An uncommon, unilateral motor variation of the intercostobrachial nerve.

The intercostobrachial nerve (ICBN) is commonly defined as a purely sensory nerve supplying the skin of the lateral chest wall, axilla, and medial arm. However, numerous branching patterns and distributions, including motor, have been reported. This report describes an uncommon variant of the right ICBN observed in both an 86-year-old white female cadaver and a 77-year-old white male cadaver. In both cases the ICBN presented with an additional muscular branch, termed the "medial pectoral branch", piercing and therefore innervating the pectoralis major and minor muscles. Clinically, the ICBN is relevant during surgical access to the axilla and can result in sensory deficits (persistent pain/loss of sensory function) to this region following injury. However, damage to the variation observed in these cadavers may result in additional partial motor loss to pectoralis major and minor.

Tackling tuberculosis in sub-Saharan Africa: EDCTP achievements and the road ahead.

The European and Developing Countries Clinical Trials Partnership (EDCTP) was established in 2003 to accelerate the development of medical interventions for tuberculosis (TB), human immunodeficiency virus (HIV) and malaria, with a particular focus on Phase II and III clinical trials. Between 2003 and 2015, the first EDCTP programme committed €65.6 million to research on TB and TB-HIV co-infection. The programme made a significant contribution to the first three elements of the DOTS TB control strategy, which mobilised European and African funding for TB-related research and generated important evidence on TB diagnostics and treatment regimens. As well as informing the development of international policy on TB diagnosis and treatment, the programme also significantly enhanced the capacity of countries in sub-Saharan Africa to undertake clinical trials and associated clinical research. The lessons learned from the first EDCTP programme have informed the development of a second, expanded EDCTP programme, EDCTP2, which was launched in 2014, and is due to run until 2024. One key lesson is the need for continued partnerships to fight the global threat of TB.

Strengthening capacity, collaboration and quality of clinical research in Africa: EDCTP Networks of Excellence.

Developing countries bear 90% of the global disease burden, but only access about 10% of globally available health research funding. Weak south-south networking hampers effective use of limited resources, production of critical mass of quality scientists, career opportunities and incentives to retain the few available scientists. The south must urgently act strategically to accelerate generation of talented scientists, create enabling environment and incentives to retain scientists and attract back those in diaspora. The creation of strong networks of excellence for clinical research among southern academic and research institutions is a novel strategic approach championed by European and Developing Countries Clinical Trials Partnership to achieve the aforementioned goals and mitigate the high disease burden. It will promote strong collaboration, resource sharing and cross-mentorship allowing each partner to grow with complementary capacities that support each other rather than compete negatively. It will enable the south and Africa in particular to participate actively and own the means for solving its own health problems and raise the professional quality and capacity of southern institutions to forge better and equal partnership with northern institutions.

Geographical Information Systems in TB control

Geographical Information Systems (GIS) is becoming a useful tool in disease control by health planners. However little is known about its potential in tuberculosis (TB) control. In 2000 the National TB Programme (NTP) in Malawi assessed its usefulness. Routinely collected case-finding data from the 3 previous years (1997 to 1999) were entered into a system containing a digital map of Malawi. District performance was mapped. We concluded that GIS may be complementary in monitoring TB programme performance; and may be useful for target setting; advocacy; and research. World Health Organisation (WHO) now provides free GIS software (Health Mapper) and training. However; the use of GIS in TB control still needs further piloting and expansion without constraining the locally available resources or disrupting the present TB data management system

Audit of outpatient department management of patients with respiratory symptoms in Lilongwe

Setting: 6 outpatient departments (OPD) of 3 hospitals and 2 health centres in Lilongwe. Objective: To assess the existing health worker practice in providing care to patients with respiratory symptoms in the OPD. Methods:Between 1 and 31 July 2002 exit interviews were conducted with patients from OPD consultation rooms and possessing a prescription for respiratory diseases. Verbal confirmation of the patients' complaints was done; patients' OPD notes were reviewed and a questionnaire was completed. Data was collected for patients aged 5 and above. Results: 3001 patients with median age of 27 years were enrolled in the study. 1203 (40) were male. 80 had made several visits to the OPD with the same symptom. In some cases verbal reports of main symptoms did not match with those recorded on OPD notes. 511 (17 ) patients reported that a clinician listened to their chest. Antibiotics were prescribed to 2501 (83.3 ) patients for various respiratory complaints. Similarly analgesics were prescribed to 2671 (89) patients. Steroids were prescribed to 32 (1.2) patients and a bronchodilator was prescribed to 185 (6.2) patients. Only 56 (2) patients were referred to another level of care. Conclusion: Management of patients with respiratory symptoms in Lilongwe is characterised by increased usage of antibiotics; analgesics and inability of health workers to examine the patients' chests. Referral to other care facilities is also uncommon. More investigations are required to understand the causes of this practice so that corrective measures are designed and implemented

Auditing the new decentralised oral treatment regimens in Malawi.

SETTING: All 44 non-private hospitals in Malawi treating tuberculosis (TB) cases in which oral regimens were used allowing patients during the initial phase to receive directly observed treatment (DOT) from health centres or guardians at home. OBJECTIVES: A country-wide audit of the oral regimens to determine: 1) TB ward bed occupancy rates, 2) patient DOT options, 3) patients' knowledge of treatment and 4) treatment outcomes compared to those obtained with previous treatment regimens. DESIGN: Retrospective data collection using registers and treatment cards. Prospective interviews with patients. Inspections of TB wards. RESULTS: There were 1513 TB beds occupied by 807 (53%) TB patients. Over 50% of 4793 patients registered with different types of TB chose guardian-based DOT. For 266 patients with pulmonary TB the correct knowledge about total duration of treatment (45%), all three DOT options (62%) and the months for giving follow-up sputum (16%), was poor. There were differences in treatment outcomes between TB patients on oral compared with previous regimens. With oral regimens, rates of unknown outcome were high. CONCLUSION: Oral treatment regimens are associated with reduced bed occupancy rates on TB wards. However, rates of unknown outcome are increased, and TB control is therefore weakened.

Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB.

SETTING: Zomba Central Hospital, Malawi. OBJECTIVES: To determine the outcome of all adult patients who were registered for tuberculosis (TB) treatment 7 years previously according to initial human immunodeficiency virus (HIV) status and type of TB. DESIGN: A retrospective cohort study of adult patients registered for TB treatment between July and December 1995. Follow-up at patients' homes was performed at the end of treatment, at 32 months and at 84 months (7 years) from the time of TB registration. FINDINGS: Eight hundred and twenty-seven TB patients were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV-positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152 (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100 person-years of observation. HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7-2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6) and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than in patients with smear-positive PTB. CONCLUSIONS: There was a high mortality rate in TB patients during and after anti-tuberculosis treatment. Adjunctive treatments to reduce death rates are urgently needed.

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.

Tuberculosis control in Malawian prisons: from research to policy and practice.

Following an operational research study in Zomba Central Prison, Malawi, in 1996, the National Tuberculosis Control Programme (NTP) and the Prison Medical Services worked together to improve the diagnosis and treatment of tuberculosis (TB) in prisoners. Prisoners are screened for TB on admission and during their prison sentences. A system was established of treating patients, according to NTP guidelines, while in prison and on discharge from prison. Monitoring and evaluation is undertaken using TB officers at district and regional level, and 6-monthly meetings are held with all stakeholders and the central unit to collate data and review prison TB control activities.

Management and outcome of tuberculosis patients who fail treatment under routine programme conditions in Malawi.

SETTING: All 43 non-private hospitals (three central, 22 district and 18 mission) in Malawi that registered and treated TB cases between 1 July 1999 and 30 June 2000. OBJECTIVES: To determine 1) the number of new smear-positive PTB patients who failed treatment, 2) the management of patients who failed, 3) their treatment outcome and 4) culture and drug sensitivity results. DESIGN: Retrospective data collection using TB registers and laboratory culture and drug sensitivity registers. RESULTS: Ninety patients failed treatment, 60 (67%) at 5 months and 30 (33%) at the end of treatment. Sixty-four (71%) failure patients were registered and commenced on anti-tuberculosis treatment. Of these, 95% were registered in the same hospital as before, 89% were given a different TB registration number, 67% were correctly registered as 'failures' and 61% were treated within one month of failing the previous regimen. Forty-eight (75%) re-treated patients were cured. Only 31 (34%) of the 90 patients had sputum sent for culture and drug sensitivity testing. In 11 patients with cultures of M. tuberculosis, eight were fully sensitive and three had mono-resistance to isoniazid. CONCLUSION: While the outcome of failure patients who start retreatment is good, there are several programmatic deficiencies that need to be corrected.

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.

Defining and assessing the maximum number of visits patients should make to a health facility to obtain a diagnosis of pulmonary tuberculosis.

SETTING: All non-private hospitals in Malawi. OBJECTIVES: To determine 1) how many patients with pulmonary tuberculosis (PTB) exceed the maximum number of visits needed for registration as defined by the National Tuberculosis Control Programme, and 2) the factors associated with this delay. DESIGN: Cross-sectional study interviewing hospitalised patients with new smear-positive and smear-negative PTB. RESULTS: Of 380 patients with PTB admitted to the 44 hospitals visited between April and June 2002, 329 (212 smear-positive and 117 smear-negative PTB) were interviewed: 64 (30%) smear-positive PTB patients needed more than five visits, and 44 (37%) smear-negative PTB patients needed more than six visits before being registered and started on treatment. Factors associated with exceeding the maximum number of visits were the first visit being to a health centre, submission of > 1 set of sputum specimens, and > 1 course of antibiotics. The main consequence of exceeding the maximum number of visits was increased duration of cough and increased time spent at health facilities. CONCLUSION: One third of patients exceed the maximum number of visits for registration of PTB. The main consequence of this is an increased duration of cough and an increased time spent at health facilities. Ways to reduce this delay need to be found.

Decentralisation of tuberculosis services in an urban setting, Lilongwe, Malawi.

SETTING: Lilongwe, the capital of Malawi, one of the countries in the world badly affected by the human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) epidemic. OBJECTIVE: In the face of a rising burden of tuberculosis (TB) fuelled by HIV, to evaluate the impact on the Lilongwe district tuberculosis programme performance of decentralisation of TB services, including extending the range of options for supervision of directly observed treatment (DOT) during the initial phase of treatment, and using a fully oral, intermittent regimen. DESIGN: Prospective assessment under programme conditions of 1) duration of hospital stay, 2) bed occupancy and 3) 8-month treatment outcomes in a cohort of patients registered before (1997) and after (1998) the introduction of decentralisation of TB services. RESULTS: The number of new patients (all forms) registered in Lilongwe district was 3144 in 1997 and 3761 in 1998. There were significant differences (P < 0.05) between all outcomes that were compared. In 1998, bed occupancy dropped by 38%; among smear-positive patients, the average length of hospital stay fell from 58 days in 1997 to 16, the cure rate was higher (64% vs. 56%), default rate was lower (5% vs. 19%), and treatment completion rate was lower (2% vs. 4%); among smear-negative patients, the treatment completion rate was higher (50% vs. 33%), default rate was lower (23% vs. 55%), and death rate was higher (17% vs. 4%). This death rate is attributable to improved follow-up and reporting of outcomes, rather than to increased deaths. CONCLUSION: Programme implementation of decentralised TB services in Lilongwe, including an extended range of supervision options for DOT and the use of an ambulatory treatment regimen, achieved reduced hospital stay and bed occupancy and good treatment outcomes.

Cost and cost-effectiveness of increased community and primary care facility involvement in tuberculosis care in Lilongwe District, Malawi.

SETTING: Lilongwe District, Malawi. OBJECTIVE: To assess the cost and cost-effectiveness of new treatment strategies for new pulmonary tuberculosis patients, introduced in 1997. METHODS: For new smear-positive pulmonary patients, two strategies were compared: 1) the strategy used until the end of October 1997, involving 2 months of hospitalisation at the beginning of treatment, and 2) a new decentralised strategy introduced in November 1997, in which patients were given the choice of in- or outpatient care during the first 2 months of treatment. For new smear-negative pulmonary patients, the two strategies compared were 1) the strategy used until the end of October 1997, which did not require any direct observation of treatment (DOT) and 2) a new community-based strategy introduced in November 1997, which required DOT by a community member 'guardian' or a health worker for the first 2 months of treatment. Costs were analysed from the perspective of health services, patients, and the community in 1998 US dollars, using standard methods. Cost-effectiveness was calculated as the cost per patient cured (smear-positive cases) and as the cost per patient completing treatment (new smear-negative cases). FINDINGS: For new smear-positive patients, the cost per patient treated was dollars 456 with the conventional hospital-based strategy, and dollars 106 with the new decentralised strategy. Costs fell by 54% for health services and 58% for patients. The cost per patient cured was dollars 787 for the conventional hospital-based strategy, and dollars 296 for decentralised treatment. For smear-negative patients, the cost per patient treated was dollars 67 with the conventional unsupervised strategy, and dollars 101 with the community-based DOT strategy. Costs increased for health services, patients and guardians. Cost-effectiveness was similar with both strategies, at around dollars 200 per patient completing treatment. When new smear-positive and new smear-negative patients were considered together, the new strategies were associated with a 50% reduction in total annual costs. CONCLUSION: There is a strong economic case for expansion of decentralisation and community-based DOT in Malawi. Further investment in training and programme supervision may help to increase effectiveness.

Decentralisation of treatment for patients with tuberculosis in Malawi: moving from research to policy and practice.

SETTING: Five districts in Malawi. OBJECTIVE: A new oral anti-tuberculosis treatment regimen with different directly observed treatment (DOT) choices in the initial phase of treatment was introduced for new patients in the five districts. The objectives were to determine 1) the site of DOT during the initial phase of treatment, and 2) the effectiveness of the new regimen. DESIGN: Prospective data collection on all tuberculosis (TB) patients registered in a phased approach between 1 July 1997 and 31 December 1998, including site of DOT option in initial phase of treatment, 2-month and 8-month treatment outcomes, 2-month sputum smear conversion in smear-positive pulmonary tuberculosis (PTB) patients and in-patient hospital bed days. RESULTS: There were 6335 new patients: 2671 (42%) with smear-positive PTB, 2211 (35%) with smear-negative PTB and 1453 (23%) with extra-pulmonary TB. The site of the initial phase of treatment was determined in 5790 patients: 1759 (30%) received DOT from guardians, 1465 (25%) from a health centre, 753 (13%) as out-patients from the hospital TB ward and 1813 (32%) remained in hospital. Eight-month treatment completion was 67% for smear-positive PTB patients, 51% for smear-negative PTB patients and 56% for extra-pulmonary TB patients. Two-month outcomes and 8-month treatment outcomes for all out-patient sites of supervision were satisfactory, except that a higher proportion of smear-positive PTB patients under guardian DOT failed to smear convert at 2 months. Over two-thirds of patients received ambulatory treatment out of hospital during the initial phase. CONCLUSION: The new treatment strategy, tested in five districts, was associated with a reduction in hospital bed days and satisfactory treatment outcomes. The results of these studies were vital in helping the National TB Control Programme make an informed decision about phased expansion of the strategy countrywide.

Preventing recurrent tuberculosis in high HIV-prevalent areas in sub-Saharan Africa: what are the options for tuberculosis control programmes?

Several studies conducted in sub-Saharan Africa have pointed to an increased risk of recurrent TB in patients who are HIV-seropositive. Routine case notification data from the Malawi Tuberculosis Programme, which has improved its registration practices in the last two years, shows that recurrent TB (smear-positive and smear-negative TB) constitutes 9% of total notifications. The objectives of reducing rates of recurrent TB are 1) to complement other interventions to decrease TB incidence rates and transmission of disease, 2) to reduce TB-specific morbidity and mortality and 3) to restore confidence amongst health care staff and patients about the effectiveness of the current TB control strategy. Four possible options for reducing recurrent TB are discussed, and for each option this includes the evidence for effectiveness, current practice and operational considerations. The options are 1) using rifampicin and isoniazid (RH) in the continuation phase of treatment, 2) extending the duration of the continuation phase, 3) providing post-treatment isoniazid prophylaxis to HIV-positive patients who have completed treatment and 4) treating HIV-positive TB patients with highly active antiretroviral therapy (HAART). The last three options all require that TB patients know their HIV serostatus. The authors suggest that this issue of recurrent TB should be considered as one of the important areas for debate and action when considering the dual TB/HIV epidemic.

TNF-alpha promoter single nucleotide polymorphisms are markers of human ancestry.

We present a map of single nucleotide polymorphisms (SNPs) in the human tumor necrosis factor (TNF)-alpha promoter based upon exploratory sequencing of 333 human TNF-alpha gene promoters from individuals of distinct ancestral backgrounds. We detect 10 TNF-alpha promoter SNPs that occur with distinct frequencies in populations of different ancestry. Consistent with these findings, we show that two TNF-alpha SNPs, the -243 SNP and the -856 SNP, are the first SNP markers of a sub-Saharan African-derived extended haplotype and an Amerindian HLA haplotype, respectively. Comparisons of TNF-alpha promoter SNP allele frequencies can thus help elucidate variation of HLA haplotypes and their distribution among existing ethnic groups and shed light into the history of human populations.

Is oral intermittent initial phase anti-tuberculosis treatment associated with higher mortality in high HIV-prevalent areas in sub-Saharan Africa?

The Malawi Tuberculosis Programme has evaluated an oral ambulatory treatment regimen (2R3H3Z3E3/6HE) in five districts, and observed a mortality rate of 23% in 2671 new patients with smear-positive pulmonary tuberculosis (PTB). Three studies were performed comparing treatment outcomes between patients treated with 2R3H3Z3E3/6HE and 2SRHZ/6HE using historical data in the same districts and concurrent data in different districts. Using historical comparisons, mortality was significantly higher with 2R3H3Z3E3/6HE than 2SRHZ/6HE. Using concurrent comparisons, mortality was similar, although there was a higher death rate in the first month with the intermittent regimen. The intermittent regimen may be inferior to the established regimen.