Epidemiology of Smear ‐ Negative Tuberculosis in Ibadan, Nigeria

Inadequate case detection has been identified as one of the reasons for high burden of tuberculosis (TB) in the world especially in poor resourced countries of Africa and Asia. This retrospective laboratory study involving the review of specimens processed at the TB laboratory of the Department of Medical Microbiology and Parasitology, University College Hospital, Ibadan, Nigeria was carried out over a period of five years (January 2006‐December 2010) to access the epidemiology of smear‐ negative TB. Of the 3468 specimens processed, 2,175 (62.7%) were from males while a lower percentage (37.3%)1293 were from females, giving a M:F = 1:0.37. Over half of the specimens, 2,046 (59.0%) were from patients aged 21 to 60 years, 392 (11.3%) from 11 to 20 years, 825 (23.8%) from 60 years and above while 205 (5.9%) were from age 1‐10 years. Most of the 2,663 (76.8%) specimens processed were sputum while 201 (5.8%) were gastric washings. Three hundred and nine (8.9%) were smear positive while 392 (11.3%) out of the 3468 specimens processed were culture positive. However, 83 (2.6%) of the 3159 smearnegative specimens were culture positive (false negative) while 66 (21.4%) of the 309 smear‐ positive specimens were negative for culture (false positive). The majority, 3010 (86.8%) were smear and culture negative while 309 (8.9%) were positive for both tests. Of the 83 false negative specimens, 51 were sputum samples representing (61.4%), 19 (22.9%) were gastric washings while 13 (15.7%) were from extra‐pulmonary sites (CSF, aspirates, ascitic fluids, etc). The findings of 2.6% smear‐negative but culture positive (false negative) specimens in this study reveals that culture of specimens in addition to smear microscopy from suspected cases is necessary as a diagnostic /confirmatory tool for tuberculosis.Keywords: Epidemiology, Smear negative, TB, Ibadan, Nigeri

EPIDEMIOLOGY OF SMEAR - NEGATIVE TUBERCULOSIS IN IBADAN, NIGERIA

Inadequate case detection has been identified as one of the reasons for high burden of tuberculosis (TB) in the world especially in poor resourced countries of Africa and Asia. This retrospective laboratory study involving the review of specimens processed at the TB laboratory of the Department of Medical Microbiology and Parasitology, University College Hospital, Ibadan, Nigeria was carried out over a period of five years (January 2006-December 2010) to access the epidemiology of smear- negative TB. Of the 3468 specimens processed, 2,175 (62.7%) were from males while a lower percentage (37.3%)1293 were from females, giving a M:F = 1:0.37. Over half of the specimens, 2,046 (59.0%) were from patients aged 21 to 60 years, 392 (11.3%) from 11 to 20 years, 825 (23.8%) from 60 years and above while 205 (5.9%) were from age 1-10 years. Most of the 2,663 (76.8%) specimens processed were sputum while 201 (5.8%) were gastric washings. Three hundred and nine (8.9%) were smear positive while 392 (11.3%) out of the 3468 specimens processed were culture positive. However, 83 (2.6%) of the 3159 smear-negative specimens were culture positive (false negative) while 66 (21.4%) of the 309 smear- positive specimens were negative for culture (false positive). The majority, 3010 (86.8%) were smear and culture negative while 309 (8.9%) were positive for both tests. Of the 83 false negative specimens, 51 were sputum samples representing (61.4%), 19 (22.9%) were gastric washings while 13 (15.7%) were from extra-pulmonary sites (CSF, aspirates, ascitic fluids, etc). The findings of 2.6% smear-negative but culture positive (false negative) specimens in this study reveals that culture of specimens in addition to smear microscopy from suspected cases is necessary as a diagnostic /confirmatory tool for tuberculosis

Statistička analiza obrade podataka u nekim seizmičkim refrakcijskim metodama: Primjer sintetičkih podataka

The delay time method has gained attention in shallow seismic refraction survey because it has the capability to map the lateral thickness of overburden and relief of bedrock. This study addresses the comparison between the performances of the plus-minus and conventional reciprocal methods using a synthetic data. The interpretations obtained from both methods are reasonably comparable to the actual geophysical models. This suggests that either of the methods can be used to construct a geologic section. However, the result of randomized complete block design (RCBD) experiment shows a significant difference in the type of method used and this necessitate the need for further test. The pairwise comparison suggests that the plus-minus method produces a model that better mimics the actual data than the conventional reciprocal method.Metoda vremenskog kašnjenja često se koristi u istraživanju plitke seizmičke refrakcije jer ima mogućnost kartiranja lateralne debljine nadsloja i reljefa stijena. Ovaj rad bavi se usporedbom svojstava plus-minus i konvencionalnih recipročnih metoda korištenjem sintetičkih podataka. Interpretacije dobivene objema metodama razumno su usporedive sa stvarnim geofizičkim modelima. To sugerira da se bilo koja od metoda može koristiti za konstrukciju geološke sekcije. Međutim, rezultat eksperimenta randomiziranog cjelovitog projekta blokiranja (RCBD) pokazuje značajne razlike ovisno o korištenoj metodi, a to nameće potrebu za daljnjim ispitivanjima. Uparena usporedba sugerira da plus-minus metoda daje model koji bolje oponaša stvarne podatke u odnosu na konvencionalnu recipročnu metodu

FACTORS ASSOCIATED WITH TB/HIV CO-INFECTION AMONG DRUG SENSITIVE TUBERCULOSIS PATIENTS MANAGED IN A SECONDARY HEALTH FACILITY IN LAGOS, NIGERIA

Background: This study assessed factors associated with TB/HIV co-infection among TB patients managed in a secondary health facility in Lagos Nigeria. Materials and Methods: A retrospective review of treatment cards of patients seen at a secondary referral hospital between January 1 2014 and December 31 2014 was conducted. Treatment outcomes and factors associated with TB/HIV co-infection were assessed. Results: Of the 334 records of patients reviewed, the proportion of patients with TB/HIV co-infection was 21.6%. The odds of having TB/HIV co-infection was 2.7 times higher among patients above 40 years than patients less than 25 years (AOR 2.7 95% CI 1.1 – 6.5, p =0.030). In addition, the odds of having TB/HIV co-infection was 3.3 higher among extrapulmonary TB cases (AOR 3.3; 95% CI 1.2 – 9.5; p = 0.026) and 2.1 times higher among retreated patients (AOR 2.1; 95% CI 1.1 – 3.9; p = 0.017) than pulmonary TB and new patients respectively. The chance of having TB/HIV co-infection was 2.7-fold more in patients with poor treatment outcomes than patients with treatment success (AOR 2.7; 95%CI 1.3 – 5.4; p =0.006). Conclusion: TB/HIV co-infection rate was high in the study area. There is need to put measures in place to improve treatment outcomes of TB/HIV co-infected patients

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance

Background Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. Methods Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009–2013 and tested for first- and second-line drug resistance. Results From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. Conclusions West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa