Lockdown measures have been introduced worldwide to contain the transmission of COVID-19. However, the term ‘lockdown’ is not well-defined. Indeed, WHO’s reference to ‘so-called lockdown measures’ indicates the absence of a clear and universally accepted definition of the term ‘lockdown’. We propose a definition of ‘lockdown’ based on a two-by-two matrix that categorises different communicable disease measures based on whether they are compulsory or voluntary; and whether they are targeted at identifiable individuals or facilities, or whether they are applied indiscriminately to a general population or area. Using this definition, we describe the design, timing and implementation of lockdown measures in nine countries in sub-Saharan Africa: Ghana, Nigeria, South Africa, Sierra Leone, Sudan, Tanzania, Uganda, Zambia and Zimbabwe. While there were some commonalities in the implementation of lockdown across these countries, a more notable finding was the variation in the design, timing and implementation of lockdown measures. We also found that the number of reported cases is heavily dependent on the number of tests carried out, and that testing rates ranged from 2031 to 63 928 per million population up until 7 September 2020. The reported number of COVID-19 deaths per million population also varies (0.4 to 250 up until 7 September 2020), but is generally low when compared with countries in Europe and North America. While lockdown measures may have helped inhibit community transmission, the pattern and nature of the epidemic remains unclear. However, there are signs of lockdown harming health by affecting the functioning of the health system and causing social and economic disruption.

To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21–0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time.DOI: http://dx.doi.org/10.7554/eLife.05166.001

Background. Recurrent tuberculosis is a major health burden and may be due to relapse with the original strain or reinfection with a new strain.Methods. In a population-based study in northern Malawi, patients with tuberculosis diagnosed from 1996 to 2010 were actively followed after the end of treatment. Whole-genome sequencing with approximately 100-fold coverage was performed on all available cultures. Results of IS6110 restriction fragment-length polymorphism analyses were available for cultures performed up to 2008.Results. Based on our data, a difference of ≤10 single-nucleotide polymorphisms (SNPs) was used to define relapse, and a difference of >100 SNPs was used to define reinfection. There was no evidence of mixed infections among those classified as reinfections. Of 1471 patients, 139 had laboratory-confirmed recurrences: 55 had relapse, and 20 had reinfection; for 64 type of recurrence was unclassified. Almost all relapses occurred in the first 2 years. Human immunodeficiency virus infection was associated with reinfection but not relapse. Relapses were associated with isoniazid resistance, treatment before 2007, and lineage-3 strains. We identified several gene variants associated with relapse. Lineage-2 (Beijing) was overrepresented and lineage-1 underrepresented among the reinfecting strains (P = .004).Conclusions. While some of the factors determining recurrence depend on the patient and their treatment, differences in the Mycobacterium tuberculosis genome appear to have a role in both relapse and reinfection.

Unacceptable levels of Mycobacterium tuberculosis transmission are noted in high burden settings and a renewed focus on reducing person-to-person transmission in these communities is needed. We review recent developments in the understanding of airborne transmission. We outline approaches to measure transmission in populations and trials and describe the Wells-Riley equation, which is used to estimate transmission risk in indoor spaces. Present research priorities include the identification of effective strategies for tuberculosis infection control, improved understanding of where transmission occurs and the transmissibility of drug-resistant strains, and estimates of the effect of HIV and antiretroviral therapy on transmission dynamics. When research is planned and interventions are designed to interrupt transmission, resource constraints that are common in high burden settings-including shortages of health-care workers-must be considered.

Abstractobjectives Given the imperative to scale up integrated tuberculosis (TB) and HIV services in settings where both are of major public health importance, we aimed to synthesise knowledge concerning implementation of TB/HIV service integration.methods Systematic review of studies describing a strategy to facilitate TB and HIV service integration, searching 15 bibliographic databases including Medline, Embase and the Cochrane library; and relevant conference abstracts.results Sixty-three of 1936 peer-reviewed articles and 70 of 170 abstracts met our inclusion criteria. We identified five models: entry via TB service, with referral for HIV testing and care; entry via TB service, on-site HIV testing, and referral for HIV care; entry via HIV service with referral for TB screening and treatment; entry via HIV service, on-site TB screening, and referral for TB diagnosis and treatment; and TB and HIV services provided at a single facility. Referral-based models are most easily implemented, but referral failure is a key risk. Closer integration requires more staff training and additional infrastructure (e.g. private space for HIV counselling; integrated records). Infection control is a major concern. More integrated models hold potential efficiencies from both provider and user perspective. Most papers report 'outcomes' (e.g. proportion of TB patients tested for HIV); few report downstream 'impacts' such as outcomes of TB treatment or antiretroviral therapy. Very few studies address the perspectives of service users or staff, or costs or cost-effectiveness.conclusions While scaling up integrated services, robust comparisons of the impacts of different models are needed using standardised outcome measures.

BackgroundThe proportion of tuberculosis attributable to transmission from close contacts is not well known. Comparison of the genome of strains from index patients and prior contacts allows transmission to be confirmed or excluded.MethodsIn Karonga District, Malawi, all tuberculosis patients are asked about prior contact with others with tuberculosis. All available strains from culture-positive patients were sequenced. Up to 10 single nucleotide polymorphisms between index patients and their prior contacts were allowed for confirmation, and ≥ 100 for exclusion. The population attributable fraction was estimated from the proportion of confirmed transmissions and the proportion of patients with contacts.ResultsFrom 1997–2010 there were 1907 new culture-confirmed tuberculosis patients, of whom 32% reported at least one family contact and an additional 11% had at least one other contact; 60% of contacts had smear-positive disease. Among case-contact pairs with sequences available, transmission was confirmed from 38% (62/163) smear-positive prior contacts and 0/17 smear-negative prior contacts. Confirmed transmission was more common in those related to the prior contact (42.4%, 56/132) than in non-relatives (19.4%, 6/31, p = 0.02), and in those with more intense contact, to younger index cases, and in more recent years. The proportion of tuberculosis attributable to known contacts was estimated to be 9.4% overall.ConclusionsIn this population known contacts only explained a small proportion of tuberculosis cases. Even those with a prior family contact with smear positive tuberculosis were more likely to have acquired their infection elsewhere.

Introduction: Globally, increasing numbers of HIV-infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss-to-follow-up (LTFU) from HIV care services among children as they transition from childhood through adolescence.Methods: Individuals aged 5–19 years initiated on ART in a public-sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age-bands namely: 5–9 (children), 10–14 (young adolescents) and 15–19 (older adolescents). The effect of age at ART initiation, current age (using a time-updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression.Results: Of 2273 participants, 1013, 875 and 385 initiated ART aged 5–9, 10–14 and 15–19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age-band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94–2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05–3.07). In older adolescents, the LTFU rate among those who started ART in that age-band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age-groups.Conclusions: Adolescents had higher rates of LTFU compared to other age-groups, with older adolescents at particularly high risk in all analyses. Age-updated analyses that examine movement across narrow age-bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes.

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