Interrupted time-series analysis of active case-finding for tuberculosis during the COVID-19 pandemic, Zambia.

Objective: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent implementation of tuberculosis response measures on tuberculosis notifications in Zambia. Methods: We used an interrupted time-series design to compare monthly tuberculosis notifications in Zambia before the pandemic (January 2019 to February 2020), after implementation of national pandemic mitigation measures (April 2020 to June 2020) and after response measures to improve tuberculosis detection (August 2020 to September 2021). The tuberculosis response included enhanced data surveillance, facility-based active case-finding and activities to generate demand for services. We used nationally aggregated, facility-level tuberculosis notification data for the analysis. Findings: Pre-pandemic tuberculosis case notifications rose steadily from 2890 in January 2019 to 3337 in February 2020. After the start of the pandemic and mitigation measures, there was a -22% (95% confidence interval, CI: -24 to -19) immediate decline in notifications in April 2020. Larger immediate declines in notifications were seen among human immunodeficiency virus (HIV)-positive compared with HIV-negative individuals (-36%; 95% CI: -38 to -35; versus -12%; 95% CI: -17 to -6). Following roll-out of tuberculosis response measures in July 2020, notifications immediately increased by 45% (95% CI: 38 to 51) nationally and across all subgroups and provinces. The trend in notifications remained stable through September 2021, with similar numbers to the predicted number had the pandemic not occurred. Conclusion: Implementation of a coordinated public health response including active tuberculosis case-finding was associated with reversal of the adverse impact of the pandemic and mitigation measures. The gains were sustained throughout subsequent waves of the pandemic.

Mortality among persons with tuberculosis in Zambian hospitals: A retrospective cohort study.

Tuberculosis (TB) mortality in Zambia remains high at 86 per 100,000 populations, translating to approximately 15,000 TB-related deaths annually. We conducted a nationwide retrospective cohort study to understand predictors, time to death, and probable causes of mortality among persons on TB treatment in Zambia. We reviewed medical records for persons with TB registered in 54 purposively selected hospitals in Zambia between January and December 2019. We fitted a Cox proportional hazards model to identify predictors of mortality. Of the 13,220 records abstracted, 10,987 were analyzed after excluding records of persons who transferred in from other hospitals, those with inconsistent dates and those whose treatment outcome was not evaluated. The majority of persons with TB were men, (61.5%, n = 6,761) with a median age of 36 years (IQR: 27-46 years). Overall, 1,063 (9.7%) died before completing TB treatment (incidence rate = 16.9 deaths per 1,000 person-months). Median age at death was 40 years (IQR: 31-52). The majority of deaths (75.7%, n = 799) occurred in the first two months of TB treatment, with a median time to death of 21 days (IQR: 6-57). Independent risk factors for TB mortality included age >54 years, being treated in Eastern, Southern, Western, Muchinga and Central provinces, receiving treatment from a third-level or mission hospital, methods of diagnosis other than Xpert MTB/RIF, extrapulmonary TB (EPTB), and positive HIV status. Probable causes of death were septic shock (18.8%), TB Immune Reconstitution Inflammatory Syndrome (TB IRIS) (17.8%), end-organ damage (13.4%), pulmonary TB (11.4%), anemia (9.6%) and TB meningitis (7.8%). These results show high mortality among people undergoing TB treatment in Zambia. Interventions targeted at persons most at risk such as the elderly, those with EPTB, and those living with HIV, can help reduce TB-related mortalities in Zambia.

A 10-year Review of TB Notifications and Mortality Trends Using a Joint Point Analysis in Zambia - a High TB burden country.

BACKGROUND: Zambia is one of the TB high-burden countries. It is important to track the progress being made towards enhancing case finding and reducing mortality. We reviewed routine TB notifications and mortality trends, over a decade from all facilities in Zambia. METHODS: A 10-year retrospective study of TB notifications and mortality trends was performed using a Joint Point Analysis version 4.9.0.0, NCI. We extracted the annual national TB program data for the period under review. RESULTS: There was a decline in annual point average for notification between 2010 and 2020 in both males and females, but the females notification rates had a higher rate of decline (AAPC = -6.7, 95%CI:-8.3 to -5.0), p<0.001) compared to the decline in males notification rate (AAPC = -4.1, 95%CI:-4.1 to -5.1, P<0.001). We found a significant growth rate in the proportion of TB patients that were bacteriologically confirmed (AAPC = 6.1, 95% CI: 3.6 to 8.7, p< 0.001), while the proportion of clinically diagnosed patients declined (AAPC= -0.1, 95%CI: -2.3 to 2.1, p<0.001). Notification of drug-resistant TB increased exponentially (AAPC=27.3, 95% CI: 13 to 41), p< 0.001) while mortality rate declined from 21.3 in 2011 to 12.7 in 2019 per 100,000 population (AAP=-5.6, 95%CI: -9.6 to -1.5, p=0.008). CONCLUSIONS: This study has illustrated the importance of reviewing and analyzing routinely collected TB data by national programs. The study revealed areas of improvement in terms of TB control and underscores the need for increased and sustained investment in case detection and diagnostics.

The HIV-associated tuberculosis epidemic--when will we act?

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV.

BACKGROUND: In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. DISCUSSION: District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. SUMMARY: Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not.

Tuberculosis care cascade in Zambia - identifying the gaps in order to improve outcomes: a population-based analysis.

OBJECTIVE: Tuberculosis (TB) remains a leading cause of morbidity and mortality in Zambia, especially for people living with HIV (PLHIV). We undertook a care cascade analysis to quantify gaps in care and align programme improvement measures with areas of need. DESIGN: Retrospective, population-based analysis. SETTING: We derived national-level estimates for each step of the TB care cascade in Zambia. Estimates were informed by WHO incidence estimates, nationally aggregated laboratory and notification registers, and individual-level programme data from four provinces. PARTICIPANTS: Participants included all individuals with active TB disease in Zambia in 2018. We characterised the overall TB cascade and disaggregated by drug susceptibility results and HIV status. RESULTS: In 2018, the total burden of TB in Zambia was estimated to be 72 495 (range, 40 495-111 495) cases. Of these, 43 387 (59.8%) accessed TB testing, 40 176 (55.4%) were diagnosed with TB, 36 431 (50.3%) were started on treatment and 32 700 (45.1%) completed treatment. Among all persons with TB lost at any step along the care cascade (n=39 795), 29 108 (73.1%) were lost prior to accessing diagnostic services, 3211 (8.1%) prior to diagnosis, 3745 (9.4%) prior to initiating treatment and 3731 (9.4%) prior to treatment completion. PLHIV were less likely than HIV-negative individuals to successfully complete the care cascade (42.8% vs 50.2%, p<0.001). Among those with rifampicin-resistant TB, there was substantial attrition at each step of the cascade and only 22.8% were estimated to have successfully completed treatment. CONCLUSIONS: Losses throughout the care cascade resulted in a large proportion of individuals with TB not completing treatment. Ongoing health systems strengthening and patient-centred engagement strategies are needed at every step of the care cascade; however, scale-up of active case finding strategies is particularly critical to ensure individuals with TB in the population reach initial stages of care. Additionally, a renewed focus on PLHIV and individuals with drug-resistant TB is urgently needed to improve TB-related outcomes in Zambia.

Who has access to counseling and testing and anti-retroviral therapy in Malawi - an equity analysis.

BACKGROUND: The HIV and AIDS epidemic in Malawi poses multiple challenges from an equity perspective. It is estimated that 12% of Malawians are living with HIV or AIDS among the 15-49 age group. This paper synthesises available information to bring an equity lens on Counselling and Testing (CT) and Antiretroviral Therapy (ART) policy, practice and provision in Malawi. METHODS: A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi. FINDINGS: At the policy level Malawi is unique in having an equity in access to ART policy, and equity considerations are also included in key CT documents. The number of people accessing CT has increased considerably from 149,540 in 2002 to 482,364 in 2005. There is urban bias in provision of CT and more women than men access CT. ART has been provided free since June 2004 and scale up of ART provision is gathering pace. By end December 2006, there were 85,168 patients who had ever started on ART in both the public and private health sector, 39% of the patients were male while 61% were female. The majority of patients were adults, and 7% were children, aged 14 years or below. Despite free ART services, patients, especially poor rural patients face significant barriers in access and adherence to services. There are missed opportunities in strengthening integration between CT and ART and TB, Sexually Transmitted Infections (STI) and maternal health services. CONCLUSION: To promote equitable access for CT and ART in Malawi there is need to further invest in human resources for health, and seize opportunities to integrate CT and ART services with tuberculosis, sexually transmitted infections and maternal health services. This should not only promote access to services but also ensure that resources available for CT and ART strengthen rather than undermine the provision of the essential health package in Malawi. Ongoing equity analysis of services is important in analyzing which groups are unrepresented in services and developing initiatives to address these. Creative models of decentralization, whilst maintaining quality of services are needed to further enhance access of poor rural women, men, girls and boys.

The Malawi National Tuberculosis Programme: an equity analysis.

BACKGROUND: Until 2005, the Malawi National Tuberculosis Control Programme had been implemented as a vertical programme. Working within the Sector Wide Approach (SWAp) provides a new environment and new opportunities for monitoring the equity performance of the programme. This paper synthesizes what is known on equity and TB in Malawi and highlights areas for further action and advocacy. METHODS: A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken and complemented by additional analysis of routine data on access to TB services. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi and a review of the international literature. RESULTS: The lack of a prevalence survey severely limits the epidemiological knowledge base on TB and vulnerability. TB cases have increased rapidly from 5,334 in 1985 to 28,000 in 2006. This increase has been attributed to HIV/AIDS; 77% of TB patients are HIV positive. The age/gender breakdown of TB notification cases mirrors the HIV epidemic with higher rates amongst younger women and older men. The WHO estimates that only 48% of TB cases are detected in Malawi. The complexity of TB diagnosis requires repeated visits, long queues, and delays in sending results. This reduces poor women and men's ability to access and adhere to services. The costs of seeking TB care are high for poor women and men - up to 240% of monthly income as compared to 126% of monthly income for the non-poor. The TB Control Programme has attempted to increase access to TB services for vulnerable groups through community outreach activities, decentralising DOT and linking with HIV services. CONCLUSION: The Programme of Work which is being delivered through the SWAp is a good opportunity to enhance equity and pro-poor health services. The major challenge is to increase case detection, especially amongst the poor, where we assume most 'missing cases' are to be found. In addition, the Programme needs a prevalence survey which will enable thorough equity monitoring and the development of responsive interventions to promote service access amongst 'missing' women, men, boys and girls.

The use of a monitoring tool to assess counselling and HIV testing in the public health sector in Malawi.

Scaling up of counselling and HIV testing (VCT) services requires a system of regular monitoring and evaluation. AVCT monitoring tool was developed through a consultative process and used to assess counselling and HIV testing services in 16 government and mission hospitals in Malawi, which had started expanded HIV-TB activities in July 2003. The essential components of theVCT monitoring tool included assessments of: (i) the hospital VCT personnel, in particular the number of counsellors (full-time and part-time) and those trained in and performing whole blood rapid HIV testing; (ii) the hospital laboratory service, in particular the protocols for HIV testing; (iii) the number, structure and function of dedicated VCT rooms; (iv) registers for patients, clients and donors having HIV tests; and (v) the quality of VCT through structured interviews with HIV-positive patients with TB. The main findings were: 9644 patients and clients were HIV tested between July and September 2003; HIV testing protocols were not standardized and differed between hospitals; there was little in the way of external quality assurance and there were deficiencies in the counselling process. In each hospital, the mean time taken to obtain the data and complete theVCT monitoring tool was 3 h. TheVCT monitoring tool is straightforward to use, and the data collected should help to improve standardization, quality and future planning of VCT services in the country.

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.