Browsing by Subject "Malawi"
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Item Open Access Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.(J Virol, 2015-10) Pollara, Justin; McGuire, Erin; Fouda, Genevieve G; Rountree, Wes; Eudailey, Josh; Overman, R Glenn; Seaton, Kelly E; Deal, Aaron; Edwards, R Whitney; Tegha, Gerald; Kamwendo, Deborah; Kumwenda, Jacob; Nelson, Julie AE; Liao, Hua-Xin; Brinkley, Christie; Denny, Thomas N; Ochsenbauer, Christina; Ellington, Sascha; King, Caroline C; Jamieson, Denise J; van der Horst, Charles; Kourtis, Athena P; Tomaras, Georgia D; Ferrari, Guido; Permar, Sallie RUNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.Item Open Access Cost utility analysis of intramedullary nailing and skeletal traction treatment for patients with femoral shaft fractures in Malawi.(Acta orthopaedica, 2021-08) Chokotho, Linda; Donnelley, Claire A; Young, Sven; Lau, Brian C; Wu, Hao-Hua; Mkandawire, Nyengo; Gjertsen, Jan-Erik; Hallan, Geir; Agarwal-Harding, Kiran J; Shearer, DavidBackground and purpose - In Malawi, both skeletal traction (ST) and intramedullary nailing (IMN) are used in the treatment of femoral shaft fractures, ST being the mainstay treatment. Previous studies have found that IMN has improved outcomes and is less expensive than ST. However, no cost-effectiveness analyses have yet compared IMN and ST in Malawi. We report the results of a cost-utility analysis (CUA) comparing treatment using either IMN or ST.Patients and methods - This was an economic evaluation study, where a CUA was done using a decision-tree model from the government healthcare payer and societal perspectives with an 1-year time horizon. We obtained EQ-5D-3L utility scores and probabilities from a prospective observational study assessing quality of life and function in 187 adult patients with femoral shaft fractures treated with either IMN or ST. The patients were followed up at 6 weeks, and 3, 6, and 12 months post-injury. Quality adjusted life years (QALYs) were calculated from utility scores using the area under the curve method. Direct treatment costs were obtained from a prospective micro costing study. Indirect costs included patient lost productivity, patient transportation, meals, and childcare costs associated with hospital stay and follow-up visits. Multiple sensitivity analyses assessed model uncertainty.Results - Total treatment costs were higher for ST ($1,349) compared with IMN ($1,122). QALYs were lower for ST than IMN, 0.71 (95% confidence interval [CI] 0.66-0.76) and 0.77 (CI 0.71-0.82) respectively. Based on lower cost and higher utility, IMN was the dominant strategy. IMN remained dominant in 94% of simulations. IMN would be less cost-effective than ST at a total procedure cost exceeding $880 from the payer's perspective, or $1,035 from the societal perspective.Interpretation - IMN was cost saving and more effective than ST in the treatment of adult femoral shaft fractures in Malawi, and may be an efficient use of limited healthcare resources.Item Open Access Estimating the effect of anticipated depression treatment-related stigma on depression remission among people with noncommunicable diseases and depressive symptoms in Malawi.(PloS one, 2023-01) Dussault, Josée M; Zimba, Chifundo; Akello, Harriet; Stockton, Melissa; Hill, Sherika; Aiello, Allison E; Keil, Alexander; Gaynes, Bradley N; Udedi, Michael; Pence, Brian WPurpose
While mental health stigma research is sparse in Malawi, research in other settings suggests that stigma represents a barrier to mental health treatment and recovery. Accordingly, we conducted an analysis to understand the role of treatment-related stigma in depression care in Malawi by estimating the effect of patients' baseline anticipated treatment-related stigma on their 3-month probability of depression remission when newly identified with depression.Methods
We conducted depression screening and treatment at 10 noncommunicable disease (NCD) clinics across Malawi from April 2019 through December 2021. Eligible cohort participants were 18-65 years with depressive symptoms indicated by a PHQ-9 score ≥5. Questionnaires at the baseline and 3-month interviews included a vignette-based quantitative stigma instrument that measured treatment-related stigma, i.e., concerns about external stigma because of receiving depression treatment. Using inverse probability weighting to adjust for confounding and multiple imputation to account for missing data, this analysis relates participants' baseline levels of anticipated treatment stigma to the 3-month probability of achieving depression remission (i.e., PHQ-9 score < 5).Results
Of 743 included participants, 273 (37%) achieved depression remission by their 3-month interview. The probability of achieving depression remission at the 3-month interview among participants with high anticipated treatment stigma (0.31; 95% Confidence Interval [CI]: 0.23, 0.39)) was 10 percentage points lower than among the low/neutral stigma group (risk: 0.41; 95% CI: 0.36, 0.45; RD: -0.10; 95% CI: -0.19, -0.003).Conclusion
In Malawi, a reduction in anticipated depression treatment-related stigma among NCD patients initiating depression treatment could improve depression outcomes. Further investigation is necessary to understand the modes by which stigma can be successfully reduced to improve mental health outcomes and quality of life among people living with depression.Item Open Access Foreign Aid Allocation and Impact: A Sub-National Analysis of Malawi(2013-04-15) De, RajlakshmiThis project estimates the first sub-national model of foreign aid allocation and impact. Newly geocoded aid project data from Malawi is used in combination with multiple rounds of living standards data to predict the allocation of health aid, water aid, and education aid. In addition, the impacts of the three aid categories are detected using both instrumentation and propensity score matching methods to adjust for aid being allocated non-randomly. The three allocation models varied greatly with respect to the significant predictive covariates of diarrhea incidence, geographic region, and rural setting, but other aid allocation was a positive predictor in all three models such that areas receiving health aid were likely to also receive substantial water aid and education aid. A significant, positive effect of health aid on decreasing disease severity and a significant, positive effect of water aid on decreasing diarrhea incidence were found through both instrumentation and propensity score matching. An appropriate instrument for education aid could not be determined, but propensity score matching methods found a positive effect of education aid on school enrollment. These results suggest that foreign aid plays a useful role in poverty alleviation in Malawi and that governments should use information about local disease severity, diarrhea incidence, and school enrollment to allocate different aid types more efficiently.Item Open Access From Community Laywomen to Breast Health Workers: A Pilot Training Model to Implement Clinical Breast Exam Screening in Malawi.(PloS one, 2016-01) Gutnik, Lily; Moses, Agnes; Stanley, Christopher; Tembo, Tapiwa; Lee, Clara; Gopal, SatishBACKGROUND:Breast cancer burden is high in low-income countries. Inadequate early detection contributes to late diagnosis and increased mortality. We describe the training program for Malawi's first clinical breast exam (CBE) screening effort. METHODS:Laywomen were recruited as Breast Health Workers (BHWs) with the help of local staff and breast cancer advocates. The four-week training consisted of lectures, online modules, role-playing, case discussions, CBE using simulators and patients, and practice presentations. Ministry of Health trainers taught health communication, promotion, and education skills. Breast cancer survivors shared their experiences. Clinicians taught breast cancer epidemiology, prevention, detection, and clinical care. Clinicians and research staff taught research ethics, informed consent, data collection, and professionalism. Breast cancer knowledge was measured using pre- and post-training surveys. Concordance between BHW and clinician CBE was assessed. Breast cancer talks by BHW were evaluated on a 5-point scale in 22 areas by 3 judges. RESULTS:We interviewed 12 women, and 4 were selected as BHWs including 1 breast cancer survivor. Training was dynamic with modification based on trainee response and progress. A higher-than-anticipated level of comprehension and interest led to inclusion of additional topics like breast reconstruction. Pre-training knowledge increased from 49% to 91% correct (p<0.0001). Clinician and BHW CBE had 88% concordance (kappa 0.43). The mean rating of BHW educational talks was 4.4 (standard deviation 0.7). CONCLUSIONS:Malawian laywomen successfully completed training and demonstrated competency to conduct CBE and deliver breast cancer educational talks. Knowledge increased after training, and concordance was high between BHW and clinician CBE.Item Open Access Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing.(J Virol, 2011-03) Salazar-Gonzalez, JF; Salazar, MG; Learn, GH; Fouda, GG; Kang, HH; Mahlokozera, T; Wilks, AB; Lovingood, RV; Stacey, A; Kalilani, L; Meshnick, SR; Borrow, P; Montefiori, DC; Denny, TN; Letvin, NL; Shaw, GM; Hahn, BH; Permar, SR; A0167854, Center for HIV AIDS Vaccine ImmunologyHIV transmission via breastfeeding accounts for a considerable proportion of infant HIV acquisition. However, the origin and evolution of the virus population in breast milk, the likely reservoir of transmitted virus variants, are not well characterized. In this study, HIV envelope (env) genes were sequenced from virus variants amplified by single-genome amplification from plasmas and milk of 12 chronically HIV-infected, lactating Malawian women. Maximum likelihood trees and statistical tests of compartmentalization revealed interspersion of plasma and milk HIV env sequences in the majority of subjects, indicating limited or no compartmentalization of milk virus variants. However, phylogenetic tree analysis further revealed monotypic virus variants that were significantly more frequent in milk (median proportion of identical viruses, 29.5%; range, 0 to 61%) than in plasma (median proportion of identical viruses, 0%; range, 0 to 26%) (P = 0.002), suggesting local virus replication in the breast milk compartment. Moreover, clonally amplified virus env genes in milk produced functional virus Envs that were all CCR5 tropic. Milk and plasma virus Envs had similar predicted phenotypes and neutralization sensitivities to broadly neutralizing antibodies in both transmitting and nontransmitting mothers. Finally, phylogenetic comparison of longitudinal milk and plasma virus env sequences revealed synchronous virus evolution and new clonal amplification of evolved virus env genes in milk. The limited compartmentalization and the clonal amplification of evolving, functional viruses in milk indicate continual seeding of the mammary gland by blood virus variants, followed by transient local replication of these variants in the breast milk compartment.Item Open Access Outcome at 1 year in patients with femoral shaft fractures treated with intramedullary nailing or skeletal traction in a low-income country: a prospective observational study of 187 patients in Malawi.(Acta orthopaedica, 2020-12) Chokotho, Linda; Wu, Hao-Hua; Shearer, David; Lau, Brian C; Mkandawire, Nyengo; Gjertsen, Jan-Erik; Hallan, Geir; Young, SvenBackground and purpose - Intramedullary nailing (IMN) is underutilized in low-income countries (LICs) where skeletal traction (ST) remains the standard of care for femoral shaft fractures. This prospective study compared patient-reported quality of life and functional status after femoral shaft fractures treated with IMN or ST in Malawi. Patients and methods - Adult patients with femoral shaft fractures managed by IMN or ST were enrolled prospectively from 6 hospitals. Quality of life and functional status were assessed using EQ-5D-3L, and the Short Musculoskeletal Function Assessment (SMFA) respectively. Patients were followed up at 6 weeks, 3, 6, and 12 months post-injury. Results - Of 248 patients enrolled (85 IMN, 163 ST), 187 (75%) completed 1-year follow-up (55 IMN, 132 ST). 1 of 55 IMN cases had nonunion compared with 40 of 132 ST cases that failed treatment and converted to IMN (p < 0.001). Quality of life and SMFA Functional Index Scores were better for IMN than ST at 6 weeks, 3 and 6 months, but not at 1 year. At 6 months, 24 of 51 patients in the ST group had returned to work, compared with 26 of 37 in the IMN group (p = 0.02). Interpretation - Treatment with IMN improved early quality of life and function and allowed patients to return to work earlier compared with treatment with ST. Approximately one-third of patients treated with ST failed treatment and were converted to IMN.Item Open Access The magnitude and kinetics of the mucosal HIV-specific CD8+ T lymphocyte response and virus RNA load in breast milk.(PLoS One, 2011) Mahlokozera, T; Kang, HH; Goonetilleke, N; Stacey, AR; Lovingood, RV; Denny, TN; Kalilani, L; Bunn, JE; Meshnick, SR; Borrow, P; Letvin, NL; Permar, SR; Immunology, Center for HIVAIDS VaccineBACKGROUND: The risk of postnatal HIV transmission is associated with the magnitude of the milk virus load. While HIV-specific cellular immune responses control systemic virus load and are detectable in milk, the contribution of these responses to the control of virus load in milk is unknown. METHODS: We assessed the magnitude of the immunodominant GagRY11 and subdominant EnvKY9-specific CD8+ T lymphocyte response in blood and milk of 10 A*3002+, HIV-infected Malawian women throughout the period of lactation and correlated this response to milk virus RNA load and markers of breast inflammation. RESULTS: The magnitude and kinetics of the HIV-specific CD8+ T lymphocyte responses were discordant in blood and milk of the right and left breast, indicating independent regulation of these responses in each breast. However, there was no correlation between the magnitude of the HIV-specific CD8+ T lymphocyte response and the milk virus RNA load. Further, there was no correlation between the magnitude of this response and markers of breast inflammation. CONCLUSIONS: The magnitude of the HIV-specific CD8+ T lymphocyte response in milk does not appear to be solely determined by the milk virus RNA load and is likely only one of the factors contributing to maintenance of low virus load in milk.Item Open Access Validation of Chichewa Short Musculoskeletal Function Assessment (SMFA) questionnaire: A cross-sectional study.(Malawi medical journal : the journal of Medical Association of Malawi, 2019-03) Chokotho, Linda; Lau, Brian C; Conway, Devin; Wu, Hao-Hua; Shearer, David; Hallan, Geir; Gjertsen, Jan-Erik; Mkandawire, Nyengo; Young, SvenBackground
The Short Musculoskeletal Function Assessment (SMFA) tool measures function and quality of life in patients with musculoskeletal conditions.Objective
This study aimed to translate and adapt culturally the SMFA into Chichewa, and assess its clinimetric properties.Methods
The translated Chichewa version was administered to 53 patients with musculoskeletal disorders. To assess repeatability, an additional 20 patients answered the questionnaire twice over a time interval of two weeks. Internal consistency, floor and ceiling effects, and repeatability were tested; construct validity was assessed with the World Health Organization Quality of Life Assessment tool (WHOQOL-BREF).Results
There was good internal consistency for both Dysfunction and Bothersome indices (Cronbach's alpha 0.90) and good construct validity between both indices with the WHOQOL-BREF. Pearson's correlation coefficient and intraclass correlation coefficient (ICC) for repeatability for the Dysfunction Index were 0.941 and 0.922 (95% CI: 0.772, 0.971) respectively, and 0.877 and 0.851 (95% CI: 0.629, 0.941) for the Bothersome Index respectively.Conclusion
The translated Chichewa SMFA is a valid tool for populations that speak the Chichewa language.