Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021.

BACKGROUND: Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. METHODS: A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). RESULTS: Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. CONCLUSION: This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.

How Real-Time Case-Based Malaria Surveillance Helps Zanzibar Get a Step Closer to Malaria Elimination: Description of Operational Platform and Resources.

Testing and treating asymptomatic populations have the potential to reduce the population's parasite reservoir and reduce malaria transmission. Zanzibar's malaria case notification (MCN) platform collects detailed sociodemographic and epidemiological data from all confirmed malaria cases to inform programmatic decision-making. We describe the design and operationalization process of the platform and other malaria surveillance resources that are enabling Zanzibar's progress toward malaria elimination.The MCN platform consists of an interactive short message service (SMS) system for case notification, a software application for Android mobile devices, a visual question set and workflow manager, a back-end database server, and a web browser-based application for data analytics, configuration, and management. Malaria case data were collected from August 2012 to December 2021 and reported via SMS from all public and private health facilities to a central database and then to district malaria surveillance officers' mobile devices. Data included patient names, shehia (administrative area), and date of diagnosis, enabling officers to track patients, ideally within 24 hours of reporting. Patients' household members were tested for malaria using conventional rapid diagnostic tests (RDTs). Treatment using artemisinin-based combination therapy was provided for persons testing positive.Between 2012 and 2021, a total of 48,899 index malaria cases were confirmed at health facilities, 22,152 (45.3%) within 24 hours of reporting; 41,886 (85.7%) cases were fully investigated and followed up to the household level. A total of 111,811 additional household members were tested with RDTs, of whom 10,602 (9.5%) were malaria positive.The MCN platform reports malaria case data in near real time, enabling prompt follow-up of index cases and prompt testing and treatment of members in index case households. Along with routine testing and treatment and other preventive interventions, the MCN platform is foundational to the programmatic efforts in further reducing malaria and ultimately eliminating autochthonous malaria transmission in Zanzibar.

The quality of malaria case management in different transmission settings in Tanzania mainland, 2017-2018.

Tanzania is undergoing an epidemiological transition for malaria transmission with some areas of the country having <10% (hypoendemic) and other areas 10% - 50% malaria prevalence (mesoendemic). It is not known whether there is a difference in the quality of malaria case management based on endemicity in Tanzania mainland. We examined the influence of endemicity on the quality of malaria case management at health facilities. We conducted a cross-sectional analysis of 1713 health facilities in Tanzania mainland, using data collected by the National Malaria Control Program through an assessment tool to evaluate quality of malaria case management. The data was gathered from September 2017 to December 2018. Using standard quality factors, mean scores from facilities in the different endemicity regions were compared by a Student's t-test. Simple and multiple linear regression analyses were performed to determine the association between facility performance (score) and endemicity (mesoendemic vs. hypoendemic). Facilities in mesoendemic regions scored higher than those in hypoendemic regions on the overall quality of services [difference in mean scores ([Formula: see text]) = 2.52; (95% Confidence Interval (CI) 1.12, 3.91)], site readiness [[Formula: see text] = 2.97; (95% CI 1.30, 4.61)], availability of malaria reference materials [[Formula: see text] = 4.91; (95% CI 2.05, 7.76)], availability of Health Management Information System tools [[Formula: see text] = 5.86; (95% CI 3.80, 7.92)] and patient satisfaction [[Formula: see text] = 6.61; (95% CI 3.75, 9.48)]. Predictors associated with lower facility scores included; being located in a hypoendemic region [ß: -2.49; (95% CI -3.83, -1.15)] and urban area [ß: -3.84; (95% CI -5.60, -2.08)]. These findings highlight the differences in quality of malaria case management based on endemicity, but there is still a need to target improvement efforts in underperforming facilities, regardless of endemicity.

Multiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania.

Zanzibar has made significant progress toward malaria elimination, but recent stagnation requires novel approaches. We developed a highly multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug-resistance loci, and successfully sequenced 290 samples from five districts covering both main islands. Here, we elucidate fine-scale Plasmodium falciparum population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. Despite high genetic diversity, we observe pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar and the mainland, suggesting recent importation. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and provides actionable insights for prioritizing malaria elimination efforts.

Similar Prevalence of Plasmodium falciparum and Non-P. falciparum Malaria Infections among Schoolchildren, Tanzania1.

Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4 Plasmodium spp. by performing PCR on dried blood spots collected within 8 regions of Tanzania during 2017. Among 3,456 schoolchildren, 22% had P. falciparum, 24% had P. ovale spp., 4% had P. malariae, and 0.3% had P. vivax infections. Most (91%) schoolchildren with P. ovale infections had low parasite densities; 64% of P. ovale infections were single-species infections, and 35% of those were detected in low malaria endemic regions. P. malariae infections were predominantly (73%) co-infections with P. falciparum. P. vivax was detected mostly in northern and eastern regions. Co-infections with >1 non-P. falciparum species occurred in 43% of P. falciparum infections. A high prevalence of P. ovale infections exists among schoolchildren in Tanzania, underscoring the need for detection and treatment strategies that target non-P. falciparum species.

Trends of insecticide resistance monitoring in mainland Tanzania, 2004-2020.

BACKGROUND: Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020. METHODS: The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed. RESULTS: Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites. CONCLUSIONS: Anopheles gambiae Tanzania's major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.

Women attending antenatal care as a sentinel surveillance population for malaria in Geita region, Tanzania: feasibility and acceptability to women and providers.

BACKGROUND: Measurement of malaria prevalence is conventionally estimated through infrequent cross-sectional household surveys that do not provide continuous information regarding malaria parasitaemia. Recent studies have suggested that malaria parasitaemia prevalence among women attending antenatal care (ANC) correlates with prevalence among children under 5 years old and that pregnant women could be a sentinel population for tracking malaria prevalence. In mainland Tanzania, 97% of women are tested for malaria parasitaemia during first ANC visits. However, acceptability among pregnant women and healthcare providers of collecting malaria risk factor data during ANC visits is limited. METHODS: A tablet-based questionnaire including 15 questions on insecticide-treated net ownership and use and care-seeking for febrile children was introduced at 40 healthcare facilities in Geita Region, Tanzania. Facilities were randomly selected from among those with 15-120 first ANC visits per month. To assess perspectives regarding introduction of the questionnaire, 21 semi-structured interviews were held with providers and facility in-charges at 12 facilities. Thirty pregnant and recently delivered women participated in focus group discussions at seven facilities to assess the acceptability of spending additional time answering questions about malaria risk. RESULTS: All pregnant women reported that introduction of ANC surveillance and spending 10 more minutes with providers answering questions about their health would be neutral or beneficial. They perceived being asked about their health as standard of care. Providers and in-charges reported that introduction of ANC surveillance was within their scope of practice. Nine of 21 indicated it could potentially benefit women's health. Six providers expressed concern about staffing shortages and need for reimbursement for extra time and noted that data management occurs after hours. CONCLUSIONS: Pregnant women and providers generally perceived ANC surveillance for malaria as acceptable and positive. Pregnant and recently delivered women saw this as a reasonable and even helpful intervention. To be seen as a part of standard practice, efforts are needed to ensure providers perceive a benefit for ANC clients and that staffing concerns are addressed. In addition, staff should receive feedback related to data submissions regarding malaria prevalence and risk factors among women at their facility, with actions to take.

Improvements in malaria surveillance through the electronic Integrated Disease Surveillance and Response (eIDSR) system in mainland Tanzania, 2013-2021.

BACKGROUND: Tanzania has made remarkable progress in reducing malaria burden and aims to transition from malaria control to sub-national elimination. In 2013, electronic weekly and monthly reporting platforms using the District Health Information System 2 (DHIS2) were introduced. Weekly reporting was implemented through the mobile phone-based Integrated Disease Surveillance and Response (eIDSR) platform and progressively scaled-up from 67 to 7471 (100%) public and private health facilities between 2013 and 2020. This study describes the roll-out and large-scale implementation of eIDSR and compares the consistency between weekly eIDSR and monthly DHIS2 malaria indicator data reporting, including an assessment of its usefulness for malaria outbreak detection and case-based surveillance (CBS) in low transmission areas. METHODS: The indicators included in the analysis were number of patients tested for malaria, number of confirmed malaria cases, and clinical cases (treated presumptively for malaria). The analysis described the time trends of reporting, testing, test positivity, and malaria cases between 2013 and 2021. For both weekly eIDSR and monthly DHIS2 data, comparisons of annual reporting completeness, malaria cases and annualized incidence were performed for 2020 and 2021; additionally, comparisons were stratified by malaria epidemiological strata (parasite prevalence: very low < 1%, low 1 ≤ 5%, moderate 5 ≤ 30%, and high > 30%). RESULTS: Weekly eIDSR reporting completeness steadily improved over time, with completeness being 90.2% in 2020 and 93.9% in 2021; conversely, monthly DHIS2 reporting completeness was 98.9% and 98.7% in 2020 and 2021, respectively. Weekly eIDSR reporting completeness and timeliness were highest in the very low epidemiological stratum. Annualized malaria incidence as reported by weekly eIDSR was 17.5% and 12.4% lower than reported by monthly DHIS2 in 2020 and 2021; for both 2020 and 2021, annualized incidence was similar across weekly and monthly data in the very low stratum. CONCLUSION: The concurrence of annualized weekly eIDSR and monthly DHIS2 reporting completeness, malaria cases and incidence in very low strata suggests that eIDSR could be useful tool for early outbreak detection, and the eIDSR platform could reliably be expanded by adding more indicators and modules for CBS in the very low epidemiological stratum.

Risk factors associated with malaria infection identified through reactive case detection in Zanzibar, 2012-2019.

BACKGROUND: Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar. METHODS: Surveillance data from Zanzibar's Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level. RESULTS: A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3-39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3-2.8) and living in Unguja (OR = 1.2; 95% CI 1.0-1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7-0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7-0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7-0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6-0.8). CONCLUSIONS: The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5-14 years and travellers are needed.

Acceptability of single screening and treatment policy for the control of malaria in pregnancy: perceptions of providers and pregnant women from selected health facilities in Lindi region, Tanzania.

BACKGROUND: Tanzania started implementing single screening and treatment (SST) for all pregnant women attending their first antenatal care (ANC) visits in 2014, using malaria rapid diagnostic tests (RDTs) and treating those who test positive according to the national guidelines. However, there is a paucity of data to show the acceptability of SST to both pregnant women and health care workers (HCWs), taking into consideration the shortage of workers and the added burden of this policy to the health system. This study assessed the perceptions and opinions of health service users and providers to determine the acceptability of SST policy. METHODS: Pregnant women and HCWs in eight health facilities in two districts of Lindi region (Kilwa and Lindi) were interviewed using semi-structured questionnaires with open and close-ended questions. Both qualitative and quantitative data were collected, including demographic characteristics, women's experience, their perception on SST and challenges they face when receiving services for malaria offered at ANC. Experience of HCWs regarding the implementation of SST as part of routine services and the challenges encountered when providing ANC services for malaria in pregnancy (MIP) were also assessed. RESULTS: Of the 143 pregnant women interviewed, 97% viewed testing favourably and would wish to be tested for malaria again, while 95% were satisfied with services and reasons for testing during the first ANC visit. Nearly all (99%) would recommend their fellow pregnant women to be tested for malaria and all women recommended that the Ministry of Health should continue the SST strategy. This was despite the fact that 76% of the women experienced pain and 16% had anxiety as a result of finger prick. Sixteen HCWs (mostly nurses) were interviewed; they also viewed SST implementation favourably and reported feeling empowered to use RDTs for malaria screening. The main challenge identified by HCWs was that nurses are not allowed to prescribe anti-malarials to women who test positive and need to refer them to the outpatient department for treatment. CONCLUSION: SST was considered an acceptable approach to control MIP by HCWs and pregnant women, and they recommended the continuation of the policy. In addition, consideration should be given to implementing a task-shifting policy to allow nurses to dispense anti-malarials to pregnant women.

Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes.

High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13-R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared.

Evaluation of a single screen and treat strategy to detect asymptomatic malaria among pregnant women from selected health facilities in Lindi region, Tanzania.

BACKGROUND: In areas of high transmission, malaria in pregnancy (MiP) primarily causes asymptomatic infections; these infections nonetheless increase the risk of adverse maternal and fetal outcomes. In 2014, Tanzania initiated a single screening and treatment (SST) strategy for all pregnant women at their first antenatal care (ANC) visit using malaria rapid diagnostic tests (RDT) for surveillance purposes. However, there is paucity of data on the effectiveness of SST in the prevention of MiP. The objective of this study was to estimate the number of asymptomatic infections among pregnant women detected by SST, which would have been missed in the absence of the policy. METHODS: Data from pregnant women attending their first ANC visits between October 2017 and June 2018, including gestational age, history of fever, and RDT results, were abstracted from ANC registers in eight health centres in two randomly selected districts, Kilwa and Lindi, in Lindi Region. The proportion of symptomatic (with history of fever in the past 48 h) and asymptomatic pregnant women with positive RDTs were calculated and stratified by trimester (first, second and third). The study areas were categorized as low transmission with prevalence < 10% or moderate/high with ≥ 10%. RESULTS: Over the study period, 1,845 women attended their first ANC visits; 22.1% were in the first trimester (< 12 weeks gestation age). Overall 15.0% of the women had positive RDTs, and there was a trend towards higher malaria prevalence in the first (15.9%) and second (15.2%) trimesters, compared to the third (7.1%), although the differences were not statistically significant (p = 0.07). In total, 6.9% of women reported fever within the past 48 h and, of these, 96.1% were RDT positive. For every 100 pregnant women in the moderate/high and low transmission areas, SST identified 60 and 26 pregnant women, respectively, with asymptomatic infections that would have otherwise been missed. Among the 15.9% of women detected in the first trimester, 50.7% were asymptomatic. CONCLUSION: In areas of moderate/high transmission, many infected women were asymptomatic, and would have been missed in the absence of SST. The benefits on maternal and fetal birth outcomes of identifying these infections depend heavily on the protection afforded by treatment, which is likely to be greatest for women presenting in the first trimester when intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is contraindicated, and in areas with high SP resistance, such as most parts of Tanzania. An evaluation of the impact and cost-effectiveness of SST across different transmission strata is warranted.

Estimating malaria burden among pregnant women using data from antenatal care centres in Tanzania: a population-based study.

BACKGROUND: More timely estimates of malaria prevalence are needed to inform optimal control strategies and measure progress. Since 2014, Tanzania has implemented nationwide malaria screening for all pregnant women within the antenatal care system. We aimed to compare malaria test results during antenatal care to two population-based prevalence surveys in Tanzanian children aged 6-59 months to examine their potential in measuring malaria trends and progress towards elimination. METHODS: Malaria test results from pregnant women screened at their first antenatal care visits at health-care facilities (private and public) in all 184 districts of Tanzania between Jan 1, 2014, and Dec 31, 2017, were collected from the Health Management Information Systems and District Health Information System 2. We excluded facilities with no recorded antenatal care attendees during the time period. We standardised results to account for testing uptake and weighted them by the timing of two population-based surveys of childhood malaria prevalence done in 2015-16 (Demographic and Health Survey) and 2017 (Malaria Indicator Survey). We assessed regional-level correlation using Spearman's coefficient and assessed the consistency of monthly district-level prevalence ranking using Kendall's correlation coefficient. FINDINGS: Correlation between malaria prevalence at antenatal care and among children younger than 5 years was high (r≥0·83 for both surveys), although declines in prevalence at antenatal care were generally smaller than among children. Consistent heterogeneity (p<0·05) in antenatal care prevalence at the district level was evident in all but one region (Kilimanjaro). Data from antenatal care showed declining prevalence in three regions (Arusha, Kilimanjaro, and Manyara) where surveys estimated zero prevalence. INTERPRETATION: Routine antenatal care-based screening can be used to assess heterogeneity in transmission at finer resolution than population-based surveys, and provides sample sizes powered to detect changes, notably in areas of low transmission where surveys lack power. Declines in prevalence at antenatal care might lag behind those among children, highlighting the value of monitoring burden and continuing prevention efforts among pregnant women as transmission declines. The pregnancy-specific benefits and cost-effectiveness of antenatal care-based screening remain to be assessed. FUNDING: None.

Evidence of sustained reductions in the relative risk of acute hepatitis B and C virus infections, and the increasing burden of hepatitis a virus infection in Egypt: comparison of sentinel acute viral hepatitis surveillance results, 2001-17.

BACKGROUND: Egypt ranks fifth for the burden of viral hepatitis worldwide. As part of Egypt's renewed national strategy for the elimination of viral hepatitis, surveillance for acute viral hepatitis (AVH) was re-established during 2014-2017 to describe the current epidemiology and associated risk factors, and changes from surveillance conducted during 2001-2004. METHODS: Patients with suspected AVH were enrolled, completed a questionnaire, and provided blood for testing for hepatitis viruses A (HAV), B (HBV), C (HCV), D, and E (HEV) infections by enzyme-linked immunosorbent assay. Odds ratios and Chi2 were used to detect differences between hepatitis types by patient characteristics and exposures. Newcombe-Wilson method was used to compare results between surveillance periods 2001-2004 and 2014-2017. RESULTS: Between 2014 and 2017, among 9321 patients enrolled, 8362 (89.7%) had one or more markers of AVH including 7806 (93.4%) HAV, 252 (3.0%) HCV, 238 (2.8%) HBV, and 31 (0.4%) HEV infection. HAV infection occurred most commonly among children < 16 years age, while HBV infection occurred among ages 16-35 years and HCV infection in ages greater than 45 years. Healthcare-associated exposures were significantly associated with HBV and HCV infections compared to HAV infection including receiving therapeutic injections, surgery, wound suture, or urinary catheter and IV line insertions, while significant lifestyle exposures included exposure to blood outside the healthcare system, IV drug use, or incarceration. Exposures significantly associated with HAV infection were attending nursery or pre-school, contact with person attending nursery or pre-school, having meals outside the home, or contact with HAV case. Compared with AVH surveillance during 2001-2004, there was a significant increase in the proportion of HAV infections from 40.2 to 89.7% (RR = 2.3) with corresponding reductions in the proportions of HBV and HCV infections from 30.0 to 2.8% (RR = 0.1) and 29.8 to 3.0% (RR = 0.1), respectively. CONCLUSIONS: Healthcare-associated exposures were significantly association with and remain the greatest risk for HBV and HCV infections in Egypt. Additional studies to evaluate factors associated with the reductions in HBV and HCV infections, and cost effectiveness of routine HAV immunization might help Egypt guide and evaluate control measures.

Use of Bibliometric Analysis to Assess the Scientific Productivity and Impact of the Global Emerging Infections Surveillance and Response System Program, 2006-2012.

BACKGROUND: Scientific publication in academic literature is a key venue in which the U.S. Department of Defense's Global Emerging Infections Surveillance and Response System (GEIS) program disseminates infectious disease surveillance data. Bibliometric analyses are tools to evaluate scientific productivity and impact of published research, yet are not routinely used for disease surveillance. Our objective was to incorporate bibliometric indicators to measure scientific productivity and impact of GEIS-funded infectious disease surveillance, and assess their utility in the management of the GEIS surveillance program. METHODS: Metrics on GEIS program scientific publications, project funding, and countries of collaborating institutions from project years 2006 to 2012 were abstracted from annual reports and program databases and organized by the six surveillance priority focus areas: respiratory infections, gastrointestinal infections, febrile and vector-borne infections, antimicrobial resistance, sexually transmitted infections, and capacity building and outbreak response. Scientific productivity was defined as the number of scientific publications in peer-reviewed literature derived from GEIS-funded projects. Impact was defined as the number of citations of a GEIS-funded publication by other peer-reviewed publications, and the Thomson Reuters 2-year journal impact factor. Indicators were retrieved from the Web of Science and Journal Citation Report. To determine the global network of international collaborations between GEIS partners, countries were organized by the locations of collaborating institutions. RESULTS: Between 2006 and 2012, GEIS distributed approximately US $330 million to support 921 total projects. On average, GEIS funded 132 projects (range 96-160) with $47 million (range $43 million-$53 million), annually. The predominant surveillance focus areas were respiratory infections with 317 (34.4%) projects and $225 million, and febrile and vector-borne infections with 274 (29.8%) projects and $45 million. The number of annual respiratory infections-related projects peaked in 2006 and 2009. The number of febrile and vector-borne infections projects increased from 29 projects in 2006 to 58 in 2012. There were 651 articles published in 147 different peer-reviewed journals, with an average Thomson Reuters 2-year journal impact factor of 4.2 (range 0.3-53.5). On average, 93 articles were published per year (range 67-117) with $510,000 per publication. Febrile and vector-borne, respiratory, and gastrointestinal infections had 287, 167, and 73 articles published, respectively. Of the 651 articles published, 585 (89.9%) articles were cited at least once (range 1-1,045). Institutions from 90 countries located in all six World Health Organization regions collaborated with surveillance projects. CONCLUSIONS: These findings summarize the GEIS-funded surveillance portfolio between 2006 and 2012, and demonstrate the scientific productivity and impact of the program in each of the six disease surveillance priority focus areas. GEIS might benefit from further financial investment in both the febrile and vector-borne and sexually transmitted infections surveillance priority focus areas and increasing peer-reviewed publications of surveillance data derived from respiratory infections projects. Bibliometric indicators are useful to measure scientific productivity and impact in surveillance systems; and this methodology can be utilized as a management tool to assess future changes to GEIS surveillance priorities. Additional metrics should be developed when peer-reviewed literature is not used to disseminate noteworthy accomplishments.

Outbreak of Drug-Resistant Mycobacterium tuberculosis Among Homeless People in Atlanta, Georgia, 2008-2015.

OBJECTIVES: Our objective was to describe and determine the factors contributing to a recent drug-resistant tuberculosis (TB) outbreak in Georgia. METHODS: We defined an outbreak case as TB diagnosed from March 2008 through December 2015 in a person residing in Georgia at the time of diagnosis and for whom (1) the genotype of the Mycobacterium tuberculosis isolate was consistent with the outbreak strain or (2) TB was diagnosed clinically without a genotyped isolate available and connections were established to another outbreak-associated patient. To determine factors contributing to transmission, we interviewed patients and reviewed health records, homeless facility overnight rosters, and local jail booking records. We also assessed infection control measures in the 6 homeless facilities involved in the outbreak. RESULTS: Of 110 outbreak cases in Georgia, 86 (78%) were culture confirmed and isoniazid resistant, 41 (37%) occurred in people with human immunodeficiency virus coinfection (8 of whom were receiving antiretroviral treatment at the time of TB diagnosis), and 10 (9%) resulted in TB-related deaths. All but 8 outbreak-associated patients had stayed overnight or volunteered extensively in a homeless facility; all these facilities lacked infection control measures. At least 9 and up to 36 TB cases outside Georgia could be linked to this outbreak. CONCLUSIONS: This article highlights the ongoing potential for long-lasting and far-reaching TB outbreaks, particularly among populations with untreated human immunodeficiency virus infection, mental illness, substance abuse, and homelessness. To prevent and control TB outbreaks, health departments should work with overnight homeless facilities to implement infection control measures and maintain searchable overnight rosters.

Human Coronavirus-Associated Influenza-Like Illness in the Community Setting in Peru.

We present findings describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru. In 2010, the prevalence of infections by human coronaviruses 229E, OC43, NL63, or HKU1 was 6.4% in participants with influenza-like illness who tested negative for influenza viruses. Ten of 11 human coronavirus infections were identified in the fall-winter season. Human coronaviruses are present in different regions of Peru and are relatively frequently associated with influenza-like illness in Peru.

Epidemiology and Genetic Characterization of Noroviruses among Adults in an Endemic Setting, Peruvian Amazon Basin, 2004-2011.

BACKGROUND: Successful vaccination strategies against norovirus will require understanding the burden of disease and relevant genotypes in populations. However, few data are available from cohort studies of adults living in low- and middle-income countries (LMIC). MATERIALS AND METHODS: We conducted a nested case-control study within a Peruvian military cohort to characterize the burden of norovirus infection, predominant genotypes, and associated symptoms from 2004 through 2011. Randomly selected case and control stools were tested for norovirus, bacteria, and parasites. The odds ratio of the association between norovirus infection and diarrhea was estimated using multiple logistic regression and co-infection adjusted attributable fractions were calculated. RESULTS: Of the 3,818 cohort study participants, 624 developed diarrhea. Overall and norovirus-associated diarrhea incidence rates were 42.3 and 6.0 per 100 person-years, respectively. The most prevalent norovirus genogroup was GII (72.5%, 29/40), which was associated with diarrhea (AOR 3.4, 95% CI: 1.3-8.7, P = 0.012). The co-infection adjusted GII attributable fraction was 6.4%. DISCUSSION: Norovirus was a frequent cause of diarrhea in an adult population followed longitudinally in an LMIC setting. Vaccine strategies should consider targeting adults in endemic settings and special populations that could serve as community transmission sources.

Reintegration of ebola survivors into their communities - Firestone District, Liberia, 2014.

The current Ebola virus disease (Ebola) epidemic in West Africa is unprecedented in size and duration. Since the outbreak was recognized in March 2014, the World Health Organization (WHO) has reported 17,145 cases with 6,070 deaths, primarily in Guinea, Liberia, and Sierra Leone. Combined data show a case-fatality rate of approximately 70% in patients with a recorded outcome; a 30% survival rate means that thousands of patients have survived Ebola. An important component of a comprehensive Ebola response is the reintegration of Ebola survivors into their communities.