Henry C Mwandumba

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kapeni, Southern Region, Malawi

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Publications (12)49.13 Total impact

  • The Journal of neuropsychiatry and clinical neurosciences 01/2011; 23(2):E32-4. · 2.34 Impact Factor
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    Chest 07/2010; 138(1):234-5. · 7.13 Impact Factor
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    ABSTRACT: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines. A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.
    Thorax 05/2008; 63(4):317-21. · 8.38 Impact Factor
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    ABSTRACT: In the developing world, early mortality within 1 month of commencing tuberculosis (TB) treatment is high, particularly with human immunodeficiency virus (HIV) co-infection. In Malawi, 40% of those who die do so in the first month of treatment. Reasons remain unclear and may include delayed diagnosis, opportunistic infections, immune restoration inflammatory syndrome (IRIS) or malnutrition. One possible contributing factor is underlying hypoadrenalism associated with TB-HIV, exacerbated by rifampicin (RMP) induction of P450 and glucocorticoid metabolism. To assess the prevalence of hypoadrenalism in TB patients before and after commencement of TB treatment, and relationship with early mortality. Prospective descriptive study assessing hypoadrenalism before and after anti-tuberculosis treatment, HIV status and outcome up to 3 months post-treatment. Of 51 patients enrolled, 29 (56.9%) were female (median age 32 years, range 18-62). Of 43 patients HIV-tested, 38 (88.3%) were HIV-positive and 15.7% died within the first month. At 3 months, 11 (21.6%) were known to have died. Adequate cortisol levels were found in 49/51 (95.9%) before commencing RMP. Neither of the two with reduced response died. All 34 patients revealed adequate cortisol responses at 2 weeks. No evidence of hypoadrenalism was found in this first study to assess adrenal function and outcome of anti-tuberculosis treatment.
    The International Journal of Tuberculosis and Lung Disease 04/2008; 12(3):314-8. · 2.76 Impact Factor
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    ABSTRACT: Infection with human immunodeficiency virus (HIV) may affect the clinical presentation of pulmonary tuberculosis (TB). To investigate the association between sputum smear status at presentation and local pulmonary immune responses in HIV-infected patients with pulmonary TB, we compared the cellular and cytokine profiles in bronchoalveolar lavage (BAL) fluid obtained from the site of lung disease in 22 sputum smear- and culture-positive, and 17 sputum smear-negative but culture-positive pulmonary TB patients. Smear-positive patients had significantly higher BAL fluid concentrations of IL-6 (p=0.007), IL-8 (p=0.02), IL-10 (p=0.03) and IFN-gamma (p=0.008) than smear-negative patients. No significant differences in the proportions of examined BAL cells were found. We concluded that sputum smear-positive TB was associated with greater pro-inflammatory and immunomodulatory cytokine responses at the site of lung disease than sputum smear-negative disease. The local immune responses may affect the clinical presentation of active pulmonary TB in HIV-infected patients.
    Tuberculosis 02/2008; 88(1):58-63. · 3.03 Impact Factor
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    ABSTRACT: The functional capacity of alveolar macrophages (AM) in human immunodeficiency virus (HIV)-infected patients with pulmonary tuberculosis (TB) is not completely understood. To investigate the capacity of AM to mediate inflammatory responses, we obtained AM from human subjects by bronchoalveolar lavage (BAL) and studied the cells ex vivo. We compared AM from HIV-infected patients with suspected pulmonary TB to AM from healthy, HIV-negative controls for their capacity to produce TNF-alpha or IL-6 spontaneously and upon stimulation with lipopolysaccharide (LPS). Cytokine-producing cells were identified by macrophage markers and intracellular cytokine staining and flow cytometry. A higher proportion of AM from patients with microbiologically confirmed pulmonary TB than patients with probable TB or controls spontaneously expressed TNF-alpha shortly after isolation (geometric means: 38.5%, 23.7% and 15.8%, respectively), suggesting endogenous cytokine production. The proportions of AM spontaneously expressing TNF-alpha positively correlated with peripheral blood CD4(+) T-lymphocyte counts in patients (partial r=0.60, p=0.003) but not controls. Stimulation with LPS resulted in a significant increase in the proportions of TNF-alpha- and IL-6-positive AM from patients and controls (p<0.01). Bronchoalveolar lavage fluid (BALF) from confirmed TB patients also contained higher concentrations of the inflammatory cytokines predominantly produced by macrophages, IL-6 and IL-8, than controls (geometric mean cytokine concentrations per gram of BALF albumin were 1291 pg/g vs. 115 pg/g, p=0.03 for IL-6 and 4739 pg/g vs. 704 pg/g, p=0.03 for IL-8). We concluded that AM from HIV-infected patients with pulmonary TB produced and released inflammatory cytokines in vivo and retained their innate ability to respond to stimulation by LPS.
    Microbes and Infection 08/2007; 9(9):1053-60. · 2.92 Impact Factor
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2007; 29.
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    ABSTRACT: Alveolar macrophages (AM) are the first professional phagocytes encountered by aerosols containing infections in the lungs, and their phagocytic capacity may be affected by these infections or environmental particles. The aim of this study was to evaluate the innate endocytic and phagocytic properties of human AM obtained from patients with pulmonary tuberculosis and to characterize the vacuoles in which Mycobacterium tuberculosis bacilli reside in vivo. AM were obtained by bronchoalveolar lavage from patients with suspected tuberculosis and from asymptomatic volunteers (controls). Clinical case definitions were based on mycobacterial culture of respiratory specimens and HIV serology. To assess phagocytosis, endocytosis, and acidification of the endosomal system, AM were cultured with IgG-coated polystyrene beads, dextran, and a pH-sensitive reporter (3-(2,4-dinitroanilino)-3-amino-N-methyldipropylamine) and were evaluated by light and immunoelectron microscopy. Cells from 89 patients and 10 controls were studied. We found no significant difference between the two groups in the ability of AM either to ingest beads and dextran or to deliver them to acidified lysosomes. In AM from patients with tuberculosis, the bacilli were located in vacuoles that failed to accumulate endocytosed material and were not acidified. We concluded that AM from patients with tuberculosis and HIV infections were competent to endocytose and phagocytose material and to deliver the material to functional, acidified lysosomes. M. tuberculosis residing in these AM arrests the progression of their phagosomes, which fail to fuse with acidified lysosomes. This confirms, for the first time in humans with tuberculosis and HIV, the conclusions from previous animal and in vitro studies.
    The Journal of Immunology 05/2004; 172(7):4592-8. · 5.52 Impact Factor
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    David G Russell, Henry C Mwandumba, Elizabeth E Rhoades
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    ABSTRACT: Pathogenic Mycobacterium reside inside vacuoles in their host macrophages. These vacuoles fail to fuse with lysosomes yet interact with early endosomes. Glycoconjugates released by the intracellular bacilli traffic through the host cell and are released through exocytosis. These molecules represent both antigens for immune recognition and modulators of immune function. The molecules play key roles in the induction and maintenance of the granuloma, a tissue response that limits bacterial spread yet ensures persistence of the infection.
    The Journal of Cell Biology 09/2002; 158(3):421-6. · 10.82 Impact Factor
  • H C Mwandumba, N J Beeching
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    ABSTRACT: Lung abscess and thoracic empyema continue to cause significant morbidity and mortality despite appropriate antibiotic therapy and various options for drainage of empyema. Multiple factors, including the patient's general state of health, the presence of underlying disease, the virulence of the pathogen responsible, and the promptness of drainage of empyema, appear to dictate the clinical outcome. However, the available data are derived from uncontrolled, retrospective studies and the high morbidity and mortality rates underscore the need for large prospective studies to better evaluate factors that may predict the clinical outcome of these conditions.
    Current opinion in pulmonary medicine 06/2000; 6(3):234-9. · 3.12 Impact Factor
  • H C Mwandumba, N J Beeching
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    ABSTRACT: Pyogenic lung infections still occur despite the availability of effective antibiotics for the treatment of patients with acute bacterial pneumonia. Our understanding of the pathogenesis and management of these conditions has steadily improved over the past few decades, although some areas remain obscure. The effect of HIV infection on the incidence of pyogenic lung infections remains largely unknown, and large studies are required to evaluate this. Burkholderia (formerly Pseudomonas) cepacia strains are now recognized as important respiratory pathogens in patients with cystic fibrosis, and the high transmissibility of some strains, combined with their inherent multiple antibiotic resistance, are continuing causes for concern.
    Current opinion in pulmonary medicine 06/1999; 5(3):151-6. · 3.12 Impact Factor
  • H. C. Mwandumba, N. J. Beeching, F. J. Nye, G. V. Gill
    Journal of Infection - J INFECTION. 01/1999; 39(1).

Publication Stats

158 Citations
49.13 Total Impact Points

Institutions

  • 2004–2008
    • Malawi-Liverpool-Wellcome Trust Clinical Research Programme
      Kapeni, Southern Region, Malawi
    • Liverpool School of Tropical Medicine
      • Clinical Research Group
      Liverpool, England, United Kingdom
  • 1999
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom