Prevalence of sexually transmitted disease in tuberculosis patients in Malawi.
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Adult↗
Biomedical subjects
D Maher
Publications and source records attributed to D Maher.
The internationally recommended tuberculosis control strategy. World Health Organization.
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Developing Countries↗
KRN8602 (MX2-hydrochloride): an active new agent for the treatment of recurrent high-grade glioma.
PURPOSE: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma. PATIENTS AND METHODS: Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score < or = 2) were treated with an intravenous bolus of 40 mg/m(2) KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles. RESULTS: A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting. CONCLUSION: KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.
Adolescent↗
Efficacy of an unsupervised ambulatory treatment regimen for smear-negative pulmonary tuberculosis and tuberculous pleural effusion in Malawi.
SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To evaluate treatment outcome of unsupervised ambulatory treatment (2R3H3Z3/2TH[EH]/4H) in Blantyre and 'standard' treatment (1STH[SEH]/11TH[EH]) in Zomba in human immunodeficiency virus (HIV) seropositive and seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB. DESIGN: All patients with smear-negative and pleural TB registered between 1 April and 31 December 1995 were assessed for enrolment in the study. Study patients were followed up and 12-month treatment outcomes were recorded. RESULTS: A total of 434 patients, 296 with smear-negative PTB and 138 with pleural TB, were enrolled: 366 (84%) of patients were HIV-positive; 220 (51%) completed treatment, and 144 (33%) died by 12 months. In patients from Blantyre and Zomba, baseline characteristics were similar, apart from older age in those from Zomba, and the proportion of patients who completed treatment and who died were similar. In both sites, significantly higher case fatality rates were found in older patients, HIV-positive patients and patients with pulmonary parenchymal lung disease. CONCLUSION: Unsupervised ambulatory treatment evaluated in this study had an efficacy similar to that of 'standard' treatment. For operational reasons, however, it will not be recommended for widespread use in Malawi's National Tuberculosis Control Programme.
Adolescent↗
Community contribution to tuberculosis care in countries with high tuberculosis prevalence: past, present and future.
Effective tuberculosis control requires the collaboration of many partners. There is increasing interest in harnessing the contribution of communities to effective ambulatory tuberculosis control, as part of national tuberculosis programme activities. Understanding the lessons learned from the 1980s about community participation in Primary Health Care is important in understanding how communities may contribute specifically to tuberculosis care. Most of the published experience of community contribution to tuberculosis care is quite recent, small scale, and reports non-standardised results of effectiveness of tuberculosis treatment. There has been little attention to the issues of cost-effectiveness and acceptability. A multi-national collaborative project is underway in sub-Saharan Africa, coordinated by the World Health Organization, and aims at evaluating in a standardised way the effectiveness, cost-effectiveness and acceptability of community contribution to tuberculosis care. This should pave the way towards the development of international policy guidelines, to promote community contribution to tuberculosis care in ways which are effective, cost-effective and acceptable.
Africa South of the Sahara↗
Direct observation of tuberculosis treatment by supervised family members in Yasothorn Province, Thailand.
SETTING: Yasothorn Province, Thailand. OBJECTIVE: To evaluate the effectiveness of a programme offering the option of direct observation of treatment (DOT) by a supervised family member. METHODS: Review of patient records and district registers in Yasothorn Province after implementation of the revised tuberculosis control strategy. RESULTS: From 1 October 1996 to 30 September 1997, the programme registered 779 patients: 366 smear-positive pulmonary, 357 smear-negative pulmonary, and 56 extra-pulmonary. DOT was given in 243 (66%) smear-positive, 83 (23%) smear-negative, and in 21 (38%) extra-pulmonary cases; the observer was a family member in 299 (86.2%) of the 347 cases. By December 1998, treatment outcomes were determined for the 695 new patients (326 smear-positive, 321 smear-negative, 48 extra-pulmonary) of the 779 registered during the period under study. In new smear-positive patients, cure rates were 184/216 (85.2%, 95% confidence interval [CI] 80.5-89.9) with DOT versus 78/110 (70.9%, 95% CI 62.4-79.4) with self-administration. CONCLUSION: The overall cure rate was 80.4% in a programme in which trained and supervised family members directly observed the treatment of two-thirds of sputum smear-positive patients. Supervised family members may contribute to more widespread effective implementation of the revised tuberculosis strategy in Thailand.
Communicable Disease Control↗
Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor.
PURPOSE: To assess the mobilization potential and safety of recombinant human stem-cell factor (SCF) when coadministered with filgrastim to untreated women with poor-prognosis breast cancer. PATIENTS AND METHODS: Eligible women had breast cancer with 10 or more positive axillary nodes, or estrogen receptor-negative tumor with 4 positive nodes, or stage III disease. Patients were randomized to receive SCF plus filgrastim or filgrastim alone. Filgrastim 12 microg/kg daily was administered for 6 days by continuous subcutaneous infusion. SCF was administered by daily subcutaneous injection at 5, 10, or 15 microg/kg concurrent with filgrastim for 7 days, or 10 microg/kg daily starting 3 days before filgrastim for a total of 10 days (SCF pretreatment). Apheresis was performed on days 5, 6, and 7 of filgrastim administration. Patients then had three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days, each supported by one third of the apheresis product. RESULTS: Sixty-two women were treated. Greater yields occurred in patients who received SCF 10 microg/kg daily plus filgastim than those who received filgrastim alone (P=.013 for CD34+ cells; P=.07 for granulocyte-macrophage colony-forming cells [GM-CFCs]). The difference was more marked with SCF-pretreatment than concurrent SCF. Fewer aphereses were required to reach the predetermined target of peripheral-blood progenitor/stem cells (PBPCs) in women who received SCF. SCF was generally well tolerated. Hematologic recovery was rapid after each of the three cycles of chemotherapy. There was no difference in recovery between the different treatment groups. CONCLUSION: Mobilization of PBPCs by filgrastim is significantly enhanced by coadministration of SCF, and commencing SCF before filgrastim can optimize this effect. SCF has the potential to reduce the number of aphereses required to collect a target number of PBPCs.
Adult↗
Phase I and pharmacokinetic study of KRN8602 alone and with filgrastim in patients with advanced cancer.
PURPOSE: To determine the recommended dose, toxicity profile, and pharmacokinetics of KRN8602 (MX2-hydrochloride), a novel morpholino anthracycline with potent cytotoxicity against anthracycline-sensitive and resistant experimental tumors in vitro and in vivo. PATIENTS AND METHODS: KRN8602 was administered alone in increasing doses to patients with advanced cancer or high-grade gliomas until dose-limiting toxicity (DLT) was observed in three or more of five patients treated in a dose level. Because neutropenia was dose limiting, further escalation was investigated with filgrastim support. RESULTS: Fifty-six assessable patients completed at least one cycle of chemotherapy. The recommended dose of KRN8602 alone was 40 mg/m2. Dose escalation was limited by neutropenia. The recommended dose of KRN8602 with filgrastim was 70 mg/m2, and limiting toxicities were neutropenia, diarrhea, and vomiting. The most commonly experienced nonhematologic toxicity was nausea and vomiting. Alopecia and mucositis were infrequent and mild. Pharmacokinetic parameters showed substantial variation, although the area under the plasma concentration-time curve (AUC) and maximum concentration both increased with dose. There was no relationship between pharmacokinetic parameters and toxicity. CONCLUSION: KRN8602 at doses of 40 mg/m2 when administered alone and 70 mg/m2 when administered with filgrastim appeared to be manageable. The major DLTs were neutropenia and, at higher doses, diarrhea and vomiting. The efficacy of this drug is currently being tested in phase II studies.
Adult↗
An approach to the problems of diagnosing and treating adult smear-negative pulmonary tuberculosis in high-HIV-prevalence settings in sub-Saharan Africa.
The overlap between the populations in sub-Saharan Africa infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis has led to an upsurge in tuberculosis cases over the last 10 years. The relative increase in the proportion of notified sputum-smear-negative pulmonary tuberculosis (PTB) cases is greater than that of sputum-smear-positive PTB cases. This is a consequence of the following: the association between decreased host immunity and reduced sputum smear positivity; the difficulty in excluding other HIV-related diseases when making the diagnosis of smear-negative PTB; and an increase in false-negative sputum smears because of overstretched resources. This article examines problems in the diagnosis and treatment of smear-negative PTB in high-HIV-prevalence areas in sub-Saharan Africa. The main issues in diagnosis include: the criteria used to diagnose smear-negative PTB; the degree to which clinicians actually follow these criteria in practice; and the problem of how to exclude other respiratory diseases that can resemble, and be misdiagnosed as, smear-negative PTB. The most important aspect of the treatment of smear-negative PTB patients is abandoning 12-month "standard" treatment regimens in favour of short-course chemotherapy. Operational research is necessary to determine the most cost-effective approaches to the diagnosis and treatment of smear-negative PTB. Nevertheless, substantial improvement could be obtained by implementing the effective measures already available, such as improved adherence to diagnostic and treatment guidelines.
AIDS-Related Opportunistic Infections↗
Commentary: making tuberculosis treatment available for all.
Tuberculosis is one of the major public health problems that WHO has tackled throughout the last 50 years. During the pre-clinical era treatment consisted of the use of special diets, bed rest in sanatoria, and lung collapse therapy. The case fatality rate 5 years after diagnosis was 50% and treatment in a sanatorium was expensive and available only to the privileged few. The demonstration in the 1960s that ambulatory treatment of tuberculosis (one year of isoniazid and p-aminosalicylic acid) was as effective for patients and their families as treatment in a sanatorium heralded the beginning of the end of the sanatorium era and the beginning of the era of domiciliary treatment, which could be made widely available to many people with the disease in countries where its prevalence was high. Subsequent refinements in combination therapy led, in the 1960s, to the development of intermittent regimens and, in the 1970s, to short-course regimens following the introduction of rifampicin. The currently recommended WHO strategy for tuberculosis control is termed DOTS, which is being promoted globally to free the world from this millennia-old scourge.
Ambulatory Care↗
Evaluation and determinants of outcome of tuberculosis treatment.
The most important determinant of the outcome of treatment of tuberculosis (TB) patients is the access that they have to reliable diagnosis and treatment services organized within a national tuberculosis programme (NTP) as part of DOTS, the name of the WHO-recommended TB control strategy. Accurate evaluation of treatment outcomes requires inclusion of all patients diagnosed, including those not registered; part of routine NTP management should therefore involve regular cross-checks between laboratory diagnostic registers and NTP treatment registers. Finally, control services should take into consideration the type of TB, the presence of concomitant infection with human immunodeficiency virus (HIV), and patient characteristics.
HIV Seropositivity↗
Management of pulmonary tuberculosis suspects with negative sputum smears and normal or minimally abnormal chest radiographs in resource-poor settings.
SETTING: Queen Elizabeth Central Hospital, Blantyre, Malawi. OBJECTIVES: 1) To determine the proportion of pulmonary tuberculosis (PTB) suspects with negative sputum smears and a normal/minimally abnormal chest radiograph (CXR) who are culture-positive for Mycobacterium tuberculosis, and 2) to determine how many develop smear or radiographic evidence of PTB (TB CXR) during follow-up. METHODS: PTB suspects with negative sputum smears and a normal/minimally abnormal CXR were given a second course of antibiotics and followed up at 3-week intervals over 3 months with repeat sputum smears and chest radiography. RESULTS: Of 79 patients (38 men and 41 women, mean age 33 years) with negative smears and a normal/minimally abnormal CXR, 16 (21%) were culture-positive for M. tuberculosis. Of 15 culture-positive patients who were alive and attended follow-up, seven (47%) developed a TB-CXR by 3 months. Of 41 culture-negative patients who were alive and attended follow-up, 13 (32%) developed a TB-CXR, including one patient who became sputum smear-positive. TB-CXRs were found only in patients with a cough. CONCLUSION: TB suspects with negative smears and normal/minimally abnormal CXRs in high human immunodeficiency virus (HIV) prevalent countries should be given a second course of antibiotics. If cough improves, patients can be advised not to return for further follow-up. If cough continues, patients should return for further follow-up with sputum smear examination and chest radiography. Approximately 50% of those who have culture-positive PTB will develop a TB-CXR by 3 months and can be identified if radiographic facilities are available.
Adult↗
Tuberculosis in a prison population in Malawi.
BACKGROUND: Much concern has been expressed about the high prevalence of tuberculosis in prisons in industrialised countries. Since there is almost no information from developing countries, we investigated the rate of pulmonary tuberculosis in a large prison in Malawi. METHODS: Between May and July, 1996; we carried out an active case-finding survey in Zomba Central Prison, Malawi, through the National Tuberculosis Control Programme. We interviewed prisoners, and those with a cough of at least 1 week's duration were screened by sputum-smear microscopy. If microscopy was negative, prisoners underwent chest radiography. We offered HIV testing, with voluntary consent and counselling before and after tests, to all prisoners, whether positive or negative for pulmonary tuberculosis. FINDINGS: 914 (70%) of 1315 prisoners were screened (905 men, nine women; mean age 30 years [SD 11]). 47 (5%) screened prisoners (all men) had pulmonary tuberculosis: 14 were taking antituberculosis treatment and 33 were undiagnosed at the start of the study; 18 were sputum-smear positive and 15 were sputum-smear negative. 16 (73%) of 22 prisoners with previously undiagnosed pulmonary tuberculosis and 30 (75%) of 40 prisoners with cough but no evidence of pulmonary tuberculosis were HIV seropositive. In all prisoners, except one, symptoms of pulmonary tuberculosis had developed after they had entered prison. INTERPRETATION: We found a high rate of pulmonary tuberculosis in Zomba Central Prison, which suggests active transmission of tuberculosis. As a result of this study, the National Tuberculosis Control Programme has implemented interventions in eight prisons in Malawi to improve tuberculosis control, including collection of health data, education of prisoners and clinical staff about tuberculosis, active screening of prisoners for pulmonary tuberculosis by sputum-smear microscopy, and active case-finding in the prisons.
Adult↗
The scourge of HIV-related tuberculosis: a cohort study in a district general hospital in Malawi.
Malawi is similar to a number of other African countries in having an escalating, HIV-related, tuberculosis (TB) epidemic. A prospective study was carried out to determine the pattern of disease and HIV serostatus in unselected, adult, TB patients consecutively admitted to a large, district general hospital in Zomba (in the Southern region of Malawi). Clinical details were obtained, from the district TB register, for the 714, adult TB patients, aged > or = 15 years, who were registered with the district TB officer between 1 July and 31 December in 1995. Patients were counselled, and offered HIV testing using an ELISA and particle agglutination test. Concordant HIV-test results were available for 686 (96%) of the subjects: 547 (80%) of these were HIV-seropositive and 139 seronegative. The HIV-positive patients were significantly younger than the HIV-negative patients and significantly more HIV-positive patients were males (P < 0.05 for each). The proportions of HIV-positive subjects who were new patients, had been previously treated for TB, had pulmonary TB (PTB), had smear-positive PTB or had different types of extrapulmonary TB were similar to those of the HIV-negative. A high percentage of an unselected cohort of adult TB patients admitted to a district, general hospital in Malawi, particularly of the younger age groups was therefore HIV-positive. The pattern of disease was uninfluenced by the HIV serostatus. The large number of cases registered emphasises the severity of the current epidemic of TB in Malawi and its impact upon young adults.
AIDS-Related Opportunistic Infections↗
Patient and surgeon satisfaction with extremity blockade for surgery in remote locations.
In a practice that may be unique to military health care, extremity nerve blocks are established by anesthesiologists before transporting the patient to a remote clinic for surgery without further monitoring by anesthesia personnel. The safety and acceptance of this practice was assessed through a prospective survey of the surgeons and their patients. Six hundred seventy-seven blocks were performed in a 1-yr period with no adverse events related to this practice. Completed surveys were received from 406 (60%) of the surgeons and 232 (34%) of the patients. Of the blocks performed, 638 (94%) were brachial plexus blocks, with axillary blocks accounting for 87% of the brachial plexus blocks. Of the responding patients, 78% stated that they would be willing to undergo a repeat block. The surgeons were satisfied with the operating conditions in 96% of the cases. This study supports the safety and efficacy of this practice.
Adolescent↗
Tuberculosis care in community care organizations in sub-Saharan Africa: practice and potential.
SETTING: Community care organizations in sub-Saharan Africa. OBJECTIVES: To evaluate current tuberculosis (TB) care in community health care organizations in sub-Saharan Africa, to assess their potential contribution to tuberculosis care, and to develop a model for expanded community participation in effective TB control. DESIGN: Quantitative assessment of tuberculosis care and cross-sectional assessment of qualitative measures in 14 community care organizations in Uganda, Zambia, South Africa and Malawi. RESULTS: The community care organizations assessed mainly provided care for human immunodeficiency virus (HIV) and aquired immune deficiency syndrome (AIDS) patients, and received funding from non-governmental organizations. Shortcomings in tuberculosis care included delays in diagnosis (which was often not based on sputum examination), drug shortages, low completion rates, high default rates, inadequate recording, little interaction with government tuberculosis programmes, and inadequate training of staff. However, one organization that provided primarily tuberculosis care and collaborated closely with the district tuberculosis programme and hospital attained a high treatment completion rate. The strong points of the community care organizations that favour a potential role of community participation in tuberculosis care were accessibility and staff motivation. CONCLUSION: Despite most community care organizations' shortcomings in tuberculosis care, they do have the potential to improve the care of tuberculosis patients, thus reducing the load on overstretched health facilities. Their potential impact on tuberculosis control depends on their population coverage and sustainability. HIV/AIDS community care organizations with strengthened management of tuberculosis care could serve as a model for expanded community participation in tuberculosis control. Operational research is needed to assess the feasibility and cost-effectiveness of community-based TB care.
AIDS-Related Opportunistic Infections↗
The pattern of tuberculosis in Queen Elizabeth Central Hospital, Blantyre, Malawi: 1986-1995.
SETTING: Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. OBJECTIVE: To determine the pattern of tuberculosis (TB) cases over a period of ten years. DESIGN: TB registers for QECH for the years 1986-1995 (January 1st to December 31st) were obtained and clinical information on the type of TB in each patient was recorded. Human immunodeficiency virus (HIV) test results of adults with smear-positive pulmonary TB (PTB) and children with TB between 1993 and 1996 were recorded from case notes. RESULTS: There were 19,377 TB cases, 10,982 men and 8,395 women, registered over the ten-year period. Of these, 4,691 (24%) cases were in children aged 0-14 years and 11,890 (61%) cases were in adults aged 15-44 years. The number of cases increased from 657 in 1986 to 2,734 in 1995, and the proportion of cases with extra-pulmonary TB (EPTB) rose from 11% in 1986 to 33% in 1995. The largest increase in cases was in children and in young adults aged 15-44 years. In all age groups, PTB was more common than EPTB. There were significant increases in the proportion of adult TB cases with pleural effusion. Of those who were tested, 72% of adults with smear-positive PTB and 64% of children with TB were found to be HIV-seropositive. CONCLUSION: There has been a dramatic increase in cases of TB and changes in disease pattern in QECH during the last 10 years, which is related to the HIV epidemic.
AIDS-Related Opportunistic Infections↗
Tuberculous pericardial effusion: a prospective clinical study in a low-resource setting--Blantyre, Malawi.
SETTING: Queen Elizabeth Central Hospital, Blantyre, Malawi. OBJECTIVE: Review of clinical and investigation findings and outcome, using a standard management protocol, in human immunodeficiency virus (HIV)-positive and HIV-negative patients with tuberculous pericardial effusion, in a low-resource setting in sub-Saharan Africa. DESIGN: A prospective study under field conditions of adult patients with tuberculous pericardial effusion admitted to Queen Elizabeth Central Hospital between May 1993 and December 1994. RESULTS: In total 77 patients fulfilled the diagnostic criteria for tuberculous pericardial effusion. Of 74 patients sero-tested, 68 (92%) were HIV seropositive. Classical clinical features of pericardial effusion were often absent. Many patients had no other clinical features of HIV infection. Outcome compared favourably with quoted survival rates from the pre-HIV era. CONCLUSION: Tuberculous pericardial effusion is a common problem in Blantyre and is strongly associated with HIV infection. Successful management using a standard protocol is possible in a low-resource setting.
AIDS-Related Opportunistic Infections↗