Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

BACKGROUND: Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. METHODS: In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. FINDINGS: A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). CONCLUSION: TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Development of a questionnaire to determine the case detection delay of leprosy: A mixed-methods cultural validation study.

BACKGROUND: Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient's indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A 'Question-by-Question Guide' was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org. CONCLUSIONS/SIGNIFICANCE: It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

The long-term impact of the leprosy post-exposure prophylaxis (LPEP) program on leprosy incidence: a modelling study

The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of SDR to eligible contacts of newly diagnosed leprosy patients in states or districts of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. This study investigated the long-term impact of the LPEP program on the leprosy new case detection rate (NCDR). Our results show that LPEP could reduce the NCDR beyond the impact of the routine leprosy control programme and that many new cases could be prevented. The benefit of LPEP increases gradually over time. LPEP could accelerate the time of reaching predicted NCDR levels of 2040 under routine program by up to six years. Furthermore, we highlighted how the impact varies between countries due to differences in the number of contacts per index patient screened and differences in leprosy epidemiology and national control programme. Generally, including both household contacts and neighbours (> 20 contacts per index patient) would yield the highest impact.

Delay in tuberculosis case detection in Pwani region, Tanzania. A cross sectional study.

BACKGROUND: Delay in Tuberculosis (TB) case detection may worsen the disease and increase TB transmission. It is also a challenge to the National TB and Leprosy control Program (NTLP). METHODS: We conducted a cross sectional study in four out of six districts in Pwani region to estimate the extent and factors responsible for delay in TB case detection in Pwani region. Delays were divided into patient, health facility and total delay. RESULTS: We enrolled a total of 226 smear positive TB patients. Out of 226 patient's results were available for 206. The majority (66.5%) of the patients were males. Mean age for males and females were 37.3 and 33.7 years respectively. Mean (SD) total delay was 125.5 (98.5) days (median 90). Out of 206 patients, 79 (38.35%) delayed to seek TB health care. Health facility delay was observed among 121 (58.7%) patients.Risk factors for delay was poor knowledge that chest pain may be a TB symptom (OR = 2.9; 95%CI 1.20- 7.03) and the belief that TB is always associated with HIV/AIDS (OR = 2.7; 95%CI 1.39-5.23). Risk for delay was low among patients who first presented to a government health facility (OR = 0.3; 95%CI 0.12- 0.71) and those presenting with chest pain (OR = 0.2; 95%CI 0.10-0.61). CONCLUSION: There is a considerable delay in TB case detection in Pwani mainly contributed by patients. Risk factors for delay include misconception about TB/HIV and poor knowledge of TB symptoms.

Prospects, achievements, challenges and opportunities for scaling-up malaria chemoprevention in pregnancy in Tanzania: the perspective of national level officers.

OBJECTIVES: To describe the prospects, achievements, challenges and opportunities for implementing intermittent preventive treatment for malaria in pregnancy (IPTp) in Tanzania in light of national antenatal care (ANC) guidelines and ability of service providers to comply with them. METHODS: In-depth interviews were made with national level malaria control officers in 2006 and 2007. Data was analysed manually using a qualitative content analysis approach. RESULTS: IPTp has been under implementation countrywide since 2001 and the 2005 evaluation report showed increased coverage of women taking two doses of IPTp from 29% to 65% between 2001 and 2007. This achievement was acknowledged, however, several challenges were noted including (i) the national antenatal care (ANC) guidelines emphasizing two IPTp doses during a woman's pregnancy, while other agencies operating at district level were recommending three doses, this confuses frontline health workers (HWs); (ii) focused ANC guidelines have been revised, but printing and distribution to districts has often been delayed; (iii) reports from district management teams demonstrate constraints related to women's late booking, understaffing, inadequate skills of most HWs and their poor motivation. Other problems were unreliable supply of free SP at private clinics, clean and safe water shortage at many government ANC clinics limiting direct observation treatment and occasionally pregnant women asked to pay for ANC services. Finally, supervision of peripheral health facilities has been inadequate and national guidelines on district budgeting for health services have been inflexible. IPTp coverage is generally low partly because IPTp is not systematically enforced like programmes on immunization, tuberculosis, leprosy and other infectious diseases. Necessary concerted efforts towards fostering uptake and coverage of two IPTp doses were emphasized by the national level officers, who called for further action including operational health systems research to understand challenges and suggest ways forward for effective implementation and high coverage of IPTp. CONCLUSION: The benefit of IPTp is appreciated by national level officers who are encouraged by trends in the coverage of IPTp doses. However, their appeal for concerted efforts towards IPTp scaling-up through rectifying the systemic constraints and operational research is important and supported by suggestions by other authors.

Monitoring the size of the leprosy problem: which epidemiological indicators should we use?

The purpose of the study was to discuss the interpretation of epidemiological trends in leprosy, using currently available indicators. A number of leprosy-endemic countries and regions were chosen for which epidemiological data have been published for a period of at least 15 years. Using these examples, relative merit of the registered prevalence rate, the case detection rate, the children proportion among new cases and proportion of new cases with grade 2 disability will examined for interpreting the leprosy situation in these countries. Considerable drop of the registered prevalence rates (PR) were evident in all endemic countries. However, this decline was due largely to shortening of treatment and 'cleaning' of leprosy registers and has not been reflected in the annual case detection rates (CDR), except in a few countries. The proportion of new cases with grade 2 impairment had decreased substantially, which indicates earlier case finding. However, the proportion of children among new cases did not change much in the past decade. It is indicate that transmission is still continuing. We reiterate the conclusion of the ILA Technical Forum that the (annual) case detection rate is the most appropriate indicator for monitoring of leprosy situation in a given country or area. Two additional indicators that helped to interpret the CDR were the proportion of new cases with grade 2 impairments, reflecting the delay between occurrence and diagnosis of the disease, and the proportion of children among new cases, which is used as a proxy indicator for recent transmission.

Structure and performance of infectious disease surveillance and response, United Republic of Tanzania, 1998.

OBJECTIVE: To assess the structure and performance of and support for five infectious disease surveillance systems in the United Republic of Tanzania: Health Management Information System (HMIS); Infectious Disease Week Ending; Tuberculosis/Leprosy; Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome; and Acute Flaccid Paralysis/Poliomyelitis. METHODS: The systems were assessed by analysing the core activities of surveillance and response and support functions (provision of training, supervision, and resources). Data were collected using questionnaires that involved both interviews and observations at regional, district, and health facility levels in three of the 20 regions in the United Republic of Tanzania. FINDINGS: An HMIS was found at 26 of 32 health facilities (81%) surveyed and at all 14 regional and district medical offices. The four other surveillance systems were found at <20% of health facilities and <75% of medical offices. Standardized case definitions were used for only 3 of 21 infectious diseases. Nineteen (73%) health facilities with HMIS had adequate supplies of forms; 9 (35%) reported on time; and 11 (42%) received supervision or feedback. Four (29%) medical offices with HMIS had population denominators to use for data analyses; 12 (86%) were involved in outbreak investigations; and 11 (79%) had conducted community prevention activities. CONCLUSION: While HMIS could serve as the backbone for IDSR in the United Republic of Tanzania, this will require supervision, standardized case definitions, and improvements in the quality of reporting, analysis, and feedback.

Association between leprosy and HIV infection in Tanzania.

SETTING: An epidemiological study of the interaction of leprosy and HIV infection in Tanzania. OBJECTIVE: To establish the prevalence of HIV infection among leprosy patients, and to measure the association of HIV and leprosy by comparing the HIV prevalence in leprosy patients and blood donors. DESIGN: Testing for HIV infection in consecutively diagnosed leprosy patients (new and relapsed after MDT) in all regions in Tanzania successively for a period of 3 to 6 months during 1991, 1992 and 1993. RESULTS: Out of the total estimated eligible leprosy patients, 697 patients (69%) entered the final analysis. The HIV prevalence among these leprosy patients was 12% (83/697) as compared to 6% (8960/ 158,971) in blood donors examined in Tanzania during the same period. There were no significant differences in HIV seroprevalence by age, sex, residence or type of disease. However, the adjusted odds ratio (OR) of the presence of a BCG scar was 1.9 [95% confidence interval (CI) 1.1-3.3] among HIV-positive leprosy cases compared to HIV-negative leprosy cases. Comparing leprosy cases with blood donors as controls, the logistic regression model, controlling for sex, age group and residence, showed the OR for HIV seropositivity among leprosy patients to be 2.5 (95% CI 2.0-3.2). This association existed in all strata, but was strongest in the 15-34-year age group. No difference of HIV status between multibacillary and paucibacillary leprosy could be shown to exist. The point estimate of the population attributable risk of HIV infection for leprosy was 7%. CONCLUSION: HIV infection is associated with leprosy and might reverse the epidemiological trend of the slow decline in case notification in Tanzania if HIV infection is increasing greatly. Previous BCG vaccination loses its protection against leprosy in the presence of HIV infection. A repeated study is recommended in order to validate these findings, whereby recording of the disability grading of the cases is necessary to adjust for delay in diagnosis.

PIP: The association between HIV infection and leprosy was investigated in 731 consecutive leprosy cases from all 20 regions of Tanzania. These cases represented 69% of total notified new and relapsed leprosy cases reported in the 1991-93 study period. HIV prevalence among the 679 patients for whom complete data were available was 12% (83 cases). Leprosy patients aged 35-54 years and those without a BCG scar were significantly less likely than their counterparts aged 15-34 years and those with a BCG scar to be HIV-infected. There were no significant differences in HIV prevalence in terms of sex, urban or rural residence, new or relapsed cases, and paucibacillary or multibacillary leprosy. Among controls--all 158,971 blood donors tested for HIV during 1991 to 1993--HIV prevalence was 6%. The overall odds ratio for HIV infection among leprosy patients compared with controls, after adjustments for sex, age, and residence, was 2.5 (95% confidence interval, 2.0-3.2). Point estimates of the attributable risk and the population attributable risk were 57% and 7%, respectively. These findings indicate that HIV infection significantly increases the risk of leprosy in Tanzania and compromises the protective effect of BCG vaccination. Although case notifications of leprosy in Tanzania have not changed appreciably in the past 13 years, expansion of the HIV epidemic could have a significant effect on the epidemiology of leprosy.

Adverse cutaneous reactions to thiacetazone for tuberculosis treatment in Tanzania.

Because thiacetazone has been linked with serious adverse cutaneous reactions, we undertook 1 year of systematic surveillance for cutaneous thiacetazone-associated adverse reactions within the national tuberculosis programme of Tanzania. For individual cases, we collected information on age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation (toxic epidermal necrolysis, rash without necrolysis, itching without rash), and outcome (dead or alive) within 2 weeks of onset. Univariate and multivariate analyses were done of variables relevant to outcome. 1273 patients with adverse reactions were reported. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients, and 19.1% among patients with toxic epidermal necrolysis. About 60% of all adverse reactions and deaths occurred within 20 days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than reported previously, suggesting that improved management might allow retention of thiacetazone in the armamentarium of national tuberculosis programmes even where infection with HIV is prevalent.

PIP: Thiacetazone is a useful and inexpensive companion drug in the treatment of tuberculosis (TB). Its main contribution is its ability to prevent failure and relapse in patients with initially isoniazid-resistant strains. Early toxicity studies showed that the drug was generally better tolerated in East Africa than in many other countries. Thiacetazone is an essential drug in the Tanzania National Tuberculosis/Leprosy Program. Under trial conditions in Tanzania, before the HIV epidemic, adverse reactions associated with thiacetazone were uncommon. Serious, and occasionally fatal, toxic cutaneous reactions to sulphur-containing drugs in HIV-infected patients have been recognized for several years. Recently, the use of thiacetazone in HIV-infected patients has been linked with serious adverse cutaneous reactions, including toxic epidermal necrolysis. Most reports, however, concerned only patients admitted to referral hospitals, so the Tanzania National Tuberculosis Program began a nationwide one-year systematic surveillance study to determine the frequency and severity of adverse cutaneous reactions. Individual-level data were collected on each case's age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation, and outcome within two weeks of onset. The study identified 1273 patients with adverse reactions. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients and 19.1% among patients with toxic epidermal necrolysis. Approximately 60% of all adverse reactions and deaths occurred within twenty days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than previously reported, suggesting that improved management may allow the retention of thiacetazone as a weapon against TB even where infection with HIV is prevalent.

The proportion of tuberculosis cases in Tanzania attributable to human immunodeficiency virus.

BACKGROUND: Routine data obtained from the National Tuberculosis and Leprosy Programme (NTLP) of Tanzania have shown a constant increase in the notified number of tuberculosis (TB) cases since 1982. Possible causes include an improved reporting system, improvement in health services after the introduction of short course chemotherapy (SCC), and human immunodeficiency virus (HIV) infection. This paper examines to what extent the increased TB case detection rate can be attributed to HIV infection, by calculating the population attributable risk for various years. METHOD: The prevalence of HIV infection was obtained from data of the National AIDS Control Programme and the relative risk of HIV for developing TB from a case-control study and the literature. RESULTS: Between 1985 and 1989 the increase was the highest among women aged 15-24 years and men aged 25-34 years; age groups in which HIV prevalence is highest. In the case-control study HIV prevalence among blood donors was 9.4% and among smear-positive pulmonary TB patients 51.6%, giving an odds ratio (OR) of 8.1 (95% confidence interval (CI): 4.4-16.3). For all TB cases the OR was 11.8. In a population with an HIV prevalence of 10%, about 40% of the smear-positive TB patients are attributable to HIV. The excess of TB cases in the entire country between 1982 and 1989 can be attributable to HIV infection. This has implications for TB control and socioeconomic consequences in the country.

PIP: The increase seen in the incidence of tuberculosis (TB) in many developing countries in the early 1980s was at first through to be the result of better case detection, but it soon became clear that HIV infections were influencing this increase. To determine the extent that HIV infection has increased TB case detection rates in Tanzania, data were analyzed from the National TB and Leprosy Programme, the National AIDS Control Programme, and a case-control study conducted for three months in 1990. Cases were all 128 newly registered cases of TB in three districts. Controls were 1558 blood donors in these districts. HIV prevalence among the cases was 51.6%, with no differences in sex, residence, or type of TB. HIV prevalence was highest among 25-34 year olds. HIV prevalence in controls was 9.4%, with no variation by age or sex. The odds ratio for association between HIV infection and new smear-positive TB, stratified by age, was 8.1. The age-stratified offs ratio for HIV infection and any type of TB was 11.8. The population attributable risk for 1990 was in the order of 30%, which means that, without HIV, the increase in TB cases seen after 1985 would not have occurred. It is essential to improve TB programs to minimize the looming increase in the annual risk of infection. Also, HIV control programs will have a large effect on TB control programs, and collaboration between the two should be encouraged.

AIDS blamed for increase in Tanzanian tuberculosis cases.

AIDS: A rising case load of tuberculosis (TB) in Tanzania is being blamed on HIV/AIDS, according to the manager of the country's TB and leprosy control program. Tanzania's Health Ministry estimates that 1.5 million Tanzanians are HIV-positive, a figure expected to double by the year 2000. The increase in TB cases is now eroding achievements gained in the national campaign to combat the disease. A greater effort is required to erase the information gap that has developed, particularly in the semi-literate rural population, about AIDS and TB.^ieng

HIV-1 infection as a risk factor for leprosy; a case-control study in Tanzania.

A case-control study was carried out in Tanzania to determine the relative risk of those with HIV-1 infection for getting leprosy. Cases were 93 consecutively diagnosed patients with leprosy aged 15-54 years from the Mwanza Region. Controls were a representative population sample of 4161 people drawn from a stratified cluster sample from urban areas, roadside settlements, and rural villages. HIV-1 infection was determined by enzyme-linked immunosorbent assay (ELISA); Western blot was used when the ELISA result was indeterminate. The HIV-1 prevalence in leprosy cases was 10% in rural (7 of 72) and in roadside and urban areas (2 of 21); in controls these prevalences were 3.4% and 9.9%, respectively. The relative risk of HIV-1 infection for the development of leprosy was estimated to be 2.2 [95% confidence interval (CI) = 1.0-4.7; p = 0.07]. HIV-1 infection was significantly associated with multibacillary (MB) leprosy (odds ratio 4.6; CI = 1.3-13.2) but not with paucibacillary leprosy (odds ratio 1.4; 95% CI = 0.4-3.8). The population etiological fraction for the development of MB leprosy attributable to HIV-1 infection in this population is estimated to be 13% (95% CI = 4%-23%). We conclude that HIV-1 is a risk factor for the development of MB leprosy. The impact of the HIV-1 epidemic on the incidence of leprosy so far has been limited since HIV-1 occurs mainly in urban areas and leprosy in rural areas.