PubMed Health⌕ Search

Biomedical subjects

R N Davidson

Publications and source records attributed to R N Davidson.

At least 19 recordsLinked to original sources

Successful miltefosine treatment of post-kala-azar dermal leishmaniasis occurring during antiretroviral therapy.

The first two patients to be treated with miltefosine for post-kala-azar dermal leishmaniasis (PKDL) are reported. One was a 26-year-old Ethiopian man who had been treated with sodium stibogluconate, for relapsing visceral leishmaniasis (VL), four times between August 2002 and March 2004. In January 2004 this patient was found to be seropositive for HIV and began antiretroviral treatment with stavudine, lamivudine and nevirapine. Five months later he developed clinical PKDL, with extensive cutaneous, conjunctival and oral mucosal involvement. The second patient was a 42-year-old Ethiopian man who was treated for relapsing VL in November 2003. He too was subsequently found to be seropositive for HIV and was treated with stavudine, lamivudine and nevirapine from May 2004. He developed a nodular rash of PKDL over his face and upper body 2 weeks after starting the antiretroviral therapy. Treatment of both patients with oral miltefosine, at 100 mg/day for 28 days, led to the complete regression of their PKDL lesions. When checked 3-6 months after the end of the miltesofine treatment, neither patient showed any signs of VL, PKDL or other HIV-associated disease.

Administration, Oral↗

Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London.

OBJECTIVES: The incidence of tuberculosis (TB) is high amongst foreign-born persons resident in developed countries. Vitamin D is important in the host defence against TB in vitro and deficiency may be an acquired risk factor for this disease. We aimed to determine the incidence and associations of vitamin D deficiency in TB patients diagnosed at an infectious diseases unit in London, UK. METHODS: Case-note analysis of 210 unselected patients diagnosed with TB who had plasma vitamin D (25(OH)D3) levels routinely measured. Prevalence of 25(OH)D3 deficiency and its relationship to ethnic origin, religion, site of TB, sex, age, duration in the UK, month of 25(OH)D3 estimation and TB diagnosis were determined. RESULTS: Of 210 patients 76% were 25(OH)D3 deficient and 56% had undetectable levels. 70/82 Indian, 24/28 East African Asian, 29/34 Somali, 14/19 Pakistani and Afghani, 16/22 Sri Lankan and 2/6 other African patients were deficient (with 58, 17, 23, 9, 6 and 1 having undetectable levels, respectively). Only 0/6 white Europeans and 1/8 Chinese/South East Asians had low plasma 25(OH)D3 levels. Muslims, Hindus and Sikhs all had equivalent rates of deficiency though Hindus were more likely to have undetectable levels (odds ratio 1.87, 95% CI 1.27-2.76). There was no significant association between 25(OH)D3 level and site of TB or duration of residence in the UK. There was no apparent seasonal variation in either TB diagnosis or 25(OH)D3 level. CONCLUSIONS: 25(OH)D3 deficiency commonly associates with TB among all ethnic groups apart from white Europeans, and Chinese/South East Asians. Our data support a lack of sunlight exposure and potentially a vegetarian diet as contributors to this deficiency.

Case-Control Studies↗

Successful liposomal amphotericin B treatment of Leishmania braziliensis cutaneous leishmaniasis.

Existing systemic treatments for New World cutaneous leishmaniasis (CL) caused by Leishmania (vianna) braziliensis are unsatisfactory. Liposomal amphotericin B has been used extensively for the treatment of visceral leishmaniasis, but in few cases of CL, and an appropriate regimen for CL has not been described. We successfully treated a patient with multiple L. braziliensis CL lesions acquired in Belize. Liposomal amphotericin B (AmBisome) was given to our patient as an inpatient for seven daily doses of 3 mg kg(-1) day(-1) and then as an outpatient at 3 mg kg(-1) twice weekly for a further three weeks, a total of 40 mg kg(-1). Liposomal amphotericin offers a well-tolerated alternative to pentavalent antimony or amphotericin B deoxycholate for the systemic treatment of New World CL.

Adult↗

Histoplasmosis as the cause of a pathological fracture.

We report the case of an 82-year-old man with a pathological fracture of the hip caused by infection with Histoplasma capsulatum var capsulatum. He was treated by a hemiarthroplasty and with oral itraconazole.

Administration, Oral↗

Pulmonary tuberculosis among political asylum seekers screened at Heathrow Airport, London, 1995-9.

BACKGROUND: Over 50% of cases of tuberculosis (TB) in the UK occur in people born overseas, and new entrants to the country are screened for TB. A study was undertaken to determine the prevalence and disease characteristics of pulmonary TB in new entrants to the UK seeking political asylum. METHODS: A retrospective analysis of the results of screening 53 911 political asylum seekers arriving at Heathrow Airport between 1995 and 1999 was performed by studying Airport Health Control Unit records and hospital medical records. Outcome measures were chest radiograph abnormalities, sputum smear, culture, and drug resistance data for Mycobacterium tuberculosis. RESULTS: The overall prevalence of active TB in political asylum seekers was 241 per 100 000. There were large variations in prevalences of TB between asylum seekers from different regions, with low rates from the Middle East and high rates from the Indian subcontinent and sub-Saharan Africa. The frequency of drug resistance was high; 22.6% of culture positive cases were isoniazid resistant, 7.5% were multidrug resistant (resistant to both isoniazid and rifampicin), and 4% of cases diagnosed with active disease had multidrug resistant TB. CONCLUSIONS: The prevalence rate of TB in political asylum seekers entering the UK through Heathrow Airport is high and more M tuberculosis isolates from asylum seekers are drug resistant than in the UK population. Extrapolating these figures, it is estimated that 101 political asylum seekers with active pulmonary TB enter the UK every year, of whom about 25 would have smear positive disease.

Adolescent↗

Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment.

The wide spectrum of clinical outcomes following infection with Mycobacterium tuberculosis is largely determined by the host immune response; therefore, we studied several clinically defined groups of individuals (n = 120) that differ in their ability to contain the bacillus. To quantitate M. tuberculosis-specific T cells directly ex vivo, we enumerated IFN-gamma-secreting CD4 T cells specific for ESAT-6, a secreted Ag that is highly specific for M. tuberculosis, and a target of protective immune responses in animal models. We found that frequencies of circulating ESAT-6 peptide-specific IFN-gamma-secreting CD4 T cells were higher in latently infected healthy contacts and subjects with minimal disease and low bacterial burdens than in patients with culture-positive active pulmonary tuberculosis (p = 0.009 and p = 0.002, respectively). Importantly, the frequency of these Ag-specific CD4 T cells fell progressively in all groups with treatment (p = 0.005), suggesting that the lower responses in patients with more extensive disease were not due to tuberculosis-induced immune suppression. This population of M. tuberculosis Ag-specific Th1-type CD4 T cells appears to correlate with clinical phenotype and declines during successful therapy; these features are consistent with a role for these T cells in the containment of M. tuberculosis in vivo. Such findings may assist in the design and evaluation of novel tuberculosis vaccine candidates.

Adult↗

Prevention and management of infections in patients without a spleen.

Patients who lack a functioning spleen become vulnerable to sepsis caused by bacteria and, occasionally, protozoa. The risk is higher in children and in those who have had immunosuppressive treatment, and the risk remains lifelong. Overwhelming post-splenectomy infection (OPSI) occurs at an estimated incidence of 0.23-0.42% per year, with a lifetime risk of 5%. Episodes of OPSI are emergencies, requiring immediate parental antibiotics and intensive care; intravenous immunoglobulins may be useful. OPSI carries a mortality of 38-69%. Streptococcus pneumoniae is the commonest infecting organism, accounting for 50-90% of isolates from blood cultures in reported series; it is particularly common in children with sickle cell disease. Less commonly, the infecting organisms are other bacteria, Babesia or Ehrlichia. OPSI may be, to some extent, preventable by several interventions. These are surgical conservation of the spleen; immunization against S. pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis; prophylactic antibiotics; stand-by antibiotics; patient information sheets; and a medical alert bracelet. Asplenic patients living in malaria-endemic areas require optimal prophylaxis. The initial step in prevention of OPSI is the creation of an asplenia register, as many patients are not covered by these simple measures.

Antibiotic Prophylaxis↗

Comparison of generic and proprietary sodium stibogluconate for the treatment of visceral leishmaniasis in Kenya.

OBJECTIVE: To compare the use of generic and proprietary sodium stibogluconate for the treatment of visceral leishmaniasis (kala-azar). METHODS: A total of 102 patients with confirmed kala-azar were treated in a mission hospital in West Pokot region, Kenya, with sodium stibogluconate (20 mg/kg/day for 30 days)--either as Pentostam (PSM) or generic sodium stibogluconate (SSG); 51 patients were allocated alternately to each treatment group. FINDINGS: There were no significant differences in baseline demographic characteristics or disease severity, or in events during treatment. There were 3 deaths in the PSM group and 1 in the SSG group; 2 patients defaulted in each group. Only 1 out of 80 test-of-cure splenic aspirates was positive for Leishmania spp.; this patient was in the SSG group. Follow-up after > or = 6 months showed that 6 out of 58 patients had relapsed, 5 in the SSG group and 1 in the PSM group. No outcome variable was significantly different between the two groups. CONCLUSION: The availability of cheaper generic sodium stibogluconate, subject to rigid quality controls, now makes it possible for the health authorities in kala-azar endemic areas to provide treatment to many more patients in Africa.

Adolescent↗

Bronchopulmonary and mediastinal leishmaniasis: an unusual clinical presentation of Leishmania donovani infection.

We describe a case of unusual leishmaniasis in a Sudanese man with a history of progressively enlarging granulomatous mediastinal lymphadenopathy, worsening hemoptysis, and an intense mucosal granulomatous inflammatory response in the large bronchi. Leishmania donovani DNA was detected in bronchial biopsies by polymerase chain reaction. This is a novel description of human leishmanial infection in an immunocompetent patient involving this anatomical site. The patient's condition improved clinically, spirometrically, and radiologically after a course of treatment with amphotericin B. The cell-mediated immune response was analyzed before, during, and after successful antileishmanial chemotherapy.

Adult↗

Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study.

BACKGROUND: Susceptibility to disease after infection by Mycobacterium tuberculosis is influenced by environmental and host genetic factors. Vitamin D metabolism leads to activation of macrophages and restricts the intracellular growth of M. tuberculosis. This effect may be influenced by polymorphisms at three sites in the vitamin D receptor (VDR) gene. We investigated the interaction between serum vitamin D (25-hydroxycholecalciferol) concentrations and VDR genotype on susceptibility to tuberculosis. METHODS: This study was a hospital-based case-control analysis of Asians of Gujarati origin, a mainly vegetarian immigrant population with a high rate of tuberculosis. We typed three VDR polymorphisms (defined by the presence of restriction endonuclease sites for Taq1, Bsm1, and Fok1) in 91 of 126 untreated patients with tuberculosis and 116 healthy contacts who had been sensitised to tuberculosis. Serum 25-hydroxycholecalciferol was recorded in 42 contacts and 103 patients. FINDINGS: 25-hydroxycholecalciferol deficiency was associated with active tuberculosis (odds ratio 2.9 [95% CI 1.3-6.5], p=0.008), and undetectable serum 25-hydroxycholecalciferol (<7 nmol/L) carried a higher risk of tuberculosis (9.9 [1.3-76.2], p=0.009). Although there was no significant independent association between VDR genotype and tuberculosis, the combination of genotype TT/Tt and 25-hydroxycholecalciferol deficiency was associated with disease (2.8 [1.2-6.5]) and the presence of genotype ff or undetectable serum 25-hydroxycholecalciferol was strongly associated with disease (5.1 [1.4-18.4]). INTERPRETATION: 25-hydroxycholecalciferol deficiency may contribute to the high occurrence of tuberculosis in this population. Polymorphisms in the VDR gene also contribute to susceptibility when considered in combination with 25-hydroxycholecalciferol deficiency.

Calcifediol↗

Tuberculosis diagnosed during pregnancy: a prospective study from London.

BACKGROUND: A study was undertaken to characterise the presentation of tuberculosis in pregnancy and the difficulties in diagnosis in an area of the UK with a high incidence of tuberculosis. METHODS: A prospective case series was investigated at Northwick Park Hospital, a university affiliated district general hospital in Brent and Harrow health authority in north-west London which incorporates a regional infectious diseases unit. Patients diagnosed with tuberculosis over the study period were included if the onset of symptoms occurred during pregnancy. RESULTS: Thirteen patients were diagnosed during a 30 month period from December 1995 to May 1998 during which 9069 mothers were delivered, a prevalence of 143.3/100 000 deliveries. Symptoms began at a median of 22 weeks gestation (range 9-40 weeks). All patients were recent immigrants of Indian subcontinent or Somali origin and their median duration of residence in the UK was 31 months (range 1-72). Prevalence broken down for racial origin of mothers was 466.3/100 000 for mothers of black African origin and 239.1/100 000 for mothers of Indian origin. Nine of the 13 patients had extrapulmonary tuberculosis. Four patients with widely disseminated disease had a negative Mantoux response and five with localised disease had a strongly positive Mantoux response. HIV co-infection was absent. The median delay between the onset of symptoms and diagnosis was seven weeks (range 2-30). The response to standard treatment was excellent and all patients were cured. CONCLUSIONS: Tuberculosis occurring in pregnancy is common in recent immigrants. Diagnosis during pregnancy is delayed because the disease is frequently extrapulmonary with few symptoms.

Antitubercular Agents↗

Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis.

Several lines of evidence suggest that host genetic factors controlling the immune response influence infection by Mycobacterium tuberculosis. The proinflammatory cytokine interleukin (IL)-1beta and its antagonist, IL-1Ra (IL-1 receptor agonist), are strongly induced by M. tuberculosis and are encoded by polymorphic genes. The induction of both IL-1Ra mRNA and secreted protein by M. tuberculosis in IL-1Ra allele A2-positive (IL-1Ra A2(+)) healthy subjects was 1.9-fold higher than in IL-1Ra A2(-) subjects. The M. tuberculosis-induced expression of mRNA for IL-1beta was higher in subjects of the IL-1beta (+3953) A1(+) haplotype (P = 0.04). The molar ratio of IL-1Ra/IL-1beta induced by M. tuberculosis was markedly higher in IL-1Ra A2(+) individuals (P < 0.05), with minor overlap between the groups, reflecting linkage between the IL-1Ra A2 and IL-1beta (+3953) A2 alleles. In M. tuberculosis-stimulated peripheral blood mononuclear cells, the addition of IL-4 increased IL-1Ra secretion, whereas interferon gamma increased and IL-10 decreased IL-1beta production, indicative of a differential influence on the IL-1Ra/IL-1beta ratio by cytokines. In a study of 114 healthy purified protein derivative-reactive subjects and 89 patients with tuberculosis, the frequency of allelic variants at two positions (-511 and +3953) in the IL-1beta and IL-1Ra genes did not differ between the groups. However, the proinflammatory IL-1Ra A2(-)/IL-1beta (+3953) A1(+) haplotype was unevenly distributed, being more common in patients with tuberculous pleurisy (92%) in comparison with healthy M. tuberculosis-sensitized control subjects or patients with other disease forms (57%, P = 0.028 and 56%, P = 0. 024, respectively). Furthermore, the IL-1Ra A2(+) haplotype was associated with a reduced Mantoux response to purified protein derivative of M. tuberculosis: 60% of tuberculin-nonreactive patients were of this type. Thus, the polymorphism at the IL-1 locus influences the cytokine response and may be a determinant of delayed-type hypersensitivity and disease expression in human tuberculosis.

Cell Division↗

Murine dendritic cells internalize Leishmania major promastigotes, produce IL-12 p40 and stimulate primary T cell proliferation in vitro.

Metacyclic Leishmania promastigotes (PM), transmitted by sand-fly bite, are likely to interact initially with cells of the dendritic cell (DC) lineage(s) in the epidermis or dermis. Epidermal Langerhans cells internalize L. major amastigotes (AM) and transport them to draining lymph nodes (Moll, H., Fuchs, H., Blank, C. and Röllinghoff, M., Eur. J. Immunol. 1993. 23: 1595) but little is known about the interaction of DC with PM. The present study demonstrates that DC are able to internalize PM and that the fate of the parasites within DC differs from that within macrophages (Mphi). DC took up small numbers of PM which did not differentiate into AM but appeared to be degraded; Mphi internalized large numbers of PM into parasitophorous vacuoles where they differentiated into AM. In response to direct stimulation with PM, DC from both C3H ("resistant" to L. major infection) and BALB/c ("susceptible") up-regulated production of IL-12 p40. In contrast, IL-12 production by Mphi was not detected. DC exposed to either metacyclic PM or PM culture supernatants were also able to stimulate proliferative responses in lymph node T cells from naive mice. These data indicate that DC have the capacity to promote protective Th1 immune responses in Leishmania infection and suggest that DC exposed to PM may be useful in immunotherapy and vaccination.

Animals↗

Kinetics and toxicity of liposomal and conventional amikacin in a patient with multidrug-resistant tuberculosis.

The pharmacokinetics and toxicity of liposomal amikacin in a patient treated for advanced pulmonary multidrug-resistant tuberculosis are described. A dose of 20 mg/kg of liposomal amikacin was given on alternate days for 14 days and weekly thereafter for 9 weeks, for a total dose of 20.1 g in 17 divided doses. Accumulation occurred with alternate-day, but not weekly, dosing. The serum levels of amikacin obtained with the liposomal preparation were considerably greater than those obtained with the conventional preparation (range, 81-457 mg/l vs. 4.1-37.7 mg/l). The liposomal amikacin was well tolerated and led to clinical improvement, but it failed to achieve a microbiological response. The patient's sputum remained smear- and culture-positive during the treatment period with liposomal amikacin and for 9 months afterward.

Aged↗

Do amoebic liver abscesses start as large lesions? Case report of an evolving amoebic liver abscess.

Amoebic liver abscesses (ALA) are characteristically large lesions at presentation, but their development in man has not previously been described. We present a case of an ALA that over the course of 2 days developed from an undetectable lesion to a 5 cm diameter lesion. This clinical history suggests that the pathogenesis of ALAs may pursue an acute rather than a chronic course.

Humans↗