Second nationwide anti-tuberculosis drug resistance survey in Namibia.

SETTING: Namibia ranks among the 30 high TB burden countries worldwide. Here, we report results of the second nationwide anti-TB drug resistance survey.OBJECTIVE: To assess the prevalence and trends of multidrug-resistant TB (MDR-TB) in Namibia.METHODS: From 2014 to 2015, patients with presumptive TB in all regions of Namibia had sputum subjected to mycobacterial culture and phenotypic drug susceptibility testing (DST) for rifampicin, isoniazid, ethambutol and streptomycin if positive on smear microscopy and/or Xpert MTB/RIF.RESULTS: Of the 4124 eligible for culture, 3279 (79.5%) had Mycobacterium tuberculosis isolated. 3126 (95%) had a first-line DST completed (2392 new patients, 699 previously treated patients, 35 with unknown treatment history). MDR-TB was detected in 4.5% (95%CI 3.7-5.4) of new patients, and 7.9% (95%CI 6.0-10.1) of individuals treated previously. MDR-TB was significantly associated with previous treatment (OR 1.8, 95%CI 1.3-2.5) but not with HIV infection, sex, age or other demographic factors. Prior treatment failure demonstrated the strongest association with MDR-TB (OR 17.6, 95%CI 5.3-58.7).CONCLUSION: The prevalence of MDR-TB among new TB patients in Namibia is high and, compared with the first drug resistance survey, has decreased significantly among those treated previously. Namibia should implement routine screening of drug resistance among all TB patients.

Community-based multi-disease prevention campaigns for controlling human immunodeficiency virus-associated tuberculosis.

Human immunodeficiency virus (HIV) infection increases the risk of tuberculosis (TB) 21-34 fold, and has fuelled the resurgence of TB in sub-Saharan Africa. The World Health Organization (WHO) recommends the Three I's for HIV/TB (infection control, intensified case finding [ICF] and isoniazid preventive therapy) and earlier initiation of antiretroviral therapy for preventing TB in persons with HIV. Current service delivery frameworks do not identify people early enough to maximally harness the preventive benefits of these interventions. Community-based campaigns were essential components of global efforts to control major public health threats such as polio, measles, guinea worm disease and smallpox. They were also successful in helping to control TB in resource-rich settings. There have been recent community-based efforts to identify persons who have TB and/or HIV. Multi-disease community-based frameworks have been rare. Based on findings from a WHO meta-analysis and a Cochrane review, integrating ICF into the recent multi-disease prevention campaign in Kenya may have had implications in controlling TB. Community-based multi-disease prevention campaigns represent a potentially powerful strategy to deliver prevention interventions, identify people with HIV and/or TB, and link those eligible to care and treatment.

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.

Evidence for high-m secondary islands induced by large low-m islands in a tokamak plasma.

Small-scale structures with high poloidal mode numbers (m=10-20) have been observed in the TEXTOR tokamak plasma with pulsed radar reflectometry and an electron cyclotron emission diagnostic, in conjunction with large 2/1 and 1/1 islands. The small islands have a peaked density profile, similar to that of the simultaneously observed large-scale 2/1 islands. This together with the observation that high-frequency density and temperature fluctuations are very pronounced near the X points of the large islands hints to a strongly perturbed magnetic topology around the X points.

[The Dutch contribution to worldwide tuberculosis control: Royal Netherlands Association for the Prevention of Tuberculosis (KNCV) Tuberculosis Foundation]. / De Nederlandse bijdrage aan de wereldwijde tuberculosebestrijding: Koninklijke Nederlandse Centrale Vereniging tot bestrijding der Tuberculose (KNCV) Tuberculosefonds.

During the 1960s and 1970s tuberculosis was severely neglected in developing countries. Less than 50% of patients diagnosed were cured. However, an international breakthrough occurred in the 1980s with the excellent results from a short-course treatment: 80% cured. This was first achieved in Tanzania. Since 1993, this innovative approach has been known throughout the world as the 'directly observed treatment, short-course' (DOTS) strategy. Over the past 15 years the interest in international tuberculosis control has substantially improved. There has been a strong increase in the number of initiatives to rapidly extend the use of DOTS so that internationally set targets for tuberculosis control can be met (by 2005, 70% of infectious patients detected and 85% of these cured). The highest priority has been given to the 22 countries with the highest incidence of tuberculosis. There has been a significant increase in the number of countries implementing DOTS. The average rate of cure using DOTS is 80%. Since the 1970s the Royal Netherlands Tuberculosis Association (Koninklijke Nederlandse Centrale Vereniging tot Bestrijding der Tuberculose (KNCV)) has been involved in many international initiatives, such as the Stop TB Partnership, and it has participated in the development and implementation of policies for tuberculosis and tuberculosis-HIV control. However, there are still causes for concern: the number of tuberculosis patients is increasing in particular due to the tuberculosis-HIV co-epidemic and it is estimated that only 1 in 4 infectious tuberculosis patients were detected and treated in DOTS programmes during the year 2000.

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.

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.

Resources for controlling tuberculosis in Malawi.

OBJECTIVE: To document resources for controlling tuberculosis (TB) in Malawi. METHODS: We performed a countrywide study of all 43 hospitals (3 central, 22 district and 18 mission) which register and treat patients with TB. To collect data for 1998 on the TB-related workload, diagnostic facilities, programme staff and treatment facilities, we used laboratory, radiographic and TB registers, conducted interviews and visited hospital facilities. FINDINGS: The data show that in 1998, 88,257 TB suspects/patients contributed approximately 230,000 sputum specimens for smear microscopy, 55,667 chest X-rays were performed and 23,285 patients were registered for TB treatment. There were 86 trained laboratory personnel, 44 radiographers and 83 TB programme staff. Of these, about 40% had periods of illness during 1998. Approximately 20% of the microscopes and X-ray machines were broken. Some 16% of the hospital beds were designated for TB patients in special wards, but even so, the occupancy of beds in TB wards exceeded 100%. Although stocks of anti-TB drugs were good, there was a shortage of full-time TB ward nurses and 50% of district hospitals conducted no TB ward rounds. In general, there was a shortage of facilities for managing associated HIV-related disease; central hospitals, in particular, were underresourced. CONCLUSION: Malawi needs better planning to utilize its manpower and should consider cross-training hospital personnel. The equipment needs regular maintenance, and more attention should be paid to HIV-related illness. The policies of decentralizing resources to the periphery and increasing diagnostic and case-holding resources for central hospitals should be continued.

A unified treatment regimen for new cases of tuberculosis in resource-poor countries: a study in a rural district in Malawi.

An oral ambulatory unified treatment regimen was introduced in Ntcheu District, Malawi, between April 1996 and June 1997 for all new patients (600) with tuberculosis (TB). There was no change in the case finding pattern compared with the previous 5 years; 65% of new smear-positive pulmonary tuberculosis (PTB) patients completed treatment, not significantly different compared with the previous 3 years. Treatment completion was significantly lower in patients with smear-negative PTB and extra-pulmonary tuberculosis, due mainly to high mortality rates (40% and 41% respectively). In a rural district with high human immunodeficiency virus sero-prevalence rates in TB patients, case finding and end of treatment outcome of the oral unified regimen were comparable to those of previous regimens.

Short-course instead of long-course chemotherapy for smear-negative patients in sub-Saharan Africa.

The use of short-course chemotherapy (SCC) in directly-observed treatment, short-course (DOTS) programmes in sub-Saharan Africa was often restricted to patients with infectious and serious forms of tuberculosis, because of high costs of such regimens. With reduced drug prices and wide-scale substitution of thiacetazone by ethambutol in the continuation phase of treatment, various short-course regimens are now available at the same or even lower costs than long-course regimens. Several DOTS programmes are considering extending access to short-course chemotherapy to non-infectious patients, or have done so already. The authors provide an overview of the issues regarding the debate on the introduction of universal SCC in national tuberculosis control programmes in low-income countries in sub-Saharan Africa. They advise on a low-risk strategy to avoid the emergence of rifampicin resistance as a consequence of the wide availability of rifampicin associated with universal short-course, and strengthening of the health system to maintain high performance levels in diagnosis and treatment.

Sputum-smear examination in patients with extrapulmonary tuberculosis in Malawi.

In Malawi, it has been the practice for several years to obtain sputum for smear microscopy of acid-fast bacilli (AFB) from all patients with extrapulmonary tuberculosis (EPTB). We audited this practice, and determined in patients aged > or = 15 years (i) the proportion of EPTB patients who had sputum smears examined, (ii) the number of sputum smears examined per patient, and (iii) the proportion of patients with EPTB who had sputum samples smear positive for AFB. Forty-one hospitals (3 central, 22 district and 16 mission) performing smear microscopy and registering EPTB patients were visited in 1998 and 1999, and a retrospective and prospective study was carried out using TB registers and laboratory sputum registers. In the retrospective study, 1124 (69%) of the 1637 patients with EPTB had sputum smears examined; 988 (88%) of the 1124 submitted 3 sputum specimens. In the prospective study, 2026 (84%) of the 2411 patients with EPTB had sputum smears examined: 94% of the 2026 submitted 3 sputum specimens. In both studies, high rates of sputum submission were found in patients with pleural effusion, miliary TB, lymphadenopathy and pericardial effusion. In the prospective study, only 34 (1.7%) EPTB patients submitting sputum were smear positive, and the proportion who were smear positive exceeded 3% only in patients with lymphadenopathy, miliary TB and TB meningitis. As a result of this study, the Malawi TB Control Programme has changed its policy, and now only insists on sputum-smear examination if patients with EPTB have a cough for > 3 weeks. These policy changes will be audited by further operational research.

Evaluation of a unified treatment regimen for all new cases of tuberculosis using guardian-based supervision.

SETTING: Ntcheu District, Malawi, using an oral antituberculosis treatment regimen. OBJECTIVE: To determine whether directly observed treatment (DOT) during the initial phase of treatment supervised either in hospital, at health centres or by guardians in the community, was associated with 1) satisfactory 2-month and 8-month treatment outcomes, and 2) with a reduction of in-patient hospital-bed days. DESIGN: Prospective data collection of all tuberculosis (TB) patients registered between 1 April 1996 and 30 June 1997, with 2-month and 8-month treatment outcomes, sputum smear conversion in smear-positive pulmonary TB patients (PTB) and in-patient hospital-bed days. RESULTS: Among the 600 new patients, 302 had smear-positive PTB, 150 smear-negative PTB and 148 extrapulmonary TB (EPTB). Eight-month treatment completion was 65% for smear-positive PTB patients, which was significantly higher than in patients with smear-negative PTB (45%) and EPTB (54%), due mainly to high 8-month mortality rates. The site of the intensive phase was determined in 596 patients: 178 (30%) received DOT from guardians, 115 (19%) from a health centre and 303 (51%) in hospital. At 2 months, mortality rates were significantly higher in hospitalised patients. Two-month treatment outcomes (including sputum smear conversion rates in smear-positive PTB patients) were similar between patients receiving DOT at health centres or from guardians. Decentralised DOT resulted in a 25% reduction in hospital-bed days in patients alive at 2 months compared with that predicted using the old regimens. CONCLUSION: Decentralising DOT to health centres and to guardians during the intensive phase is associated with satisfactory treatment outcomes.

HIV sero-prevalence among tuberculosis patients in Kenya.

OBJECTIVE: To determine HIV seroprevalence among tuberculosis patients and the burden of HIV attributable tuberculosis among notified patients in Kenya. DESIGN: A cross-sectional anonymous unlinked HIV seroprevalence survey. SETTING: Tuberculosis diagnostic clinics of the National Leprosy Tuberculosis Programme in 19 districts. SUBJECTS: One thousand nine hundred and fifty-two newly notified tuberculosis patients. INTERVENTIONS: Selection and registration of eligible subjects followed by obtaining 5 ml of full blood for haemoglobin testing and separation of serum for HIV testing by ELISA. MAIN OUTCOME MEASURES: HIV seroprevalence per district and burden of HIV attributable tuberculosis among tuberculosis patients. RESULTS: A total of 1,952 eligible patients were enrolled. The weighted seroprevalence in the sample was 40.7% (range 11.8-79.6% per district). The seroprevalence was significantly higher among females and patients with sputum-smear negative tuberculosis. Chronic diarrhoea, female sex, oral thrush and a negative sputum were independent risk factors for HIV infection. The Odds ratio for HIV infection in female tuberculosis patients aged 15-44 years, was 5.6 (95% CI 4.5-6.9) compared with ante-natal clinic attenders. The population attributable risk was 0.22 in 1994. CONCLUSION: The HIV epidemic has had a profound impact on the tuberculosis epidemic in Kenya and explains about 41% of the 94.5% increase of registered patients in the period 1990-1994 and 20% of all registered patients in 1994. Repetition of the survey with inclusion of a more representative control group from the general population may provide a more accurate estimation of the burden of HIV attributable tuberculosis.

PIP: This cross-sectional survey determined HIV seroprevalence among tuberculosis patients and the burden of HIV attributable tuberculosis among notified patients in Kenya. Data were collected from 1952 patients. The information gathered included demographic data, date of treatment initiation, type of patient, type of tuberculosis, sputum-smear results, and data concerning the signs and symptoms related to tuberculosis and HIV disease. Findings demonstrated that the weighted seroprevalence in the study sample was 40.7% (range, 11.8-79.6% per district), which is significantly higher in females and patients with sputum-smear negative tuberculosis. Chronic diarrhea, female sex, oral thrush, and negative sputum were independent risk factors for HIV infection. The odds ratio for HIV infection in female tuberculosis patients aged 15-44 years was 5.6 compared with antenatal clinic attenders.

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.

[Annual epidemics of hepatitis A in four large cities related to holiday travel among immigrant children]. / Jaarlijkse epidemie van hepatitis A in verband gebracht met reisgedrag van kinderen van immigranten in de vier grote steden.

OBJECTIVE: Analysis of the transmission pattern of hepatitis A in relation to ethnicity and travel behaviour in Amsterdam. Utrecht, Rotterdam and The Hague. DESIGN: Descriptive study of notified cases. SETTING: Municipal Health Services of the four major cities in the Netherlands. METHOD: Notification data of hepatitis A in Amsterdam, Utrecht, Rotterdam and The Hague were analysed over the period 1992-1995. Cases were analysed according to age (0-19 years or > 19 years), whether or not they travelled abroad in the period of six weeks before the onset of the first symptoms of disease, and endemicity of hepatitis A in the country of ethnic origin. RESULTS: The strong increase of hepatitis A after the summer holidays could be divided into several smaller epidemics starting with an epidemic among children of Moroccan and Turkish descent who had spent the summer holidays in these countries, among children of the same ethnic background who had not travelled abroad, followed by epidemics among non-travelling children and adults of mainly Dutch descent, respectively. A strong correlation was found in Amsterdam between the incidence in the former two groups and the latter two groups (Pearsons r = 0.68; p = 0.004). CONCLUSION: Children who spent the summer holidays in a hepatitis A endemic country, particularly Morocco and Turkey, appeared to be the main importers of hepatitis A in the four major cities. Active immunization of all children born in the Netherlands of Moroccan and Turkish descent is the most preferable intervention.

Antituberculosis drug resistance surveillance in Kenya, 1995.

SETTING: Twenty-two of the 42 administrative districts in Kenya. OBJECTIVE: To determine the prevalence of drug resistance in newly diagnosed patients with pulmonary tuberculosis, to determine possible risk factors associated with resistance, and to establish standard routine surveillance of drug resistance. DESIGN: Cross-sectional study. METHODS: Sputum samples from newly diagnosed patients with smear-positive pulmonary tuberculosis were analysed using standard procedures. RESULTS: Of 638 patients, 85% were culture positive for Mycobacterium tuberculosis. Of 491 patients tested for susceptibility to isoniazid, streptomycin, rifampicin and ethambutol, 90.8% had fully sensitive strains and 9.2% had a strain resistant to one or more drugs. Of 445 patients with no history of previous chemotherapy, 6.3% had a resistant strain. Of 46 patients with a history of previous chemotherapy, 37% had a resistant strain. No resistance to either rifampicin or ethambutol was detected. There was a strong association between previous chemotherapy and resistance. Resistance was not associated with age or sex. High concordance between Kenya's results and those of the Mycobacterium Reference Unit in the UK on both drug-sensitive and drug-resistant strains indicates that clinically significant and comparable data can be obtained from laboratories employing unsophisticated and inexpensive standard procedures. CONCLUSION: Rates of initial drug resistance are still low in Kenya. The increase in acquired resistance to isoniazid requires monitoring.

Cost-effectiveness and total costs of three alternative strategies for the prevention and management of severe skin reactions attributable to thiacetazone in the treatment of Human Immunodeficiency Virus positive patients with tuberculosis in Kenya.

SETTING: Severe skin reactions due to thiacetazone (T) in Human Immunodeficiency Virus (HIV) positive tuberculosis patients have been reported in several publications, one of them from Kenya. However, the abandoning of T may not be feasible in Kenya as this may increase the cost of drugs by about three-fold per regimen. OBJECTIVE: To compare the cost-effectiveness and total cost of three strategies in which T is replaced with ethambutol (E). DESIGN: Three strategies are compared with a baseline strategy in which T is not replaced. The indicator for cost-effectiveness is the cost-per-averted-death attributable to T. RESULTS: Education of patients on the possibility of side-effects and replacement of T with E is the most cost-effective strategy at HIV prevalence rates of 1-90%. Abandonment of T and replacement with E is the most cost-effective at over 90% HIV prevalence. CONCLUSION: In Kenya, education of patients on the possibility of skin reactions should be preferred at low range HIV prevalence rates. Routine HIV testing would be the most attractive strategy in the middle range, and total replacement of T with E is to be preferred in the higher range of HIV prevalence.

PIP: In Kenya, the National Leprosy Tuberculosis Programme (NLTP) used previously reported data from Nairobi to compare the cost-effectiveness and total costs of a hypothetical strategy with three intervention strategies for the prevention and management of severe skin reactions caused by thiacetazone in treating HIV-positive patients with tuberculosis (TB). The hypothetical strategy was continued use of thiacetazone despite adverse skin reactions. The intervention strategies included patient education about possible side effects of anti-TB drugs (discontinue use if skin rash develops, report situation to clinic, replace thiacetazone with ethambutol when other skin diseases have been excluded), abandonment of thiacetazone and replacement with ethambutol, and HIV testing and pre- and post-test counseling. NLTP currently used the education strategy. It assumed a mortality rate of 5%. When the HIV prevalence rate is 1-90%, the education strategy is the most cost-effective strategy. In terms of total costs, the education strategy was also the most inexpensive strategy regardless of the HIV prevalence. At an HIV prevalence rate greater than 65%, the abandonment of thiacetazone strategy was the cheapest strategy. When the assumed mortality rate was 3%, the cost per averted death for the education strategy was reduced from about US$120 to about US$80 and the education strategy became the most cost-effective strategy over the entire range of HIV prevalence. In addition, the cost of HIV testing significantly increased the cost per averted death. Thus, the findings of this study are truly sensitive to different program conditions. Based on these findings, the authors recommended that the education strategy be applied with a range of HIV prevalence of 1-45%, that HIV testing be applied with a range of 46-72%, and that total abandonment be applied with an HIV prevalence greater than 72%.