BACKGROUND: In Zambia, the true extent of SARS-CoV-2 infections is unknown because initial surveillance focused on patients with symptoms or severe disease. Antenatal sentinel surveillance had not been used to assess infection trends. The ANC COVID-19 surveillance study sought to determine SARS-CoV-2 seroprevalence and COVID-19 vaccine uptake among pregnant women. We provide insight into the study implementation, challenges encountered, best practices, and lessons learned. METHODS: A repeated cross-sectional seroprevalence survey was implemented at 39 health facilities in four districts from September 2021 to September 2022. Pregnant women aged 15-49 years were enrolled at their first antenatal care visits. An electronic questionnaire gathered demographics and other COVID-19 related information from consenting participants. A dried blood sample was collected to detect IgG antibodies using a multiplex bead assay. Seropositive results were categorized as infection, infection and vaccination or infection based on anti-RBD and anti-nucleocapsid test results. Problems and their root causes were identified as they occurred. Practical problem-solving strategies were devised, implemented, and monitored to ensure that goals were accomplished. RESULTS: In the primary analysis, 7% of the 9,221 samples collected from participants were not tested because they were missing. COVID-19 vaccine uptake of 9,111 pregnant women was assessed. Approximately 64% of participants were cumulatively seropositive for SARS-CoV-2 antibodies. Seroprevalence increased from 27.8% in September 2021 to 56.6% in July 2022. We observed an increase in vaccine coverage (0.5-27%) over time. Women aged 40-49 years old, without education and with prior COVID-19 infection were associated with higher vaccine uptake. The Delta variant of COVID-19 and the reallocation of health facilities between two partners delayed surveillance activities and increased the cost of implementation (e.g., the purchase of additional calibration and validation kits and DBS cards). Protocol deviations were attributed to the lack of experience in conducting research but, the district RAs repeatedly trained health facility staff to enhance their research knowledge. CONCLUSIONS: Incorporating SARS-CoV-2 surveillance into routine antenatal care is feasible and potentially sustainable when existing health system infrastructure, human resources, and surveillance systems are leveraged. Yet, careful planning is needed to anticipate implementation challenges and ensure high-quality data collection.

Pregnant women are considered a high-risk group for COVID-19, and a priority for vaccination. Routine antenatal care (ANC) provides an opportunity to track trends and factors associated with vaccine uptake. We sought to evaluate COVID-19 vaccine uptake among pregnant women attending ANC and assess the factors associated with vaccine in Zambia. We conducted a repeated cross-sectional study in 39 public health facilities in four districts in Zambia from September 2021 to September 2022. Pregnant women who were aged 15-49 years were enrolled during their first ANC visit. Every month, ~20 women per facility were interviewed during individual HIV counseling and testing. We estimated vaccine uptake as the proportion of eligible participants who self-reported having received the COVID-19 vaccine. A total of 9,203 pregnant women were screened, of which 9,111 (99%) were eligible and had vaccination status. Of the 9,111 included in the analysis, 1,818 (20%) had received the COVID-19 vaccine during the study period, with a trend of increasing coverage with time (0.5% in September 2020, 27% in September 2022). Conversely, 3,789 (42%) reported not being offered a COVID-19 vaccine. We found that women aged 40-49 years, had no education or attained some primary school education, were not employed, and had prior COVID-19 infection were significantly associated with vaccine uptake. COVID-19 vaccine uptake among pregnant women was lower than estimates from the general population (27% across the four districts in September 2022), pointing to missed opportunities to protect this high-risk group. ANC visits were a viable point for conducting COVID-19 surveillance. Incorporating the vaccine as part of the routine ANC package might increase coverage in this group.

BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies.

BACKGROUND: Low levels of COVID-19 vaccination coverage in many countries prompted the use of rapid assessments to characterize barriers to vaccination and identify corrective measures. The World Health Organization recommended the use of intra-action reviews (IARs) to identify best practices, gaps, and lessons learned to make real-time improvements to the COVID-19 vaccination response. OBJECTIVE: The Democratic Republic of the Congo (DRC) implemented a national IAR in July 2021 that was poorly attended by the provincial health level, where vaccination activities are planned and implemented. To bridge this gap, we proposed sub-national IARs focused on COVID-19 vaccine program implementation at the provincial level. METHODS: Using the WHO methodology, we organized a four-day provincial IAR workshop and invited national, provincial and health zone Ministry of Health (MoH) representatives and private and non-governmental organizations involved in the provincial COVID-19 vaccination response. Participants were divided into six groups based on their expertise, affiliation, and role within the health system to assess and identify lessons learned, challenges and the solutions within each of the six technical areas: (1) coordination, planning and monitoring; (2) service delivery; (3) risk communication and community engagement; (4) adverse effects following immunization (AEFI); (5) logistics; (6) and data management, monitoring and evaluation. RESULTS: The first provincial COVID-19 IAR was conducted in Goma, North Kivu, from January 19-22, 2022. A total of 56 participants came from provincial and health zone offices, and non-governmental organizations. Through work group discussions, they identified best practices, challenges, and lessons learned, and made recommendations to improve implementation of vaccination activities and reach coverage targets. Activities were proposed to operationalize recommendations and address challenges to improve the provincial response. CONCLUSION: This provincial IAR was a useful tool for reviewing progress and areas of improvement, while evaluating aspects of the COVID-19 vaccine rollout. It provided a means to share information with vaccination partners on areas of intervention, tailored to the local context.

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

Incidence of human monkeypox (mpox) has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in the DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, Rt, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated Rt of 0.82 (95% CI: 0.79-0.85) and a rate of 132 (95% CI: 122-143) spillovers per year assuming a reporting rate of 25%. This estimate of Rt is larger than most previous estimates. One potential explanation for this result is that Rt could have increased in the DRC over time owing to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. Rt could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province.

Incidence of human mpox has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, R<inf>t</inf>, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated R<inf>t</inf> of 0.82 (95% CI: 0.79 - 0.85) and a rate of 132 (95% CI: 122 - 143) spillovers per year assuming a reporting rate of 0.25. This estimate of R<inf>t</inf> is larger compared to most previous estimates. One potential explanation for this result is that R<inf>t</inf> could have increased in DRC over time due to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. R<inf>t</inf> could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.

BACKGROUND: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. METHODS: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of PCR-confirmed cases by sex and age. RESULTS: We report 1,057 confirmed cases. Average annual incidence was 14·1 per 100,000 (95% CI: 13·3-15·0). Incidence was higher in males (incidence rate ratio [IRR] males: females: 1·21, 95% CI 1·07-1·37), except among 20-29-year-old (IRR: 0·70, 95% CI: 0·51-0·95). Females aged 20-29 years also reported a high frequency of exposures (26·2%) to people with monkeypox-like symptoms. Highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37·5%). Incidence was lower among those presumed to have received smallpox vaccination versus those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. CONCLUSIONS: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow socio-cultural norms.

Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.

On April 10, 2020, just 2 days before the anticipated declaration of the end of the North Kivu and Ituri Ebola virus disease (EVD) outbreak in DR Congo, and 53 days after the last confirmed case of EVD had been reported, a new case was confirmed. Sequencing of patient samples from the case in April and six others that followed indicated that these cases were likely to have come from a reintroduction of the virus from a persistently infected survivor.1 This group of cases marked the second flare-up linked to an EVD survivor during this outbreak. In November, 2019, a relapse case in North Kivu resulted in widespread transmission across multiple health zones, helping to extend the outbreak by at least 3 months.

BACKGROUND: The World Health Organization recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data about the performance of established influenza surveillance systems are limited in Africa, including in the Democratic Republic of Congo (DRC). METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza sentinel surveillance system (ISSS) in DRC during 2012-2015. The performance of the system was evaluated using eight surveillance attributes: (i) data quality and completeness for key variables, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability and (viii) utility. For each attribute, specific indicators were developed and described using quantitative and qualitative methods. Scores for each indicator were as follows: < 60% weak performance; 60-79% moderate performance; >/=80% good performance. RESULTS: During 2012-2015, we enrolled and tested 4339 patients with influenza-like illness (ILI) and 2869 patients with severe acute respiratory illness (SARI) from 11 sentinel sites situated in 5 of 11 provinces. Influenza viruses were detected in 446 (10.3%) samples from patients with ILI and in 151 (5.5%) samples from patients with SARI with higher detection during December-May. Data quality and completeness was > 90% for all evaluated indicators. Other strengths of the system were timeliness, simplicity, stability and utility that scored > 70% each. Representativeness, flexibility and acceptability had moderate performance. It was reported that the ISSS contributed to: (i) a better understanding of the epidemiology, circulating patterns and proportional contribution of influenza virus among patients with ILI or SARI; (ii) acquisition of new key competences related to influenza surveillance and diagnosis; and (iii) continuous education of surveillance staff and clinicians at sentinel sites about influenza. However, due to limited resources no actions were undertaken to mitigate the impact of seasonal influenza epidemics. CONCLUSIONS: The system performed overall satisfactorily and provided reliable and timely data about influenza circulation in DRC. The simplicity of the system contributed to its stability. A better use of the available data could be made to inform and promote prevention interventions especially among the most vulnerable groups.

OBJECTIVE: To describe varicella cases in Tshuapa Province of the Democratic Republic of the Congo identified during monkeypox surveillance. METHODS: Demographic, clinical, and epidemiological data were collected from each suspected monkeypox case 2009-2014. Samples were tested by PCR for both Orthopoxviruses and varicella-zoster virus (VZV); a subset of VZV positive samples were genotyped. We defined a varicella case as a rash illness with laboratory-confirmed VZV. RESULTS: 366 varicella cases were identified; 66% were </=19 years old. Most patients had non-typical varicella rash with lesions reported as the same size and stage of evolution (86%), deep and profound (91%), on palms of hands and/or soles of feet (86%), and not itchy (49%). Many had non-typical signs and symptoms, such as lymphadenopathy (70%) and sensitivity to light (23%). A higher proportion of persons aged >/=20 years than persons aged </=19 years had >/=50 lesions (79% versus 65%, p = 0.007) and were bedridden (15% versus 9%, p = 0.056). All VZV isolates genotyped from 79 varicella cases were clade 5. During the surveillance period, one possible VZV-related death occurred in a 7 year-old child. CONCLUSIONS: A large proportion of patients presented with nontypical varicella rash and clinical signs and symptoms, highlighting challenges identifying varicella in an area with endemic monkeypox. Continued surveillance and laboratory diagnosis will help in rapid identification and control of both monkeypox and varicella and improve our understanding of varicella epidemiology in Africa. This article is protected by copyright. All rights reserved.

Endemic to the Democratic Republic of the Congo (DRC), monkeypox is a zoonotic disease that causes smallpox-like illness in humans. Observed fluctuations in reported cases over time raises questions about when it is appropriate to mount a public health response, and what specific actions should be taken. We evaluated three different thresholds to differentiate between baseline and heightened disease incidence, and propose a novel, tiered algorithm for public health action. Monkeypox surveillance data from Tshuapa Province, 2011-2013, were used to calculate three different statistical thresholds: Cullen, c-sum, and a World Health Organization (WHO) method based on monthly incidence. When the observed cases exceeded the threshold for a given month, that month was considered to be 'aberrant'. For each approach, the number of aberrant months detected was summed by year-each method produced vastly different results. The Cullen approach generated a number of aberrant signals over the period of consideration (9/36 months). The c-sum method was the most sensitive (30/36 months), followed by the WHO method (12/24 months). We conclude that triggering public health action based on signals detected by a single method may be inefficient and overly simplistic for monkeypox. We propose instead a response algorithm that integrates an objective threshold (WHO method) with contextual information about epidemiological and spatiotemporal links between suspected cases to determine whether a response should be operating under i) routine surveillance ii) alert status, or iii) outbreak status. This framework could be modified and adopted by national and zone level health workers in monkeypox-endemic countries. Lastly, we discuss considerations for selecting thresholds for monkeypox outbreaks across gradients of endemicity and public health resources.

Healthcare-associated transmission of monkeypox has been observed on multiple occasions in areas where the disease is endemic. Data collected by the US Centers for Disease Control and Prevention (CDC) from an ongoing CDC-supported program of enhanced surveillance in the Tshuapa Province of the Democratic Republic of the Congo, where the annual incidence of human monkeypox is estimated to be 3.5-5/10,000, suggests that there is approximately one healthcare worker infection for every 100 confirmed monkeypox cases. Herein, we describe a study that commenced in February 2017, the intent of which is to evaluate the effectiveness, immunogenicity, and safety of a third-generation smallpox vaccine, IMVAMUNE((R)), in healthcare personnel at risk of monkeypox virus (MPXV) infection. We describe procedures for documenting exposures to monkeypox virus infection in study participants, and outline lessons learned that may be of relevance for studies of other investigational countermeasures in hard to reach, under-resourced populations.

BACKGROUND: Estimates of influenza-associated outpatient consultations and hospitalizations are severely limited in low- and middle-income countries, especially in Africa. METHODS: We conducted active prospective surveillance for influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 5 healthcare facilities situated in Kinshasa Province during 2013-2015. We tested upper respiratory tract samples for influenza viruses using a reverse transcription polymerase chain reaction assay. We estimated age-specific numbers and rates of influenza-associated ILI outpatient consultations and SARI hospitalizations for Kinshasa Province using a combination of administrative and influenza surveillance data. These estimates were extrapolated to each of the remaining 10 provinces accounting for provincial differences in prevalence of risk factors for pneumonia and healthcare seeking behavior. Rates were reported per 100,000 population. RESULTS: During 2013-2015 the mean annual national number of influenza-associated ILI outpatient consultations was 1,003,212 (95% Confidence Incidence [CI]: 719,335-1,338,050 - Rate: 1,205.3; 95% CI: 864.2-1,607.5); 199,839 (95% CI: 153,563-254,759 - Rate: 1,464.0; 95% CI: 1,125.0-1,866.3) among children aged <5 years and 803,374 (95% CI: 567,772-1,083,291 - Rate: 1,154.5; 95% CI: 813.1-1,556.8) among individuals aged >/=5 years. The mean annual national number of influenza-associated SARI hospitalizations was 40,361 (95% CI: 24,014-60,514 - Rate: 48.5; 95% CI: 28.9-72.7); 25,452 (95% CI: 19,146-32,944 - Rate: 186.5; 95% CI: 140.3-241.3) among children aged <5 years and 14,909 (95% CI: 4,868-27,570 - Rate: 21.4; 95% CI: 28.9-72.7) among individuals aged >/=5 years. CONCLUSIONS: The burden of influenza-associated ILI outpatient consultations and SARI hospitalizations was substantial and was highest among hospitalized children aged <5 years. This article is protected by copyright. All rights reserved.

Preventing zoonotic diseases requires coordinated actions by government authorities responsible for human and animal health. Constructing the frameworks needed to foster intersectoral collaboration can be approached in many ways. We highlight 3 examples of approaches to implement zoonotic disease prevention and control programs. The first, rabies control in Ethiopia, was implemented using an umbrella approach: a comprehensive program designed for accelerated impact. The second, a monkeypox program in Democratic Republic of the Congo, was implemented in a stepwise manner, whereby incremental improvements and activities were incorporated into the program. The third approach, a pathogen discovery program, applied in the country of Georgia, was designed to characterize and understand the ecology, epidemiology, and pathogenesis of a new zoonotic pathogen. No one approach is superior, but various factors should be taken into account during design, planning, and implementation.

BACKGROUND: Human monkeypox (MPX) occurs at appreciable rates in the Democratic Republic of Congo (DRC). Infection with varicella zoster virus (VZV) has a similar presentation to that of MPX, and in areas where MPX is endemic these two illnesses are commonly mistaken. This study evaluated the diagnostic utility of two surveillance case definitions for MPX and specific clinical characteristics associated with laboratory-confirmed MPX cases. METHODOLOGY/PRINCIPAL FINDINGS: Data from a cohort of suspect MPX cases (identified by surveillance over the course of a 42 month period during 2009-2014) from DRC were used; real-time PCR diagnostic test results were used to establish MPX and VZV diagnoses. A total of 333 laboratory-confirmed MPX cases, 383 laboratory-confirmed VZV cases, and 36 cases that were determined to not be either MPX or VZV were included in the analyses. Significant (p<0.05) differences between laboratory-confirmed MPX and VZV cases were noted for several signs/symptoms including key rash characteristics. Both surveillance case definitions had high sensitivity and low specificities for individuals that had suspected MPX virus infections. Using 12 signs/symptoms with high sensitivity and/or specificity values, a receiver operator characteristic analysis showed that models for MPX cases that had the presence of 'fever before rash' plus at least 7 or 8 of the 12 signs/symptoms demonstrated a more balanced performance between sensitivity and specificity. CONCLUSIONS: Laboratory-confirmed MPX and VZV cases presented with many of the same signs and symptoms, and the analysis here emphasized the utility of including 12 specific signs/symptoms when investigating MPX cases. In order to document and detect endemic human MPX cases, a surveillance case definition with more specificity is needed for accurate case detection. In the absence of a more specific case definition, continued emphasis on confirmatory laboratory-based diagnostics is warranted.

Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (qPCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluate the accuracy and utility of a multiplex MPXV assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific qPCR test, OPX-generic qPCR test, and an internal control qPCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa District, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX qPCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were tested in parallel with a q-specific MPX qPCR assay at the Centers for Disease Control and Prevention. The results of the MPX qPCR were used as the gold standard for all analyses. The GeneXpert MPX/OPX assay performed at INRB had a sensitivity of 98.8% and specificity of 100%. The GeneXpert assay performed well with both crust and vesicle samples. The GeneXpert MPX/OPX test incorporates a simple methodology that performs well in both laboratory and field conditions, suggesting its viability as a diagnostic platform that may expand and expedite current MPX detection capabilities.

A 600-fold increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9.6%) tested negative for monkeypox virus (MPXV) infection. The household attack rate (i.e., rate of persons living with an infected person that develop symptoms of MPXV infection) was 50%. Nine families showed >1 transmission event, and >6 transmission events occurred within this health zone. Mean incubation period was 8 days (range 4-14 days). The high attack rate and transmission observed in this study reinforce the importance of surveillance and rapid identification of monkeypox cases. Community education and training are needed to prevent transmission of MPXV infection during outbreaks.

Monkeypox (MPX) is a zoonotic Orthopoxvirus infection endemic in central and western Africa. Human MPX cases occur in the central and northern regions of the Democratic Republic of the Congo (DRC), and this is the first report of confirmed MPX cases in the forested areas of North and South Kivu Provinces, with a detailed epidemiological investigation for one case. The location of each case is within areas predicted to be suitable for MPX virus transmission based on an ecological niche model. Phylogenetic analysis places these viruses in the Congo Basin clade.

An increased incidence of monkeypox (MPX) infections in the Democratic Republic of the Congo was noted by the regional surveillance system in October 2013. Little information exists regarding how MPX is introduced into the community and the factors associated with transmission within the household. Sixty-eight wild animals were collected and tested for Orthopoxvirus. Two of three rope squirrels (Funisciurus sp.) were positive for antibodies to Orthopoxviruses; however, no increased risk was associated with the consumption or preparation of rope squirrels. A retrospective cohort investigation and a case-control investigation were performed to identify risk factors affecting the introduction of monkeypox virus (MPXV) into the community and transmission within the home. School-age males were the individuals most frequently identified as the first person infected in the household and were the group most frequently affected overall. Risk factors of acquiring MPXV in a household included sleeping in the same room or bed, or using the same plate or cup as the primary case. There was no significant risk associated with eating or processing of wild animals. Activities associated with an increased risk of MPXV transmission all have potential for virus exposure to the mucosa.

BACKGROUND: Monkeypox (MPX) is an endemic disease of public health importance in the Democratic Republic of the Congo (DRC). In 2010, the DRC Ministry of Health joined with external partners to improve MPX surveillance in the Tshuapa Health District of DRC. A pivotal component of the program is training of health zone personnel in surveillance methods and patient care. In this report we evaluate outcomes of the training program. METHODS: Health care worker knowledge of key concepts in the MPX training curriculum was assessed using an anonymous self-administered survey. Additionally, evaluators collected feedback about the capacity of participants to perform the surveillance tasks. Training impacts were determined by assessing various surveillance performance metrics. RESULTS: Correct trainee responses to questions about MPX symptoms and patient care increased significantly upon completion of training events. During the 12 months after the initial training, the proportion of suspected cases investigated increased significantly (from 6.7 to 37.3%), as compared to the 5 months prior. However, the proportion of reported cases that were ultimately confirmed remained unchanged, 20.1% (5/24) vs 23.3% (60/257). CONCLUSIONS: We have demonstrated that the MPX curriculum developed for this initiative was effective in transferring knowledge and was associated with improved detection of human MPX cases.