A challenging case of invasive pulmonary aspergillosis after near-drowning: a case report and literature review.

Near-drowning, a relatively common event, is often complicated by subsequent pneumonia. While endogenous and exogenous bacteria are typical pathogens, rarely fungi are as well. We report a complicated case of invasive pulmonary aspergillosis in a 30-year-old man after a near-drowning event. We also review the medical literature for similar cases. All cases of invasive pulmonary aspergillosis after near-drowning reported in the literature involve Aspergillus fumigatus. The majority of cases involved submersion in stagnant water after a motor vehicle accident (MVA). Treatment varied considerably, with amphotericin B used in the majority of cases. Morbidity was considerable with prolonged hospitalization occurring in every case, and mortality occurring in fifty percent of the reported cases. Although a rare complication of near-drowning, invasive pulmonary aspergillosis can occur and lead to significant morbidity and mortality. After near-drowning A. fumigatus isolated from the respiratory tract should be assumed to be a true pathogen and treated accordingly.

Strengthening research capacity through the medical education partnership initiative: the Mozambique experience.

BACKGROUND: Since Mozambique's independence, the major emphasis of its higher educational institutions has been on didactic education. Because of fiscal and human resource constraints, basic and applied research activities have been relatively modest in scope, and priorities have often been set primarily by external collaborators. These factors have compromised the scope and the relevance of locally conducted research and have limited the impact of Mozambique's universities as major catalysts for national development. CASE DESCRIPTION: We developed a multi-institutional partnership to undertake a comprehensive analysis of the research environment at Mozambique's major public universities to identify factors that have served as barriers to the development of a robust research enterprise. Based on this analysis, we developed a multifaceted plan to reduce the impact of these barriers and to enhance research capacity within Mozambique. INTERVENTIONS: On the basis of our needs assessment, we have implemented a number of major initiatives within participating institutions to facilitate basic and applied research activities. These have included specialized training programmes, a reorganization of the research administration infrastructure, the development of multiple collaborative research projects that have emphasized local research priorities and a substantial investment in bioinformatics. We have established a research support centre that provides grant development and management services to Mozambique's public universities and have developed an independent Institutional Review Board for the review of research involving human research subjects. Multiple research projects involving both communicable and non-communicable diseases have been developed and substantial external research support has been obtained to undertake these projects. A sizable investment in biomedical informatics has enhanced both connectivity and access to digital reference material. Active engagement with relevant entities within the Government of Mozambique has aligned institutional development with national priorities. CONCLUSIONS: Although multiple challenges remain, over the past 3 years significant progress has been made towards establishing conditions within which a broad range of basic, translational and clinical and public health research can be undertaken. Ongoing development of this research enterprise will enhance capacity to address critical locally relevant research questions and will leverage resources to accelerate the development of Mozambique's national universities.

Microbiological analysis of nontyphoidal Salmonella strains causing distinct syndromes of bacteremia or enteritis in HIV/AIDS patients in San Diego, California.

Recurrent invasive nontyphoidal Salmonella (NTS) infection is an AIDS-defining illness that has become less common in the developed world in the era of highly active antiretroviral therapy (HAART), while it has emerged as a major public health problem in developing countries, particularly sub-Saharan Africa. We retrospectively analyzed Salmonella (NTS) infection in HIV/AIDS patients from June 2003 until December 2009 at the University of California, San Diego (UCSD), Medical Center. Bacterial isolates from all patients were tested for selected microbiological properties, including major Salmonella (NTS) virulence loci rpoS, sodCI, spvB, and sseI. Fourteen percent of all Salmonella (NTS) cases recorded at the UCSD Medical Center during this period occurred in known HIV/AIDS patients. The clinical presentations in HIV patients fell into two distinct groups, bacteremia and enteritis. There was little clinical overlap between these two syndromes. All strains were positive for the presence of the rpoS and sodCI virulence loci, and 75% of strains were positive for the presence of the spvB and sseI loci. Antibiotic susceptibility assay showed that all strains were susceptible to trimethoprim-sulfamethoxazole and ciprofloxacin. The clinical presentation did not have a clear relationship to the CD4(+) cell count. Of the bacteremic isolates, all but one isolate, drawn from a patient with substantial enteric comorbidities, had all of the virulence genes tested, but 66% of nonbacteremic, enteritis strains also contained all the tested virulence loci. In conclusion, neither patients' CD4(+) cell count nor bacterial strain properties necessarily predicted the clinical presentation of HIV/AIDS patients with Salmonella (NTS) infection, and AIDS patients can have episodes of Salmonella enteritis without dissemination.

Tuberculosis due to Mycobacterium bovis in patients coinfected with human immunodeficiency virus.

We reviewed 86 cases of human immunodeficiency virus and tuberculosis coinfection; 34.9% were caused by Mycobacterium bovis. Patients with M. bovis infection were more likely to have advanced immunosuppression (CD4 T cell counts ≤200 cells/µL). Hispanic ethnicity, male sex, and abdominal disease were strongly associated with M. bovis disease.

mTOR activity in AIDS-related diffuse large B-cell lymphoma.

BACKGROUND: Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway. MATERIALS AND METHODS: We evaluated tissue samples from 126 patients with AR-DLBCL. Among them, 98 samples were from tissue microarrays (TMAs) supplied by the Aids and Cancer Specimen Resource (ACSR), the remaining 28 samples were from cases diagnosed and treated at the University of California, San Diego (UCSD). The presence of p70S6K was evaluated with two antibodies directed against the combined epitopes Ser235/236 and Ser240/244, respectively; and additional monoclonal anti-bodies were used to identify pPTEN and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40). The degree of intensity and percentage of cells positive for p70S6K and pPTEN were assessed in all the samples. In addition, a subgroup of 28 patients from UCSD was studied to assess the presence of pPRAS40, an insulin-regulated activator of the mTORC1. The expression of each of these markers was correlated with clinical and histopathologic features. RESULTS: The majority of the patients evaluated were males (88%); only two cases (1.6%) were older than 65 years of age. We found high levels of both p70S6K-paired epitopes studied, 48% positivity against Ser235/236 (44% in ACSR and 64% in UCSD group), and 86% positivity against Ser240/244 (82% in ACSR and 100% in UCSD group). We observed more positive cells and stronger intensity with epitope Ser240/244 in comparison to Ser235/236 (p<0.0001). The degree of intensity and percentage of cells positive for pPTEN was positively correlated with p70S6K levels (p = 0.016 for 235/236 and p = 0.007 for 240/244). High levels of pPRAS40 were observed in the majority of the cases evaluated (64.3%), but no correlation was found with either pPTEN (p = 0.9) or p70S6K (p = 0.9) levels. CONCLUSION: AR-DLBCL frequently contain p70S6K, a main downstream effector of the mTOR pathway. The presence of p70S6K is positively correlated with pPTEN, an inactive form of PTEN, which makes mTORC1 activated. The presence of p70S6K was independent of HIV viral load or CD4 (+) counts. These results suggest that the mTOR pathway is active in the majority of AR-DLBCL, and p70S6K, particularly the Ser240/244 epitope immunohistochemistry is an excellent surrogate biomarker, which could be used to identify cases expected to be responsive to mTOR inhibitors.

Oncogenic and metastatic properties of preprotachykinin-I and neurokinin-1 genes.

Breast cancer (BC) remains the cancer with highest mortality among women in the United States. Entry of BC cells (BCCs) in bone marrow (BM) leads to poor prognosis. This review discusses studies showing interactions between BCCs and BM stroma, consequently providing BCCs with advantages of survival within BM. Myc transcription factor is investigated as a link between the transforming properties of peptides derived from the preprotachykinin-I gene (PPT-I) and Neurokinin-1 (NK1) receptor. A co-culture method previously described to model early integration of BCC in BM is used to study timeline changes of PPT-I and TGF-beta using northern analyses and a bioassay, respectively. The results show changes of both genes in BCCs and BM stroma. Relevance of these changes to homeostasis in BM is discussed. Myc has been shown to link the expressions of TGF-beta1 and PPT-I in BCCs. We now show a role for Myc in the expression of NK1. PPT-I and the chemokine SDF-1alpha induce the expression of each other through an autocrine mechanism. Since a role for Myc in SDF-1alpha-PPT-I axis has not been studied, we speculate on this finding, based on the cell-homing property of SDF-1alpha. Since Myc could be oncogenic, it might be involved in the transforming properties of PPT-I and NK1 while SDF-1alpha could be involved in cell-homing of BCCs through the regulation of PPT-I. The findings are discussed in the context of other related reports.

A prospective observational study of bacteraemia in adults admitted to an urban Mozambican hospital.

BACKGROUND: Bacteraemia is a common cause of fever among patients presenting to hospitals in sub-Saharan Africa. The worldwide rise of antibiotic resistance makes empirical therapy increasingly difficult, especially in resource-limited settings. OBJECTIVES: To describe the incidence of bacteraemia in febrile adults presenting to Maputo Central Hospital (MCH), an urban referral hospital in the capital of Mozambique, and characterise the causative organisms and antibiotic susceptibilities. We aimed to describe the antibiotic prescribing habits of local doctors, to identify areas for quality improvement. METHODS: Inclusion criteria were: (i) ≥18 years of age; (ii) axillary temperature ≥38°C or ≤35°C; (iii) admission to MCH medical wards in the past 24 hours; and (iv) no receipt of antibiotics as an inpatient. Blood cultures were drawn from enrolled patients and incubated using the BacT/Alert automated system (bioMérieux, France). Antibiotic susceptibilities were tested using the Kirby-Bauer disc diffusion method. RESULTS: Of the 841 patients enrolled, 63 (7.5%) had a bloodstream infection. The most common isolates were Staphylococcus aureus, Escherichia coli, and non-typhoidal Salmonella. Antibiotic resistance was common, with 20/59 (33.9%) of all bacterial isolates showing resistance to ceftriaxone, the broadest-spectrum antibiotic commonly available at MCH. Receipt of insufficiently broad empirical antibiotics was associated with poor in-hospital outcomes (odds ratio 8.05; 95% confidence interval 1.62 - 39.91; p=0.04). CONCLUSION: This study highlights several opportunities for quality improvement, including educating doctors to have a higher index of suspicion for bacteraemia, improving local antibiotic guidelines, improving communication between laboratory and doctors, and increasing the supply of some key antibiotics.

Innovative strategies for transforming internal medicine residency training in resource-limited settings: the Mozambique experience.

With approximately 4 physicians per 100,000 inhabitants, Mozambique faces one of the most severe health care provider shortages in Sub-Saharan Africa. The lack of sufficient well-trained medical school faculty is one of Mozambique's major barrier to producing new physicians annually. A partnership between the Universidade Eduardo Mondlane and the University of California, San Diego, has addressed this challenge with support from the Medical Education Partnership Initiative. After an initial needs assessment involving questionnaires and focus groups of residents, and working with key members from the Ministry of Health, the Medical Council, and Maputo Central Hospital, a set of interventions was designed. The hospital's internal medicine residency program was chosen as the focus for the plan. Interventions included curriculum design, new teaching methodologies, investment in an informatics infrastructure for access to digital references, building capacity to support clinical research, and providing financial incentives to retain junior faculty. The number of candidates entering the internal medicine residency program has increased, and detailed monitoring and evaluation is measuring the impact of these changes on the quality of training. These changes are expected to improve the long-term quality of postgraduate training in general through dissemination to other departments. They also have the potential to facilitate equitable distribution of specialists nationwide by expanding postgraduate training to other hospitals and universities.