Tuberculosis in prisons in sub-Saharan Africa--a potential time bomb.

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Application of highly portable MinION nanopore sequencing technology for the monitoring of nosocomial tuberculosis infection

Referral hospitals in sub-Saharan Africa concentrate large numbers of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) patients, failed by community TB services. We have previously shown, from enhanced screening and through autopsy studies, a significant burden of missed TB infections at the University Teaching Hospital, Lusaka, Zambia, with many patients dying or being discharged without treatment. With minimal TB isolation facilities and minimal political will to invest in broader screening and isolation, the risk of nosocomial transmission is likely to be extremely high. Studies from other hospitals in low burden settings and in South Africa have shown that next generation sequencing (NGS) is a very powerful tool for rapidly sequencing whole TB genomes and comparing them to confirm or rule out nosocomial transmission. The established platforms for NGS analysis, such as Illumina, are very expensive, immobile, and require regular maintenance, making them a costly inclusion on a research proposal or programmatic intervention grant in Africa. MinION nanopore sequencing has changed the NGS landscape with cheap portable sequencers, rapid simple library preparation (15min), and automated real-time analysis tools. The application of highly portable MinION nanopore sequencing technology for the monitoring of nosocomial TB infection will be discussed. Preliminary data from our pediatric pneumonia study will demonstrate the detection of TB in induced sputum from children admitted to the University Teaching Hospital

Perspectives on tuberculosis in pregnancy

Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations. (c) 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

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

Factors associated with Coronavirus disease 2019 (COVID-19) and an assessment of adherence to infection prevention and control (IPC) guidelines among health workers —Nakonde District, Zambia, 2020

Introduction: Health workers play a critical role in the clinical management of COVID-19 patients. However, research on their infection risk and clinical characteristics, particularly in Africa, is emerging. We investigated risk factors for COVID-19 infection and assessed adherence to infection prevention and control (IPC) guidelines among health workers in Nakonde District. Methods: A case-control study among health workers at Nakonde Urban Health Centre and Nakonde District Hospital was conducted from 15 to 25 May 2020. A standardized questionnaire covering demographic information; possible exposure to persons with COVID-19; adherence to infection prevention and control measures was administered to all health workers present at these facilities. Descriptive statistics were performed and logistic regression was used to calculate the odds ratio (OR) and 95% CIs. Results: A total of 197 HCWs are deployed in the two facilities out of which we obtained 138 responses. Seventy-five (54%) had complete responses that were analyzed in this study. Among the 75, 54 (72%) were female. The median age for all the HCWs that responded was 30 years (IQR 26-33). Thirty-seven (49%) were laboratory-confirmed COVID-19 cases. Symptoms that were exhibited among HCWs with COVID-19 included cough (49%), headache (43%), runny nose (32%) and fatigue (18%); fever was rarely reported (8%). Cough was associated with being a case of COVID-19 (OR 4.2 95% CI 1.5-11.9). Coexisting conditions were similar among the cases and controls. There were no statistically significant differences in exposures between HCWs with confirmed COVID-19 and those without (OR 0.96; 95% CI 0.4-2.5). The WHO five moments of hand hygiene recommended for health workers were practiced by (64%). Non availability of Personal Protective Equipment was reported by 70% of HCWs and this was similar among the cases of COVID-19 and the non-cases. Conclusion: Given the critical role HCWs play in looking after the sick, continued protection of this population at work, at home, and in the community through surveillance should be a national priority

Digital CXR with computer aided diagnosis versus symptom screen to define presumptive tuberculosis among household contacts and impact on tuberculosis diagnosis.

BACKGROUND: Household (HH) contact tracing is a strategy that targets high risk groups for TB. Symptom based screening is the standard used to identify HH contacts at risk for TB during HH contact tracing for TB. However, this strategy may be limited due to poor performance in predicting TB. The objective of this study was to compare CXR with Computer Aided Diagnosis (CAD) against symptom screen for defining presumptive TB and how TB detection changes with each method. METHODS: Household contacts of consecutive index bacteriologically confirmed TB cases were visited by study teams and given TB/HIV education to raise awareness of the risk of TB following close contact with a TB patient. Contacts were encouraged to visit the health facility for screening; where symptoms history was obtained and opt out HIV testing was provided as part of the screening process. CXR was offered to all regardless of symptoms, followed by definitive sputum test with either Xpert MTB RIF or smear microscopy. RESULTS: Among 919 HH contacts that presented for screening, 865 were screened with CXR and 464 (53.6%) had an abnormal CXR and the rest had a normal CXR. Among 444 HH contacts with valid sputum results, 274 (61.7%) were symptom screen positive and 255 (57.4%) had an abnormal CXR. Overall, TB was diagnosed in 32/444 (7.2%); 13 bacteriologically unconfirmed and 19 bacteriologically confirmed. Of 19 bacteriologically confirmed TB 8 (42.1%) were symptom screen negative contacts with an abnormal CXR and these 6/8 (75.0%) were HIV positive. Among the 13 bacteriologically unconfirmed TB cases, 7 (53.8%) were HIV positive and all had an abnormal CXR. CONCLUSION: Symptom screen if used alone with follow on definitive TB testing only for symptom screen positive individuals would have missed eight of the 19 confirmed TB cases detected in this study. There is need to consider use of other screening strategies apart from symptom screen alone for optimal rule out of TB especially in HIV positive individuals that are at greatest risk of TB and present atypically

Minimizing the impact of the triple burden of COVID-19, tuberculosis and HIV on health services in sub-Saharan Africa

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of TB and HIV. As with these dual epidemics, inadequate resources and poor case identification and reporting may be contributing to underestimations of the COVID-19 case burden in SSA. Modelling studies predict that the pandemic-related disruptions in TB and HIV services will result in significant increases in associated morbidity and mortality over the next five years. Furthermore, limited empirical evidence suggests that SARS-CoV-2 coinfections with TB and HIV are associated with increased mortality risk in SSA. However, predictive models require a better evidence-base to accurately define the impact of COVID-19, not only on communicable diseases such as TB and HIV, but on non-communicable disease comorbidities. Further research is needed to assess morbidity and mortality data among both adults and children across the African continent, paying attention to geographic disparities, as well as the clinical and socio-economic determinants of COVID-19 in the setting of TB and/or HIV

Factors associated with unfavourable tuberculosis treatment outcomes in Lusaka, Zambia, 2015: a secondary analysis of routine surveillance data

Introduction:&nbsp;focus has been put on strengthening surveillance systems in high tuberculosis (TB) burden countries, like Zambia, however inadequate information on factors associated with unfavourable TB treatment outcomes is generated from the system. We determined the proportion of tuberculosis treatment outcomes and their associated factors. Methods:&nbsp;we defined unfavourable outcome as death, lost-to-follow-up, treatment-failure, or not-evaluated and favourable outcome as a patient cured or completed-treatment. We purposively selected a 1st&nbsp;level hospital, an urban-clinic and a peri-urban clinic. We abstracted data from TB treatment registers at these three health facilities, for all TB cases on treatment from 1st&nbsp;January to 31st&nbsp;December, 2015. We calculated proportions of treatment outcomes and analysed associations between unfavourable outcome and factors such as age, HIV status, health facility, and patient type, using univariate logistics regression. We used multivariable stepwise logistic regression to control for confounding and reported the adjusted odds ratios (AOR) and 95% confidence intervals (CI). Results:&nbsp;we included a total of 1,724 registered TB patients, from one urban clinic 694 (40%), a 1st&nbsp;Level Hospital 654 (38%), and one peri-urban-clinic 276 (22%). Of the total patients, 43% had unfavourable outcomes. Of the total unfavourable outcomes, were recorded as treatment-failure (0.3%), lost-to-follow-up (5%), death (9%) and not evaluated (29%). The odds of unfavourable outcome were higher among patients &gt; 59 years (AOR=2.9, 95%CI: 1.44-5.79), relapses (AOR=1.65, 95%CI: 1.15-2.38), patients who sought treatment at the urban clinic (AOR=1.76, 95%CI:1.27-2.42) and TB/HIV co-infected patients (AOR=1.56, 95%CI:1.11-2.19). Conclusion:&nbsp;unfavourable TB treatment outcomes were high in the selected facilities. We recommend special attention to TB patients who are &gt; 59 years old, TB relapses and TB / HIV co-infected. The national TB programme should strengthen close monitoring of health facilities in increasing efforts aimed at evaluating all the outcomes. Studies are required to identify and test interventions aimed at improving treatment outcomes

Implementation Research to Inform the Use of Xpert MTB/RIF in Primary Health Care Facilities in High TB and HIV Settings in Resource Constrained Settings.

BACKGROUND: The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. OBJECTIVE: To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. METHOD: Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM ("CXR algorithm"). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM ("HIV algorithm"). RESULTS: Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. CONCLUSION: Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR