Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-30 (of 72 Records) |
Query Trace: Tappero JW [original query] |
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HIV incidence and risk behaviours of people who inject drugs in Bangkok, 19952012
Martin M , Vanichseni S , Sangkum U , Mock PA , Leethochawalit M , Chiamwongpaet S , Pitisuttithum P , Kaewkungwal J , van Griensven F , McNicholl JM , Tappero JW , Mastro TD , Kittimunkong S , Choopanya K . EClinicalMedicine 2019 9 44-51 Background: Three consecutive prospective studies were conducted among people who inject drugs (PWID) from May 1995 through June 2012 in Bangkok, Thailand. We examined data from these studies to evaluate HIV incidence and explore trends in risk behaviours. Methods: We used data from a 1995–1998 cohort study, a 1999–2004 HIV vaccine trial, and a 2005–2012 HIV pre-exposure prophylaxis (PrEP) study to examine per-quarter trends in HIV incidence, using a restricted cubic spline function for time in a Poisson regression. We also examined temporal trends in HIV-associated risk behaviours. Findings: HIV incidence declined from 5.7 per 100 person-years during the cohort study, to 2.7 per 100 person-years in the vaccine trial, to 0.7 per 100 person-years among PrEP study placebo recipients. Incidence peaked at 12.1 per 100 person-years in 1996 and declined to < 1.0% during 2005–2012. Reports of injecting drugs and sharing needles also declined from the cohort study to the PrEP study (p < 0.0001). Heroin was the most common drug injected during the cohort study and the vaccine trial, but stimulants (e.g., methamphetamine) and sedatives (e.g., midazolam) were injected more often during the PrEP study. Interpretation: HIV incidence among PWID declined during 2005–2012. Several factors likely contributed to the decline, including decreases in the frequency of injecting and sharing, improved access to HIV testing and antiretroviral therapy, and the use of PrEP. Expanding access to effective HIV prevention tools can hasten control of the HIV epidemic among PWID. Funding: The Bangkok Metropolitan Administration and U.S. Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention. |
Contributions of the US Centers for Disease Control and Prevention in implementing the global health security agenda in 17 partner countries
Fitzmaurice AG , Mahar M , Moriarty LF , Bartee M , Hirai M , Li W , Gerber AR , Tappero JW , Bunnell R . Emerg Infect Dis 2017 23 (13) S15-24 The Global Health Security Agenda (GHSA), a partnership of nations, international organizations, and civil society, was launched in 2014 with a mission to build countries' capacities to respond to infectious disease threats and to foster global compliance with the International Health Regulations (IHR 2005). The US Centers for Disease Control and Prevention (CDC) assists partner nations to improve IHR 2005 capacities and achieve GHSA targets. To assess progress through these CDC-supported efforts, we analyzed country activity reports dating from April 2015 through March 2017. Our analysis shows that CDC helped 17 Phase I countries achieve 675 major GHSA accomplishments, particularly in the cross-cutting areas of public health surveillance, laboratory systems, workforce development, and emergency response management. CDC's engagement has been critical to these accomplishments, but sustained support is needed until countries attain IHR 2005 capacities, thereby fostering national and regional health protection and ensuring a world safer and more secure from global health threats. |
Progress and opportunities for strengthening global health security
Angulo FJ , Cassell CH , Tappero JW , Bunnell RE . Emerg Infect Dis 2017 23 (13) S1-S4 In today’s interconnected world, an infectious disease outbreak that is not rapidly detected and controlled at its source can become a costly global health threat, both in lives lost and economic turmoil (1,2). Every year, thousands of outbreaks occur worldwide, many of which involve pathogens with pandemic potential. Since 2009, the World Health Organization (WHO) has declared public health emergencies of international concern for outbreaks of influenza A(H1N1) in 2009, Ebola in West Africa in 2014, and Zika in the Americas in 2015 (2). In 2007, the International Health Regulations 2005 (IHR 2005) entered into force, and all 196 state parties were legally bound to implement the core capacity required under the regulations. However, in 2014, almost two thirds of member states reported not being in compliance (3). To accelerate progress toward IHR 2005 compliance, the Global Health Security Agenda (GHSA) was launched by 29 countries, WHO, the Food and Agriculture Organization of the United Nations, and the World Organisation for Animal Health in 2014 and now includes >60 nations (4). |
US Centers for Disease Control and Prevention and its partners' contributions to global health security
Tappero JW , Cassell CH , Bunnell RE , Angulo FJ , Craig A , Pesik N , Dahl BA , Ijaz K , Jafari H , Martin R . Emerg Infect Dis 2017 23 (13) S5-S14 To achieve compliance with the revised World Health Organization International Health Regulations (IHR 2005), countries must be able to rapidly prevent, detect, and respond to public health threats. Most nations, however, remain unprepared to manage and control complex health emergencies, whether due to natural disasters, emerging infectious disease outbreaks, or the inadvertent or intentional release of highly pathogenic organisms. The US Centers for Disease Control and Prevention (CDC) works with countries and partners to build and strengthen global health security preparedness so they can quickly respond to public health crises. This report highlights selected CDC global health protection platform accomplishments that help mitigate global health threats and build core, cross-cutting capacity to identify and contain disease outbreaks at their source. CDC contributions support country efforts to achieve IHR 2005 compliance, contribute to the international framework for countering infectious disease crises, and enhance health security for Americans and populations around the world. |
Joint External Evaluation - development and scale-up of global multisectoral health capacity evaluation process
Bell E , Tappero JW , Ijaz K , Bartee M , Fernandez J , Burris H , Sliter K , Nikkari S , Chungong S , Rodier G , Jafari H . Emerg Infect Dis 2017 23 (13) S33-9 The Joint External Evaluation (JEE), a consolidation of the World Health Organization (WHO) International Health Regulations 2005 (IHR 2005) Monitoring and Evaluation Framework and the Global Health Security Agenda country assessment tool, is an objective, voluntary, independent peer-to-peer multisectoral assessment of a country's health security preparedness and response capacity across 19 IHR technical areas. WHO approved the standardized JEE tool in February 2016. The JEE process is wholly transparent; countries request a JEE and are encouraged to make its findings public. Donors (e.g., member states, public and private partners, and other public health institutions) can support countries in addressing identified JEE gaps, and implementing country-led national action plans for health security. Through July 2017, 52 JEEs were completed, and 25 more countries were scheduled across WHO's 6 regions. JEEs facilitate progress toward IHR 2005 implementation, thereby building trust and mutual accountability among countries to detect and respond to public health threats. |
Public Health Progress in Haiti
Lowrance DW , Tappero JW , Poncelet JL , Etienne C , Frieden TR , Delsoins D . Am J Trop Med Hyg 2017 97 1-3 Although the attention of the Haitian public and international community has understandably turned to the recurrent political challenges facing the country and recovery from Hurricane Mathew, it is important that public health stakeholders take stock of progress made, remaining gaps, and fundamental public health priorities. In the past year, the global community has assessed progress toward the Millennium Development Goals (MDGs) and established new health targets under the Sustainable Development Goals framework.1 Haiti has made progress toward the MDGs and many of the objectives established in the aftermath of the earthquake.1–7 Important lessons regarding the association between various global health emergency responses, such as to human immunodeficiency virus (HIV), tuberculosis (TB), Ebola (Haitian public health professionals deployed to Guinea), and health sector resiliency have been identified.8,9 Yet much remains to be done to increase health service access and to reduce morbidity and mortality from preventable causes in the country. Although the public health system in Haiti has been improved since the earthquake, emergency response and health recovery funding has largely focused on new and acute threats such as Zika virus.10 Moreover, the health-care delivery infrastructure remains fragile, with limited coverage of primary care services, suboptimal health-care performance, and excessive health risk and vulnerability for the Haitian population. It is in this context that the Supplement, entitled “Public Health Progress in Haiti,” was developed. The reports enclosed span HIV, TB, malaria, cholera, immunizations, rabies, water, sanitation and hygiene, and lymphatic filariasis, and also address notifiable disease surveillance reporting and national laboratory capacity.11–20 Collectively, they appraise some of the key programs and services that have been the focus of postearthquake response and recovery planning and which have central roles informing current and future strengthening and prioritization within the health sector. |
Burden and characteristics of HIV infection among female sex workers in Kampala, Uganda - a respondent-driven sampling survey
Hladik W , Baughman AL , Serwadda D , Tappero JW , Kwezi R , Nakato ND , Barker J . BMC Public Health 2017 17 (1) 565 BACKGROUND: Sex workers in Uganda are at significant risk for HIV infection. We characterized the HIV epidemic among Kampala female sex workers (FSW). METHODS: We used respondent-driven sampling to sample FSW aged 15+ years who reported having sold sex to men in the preceding 30 days; collected data through audio-computer assisted self-interviews, and tested blood, vaginal and rectal swabs for HIV, syphilis, neisseria gonorrhea, chlamydia trachomatis, and trichomonas vaginalis. RESULTS: A total of 942 FSW were enrolled from June 2008 through April 2009. The overall estimated HIV prevalence was 33% (95% confidence intervals [CI] 30%-37%) and among FSW 25 years or older was 44%. HIV infection is associated with low levels of schooling, having no other work, never having tested for HIV, self-reported genital ulcers or sores, and testing positive for neisseria gonorrhea or any sexually transmitted infections (STI). Two thirds (65%) of commercial sex acts reportedly were protected by condoms; one in five (19%) FSW reported having had anal sex. Gender-based violence was frequent; 34% reported having been raped and 24% reported having been beaten by clients in the preceding 30 days. CONCLUSIONS: One in three FSW in Kampala is HIV-infected, suggesting a severe HIV epidemic in this population. Intensified interventions are warranted to increase condom use, HIV testing, STI screening, as well as antiretroviral treatment and pre-exposure prophylaxis along with measures to overcome gender-based violence. |
Intimate partner violence and adherence to HIV pre-exposure prophylaxis (PrEP) in African women in HIV serodiscordant relationships: A prospective cohort study
Roberts ST , Haberer J , Celum C , Mugo N , Ware NC , Cohen CR , Tappero JW , Kiarie J , Ronald A , Mujugira A , Tumwesigye E , Were E , Irungu E , Baeten JM . J Acquir Immune Defic Syndr 2016 73 (3) 313-322 BACKGROUND: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP). METHODS: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence. RESULTS: Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0-35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away. CONCLUSIONS: Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated. |
Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria
Tchaparian E , Sambol NC , Arinaitwe E , McCormack SA , Bigira V , Wanzira H , Muhindo M , Creek DJ , Sukumar N , Blessborn D , Tappero JW , Kakuru A , Bergqvist Y , Aweeka FT , Parikh S . J Infect Dis 2016 214 (8) 1243-51 BACKGROUND: The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely-used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children. METHODS: Capillary whole blood was collected in 105 Ugandan children, ages 6 months to 2 years, treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine. RESULTS: Population pharmacokinetics for lumefantrine employed a 2-compartment open model with first-order absorption. Age had a significant positive correlation with bioavailability in a model that included allometric scaling. Children not on trimethoprim-sulfamethoxazole with concentrations below 200 ng/mL had a 3-fold higher hazard of 28-day recurrent parasitemia compared to those above 200 ng/mL(p=0.0007). However, for children on trimethoprim-sulfamethoxazole, the risk of recurrent parasitemia did not differ significantly based on this threshold. Day 3 concentrations were a stronger predictor of 28-day recurrence than day 7 concentrations. CONCLUSIONS: We demonstrate that age, in addition to weight, is a determinant of lumefantrine exposure, and in the absence of TS, lumefantrine exposure is a determinant of recurrent parasitemia. Exposure in children 6 months to 2 years was generally lower than those published for older children and adults. Further refinement of artemether-lumefantrine dosing to improve exposure in infants and very young children may be warranted. |
Overview, control strategies, and lessons learned in the CDC response to the 2014-2016 Ebola epidemic
Bell BP , Damon IK , Jernigan DB , Kenyon TA , Nichol ST , O'Connor JP , Tappero JW . MMWR Suppl 2016 65 (3) 4-11 During 2014-2016, CDC, working with U.S. and international partners, mounted a concerted response to end the unprecedented epidemic of Ebola virus disease (Ebola) in West Africa. CDC's response, which was the largest in the agency's history, was directed simultaneously at controlling the epidemic in West Africa and strengthening preparedness for Ebola in the United States. Although experience in responding to approximately 20 Ebola outbreaks since 1976 had provided CDC and other international responders an understanding of the disease and how to stop its spread, the epidemic in West Africa presented new and formidable challenges. The initial response was slow and complicated for several reasons, including wide geographic spread of cases, poor public health and societal infrastructure, sociodemographic factors, local unfamiliarity with Ebola, and distrust of government and health care workers. In the United States, widespread public alarm erupted after Ebola cases were diagnosed in Dallas, Texas, and New York City, New York. CDC, in collaboration with its U.S. and international counterparts, applied proven public health strategies as well as innovative new approaches to help control the Ebola epidemic in West Africa and strengthen public health readiness in the United States. Lessons learned include the recognition that West African and other countries need effective systems to detect and stop infectious disease threats, the need for stronger international surge capacity for times when countries are overwhelmed by an outbreak, and the importance of improving infection prevention and control in health care settings. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). |
Public health surveillance: At the core of the Global Health Security Agenda
Wolicki SB , Nuzzo JB , Blazes DL , Pitts DL , Iskander JK , Tappero JW . Health Secur 2016 14 (3) 185-8 Global health security involves developing the infrastructure and capacity to protect the health of people and societies worldwide. The acceleration of global travel and trade poses greater opportunities for infectious diseases to emerge and spread. The International Health Regulations (IHR) were adopted in 2005 with the intent of proactively developing public health systems that could react to the spread of infectious disease and provide better containment. Various challenges delayed adherence to the IHR. The Global Health Security Agenda came about as an international collaborative effort, working multilaterally among governments and across sectors, seeking to implement the IHR and develop the capacities to prevent, detect, and respond to public health emergencies of international concern. When examining the recent West African Ebola epidemic as a case study for global health security, both strengths and weaknesses in the public health response are evident. The central role of public health surveillance is a lesson reiterated by Ebola. Through further implementation of the Global Health Security Agenda, identified gaps in surveillance can be filled and global health security strengthened. |
Rethinking dosing regimen selection of piperaquine for malaria chemoprevention: A simulation study
Sambol NC , Tappero JW , Arinaitwe E , Parikh S . PLoS One 2016 11 (5) e0154623 BACKGROUND: The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP) is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ) based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children. METHODS: Based on a prior population pharmacokinetic model of PQ in young Ugandan children, we simulated capillary plasma concentration-time profiles (including their variability) of candidate chemoprevention regimens for a reference population of 1-2 year olds weighing at least 11 kg. Candidate regimens that were tested included monthly administration of standard therapeutic doses, bimonthly dosing, and weekly dosing (with and without a loading dose). RESULTS: Once daily doses of 320 mg for three days (960 mg total) at the beginning of each month are predicted to achieve an average steady-state trough capillary piperaquine concentration of 35 ng/mL, with 60% achieving a level of 30 ng/mL or higher. In contrast, weekly dosing of 320 mg (i.e., 33% higher amount per month) is predicted to approximately double the average steady-state trough concentration, increase the percent of children predicted to achieve 30 ng/mL or higher (94%), while at the same time lowering peak concentrations. Exposure at steady-state, reached at approximately 3 months of multiple dosing, is expected to be approximately 2-fold higher than exposure following initial dosing, due to accumulation. A loading dose improves early exposure, thereby reducing the risk of breakthrough infections at the initiation of chemoprevention. CONCLUSIONS: Once weekly chemoprevention of DP predicts favourable exposures with respect to both trough and peak concentrations. These predictions need to be verified, as well as safety evaluated, in field-based clinical studies of young children. Simulations based on prior knowledge provide a systematic information-driven approach to evaluate candidate DP chemopreventive regimens for future trial designs. |
B cell sub-types following acute malaria and associations with clinical immunity
Sullivan RT , Ssewanyana I , Wamala S , Nankya F , Jagannathan P , Tappero JW , Mayanja-Kizza H , Muhindo MK , Arinaitwe E , Kamya M , Dorsey G , Feeney ME , Riley EM , Drakeley CJ , Greenhouse B , Sullivan R . Malar J 2016 15 (1) 139 BACKGROUND: Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria. METHODS: To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria-lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia. RESULTS: Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria. CONCLUSIONS: These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria. |
Population Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin-Piperaquine for Uncomplicated Malaria
Sambol NC , Yan L , Creek DJ , McCormack SA , Arinaitwe E , Bigira V , Wanzira H , Kakuru A , Tappero JW , Lindegardh N , Tarning J , Nosten F , Aweeka FT , Parikh S . Clin Pharmacol Ther 2015 98 (1) 87-95 This prospective trial investigated the population pharmacokinetics of piperaquine given with dihydroartemisinin to treat uncomplicated malaria in 107 Ugandan children 6 months to 2 years old, an age group previously unstudied. Current weight-based dosing does not adequately address physiological changes in early childhood. Patients were administered standard 3-day oral doses and provided 1,282 capillary plasma concentrations from 218 malaria episodes. Less than 30% of treatments achieved 57 ng/mL on day 7. A three-compartment model with first-order absorption described the data well. Age had a statistically significant effect (P < 0.005) on clearance/bioavailability in a model that accounts for allometric scaling. Simulations demonstrated that higher doses in all children, but especially in those with lower weight for age, are required for adequate piperaquine exposure, although safety and tolerance will need to be established. These findings support other evidence that both weight- and age-specific guidelines for piperaquine dosing in children are urgently needed. |
Global health security: the wider lessons from the West African Ebola virus disease epidemic
Heymann DL , Chen L , Takemi K , Fidler DP , Tappero JW , Thomas MJ , Kenyon TA , Frieden TR , Yach D , Nishtar S , Kalache A , Olliaro PL , Horby P , Torreele E , Gostin LO , Ndomondo-Sigonda M , Carpenter D , Rushton S , Lillywhite L , Devkota B , Koser K , Yates R , Dhillon RS , Rannan-Eliya RP . Lancet 2015 385 (9980) 1884-901 The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing. |
Rapid response to Ebola outbreaks in remote areas - Liberia, July-November 2014
Kateh F , Nagbe T , Kieta A , Barskey A , Gasasira AN , Driscoll A , Tucker A , Christie A , Karmo B , Scott C , Barradas D , Blackley D , Dweh E , Warren F , Mahoney F , Kassay G , Calvert GM , Castro G , Logan G , Appiah G , Kirking H , Koon H , Papowitz H , Walke H , Cole IB , Montgomery J , Neatherlin J , Tappero JW , Forrester J , Woodring J , Mott J , Attfield K , DeCock K , Lindblade KA , Powell K , Yeoman K , Adams L , Broyles LN , Slutsker L , Belcher L , Cooper L , Santos M , Westercamp M , Weinberg MP , Massoudi M , Dea M , Patel M , Hennessey M , Fomba M , Lubogo M , Maxwell N , Moonan P , Arzoaquoi S , Gee S , Zayzay S , Pillai S , Williams S , Zarecki SM , Yett S , James S , Grube S , Gupta S , Nelson T , Malibiche T , Frank W , Smith W , Nyenswah T . MMWR Morb Mortal Wkly Rep 2015 64 (7) 188-192 West Africa is experiencing its first epidemic of Ebola virus disease (Ebola). As of February 9, Liberia has reported 8,864 Ebola cases, of which 3,147 were laboratory-confirmed. Beginning in August 2014, the Liberia Ministry of Health and Social Welfare (MOHSW), supported by CDC, the World Health Organization (WHO), and others, began systematically investigating and responding to Ebola outbreaks in remote areas. Because many of these areas lacked mobile telephone service, easy road access, and basic infrastructure, flexible and targeted interventions often were required. Development of a national strategy for the Rapid Isolation and Treatment of Ebola (RITE) began in early October. The strategy focuses on enhancing capacity of county health teams (CHT) to investigate outbreaks in remote areas and lead tailored responses through effective and efficient coordination of technical and operational assistance from the MOHSW central level and international partners. To measure improvements in response indicators and outcomes over time, data from investigations of 12 of 15 outbreaks in remote areas with illness onset dates of index cases during July 16-November 20, 2014, were analyzed. The times to initial outbreak alerts and durations of the outbreaks declined over that period while the proportions of patients who were isolated and treated increased. At the same time, the case-fatality rate in each outbreak declined. Implementation of strategies, such as RITE, to rapidly respond to rural outbreaks of Ebola through coordinated and tailored responses can successfullyreduce transmission and improve outcomes. |
Challenges in responding to the Ebola epidemic - four rural counties, Liberia, August-November 2014
Summers A , Nyenswah TG , Montgomery JM , Neatherlin J , Tappero JW . MMWR Morb Mortal Wkly Rep 2014 63 (50) 1202-4 The first cases of Ebola virus disease (Ebola) in West Africa were identified in Guinea on March 22, 2014. On March 30, the first Liberian case was identified in Foya Town, Lofa County, near the Guinean border. Because the majority of early cases occurred in Lofa and Montserrado counties, resources were concentrated in these counties during the first several months of the response, and these counties have seen signs of successful disease control. By October 2014, the epidemic had reached all 15 counties of Liberia. During August 27-September 10, 2014, CDC in collaboration with the Liberian Ministry of Health and Social Welfare assessed county Ebola response plans in four rural counties (Grand Cape Mount, Grand Bassa, Rivercess, and Sinoe, to identify county-specific challenges in executing their Ebola response plans, and to provide recommendations and training to enhance control efforts. Assessments were conducted through interviews with county health teams and health care providers and visits to health care facilities. At the time of assessment, county health teams reported lacking adequate training in core Ebola response strategies and reported facing many challenges because of poor transportation and communication networks. Development of communication and transportation network strategies for communities with limited access to roads and limited means of communication in addition to adequate training in Ebola response strategies is critical for successful management of Ebola in remote areas. |
Protective efficacy of prolonged co-trimoxazole prophylaxis in HIV-exposed children up to age 4 years for the prevention of malaria in Uganda: a randomised controlled open-label trial
Homsy J , Dorsey G , Arinaitwe E , Wanzira H , Kakuru A , Bigira V , Muhindo M , Kamya MR , Sandison TG , Tappero JW . Lancet Glob Health 2014 2 (12) e727-36 BACKGROUND: WHO recommends daily co-trimoxazole for children born to HIV-infected mothers from 6 weeks of age until breastfeeding cessation and exclusion of HIV infection. We have previously reported on the effectiveness of continuation of co-trimoxazole prophylaxis up to age 2 years in these children. We assessed the protective efficacy and safety of prolonging co-trimoxazole prophylaxis until age 4 years in HIV-exposed children. METHODS: We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern Uganda, an area with high HIV prevalence, malaria transmission intensity, and antifolate resistance. We enrolled HIV-exposed infants between 6 weeks and 9 months of age and prescribed them daily co-trimoxazole until breastfeeding cessation and HIV-status confirmation. At the end of breastfeeding, children who remained HIV-uninfected were randomly assigned (1:1) to discontinue co-trimoxazole or to continue taking it up to age 2 years. At age 2 years, children who continued co-trimoxazole prophylaxis were randomly assigned (1:1) to discontinue or continue prophylaxis from age 2 years to age 4 years. The primary outcome was incidence of malaria (defined as the number of treatments for new episodes of malaria diagnosed with positive thick smear) at age 4 years. For additional comparisons, we observed 48 HIV-infected children who took continuous co-trimoxazole prophylaxis and 100 HIV-unexposed uninfected children who never received prophylaxis. We measured grade 3 and 4 serious adverse events and hospital admissions. All children were followed up to age 5 years and all analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00527800. FINDINGS: 203 HIV-exposed infants were enrolled between Aug 10, 2007, and March 28, 2008. After breastfeeding ended, 185 children were not infected with HIV and were randomly assigned to stop (n=87) or continue (n=98) co-trimoxazole up to age 2 years. At age 2 years, 91 HIV-exposed children who had remained on co-trimoxazole prophylaxis were randomly assigned to discontinue (n=46) or continue (n=45) co-trimoxazole from age 2 years to age 4 years. We recorded 243 malaria episodes (2.91 per person-years) in the 45 HIV-exposed children assigned to continue co-trimoxazole until age 4 years compared with 503 episodes (5.60 per person-years) in the 46 children assigned to stop co-trimoxazole at age 2 years (incidence rate ratio 0.53, 95% CI 0.39-0.71; p<0.0001). There was no evidence of malaria incidence rebound in the year after discontinuation of co-trimoxazole in the HIV-exposed children who stopped co-trimoxazole at age 2 years, but incidence increased significantly in HIV-exposed children who stopped co-trimoxazole at age 4 years (odds ratio 1.78, 95% CI 1.19-2.66; p=0.005). Incidence of grade 3 or 4 serious adverse events, hospital admissions, or deaths did not significantly differ between HIV-exposed, HIV-unexposed, and HIV-infected children. INTERPRETATION: Continuation of co-trimoxazole prophylaxis up to 4 years of age seems safe and efficacious to protect HIV-exposed children living in malaria-endemic areas. FUNDING: Centers for Disease Control and Prevention Global AIDS Program, Doris Duke Charitable Foundation. |
Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial
Baeten JM , Donnell D , Mugo NR , Ndase P , Thomas KK , Campbell JD , Wangisi J , Tappero JW , Bukusi EA , Cohen CR , Katabira E , Ronald A , Tumwesigye E , Were E , Fife KH , Kiarie J , Farquhar C , John-Stewart G , Kidoguchi L , Coombs RW , Hendrix C , Marzinke MA , Frenkel L , Haberer JE , Bangsberg D , Celum C . Lancet Infect Dis 2014 14 (11) 1055-1064 BACKGROUND: Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP. METHODS: We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov, number NCT00557245. FINDINGS: 4410 (99.6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0.71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0.48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio [HR] 0.67, 95% CI 0.39-1.17; p=0.16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0.15, 95% CI 0.06-0.37; p<0.0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0.07, 0.02-0.23; p<0.0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups. INTERPRETATION: These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health. |
Loss and dysfunction of Vdelta2+ gammadelta T cells are associated with clinical tolerance to malaria
Jagannathan P , Kim CC , Greenhouse B , Nankya F , Bowen K , Eccles-James I , Muhindo MK , Arinaitwe E , Tappero JW , Kamya MR , Dorsey G , Feeney ME . Sci Transl Med 2014 6 (251) 251ra117 Although clinical immunity to malaria eventually develops among children living in endemic settings, the underlying immunologic mechanisms are not known. The Vdelta2(+) subset of gammadelta T cells have intrinsic reactivity to malaria antigens, can mediate killing of Plasmodium falciparum merozoites, and expand markedly in vivo after malaria infection in previously naive hosts, but their role in mediating immunity in children repeatedly exposed to malaria is unclear. We evaluated gammadelta T cell responses to malaria among 4-year-old children enrolled in a longitudinal study in Uganda. We found that repeated malaria was associated with reduced percentages of Vdelta2(+) gammadelta T cells in peripheral blood, decreased proliferation and cytokine production in response to malaria antigens, and increased expression of immunoregulatory genes. Further, loss and dysfunction of proinflammatory Vdelta2(+) gammadelta T cells were associated with a reduced likelihood of symptoms upon subsequent P. falciparum infection. Together, these results suggest that repeated malaria infection during childhood results in progressive loss and dysfunction of Vdelta2(+) gammadelta T cells that may facilitate immunological tolerance of the parasite. |
Longitudinal outcomes in a cohort of Ugandan children randomized to artemether-lumefantrine versus dihydroartemisinin-piperaquine for the treatment of malaria
Wanzira H , Kakuru A , Arinaitwe E , Bigira V , Muhindo MK , Conrad M , Rosenthal PJ , Kamya MR , Tappero JW , Dorsey G . Clin Infect Dis 2014 59 (4) 509-16 BACKGROUND: Artemisinin-based combination therapy (ACT) has become the standard of care for the treatment of uncomplicated Plasmodium falciparum malaria. Although several ACT regimens are approved, data guiding optimal choices of ACTs are limited. We compared short- and long-term outcomes in a cohort of young Ugandan children randomized to 2 leading ACTs. METHODS: Overall, 312 children were randomized to artemether-lumefantrine or dihydroartemisinin-piperaquine (DP) at the time of the first episode of uncomplicated malaria (median age, 10.5 months). The same treatment was given for all subsequent episodes of uncomplicated malaria and children were followed until they reached 5 years of age. The cohort included a subgroup that was human immunodeficiency virus (HIV) infected (n = 44) or HIV exposed (n = 175) and prescribed trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Outcomes included time to recurrent malaria following individual treatments and the overall incidences of treatments for malaria, complicated malaria, and hospitalizations. RESULTS: Among children not prescribed TMP-SMX prophylaxis, 4443 treatments for malaria were given over 790 person-years following randomization. Treatment with DP was associated with a lower hazard of recurrent malaria over the 84 days after treatment (hazard ratio, 0.66; 95% confidence interval [CI], .61-.70; P < .001). Children randomized to DP had a lower incidence of all treatments for malaria (incidence rate ratio [IRR], 0.85; 95% CI, .75-.96; P = .01), complicated malaria (IRR, 0.12; 95% CI, .04-.39; P < .001), and hospitalizations (IRR, 0.31; 95% CI, .13-.77; P = .01). Among children prescribed TMP-SMX prophylaxis, there were no significant differences in longitudinal outcomes. CONCLUSIONS: Compared to artemether-lumefantrine, the use of DP to treat uncomplicated malaria delayed the time to recurrent malaria and reduced the incidences of treatments for malaria, complicated malaria, and hospitalizations. Clinical Trials Registration. NCT00527800. |
Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children
Kakuru A , Achan J , Muhindo MK , Ikilezi G , Arinaitwe E , Mwangwa F , Ruel T , Clark TD , Charlebois E , Rosenthal PJ , Havlir D , Kamya MR , Tappero JW , Dorsey G . Clin Infect Dis 2014 59 (3) 446-53 BACKGROUND: Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited. METHODS: We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor-based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes. RESULTS: There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated. CONCLUSIONS: Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART. |
Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children.
Conrad MD , LeClair N , Arinaitwe E , Wanzira H , Kakuru A , Bigira V , Muhindo M , Kamya MR , Tappero JW , Greenhouse B , Dorsey G , Rosenthal PJ . J Infect Dis 2014 210 (3) 344-53 BACKGROUND: Artemisinin-based combination therapies, including artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), are recommended to treat uncomplicated falciparum malaria. Sensitivities to components of AL and DP are impacted by polymorphisms in pfmdr1 and pfcrt. We monitored changes in prevalences of polymorphisms in Tororo, Uganda, from 2008 to 2012. METHODS: Polymorphic loci in pfmdr1 and pfcrt were characterized in samples from 312 children randomized to AL or DP for each episode of uncomplicated malaria (50 samples per arm for each 3-month interval) utilizing a fluorescent microsphere assay. Treatment outcomes and impacts of prior therapies were also characterized. RESULTS: Prevalence increased significantly over time for pfmdr1 N86 (AL: odds ratio [OR], 2.08 [95% confidence interval {CI}, 1.83-2.38]; DP: 1.41 [95% CI, 1.25-1.57]), pfmdr1 D1246 (AL: 1.46 [95% CI, 1.29-1.64]; DP: 1.36 [95% CI, 1.23-1.50]), and pfcrt K76 (AL: 3.37 [95% CI, 1.85-6.16]; DP: 5.84 [95% CI, 1.94-17.53], and decreased for pfmdr1 Y184 (AL: 0.78 [95% CI, .70-.86]; DP: 0.84 [95% CI, .76-1.50]); changes were consistently greater in the AL arm. Recent AL treatment selected for pfmdr1 N86, D1246, and 184F in subsequent episodes; DP selected for the opposite alleles. CONCLUSIONS: Genotypes with decreased sensitivity to AL components increased over time. This increase was greater in children receiving AL, suggesting that the choice of treatment regimen can profoundly influence parasite genetics and drug sensitivity. CLINICAL TRIALS REGISTRATION: NCT00527800. |
Measles and rubella vaccination coverage in Haiti, 2012: progress towards verifying and challenges to maintaining measles and rubella elimination
Tohme RA , Francois J , Wannemuehler K , Magloire R , Carolina Danovaro-Holliday M , Flannery B , Cavallaro KF , Fitter DL , Purcell N , Dismer A , Tappero JW , Vertefeuille JF , Hyde TB . Trop Med Int Health 2014 19 (9) 1105-15 OBJECTIVES: We conducted a nationwide survey to assess measles containing vaccine (MCV) coverage among children aged 1-9 years in Haiti and identify factors associated with vaccination before and during the 2012 nationwide supplementary immunisation activities (SIA). METHODS: Haiti was stratified into five geographic regions (Metropolitan Port-au-Prince, North, Centre, South and West), 40 clusters were randomly selected in each region, and 35 households were selected per cluster. RESULTS: Among the 7000 visited households, 75.8% had at least one child aged 1-9 years; of these, 5279 (99.5%) households consented to participate in the survey. Of 9883 children enrolled, 91% received MCV before and/or during the SIA; 31% received MR for the first time during the SIA, and 50.7% received two doses of MCV (one before and one during the 2012 SIA). Among the 1685 unvaccinated children during the SIA, the primary reason of non-vaccination was caregivers not being aware of the SIA (31.0%). Children aged 1-4 years had significantly lower MR SIA coverage than those aged 5-9 years (79.5% vs. 84.8%) (P < 0.0001). A higher proportion of children living in the West (12.3%) and Centre (11.2%) regions had never been vaccinated than in other regions (4.8-9.1%). Awareness, educational level of the mother and region were significantly associated with MR vaccination during and before the SIA (P < 0.001). CONCLUSIONS: The 2012 SIA successfully increased MR coverage; however, to maintain measles and rubella elimination, coverage needs to be further increased among children aged 1-4 years and in regions with lower coverage. |
First confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014
Bialek SR , Allen D , Alvarado-Ramy F , Arthur R , Balajee A , Bell D , Best S , Blackmore C , Breakwell L , Cannons A , Brown C , Cetron M , Chea N , Chommanard C , Cohen N , Conover C , Crespo A , Creviston J , Curns AT , Dahl R , Dearth S , DeMaria A , Echols F , Erdman DD , Feikin D , Frias M , Gerber SI , Gulati R , Hale C , Haynes LM , Heberlein-Larson L , Holton K , Ijaz K , Kapoor M , Kohl K , Kuhar DT , Kumar AM , Kundich M , Lippold S , Liu L , Lovchik JC , Madoff L , Martell S , Matthews S , Moore J , Murray LR , Onofrey S , Pallansch MA , Pesik N , Pham H , Pillai S , Pontones P , Poser S , Pringle K , Pritchard S , Rasmussen S , Richards S , Sandoval M , Schneider E , Schuchat A , Sheedy K , Sherin K , Swerdlow DL , Tappero JW , Vernon MO , Watkins S , Watson J . MMWR Morb Mortal Wkly Rep 2014 63 (19) 431-6 Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014. |
Early parasite clearance following artemisinin-based combination therapy among Ugandan children with uncomplicated Plasmodium falciparum malaria
Muhindo MK , Kakuru A , Jagannathan P , Talisuna A , Osilo E , Orukan F , Arinaitwe E , Tappero JW , Kaharuza F , Kamya MR , Dorsey G . Malar J 2014 13 32 BACKGROUND: Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance. METHODS: Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient. RESULTS: A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR = 1.34, 95% CI 1.20-1.50, p < 0.001), having a temperature ≥38.0 degrees C vs < 37.0 degrees C (RR = 1.19, 95% CI 1.05-1.35, p = 0.007) and having a parasite density >20,000/muL vs <4,000/muL (RR = 3.37, 95% CI 2.44-4.49, p < 0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected. CONCLUSIONS: Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy. TRIAL REGISTRATION: Current Controlled Trials Identifier NCT00527800. |
Safer countries through global health security
Frieden TR , Tappero JW , Dowell SF , Hien NT , Guillaume FD , Aceng JR . Lancet 2014 383 (9919) 764-6 Countries around the world face a perfect storm of converging threats that might substantially increase the risk from infectious disease epidemics, despite improvements in technologies, communication, and some health systems. New pathogens emerge each year, some of which have high mortality and the potential for efficient transmission—eg, severe acute respiratory syndrome (SARS),1 Middle East respiratory syndrome coronavirus,2 and avian influenza A H7N9.3 Existing pathogens are becoming resistant to available antibiotics and several are now resistant to virtually all available treatment.4 There is also the potential threat of intentional release of biological agents, which can be developed or synthesised biologically and disseminated at low cost and with little scientific expertise. Moreover, the accelerated pace of globalisation amplifies these risks: a disease is just a plane trip away, and an outbreak anywhere is a threat everywhere. | One of the primary responsibilities of any government is to protect the health and safety of its people. There are three key elements of health security: prevention wherever possible, early detection, and timely and effective response. Although many countries are now better able to manage infectious disease threats than in the past, these improvements have often been small in scale and limited in scope. The International Health Regulations (IHR), revised by WHO in 2005 to more directly address new and emerging epidemic threats,5 require all 194 signatory countries to improve capacity in these and other areas as part of their commitment to protecting health.6 Yet, at least 80% of countries did not report full IHR compliance by the 2012 deadline.7 |
Strengthening global health security capacity - Vietnam demonstration project, 2013
Tran PD , Vu LN , Nguyen HT , Phan LT , Lowe W , McConnell MS , Iademarco MF , Partridge JM , Kile JC , Do T , Nadol PJ , Bui H , Vu D , Bond K , Nelson DB , Anderson L , Hunt KV , Smith N , Giannone P , Klena J , Beauvais D , Becknell K , Tappero JW , Dowell SF , Rzeszotarski P , Chu M , Kinkade C . MMWR Morb Mortal Wkly Rep 2014 63 (4) 77-80 Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and communication. |
Rapidly building global health security capacity - Uganda demonstration project, 2013
Borchert JN , Tappero JW , Downing R , Shoemaker T , Behumbiize P , Aceng J , Makumbi I , Dahlke M , Jarrar B , Lozano B , Kasozi S , Austin M , Phillippe D , Watson ID , Evans TJ , Stotish T , Dowell SF , Iademarco MF , Ransom R , Balajee A , Becknell K , Beauvais D , Wuhib T . MMWR Morb Mortal Wkly Rep 2014 63 (4) 73-6 Increasingly, the need to strengthen global capacity to prevent, detect, and respond to public health threats around the globe is being recognized. CDC, in partnership with the World Health Organization (WHO), has committed to building capacity by assisting member states with strengthening their national capacity for integrated disease surveillance and response as required by International Health Regulations (IHR). CDC and other U.S. agencies have reinforced their pledge through creation of global health security (GHS) demonstration projects. One such project was conducted during March-September 2013, when the Uganda Ministry of Health (MoH) and CDC implemented upgrades in three areas: 1) strengthening the public health laboratory system by increasing the capacity of diagnostic and specimen referral networks, 2) enhancing the existing communications and information systems for outbreak response, and 3) developing a public health emergency operations center (EOC) (Figure 1). The GHS demonstration project outcomes included development of an outbreak response module that allowed reporting of suspected cases of illness caused by priority pathogens via short messaging service (SMS; i.e., text messaging) to the Uganda District Health Information System (DHIS-2) and expansion of the biologic specimen transport and laboratory reporting system supported by the President's Emergency Plan for AIDS Relief (PEPFAR). Other enhancements included strengthening laboratory management, establishing and equipping the EOC, and evaluating these enhancements during an outbreak exercise. In 6 months, the project demonstrated that targeted enhancements resulted in substantial improvements to the ability of Uganda's public health system to detect and respond to health threats. |
IFNgamma/IL-10 co-producing cells dominate the CD4 response to malaria in highly exposed children
Jagannathan P , Eccles-James I , Bowen K , Nankya F , Auma A , Wamala S , Ebusu C , Muhindo MK , Arinaitwe E , Briggs J , Greenhouse B , Tappero JW , Kamya MR , Dorsey G , Feeney ME . PLoS Pathog 2014 10 (1) e1003864 Although evidence suggests that T cells are critical for immunity to malaria, reliable T cell correlates of exposure to and protection from malaria among children living in endemic areas are lacking. We used multiparameter flow cytometry to perform a detailed functional characterization of malaria-specific T cells in 78 four-year-old children enrolled in a longitudinal cohort study in Tororo, Uganda, a highly malaria-endemic region. More than 1800 episodes of malaria were observed in this cohort, with no cases of severe malaria. We quantified production of IFNgamma, TNFalpha, and IL-10 (alone or in combination) by malaria-specific T cells, and analyzed the relationship of this response to past and future malaria incidence. CD4(+) T cell responses were measurable in nearly all children, with the majority of children having CD4(+) T cells producing both IFNgamma and IL-10 in response to malaria-infected red blood cells. Frequencies of IFNgamma/IL10 co-producing CD4(+) T cells, which express the Th1 transcription factor T-bet, were significantly higher in children with ≥2 prior episodes/year compared to children with <2 episodes/year (P<0.001) and inversely correlated with duration since malaria (Rho = -0.39, P<0.001). Notably, frequencies of IFNgamma/IL10 co-producing cells were not associated with protection from future malaria after controlling for prior malaria incidence. In contrast, children with <2 prior episodes/year were significantly more likely to exhibit antigen-specific production of TNFalpha without IL-10 (P = 0.003). While TNFalpha-producing CD4(+) T cells were not independently associated with future protection, the absence of cells producing this inflammatory cytokine was associated with the phenotype of asymptomatic infection. Together these data indicate that the functional phenotype of the malaria-specific T cell response is heavily influenced by malaria exposure intensity, with IFNgamma/IL10 co-producing CD4(+) T cells dominating this response among highly exposed children. These CD4(+) T cells may play important modulatory roles in the development of antimalarial immunity. |
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