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Biomedical subjects

P Nunn

Publications and source records attributed to P Nunn.

At least 19 recordsLinked to original sources

Comparison of intermittent ethambutol with rifampicin-based regimens in HIV-infected adults with PTB, Kampala.

BACKGROUND: The human immunodeficiency virus (HIV) is a key factor responsible for the high rates of tuberculosis (TB) in sub-Saharan Africa. Treatment of TB with rifampicin (R, RMP) containing short-course regimens is highly effective in HIV-infected adults. We conducted a study to compare the efficacy and safety of intermittent ethambutol (E, EMB) with two RMP-containing regimens to treat pulmonary TB in HIV-infected patients. SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. DESIGN: This was a prospective cohort compared to two non-randomised control groups. The study group and the two control arms were treated with 2 months of isoniazid (H), RMP, pyrazinamide (Z) and EMB followed by 6 E3H3 for the study group and 4HR or 6HR for controls. RESULTS: Between April 1993 and March 2000, 136 patients were enrolled in the 2EHRZ/E3H3 arm, 147 in the 2EHRZ/4HR arm and 266 in the 2EHRZ/6HR arm. The relapse rate was 18.2 per 100 person-years observation (PYO) for the study regimen compared to 9.7/100 PYO (P = 0.0063) and 4.8/100 PYO (P = 0.0001) in patients treated with 2 EHRZ/4HR or 2EHRZ/6HR, respectively. CONCLUSION: The 2EHRZ/6E3H3 regimen is safe and effective but has a significant risk of relapse.

AIDS-Related Opportunistic Infections↗

Can we get more HIV-positive tuberculosis patients on antiretroviral treatment in a rural district of Malawi?

The World Health Organization (WHO) has set a target of treating 3 million people with antiretroviral treatment (ART) by 2005. In sub-Saharan Africa, HIV-positive tuberculosis (TB) patients could significantly contribute to this target. ART (stavudine/lamivudine/nevirapine) was initiated in Thyolo district, Malawi, in April 2003, and all HIV-positive TB patients were considered eligible and offered ART. Despite this, only 44 (13%) of 352 TB patients were eventually started on ART by the end of November 2003. Most TB patients leave hospital after 2 weeks to complete the initial phase of anti-tuberculosis treatment (rifampicin-based) in the community, and ART is offered to HIV-positive TB patients after they have started the continuation phase of treatment (isoniazid/ ethambutol). ART is only offered at hospital, while the majority of TB patients take their continuation phase of anti-tuberculosis treatment from health centres. HIV-positive TB patients therefore find it difficult to access ART. In this paper, we discuss a series of options to increase the uptake of ART among HIV-positive TB patients. The main options are: 1) to hospitalise HIV-positive TB patients with a view to starting ART in the continuation phase in hospital; 2) to decentralise ART delivery so ART can be delivered at health centres; 3) to replace nevirapine with efavirenz so ART can be started earlier in the initial phase of anti-tuberculosis treatment. Decentralisation of ART from hospitals to health centres would greatly improve ART access.

Anti-HIV Agents↗

WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts.

SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy.

Adolescent↗

The global control of tuberculosis: what are the prospects?

Tuberculosis (TB) still imposes a huge burden of ill health, premature death and emotional suffering on the developing world. Over the past 30 y it has been greatly neglected by those concerned about international public health and there are now nearly 8 million new cases annually and 1.86 million deaths. An epidemic of HIV-associated TB is now affecting Africa and threatening parts of Asia. Multidrug-resistant TB has emerged as a huge threat in Russia and its former satellites. However, with the advent of the directly observed treatment, short-course (DOTS) strategy in 1995, high-burden countries have started to seriously address the problem. Recent political commitment on the part of the rich nations, together with significant increases in funding from private foundations and great scientific advances in our understanding of Mycobacterium tuberculosis, give rise to cautious optimism that TB will be controlled during this century.

AIDS-Related Opportunistic Infections↗

Gender and tuberculosis: a comparison of prevalence surveys with notification data to explore sex differences in case detection.

OBJECTIVE: To explore whether lower tuberculosis notification rates among women are due to a reduced access to health care, particularly diagnostic services, for women. METHODS: Age- and sex-specific tuberculosis prevalence rates of smear-positive tuberculosis were obtained from tuberculosis prevalence surveys reported to the WHO or published in the literature. Age- and sex-specific notification rates from the same countries in 1996 were used. RESULTS: Prevalence data and notifications from 29 surveys in 14 countries were used. Notification rates varied strongly among countries, but the female/male ratio was below 1 and decreased with increasing age in almost all. The female/male (F/M) prevalence ratios were less than 0.5 in surveys in the South-East Asia and Western Pacific Region, and approximately 1 in the African Region. CONCLUSION: In most countries the F/M sex ratio in prevalent cases was similar or lower than that in notified cases, suggesting that F/M differences in notification rates may be largely due to epidemiological differences and not to differential access to health care. However, available data are limited as the prevalence surveys in Africa were carried out many years ago, and in Asia notification rates may be distorted by a large private sector with deficiencies in notification.

Adolescent↗

Mortality rates and recurrent rates of tuberculosis in patients with smear-negative pulmonary tuberculosis and tuberculous pleural effusion who have completed treatment.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To follow-up human immunodeficiency virus (HIV) seropositive and HIV-seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB who had completed treatment with two different regimens in Blantyre and Zomba, and to assess rates of mortality and recurrent TB. DESIGN: Patients with smear-negative and pleural TB who had completed 8 months ambulatory treatment in Blantyre or 12 months standard treatment in Zomba and who were smear and culture negative for acid-fast bacilli at the completion of treatment were actively followed every 4 months for a total of 20 months. RESULTS: Of 248 patients, 150 with smear-negative PTB and 98 with pleural TB, who completed treatment and were enrolled, 205 (83%) were HIV-positive. At 20 months, 145 (58%) patients were alive, 85 (34%) had died and 18 (7%) had transferred out of the district. The mortality rate was 25.7 per 100 person-years, with increased rates strongly associated with HIV infection and age >45 years. Forty-nine patients developed recurrent TB. The recurrence rate of TB was 16.1 per 100 person-years, with increased rates strongly associated with HIV infection, having smear-negative PTB and having received 'standard treatment'. CONCLUSION: High rates of mortality and recurrent TB were found in patients with smear-negative PTB and pleural effusion during 20 months of follow-up. TB programmes in sub-Saharan Africa must consider appropriate interventions, such as co-trimoxazole and secondary isoniazid prophylaxis, to reduce these adverse outcomes.

Adult↗

Medical emergencies in the oral health care setting.

On any given day a patient seen by the dental hygienist has the potential of experiencing a life-threatening medical emergency. All dental hygiene practitioners should be aware of potential risks that a patient may present, take steps to prevent life-threatening events from occurring, and plan for problems in advance of their happening. The primary goal of this course is to help dental hygienists carry out the ethical, moral, legal, and professional obligation owed any patient. The course will review the basics of medical emergencies, with particular emphasis on those that are most likely to occur in the dental office. Discussion will center on general aspects of prevention and preparation, and will focus on the recognition and emergency treatment of specific conditions. Vasodepressor syncope, orthostatic hypotension, acute adrenal insufficiency, hyperventilation, asthma, heart failure and acute pulmonary edema, cerebrovascular accident seizures, hyperglycemia, hypoglycemia, myocardial infarction, angina pectoris, and anaphylaxis will be emphasized.

Adrenal Insufficiency↗

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↗

Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.

BACKGROUND: Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organization-International Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997. METHODS: The data are from cross-sectional surveys and surveillance reports. Participating countries followed guidelines to ensure the use of representative samples, accurate histories of treatment, standardized laboratory methods, and common definitions. A network of reference laboratories provided quality assurance. The median number of patients studied in each country or region was 555 (range, 59 to 14,344). RESULTS: Among patients with no prior treatment, a median of 9.9 percent of Mycobacterium tuberculosis strains were resistant to at least one drug (range, 2 to 41 percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5 percent) was more common than resistance to rifampin (1.8 percent) or ethambutol (1.0 percent). The prevalence of primary multidrug resistance was 1.4 percent (range, 0 to 14.4 percent). Among patients with histories of treatment for one month or more [corrected], the prevalence of resistance to any of the four drugs was 36.0 percent (range, 5.3 to 100 percent), and the prevalence of multidrug resistance was 13 percent (range, 0 to 54 percent). The overall prevalences were 12.6 percent for resistance to any of the four drugs [corrected] (range, 2.3 to 42.4 percent) and 2.2 percent for multidrug resistance (range, 0 to 22.1 percent). Particularly high prevalences of multidrug resistance were found in the former Soviet Union, Asia, the Dominican Republic, and Argentina. CONCLUSIONS: Resistance to antituberculosis drugs was found in all 35 countries and regions surveyed, suggesting that it is a global problem.

Antitubercular Agents↗

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↗

Tuberculosis patients and practitioners in private clinics in India.

SETTING: Rural and urban areas of Maharashtra, a large state in Western India. OBJECTIVE: To understand tuberculosis (TB) management practices among private medical practitioners (PPs) and the treatment behaviour of the patients they manage. DESIGN: Prospective study of help-seeking patterns and treatment behaviour among 173 pulmonary TB patients diagnosed in private clinics, and the TB management practices of 122 PPs treating these patients. RESULTS: The first source of help for 86% of patients was a PP. The diagnostic and treatment practices of PPs were inadequate; 15% did not consider sputum examination to be necessary, and 79 different treatment regimens were prescribed by 105 reporting PPs. Sixty-seven percent of the patients diagnosed in private clinics remained with the private sector, and the rest shifted to public health services within six months of treatment. The treatment adherence rate among the patients in private clinics was 59%. There were discrepancies between the reported management practices of the PPs and what their patients actually followed. CONCLUSION: The study identifies and highlights the need to educate PPs and their TB patients, and indicates ways in which PPs could be meaningfully involved in efforts to revitalize the national TB control programme.

Adolescent↗

A review of sex differences in the epidemiology of tuberculosis.

Globally, the prevalence of infection with Mycobacterium tuberculosis is similar in males and females until adolescence, after which it is higher in males. In industrialized countries in the middle of this century (1930s to 1950s), females aged 15 to 34 years had higher tuberculosis notification rates than males of the same age. However, as notification rates in these countries decreased over time, rates in males became higher than those of females for all ages over 15. Present notification rates of both sexes combined in many developing countries are similar to those of industrialized countries in the middle of the century, although the sex and age pattern is similar to that in industrialized countries at present, with men's disease rates exceeding women's after the age of 15. These findings raise the possibility that cases of tuberculosis among women are being under-reported in developing regions. This is supported by the results of a study comparing active and passive case-finding in which women with tuberculosis were under-notified to public health authorities when relying on passive case-finding. In addition, epidemiological evidence from the pre-human immunodeficiency virus (HIV) era shows that young to early-middle-aged women progress from infection to disease with greater frequency than do men. This elevated frequency of progression among women now coincides with a peak in HIV prevalence among women of the same age. National Tuberculosis Programmes must assess possible sex differences that exist in their countries. In addition, information about the risks of tuberculosis in younger women should be incorporated into maternal and child health, and HIV/AIDS programmes. Further research comparing sex differences in tuberculosis rates, preferably using active as well as passive case-finding, would be necessary to determine whether young women are undernotified in developing countries.

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↗