Relapse and recurrent tuberculosis in the context of a national tuberculosis control programme

The proportion of patients with recurrent tuberculosis (TB) is reported to be increased in TB patients with human immunodeficiency virus (HIV) infection after they have completed treatment. Despite rising HIV seroprevalence amongst TB patients in Malawi, notifications of patients with relapse smear-positive pulmonary TB (PTB) and recurrent smear-negative TB have remained stable during the past 12 years. We suspected that patients with recurrent or relapse TB were being missed under routine programme conditions. Forty-three hospitals in Malawi were visited in 1999, and TB inpatients who had been registered as 'new' cases in the TB register and treatment card were interviewed about previous episodes of TB. A previous history of TB was elicited in 94 (7.5%) of 1254 patients who were being treated as new cases. Compared with patients with smear-positive PTB, a previous episode of TB was significantly more common in patients with smear-negative PTB (OR 3.5, [95% CI 2.1-5.7], P < 0.001) and patients with extrapulmonary TB (OR 2.0, [95% CI 1.1-3.7], P < 0.05). Of 94 patients with a previous episode of TB, 76 had completed treatment and 18 had defaulted from treatment during this episode. Patients with recurrent or relapse TB are being incorrectly registered within the Malawi TB Control Programme, and in the case of smear-positive PTB patients this is associated with administration of incorrect treatment. Measures have been put in place to rectify the situation, and further operational research is planned to monitor treatment outcomes of patients with recurrent smear-negative TB.     

Treatment outcome of patients with smear-negative and smear-positive pulmonary tuberculosis in the National Tuberculosis Control Programme, Malawi

National tuberculosis control programmes (NTPs) in sub-Saharan Africa do not routinely record or report treatment outcome data on smear-negative pulmonary tuberculosis (PTB) patients. Twelve-month treatment outcome on patients with smear-negative PTB registered in all district and mission hospitals in Malawi during the year 1995 was collected, and was compared with 8-month treatment outcome in smear-positive PTB patients registered during the same period. Of 4240 patients with smear-negative PTB, 35% completed treatment, 25% died, 9% defaulted and 7% were transferred to another district with no treatment outcome results available. In 24% of patients treatment cards were lost and treatment outcome was unknown. These results were significantly inferior to those obtained in 4003 patients with smear-positive PTB in whom 72% completed treatment, 20% died, 4% defaulted, 2% were transferred and 1% had positive smears at the end of treatment. These differences between patients with smear-negative and smear-positive PTB were similar when analysed by sex and by most age-groups. Higher mortality rates in patients with smear-negative PTB are probably attributable to advanced HIV-related immunosuppression, and higher default and treatment unknown rates probably reflect the lack of attention paid by TB programme staff to this group of patients. As a result of this country-wide study the Malawi NTP has started to record routinely the treatment outcomes of smear-negative TB patients and has set treatment completion targets of 50% or higher for this group of patients.     

High mortality rates in tuberculosis patients in Zomba Hospital, Malawi, during 32 months of follow-up

There is little information about long-term follow-up in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) who have been treated under routine programme conditions in sub-Saharan Africa. A prospective study was carried out to determine outcome 32 months from start of treatment in an unselected cohort of 827 adults TB inpatients registered at Zomba Hospital, Malawi, in 1 July-31 December 1995. By 32 months, 351 (42%) patients had died. Death rates were 30% (95% confidence interval [95% CI] 25-35%) in 386 patients with smear-positive PTB, 60% (95% CI 53-67%) in 211 patients with smear-negative PTB and 47% (95% CI 40-54%) in 230 patients with EPTB. Of the 793 patients with concordant HIV test results 612 (77%) were HIV seropositive: 47% HIV-positive patients were dead by 32 months compared with 27% HIV-negative patients (adjusted hazard ratio [HR] 2.3; 95% CI 1.7-3.1, P < 0.001). Smear-negative PTB patients had the highest death rates during the 32-month follow-up (HR 2.7; 95% CI 2.1-3.5, P < 0.001 compared to smear-positive patients), followed by EPTB patients (HR 1.9; 95% CI 1.5-2.5, P < 0.001 compared to smear-positive patients). When analysis was restricted to after the treatment period had finished (i.e., months 12-32), the differences in mortality were maintained for HIV-serostatus and for types of TB. Low-cost, easy to implement strategies for reducing mortality in HIV-positive TB patients in sub-Saharan Africa (such as the use of trimethoprim-sulphamethoxazole prophylaxis) need to be tested urgently in programme settings.     

The missing cases of tuberculosis in Malawi: the contribution from cross-border registrations

Low case detection rates of new smear-positive pulmonary tuberculosis (PTB) patients globally are a cause for concern. The aim of this study was to determine for patients registered for TB in Malawi the number and percentage who lived in a neighbouring country and the registration, recording and reporting practices for these 'foreign' patients. All 44 non-private hospitals, which register and treat all TB patients in the public health sector in Malawi, were visited. Ten (23%) hospitals in 2001 and 14 (32%) in 2002 maintained a separate register for cross-border TB cases. Patients recorded in these registers were not formally reported to the Malawi National TB Programme (NTP), the neighbouring country's NTP, nor to WHO. They therefore constitute missing cases. In Malawi, the number of cross-border new smear-positive PTB cases was 77 in 2001 and 91 in 2002, constituting about 3% of missing smear-positive cases in those hospitals that maintain cross-border registers and about 1% of missing cases nationally.     

Differences in tuberculosis incidence rates in township and in rural populations in Ntcheu District, Malawi

There has been a large upsurge of tuberculosis (TB) in many countries in sub-Saharan Africa, mainly as a result of the co-existing human immunodeficiency virus (HIV) epidemic. Malawi has had a well-run National TB Control Programme (NTP) with good registration and recording of cases. For some years the NTP has had the impression that TB in the country is concentrated around townships and is less prevalent in the rural areas. This impression was investigated in a rural district (Ntcheu District) in Malawi. Data on new TB cases were collected from the district TB register for the years 1992-96 and average annual TB incidence rates per 100,000 for semi-urban and rural populations were calculated for this period. There was a significantly higher incidence of TB, particularly amongst cases with smear-negative pulmonary TB and extrapulmonary TB, in the semi-urban population compared with the rural population. Possible explanations could be higher HIV seroprevalence rates in semi-urban areas compared with rural areas, under-diagnosis at health centres or poor access to medical facilities for rural people.     

Preventing tuberculosis among health workers in Malawi

OBJECTIVE: Following the introduction of guidelines for the control of tuberculosis (TB) infection in all hospitals in Malawi, a study was carried out to determine whether the guidelines were being implemented, the time between admission to hospital and the diagnosis of pulmonary TB had been reduced, and the annual case notification rates among health workers had fallen and were comparable to those of primary-school teachers. METHODS: The study involved 40 district and mission hospitals. Staff and patients were interviewed in order to determine whether the guidelines had been adopted. In four hospitals the diagnostic process in patients with smear-positive pulmonary TB was evaluated before and after the introduction of the guidelines, with the aid of case notes and TB registers. In all hospitals the proportion of health workers registered with TB before and after the guidelines were introduced, in 1996 and 1999, respectively, was determined by conducting interviews and consulting staff lists and TB registers. A similar method was used to determine the proportion of primary-school teachers who were registered with TB in 1999. FINDINGS: The guidelines were not uniformly implemented. Only one hospital introduced voluntary counselling and testing for its staff. Most hospitals stated that they used rapid systems to diagnose pulmonary TB. However, there was no significant change in the interval between admission and diagnosis or between admission and treatment of patients with smear-positive pulmonary TB. The TB case notification rate for 2979 health workers in 1999 was 3.2%; this did not differ significantly from the value of 3.7% for 2697 health workers in 1996 but was significantly higher than that of 1.8% for 4367 primary-school teachers in 1999. CONCLUSION: The introduction of guidelines for the control of TB infection is an important intervention for reducing nosocomial transmission of the disease, but rigorous monitoring and follow-up are needed in order to ensure that they are implemented.     

HIV and tuberculosis in rural sub-Saharan Africa: a cohort study with two year follow-up.

The objective was to examine the effect of HIV seropositivity on outcomes in tuberculosis (TB) patients in a rural African setting, including rates of TB relapse, other morbid events and mortality. The study setting was a district level hospital in Mzuzu, Malawi. Adult TB patients presenting between November 1991 and May 1993 were included in the study. Treatment was given according to national guidelines. Patients with smear-positive TB received 8 months of rifampicin-containing short-course chemotherapy. Patients with smear-negative or extrapulmonary TB received 12 months of 'standard' treatment. Subjects were followed until they died or until the study concluded (December 1994). There were 225 eligible patients; 187 were tested for HIV and enrolled in the study (66.8% HIV seropositive). Ninety-four percent had complete follow-up information. The cure rate in smear-positive patients who survived to the end of treatment was over 90% and not significantly affected by HIV. Disorders of the gastrointestinal, neurological and dermatological systems were significantly more common in HIV-seropositive patients. HIV had a significant effect on the risk of relapse of TB (hazard ratio [HR] = 10.55 [95% CI 1.38, 80.93]) and on all-cause mortality (HR = 2.81 [95% CI 1.63, 4.64]). Despite high HIV prevalence, high rates of TB cure are achievable using the usual treatment protocols. However, excess TB relapse, other illnesses and mortality associated with HIV seropositivity have serious implications for TB control. There is an urgent need to identify effective intervention strategies aimed at prevention, early diagnosis and treatment of these illnesses.     

High death rates in health care workers and teachers in Malawi

High death rates are reported in health care workers (HCWs) and teachers in urban areas of Malawi. The present study was carried out to determine the annual death rate in HCWs and primary school teachers working in semi-urban and rural areas of Malawi, and to try to ascertain the main causes of death. Forty district and mission hospitals in Malawi were visited. A record was made of the number of clinical and nursing-based HCWs in each hospital in 1999, the number of deaths in that calendar year and reported causes of death. A record was also made of the number of teachers working in 4 primary schools nearest to each hospital in 1999, the number of deaths in that calendar year and reported causes of death. There were 2979 HCWs, of whom 60 (2.0%) died. There were 4367 teachers of whom 101 (2.3%) died. Annual death rates, calculated per 100,000 people, were significantly higher in male HCWs compared with female HCWs (2495 versus 1770, RR 1.17, 95% CI 1.14-1.20, P < 0.001), and significantly higher in female teachers compared with male teachers (2521 versus 1934, RR 1.14, 95% CI 1.11-1.17, P < 0.001). In male HCWs and teachers the highest death rates were in those aged 35-44 years. In female HCWs and teachers, the highest death rates were in those aged 25-34 years and 35-44 years, respectively. Reported causes of death in HCWs were tuberculosis (TB) in 47%, chronic illness in 45% and acute illness in the remainder, while in teachers the causes were TB in 27%, chronic illness in 49% and acute illness in 25%. Chronic illness, thought to be due to AIDS, and TB were the common causes of death. The current high death rates from AIDS and TB will have a crippling toll on the health and education sectors, and effective ways of reducing these death rates must be found.     

Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi

From 2000 to 2012, Malawi scaled up antiretroviral therapy (ART) from <3000 to 404 905 persons living with HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome), representing an ART coverage of 40.6% among those living with HIV. During this time, annual tuberculosis (TB) notifications declined by 28%, from 28 234 to 20 463. Percentage declines in annual TB case notifications were as follows: new TB (26%), recurrent TB (40%), new smear-positive pulmonary TB (19%), new smear-negative pulmonary TB (42%), extra-pulmonary TB (19%), HIV-positive TB (30%) and HIV-negative TB (10%). The decline in TB notifications is associated with ART scale-up, supporting its value in controlling TB in high HIV prevalence areas in sub-Saharan Africa.     

2000—2009年上海市金山区活动性肺结核流行病学分析

目的了解上海市金山区肺结核病人发病情况、分布、临床特征及治疗转归情况,为制定结核病防治策略提供依据。方法对2000—2009年金山区活动性肺结核病报告登记管理资料进行分析。结果金山区2000—2009年共新登记该区活动性肺结核病例1 808例,合计发病率为34.42/10万,其中菌阳884例,菌阳率48.89%。金山区共新登记外来流动人口活动性肺结核病例556例,其中菌阳230例,菌阳率41.37%;该区肺结核患者以60岁以上老年人为主,占38.66%,男女性别比为3.26∶1。外来流动人口以青壮年为主,19～40岁占总病例数70.14%,男女性别比为1.79∶1,患者分型以Ⅲ型为主,该区查痰率97.79%,外来流动人口查痰率95.32%。2000—2009年该区涂阳肺结核患者治愈率89.29%,涂阴患者完成疗程率92.73%;2007—2009年外来流动人口涂阳肺结核患者治愈率为67.95%,涂阴患者完成疗程率为81.51%。结论该区活动性肺结核发病率总体趋势略有下降,而菌阳发病率下降趋势不明显;外来流动人口活动性肺结核发病人数呈现上升趋势,菌阳也呈现上升趋势。加强外来流动人口结核病管理,有必要采取切实有效的措施落实外来流动人口的结核病管理。     

Epidemiology of Tuberculosis in the Southeastern Iran

In order to study the epidemiology of tuberculosis (TB) in Zabol, situated in the Southeast of Iran, this study was performed. Two thousand seven hundred and twenty-nine cases of tuberculosis disease were identified during 1998–2002. The notification rate was 135/100,000 population in 2002, which was higher than this rate in previous years. The notification rate of TB in Afghan population was significantly higher than Iranian population (202 cases/100,000 in Afghan and 122 cases/100,000 in Iranian population. The case notifications in 1998–2001 were 134, 131, 130, and 130 in 100,000 populations, respectively. The prevalence of smear-positive cases was 76/100,000 population in 2002 and the ratio of smear-positive cases to smear-negative and extrapulmonary cases was 1.46. This region remains high TB rates. It is necessary to pay attention to the detection of TB, by making their register in order to enhance the effectiveness and to reduce the cost of existing methods.     

Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi

The National TB Control Programme of Malawi registers and treats large numbers of patients with chronic cough for smear-negative pulmonary tuberculosis (PTB). Smear-negative PTB is diagnosed according to clinical and radiographic criteria, as mycobacterial cultures are not routinely available. In an area of high HIV seroprevalence there is a concern that other opportunistic infections apart from TB, such as Pneumocystis carinii, may be missed owing to lack of diagnostic facilities. The aims of this study were to investigate (i) the extent of P. carinii pneumonia (PCP) in patients about to be registered for smear-negative PTB; (ii) whether there were any clinical or radiological features that could help identify PCP in the absence of more detailed investigations; and (iii) the treatment outcome of PCP patients. A cohort of 352 patients who were about to be started on treatment for smear-negative PTB were investigated further in 1997-99 by clinical assessment, HIV testing and bronchoscopy. HIV sero-prevalence was 89% (278/313). A total of 186 patients underwent bronchoscopy and bronchoalveolar lavage, and PCP was diagnosed by indirect immunofluorescence or polymerase chain reaction in 17 (9%) of this subgroup. Dyspnoea was significantly more common in PCP cases compared to non-PCP cases (RR 1.35; 95% CI 1.24-1.48; P = 0.008), but discrimination between the groups was difficult using clinical criteria alone. The outcome of PCP cases was poor despite management with high-dose co-trimoxazole and secondary co-trimoxazole prophylaxis, with a median survival of 4 months (25-75% range: 2-12 months).     

龙岩市2008年结核病控制工作分析

目的了解龙岩市肺结核病治疗与管理情况。方法分析2008年龙岩市结核病控制项目季报表及年报表资料。结果初诊率、查痰率分别为2.72%、99.05%,涂阳及涂阴病人进度分别为102.95%、40.02%,平均治愈率为89.49%,全市平均丢失率为1.70%（17/999）。结论龙岩市结核病控制工作取得一定成绩,治愈率较高,但仍存在一些问题,还要继续认真实施全程督导短程化疗策略。     

湖北省网络直报疑似肺结核病人转诊追踪工作分析

[目的]分析综合医院疑似肺结核病人报告、转诊、追踪和定诊情况,探讨提高涂阳肺结核病人发现措施。[方法]根据2005年6月～2006年5月,60个FIDELIS项目县结核病控制工作月报表和FIDELIS项目相关报表数据,进行综合分析和评价,统计分析采用SAS软件。[结果]在FIDELIS项目实施期间,60项目县综合医院实际报告疑似肺结核24 666例,转诊到结防机构8 006例,转诊到位率为32.5%;结防机构追踪到位7 049例,追踪到位率为47.1%;转诊追踪到位共计15 055例病例,其中4 994例（33.2%）在结防机构重新定诊为涂阳肺结核,4 542例（30.2%）定诊为涂阴肺结核,3 756例（24.6%）被排除肺结核。[结论]加强综合医院痰检质量控制和转诊,提高结防专业机构对综合医院网络直报疑似肺结核病人的追踪工作,是提高肺结核病人发现水平的有效途径。     

巢湖市居巢区2003～2005年结核病控制项目实施效果分析

目的评价巢湖市居巢区2003~2005年实施结核病控制项目的3年成效。方法收集并分析项目期间涂阳肺结核病人登记管理卡、初诊登记本、实验室登记本、结核病人登记本、结核病月报表、季报表、年报表等资料。结果3年共接诊可疑对象2 169人,发现活动性肺结核病人919例,其中涂阳病人764例、重症涂阴病人37例,免费治疗涂阳病人750例、治愈512例,免费治疗重症涂阴病人37例,初治和复治涂阳病人治愈率分别为80.48%和64.00%。结论居巢区结核病控制项目的实施已初见成效,获得了较好的社会效益和经济效益,取得了可行经验,但仍有不少问题存在,尚未达到结核病的高发现率和高治愈率,需要采取有力措施,进一步完善结核病控制工作。     

2015－2021年灌云县肺结核流行病学特征分析

目的 分析近年来灌云县的肺结核流行病学特征,为肺结核防控提供科学依据。方法 收集2015—2021年灌云县的肺结核疫情数据,描述患者性别、年龄、职业和地区分布,肺结核发病时间、耐药性以及合并肺外结核等,并进行组间比较。结果 2015—2021年灌云县共报告肺结核1 871例,发病率呈下降趋势,从34.63/10 万下降至 20.45/10 万,年均25.78/10 万。每月均有肺结核报告病例,月发病占比率在5.83% ~10.53%波动,以第二季度4月份占比率最高(10.53%);男性发病率(37.50/10万 高于女性( 12.71/10万),差异有统计学意义(χ2=431.22,P<0.001);患者年龄从11岁到92岁,发病年龄呈现出双高峰,分别为≥20～30岁青壮年和≥70～80岁老年人;农民患病率占比最高(73.06%),五图河农场肺结核发病率最高(118.03/10 万)。本调查还发现2.89%耐利福平结核病和6.57%耐异烟肼结核病以及9.19%肺结核合并肺外结核病例。结论 2015—2021年灌云县的肺结核发生率呈下降趋势,但存在一定数量的耐利福平或异烟肼结核病和肺外结核病例,因此,应积极开展有针对性的高危人群预防和干预,减少耐药肺结核的发生。     

安徽省实施《卫生部结核病控制项目》5年效果分析

报告安徽省实施卫生部加强与促进结核病控制项目 5年来 ,按项目规程 ,建立标准的资料记录和报告系统 ,配合现场督导获取信息。结果表明项目县占全省总县数的 19.4% ,人口覆盖率为 2 2 .8% ,涂阳肺结核病人发现占全省报告的涂阳肺结核病人的 42 .8% ,痰检质控阳性片符合率 10 0 .0 % ,阴性片符合率 97.0 % ,涂阳病人队列分析治愈率 89.4% ,其中初治涂阳治愈率 91.6 % ,复治 82 .0 %。认为卫生部项目实施 5年取得了较少投入较大产出的明显效益 ,达到了高发现率和高治愈率的预期目标[1 ] 。     

江华县1993-2008年结核病控制项目实施效果分析

目的评价1993-2008年江华县结核病控制项目实施效果。方法对江华县项目实施期间登记管理的肺结核病例资料进行统计分析。结果 16年来共发现并登记管理活动性肺结核病人4489例。其中涂阳病人2618例,新发涂阴病人1871例。可疑肺结核平均就诊率176.0/10万,新涂阳病人平均登记率31.5/10万;初治涂阳病人平均治愈率97.3%,复治涂阳病人平均治愈率86.9%,新发涂阴病人治疗成功率95.6%。结论现代结核病控制策略的实施,极大地促进并规范了江华县结核病防治工作,实现了结核病人高发现率和高治愈率的目标,取得了显著的社会效益和经济效益。但仍有不少问题存在,结核病控制工作有待进一步加强。     

The persistence of tuberculosis in the age of DOTS: reassessing the effect of case detection

Objective

To investigate whether short-term annual declines of 5–10% in the incidence of tuberculosis (TB) can be sustained over the long term by maintaining high case detection rates (CDRs).

Methods

We constructed a compartmental difference-equation model of a TB epidemic in a hypothetical population of constant size with a treatment success rate of 85%. The impact of CDR on TB incidence was then investigated by generating an equilibrium population with no TB case detection and increasing the smear-positive CDR under two scenarios: (i) rapid expansion by 10% per year to a CDR of 80% after 8 years, and (ii) gradual expansion by 1% per year to a CDR of 90% after 90 years. The model was applied in two hypothetical populations: one without HIV and the other with a stable HIV incidence representative of the African Region. The CDR for smear-negative TB was assumed to be a constant fraction of the smear-positive CDR.

Findings

In the absence of a TB control programme, the projected annual incidence of TB was 513 cases per 100 000 population, with a point prevalence of 1233 per 100 000 and an annual TB-specific mortality rate of 182 per 100 000. Immediately increasing the TB CDR from 0% to 70% caused a 74% reduction in TB incidence within 10 years. However, once case detection stabilized at any constant level ≤ 80%, projected TB incidence also stabilized. Ten years after a CDR of 70% was reached, the annual decline in TB incidence was < 1.5%, regardless of how rapidly case detection was scaled up and despite wide variation of all model parameters.

Conclusion

While improved CDRs have a dramatic short-term effect on TB incidence, maintaining those rates, even at current target levels, may not reduce long-term incidence by more than 1–2% per year. TB control programmes and researchers should vigorously pursue improvements in case detection, regardless of current CDRs.     

2005-2009年威海市结核病防治效果分析

[目的]评价威海市2005～2009年结核病防治效果。[方法]对威海市2005～2009年扩展现代结核病控制策略时期结核病控制工作情况进行分析。[结果]2005～2009年威海市累计接诊18737例可疑症状者,年均就诊率为149．28／10万,初诊年均查痰率为63．37％,年均涂阳检出率为18．99％,年均涂阳登记率为17．97／10万。可疑症状者因症就诊率为33．55％,初、复治涂阳患者平均治愈率分别为87．23％、81．82％。[结论]2005～2009年威海市结核病防治效果明显。