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Biomedical subjects

S B Squire

Publications and source records attributed to S B Squire.

At least 19 recordsLinked to original sources

Developing a socio-economic measure to monitor access to tuberculosis services in urban Lilongwe, Malawi.

OBJECTIVES: To develop locally appropriate measures of poverty for the National Tuberculosis Programme (NTP), Malawi, and to assess access to tuberculosis (TB) services by different socio-economic groups by establishing a socio-economic profile of current TB patients DESIGN: A quantitative proxy measure of poverty was developed through regression analysis of data from the 1998 national Malawi Integrated Household Survey. A qualitative assessment of poverty was conducted in poor and non-poor settlements in urban Lilongwe to identify key indicators of socio-economic status. Both quantitative and qualitative indicators were used to assess the socioeconomic status of 179 TB patients who participated in a cross-sectional survey. FINDINGS: The proxy measure of poverty and the qualitative indicators demonstrated similar ability to measure the poverty status of patients. The poverty head count among patients using the quantitative and qualitative indicators were 78% and 70%, respectively. Geographical analysis showed that 60% were from non-poor areas and only 15% (26/139) were from squatter settlements. CONCLUSION: This study established a strategy for monitoring access to TB services using a proxy measure of poverty and qualitative indicators. This is a vital first step in developing an evidence base for pro-poor equitable TB services.

Adult↗

A one-day method for the diagnosis of pulmonary tuberculosis in rural Ethiopia.

Smear diagnosis of pulmonary tuberculosis (PTB) requires three sputum examinations over 2 days. We evaluated the performance of two sputum specimens obtained on a single day (the second specimen submitted 1 h after the first) against the standard 2-day method in rural Ethiopia. A total of 243 suspects were enrolled; 52 had confirmed PTB: 49 (94%) were detected by the same-day method and 51 (98%) by the standard method (P > 0.5). The same-day approach would reduce the number of visits required for diagnosis, save resources for the health system and the patient, and ultimately improve case detection in poorer countries.

Ethiopia↗

The bleach microscopy method and case detection for tuberculosis control.

The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (The Union) recommend direct sputum smear microscopy for tuberculosis (TB) case finding in resource-poor settings. This method is associated with poor sensitivity. Digestion of sputum with bleach prior to smear preparation has been reported to increase sensitivity. Some workers, having reviewed the relevant literature, have called for the WHO and The Union to advocate for a shift to this methodology for TB case finding. This article highlights deficiencies in the scope and detail of available evidence, and cautions against the premature, and possibly counter-productive, adoption of so-called 'bleach microscopy'. Further well-guided research is required to answer policy-relevant gaps in our knowledge about this promising technology.

Humans↗

Screening for pulmonary tuberculosis: an acceptable intervention for antenatal care clients and providers?

SETTING: Five purposively sampled health facilities in Kasungu District, Malawi. OBJECTIVES: To explore 1) the acceptability of introducing pulmonary tuberculosis (PTB) screening into antenatal care (ANC) clinics amongst ANC clients and ANC service providers; and 2) the acceptability of tuberculosis (TB) treatment during and after pregnancy among women registered for TB treatment. METHODS: Fourteen focus group discussions and 40 in-depth interviews with ANC clients (15), ANC service providers (10) and women registered for TB treatment (15). RESULTS: Most clients found the introduction of PTB screening into ANC clinics acceptable. Some expressed concern at submitting a second sputum specimen, citing transportation/distance as the main obstacle. Other concerns were stigma and fear relating to the human immunodeficiency virus and the acquired immune-deficiency syndrome (HIV/AIDS) and taking TB treatment during pregnancy and breast-feeding. All ANC service providers supported the idea, but were concerned about increased workload. CONCLUSION: PTB screening in the ANC setting would be an acceptable intervention and could serve to increase PTB case notification in Malawi. However, alternative diagnostic strategies need to be explored. The negative associations with HIV/AIDS and some of the misconceptions surrounding TB treatment need to be addressed to avoid PTB screening becoming a potential barrier to seeking ANC. The main challenge will be whether over-stretched staff will be able to cope with this additional service.

Breast Feeding↗

Providing HIV care for tuberculosis patients in sub-Saharan Africa.

Human immunodeficiency virus (HIV)/acquired immunedeficiency syndrome (AIDS) and tuberculosis (TB) cause an immense burden of disease in sub-Saharan Africa. A large amount of knowledge has been gathered in the last 15 years about the negative impact that HIV has on TB control, both at a programme level and at the level of the individual patient. Equally, interventions that are known to benefit patients have been tested and piloted, and these form important components of international TB-HIV guidelines, a TB-HIV strategic framework and an interim policy on TB-HIV coordination. Unfortunately, in sub-Saharan Africa there is little evidence that these interventions are being implemented on the ground, and one of the reasons for this paralysis is that the operational details are not well developed. This paper takes the three important HIV interventions of HIV testing and counselling, cotrimoxazole preventive treatment and antiretroviral treatment, and discusses some of the practical details of on-the-ground implementation. We hope that this will generate discussion, but above all, the impetus to start delivering services to patients.

Africa South of the Sahara↗

Microbiological validation of smear microscopy after sputum digestion with bleach; a step closer to a one-stop diagnosis of pulmonary tuberculosis.

BACKGROUND: Smear microscopy is relatively insensitive for the diagnosis of TB. The digestion of sputum with household bleach prior to smear preparation has been reported to improve its sensitivity. This method has not been validated. METHODS: Seven hundred and fifty six patients with symptoms suggestive of pulmonary TB (PTB) were asked to submit 3 sputum specimens for direct microscopy. One specimen was selected at random for culture and another specimen was digested to prepare a further smear. The WHO case definition (>or=2 positive smears or one positive smear and positive culture) was used to compare the sensitivity and specificity of the smears. FINDINGS: Four hundred and fifty five (60%) patients were culture-positive. Of these, 235 (31%) had "definite" PTB and 223 (29%) "very likely" PTB (smear-negative, culture-positive). The WHO case definition identified 51% (235/458) of the patients with "definite" or "very likely" PTB. One digested smear detected 219 (93%) of the 235 patients with "definite" PTB and 10 patients with "very likely" PTB (sensitivity (95%CI) 50% (45-55%); specificity 99% (97-100%)). The positive and negative predictive values for one digested smear were 98% (95-99%) and 56% (52-60%) respectively, which were not different (p>0.5) to the WHO case definition (100% and 57%, respectively). INTERPRETATION: One bleach-digested smear is as sensitive and specific as the WHO case definition for the diagnosis of PTB.

Bacteriological Techniques↗

Fluoroquinolones for treating tuberculosis.

BACKGROUND: Fluoroquinolones are sometimes used to treat multiple-drug-resistant and drug-sensitive tuberculosis. The effects of fluoroquinolones in tuberculosis regimens need to be assessed. OBJECTIVES: To assess fluoroquinolones as additional or substitute components to antituberculous drug regimens for drug-sensitive and drug-resistant tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1940 to April 2005), and Russian database (1988 to April 2005). We also scanned reference lists of all identified studies and contacted researchers. SELECTION CRITERIA: Randomized controlled trials of antituberculous regimens containing fluoroquinolones in people diagnosed with bacteriologically positive (sputum smear or culture) pulmonary tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria, assessed methodological quality, and extracted data. We used relative risk (RR) for dichotomous data, weighted mean difference (WMD) for continuous data (both with 95% confidence intervals (CI)), and the random-effects model if we detected heterogeneity and appropriate to combine data. MAIN RESULTS: Ten trials (1178 participants) met the inclusion criteria. No statistically significant difference was found in trials substituting ciprofloxacin or ofloxacin for first-line drugs in relation to cure (89 participants, 2 trials), treatment failure (388 participants, 3 trials), or clinical or radiological improvement (216 participants, 2 trials). Substituting ciprofloxacin into first-line regimens in drug-sensitive tuberculosis led to a higher incidence of relapse (RR 7.17, 95% CI 1.33 to 38.58; 384 participants, 3 trials) and longer time to sputum culture conversion (WMD 0.50 months, 95% CI 0.18 to 0.82; 168 participants, 1 trial), although this was confined to HIV-positive participants. Adding or substituting levofloxacin to basic regimens in drug-resistant areas had no effect. A comparison of sparfloxacin versus ofloxacin added to regimens showed no statistically significant difference in cure (184 participants, 2 trials), treatment failure (149 participants, 2 trials), or total number of adverse events (253 participants, 3 trials). AUTHORS' CONCLUSIONS: Only ciprofloxacin, ofloxacin, levofloxacin, and sparfloxacin have been tested in randomized controlled trials for treating tuberculosis. We cannot recommend ciprofloxacin in treating tuberculosis. Trials of newer fluoroquinolones for treating tuberculosis are needed. No difference has been demonstrated between sparfloxacin and ofloxacin in drug-resistant tuberculosis.

Antitubercular Agents↗

'Lost' smear-positive pulmonary tuberculosis cases: where are they and why did we lose them?

SETTING: Ntcheu District, rural Malawi. OBJECTIVES: 1) To locate smear-positive pulmonary tuberculosis patients who were identified during the first 6 months of 2000 but did not start treatment ('lost cases'); 2) to describe these patients' pathways to diagnosis, health status and socio-demographic characteristics; and 3) to explore why these patients did not start treatment. METHODS: Lost cases were traced from programme registers and interviewed using the qualitative research critical incidents narrative (CIN) interviews technique. Results were triangulated with responses from health care workers through focus group discussions. RESULTS: The laboratory registered 157 new smear-positive patients. Twenty three (15%) of these were 'lost' (did not appear in the treatment register). CIN interviews were conducted with five lost patients and 14 carers of lost patients who had died. Long pathways to diagnosis were the norm. Health system structural barriers were the main factors behind these pathways, including requirement for hospital attendance, delays in symptom recognition and receipt of sputum results, and the misconception that negative smears excluded tuberculosis. CONCLUSION: Some smear-positive cases experience very long pathways to diagnosis and are lost from this free public health system. The diagnostic process needs to become more responsive to patients' needs.

Adult↗

Comparison of scanty AFB smears against culture in an area with high HIV prevalence.

To verify among tuberculosis (TB) suspects attending hospitals in Abuja, Nigeria, if sputum smears graded as scanty are false-positive, sputum smears from 1068 patients were graded with the International Union Against Tuberculosis and Lung Disease classification. One specimen was cultured. Eight hundred and twenty-four (26%) smears were positive, 137 (4%) scanty and 2243 negative. Of 1068 cultures, 680 (64%) were positive. One hundred and thirty (95%) scanty and 809 (98%) positive smears were culture-positive. Twelve of 18 patients with a single scanty smear and 51 of 52 with > or = 2 scanty smears were culture-positive. Fewer than < 5% scanty results, < 1% of the patients treated for TB, are false-positive.

Colony Count, Microbial↗

Using a bus service for transporting sputum specimens to the Central Reference Laboratory: effect on the routine TB culture service in Malawi.

SETTING: All non-private hospitals in Malawi that registered TB cases in 2001, during which there was a bus service for transporting sputum specimens to the Central Reference Laboratory (CRL) for mycobacterial culture and drug sensitivity testing (CDST). OBJECTIVES: To determine the performance of the system of collecting and processing sputum specimens from patients with recurrent smear-positive pulmonary TB through to CDST. DESIGN: Structured interviews with TB Officers, and retrospective data collection using TB and laboratory registers. RESULTS: There were 964 patients with recurrent smear-positive PTB. TB Officers took responsibility for collecting and transporting sputum to the CRL, and 73% reported using the bus service. Sputum specimens from 384 (40%) patients arrived at the CRL. Of these, 40% were found to have negative concentrated smears at the CRL, and 36% of specimen sets arriving at CRL were successfully cultured for DST. Most specimens had been collected after the start of anti-tuberculosis treatment. Although delays in collection adversely affected culture, only 43% of specimen sets collected on or before the first day of treatment yielded Mycobacterium tuberculosis. CONCLUSION: Problems were identified at all stages of the system and strategies to remedy these are being put in place.

Disease Notification↗

Efficacy and safety of short-term bleach digestion of sputum in case-finding for pulmonary tuberculosis in Ethiopia.

BACKGROUND: In many settings, the diagnosis of pulmonary tuberculosis depends on sputum microscopy. However, this technique has low sensitivity. We studied the efficacy and safety of sputum digestion with bleach prior to Ziehl-Neelsen (ZN) staining. METHODS: Positive sputum smears were assessed for staining quality and viability of mycobacteria after varying bleaching times. Two hundred smears were then prepared from the first, second and third sputum sample of tuberculosis suspects. Equal amounts of 5% bleach were added to the remaining first sputum and ZN smears were prepared. FINDINGS: Optimal quality and staining was achieved with 30-45 min of bleaching. No growth was observed from positive samples after 15 min. Bleached specimens had 26% (52/200) positivity compared to 17.5% (35/ 200) of unbleached smears (P < 0.001). The bleached smears had 92.3% sensitivity, 93.4% specificity, 78.3% and 97.7% positive and negative predictive values, respectively, against a case definition. Ten patients failed to submit a second or third sputum. Six patients were positive on either the standard or bleach-digested smears, or both. INTERPRETATION: Bleach digestion is simple, cheap and kills mycobacteria. Its positivity rate is as good as three standard smears. This method has the potential to improve over-burdened services in developing countries.

Cytological Techniques↗

Teaching tuberculosis control to medical undergraduates: the Malawi experience.

SETTING: National Tuberculosis (TB) Control Programme (NTP) and College of Medicine (COM), Malawi. OBJECTIVES: To develop a TB/HIV module, incorporating TB control and the DOTS strategy, for 4th year medical undergraduates. To describe 1) the way in which the module was developed, 2) the contents and structure of the module, 3) the experience of teaching the module from 2000-2002, and d) the financial costs to the NTP. DESIGN: A descriptive study. RESULTS: The TB/HIV module, including the teaching manual, resource materials and undergraduate assessments, was developed between June and December 1999 by NTP, College of Medicine, interested stakeholders and an external consultant. The module was well received by medical undergraduates. Student knowledge, based on pre-module and post-module assessments, increased to satisfactory levels. Novel aspects of teaching, which included reading chapters in class followed by student-led knowledge reviews, modular assessments and using NTP staff as facilitators, were highly rated. The cost of developing the module was 14,070 US dollars, and the recurrent annual cost of teaching the module was 900 US dollars. CONCLUSION: The results show that a national tuberculosis control programme can work effectively with an academic medical institution in teaching medical undergraduates the important principles of country-wide TB control.

Adult↗

Characteristics, management and outcome of patients with recurrent tuberculosis under routine programme conditions in Malawi.

SETTING: All 43 non-private hospitals in Malawi, which registered TB cases between 1 July 1999 and 30 June 2000. OBJECTIVES: To determine 1) the characteristics, management and treatment outcome, 2) timing of the previous episode of TB, and 3) pattern of drug resistance in patients registered with recurrent smear-positive pulmonary TB. DESIGN: Retrospective data collection using TB registers and laboratory culture and drug sensitivity registers. RESULTS: There were 748 recurrent patients; data were available for 747. Of these, 487 (65%) successfully completed a re-treatment regimen, 185 (25%) died and the remainder had another outcome. Information about previous TB was recorded for 491 (66%) patients. In 286 (58%) there were 2 years or less between completing and re-starting treatment. Only 307 (41%) patients had sputum sent for culture and drug sensitivity tests. In 164 patients with cultures of Mycobacterium tuberculosis, 122 (81%) were fully sensitive, 25 (15%) had resistance to isoniazid and/or streptomycin, and 6 (4%) had resistance to isoniazid and rifampicin (MDR-TB). CONCLUSION: Patients with recurrent TB had acceptable treatment outcomes, and most had fully sensitive organisms. Over half had recurrent TB 2 years or less after completing treatment. Ways to prevent recurrence need to be investigated and implemented in the field.

Humans↗

Are intestinal helminths a risk factor for non-typhoidal Salmonella bacteraemia in adults in Africa who are seropositive for HIV? A case-control study.

In Africa, invasive, non-typhoidal Salmonella (NTS) infections are a common but life-threatening complication in adults who are seropositive for HIV. The high prevalence of human infection with intestinal helminths which penetrate the gut could explain the greater importance of NTS bacteraemia in Africa compared with that in industrialized countries. If helminth infection is a major risk factor for NTS it would provide a locally relevant, public-health target. Intestinal helminth carriage in 57 HIV-positive patients with NTS bacteraemia (the cases) was compared with that in 162 HIV-positive controls who were similar to the cases in terms of age, sex, urban dwelling and socio-economic factors. The prevalence of helminth infection, 29% overall, was lower among the cases (18%) than among the controls (33%), giving a crude odds ratio of 0.40 [with a 95% confidence interval (CI) of 0.21-0.9] and an adjusted odds ratio (aOR) of 0.79 (CI = 0.4-1.8). Five (9%) of the cases and 12 (7%) of the controls were infected with nematodes which penetrate the gut (Ascaris lumbricoides and/or Strongyloides stercoralis). The aOR for infection with these penetrating worms, corrected for age, sex, urban dwelling and phase of study, was 1.40 (CI = 0.4-4.5). The present results do not exclude the possibility that helminths play a role in invasive NTS infections, but are not consistent with helminths being a sufficient risk factor in this population to be a public-health target. Anthelmintics are unlikely to have a major impact on preventing NTS bacteraemia in patients diagnosed HIV-positive in Africa.

AIDS-Related Opportunistic Infections↗

Quality assessment of sputum transportation, smear preparation and AFB microscopy in a rural district in Malawi.

SETTING: Ntcheu District, Central Region of Malawi. OBJECTIVES: To assess 1) the feasibility of introducing simple internal quality control procedures for acid-fast bacilli (AFB) microscopy, and 2) the quality of the district sputum smear microscopy service. DESIGN: A simple internal quality control system was piloted in which district laboratory staff assessed: 1) specimen suitability, 2) time between sputum submission and smear examination, 3) smear preparation and staining, and 4) microscopy. Actual times for processing specimens were compared with recommended times. External quality validation was carried out. RESULTS: Of 4805 sputum specimens: 1) documentation was complete in 95%, 2) 93% reached the laboratory within 7 days of collection, 3) 96% of smears were well prepared and stained, and 4) 97% concordance (96.4% smear-positive and 97.6% smear-negative) was demonstrated when 208 smears were re-examined by a second technician. The aggregate index of reliability was 86%. The mean time spent on microscopic examination was 3.8 minutes, compared with the recommended time of 10 minutes. When all smears from 164 patients were assessed externally, 98.2% concordance (98.1% smear-positive and 98.2% smear-negative) was demonstrated. False smear-negative and smear-positive rates were less than 2% each. CONCLUSION: District laboratory staff were able to incorporate simple quality control procedures for AFB microscopy into their routine practice, resulting in a reliable service. The lessons learnt are widely relevant and potentially useful for implementation of a national quality assurance scheme.

Chi-Square Distribution↗

Opsonic phagocytosis of Streptococcus pneumoniae by alveolar macrophages is not impaired in human immunodeficiency virus-infected Malawian adults.

Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis, especially among adults infected with the human immunodeficiency virus (HIV). Alveolar macrophages (AMs) are critical components of cellular defense against bacterial infection and are both infected and affected by HIV. In this study, AMs obtained at bronchoscopy from 44 Malawian adults (24 HIV positive and 20 HIV negative) were exposed in vitro to opsonized S. pneumoniae and coagulase-negative staphylococci. AMs from HIV-positive and -negative volunteers showed no significant difference in binding to or internalization of either S. pneumoniae or coagulase-negative staphylococci. In HIV-positive subjects, the presence of detectable HIV in lung fluid was not associated with AM impairment. AMs from HIV-infected adults did not exhibit impaired pneumococcal phagocytosis in the assay used. This suggests that an alternative mechanism of susceptibility is operating in these individuals.

Adult↗

What causes smear-negative pulmonary tuberculosis in Malawi, an area of high HIV seroprevalence?

SETTING: The Central Hospital and the District Tuberculosis (TB) Registry in Lilongwe, the capital of Malawi. In this setting smear-negative pulmonary tuberculosis (PTB) is diagnosed using clinical and radiographic criteria for TB, and mycobacterial cultures are not routinely available. OBJECTIVE: To determine the proportion of patients being registered for smear-negative PTB treatment in Lilongwe who have TB that can be confirmed microbiologically. DESIGN: Prospective cohort study of patients about to start treatment under operational conditions for smear-negative PTB in Lilongwe between October 1997 and June 1998. Patients referred to the study team underwent a detailed clinical re-assessment, testing for human immunodeficiency virus (HIV), repeat sputum smear microscopy for acid-fast bacilli and mycobacterial cultures of sputum and blood. Bronchoscopy and bronchoalveolar lavage (BAL) were performed and BAL fluid was examined for TB, Pneumocystis carinii and other fungi. RESULTS: Of 352 smear-negative PTB suspects assessed, the diagnosis of TB was confirmed in 137 (39%) cases. Eighty-nine per cent of patients assessed were HIV-positive, of whom 81% met the expanded case definition for the acquired immune-deficiency syndrome (AIDS). CONCLUSION: TB was the most commonly confirmed diagnosis amongst patients about to start treatment for smear-negative PTB in an area of high background HIV seroprevalence.

Adolescent↗

'Smear-negative' pulmonary tuberculosis in a DOTS programme: poor outcomes in an area of high HIV seroprevalence.

SETTING: Lilongwe Central Hospital, Malawi. OBJECTIVES: To investigate 1) treatment outcome of a cohort of smear-negative pulmonary TB (snPTB) patients in an area of high human immunodeficiency virus (HIV) seroprevalence, and 2) whether poor treatment outcomes are due to non-TB patients being mistakenly treated for TB due to lack of diagnostic facilities. DESIGN: Patients about to be registered for snPTB treatment by the National TB Programme underwent further assessment including TB culture, bronchoscopy and bronchoalveolar lavage. All patients were followed up for 8 months. Standard TB control treatment outcomes were recorded. RESULTS: Of 352 snPTB patients assessed, 137 patients had bacteriologically confirmed TB, 136 had possible TB, and 79 had other non-TB diagnoses. The HIV seroprevalence rate was 89%. Outcomes were known for 325 (92%) patients: 129 (40%) died within 8 months. Death rates on TB treatment were 31% for bacteriologically confirmed TB patients and 35% for patients with possible TB but no bacteriological diagnosis. The death rate among patients with non-TB diagnoses was 53%. HIV infection significantly increased the risk of death (OR 3.9; P = 0.01). CONCLUSION: SnPTB is strongly associated with HIV infection in Malawi, where patients treated for snPTB have a poor prognosis. The high mortality is not fully explained by non-TB patients being mistakenly treated for TB.

Adolescent↗