Tuberculosis and Sexual and Reproductive Health of Women in Four African Countries.

Tuberculosis (TB) is a major reason of maternal mortality in low-income countries, and it increases the probability of adverse sexual and reproductive health (SRH) outcomes, including ectopic pregnancy and perinatal mortality. The data presented here is from the TB Sequel observational cohort conducted in four African countries. For this sub-study, we selected only female participants, who were diagnosed with drug susceptible TB and followed-up until the end of anti-TB treatment. The data collection included questionnaires, clinical examination and laboratory tests at TB diagnosis, day 14, month 2, 4 and 6. A total of 486 women, with 88.3% being 18-49 years old, were included in the analysis. Around 54.7% were HIV positive. Most of the participants (416/486; 85.6%) in our cohort were considered cured at month 6. Only 40.4% of non-pregnant women of reproductive age used contraception at TB diagnosis. A total of 31 out of 486 women experienced pregnancy during TB treatment. Pregnancy outcomes varied between live birth (16/31; 51.6%), induced abortion (6/31; 19.4%), miscarriage (4/31; 12.9%) and stillbirth (3/31; 9.6%). Integration and linking of SRH services with TB programmes are vital to increase contraception use and protect women from obstetric risks associated with pregnancy during TB treatment.

Dyslipidaemia-related cardiovascular risk among pregnant women attending Aminu Kano Teaching Hospital Kano: A longitudinal study.

OBJECTIVE: Maternal dyslipidaemia and atherogenic lipid profiles have undesirable effects on maternal and foetal well-being throughout gestation. This study investigates the changes in serum lipid profiles, the prevalence of dyslipidaemia, and the risk of cardiovascular disease among pregnant women attending the antenatal care unit of the Aminu Kano Teaching Hospital (AKTH), Kano. METHODS: A total of 112 pregnant women visiting AKTH in their second trimester were recruited and followed up within their third trimester. The demographic characteristics, daily dietary consumption patterns, and lipid profiles of all women were assessed using standard methods. RESULTS: The results revealed that the mean age and gestational age of the pregnant women were approximately 29 ± 6 years and 20 ± 3 weeks, respectively. Most pregnant women were multiparous (76) and multigravida (93). Regarding daily dietary consumption patterns, 20.5%, 63.4%, 13.4%, and 8.0% of the pregnant women consumed nuts, palm oil, butter, and sardines at least one to three times, respectively. Moreover, the serum lipid profiles revealed that the prevalence of dyslipidaemia, hypercholesterolaemia, hypertriglyceridaemia, increased low-density lipoprotein levels, and decreased high-density lipoprotein levels among pregnant women during the second trimester were 69.6%, 19.6%, 36.6%, 18.8%, and 49.1%, respectively. All these parameters significantly increased to 91.8%, 54.1%, 75.3%, 40.0%, and 62.4%, respectively, in the third trimester. Pregnant women showed a high risk of cardiovascular disease in both the second (81.0%) and third (85.0%) trimesters. CONCLUSION: Progression from mid-pregnancy to delivery is associated with an increased risk of maternal dyslipidaemia and cardiovascular diseases among pregnant women.

Delay in the diagnosis of pulmonary tuberculosis in The Gambia, West Africa: A cross-sectional study.

OBJECTIVES: To investigate the pattern of tuberculosis (TB) care initiation and risk factors for TB diagnostic delay in The Gambia. METHODS: In this cross-sectional study, adult patients diagnosed with pulmonary TB (pTB) in public facilities in the Greater Banjul Area of The Gambia were consecutively recruited from October 2016 to March 2017. Diagnostic delay was defined as >21 days from the onset of at least one symptom suggestive of pTB to diagnosis. Logistic regression analyses were used to investigate risk factors for diagnostic delay. RESULTS: Overall, 216 pTB patients were included in the study; the median (Interquartile Range (IQR)) age was 30 (23-39) years and 167 (77%) were male patients. Of the 216 patients, 110 (50.9%) of them initiated care-seeking in the formal and informal private sector and 181/216 (83.8%) had TB diagnostic delay. The median (IQR) duration from the onset of symptoms to TB diagnosis was 34 (28-56) days. Age groups 18-29 years (aOR 3.2; 95% CI 1.2-8.8 [p = 0.02]) and 30-49 years (aOR 5.1; 95% CI 1.6-16.2 [p = 0.006]) and being employed (aOR 4.2; 95% CI 1.7-10.5 [p = 0.002]) were independent risk factors for TB diagnostic delay. CONCLUSION: There is considerable TB diagnostic delay in The Gambia, and this is likely to be worsened by the COVID-19 pandemic.

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Lessons in participant retention in the course of a randomized controlled clinical trial.

BACKGROUND: Clinical trials are increasingly being conducted as new products seek to enter the market. Deployment of such interventions is based on evidence obtained mainly from the gold standard of randomized controlled clinical trials (RCCT). A crucial factor in the ability of RCCTs to provide credible and generalisable data is sample size and retention of the required number of subjects at completion of the follow-up period. However, recruitment and retention in clinical trials are hindered by prevalent peculiar challenges in Africa that need to be circumvented. This article shares experiences from a phase II trial that recorded a high retention rate at 14 months follow-up at a new clinical trial site. METHODS: Mothers bringing children less than two months of age to the health facility were given information and invited to have their child enrolled if the inclusion criteria were fulfilled. Participants were enrolled over 8 months. Trial procedures, duration and risks/benefits were painstakingly and sequentially explained to the communities, parents and relevant relatives before and during the trial period. The proportions of participants that completed or did not complete the trial were analyzed including the reasons for failure to complete all trial procedures. RESULTS: 1044 individuals received information regarding the trial of which 371 returned for screening. 300 (81%) of them who fulfilled the inclusion criteria and did not meet any exclusion criteria were enrolled and 94% of these completed the trial. Consent withdrawal was the main reason for not completing the trial largely (75%) due to the father not being involved at the point of consenting or parents no longer being comfortable with blood sampling. CONCLUSIONS: Participant retention in clinical trials remains a crucial factor in ensuring generalisability of trial data. Appropriate measures to enhance retention should include continuous community involvement in the process, adequate explanation of trial procedures and risks/benefits; and innovative tracing of participants adapted for the setting.

Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine when given as a booster to BCG in Gambian infants: an open-label randomized controlled trial.

UNLABELLED: We evaluated the candidate tuberculosis vaccine M72/AS01 in Bacille-Calmette-Guérin (BCG)-vaccinated infants after or concomitantly with Expanded-Programme-on-Immunization (EPI) vaccines. METHODS: In a Phase-II study in The Gambia (NCT01098474), 2 cohorts of 150 BCG-vaccinated infants each were randomized 1:1:1. The 'Outside-EPI' cohort received one or two M72/AS01 doses, or meningitis vaccine, 1-2 months after primary EPI vaccination. The 'Within-EPI' cohort received one or two M72/AS01 doses concomitantly with the third or last two doses of their primary EPI-regimen, respectively, or EPI vaccines alone. Safety, M72-specific humoral (ELISA) and cell-mediated (whole-blood ICS) responses, and humoral responses to EPI vaccines were assessed. RESULTS: M72/AS01 was acceptably tolerated with no vaccine-related serious adverse events reported. Seropositivity/seroprotection rates against EPI antigens in the Within-EPI cohort were comparable between groups, irrespective of M72/AS01 co-administration. Up to one year post M72/AS01 vaccination, M72-specific humoral and CD4(+) T-cell responses were higher after 2 doses versus 1 dose in both cohorts (p < 0.0001), and comparable between cohorts after either 1 or 2 doses (p > 0.05). CONCLUSION: M72/AS01 given to infants after or concomitantly with EPI vaccines had an acceptable safety profile. Our results suggest no interference of immunogenicity profiles occurred following co-administration of M72/AS01 and EPI vaccines. Two M72/AS01 doses elicited higher immune responses than one dose.

Haematological and biochemical reference values of Gambian infants.

OBJECTIVE: To establish haematological and biological reference values for Gambian infants. METHODS: Basic haematological and biochemical indices were analysed in blood samples obtained from healthy infants from Sukuta in the Western Division of The Gambia. The 2.5 and the 97.5 centiles for these indices were estimated. RESULTS: Reference ranges for haematological and biochemical indices were determined. Haemoglobin, total white cell count (WBC) and platelet levels decreased with age (P < 0.001), whereas most of the white cell count subsets except monocytes did not vary with age. Potassium and alkaline phosphatase fell significantly with increasing age (P < 0.001; P < 0.001), whereas urea and creatinine rose with increasing age (P = 0.002; P < 0.001, respectively). CONCLUSION: Our set of haematological and biochemical reference values for healthy infants in The Gambia differs from values in other settings, thus underscoring the importance of establishing region-specific paediatric reference ranges to ensure optimal patient management and evaluate the impact of interventions in clinical research.

Knowledge, attitude and practice of home management of childhood diarrhoea among caregivers of under-5 children with diarrhoeal disease in Northwestern Nigeria.

OBJECTIVES: Diarrhoeal diseases (DDs) constitute public health problem. Reduction in related mortality and morbidity hinges on active participation of home caregivers. It is pertinent to determine the degree of their empowerment. DESIGN: Cross-sectional study. SETTING: Randomly selected community primary health centres in northwestern Nigerian. SUBJECTS: Home caregivers presenting with children aged 1-59 months having DD. OUTCOME MEASURES: Knowledge, attitude and practice regards home management of DD. RESULTS: Less than 1% of caregivers was knowledgeable about home management of DD. Antibiotics and anti-diarrhoeal agents use was common at 36%. ORS use was abysmally low at 8.6%. Only 32% of caregivers were aware of the use of zinc in the management of DD. Adherence to 10-day zinc supplementation was encouraging at 75.5%. CONCLUSION: There is an urgent need to scale up educational and promotional activities with regards to the home management of DD if the millennium development goals are to be met.

Immunogenicity of the tuberculosis vaccine MVA85A is reduced by coadministration with EPI vaccines in a randomized controlled trial in Gambian infants.

New tuberculosis vaccines are urgently needed to curtail the current epidemic. MVA85A is a subunit vaccine that could enhance immunity from BCG vaccination. To determine MVA85A safety and immunogenicity as well as interactions with other routine vaccines administered in infancy, we randomized healthy 4-month-old infants who had received Bacille Calmette-Guérin at birth to receive Expanded Program on Immunization (EPI) vaccines alone, EPI and MVA85A simultaneously, or MVA85A alone. Adverse events were monitored throughout. Blood samples obtained before vaccination and at 1, 4, and 20 weeks after vaccination were used to assess safety and immunogenicity. The safety profile of both low and standard doses was comparable, but the standard dose was more immunogenic and therefore was selected for the second stage of the study. In total, 72 (first stage) and 142 (second stage) infants were enrolled. MVA85A was safe and well tolerated and induced a potent cellular immune response. Coadministration of MVA85A with EPI vaccines was associated with a significant reduction in MVA85A immunogenicity, but did not affect humoral responses to the EPI vaccines. These results provide important information regarding timing of immunizations, which is required for the design of infant efficacy trials with MVA85A, and suggest that modifications to the standard EPI schedule may be required to incorporate a new generation of T cell-inducing vaccines.