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Coronavirus disease 2019 (COVID-19) in pregnancy is associated with excess maternal and infant morbidity and mortality in both African and higher-resource settings. Furthermore, mounting evidence demonstrates the safety and efficacy of COVID-19 vaccination for pregnant women and infants. However, national guidelines in many African countries are equivocal or lack recommendations on COVID-19 vaccine in pregnancy. We summarize key data on COVID-19 epidemiology and vaccination among pregnant African women to highlight major barriers to vaccination and recommend 4 interventions. First, policymakers should prioritize pregnant women for COVID-19 vaccination, with a target of 100% coverage. Second, empirically supported public health campaigns should be sustainably implemented to inform and support pregnant women and their healthcare providers in overcoming vaccine hesitancy. Third, COVID-19 vaccination for pregnant women should be expanded to include antenatal care, obstetrics/gynecology, and targeted mass vaccination campaigns. Fourth, national monitoring and evaluation of COVID-19 vaccine uptake, safety, surveillance, and prospective outcomes assessment should be conducted. [ABSTRACT FROM AUTHOR]

Background Suboptimal anti-TB drugs exposure may cause multidrug-resistant TB. The role of African predominant SLCO1B1 variant alleles on rifampicin pharmacokinetics and the subsequent effect on the occurrence of Mycobacterium tuberculosis– rifampicin sensitivity needs to be defined. We describe the rifampicin population pharmacokinetics profile and investigate the relevance of SLCO1B1 genotypes to rifampicin pharmacokinetics and rifampicin-TB sensitivity status. Methods Fifty patients with TB (n=25 with rifampicin-resistant TB and n=25 with rifampicin-susceptible TB) were genotyped for SLOC1B1 rs4149032 (g.38664C>T), SLOC1B1*1B (c.388A>G) and SLOC1B1 * 5 (c.521 T>C). Steady state plasma rifampicin levels were determined among patients infected with rifampicin-sensitive TB. Data were analysed using NONMEM to estimate population rifampicin pharmacokinetics as well as the effect of SLOC1B1 genotypes on rifampicin pharmacokinetics and on rifampicin-TB sensitivity status. Results Overall allele frequencies of SLOC1B1 rs4149032 , *1B and * 5 were 0.66, 0.90 and 0.01, respectively. Median (IQR) Cmax and Tmax were 10.2 (8.1–12.5) mg/L and 1.7 (1.125–2.218) h, respectively. Twenty-four percent of patients exhibited Cmax below the recommended 8–24 mg/L range. SLOC1B1 genotypes, gender and age did not influence rifampicin pharmacokinetics or TB-rifampicin sensitivity. Conclusions Although SLOC1B1 genotype, age and gender do not influence either rifampicin pharmacokinetics or rifampicin-TB sensitivity status, one in every four Ugandan TB patients achieve subtherapeutic plasma rifampicin concentrations. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The African Region bears the highest global TB/HIV burden and over 50% of TB cases in SSA are co-infected with HIV. An estimated 1.5 million died from the TB globally in 2013. A large majority of the 360,000 HIV-positive TB cases who died were from sub-Saharan Africa. Research and development is an important pillar of the WHO post-2015 global TB strategy. Advances in development of diagnostics, drugs, host-directed therapies, and vaccines will require evaluation under field conditions through multi-centre clinical trials at different geographical locations. Thus it is critically important that these evaluations are fully supported by all African governments and the capacity, trained staff and infrastructure required to perform the research and evaluations is built and made available. This viewpoint article reviews the opportunities provided by recently launched second programme (2015-2024) of the European & Developing Countries Clinical Trials Partnership (EDCTP2) for tackling the TB epidemic in Africa through its magnanimous portfolio. The unique opportunities provided by EDCTP2 for leadership of scientific research in TB and other diseases fully devolving to Africa are also covered. [ABSTRACT FROM AUTHOR]

Objective: To study trends in HIV case notification rates in the Kingdom of Saudi Arabia. Design: A ten year retrospective review of annual HIV case notification returns to the Ministry of Health, Kingdom of Saudi Arabia. Methods: Annual Registry statistics covering the period 2000 to 2009 were reviewed. Annual incidence trends were stratified according to the following demographics: age, nationality, geographical region of residence, gender, and mode of disease acquisition. Results: 10,217 new HIV cases (2,956 in Saudi nationals and 7,261 in non-Saudis) were reported. Africans of Sub-Saharan Africa origin accounting for 3,982/7,261 (53%) of non-Saudi cases constituted: Ethiopians (2,271), Nigerians (1,048), and Sudanese nationals (663). The overall average annual incidence was <4 cases per 100,000; 1.5 cases per 100,000 for Saudis (range 0.5-2.5), and 13.2 per 100,000 for non-Saudis (range 5.7-19.0). Notifications increased yearly from 2000 for both groups until a plateau was reached in 2006 at 1,390 new cases. Case notification in Saudi nationals increased from 20% in the early 2001 to 40% in 2009. 4% (124/2,956) of cases were reported in Saudi children. The male to female ratio was 1.6:1 for non-Saudi nationals (43.8% male, 27.3% female) and 4.4:1 for Saudis (23.5% male, 5.4% female). Conclusions: Whilst the numbers of reported HIV cases have stabilised since 2006, HIV/AIDS remains an important public health problem in KSA, both in migrants and Saudi nationals. HIV transmission to Saudi children is also of concern. Optimization of data collection, surveillance, and pro-active screening for HIV is required. [ABSTRACT FROM AUTHOR]

Background: A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with noncommunicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre. Methodology/Principal Findings: In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB comorbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706-25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected. Conclusions/Significance: A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study. [ABSTRACT FROM AUTHOR]

Summary: Prisons have long been associated with rapid transmission of infectious diseases. The HIV/AIDS epidemic in sub-Saharan Africa (SSA) has fuelled the spread of TB and HIV in prisons. The poor living conditions and ineffective health services in prisons in SSA are a major breeding ground of Mycobacterium tuberculosis (Mtb). The spread of TB between prisoners, prison staff and visitors and the emergence of drug-resistant TB in prisons now poses a threat to control efforts of national TB programmes in SSA. Accurate data required to develop appropriate interventions to tackle the ominous problem of TB in African prisons are scanty and unreliable. The health of prisoners is by default a neglected political issue. This article reviews the available literature on TB and drug-resistant TB in prisons from SSA countries, discusses the risk factors for acquiring TB and highlights the priorities for further translational research in prisons. Ethical issues pertaining to research on captive African populations are discussed. Scientific, political and funder attention is required urgently to improve prison health services. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a serious infectious disease continuing to cause around 1.8 million deaths annually. The great paradox is that despite the availability of effective treatment for the past 60 years, it continues to spread relentlessly, particularly in sub-Saharan Africa due to the fuelling effect of the HIV/AIDS epidemic. It is no longer a medical epidemic, but an epidemic of injustice. Increased political and financial investment by the industrially developed nations, as well as sustained political will in the affected countries, is required to bring TB under control. It is imperative that the control should be linked to that of HIV which is also closely associated with poverty, poor housing and malnutrition. The historical, social, philosophical and political perspectives that may have influenced the failure of TB control are discussed. Once again, therefore, the question is raised -- can TB be brought under control? [ABSTRACT FROM AUTHOR]

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We describe the initiation and establishment of The University of Zambia – University College London Medical School (UNZA-UCLMS) Research and Training Project, an entirely African scientist-led, south–north partnership. In its 16 year existence, the project, by successfully obtaining competitive grant funding, has transformed itself into one of Africa’s most productive African-led R&D programmes with training and visible research outputs. The project serves as a role model and now networks R&D and training activities with six southern African (10 institutions) and six European countries. This project case study illustrates that deep commitment is essential for success and that the factors which facilitate success in R&D in Africa need to be evaluated. The long-term prospects for sustaining the UNZA-UCLMS Project appear bright and are dependent on several factors: the ability to retain trained African scientists; obtaining continued competitive or donor grant funding support; and serious investment by the African governments involved. The recent 255 million Euros EDCTP investment in sub-Saharan Africa through south–north partnerships is expected to enhance existing African-led R&D programmes. African governments and scientists must rise to the challenge. [ABSTRACT FROM AUTHOR]

Summary: Tuberculosis continues to be one of the leading causes of morbidity and mortality from infectious disease worldwide. When WHO declared tuberculosis a global emergency in 1993, the initial response from the international community was sluggish and inadequate. A resurgence of the disease, the emergence of multidrug-resistant and extensively drug-resistant strains, and the detrimental effect of the concurrent tuberculosis and HIV/AIDS epidemics on national control programmes in sub-Saharan Africa have all occurred despite the availability of effective combination treatment regimens. On the positive side, funding agencies and donor governments are at long last taking a serious interest in investing in tuberculosis research priorities defined by the Stop TB Partnership. Although this investment introduces optimism for eventual control of the White Plague, past failures remind us not to be complacent. [Copyright &y& Elsevier]

Abstract: Every year, approximately 250000 African women die during pregnancy, delivery, or the puerperium. Maternal mortality rates due to infectious diseases in Sub-Saharan Africa now supersede mortality from obstetric causes. Evidence is accumulating that tuberculosis associated with HIV/AIDS, malaria, sepsis, and other opportunistic infections are the main infectious causes of maternal deaths. Screening for these killer infections within prenatal healthcare programs is essential at this stage to prevent and treat causes of maternal mortality. The combination of proven effective interventions that avert the greatest number of maternal deaths should be prioritized and expanded to cover the greatest number of women at risk, and incorporated into a “prophylaxis and treatment community package of care.” The effectiveness of these “packages of care” will need to be determined subsequently. Maternal deaths from tuberculosis are now on the increase in the UK, and due diligence and watchful surveillance are required in European prenatal services. [Copyright &y& Elsevier]

Background: Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie. Methods: SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region. Findings: The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship. Conclusions: The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach. [ABSTRACT FROM AUTHOR]

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa. [ABSTRACT FROM AUTHOR]

The article focuses on the elimination of tuberculosis and tuberculosis-associated HIV comorbidity in the 21st century. Tuberculosis is one of the most important causes of death from an infectious disease. The emergence and spread of tuberculosis poses a threat with existing strategies failing to slow down the tuberculosis pandemic, particularly in sub-Saharan Africa where human immunodeficiency virus (HIV) is a major risk factor for tuberculosis.

Frequently quoted statistics that tuberculosis and human immunodeficiency virus (HIV)/AIDS are the most important infectious causes of death in high-burden countries are based on clinical records, death certificates, and verbal autopsy studies. Causes of death ascertained through these methods are known to be grossly inaccurate. Most data from Africa on mortality and causes of death currently used by international agencies have come from verbal autopsy studies, which only provide inaccurate estimates of causes of death. Autopsy rates in most sub-Saharan African countries have declined over the years, and actual causes of deaths in the community and in hospitals in most sub-Saharan African countries remain unknown. The quality of cause-specific mortality statistics remains poor. The effect of various interventions to reduce mortality rates can only be evaluated accurately if cause-specific mortality data are available. Autopsy studies could have particular relevance to direct public health interventions, such as vaccination programs or preventive therapy, and could also allow for study of background levels of subclinical tuberculosis disease, Mycobacterium tuberculosis–HIV coinfection, and other infectious and noncommunicable diseases not yet clinically manifest. Autopsies performed soon after death may represent a unique opportunity to understand the pathogenesis of M. tuberculosis and the pathogenesis of early deaths after initiation of antiretroviral therapy. The few autopsies performed so far for research purposes have yielded invaluable information and insights into tuberculosis, HIV/AIDS, and other opportunistic infections. Accurate cause-specific mortality data are essential for prioritization of governmental and donor investments into health services to reduce morbidity and mortality from deadly infectious diseases such as tuberculosis and HIV/AIDS. There is an urgent need for reviving routine and research autopsies in sub-Saharan African countries. [ABSTRACT FROM PUBLISHER]

• The COVID-19 pandemic has impacted negatively on Africa's health systems • COVID-19 disruptions on TB and other health services need to be urgently addressed • Strengthening health systems will require visionary political leadership • Innovations in service delivery and technological adaptations remain critical • Beyond modeling, actual country-level data is required to guide decision making The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries' health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa's economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services. [ABSTRACT FROM AUTHOR]

• Sub-Saharan Africa (SSA) bear a high proportion of the global burden of TB and HIV cases. • COVID-19 is negatively impacting on TB/HIV health services in SSA. • SARS-CoV-2 coinfection with TB and HIV adds an increased mortality risk in SSA. • Predictive models and further research is required to accurately define the actual impact of COVID-19 on CDs and NCDs. 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. [ABSTRACT FROM AUTHOR]

• Recurrent pulmonary tuberculosis (RPTB) is a growing, neglected problem worldwide. • We performed a case-controlled study to ascertain main clinical features of RPTB. • Hemoptysis was significantly more common in patients with RPTB than controls. • A higher proportion of RPTB presented with cavitation and lung tissue damage. • Patients being older than 45 years of age are significant features of RPTB. Recurrent pulmonary tuberculosis (RPTB) is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations. Between September 1st 2019 and January 31st 2020, we performed a prospective case controlled study of clinical and imaging features of patients with recurrent pulmonary tuberculosis and compared them with those of newly diagnosed PTB cases. Recurrent PTB was defined as a patient with bacteriologically confirmed active PTB who was previously successfully treated for PTB and was cured. A control was defined as a patient who presents for the first time with bacteriologically confirmed PTB. Clinical and radiological features were assessed and documented. Chi-square and t-test were used to test the difference between proportion and continuous data, respectively. Logistic regression analysis was done to determine factors associated with RPTB using SPSS version 23 software. A total of 312 patients with PTB were enrolled (104 RPTB cases and 208 newly diagnosed controls). Clinically hemoptysis was more common in RPTB compared to controls 28/104 (26.9%) vs 35/208 (16.8%), P = 0.036. Chest pain was significantly less common among patients with RPTB compared to controls 33 (31.7%) vs 92 (44.2%), P = 0.034. A higher proportion of RPTB presented with cavitation 34/104 (32.7%) compared to control 44/208 (21.2%) P = 0.027. The median score for lung pathology was higher among patients with RPTB (50) compared to controls (30); P = 0.001. Lung function of patients with RPTB at diagnosis of index TB were more likely to show mixed restrictive and obstructive pattern 36/104 (34.6%) compared to controls 31/208 (14.9%). p<0.001. Multivariate analysis showed that patients older than 45 years of age (adjusted odds ratio [aOR]: 3.59, 95% CI: 1.38 – 9.32), those with hemoptysis (aOR 1.96, 95% CI: 1.04 – 3.69) p=0.04) and fibrosis on chest x rays (aOR 2.18, 95% CI: 1.16 – 4.10) were significantly associated with recurrent PTB. Hemoptysis, lung parenchymal damage, and patients being older than 45 years of age are significant features of RPTB. Management should focus on risk factors for recurrence, and a more holistic model of care to prevent long term lung injury. [ABSTRACT FROM AUTHOR]

OBJECTIVE Nine out of ten tuberculosis deaths occur in tuberculosis-burdened countries, particularly Sub Saharan Africa. In these setting mortality has not been fully described. We describe the magnitude and pattern of TB mortality in Tanzania. METHODS A multicenter prospective cohort study was conducted among HIV infected and uninfected pulmonary tuberculosis patients from time of anti-TB treatment initiation to completion. Patients were censored at the time of treatment completion, or at their last visit for those who did not complete TB treatment. Kaplan-Meier curves were used to estimate time to death; cox proportional hazards model was used to examine risk factors for mortality. RESULTS A total of 58 deaths out of 1696 patients (3.4%) occurred, two thirds (n = 39) during the first two months of treatment. Compared to HIV un-infected TB patients, mortality risk for TB/HIV co-infected patients was least when antiretroviral therapy (ART) was initiated after 14 days of anti-TB (RR = 3.55; 95% CI: 1.44, 8.73 p < 0.0001) and highest when ART was initiated 90 days or less prior to anti-TB and within the first 14 days of anti-TB therapy (RR = 10; 95% CI: 3.28, 30.54; p < 0.0001). CONCLUSION Meticulously planned and supervised antiretroviral therapy reduces mortality among TB/HIV patients. Among patients with TB/HIV naïve of ART, withholding ART until the third week of anti-tuberculosis therapy will likely reduce TB mortality in Tanzania. Patients on ART and later develop tuberculosis should be closely monitored. [ABSTRACT FROM AUTHOR]

Summary Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100 000 population—more than double the global average of 133 per 100 000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480 000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190 000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is ‘Unite to End TB’. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host– Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed. [ABSTRACT FROM AUTHOR]

Summary Background Patients with subclinical tuberculosis, smear-negative tuberculosis, extrapulmonary tuberculosis, multidrug-resistant tuberculosis, and asymptomatic tuberculosis are difficult to diagnose and may be missed at all points of health care. We did an autopsy study to ascertain the burden of tuberculosis at post mortem in medical inpatients at a tertiary care hospital in Lusaka, Zambia. Methods Between April 5, 2012, and May 22, 2013, we did whole-body autopsies on inpatients aged at least 16 years who died in the adult inpatient wards at University Teaching Hospital, Lusaka, Zambia. We did gross pathological and histopathological analysis and processed lung tissues from patients with tuberculosis through the GeneXpert MTB/RIF assay to identify patients with multidrug-resistant tuberculosis. The primary outcome measure was specific disease or diseases stratified by HIV status. Secondary outcomes were missed tuberculosis, multidrug-resistant tuberculosis, and comorbidities with tuberculosis. Data were analysed using Pearson χ 2 , the Mann-Whitney U test, and binary logistic regression. Findings The median age of the 125 included patients was 35 years (IQR 29–43), 80 (64%) were men, and 101 (81%) were HIV positive. 78 (62%) patients had tuberculosis, of whom 66 (85%) were infected with HIV. 35 (45%) of these 78 patients had extrapulmonary tuberculosis. The risk of extrapulmonary tuberculosis was higher among HIV-infected patients than among uninfected patients (adjusted odds ratio 5·14, 95% CI 1·04–24·5; p=0·045). 20 (26%) of 78 patients with tuberculosis were not diagnosed during their life and 13 (17%) had undiagnosed multidrug-resistant tuberculosis. Common comorbidities with tuberculosis were pyogenic pneumonia in 26 patients (33%) and anaemia in 15 (19%). Interpretation Increased clinical awareness and more proactive screening for tuberculosis and multidrug-resistant tuberculosis in inpatient settings is needed. Further autopsy studies are needed to ascertain the generalisability of the findings. Funding UBS Optimus Foundation, EuropeAID, and European Developing Countries Clinical Trials Partnership (EDCTP). [ABSTRACT FROM AUTHOR]

Summary: Background: Rapid and accurate diagnosis of pulmonary tuberculosis in children remains challenging because of difficulties in obtaining sputum samples and the paucibacillary nature of the disease. The Xpert MTB/RIF assay is useful for rapid diagnosis of childhood tuberculosis with sputum and nasopharyngeal samples. We assessed this assay for the detection of tuberculosis and multidrug resistant (MDR) tuberculosis with gastric lavage aspirate (GLA) samples in children admitted to hospital. Methods: We did a prospective study to assess the sensitivity and specificity of the Xpert MTB/RIF assay with GLA samples for the detection of pulmonary tuberculosis and MDR tuberculosis in new paediatric inpatient admissions at the University Teaching Hospital, Lusaka, Zambia. Children aged 15 years or younger were recruited between June, 2011, and May, 2012. GLA and sputum were analysed by standard smear-microscopy, mycobacterial growth indicator tube (MGIT) culture, MGIT drug-susceptibility testing, and the Xpert MTB/RIF assay. Sensitivity of the Xpert MTB/RIF assay was assessed with the Pearson χ2 or Fishers exact test. Findings: Of 930 children, 142 produced sputum and GLA was obtained from 788 non-sputum producers. Culture-positive tuberculosis was identified in 58 (6·2%) of 930 children: ten from sputum producers and 48 from GLA of non-sputum producers. The sensitivity and specificity of the Xpert MTB/RIF assay were similar: sensitivity was 68·8% (95% CI 53·6–80·9) for GLA versus 90·0% (54·1–99·5; p=0·1649) for sputum samples; specificity was 99·3% (98·3–99·8) for GLA and 98·5% (94·1–99·7; p=0·2871) for sputum samples. The Xpert MTB/RIF assay detected an extra 28 tuberculosis cases compared with smear microscopy and was significantly more sensitive than smear microscopy for both sputum (90·0% [54·1–99·5] vs 30·0% [8·1–64·6], p=0·01) and GLA (68·8% [53·6–80·9] vs 25·0% [14·1–40·0], p<0·0001). The assay load did not differ significantly by sample type (p=0·791). 22 children were infected with HIV and tuberculosis and significant differences in assay performance could not be detected when stratifying by HIV status for either sample type. The Xpert MTB/RIF assay detected rifampicin resistance in three GLA samples: two confirmed as MDR tuberculosis and one false positive. Interpretation: Analyses of GLA samples with the Xpert MTB/RIF assay is a sensitive and specific method for rapid diagnosis of pulmonary tuberculosis in children who cannot produce sputum. The single site nature of our study invites caution. Funding: European Commission, European Developing Countries Clinical Trials Partnership, and UBS Optimus Foundation. [Copyright &y& Elsevier]