Indian Subcontinent Patients Research Articles

Giant cell arteritis in patients of Indian Subcontinental descent in the UK

GCA in the Indian Subcontinent (ISC) is rare. Our centre in London, UK, serves an ethnically diverse population, including a significant population of patients of ISC descent. We hypothesise that patients of ISC descent are no less likely than others to present with symptoms suggestive of GCA and therefore to undergo temporal artery biopsy (TAB). A retrospective audit of all TABs performed at our institution over an 8 year period, to identify ethnicity (white, black, ISC, other, unknown) and biopsy result. We compared the proportion of all patients of ISC descent attending the ED to the proportion of ISC patients undergoing TAB. We compared the proportion of positive TABs among ISC patients with positive TABs among white patients. We also compared the proportion of TAB in ISC patients with all non-ISC ethnicities combined. The proportion of patients undergoing TAB who were of ISC descent (16.3% of 92) was comparable to the proportion of A&E attendances made up by ISC patients [p = 0.1339]. 3.8% (1/26) of positive biopsies were among patients of ISC descent. White patients were significantly more likely to have a positive biopsy than patients of ISC ethnicity (33% of 61 white patients vs. 7% of 15 ISC [p = 0.0456]), as were patients of non-ISC ethnicity (32.5% of 77 non-ISC patients vs. 7% of 15 ISC patients [p = 0.0464]). At our centre, biopsy proven GCA occurs in patients of ISC descent, but rarely. Full investigation for GCA continues to be appropriate where it is suspected, regardless of ethnicity.

Importance of secondary screening with clinical isolates for anti-leishmania drug discovery

The growing drug resistance (DR) raises major concerns for the control of visceral leishmaniasis (VL), a neglected disease lethal in 95 percent of the cases if left untreated. Resistance has rendered antimonials (SSG) obsolete in the Indian Sub-Continent (ISC) and the first miltefosine-resistant Leishmania donovani were isolated. New chemotherapeutic options are needed and novel compounds are being identified by high-throughput screening (HTS). HTS is generally performed with old laboratory strains such as LdBOB and we aimed here to validate the activity of selected compounds against recent clinical isolates. In this academic/industrial collaboration, 130 compounds from the GSK “Leishbox” were screened against one SSG-sensitive and one SSG-resistant strain of L. donovani recently isolated from ISC patients, using an intracellular assay of L. donovani-infected THP1-derived macrophages. We showed that only 45% of the compounds were active in both clinical isolates and LdBOB. There were also different compound efficiencies linked to the SSG susceptibility background of the strains. In addition, our results suggested that the differential susceptibility profiles were chemical series-dependent. In conclusion, we demonstrate the potential value of including clinical isolates (as well as resistant strains) in the HTS progression cascade.

A case control study in the Indian subcontinent ethnic population on the effect of return visits and the subsequent development of tuberculosis

A local government area in North West England with a significant population of Indian subcontinent (ISC) ethnic origin and a high incidence of tuberculosis. To assess whether return visits to the ISC are associated with an increased risk of developing clinical tuberculosis. Analysis of data prospectively obtained from ISC patients diagnosed with TB in 1998-2002 (cases) and age and sex matched ISC patients in two local GP practices (controls). There is at best weak evidence of association between case status and whether individuals have had a repeat visit to the subcontinent within 3 years of notification in this cohort; odds ratio 1.26 (95% CI (0.95, 1.76)); Fishers exact test P=0.09.

Demographics of the UK cystic fibrosis population: implications for neonatal screening.

The objective was to determine the composition of the Cystic Fibrosis (CF) Population attending specialist UK CF centres in terms of age, gender, age at diagnosis, genotype and ethnicity. With the planned introduction of the national CF screening programme in the UK, cystic fibrosis transmembrane regulator (CFTR) mutations were compared between different ethnic groups enabling a UK-specific frequency of mutations to be defined. Data were analysed from the patient biographies held in the UK CF Database (see www.cystic-fibrosis.org.uk). The currently registered population of 5,274 CF patients is 96.3% Caucasian with a male preponderance that significantly increases with age. The majority of the 196 non-Caucasian CF patients are from the Indian Subcontinent (ISC), of which one in 84 UK CF patients are of Pakistani origin. The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4). The distribution of Caucasian patients with deltaF508/deltaF508, deltaF508/Other and Other/Other does not fit the expected distribution with a Hardy-Weinberg model unless those patients without a detected mutation are excluded (P<0.001). The UK CF Database has shown the UK CF population to have distinct characteristics separate from the North American and European CF Registries. The ISC group contains many mutations not recognised by current genetic analysis, and one in four ISC patients have no CFTR mutations identified. The CFTR analysis proposed for the screening programme would detect 96% of patients registered in the database, but is unlikely to achieve the desired >80% detection rates in the ethnic minority groups. Screen-positive, non-Caucasian infants without an identifiable CFTR mutation should be referred for a sweat test and genetic counselling when serum trypsinogen concentrations remain elevated after birth.

Miliary tuberculosis in a high prevalence area of the U.K.: Blackburn 1978–1993

Thirty-nine cases of miliary tuberculosis treated between 1978–1993 in a district with a high incidence of tuberculosis are reported. Twenty-eight patients were of Indian Subcontinent (ISC) ethnic origin, 10 patients were Caucasian and one patient was Chinese. Mortality at 10% in both Caucasian (x 2 4·94; 0·05> P>0·01) and ISC patients (x 2 10·22; 0·001>P) were significantly lower than in a recently reported series from Edinburgh, as was the proportion of post mortem diagnoses of miliary tuberculosis (x 2 6·35; 0·02>P>0·01). Both the rate of miliary tuberculosis and the average age at diagnosis in Caucasian patients were lower than in the Edinburgh series suggesting that miliary tuberculosis could be under-diagnosed in the elderly Caucasian population in the Blackburn district. The better outcome of those diagnosed in life may be partly due to heightened awareness of tuberculosis locally and partly due to treatment by a centralized tuberculosis service.

Tuberculosis epidemiology in Croydon

A survey of tuberculosis in Croydon between 1988 and 1991, using Chest Clinic health visitor records, showed that the disease occurred most frequently in those of Indian Sub-Continent (ISC) ethnic origin. Of the 222 cases during the 4-year period, 65% were of ISC ethnic origin, 22% were Caucasian and 11% Afro-Caribbean. Non-Caucasian cases were younger (P < 0.0001), and more likely to be female (P = 0.064) or present with non-pulmonary disease (P = 0.064). One-quarter of ISC patients developed active tuberculosis more than 15 years after immigration into the UK. Only seven cases were children. The contact tracing procedure resulted in three additional cases, all of whom were contacts of smear-positive index cases. There were significantly fewer Heaf or radiologically positive contacts of non-smear positive pulmonary, or non-pulmonary index cases (P = 0.0002). The value of the current contact tracing system is discussed.

Factors determining ethnic differences in the incidence of bacteriologically confirmed genitourinary tuberculosis in South East England

In South East England, genitourinary (GU) tuberculosis is a much less common manifestation of non-respiratory tuberculosis in patients of Indian subcontinent (ISC) ethnic origin than in those of European ethnic origin. When considered in relation to all bacteriologically confirmed cases of tuberculosis, both respiratory and non-respiratory, the ethnic difference in the occurrence of GU tuberculosis is much less evident, while there is a highly significant excess of other forms of non-respiratory tuberculosis among the ethnic ISC patients. Unlike other forms of non-respiratory tuberculosis, GU disease tends to occur in an older age range in the ethnic ISC population and, when stratified for age, the ethnic difference in the occurrence of this form of tuberculosis is not significant while that of lymph node tuberculosis remains significantly high. Thus, after elimination of the confounding factor of age, the occurrence of GU tuberculosis is very similar in the two ethnic groups while other forms of non-respiratory tuberculosis differ considerably.

A bacteriological survey of tuberculosis due to the human tubercle bacillus (Mycobacterium tuberculosis) in south-east England: 1984-91.

The occurrence and nature of bacteriologically confirmed tuberculosis due to Mycobacterium tuberculosis in South-East England in the period 1984-91 is reported and compared with the results of a study for 1977-83. Registered new cases reached a low of 1028 in 1988 but increased to 1252 in 1991. This appeared to be due to a halt in the previous decline in new cases of European patients, a small increase in the number of Indian subcontinent (ISC) patients and an increase in patients from Africa. A total of 122 patients, mostly of European ethnic origin, were known to be HIV positive. As in the 1977-83 study, disease in the ISC group affected younger patients than in the European group, tubercle bacilli were more frequently isolated from a non-pulmonary site in the ISC group (45%) than in the European group (19%) and there was a higher incidence of the South Indian variant of M. tuberculosis in the former group (17%) than in the latter (9%). The overall incidence of drug resistance has not altered significantly since the 1977-83 study but 46 strains resistant to 3 or more drugs were isolated from 4099 ISC patients, compared with 3 of 4594 strains from European patients. Six of the 122 isolates from HIV positive patients were drug-resistant but none was multi-drug resistant. The slight rise in registered bacteriologically proven cases of tuberculosis, the presence of multi-drug resistant strains, the occurrence of HIV-related tuberculosis and reports of the emergence of multi-drug-resistant HIV-related tuberculosis in other countries strongly indicate the need for continued careful surveillance.

National survey of tuberculosis notifications in England and Wales in 1983: Characteristics of disease

The number of newly notified, previously untreated patients in a survey of notifications of tuberculosis in England and Wales conducted by the MRC in 1983 was 26 % lower than in the previous MRC survey in 1978/79. In both surveys the great majority of patients were of White (about half) or Indian subcontinent (Indian, Pakistani or Bangladeshi) ethnic origin (just over a third). The notification rates in the Indian subcontinent (ISC) ethnic groups were much higher than for the White group and were highest in those most recently arrived in the UK. There were a number of differences in the findings for the White and the ISC ethnic groups.Nearly two-thirds of the White patients but less than half of the ISC patients were male and the White patients were, on average, older, about half aged 55 years or more compared with 14 % of the ISC patients.Respiratory disease occurred in 82 % of the White patients compared with 66 % of the ISC patients. Radiographically, at independent assessment, more of the White patients had pulmonary lesions, 88 % compared with 63 % and these were, on average, more extensive and cavitated than in the ISC patients. Isolated mediastinal lymphadenopathy, however, was more common in the ISC patients. The diagnosis was confirmed bacteriologically on culture of a respiratory specimen in a higher proportion of the White than the ISC patients (65 % and 41 % respectively) and more were positive on smear as well (45 % and 25 % respectively). The level of initial drug resistance was lower in the White patients: only 10 (1.6 %) of the 623 strains tested were resistant compared to 23 (12.8 %) of the 179 from ISC patients.In both White and ISC ethnic groups the commonest non-respiratory lesion was peripheral lymph node involvement, namely 37 % of the 369 White and 53 % of the 503 ISC patients with non-respiratory disease. The diagnosis was confirmed by bacteriological examination of the lymph node in 47 % of the ISC patients compared with 29 % of the White patients with a lesion. Bone or joint disease occurred in 11 % of the White and 20 % of the ISC patients; the commonest site in both groups was the spine. Genitourinary disease was present in 98 (27 %) of White and 24 (5 %) of ISC patients with a non-respiratory lesion. There were 61 patients with tuberculosis involving the central nervous system, including 55 with meningitis, the proportions being similar for the White and the ISC ethnic groups, 7 % and 5 % respectively.