**4. Discussion**

This is the first study in Malawi to assess the impact of COVID-19 on TB and HIV services in selected health facilities in Lilongwe, the capital city. In summary, there was a large negative impact on TB case detection and HIV testing, while TB treatment outcomes for those enrolled to anti-TB treatment and the referral of HIV-positive persons to ART were essentially unaffected.

With respect to TB programme activities, the number of people presenting to health facilities with presumptive PTB declined considerably over the 12-month COVID-19 period, the negative effect being worse in the first 6 months compared with the second 6 months of the COVID-19 period. Children and women were particularly affected. There is little information in the literature to explain these findings, so the reasons have to be speculative. A qualitative study in neighbouring Zambia found that patients recently diagnosed with TB during the COVID-19 pandemic were very concerned about contracting COVID-19 during

clinic visits, perceiving the disease to be highly transmissible, deadly, and without effective treatment [27]. It is possible that these concerns were felt more keenly amongs<sup>t</sup> mothers and their children, thus reducing the desire of the family unit to attend health facilities. A large decline in children being admitted to and diagnosed with TB in two hospitals in Johannesburg, South Africa, during COVID-19 would support this hypothesis [28]. The decline in persons presenting with presumptive PTB was similar to what was observed in the early months of COVID-19 in clinics in Tehran, Iran [29], and Nigeria [30], where transportation difficulties, as well as community fear of health facilities, were thought to hinder health facility access.

The bacteriological positivity rate in those being investigated for presumptive PTB in our study was almost twice as high in the COVID-19 period compared with the previous year, and this may partly explain the less severe decline observed in cases diagnosed and registered with TB. This finding suggests the possibility that those with more severe symptoms and who were more likely to have TB continued trying to access health facilities and that laboratory operating procedures remained relatively intact during the COVID-19 period.

There was a decline in the number of people registered for TB treatment. These findings are also in line with reports from elsewhere where the decreases in TB case notifications in the early months of COVID-19 compared with previous years were 48% in clinics in China [31], 48% in clinics in Brazil [32], and 56% in India [33].

A recent report on 84 countries from WHO showed an overall 21% decrease in TB case notifications in 2020 compared with 2019 [34], attributed essentially to the COVID-19 pandemic. A modelling analysis at the start of the pandemic suggested that a 3-month suspension of TB services due to COVID-19 lockdown followed by 10 months restoration back to normal would cause over a 5 year period an additional 1.2 million TB cases in India, 25,000 additional TB cases in Kenya, and 4000 additional cases in Ukraine, mainly as a result of the accumulation of undetected TB during lockdown [6]. A further modelling study in high-burden, low-income, and middle-income countries predicted a 20% increase in TB mortality, with most of this occurring as a result of reductions in timely diagnosis and treatment of new cases of TB [7]. These statistics, worrying as they are, were obtained early on in the pandemic when it was hoped that service disruption would be temporary. The reality, however, is that service disruption in Malawi has continued throughout the year and is likely to continue into 2021 and beyond, with even worse impacts on the TB epidemic than originally forecasted.

On an encouraging note, however, TB treatment success rates were maintained at high levels during the COVID-19 pandemic. These high rates above 90% were surprising but were verified each month with the TB programme and the Lighthouse staff. It is possible that the smaller number of patients enrolled on treatment during the COVID-19 period made the workload of follow-up easier. At the start, we had been concerned that COVID-19 restrictions would hinder patients collecting anti-TB medications, would compromise drug adherence, and reduce the ability of TB programme staff from obtaining information about final treatment outcomes. Patients coinfected with TB and COVID-19 are at increased risk of death [35,36], and we also had concerns that there might be TB patients with undetected COVID-19, and this might increase TB treatment deaths. Fortunately, this was not the case in our study, and there was a slight decrease in the risk of death.

With respect to HIV services, there was a significant decrease in numbers presenting for HIV testing, this improving slightly during the latter half of the COVID-19 period. This is similar to the reductions in HIV testing that have been observed in Europe [37], the United States [38], and Africa [39]. The fall-off in HIV testing threatens access to diagnosis and treatment of people living with HIV that, in turn, could result in excess HIV-related deaths and ongoing transmission of HIV in the community. The increase in HIV-positivity observed in the COVID-19 period in our study is probably a result of health facility testing being more directed to targeted testing of high-risk groups and the confirmation of positive results in those identified HIV-positive through self-testing. It was encouraging to see that

referrals to ART were maintained at a very high level over the whole 24 months, with only a slight decrease in the COVID-19 period. Again, this reflects the fact that any person diagnosed HIV positive is now eligible for ART.

This study had several strengths. First, the real-time monthly surveillance was embedded within the routine services of the eight health facilities. Second, there was crosschecking and validation of the data each month between the country coordinator and the overall study monitoring and evaluation officer, and we believe, therefore, that the data are accurate. Third, we used two 12-month periods to compare data, and this enabled us to account for any seasonal changes that might have affected access to health facilities, e.g., during the rainy season. Finally, the conduct and reporting of the study were in line with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [40].

There were, however, some limitations. Our study was limited to health facilities in Lilongwe, and therefore may not be representative of Malawi as a whole. The use of aggregate data limits our understanding of the cascade of care for TB case detection and HIV testing. We only assessed referral to ART and did not document whether ART was initiated or whether patients were retained on treatment once it had started. Previous studies have suggested that ART interruption has been a problem during the COVID-19 pandemic [41]. It would have been interesting to assess this in Malawi, especially as an interruption to ART is thought to be the most important determinant of HIV-related mortality during the COVID-19 pandemic [42]. Finally, the official monthly reports to WHO of COVID-19 cases and deaths may have underestimated the true burden of COVID-19 in the country. A study on deceased people at the University Teaching Hospital morgue in Lusaka, Zambia, found that just 9% of 70 people who were SARS-CoV-2 confirmed from postmortem nasopharyngeal swabs within 48 h of death had ever been tested before death [43]. It is likely that this type of finding is not confined to Zambia and that large numbers of unreported cases and deaths due to COVID-19 are occurring in other countries in Africa, including Malawi.

Despite these limitations, there are some important programmatic implications from this study. First, the strengthened monthly surveillance system worked well with both disease control programme directors looking each month at the monthly reports and using the data. While there were improvements in TB case detection and HIV testing in the latter half of the COVID-19 pandemic, there were still significant shortfalls in numbers, and these could not be redressed or brought back to pre-COVID-19 levels. Whether the inability to turn around this negative impact was due to ongoing anxiety and fear amongs<sup>t</sup> the community about attending health facilities and/or to continued restrictions imposed by partial lockdown and then full lockdown is difficult to say and requires more in-depth mixed-methods research. Monthly surveillance required effort and external support, and while this was acknowledged to be useful during a crisis such as COVID-19, both programme directors felt it would be difficult to sustain this as a routine activity. Monthly surveillance in sentinel sites might be a less expensive way of doing this and should be considered.

Second, with COVID-19 likely to become endemic, there is an urgen<sup>t</sup> need to bring TB case detection back to pre-COVID-19 levels. Several suggestions have been made about how to do this. These include: integrating TB and COVID-19 control programmes in terms of fast-tracking patients with respiratory symptoms for TB and COVID-19; screening for both diseases at community and health facility level; sharing testing algorithms and diagnostic equipment within the laboratories; ensuring effective infection, prevention, and control activities within health facilities; having longer 3-month follow-up appointments for patient check-ups and drug collection; providing health information education in health facilities and the community; and mobilizing support networks of TB survivors and TB communities [44–46]. More use of electronic platforms for case finding, drug adherence, managemen<sup>t</sup> of adverse drug reactions, and training has also been recommended as a way of rapidly restoring TB care and prevention services [47], and Malawi could consider all of these innovative approaches.

Third, HIV self-testing and home-based HIV testing services have allowed HIV testing numbers to rebound in some other African countries [48–50]. Malawi has already moved in this direction with the scale-up of HIV self-testing and index testing, especially during the second half of the COVID-19 period. This needs to continue while at the same time ensuring that numbers and results are recorded and reported, so that HIV-infected persons in need of ART do not slip through the net.
