Scaling up Ghana's national newborn care initiative: integrating 'helping babies breathe' (HBB), 'essential care for every baby' (ECEB), and newborn 'infection prevention' (IP) trainings.

BACKGROUND: Responding to stagnating neonatal mortality rates in Ghana, a five-year collaboration called Making Every Baby Count Initiative (MEBCI) was undertaken to improve the quality of newborn care provided around the time of birth. A multi-pronged approach was used to build health worker (HW) capacity in resuscitation, essential newborn care, and infection prevention using a curriculum built on the American Academy of Pediatric's (AAP) Helping Babies Breathe (HBB) and Essential Care for Every Baby (ECEB) modules with an added section on infection prevention (IP). METHODS: MEBCI used a training of trainer's approach to train 3688 health workers from district-level facilities in four regions in Ghana between June 2015 and July 2017. Prior to training, HWs familiarized themselves with the learning materials. Concurrently, MEBCI worked to improve enabling environments that would sustain the increased capacity of trained health workers. Knowledge and skills gained were tested using AAP's Knowledge checklist and validated single-scenario Objective Structured Clinical Examinations (OSCEs) tools. FINDINGS: Majority of HWs trained were midwives (58.8%) and came from district-level hospitals (88.4%). Most HWs passed the HBB OSCE (99.9%, 3436/3440). Age of doctors was negatively associated with HBB scores (r = - 0.16, p = 0.0312). Similarly, older midwives had lower HBB scores (r = - 0.33, p value < 0.001). Initiating ventilation within the Golden Minute was challenging for HWs (78.5% passed) across all regions. Overall, the pass rate for ECEB OSCEs was 99.9% in all regions. Classify newborn for further care and communicate plan to family were frequent challenges observed in Volta Region (69.5% and 72.0% pass rate respectively). HWs less than 40 years of age performed significantly better than health workers older than 40 years (p = 0.023). Age of only paediatricians was positively associated with ECEB scores (r = 0.77, p < 0.001) while age of midwives was negatively associated with ECEB scores (r = - 0.08, p < 0.001). CONCLUSION: MEBCI's integrated HBB-ECEB-IP training resulted in significant mastery of the clinical knowledge and skills of HWs. Harmonization and standardization of the course delivery by trainers and having a core team to ensure training fidelity are essential to maintaining high quality while scaling a program nationally. FUNDING: Children's Investment Fund Foundation (CIFF).

MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa.

Current endeavour focuses on human genetic factors that contribute to susceptibility to or protection from tuberculosis (TB). Monocytes are crucial in containing Mycobacterium tuberculosis infection, and the monocyte chemoattractant protein-1 (MCP-1) cytokine plays a role in their recruitment to the site of infection. The G allele of the MCP-1 promoter polymorphism at position -2581 relative to the ATG transcription start codon has been described to be associated in Mexican and Korean TB patients with increased susceptibility to TB. We genotyped this and additional MCP-1 variants in sample collections comprising more than 2000 cases with pulmonary TB and more than 2300 healthy controls and 332 affected nuclear families from Ghana, West Africa, and more than 1400 TB patients and more than 1500 controls from Russia. In striking contrast to previous reports, MCP-1 -2581G was significantly associated with resistance to TB in cases versus controls [odds ratio (OR) 0.81, corrected P-value (P(corr)) = 0.0012] and nuclear families (OR 0.72, P(corr) = 0.04) and not with disease susceptibility, whereas in the Russian sample no evidence of association was found (P = 0.86). Our and other results do not support an association of MCP-1 -2581 with TB. In the Ghanaian population, eight additional MCP-1 polymorphisms were genotyped. MCP-1 -362C was associated with resistance to TB in the case-control collection (OR 0.83, P(corr) = 0.00017) and in the affected families (OR 0.7, P(corr) = 0.004). Linkage disequilibrium (LD) and logistic regression analyses indicate that, in Ghanaians, the effect results exclusively from the MCP-1 -362 variant, whereas the effect of -2581 may in part be explained by its LD with -362.

Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis.

Structural variants of the Mannose Binding Lectin (MBL) cause quantitative and qualitative functional deficiencies, which are associated with various patterns of susceptibility to infectious diseases and other disorders. We determined genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls and characterized the mycobacterial isolates of the patients. Assuming a recessive mode of inheritance, we found a protective association between TB and the MBL2 G57E variant (odds ratio 0.60, confidence interval 0.4-0.9, P 0.008) and the corresponding LYQC haplotype (P(corrected) 0.007) which applied, however, only to TB caused by M. africanum but not to TB caused by M. tuberculosis. In vitro, M. africanum isolates bound recombinant human MBL more efficiently than did isolates of M. tuberculosis. We conclude that MBL binding may facilitate the uptake of M. africanum by macrophages, thereby promoting infection and that selection by TB may have favoured the spread of functional MBL deficiencies in regions endemic for M. africanum.

Rare human IFNG variants.

After the identification of the human interferon-gamma (IFNG) variant G54D (c.287G>A, ss105106770) in DNA samples from Ghana, West Africa, systematic mutation screening of IFNG by the LightCycler((R))-based procedure of high-resolution melting (HRM) revealed additional rare mutations. All variants occurred heterozygously only and were confirmed either by their detection in other individuals and/or by repeated DNA sequencing of independent PCR products.

CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population.

The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (P(corrected [cor]) = 0.002, P(cor) = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB.

Pulmonary tuberculosis: virulence of Mycobacterium africanum and relevance in HIV co-infection.

Although Mycobacterium africanum is being isolated in a significant proportion of cases of pulmonary tuberculosis in West Africa, its pathogenic potential remains a matter of discussion. Recent reports leave the question of whether M. africanum causes more severe pathology than M. tuberculosis or resembles opportunistic pathogens and might gain importance in the course of the HIV pandemic. Patients with pulmonary tuberculosis associated with M. africanum (n=556) and M. tuberculosis (n=1350) were studied in Ghana, West Africa, and compared regarding self-reported signs and symptoms, chest radiography, HIV status, mycobacterial drug resistance and mycobacterial clustering as determined by spoligotyping and IS6110 fingerprints. The rate of M. africanum infections was similar in HIV-positive (27%) and HIV-negative (30%) patients. M. africanum clustered less than M. tuberculosis (21% vs 79%; OR, 0.38; 95% CI, 0.3-0.5; p<0.001) corresponding to its lower prevalence (29% vs 70%). Clinically and radiographically, no significant differences were found except that M. africanum caused lower-lobe disease less frequently than M. tuberculosis (OR, 0.39; 95% CI, 0.2-0.7; Pc=0.01), whereby this association applied to HIV-negative patients only. No difference in virulence, as assessed by the severity of radiological presentation, was found when the two M. africanum subtypes West African 1 and West African 2 were compared. In the population studied, M. africanum closely resembled M. tuberculosis in pathology and cannot be considered an opportunistic pathogen.