OBJECTIVES: Malaria and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are associated with adverse pregnancy outcomes. This study reports the prevalence and risk factors of curable STIs/RTIs, STI/RTI co-infection and STI/RTI and malaria co-infection among HIV-negative pregnant women at their first antenatal care visit in Kenya, Malawi and Tanzania. METHODS: HIV-negative pregnant women of all gravidae (n=4680) were screened for syphilis with point-of-care tests and treated if positive. Separately, women provided blood samples (n=4569) for rapid plasma reagin (RPR) testing; positive cases were confirmation by Treponema pallidum particle agglutination (TPPA). Women also provided dried blood spots for batch testing of malaria by retrospective polymerase chain reaction (PCR (n=4226) methods. A randomly selected subgroup of women provided vaginal swabs for chlamydia, gonorrhoea and trichomoniasis testing by retrospective PCR batch testing (n=1431), and bacterial vaginosis diagnosis by Nugent scoring (n=1402). RESULTS: Malaria prevalence was 14.6% (95% CI 13.6 to 15.7), 45.9% (43.4 to 48.4) of women were positive for at least one curable STI/RTI and 6.7% (5.5 to 8.1) were co-infected with malaria and a curable STI/RTI. Prevalence of individual STIs/RTIs ranged from 28.5% (26.2 to 30.9) for bacterial vaginosis to 14.5% (12.7 to 16.4) for trichomoniasis, 13.8% (12.1 to 15.7) for chlamydia, 2.7% (1.9 to 3.6) for gonorrhoea and 1.7% (1.4 to 2.2) for RPR/TPPA-confirmed syphilis. The prevalence of STI/RTI co-infection was 10.1% (8.7 to 11.8). Paucigravidae, at highest risk of malaria, were also at greater risk of having chlamydia, gonorrhoea and bacterial vaginosis than multigravidae. CONCLUSIONS: Of women infected with malaria, 49.0% also had a curable STI/RTI and one in five women with at least one STI/RTI were co-infected with more than one STI/RTI. Current antenatal interventions that address malaria and curable STIs/RTIs remain suboptimal. New approaches to preventing and managing these infections in pregnancy are urgently needed. TRIAL REGISTRATION NUMBER: NCT03208179.

The COVID-19 pandemic magnified long-standing health disparities, showing that certain populations are at higher risk for effects of public health emergencies than others. The pandemic response also put demands on the nation's health departments and stretched their limited resources. In 2021, the Centers for Disease Control and Prevention launched the National Initiative to Address COVID-19 Health Disparities Among Populations at High-Risk and Underserved, Including Racial and Ethnic Minority Populations and Rural Communities (hereinafter, COVID-19 Health Disparities Grant) to reduce COVID-19 health disparities and advance health equity. Health departments in all 50 states, 50 localities, 5 territories, and 3 freely associated states were recipients of approximately $2.25 billion. This study explored the extent to which investments from the COVID-19 Health Disparities Grant, through the allocation of funds across 5 strategies, correspond to reported changes in recipient health departments' capacity to address the COVID-19 public health emergency and future emergencies as measured in the Health Department and Jurisdiction Capacity Survey in 2023. The survey measured capacity along 4 domains: workforce and human resources, interorganizational relationships, data and informational resources, and governance and planning. In total, 70 of 75 recipients who responded to the survey reported that they began with low capacity in at least 1 capacity domain and advanced their capacity during grant implementation. This study demonstrated the reported value of investments in health departments to build capacity and infrastructure to address health disparities and advance health equity to respond to future public health emergencies.

BACKGROUND: In sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections. METHODS: We searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental Plasmodium falciparum at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789. FINDINGS: Five trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where dhfr/dhps quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I(2)=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I(2)=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I(2)=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I(2)=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57). INTERPRETATION: ISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections. FUNDING: Centers for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. METHODS: Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. RESULTS: 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1-3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6-38.8%). CONCLUSIONS: Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation. METHODS: Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3-59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted. RESULTS: The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34% and 31%, respectively. Incentives (payment other than salary for efforts beyond routine activities) accounted for 25% of total implementation costs. Average financial and economic unit costs per child per round were US $0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US $2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US $6.38 and US $4.69, if weighted highly adherent, (receiving 3 or 4 rounds of SMC). When costs were combined with modelled effects, the economic cost per malaria episode averted in children was US $4.26 (uncertainty bound 2.83-7.17), US $144 (135-153) per DALY averted and US $ 14,503 (13,604-15,402) per death averted. CONCLUSIONS: When implemented at fixed point distribution through the routine health system in Mali, SMC was highly cost-effective. As in previous SMC implementation studies, financial incentives were a large cost component.

Plasmodium falciparum in pregnancy is a major cause of adverse pregnancy outcomes. We combine performance estimates of standard rapid diagnostic tests (RDT) from trials of intermittent screening and treatment in pregnancy (ISTp) with modelling to assess whether screening at antenatal visits improves upon current intermittent preventative therapy with sulphadoxine-pyrimethamine (IPTp-SP). We estimate that RDTs in primigravidae at first antenatal visit are substantially more sensitive than in non-pregnant adults (OR = 17.2, 95% Cr.I. 13.8-21.6), and that sensitivity declines in subsequent visits and with gravidity, likely driven by declining susceptibility to placental infection. Monthly ISTp with standard RDTs, even with highly effective drugs, is not superior to monthly IPTp-SP. However, a hybrid strategy, recently adopted in Tanzania, combining testing and treatment at first visit with IPTp-SP may offer benefit, especially in areas with high-grade SP resistance. Screening and treatment in the first trimester, when IPTp-SP is contraindicated, could substantially improve pregnancy outcomes.

INTRODUCTION: Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false-negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. DISCUSSION: Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. CONCLUSIONS: With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.

BACKGROUND: Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. METHODS AND FINDINGS: We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%-97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%-73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%-87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting. CONCLUSIONS: The age distribution of measles cases changes in response to both demographic and vaccination processes. Combining both processes in a novel catalytic model, we illustrate that age-specific incidence patterns reveal regional differences in the progress to measles elimination and the impact of vaccination controls in China. The shift in the age distribution of measles susceptibility in response to demographic and vaccination processes emphasizes the importance of progressive control strategies and measures to evaluate program success that anticipate and react to this transition in observed incidence.

Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness.Interventions Rapid diagnostic tests for malaria.Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.

On November 23, 1965, President Lyndon Johnson announced plans for a 5-year smallpox eradication and measles control program in West Africa that enabled the Centers for Disease Control and Prevention (CDC) to establish a Smallpox Eradication Program in January 1966. Since then, CDC’s global immunization endeavors have encompassed global smallpox eradication, the establishment and growth of the Expanded Program on Immunization (EPI) to strengthen national immunization programs, global efforts to eradicate polio and eliminate measles and rubella, and vaccine introduction into national immunization schedules beyond the original 6 EPI vaccines. CDC has provided scientific leadership, evidence-based guidance, and programmatic strategies to build public health infrastructure around the world, needed to achieve and measure the impact of these global immunization initiatives. This article marks the 50th anniversary of CDC’s global immunization leadership, highlights key historical events, and provides an overview of CDC’s future directions. | Before 1955, smallpox and diphtheria-tetanus-pertussis vaccines were the only routinely recommended childhood vaccines in the United States. The roots of global immunization at CDC began after clinical trials for the Salk inactivated polio vaccine (IPV) in 1954. After investigators announced on April 12, 1955, that Salk IPV was safe and effective, large-scale vaccination campaigns were implemented across the United States, and IPV was set to join diphtheria-tetanus-pertussis and smallpox vaccines in the childhood vaccination schedule. However, improperly prepared IPV by Cutter Pharmaceuticals used for the vaccination campaigns led to 200 cases of paralysis and 10 deaths.1

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case-control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0-7 months. METHODS: Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. RESULTS: Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5-7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. CONCLUSIONS: Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.

Strong working relationships between infectious disease (ID) physicians and public health have resulted in the early detection of emerging infectious threats. From May 6 through June 5, 2015, we surveyed ID physicians in the Infectious Diseases Society of America's Emerging Infections Network about communications with public health. A total of 688 of 1491 (46%) members completed the survey, 624 (91%) of whom knew how to reach their health department directly for an urgent issue. Only 38 (6%) described communications with their health department as poor. Interest in newer technologies (eg, mobile smartphone applications) showed mixed results. Interest in a smartphone application differed significantly by years of ID experience,with 81 of 146 (55%) respondents with <5 years of ID experience, 172 of 359 (48%) respondents with 5 to 24 years of ID experience, and 61 of 183 (33%) respondents with >25 years of ID experience in favor of a smartphone application (P < .001). As more physicians adopt newer communication technologies, health departments should be prepared to incorporate these tools to communicate with ID physicians.

BACKGROUND: The arboviruses West Nile virus (WNV), dengue virus (DENV) and Ross River virus (RRV) have been demonstrated to be blood transfusion-transmissible. A model to estimate the risk of WNV to the blood supply using a Monte Carlo approach has been developed and also applied to Chikungunya virus. Also, a probabilistic model was developed to assess the risk of DENV to blood safety, which was later adapted to RRV. To address efficacy and limitations within each model we present a hybrid model that promises improved accuracy, and is broadly applicable to assess the risk of arboviral transmission by blood transfusion. MATERIAL AND METHODS: Data were drawn from the Cairns Public Health Unit (Australia) and published literature. Based on the published models and using R code, a novel 'combined' model was developed and validated against the BP model using sensitivity testing. RESULTS: The mean risk per 10,000 of the combined model is 0.98 with a range from 0.79 to 1.25, while the maximum risk was 4.45 ranging from 2.62 to 7.67 respectively. These parameters for the BP model were 1.20 ranging from 0.84 to 1.55, and 2.86 ranging from 1.33 to 5.23 respectively. CONCLUSION: The combined simulation model is simple and robust. We propose it can be applied as a 'generic' arbovirus model to assess the risk from known or novel arboviral threats to the blood supply.

BACKGROUND: Self-report is the most common and feasible method for assessing patient adherence to medication, but can be prone to recall bias and social desirability bias. Most studies assessing adherence to artemisinin-based combination therapies (ACTs) have relied on self-report. In this study, we use a novel customised electronic monitoring device-termed smart blister packs-to examine the validity of self-reported adherence to artemether-lumefantrine (AL) in southern Tanzania. METHODS: Smart blister packs were designed to look identical to locally available AL blister packs and to record the date and time each tablet was removed from packaging. Patients obtaining AL at randomly selected health facilities and drug stores were followed up at home three days later and interviewed about each dose of AL taken. Blister packs were requested for pill count and extraction of smart blister pack data. RESULTS: Data on adherence from both self-report verified by pill count and smart blister packs were available for 696 of 1,204 patients. There was no difference between methods in the proportion of patients assessed to have completed treatment (64% and 67%, respectively). However, the percentage taking the correct number of pills for each dose at the correct times (timely completion) was higher by self-report than smart blister packs (37% vs. 24%; p<0.0001). By smart blister packs, 64% of patients completing treatment did not take the correct number of pills per dose or did not take each dose at the correct time interval. CONCLUSION: Smart blister packs resulted in lower estimates of timely completion of AL and may be less prone to recall and social desirability bias. They may be useful when data on patterns of adherence are desirable to evaluate treatment outcomes. Improved methods of collecting self-reported data are needed to minimise bias and maximise comparability between studies.

BACKGROUND: Healthcare-associated infections (HAIs) are preventable. Globally, laws aimed at reducing HAIs have been implemented. In the USA, these laws are at the federal and state levels. It is not known whether the state interventions are more effective than the federal incentives alone. OBJECTIVE: The aims of this study were to explore the impact federal and state HAI laws have on state departments of health and hospital stakeholders in the USA and to explore similarities and differences in perceptions across states. METHODS: A qualitative study was conducted. In 2012, we conducted semistructured interviews with key stakeholders from states with and without state-level laws to gain multiple perspectives. Interviews were transcribed and open coding was conducted. Data were analysed using content analysis and collected until theoretical saturation was achieved. RESULTS: Ninety interviews were conducted with stakeholders from 12 states (6 states with laws and 6 states without laws). We found an increase in state-level collaboration. The publicly reported data helped hospitals benchmark and focus leaders on HAI prevention. There were concerns about the publicly reported data (eg, lack of validation and timeliness). Resource needs were also identified. No major differences were expressed by interviewees from states with and without laws. CONCLUSIONS: While we could not tease out the impact of specific interventions, increased collaboration between departments of health and their partners is occurring. Harmonisation of HAI definitions and reporting between state and federal laws would minimise reporting burden. Continued monitoring of the progress of HAI prevention is needed.

BACKGROUND: Artemisinin combination therapy (ACT) is first-line treatment for malaria in most endemic countries and is increasingly available in the private sector. Most studies on ACT adherence have been conducted in the public sector, with minimal data from private retailers. METHODS: Parallel studies were conducted in Tanzania, in which patients obtaining artemether-lumefantrine (AL) at 40 randomly selected public health facilities and 37 accredited drug dispensing outlets (ADDOs) were visited at home and questioned about doses taken. The effect of sector on adherence, controlling for potential confounders was assessed using logistic regression with a random effect for outlet. RESULTS: Of 572 health facility patients and 450 ADDO patients, 74.5% (95% CI: 69.8, 78.8) and 69.8% (95% CI: 64.6, 74.5), respectively, completed treatment and 46.0% (95% CI: 40.9, 51.2) and 34.8% (95% CI: 30.1, 39.8) took each dose at the correct time ('timely completion'). ADDO patients were wealthier, more educated, older, sought care later in the day, and were less likely to test positive for malaria than health facility patients. Controlling for patient characteristics, the adjusted odds of completed treatment and of timely completion for ADDO patients were 0.65 (95% CI: 0.43, 1.00) and 0.69 (95% CI: 0.47, 1.01) times that of health facility patients. Higher socio-economic status was associated with both adherence measures. Higher education was associated with completed treatment (adjusted OR = 1.68, 95% CI: 1.20, 2.36); obtaining AL in the evening was associated with timely completion (adjusted OR = 0.35, 95% CI: 0.19, 0.64). Factors associated with adherence in each sector were examined separately. In both sectors, recalling correct instructions was positively associated with both adherence measures. In health facility patients, but not ADDO patients, taking the first dose of AL at the outlet was associated with timely completion (adjusted OR = 2.11, 95% CI: 1.46, 3.04). CONCLUSION: When controlling for patient characteristics, there was some evidence that the adjusted odds of adherence for ADDO patients was lower than that for public health facility patients. Better understanding is needed of which patient care aspects are most important for adherence, including the role of effective provision of advice.

BACKGROUND: To develop a successful model for accelerating measles elimination in poor areas of China, we initiated a seven-year project in Guizhou, one of the poorest provinces, with reported highest measles incidence of 360 per million population in 2002. METHODS: Project strategies consisted of strengthening routine immunization services, enforcement of school entry immunization requirements at kindergarten and school, conducting supplemental measles immunization activities (SIAs), and enhancing measles surveillance. We measured coverage of measles containing vaccines (MCV) by administrative reporting and population-based sample surveys, systematic random sampling surveys, and convenience sampling surveys for routine immunization services, school entry immunization, and SIAs respectively. We measured impact using surveillance based measles incidence. RESULTS: Routine immunization coverage of the 1st dose of MCV (MCV1) increased from 82% to 93%, while 2nd dose of MCV (MCV2) coverage increased from 78% to 91%. Enforcement of school entry immunization requirements led to an increase in MCV2 coverage from 36% on primary school entry in 2004 to 93% in 2009. Province-wide SIAs achieved coverage greater than 90%. The reported annual incidence of measles dropped from 200 to 300 per million in 2003 to 6 per million in 2009, and sustained at 0.9-2.2 per million in 2010-2013. CONCLUSIONS: This project found that a package of strategies including periodic SIAs, strengthened routine immunization, and enforcing school entry immunization requirements, was an effective approach toward achieving and sustaining measles elimination in less-developed area of China.

Artemisinin combination therapies are available in private outlets, but patient adherence might be compromised by poor advice from dispensers. In this cluster randomized trial in drug shops in Tanzania, 42 of 82 selected shops were randomized to receive text message reminders about what advice to provide when dispensing artemether-lumefantrine (AL). Eligible patients purchasing AL at shops in both arms were followed up at home and questioned about each dose taken. Dispensers were interviewed regarding knowledge of AL dispensing practices and receipt of the malaria-related text messages. We interviewed 904 patients and 110 dispensers from 77 shops. Although there was some improvement in dispenser knowledge, there was no difference between arms in adherence measured as completion of all doses (intervention 68.3%, control 69.8%, p [adjusted] = 0.6), or as completion of each dose at the correct time (intervention 33.1%, control 32.6%, p [adjusted] = 0.9). Further studies on the potential of text messages to improve adherence are needed.

BACKGROUND: The Affordable Medicines Facility - malaria (AMFm) is primarily an artemisinin combination therapy (ACT) subsidy, aimed at increasing availability, affordability, market share and use of quality-assured ACTs (QAACTs). Mainland Tanzania was one of eight national scale programmes where AMFm was introduced in 2010. Here we present findings from outlet and household surveys before and after AMFm implementation to evaluate its impact from both the supply and demand side. METHODS: Outlet surveys were conducted in 49 randomly selected wards throughout mainland Tanzania in 2010 and 2011, and data on outlet characteristics and stocking patterns were collected from outlets stocking antimalarials. Household surveys were conducted in 240 randomly selected enumeration areas in three regions in 2010 and 2012. Questions about treatment seeking for fever and drugs obtained were asked of individuals reporting fever in the previous two weeks. RESULTS: The availability of QAACTs increased from 25.5% to 69.5% among all outlet types, with the greatest increase among pharmacies and drug stores, together termed specialised drug sellers (SDSs), where the median QAACT price fell from $5.63 to $0.94. The market share of QAACTs increased from 26.2% to 42.2%, again with the greatest increase in SDSs. Household survey results showed a shift in treatment seeking away from the public sector towards SDSs. Overall, there was no change in the proportion of people with fever obtaining an antimalarial or ACT from baseline to endline. However, when broken down by treatment source, ACT use increased significantly among clients visiting SDSs. DISCUSSION: Unchanged ACT use overall, despite increases in QAACT availability, affordability and market share in the private sector, reflected a shift in treatment seeking towards private providers. The reasons for this shift are unclear, but likely reflect both persistent stockouts in public facilities, and the increased availability of subsidised ACTs in the private sector.

BACKGROUND: Historically, China's Japanese encephalitis vaccination program was a mix of household purchase of vaccine and government provision of vaccine in some endemic provinces. In 2006, Guizhou, a highly endemic province in South West China, integrated JE vaccine into the provincial Expanded Program on Immunization (EPI); later, in 2007 China fully integrated 28 provinces into the national EPI, including Guizhou, allowing for vaccine and syringe costs to be paid at the national level. We conducted a retrospective economic analysis of JE integration into EPI in Guizhou province. METHODS: We modeled two theoretical cohorts of 100,000 persons for 65 years; one using JE live-attenuated vaccine in EPI (first dose: 95% coverage and 94.5% efficacy; second dose: 85% coverage and 98% efficacy) and one not. We assumed 60% sensitivity of surveillance for reported JE rates, 25% case fatality, 30% chronic disability and 3% discounting. We reviewed acute care medical records and interviewed a sample of survivors to estimate direct and indirect costs of illness. We reviewed the EPI offices expenditures in 2009 to estimate the average Guizhou program cost per vaccine dose. RESULTS: Use of JE vaccine in EPI for 100,000 persons would cost 434,898 US$ each year (46% of total cost due to vaccine) and prevent 406 JE cases, 102 deaths, and 122 chronic disabilities (4554 DALYs). If we ignore future cost savings and only use EPI program cost, the program would cost 95.5 US$/DALY, less than China Gross Domestic Product per capita in 2009 (3741 US$). From a cost-benefit perspective taking into account future savings, use of JE vaccine in EPI for a 100,000-person cohort would lead to savings of 1,591,975 US$ for the health system and 11,570,989 US$ from the societal perspective. CONCLUSIONS: In Guizhou, China, use of JE vaccine in EPI is a cost effective investment. Furthermore, it would lead to savings for the health system and society.

BACKGROUND: Few population-based studies of infectious etiologies of fever-rash illnesses have been conducted. This study reports on enhanced febrile-rash illness surveillance in Campinas, Brazil, a setting of low measles and rubella virus transmission. METHODS: Cases of febrile-rash illnesses in individuals aged <40 years that occurred during the period 1 May 2003-30 May 2004 were reported. Blood samples were collected for laboratory diagnostic confirmation, which included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV), enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19, Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections. Notification rates were compared with the prestudy period. RESULTS: A total of 1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these, HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30 cases), and GAS (30 cases) were the most frequent causes of infection. Only 10 rubella cases met the rubella clinical case definition currently in use. Notification rates were higher during the study than in the prestudy period (181 vs 52.3 cases per 100,000 population aged <40 years). CONCLUSIONS: Stimulating a passive surveillance system enhanced its sensitivity and resulted in additional rubella cases detected. In settings with rubella elimination goals, rubella testing may be considered for all cases of febrile-rash illness, regardless of suspected clinical diagnosis.

BACKGROUND: Measles caused mortality in >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals. METHODS: We searched literature published during 1995-2009 for papers reporting on measles outbreaks. Papers identified were reviewed by 2 reviewers to select those that mentioned ORI. World Bank classification of country income was used to identify reports of outbreaks in middle- and low-income countries. RESULTS: We identified a total of 485 articles, of which 461 (95%) were available. Thirty-eight of these papers reported on a total of 38 outbreaks in which ORI was used. ORI had a clear impact in 16 (42%) of these outbreaks. In the remaining outbreaks, we were unable to independently assess the impact of ORI. CONCLUSIONS: These findings generally support ORI in middle- and low-income countries. However, the decision to conduct ORI and the nature and extent of the vaccination response need to be made on a case-by-case basis.

BACKGROUND: In China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination. METHODS: We conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth. RESULTS: Three-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992-1997 to 93.2% for children born in 2002-2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992-2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose (p=0.04), birth after 1998 (p<0.001), living in an urban setting (p=0.008) and hospital birth (p=0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87). CONCLUSIONS: Hospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.

OBJECTIVE: The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV). METHODS: Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics. RESULTS: Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3,129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with "variably protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in the PrP gene coding region. INTERPRETATION: Because all 3,129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Straussler-Scheinker disease.

Measles, a highly infectious vaccine-preventable viral disease, is potentially fatal. Historically, measles case-fatality ratios (CFRs) have been reported to vary from 0.1% in the developed world to as high as 30% in emergency settings. Estimates of the global burden of mortality from measles, critical to prioritizing measles vaccination among other health interventions, are highly sensitive to the CFR estimates used in modeling; however, due to the lack of reliable, up-to-date data, considerable debate exists as to what CFR estimates are appropriate to use. To determine current measles CFRs in high-burden settings without vital registration we have conducted six retrospective measles mortality studies in such settings. This paper examines the methodological challenges of this work and our solutions to these challenges, including the integration of lessons from retrospective all-cause mortality studies into CFR studies, approaches to laboratory confirmation of outbreaks, and means of obtaining a representative sample of case-patients. Our experiences are relevant to those conducting retrospective CFR studies for measles or other diseases, and to those interested in all-cause mortality studies.

We conducted a measles outbreak investigation in Dar es Salaam, Tanzania. Surveillance data were analyzed; a susceptibility profile developed, and case-control study conducted. The age distribution of cases peaked among those <2, 5-7, and ≥18 years, corresponding to the age distribution of susceptibles. Risk factors included being unvaccinated (aOR=5.7, p<0.01) or having received one dose of vaccine compared to two (aOR=2.4, p=0.01), being younger, and having a less-educated caretaker. Vaccine effectiveness was 88% (one dose) and 96% (two doses). Results highlight the importance of receiving one dose of measles vaccine, and the added benefit of two doses.

Since the rates and causes of mortality are critical indicators of the overall health of a population, it is important to evaluate mortality even where no complete vital statistics reporting exists. Such settings include humanitarian emergencies. Experience in cross-sectional survey methods to assess retrospectively crude, age-specific, and maternal mortality in stable settings has been gained over the past 40 years, and methods appropriate to humanitarian emergencies have been developed. In humanitarian emergencies, crude and age-specific mortality can be gauged using methods based on the enumeration of individuals resident in randomly selected households-frequently referred to as a household census. Under-five mortality can also be assessed through a modified prior birth history method in which a representative sample of reproductive-aged women are questioned about dates of child births and deaths. Maternal mortality can be appraised via the initial identification of maternal deaths in the study population and a subsequent investigation to determine the cause of each death.

OBJECTIVE: To characterize patients with suspected measles, determine the magnitude of the outbreak in selected areas, and perform laboratory testing on patients with suspected measles to confirm the etiology of the outbreak. STUDY DESIGN: Cross-sectional survey. PLACE AND DURATION OF STUDY: Islamabad and Rawalpindi in June 2006. METHODOLOGY: Survey and specimen collection from households was carried out in areas affected by rash and fever during the outbreak. Teams asked if household members had rash and fever and administered a detailed questionnaire of clinical signs and symptoms for measles for each person who reported a rash and fever episode. A sample of cases with fever, rash, and either cough, conjunctivitis, or coryza was laboratory tested for measles and rubella. RESULTS: Of 2,225 households visited, 284 individuals met the rash and fever case definition. Laboratory testing of eleven blood specimens revealed that the rash and fever outbreak was caused by rubella in 6 and measles in 2 with three equivocal results. CONCLUSION: Laboratory confirmation of suspected measles cases is essential during measles elimination activities in Pakistan and other countries with endemic rubella.

We assessed the impact of a measles outbreak response vaccination campaign (ORV) in Dar es Salaam, Tanzania. Age-specific incidence rates were calculated before and after the ORV. Incidence rate ratios for the two time periods were compared and used to estimate expected cases and deaths prevented by ORV. The ratio of measles incidence rates in the age groups targeted and not targeted by ORV decreased from 5.8 prior to ORV to 1.8 (p<0.0001) after; 506 measles cases and 18 measles deaths were likely averted. These results support the need for revised recommendations concerning ORV in general settings in Africa.