Center for Global Health and Development Papers

Permanent URI for this collection

Browse

Recent Submissions

Now showing 1 - 20 of 65
  • Item
    Baseline assessment of WHO’s target for both availability and affordability of essential medicines to treat non-communicable diseases.
    (PLoS One, 2017-02) Ewen, Magaret; Zweekhorst, Marjolein; Regeer, Barbara; Laing, Richard
    BACKGROUND: WHO has set a voluntary target of 80% availability of affordable essential medicines, including generics, to treat major non-communicable diseases (NCDs), in the public and private sectors of countries by 2025. We undertook a secondary analysis of data from 30 surveys in low- and middle-income countries, conducted from 2008-2015 using the World Health Organization (WHO)/Health Action International (HAI) medicine availability and price survey methodology, to establish a baseline for this target. METHODS: Data for 49 medicines (lowest priced generics and originator brands) to treat cardiovascular diseases (CVD), diabetes, chronic obstructive pulmonary diseases (COPD) and central nervous system (CNS) conditions were analysed to determine their availability in healthcare facilities and pharmacies, their affordability for those on low incomes (based on median patient prices of each medicine), and the percentage of medicines that were both available and affordable. Affordability was expressed as the number of days' wages of the lowest-paid unskilled government worker needed to purchase 30 days' supply using standard treatment regimens. Paying more than 1 days' wages was considered unaffordable. FINDINGS: In low-income countries, 15.2% and 18.9% of lowest-priced generics met WHO's target in the public and private sectors, respectively, and 2.6% and 5.2% of originator brands. In lower-middle income countries, 23.8% and 23.2% of lowest priced generics, and 0.8% and 1.4% of originator brands, met the target in the public and private sectors, respectively. In upper-middle income countries, the situation was better for generics but still suboptimal as 36.0% and 39.4% met the target in public and private sectors, respectively. For originator brands in upper-middle income countries, none reached the target in the public sector and 13.7% in the private sector. Across the therapeutic groups for lowest priced generics, CVD medicines in low-income countries (11.9%), and CNS medicines in lower-middle (10.2%) and upper-middle income countries (33.3%), were least available and affordable in the public sector. In the private sector for lowest priced generics, CNS medicines were least available and affordable in all three country income groups (11.4%, 5.8% and 29.3% in low-, lower-middle and upper-middle income countries respectively). INTERPRETATION: This data, which can act as a baseline for the WHO target, shows low availability and/or poor affordability is resulting in few essential NCD medicines meeting the target in low- and middle-income countries. In the era of Sustainable Development Goals, and as countries work to achieve Universal Health Coverage, increased commitments are needed by governments to improve the situation through the development of evidence-informed, nationally-contextualised interventions, with regular monitoring of NCD medicine availability, patient prices and affordability.
  • Item
    Comparison of medicines management strategies in insurance schemes in middle-income countries: four case studies
    (BioMed Central, 2017-05) Kaplan, Warren A.; Ashigbie, Paul Gamelie Kwame; Brooks, Mohamad I.; Wirtz, Veronika J.
    BACKGROUND: Many middle-income countries are scaling up health insurance schemes to provide financial protection and access to affordable medicines to poor and uninsured populations. Although there is a wealth of evidence on how high income countries with mature insurance schemes manage cost-effective use of medicines, there is limited evidence on the strategies used in middle-income countries. This paper compares the medicines management strategies that four insurance schemes in middle-income countries use to improve access and cost-effective use of medicines among beneficiaries. METHODS: We compare key strategies promoting cost-effective medicines use in the New Rural Cooperative Medical Scheme (NCMS) in China, National Health Insurance Scheme in Ghana, Jamkesmas in Indonesia and Seguro Popular in Mexico. Through the peer-reviewed and grey literature as of late 2013, we identified strategies that met our inclusion criteria as well as any evidence showing if, and/or how, these strategies affected medicines management. Stakeholders involved and affected by medicines coverage policies in these insurance schemes were asked to provide relevant documents describing the medicines related aspects of these insurance programs. We also asked them specifically to identify publications discussing the unintended consequences of the strategies implemented. RESULTS: Use of formularies, bulk procurement, standard treatment guidelines and separation of prescribing and dispensing were present in all four schemes. Also, increased transparency through publication of tender agreements and procurement prices was introduced in all four. Common strategies shared by three out of four schemes were medicine price negotiation or rebates, generic reference pricing, fixed salaries for prescribers, accredited preferred provider network, disease management programs, and monitoring of medicines purchases. Cost-sharing and payment for performance was rarely used. There was a lack of performance monitoring strategies in all schemes. CONCLUSION: Most of the strategies used in the insurance schemes focus on containing expenditure growth, including budget caps on pharmaceutical expenditures (Mexico) and ceiling prices on medicines (all four countries). There were few strategies targeting quality improvement as healthcare providers are mostly paid through fixed salaries, irrespective of the quality of their prescribing or the health outcomes actually achieved. Monitoring healthcare system performance has received little attention.
  • Item
    Study protocol for a cluster-randomized controlled trial of an NCD access to medicines initative: Evaluation of Novartis Access in Kenya
    (BMJ Publishing Group Ltd, 2017-11) Rockers, Peter C.; Wirtz, Veronika J.; Vian, Taryn; Onyango, Monica A.; Ashigbie, Paul Gamelie Kwame; Laing, Richard
    INTRODUCTION: Novartis recently launched Novartis Access, an initiative to provide a basket of reduced price medicines for non-communicable diseases (NCDs) to be sold through the public and private nonprofit sectors in programme countries. This study will evaluate the impact of Novartis Access on the availability and price of NCD medicines at health facilities and households in Kenya, the first country to receive the programme. METHODS: This study will be a cluster randomised controlled trial. 8 counties in Kenya will be randomly assigned to the intervention or control group using a covariate constrained randomisation method to maximise balance on demographic and health characteristics. In intervention counties, public and private non-profit health facilities will be able to order Novartis Access NCD medicines from the Mission for Essential Drugs and Supplies (MEDS). Data will be collected from a random sample of 384 health facilities and 800 households at baseline, midline after 1-year of intervention, and end-line after 2 years. Quarterly surveillance data will also be collected from health facilities and a subsample of households through phone-based interviews. Households will be eligible if at least one resident has been previously diagnosed and prescribed a medicine for an NCD addressed by Novartis Access, including hypertension and diabetes. The primary outcomes will be availability and price of NCD medicines at health facilities, and availability, price, and expenditures on NCD medicines at households. Impacts will be estimated using intention-to-treat analysis. ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Boards at Strathmore University and at Boston University. Informed consent will be obtained from all participants at the start of the trial. The findings of the trial will be disseminated through peer-reviewed journals, international conferences, and meetings and events organised with local stakeholders.
  • Item
    Systematic differences between Cochrane and non-Cochrane meta-analyses on the same topic: a matched pair analysis
    (PLoS One., 2017-01) Useem, Johanna; Brennan, Alana Teresa; LaValley, Michael; Vickery, Michelle; Ameli, Omid; Reinen, Nichole; Gill, Christopher J.
    BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta-analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta-analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non-Cochrane reviews reported significantly higher effect sizes (P < 0.001) and lower precision (P < 0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSIONS: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question.
  • Item
    Travelers’ diarrhea and other gastrointestinal symptoms among Boston-area international travelers
    (The American Society of Tropical Medicine and Hygiene, 2017-06) Stoney, Rhett J.; Han, Pauline V.; Barnett, Elizabeth D.; Wilson, Mary E.; Jentes, Emily S.; Benoit, Christine M.; NacLeod, William B.; Hamer, Davidson H.; Chen, Lin H.
    INTRODUCTION: Travelers' diarrhea (TD) and non-TD gastrointestinal (GI) symptoms are common among international travelers. In a study of short-term travelers from Switzerland to developing countries, the most common symptom experienced was severe diarrhea (8.5%) followed by vomiting or abdominal cramps (4%).1 GI illnesses were the most frequently reported diagnoses (34%) among ill-returned travelers to GeoSentinel clinics.2 Of those returning to U.S. GeoSentinel clinics, acute diarrhea (30%) was the most common diagnosis.3 In one cohort of U.S. travelers, 46% reported diarrhea.4 GI illnesses can last from 2 days to weeks or longer,5 disrupting plans during travel or after returning home. Eighty percent of those who experienced diarrhea during travel treated themselves with medication and 6% sought medical care. METHODS: The Boston Area Travel Medicine Network (BATMN) is a research collaboration of travel clinics in the greater Boston area representing urban-, suburban-, academic-, and university-affiliated facilities. A convenience sample of travelers ≥ 18 years of age attending three BATMN clinics between 2009 and 2011 for pre-travel consultations completed pre-travel surveys, at least one survey weekly during travel, and a post-travel survey 2–4 weeks after return. Travelers were asked to complete a survey at the end of each week of their trip. Institutional review board approvals were obtained at all sites and the Centers for Disease Control and Prevention, and participants provided written informed consent. Information collected included demographic and trip characteristics, vaccines and medications recommended/prescribed before travel, medications taken during travel, dietary practices during travel (consumption of tap water, ice in drinks, unpasteurized dairy products, and salads), symptoms experienced, and impact of illness during and after travel. Vaccinations, prescriptions, and travel health advice given during the pre-travel consultation were recorded by a clinician, and the remainder of the surveys were completed by the traveler. Data were entered into a password-protected database (CS Pro, U.S. Census Bureau, Washington, DC). RESULTS: We enrolled 987 travelers; 628 (64%) completed all three parts (pre-, during, and post-travel) and were included in the study. Comparison of the 628 to the 359 who did not complete all three parts (noncompleters) revealed no differences, except that completion rates were higher for white travelers than all other racial/ethnic groups (P < 0.001) and for older travelers (median age 47 years versus 32 years in noncompleters, P < 0.001).11 Of those 628 travelers, 208 (33%) experienced TD, 45 (7%) experienced non-TD GI symptoms, 147 (23%) experienced non-GI symptoms, and 228 (36%) did not experience any symptoms during or after travel. Of the 208 with TD, 140 (67%) reported diarrhea as their only symptom, whereas 33 (16%) also experienced nausea/vomiting, 23 (11%) abdominal pain, and 27 (13%) fever (Table 1). Of the 45 who reported non-TD GI symptoms, 21 (47%) experienced nausea/vomiting, 19 (42%) experienced constipation, and 10 (22%) experienced abdominal pain during or after travel (Table 2). Almost all travelers (99%) received advice about food and water precautions and diarrhea management during pre-travel consultation.
  • Item
    Deaths attributable to diabetes in the United States: comparison of data sources and estimation approaches
    (PLoS ONE, 2017-01) Stokes, Andrew; Preston, Samuel
    OBJECTIVE: The goal of this research was to identify the fraction of deaths attributable to diabetes in the United States. RESEARCH DESIGN AND METHODS: We estimated population attributable fractions (PAF) for cohorts aged 30±84 who were surveyed in the National Health Interview Survey (NHIS) between 1997 and 2009 (N = 282,322) and in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010 (N = 21,814). Cohort members were followed prospectively for mortality through 2011. We identified diabetes status using self-reported diagnoses in both NHIS and NHANES and using HbA1c in NHANES. Hazard ratios associated with diabetes were estimated using Cox model adjusted for age, sex, race/ethnicity, educational attainment, and smoking status. RESULTS: We found a high degree of consistency between data sets and definitions of diabetes in the hazard ratios, estimates of diabetes prevalence, and estimates of the proportion of deaths attributable to diabetes. The proportion of deaths attributable to diabetes was estimated to be 11.5% using self-reports in NHIS, 11.7% using self-reports in NHANES, and 11.8% using HbA1c in NHANES. Among the sub-groups that we examined, the PAF was highest among obese persons at 19.4%. The proportion of deaths in which diabetes was assigned as the underlying cause of death (3.3±3.7%) severely understated the contribution of diabetes to mortality in the United States. CONCLUSIONS: Diabetes may represent a more prominent factor in American mortality than is commonly appreciated, reinforcing the need for robust population-level interventions aimed at diabetes prevention and care.
  • Item
    Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial
    (Lancet Global Health., 2016-9) Semrau, Katherine E. A.; Herlihy, Julie; Grogan, Caroline; Musokotwane, Kebby; Yeboah-Antwi, Kojo; Mbewe, Reuben; Banda, Bowen; Mpamba, Chipo; Hamomba, Fern; Pilingana, Portipher; Zulu, Andisen; Chanda-Kapata, Pascalina; Biemba, Godfrey; Thea, Donald M.; MacLeod, William B.; Simon, Jonathon L.; Hamer, Davidson H.
    BACKGROUND: Chlorhexidine umbilical cord washes reduce neonatal mortality in south Asian populations with high neonatal mortality rates and predominantly home-based deliveries. No data exist for sub-Saharan African populations with lower neonatal mortality rates or mostly facility-based deliveries. We compared the e ect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia. METHODS: We undertook a cluster-randomised controlled trial in Southern Province, Zambia, with 90 health facility- based clusters. We enrolled women who were in their second or third trimester of pregnancy, aged at least 15 years, and who would remain in the catchment area for follow-up of 28 days post-partum. Newborn babies received clean dry cord care (control) or topical application of 10 mL of a 4% chlorhexidine solution once per day until 3 days after cord drop (intervention), according to cluster assignment. We used strati ed, restricted randomisation to divide clusters into urban or two rural groups (located <40 km or ≥40 km to referral facility), and randomly assigned clusters (1:1) to use intervention (n=45) or control treatment (n=45). Sites, participants, and eld monitors were aware of their study assignment. The primary outcomes were all-cause neonatal mortality within 28 days post-partum and all-cause neonatal mortality within 28 days post-partum among babies who survived the rst 24 h of life. Analysis was by intention to treat. Neonatal mortality rate was compared with generalised estimating equations. This study is registered at http://ClinicalTrials.gov (NCT01241318). FINDINGS: From Feb 15, 2011, to Jan 30, 2013, we screened 42356 pregnant women and enrolled 39679 women (mean 436·2 per cluster [SD 65·3]), who had 37856 livebirths and 723 stillbirths; 63·8% of deliveries were facility-based. Of livebirths, 18 450 (99·7%) newborn babies in the chlorhexidine group and 19 308 (99·8%) newborn babies in the dry cord care group were followed up to day 28 or death. 16660 (90·0%) infants in the chlorhexidine group had chlorhexidine applied within 24 h of birth. We found no signi cant di erence in neonatal mortality rate between the chlorhexidine group (15·2 deaths per 1000 livebirths) and the dry cord care group (13·6 deaths per 1000 livebirths; risk ratio [RR] 1·12, 95% CI 0·88–1·44). Eliminating day 0 deaths yielded similar ndings (RR 1·12, 95% CI 0·86–1·47). INTERPRETATION: Despite substantial reductions previously reported in south Asia, chlorhexidine cord applications did not signi cantly reduce neonatal mortality rates in Zambia. Chlorhexidine cord applications do not seem to provide clear bene ts for newborn babies in settings with predominantly facility-based deliveries and lower (<30 deaths per 1000 livebirths) neonatal mortality rates.
  • Item
    Benefits and limitations of text messages to stimulate higher learning among community providers: participants’ views of an mHealth intervention to support continuing medical education in Vietnam
    (Johns Hopkins Center for Communication Programs, 2017-06) Sabin, Lara L.; Williams, Anna Larson; Le, Bao Ngoc; Herman, Augusta R.; Nguyen, Ha Viet; Albanese, Rebecca R.; Xiong, Wenjun; Shobiye, Hezekiah O.A.; Halim, Nafisa; Tran, Lien Thi Ngoc; McNabb, Marion; Hoang, Hai; Falconer, Ariel; Nguyen, Tam Thi Thanh; Gill, Christopher J.
    BACKGROUND: A randomized controlled trial was conducted in 2015 to evaluate a mobile continuing medical education (mCME) intervention that provided daily text messages to community-based physicians’ assistants (CBPAs) in Thai Nguyen Province, Vietnam. Although the intervention failed to improve medical knowledge over a 6-month period, a companion qualitative study provided insights on the views and experiences of intervention participants. METHODS: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) among participants randomized to receive text messages containing either simple medical facts or quiz questions. Trained interviewers collected data immediately following the conclusion of the trial in December 2015. Using semi-structured question guides, respondents were queried on their views of the intervention, positive and negative, and perceived impacts of the intervention. During analysis, after learning that the intervention had failed to increase knowledge among participants, we also examined reasons for lack of improvement in medical knowledge. All analyses were performed in NVivo using a thematic approach. RESULTS: A total of 70 CBPAs engaged in one of 8 FGDs or an IDI. One-half were men; average age among all respondents was 40 years. Most (81%) practiced in rural settings and most (51%) focused on general medicine. The mean length of work experience was 3 years. All respondents made positive comments about the intervention; convenience, relevance, and quick feedback (quiz format) were praised. Downsides encompassed lack of depth of information, weak interaction, technology challenges, and challenging/irrelevant messages. Respondents described perceived impacts encompassing increased motivation, knowledge, collegial discussions, Internet use to search for more information, and clinical skills. Overall, they expressed a desire for the intervention to continue and recommended expansion to other medical professionals. Overreliance on the text messages, lack of effective self-study, and technical/language-based barriers may be potential explanations for intervention failure. CONCLUSION: As a form of mCME, daily text messages were well-received by community-level health care providers in Vietnam. This mCME approach appears very promising in low-resource environments or where traditional forms of CME are impractical. Future models might consider enhancements to foster linkages to relevant medical materials, improve interaction with medical experts, and tailor medical content to the daily activities of medical staff.
  • Item
    Benefits and limitations of text messages to stimulate higher learning among community providers: participants’ views of an mHealth intervention to support continuing medical education in Vietnam
    (Johns Hopkins Center for Communication Programs, 2017-06) Sabin, Lara L.; Williams, Anna Larson; Le, Bao Ngoc; Herman, Augusta R.; Nguyen, Ha Viet; Albanese, Rebecca R.; Xiong, Wenjun; Shobiye, Hezekiah O.A.; Halim, Nafisa; Tran, Lien Thi Ngoc; McNabb, Marion; Hoang, Hai; Falconer, Ariel; Nguyen, Tam Thi Thanh; Gill, Christopher J.
    BACKGROUND: A randomized controlled trial was conducted in 2015 to evaluate a mobile continuing medical education (mCME) intervention that provided daily text messages to community-based physicians’ assistants (CBPAs) in Thai Nguyen Province, Vietnam. Although the intervention failed to improve medical knowledge over a 6-month period, a companion qualitative study provided insights on the views and experiences of intervention participants. METHODS: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) among participants randomized to receive text messages containing either simple medical facts or quiz questions. Trained interviewers collected data immediately following the conclusion of the trial in December 2015. Using semi-structured question guides, respondents were queried on their views of the intervention, positive and negative, and perceived impacts of the intervention. During analysis, after learning that the intervention had failed to increase knowledge among participants, we also examined reasons for lack of improvement in medical knowledge. All analyses were performed in NVivo using a thematic approach. RESULTS: A total of 70 CBPAs engaged in one of 8 FGDs or an IDI. One-half were men; average age among all respondents was 40 years. Most (81%) practiced in rural settings and most (51%) focused on general medicine. The mean length of work experience was 3 years. All respondents made positive comments about the intervention; convenience, relevance, and quick feedback (quiz format) were praised. Downsides encompassed lack of depth of information, weak interaction, technology challenges, and challenging/irrelevant messages. Respondents described perceived impacts encompassing increased motivation, knowledge, collegial discussions, Internet use to search for more information, and clinical skills. Overall, they expressed a desire for the intervention to continue and recommended expansion to other medical professionals. Overreliance on the text messages, lack of effective self-study, and technical/language-based barriers may be potential explanations for intervention failure. CONCLUSION: As a form of mCME, daily text messages were well-received by community-level health care providers in Vietnam. This mCME approach appears very promising in low-resource environments or where traditional forms of CME are impractical. Future models might consider enhancements to foster linkages to relevant medical materials, improve interaction with medical experts, and tailor medical content to the daily activities of medical staff.
  • Item
    Impact of a community-based package of interventions on child development in Zambia: a cluster-randomised controlled trial
    (BMJ Global Health., 2017-12) Rockers, Peter C.; Fink, Günther; Zanolini, Arianna; Banda, Bowen; Biemba, Godfrey; Sullivan, Cierra; Mutembo, Simon; Silavwe, Vichaels; Hamer, Davidson H.
    BACKGROUND: Community-based programmes are a critical platform for improving child health and development. We tested the impact of a community based early childhood intervention package in rural Zambia. Methods: We conducted a non-blinded cluster randomised controlled trial in Southern Province, Zambia. 30 clusters of villages were matched based on population density and distance from the nearest health centre, and randomly assigned to intervention (15 clusters and 268 caregiver–child dyads) or control (15 clusters and 258 caregiver–child dyads). Caregivers were eligible if they had a child aged 6–12 months at baseline. In intervention clusters, health workers screened children for infections and malnutrition, and invited caregivers to attend fortnightly group meetings covering a nutrition and child development curriculum. 220 intervention and 215 control dyads were evaluated after 1 year. The primary outcomes were stunting and INTERGROWTH-21st neurodevelopmental assessment (NDA) scores. Weight-for-age and height-for-age z-scores based on WHO growth standards were also analysed. Secondary outcomes were child illness symptoms, dietary intake and caregiver–child interactions based on self-report. Impact was estimated using intention to-treat analysis. RESULTS: The intervention package was associated with a 0.12 SD increase in weight-for-age (95% CI−0.14 to 0.38), a 0.15 SD increase in height-for-age (95% CI −0.18 to 0.48) and a reduction in stunting (OR 0.68; 95% CI 0.36 to 1.28), whereas there was no measurable impact on NDA score. Children receiving the intervention package had fewer symptoms, a more diverse diet and more caregiver interactions. CONCLUSIONS: In settings like Zambia, community based early childhood programmes appear to be feasible and appreciated by caregivers, as evidenced by high rates of uptake. The intervention package improved parenting behaviours and had a small positive, though statistically insignificant, impact on child development. Given the short time frame of the project, larger developmental impact is likely if differential parenting behaviours persist.
  • Item
    Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report
    (Journal of Travel Medicine, 2017-04) Riddle, Mark S.; Connor, Bradley A.; Beeching, Nicholas; Dupont, Herbert L.; Hamer, Davidson H.; Kozarsky, Phyllis; Libman, Michael; Steffen, Robert; Taylor, David; Tribble, David R.; Vila, Jordi; Zanger, Phillip; Ericsson, Charles D.
    BACKGROUND: Travelers' diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts. METHODS: This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers' diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology. RESULTS: New definitions for severity of travelers' diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted. CONCLUSION: Prevention and treatment of travelers' diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers' diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea.
  • Item
    Trends in the burden of HIV mortality after roll-out of antiretroviral therapy in KwaZulu-Natal, South Africa: an observational community cohort study
    (The Lancet, 2017-12) Reniers, Georges; Blom, Sylvia; Calvert, Clara; Martin-Onraet, Alexandra; Herbst, Abraham J.; Eaton, Jeffrey W.; Bor, Jacob; Slaymaker, Emma; Li, Zehang R.; Clark, Samuel J.; Bärnighausen, Till; Zaba, Basia; Hosegood, Victoria
    BACKGROUND: Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world. METHODS AND FINDINGS: Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy defi cit). Life expectancy gains and defi cits were further disaggregated by age and cause of death with demographic decomposition methods. FINDINGS: Covering the calendar years 2001 through to 2014, we obtained information on 93 903 adults who jointly contribute 535 42 8 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15·2 years for men (95% CI 12·4–17·8) and 17·2 years for women (14·5–20·2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79·7% of the total life expectancy gains in men (8·4 adult life-years), and 90·7% in women (12·8 adult life-years). For men, 9·5% is the result of a decline in external injuries. By 2014, the life expectancy defi cit had decreased to 1·2 years for men (–2·9 to 5·8) and to 5·3 years for women (2·6–7·8). In 2011–14, pulmonary tuberculosis and HIV were responsible for 84·9% of the life expectancy deficit in men and 80·8% in women. INTERPRETATION: The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better engagement with HIV-care services. Gains in adult life-years lived as well as the present life expectancy defi cit are almost exclusively due to differences in mortality attributed to HIV and pulmonary tuberculosis.
  • Item
    Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women.
    (Wolters Kluwer Health, Inc, 2017-06) Onoya, Dorina; Sineke, Tembeka; Brennan, Alana Teresa; Long. Lawrence; Fox, Matthew P.
    BACKGROUND: We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. METHODS: The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. RESULTS: The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1-2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4 cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1-3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4 cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7-1.1) and those who initiated ART in pregnancy. CONCLUSION: The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART.
  • Item
    Imputing HIV treatment start dates from routine laboratory data in South Africa: a validation study.
    (BMC Health Serv Res., 2017-02) Maskew, Mhairi; Bor, Jacob; Hendrickson, Cheryl; MacLeod, William; Bärnighausen, Till; Pillay, Deenan; Sanne, Iane; Carmona, Sergio; Stevens, Wendy; Fox, Matthew P.
    BACKGROUND: Poor clinical record keeping hinders health systems monitoring and patient care in many low resource settings. We develop and validate a novel method to impute dates of antiretroviral treatment (ART) initiation from routine laboratory data in South Africa's public sector HIV program. This method will enable monitoring of the national ART program using real-time laboratory data, avoiding the error potential of chart review. METHODS: We developed an algorithm to impute ART start dates based on the date of a patient's "ART workup", i.e. the laboratory tests used to determine treatment readiness in national guidelines, and the time from ART workup to initiation based on clinical protocols (21 days). To validate the algorithm, we analyzed data from two large clinical HIV cohorts: Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal; and Right to Care Cohort in urban Gauteng. Both cohorts contain known ART initiation dates and laboratory results imported directly from the National Health Laboratory Service. We assessed median time from ART workup to ART initiation and calculated sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of our imputed start date vs. the true start date within a 6 month window. Heterogeneity was assessed across individual clinics and over time. RESULTS: We analyzed data from over 80,000 HIV-positive adults. Among patients who had a workup and initiated ART, median time to initiation was 16 days (IQR 7,31) in Hlabisa and 21 (IQR 8,43) in RTC cohort. Among patients with known ART start dates, SE of the imputed start date was 83% in Hlabisa and 88% in RTC, indicating this method accurately predicts ART start dates for about 85% of all ART initiators. In Hlabisa, PPV was 95%, indicating that for patients with a lab workup, true start dates were predicted with high accuracy. SP (100%) and NPV (92%) were also very high. CONCLUSIONS: Routine laboratory data can be used to infer ART initiation dates in South Africa's public sector. Where care is provided based on protocols, laboratory data can be used to monitor health systems performance and improve accuracy and completeness of clinical records.
  • Item
    The disease of corruption: views on how to fight corruption to advance 21st century global health goals
    (BMC Medicine, 2016-9) Mackey, Tim; Clare, Jillian; Savedoff, William; Vogl, Frank; Lewis, Maureen; Sale, James
    Corruption has been described as a disease. When corruption infiltrates global health, it can be particularly devastating, threatening hard gained improvements in human and economic development, international security, and population health. Yet, the multifaceted and complex nature of global health corruption makes it extremely difficult to tackle, despite its enormous costs, which have been estimated in the billions of dollars. In this forum article, we asked anti-corruption experts to identify key priority areas that urgently need global attention in order to advance the fight against global health corruption. The views shared by this multidisciplinary group of contributors reveal several fundamental challenges and allow us to explore potential solutions to address the unique risks posed by health-related corruption. Collectively, these perspectives also provide a roadmap that can be used in support of global health anti-corruption efforts in the post-2015 development agenda.
  • Item
    Treatment outcomes and costs of providing antiretroviral therapy at a primary health clinic versus a hospital-based HIV clinic in South Africa
    (PLoS ONE, 2017-01) Long, Lawrence C.; Rosen, Sydney B.; Brennan, Alana Teresa; Moyo, Faith; Sauls, Celeste; Evans, Denise; Modi, Shookdev L.; Sanne, Ian; Fox, Matthew P.
    BACKGROUND:In 2010 South Africa revised its HIV treatment guidelines to allow the initiation and management of patients on antiretroviral therapy (ART) by nurses, rather than solely doctors, under a program called NIMART (Nurse Initiated and Managed Antiretroviral Therapy). We compared the outcomes and costs of NIMART between the two major public sector HIV treatment delivery models in use in South Africa today, primary health clinics and hospital-based HIV clinics. METHODS AND FINDINGS:The study was conducted at one hospital-based outpatient HIV clinic and one primary health clinic (PHC) in Gauteng Province. A retrospective cohort of adult patients initiated on ART at the PHC was propensity-score matched to patients initiated at the hospital outpatient clinic. Each patient was assigned a 12-month outcome of alive and in care or died/lost to follow up. Costs were estimated from the provider perspective for the 12 months after ART initiation. The proportion of patients alive and in care at 12 months did not differ between the PHC (76.5%) and the hospital-based site (74.2%). The average annual cost per patient alive and in care at 12 months after ART initiation was significantly lower at the PHC (US$238) than at the hospital outpatient clinic (US$428). CONCLUSIONS: Initiating and managing ART patients at PHCs under NIMART is producing equally good outcomes as hospital-based HIV clinic care at much lower cost. Evolution of hospital-based clinics into referral facilities that serve complicated patients, while investing most program expansion resources into PHCs, may be a preferred strategy for achieving treatment coverage targets.
  • Item
    Etiology of severe pneumonia in Ecuadorian children
    (PLOS One., 2017-02) Jonnalagadda, Sivani; Rodriguez, Oswaldo; Estrella, Bertha; Sabin, Lora L.; Sempértegui, Fernando; Hamer, Davidson H.
    INTRODUCTION: In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. METHODS: This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2–59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated. RESULTS: Among 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03). CONCLUSION: These results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available.
  • Item
    Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016
    (Annals of Internal Medicine., 2016-11) Hamer, Davidson; Barbre, Kira A.; Chen, Lin H.; Grobusch, Martin P.; Schlagenhauf, Patricia; Goorhulis, Abraham; Genderen, Perry J.Jl van; Molina, Israel; Asgeirsson, Hilmir; Kozarsky, Phyllis E.; Caumes, Eric; Hagmann, Stefan H.
    BACKGROUND: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. OBJECTIVE: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. DESIGN: Descriptive, using GeoSentinel records. SETTING: 63 travel and tropical medicine clinics in 30 countries. PATIENTS: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. MEASUREMENTS: Frequencies of demographic, trip, and clinical characteristics and complications. RESULTS: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain–Barre syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). LIMITATION: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. CONCLUSION: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission.
  • Item
    Cohort profile: the Right to Care Clinical HIV Cohort, South Africa
    (BMJ Publishing Group, 2017-06) Fox, Matthew P.; Maskew, Mhairi; Brennan, Alana Teresa; Evans, Denise; Onoya, Dorina; Malete, Given; MacPhail, Patrick; Bassett, Jean; Ebrahim, Osman; Mabotja, Dikeledi; Mashamaite, Sello; Long, Lawrence; Sanne, Ian
    PURPOSE: The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. PARTICIPANTS: The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3–6 months for clinical and laboratory monitoring. FINDINGS TO DATE: Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. FUTURE PLANS: Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa.
  • Item
    Vitamin A and zinc supplementation among pregnant women to prevent placental malaria: a randomized, double-blind, placebo-controlled trial in Tanzania
    (Am. J. Trop. Med, 2017-04) Darling, Anne Marie; Mugusi, Ferdinand M.; Etheredge, Analee J.; Gunaratna, Nilupa S.; Abioye, Aijibola Ibraheem; Aboud, Said; Duggan, Christopher; Mongi, Robert; Spiegelman, Donna; Roberts, Drucilla; Hamer, Davidson H.; Kain, Kevin C.; Fawzi, Wafaie W.
    BACKGROUND: Malaria causes nearly 200 million clinical cases and approximately half a million deaths each year, primarily in sub-Saharan Africa.1 The risk of malaria increases during pregnancy,2 a period during which its prevention is especially important. Not only do pregnant women experience greater severity of illness compared with nonpregnant women,2 but studies have shown strong associations between prenatal malaria and maternal anemia,2 fetal loss, low birthweight, and infant mortality.2 Improving preventive measures that specifically target malaria in pregnancy is a global health priority.3 METHODS: Study design and participants. This randomized, doubleblind, placebo-controlled trial was implemented at 8 antenatal care clinics in the urban Temeke and Ilala districts of Dar es Salaam, Tanzania. The trial was registered RESULTS: A total of 2,500 screened participants were enrolled in the trial. The trial profile is shown in Figure 1. It was not possible to collect placentas from 875 participants for the following reasons: miscarriages (fetal loss before 28 weeks of gestation) (N = 234), delivery outside of Dar es Salaam or at a non-study hospital (N = 577), or withdrawal from the study (N = 34). Of the remaining 1,589 women, 1,404 placental samples were obtained (88%); histology results were available for 1,361 participants. PCR results were available for 1,158 participants, and 1,404 participants had either histology or PCR results available. CONCLUSION: This study is the first to examine the impact of vitamin A and zinc supplementation starting in early pregnancy on placental malaria. We observed that supplementation with 25 mg zinc per day from the first trimester until delivery was associated with a 36% (95% CI = 9–56%) reduced risk of histopathology-positive placental infection, but not PCRpositive infection. Vitamin A supplementation had no impact on placental malaria, but was associated with an increased risk for severe anemia.