Burden of disease and risk factors for death among children treated for tuberculosis in Malawi.

SETTING: Tuberculosis (TB) is a leading cause of childhood death. Patient-level data on pediatric TB in Malawi that can be used to guide programmatic interventions are limited. OBJECTIVE: To describe pediatric TB case burden, disease patterns, treatment outcomes, and risk factors for death and poor outcome. DESIGN: We conducted a retrospective cohort study utilizing routine data. Odds ratios (ORs) for factors associated with poor outcome and death were calculated using generalized estimating equations. RESULTS: Children represented 8% (371/4642) of TB diagnoses. The median age was 7 years (interquartile range 2.8-11); 32.8% (113/345) were human immunodeficiency virus (HIV) infected. Of these, 54.0% were on antiretroviral therapy (ART) at the time of anti-tuberculosis treatment (ATT) initiation, 21.2% started ART during ATT, and 24.8% had no documented ART. The treatment success rate was 77.3% (11.2% cured, 66.1% completed treatment), with 22.7% experiencing poor outcomes (9.5% died, 13.2% were lost to follow-up). Being on ART at the time of ATT initiation was associated with increased odds of death compared to beginning ART during treatment (adjusted OR 2.75, 95%CI 1.27-5.96). CONCLUSION: Children represent a small proportion of diagnosed TB cases and experience poor outcomes. Higher odds of death among children already on ART raises concerns over the management of these children. Further discussion of and research into pediatric-specific strategies is required to improve case finding and outcomes.

Association between parity and fistula location in women with obstetric fistula: a multivariate regression analysis.

OBJECTIVE: To compare primiparous and multiparous women who develop obstetric fistula (OF) and to assess predictors of fistula location. DESIGN: Cross-sectional study. SETTING: Fistula Care Centre at Bwaila Hospital, Lilongwe, Malawi. POPULATION: Women with OF who presented between September 2011 and July 2014 with a complete obstetric history were eligible for the study. METHODS: Women with OF were surveyed for their obstetric history. Women were classified as multiparous if prior vaginal or caesarean delivery was reported. The location of the fistula was determined at operation: OF involving the urethra, bladder neck, and midvagina were classified as low; OF involving the vaginal apex, cervix, uterus, and ureters were classified as high. MAIN OUTCOME MEASURES: Demographic information was compared between primiparous and multiparous women using chi-squared and Mann-Whitney U-tests. Multivariate logistic regression models were implemented to assess the relationship between variables of interest and fistula location. RESULTS: During the study period, 533 women presented for repair, of which 452 (84.8%) were included in the analysis. The majority (56.6%) were multiparous when the fistula formed. Multiparous women were more likely to have laboured <1 day (62.4 versus 44.5%, P < 0.001), delivered a live-born infant (26.8 versus 17.9%, P = 0.026), and have a high fistula location (37.5 versus 11.2%, P < 0.001). Multiparity [adjusted odds ratio (aOR) = 4.55, 95% confidence interval (CI) 2.27-9.12)] and history of caesarean delivery (aOR = 4.11, 95% CI 2.45-6.89) were associated with development of a high fistula. CONCLUSIONS: Multiparity was common in our cohort, and these women were more likely to have a high fistula. Additional research is needed to understand the aetiology of high fistula including potential iatrogenic causes. TWEETABLE ABSTRACT: Multiparity and caesarean delivery were associated with a high tract fistula in our Malawian cohort.

Environmental risk factors for oesophageal cancer in Malawi: A case-control study.

AIM: There is a high burden of oesophageal cancer in Malawi with dismal outcomes. It is not known whether environmental factors are associated with oesophageal cancer. Without knowing this critical information, prevention interventions are not possible. The purpose of this analysis was to explore environmental factors associated with oesophageal cancer in the Malawian context. METHODS: A hospital-based case-control study of the association between environmental risk factors and oesophageal cancer was conducted at Kamuzu Central Hospital in Lilongwe, Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi. Ninety-six persons with squamous cell carcinoma and 180 controls were enrolled and analyzed. These two groups were compared for a range of environmental risk factors, using logistic regression models. Unadjusted and adjusted odds ratios and 95% confidence intervals (CI) were calculated. RESULTS: Firewood cooking, cigarette smoking, and use of white maize flour all had strong associations with squamous cell carcinoma of the oesophagus, with adjusted odds ratios of 12.6 (95% CI: 4.2-37.7), 5.4 (95% CI: 2.0-15.2) and 6.6 (95% CI: 2.3-19.3), respectively. CONCLUSIONS: Several modifiable risk factors were found to be strongly associated with squamous cell carcinoma. Research is needed to confirm these associations and then determine how to intervene on these modifiable risk factors in the Malawian context.

Womens experiences of HIV testing and counselling in the labour ward: a case of Bwaila hospital.

INTRODUCTION: HIV counseling and testing during labour can be emotional, but is important because it allows mothers and babies to receive PMTCT prophylaxis if previous identification of HIV infection has not occurred. The study explores how HIV testing and counseling during early labour affects women. METHODOLOGY: This was a qualitative exploratory study to understand women's experiences during early labor. From September to October 2009, we conducted 10 indepth interviews with women who tested for HIV during early labour. We recruited women who tested > 3 months previously and those who had never tested for HIV from the postpartum ward of Bwaila Hospital. Data were analyzed manually using the life story approach in order to examine and analyse subjective experiences of women and their constructions of the social world. Transcripts were read multiple times to understand meanings which participants attached to their experiences. We coded data according to emerging themes and subthemes. RESULTS: Ten women 20-35 years were interviewed. Eight women had unknown HIV status while two had known HIV results but re-tested to update their status. Four women were found HIV-positive while 6 were HIV-negative. The primary theme was that women appreciated and accepted HIV testing and counseling. Testing was accepted as a necessary step to protect the infant from HIV infection. Counseling was viewed as helpful for acceptance of HIV status. One key subtheme was that HIV positive women experienced disappointment about their HIV diagnosis, though this was outweighed by the knowledge that one could protect her infant. All women viewed the short time to complete the counseling and testing procedures as favourable. CONCLUSION: Labour testing is acceptable and should be promoted to enhance PMTCT services by identifying HIV positive women with unknown status. Counseling helps women to accept being found with HIV and seek appropriate services.

A membrane-associated, carbohydrate-modified form of the v-abl protein that cannot be phosphorylated in vivo or in vitro.

Abelson murine leukemia virus encodes a transforming protein which contains tyrosine kinase activity and is phosphorylated in vivo and in vitro. We found that P160 and P160-derived virus strains expressed an additional, altered v-abl protein which could not be phosphorylated. The altered v-abl protein (L-v-abl) differed from the phosphorylated form (K-v-abl) in that it was glycosylated and localized exclusively to the membrane fraction. Tunicamycin inhibition of N-linked carbohydrate addition did not restore phosphorylation. It did, however, reveal that L-v-abl had additional sequences relative to K-v-abl. The coding sequences required for this region and for the expression of L-v-abl were identified by replacing sequences in the P120 virus genome, which did not express L-v-abl, with sequences from the P160 virus genome. The necessary sequences were localized to the Moloney murine leukemia virus-derived gag gene. Comparison between the in vitro altered P120 and wild-type P120 virus strains indicated that expression of L-v-abl did not increase the efficiency of lymphoid transformation. Although the biological role of L-v-abl is not clear, our analyses have revealed that a specific amino terminal gag sequence can prevent v-abl from acting as a kinase substrate and can alter the cellular localization and modification of v-abl. These properties distinguish L-v-abl from previously reported v-abl proteins.

Proposal for naming host cell-derived inserts in retrovirus genomes.

We propose a system for naming inserted sequences in transforming retroviruses (i.e., onc genes), based on using trivial names derived from a prototype strain of virus.

Abelson murine leukemia virus mutants deficient in kinase activity and lymphoid cell transformation.

Abelson murine leukemia virus transforms both lymphoid cells and fibroblasts in vitro and induces a unique type of thymus-dependent lymphoma in vivo. Four fibroblast-transforming strains of Abelson murine leukemia virus were identified, based on the sizes of the Abelson murine leukemia virus-specific phosphoproteins produced by these isolates. Two of these strains, the standard P120- and the P160-producing viruses, transformed lymphoid cells efficiently in vitro and induced Abelson disease in vivo. Two other strains, which synthesized small Abelson murine leukemia virus-specific proteins with molecular weights of 90,000 (P90) and 100,000 (P100), transformed lymphoid cells very poorly both in vitro and in vivo. The reduced oncogenic potentials of these isolates were correlated with a high level of synthesis of fairly unstable P90 and P100. In addition, neither P90 nor P100 functional efficiently in protein kinase assays. The correlation of abnormal metabolism and deficient protein kinase activity with the reduced oncogenic potentials of these virus strains supported a direct role for these proteins and the kinase activity in transformation. Furthermore, these results suggested that the requirements for lymphoid cell transformation and fibroblast transformation are different.

Monoclonal rat anti-mouse brain antibody detects Abelson murine leukemia virus target cells in mouse bone marrow.

We report the characterization of a monoclonal antibody which detects a surface antigen expressed by the bone marrow target cell of A-MuLV. Treatment of bone marrow cells with this antibody and complement results in greater than loss 95% loss of the A-MuLV-derived in vitro transformed foci. The surface antigen detected by this antibody is also expressed on A-MuLV-transformed lymphoid cell lines, thymocytes, and some peripheral lymphocytes. This antigen is not expressed, however, by the pluripotent hematopoietic stem cell defined by the spleen colony-forming assay. We present evidence that the antigen detected is neither a virally encoded product, nor exclusively associated with the BALB/c genome.

Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus.

The majority of cell lines derived by infection of murine bone marrow cells with Abelson murine leukemia virus (A-MuLV) synthesize a mu chain but no detectable light chain. Aside from this mu-only phenotype, lines that make only light chain, both chains or no immunoglobulin-related polypeptides have also been found. Two lines have been studied in detail: one that makes only mu chain and one that makes only kappa light chain. Synthesis of both polypeptides can be increased by modifying the culture conditions so as to decrease the growth rate of the cells. Although some kappa chain secretion was observed, neither secreted nor surface mu was detected. We suggest that the mu- only phenotype may be an early normal step in the pathway of B lymphocyte maturation.