. Further understanding of the molecular basis of this pathogenesis may pave the way for effective immunotherapies for the treatment of PR and IRIS

Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult.

A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood

Incidence and significance of elevated platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios among hospitalised HIV-positive adult patients

There is increasing interest in the peripheral blood platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation. We audited records of unselected hospitalised HIV-positive adults to identify the frequency of elevated PLR and NLR, potential associations with specific diagnoses, and outcome. Of 259 patients audited, their median age was 47 years (interquartile range = 41–54); 188 (73%) were men. An elevated PLR occurred in 87 patients (33.6%); 67 (25.9%) had an elevated NLR; 200 (77%) had an elevated C-reactive protein (CRP). Elevated PLR and NLR was associated with a variety of infectious, inflammatory, and malignant conditions similar to conditions described in the general non-HIV-infected adult population. Additionally, elevated PLR and NLR occurred both in patients in receipt of antiretroviral therapy (with undetectable viral loads), as well as in those with newly-diagnosed and poorly-controlled infection. Fourteen patients with infectious and inflammatory conditions had an elevated PLR and normal CRP, with/without elevated NLR. There was no association between elevated PLR or NLR and ICU admission, p = 0.1001 and p = 0.605, respectively. Elevated NLR, but not PLR was associated with death, p = 0.0405 and p = 1.000, respectively: two-tailed Fisher’s exact test. The single site nature of the audit and relatively small number of patients limits these observations