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Background Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with sporadic outbreaks in Cameroon since 2006. Viral whole genomes were generated to analyze the origins of evolutionary lineages, the potential of emergence/re-emergence, and to infer transmission dynamics of recent Cameroon CHIKV outbreak strains. Methods Samples collected between 2016 and 2019 during CHIKV outbreaks in Cameroon were screened for CHIKV using reverse transcription PCR (RT-PCR), followed by whole genome sequencing of positive samples. Results Three coding-complete CHIKV genomes were obtained from samples, which belong to an emerging sub-lineage of the East/Central/South African genotype and formed a monophyletic taxon with previous Central African strains. This clade, which we have named the new Central African clade, appears to be evolving at 3.0 × 10−4 nucleotide substitutions per site per year (95% highest posterior density (HPD) interval of 1.94 × 10−4 to 4.1 × 10−4). Notably, mutations in the envelope proteins (E1-A226V, E2-L210Q, and E2-I211T), which are known to enhance CHIKV adaptability and infectious potential in Aedes albopictus, were present in all strains and mapped to established high-density Ae. albopictus populations. Conclusions These new CHIKV strains constitute a conserved genomic pool of an emerging sub-lineage, reflecting a putative vector host adaptation to Ae. albopictus, which has practically displaced Aedes aegypti from select regions of Cameroon.

Influenza is known to cause severe respiratory illness in HIV-infected adults, but there are few data describing the relationship between HIV infection and influenza in West African countries such as Ghana. We conducted a prospective cohort study in the Shai-Osudoku and Ningo Prampram districts of Ghana from 2014 to 2016. Beginning May 2014, 266 HIV-infected and 510 HIV-uninfected participants age 18 to 73 years were enrolled and monitored for 12 months. We observed 4 and 11 laboratory-confirmed influenza cases among HIV-infected and HIV-uninfected persons, respectively. The overall rate of laboratory-confirmed influenza among HIV-infected participants was 15.0 per 1,000 person years (PY) (95% CI, 0.3–29.80 per 1,000 PY), whereas that among HIV-uninfected participants was 21.6 per 1,000 PY (95% CI, 8.8–34.3 per 1,000 PY) (incidence density ratio, 0.70; P = 0.56). Our study found no significant difference in the incidence of laboratory-confirmed influenza-associated illness among HIV-infected and HIV-uninfected individuals in Ghana.

Summary Background A novel coronavirus, SARS-CoV-2 is currently causing a worldwide pandemic. The first cases of SARS-CoV-2 infection were recorded in Ghana on March 12, 2020. Since then, the country has been combatting countrywide community spread. This report describes how the Virology Department, Noguchi Memorial Institute for Medical Research (NMIMR) is supporting the Ghana Health Service (GHS) to diagnose infections with this virus in Ghana. Methods The National Influenza Centre (NIC) in the Virology Department of the NMIMR, adopted real-time Polymerase Chain Reaction (rRT-PCR) assays for the diagnosis of the SARS-CoV-2 in January 2020. Samples from suspected cases and contact tracing across Ghana were received and processed for SARS-CoV-2. Samples were ‘pooled’ to enable simultaneous batch testing of samples without reduced sensitivity. Outcomes From February 3 to August 21, the NMIMR processed 283 946 (10%) samples. Highest number of cases were reported in June when the GHS embarked on targeted contact tracing which led to an increase in number of samples processed daily, peaking at over 7,000 samples daily. There were several issues to overcome including rapid consumption of reagents and consumables. Testing however continued successfully due to revised procedures, additional equipment and improved pipeline of laboratory supplies. Test results are now provided within 24 to 48 hours of sample submission enabling more effective response and containment. Conclusion Following the identification of the first cases of SARS-CoV-2infection by the NMIMR, the Institute has trained other centres and supported the ramping up of molecular testing capacity in Ghana. This provides a blueprint to enable Ghana to mitigate further epidemics and pandemics. Funding The laboratory work was supported with materials from the Ghana Health Service Ministry of Health, the US Naval Medical Research Unit #3, the World Health Organization, the Jack Ma Foundation and the University of Ghana Noguchi Memorial Institute for Medical Research. Other research projects hosted by the Noguchi Memorial Institute for Medical Research contributed reagents and laboratory consumables. The funders had no role in the preparation of this manuscript.

Tuberculosis (TB) and HIV are strongly linked. There is a 19 times increased risk of developing active TB in people living with HIV than in HIV-negative people with Sub-Saharan Africa being the hardest hit region. According to the WHO, 1.3 million people died from TB, and an additional 300,000 TB-related deaths among people living with HIV. Although some progress has been made in reducing TB-related deaths among people living with HIV due to the evolution of diagnostics, treatment and antiretroviral HIV treatment, multi drug resistant TB is becoming a source of worry. Though significant progress has been made at the national level, understanding the state of the evidence and the challenges will better inform the national response of the opportunities for improved patient outcomes.Keywords: Tuberculosis, management, HIV, MDR TB, GhanaFunding: None

Background: Viral hemorrhagic fevers (VHFs) are infectious illnesses that can cause serious morbidity and mortality to infected persons. During the 2014 Ebola virus disease outbreak in some West African countries, Ghana revamped its surveillance system across the country to prepare, effectively respond and pre-empt any public health concerns Objective: We report on suspected VHF clinical specimens submitted to the Noguchi Memorial Institute for Medical Research (NMIMR) from health facilities across the country for diagnosis within the period under review. This was partly to provide rapid response and to alert the health system to prevent outbreaks and its spread. Methods: From January 2017 to December 2018 clinical specimens of blood from 149 cases of suspected VHFs were collected at health facilities across the country and sent to NMIMR. Patient specimens were tested for viral pathogens including Lassa fever, Yellow fever, Dengue fever, Chikungunya, Zika, Ebola and Marburg by real-time reverse transcription-polymerase chain reaction. A case was however tested for influenza as the patient exhibited respiratory distress symptoms as well. Demographic and clinical information collected on a structured case-based forms were analyzed for each patient. Results: Out of the 149 clinical specimens tested, three (3) were found to be positive, with two (2) being Dengue and one (1) seasonal Influenza A H1N1. Analysis of the case-based forms revealed shortcomings with regards to standard case definitions used to enroll suspected cases. Conclusion: Our results buttress the need for a routine surveillance activity for VHFs to minimize spread and possibly forestall outbreaks. Moreover, febrile illnesses can be caused by a host of pathogens hence there is a need for enhanced diagnosis to help in patient management.

Objectives: To determine the prevalence of SARS-CoV-2 detection among international travellers to Ghana during mandatory quarantine. Design: A retrospective cross-sectional study. Setting: Air travellers to Ghana on 21st and 22nd March 2020. Participants: On 21st and 22nd March 2020, a total of 1,030 returning international travellers were mandatorily quarantined in 15 different hotels in Accra and tested for SARS-CoV-2. All of these persons were included in the study. Main outcome measure: Positivity for SARS-CoV-2 by polymerase chain reaction. Results: The initial testing at the beginning of quarantine found 79 (7.7%) individuals to be positive for SARS-CoV- 2. In the exit screening after 12 to 13 days of quarantine, it was discovered that 26 of those who tested negative for SARS-CoV-2 in the initial screening subsequently tested positive. Conclusions: Ghana likely averted an early community spread of COVID-19 through the proactive approach to quarantine international travellers during the early phase of the pandemic. © 2021 Clinical Archives of Communication Disorders. All rights reserved.

The COVID-19 pandemic caused by SARS-CoV-2 is an important subject for global health. Ghana experienced lowmoderate transmission of the disease when the first case was detected in March 12, 2020 until the middle of July when the number of cases begun to drop. By August 24, 2020, the country's total number of confirmed cases stood at 43,622, with 263 deaths. By the same time, the Noguchi Memorial Institute for Medical Research (NMIMR) of the University of Ghana, the primary testing centre for COVID-19, had tested 285,501 with 28,878 confirmed cases. Due to database gaps, there were initial challenges with timely reporting and feedback to stakeholders during the peak surveillance period. The gaps resulted from mismatches between samples and their accompanying case investigation forms, samples without case investigation forms and vice versa, huge data entry requirements, and delayed test results. However, a revamp in data management procedures, and systems helped to improve the turnaround time for reporting results to all interested parties and partners. Additionally, inconsistencies such as multiple entries and discrepant patient-sample information were resolved by introducing a barcoding electronic capture system. Here, we describe the main challenges with COVID-19 data management and analysis in the laboratory and recommend measures for improvement. © 2021 Clinical Archives of Communication Disorders. All rights reserved.

The Coronavirus disease 2019 (COVID-19) outbreak in Ghana is part of an ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The first two cases of COVID-19 were confirmed in Ghana on 12th March 2020. COVID-19 was consequently declared a Public Health Emergency of National Concern, triggering several response actions, including enhanced surveillance, case detection, case management and contact tracing, closure of borders, suspension of international flights, ban on social gatherings and closure of schools. Preparedness and response plans were activated for implementation at the national, regional, district and community levels. Ghana's Strategic approaches were to limit and stop the importation of cases;detect and contain cases early;expand infrastructure, logistics and capacity to provide quality healthcare for the sick;minimise disruption to social and economic life and increase the domestic capacity of all sectors to deal with existing and future shocks. The health sector strategic frame focused on testing, treatment, and tracking. As of 31st December 2020, a total of 535,168 cases, including 335 deaths (CFR: 0.61%), have been confirmed with 53,928 recoveries and 905 active cases. All the regions have reported cases, with Greater Accra reporting the highest number. The response actions in Ghana have seen highlevel political commitment, appropriate and timely decisions, and a careful balance of public health interventions with economic and socio-cultural dynamics. Efforts are ongoing to intensify non-pharmaceutical interventions, sustain the gains made so far and introduce COVID-19 vaccines to reduce the public health burden of the disease in Ghana. © 2021 Ghana Medical Association. All Rights Reserved.

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.

To estimate the level of community exposure to SARS-CoV-2 in Ghana, we conducted phased seroprevalence studies of 2729 participants in selected locations across Ghana. Phase I screening (August 2020) covered a total of 1305 individuals screened at major markets/lorry stations, major shopping malls, hospitals and research institutions involved in COVID-19 work. The screening was performed using a strip-in-cassette lateral flow type Rapid Diagnostic Test (RDT) kit that simultaneously and separately detected IgM and IgG antibodies against SARS-CoV-2 nucleocapsid protein. In Phase I, 252/1305 (19%) tested positive for IgM or IgG or both. Exposure rate was significantly higher among individuals tested at markets/lorry stations (26.9%) compared to those at Shopping Malls (9.4%). The 41–60-years age group had the highest exposure rate (27.2%). People with only a basic level or no formal education had a higher exposure rate (26.2%) than those with tertiary level education (13.1%); and higher in informally employed workers (24.0%) than those in the formal sector (15.0%). Phases II and III screening activities in October and December 2020, respectively, showed no evidence of increased seroprevalence, indicating either a reduced transmission rate or loss of antibody expression in a subset of the participants. The Upper East region has the lowest exposure rate, with only 4 of 200 participants (2%) seropositivity. Phase IV screening in February 2021 showed that exposure rates in the upper income earners (26.2%) had almost doubled since August 2020, reflective of Ghana’s second wave of symptomatic COVID-19 cases, which began in December 2020. The Phase IV results suggest that seroprevalence levels have become so high that the initial socioeconomic stratification of exposure has been lost. Overall, the data indicates a much higher COVID-19 seroprevalence in the Greater Accra Region than was officially acknowledged, likely implying a considerably lower case fatality rate than the current national figure of 0.84%. Additionally, the high exposure levels seen in the communities suggest that COVID-19 in Ghana still predominantly presents with none-to-mild symptoms. Our results lay the foundation for more extensive SARS-CoV-2 surveillance in Ghana and the West African sub-region, including deploying rapid antigen test kits in concert to determine the actual infection burden since antibody development lags infection.

In human immunodeficiency virus type-1 (HIV-1) infections, cytotoxic T-lymphocyte (CTL) responses targeting human leukocyte antigen (HLA)-restricted viral epitopes exert strong suppressive pressure on viral replication and frequently select for mutations resulting in viral escape from CTL recognition. Numerous data on these HLA-associated mutations in HIV-1 subtypes B and C have been amassed with few reports described in other subtypes. In the present study, we investigated the HLA-associated mutations in HIV-1 subtype CRF02_AG prevailing in Ghana, Western Africa. We determined viral gag sequences in 246 out of 324 HIV-1-infected Ghanaians. Phylogeny analysis revealed that 200 (81.3%) individuals were infected with HIV-1 CRF02_AG. Full gag and vif sequences were obtained from 199 and 138, respectively, out of the 200 individuals infected with CRF02_AG and subjected to determination of HLA-associated mutations. The analysis found HLA-associated HIV-1 CRF02_AG non-synonymous polymorphisms at 19 sites; 13 in gag and six in vif, including those that were newly determined. Generation of this data is an important contribution to our understanding of HIV-1 CRF02_AG and host T cell interaction.

Background: To better understand the extent of the magnitude of tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection in Ghana, a baseline study was conducted to establish the national prevalence of the dual infection. The study aimed to determine the most prevalent HIV serotype (HIV-1 or HIV-2) in TB patients (new and old cases); genotype mycobacterial species causing TB/HIV co-infection and determine their drug susceptibility patterns. Methods: Sputum and dried blood samples were collected from 503 TB patients from 67 health facilities nationwide between December 2007 and November 2008. All samples were processed for mycobacterial and HIV testing using conventional and molecular methods. Results: A total of 517 paired sputum samples were received from 517 patients. A total 503 patients [335 (66.6%) males; 168 (33.4%) females] had at least one culture positive sample. Majority (93.0%) of the patients were new cases while 7.0% were old cases. All 503 TB isolates were Mycobacterium tuberculosis complex. Of 503 blood samples, 74 were positive for HIV (14.7%), comprising 71 (14.1%) and 3 (0.6%) for HIV-1 and HIV-1 & 2 respectively; none was positive for HIV-2 alone. The seroprevalence of HIV in newly diagnosed TB patients and those already on treatment, was 69/468 (14.7%) and 5/35 (14.3%) respectively (p > 0.05). Differentiation of isolates from TB/HIV co-infected patients showed that 70/74 (94.6%) were Mycobacterium tuberculosis while 4/74 (5.4%) were Mycobacterium africanum. Monoresistance to isoniazid and rifampicin were 4/74 (5.4%) and 1/74 (1.4%) respectively; resistance to both drugs (multi-drug resistant-MDR) was not observed. Sixty nine (93.2%) isolates were susceptible to both drugs. Conclusion: The prevalence of HIV infection in TB patients was 14.7%. TB/HIV was common among the sexually active age group (25 - 34 years). Majority of the TB isolates were M. tuberculosis which were susceptible to both isoniazid and rifampicin. HIV-1 was the common serotype infecting TB patients in Ghana.

Identification of a universal influenza vaccine candidate has remained a global challenge for both humans and animals. This study describes an approach that uses consensus sequence building to generate chimeric HAs (cHAs): two resultant H1 HA-based chimeras comprising of conserved sequences (within several areas spanning the head and stalk regions) of H1 and H5 or H9 HAs. These cHAs expressed in Drosophila cells (S2) were used to immunize mice. All immunized mice were protected from an infectious H1 virus challenge. Seroconverted mice sera to the H1 cHAs inhibited both the challenge virus and an H5 virus isolate by haemagglutination inhibition (HI) assay. These findings further emphasize that cHAs induce cross-reactive antibodies against conserved areas of both head and stalk regions of the seasonal influenza A (H1N1) pdm09 virus’ HA and holds potential for further development of a universal influenza vaccine.

Background Diarrhea is an important cause of morbidity and mortality worldwide. In Africa and Ghana in particular, it is estimated to contribute directly to 19 and 25% of pediatric mortality among children under 5 years, respectively. Methods Surveillance for hospitalized acute diarrheal illness was initiated in November 2010 through October 2012 in a referral hospital in southern Ghana, and a teaching hospital in northern Ghana. Consenting hospitalized patients who met a standardized case definition for acute diarrheal illness provided demographic and epidemiologic data. Stool samples were collected and tested by culture for bacteria and by enzyme immunoassays for a panel of viruses and parasites. Results A total of 429 patients were enrolled; 216 (50.3%) were under 5 years, and 221 (51.5%) were females. Stool samples were received from 153 patients. Culture isolates included Shigella sp., Salmonella spp., Plesiomonas sp. and Vibrio cholerae. Of 147 samples tested for viruses, 41 (27.9%) were positive for rotaviruses, 11 (7.5%) for astroviruses, 10 (6.8%) for noroviruses, and 8 (5.4%) for adenoviruses. Of 116 samples tested for parasitic infections; 4 (3.4%) were positive for Cryptosporidium sp. and 3 (2.6%) for Giardia lamblia. Of the enrolled patients, 78.8% had taken antibiotics prior to sample collection. Conclusions Diarrheal pathogens were identified across all ages, however, predominantly (81%) in the children under 5 years of age. This study also detected high antibiotic use which has the potential of increasing antibiotic resistance. The most common enteric pathogen detected (49.4%) was rotavirus. Electronic supplementary material The online version of this article (doi:10.1186/s13104-017-2621-x) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text, This study sought to determine the dominant circulating human immunodeficiency virus type 1 (HIV-1) subtype and associated drug resistance mutations in Ghana. This cross-sectional study was conducted with archived samples collected from patients who received care at 2 hospitals in Ghana from 2014 to 2016. Blood samples were earlier processed into plasma and peripheral blood mononuclear cells and stored at −80 °C. Ribonucleic acid (RNA) was extracted from the archived plasma. Two HIV-1 genes; protease and reverse transcriptase, were amplified, sequenced using gene-specific primers and analyzed for subtype and drug resistance mutations using the Stanford HIV Database. Of 16 patient samples successfully sequenced, we identified the predominance of HIV-1 subtype CRF02_AG (11/16, 68%). Subtypes G (2/16, 13%), dual CRF02_AG/G (2/16, 13%), and CRF01_AE (1/16, 6%) were also observed. Major nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, M184I/V, D67N, T215F, and K70R/E were found. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, K103N, Y181C, V90I, F227L, and V106A were also prevalent. Additionally, and at a lower level, protease inhibitor (PI)-resistance mutations, M46I, I54 V, V82A, L90 M, and I471 V, were also present in the sequences from antiretroviral therapy (ART)-experienced individuals. Two NRTI-associated drug resistance mutations (DRMs) (D67N and T69N) were present in sequences from 1 ART-naive individual. HIV-1 subtype CRF02_AG was most frequently detected in this study thus confirming earlier reports of dominance of this subtype in the West-African sub-region and Ghana in particular. The detection of these drug resistance mutations in individuals on first-line regimen composed of NRTI and NNRTI is an indication of prolonged drug exposure without viral load monitoring. Routine viral load monitoring is necessary for early detection of virologic failure and drug resistance testing will inform appropriate choice of regimens for such patients.

Ultrasound scans have become an essential requirement of pregnancy care in countries with developed health services and increasingly being used in medical practice in Ghana as well. The aim of this study was to find out the perception of primigravidas experiencing antenatal ultrasonography for the first time in Cape Coast. This was a descriptive, prospective study which employed the use of a questionnaire to obtain data from 384 consented respondents, who were primigravidas experiencing antenatal ultrasonography for the first time in three selected public health facilities in Cape Coast Metropolis over a six-month period. Sociodemographic data, reasons for undergoing antenatal ultrasound, their expectations, knowledge in fetal abnormalities, and suggestions to help improve their future experiences were collected. The data were analyzed using SPSS software, version 20.0 (SPSS Inc., Chicago, IL, USA). Out of a total number of 384 respondents, 87.8% of them knew about what ultrasound is used for. 87.5% scanned because a doctor or midwife requested for the scan whilst 53.9% scanned to check for fetal abnormalities. 98.4% indicated that ultrasound scanning has positive effects on pregnancy outcome. An expensive service was stated as a negative reason that would influence the decision to undergo the examination next time; nonetheless, 90.4% would recommend it to other women and suggested showing the fetus on monitor while scanning and providing accurate findings would make their future experiences better. The perception of the primigravidas was largely positive. Checking for fetal abnormalities was a major reason for the scans, although their knowledge in specific fetal abnormalities was low. They expected to know the fetal sex, but that was not a major reason for scanning. Showing them the monitor was the most frequent suggestion to make future experience better.

Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatching between the circulating viruses and vaccine strains, mutations arising due to egg adaptation, and potential contamination of the vaccine virus stock. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines are also less effective for certain populations, including the young, old, and immunocompromised. This warrants for diverse efficacious vaccine developmental approaches, involving both active and passive immunization. As opposed to active immunization platforms (requiring the use of whole or portions of pathogens as vaccines), the rapidly developing passive immunization involves administration of either pathogen-specific or broadly acting antibodies against a kind or class of pathogens as a prophylactic treatment to corresponding acute infection. Several antibodies with broadly acting capacities have been discovered that may serve as means to suppress influenza viral infection and allow the process of natural immunity to engage opsonized pathogens whilst boosting immune system by antibody-dependent mechanisms that bridge the innate and adaptive arms. By that, passive immunotherapeutics approach assumes a robust tool that could aid control of influenza viruses. In this review, we comment on some improvements in influenza management and promising vaccine development platforms, with emphasis on the capacity of passive immunotherapeutics especially when coupled with the use of antivirals in the management of influenza infection.

Background: We set out to estimate the community-level exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ghana. Methods: Phased seroprevalence studies of 2729 participants at selected locations across Ghana were conducted. Phase I (August 2020) sampled 1305 individuals at major markets/lorry stations, shopping malls, hospitals and research institutions involved in coronavirus disease 2019 (COVID-19) work. The study utilized a lateral flow rapid diagnostic test (RDT) which detected IgM and IgG antibodies against SARS-CoV-2 nucleocapsid protein. Results: During Phase I, 252/1305 (19%) tested positive for IgM or IgG or both. Exposure was significantly higher at markets/lorry stations (26.9%) compared to malls (9.4%), with 41–60-year group demonstrating highest seropositivity (27.2%). Exposure was higher in participants with no formal education (26.2%) than those with tertiary education (13.1%); and higher in informally employed workers (24.0%) than those in the formal sector (15.0%). Results from phases II and III, in October and December 2020 respectively, implied either reduced transmissions or loss of antibody expression in some participants. The Upper East region showed the lowest seropositivity (2%). Phase IV, in February 2021, showed doubled seropositivity in the upper income bracket (26.2%) since August 2020, reflective of Ghana’s second wave of symptomatic COVID-19 cases. This suggested that high transmission rates had overcome the initial socioeconomic stratification of exposure risk. Reflective of second wave hospitalisation trends, the 21-40 age group demonstrated modal seropositivity (24.9) in Phase IV whilst 40-60 years and 60+ previously demonstrated highest prevalence. Conclusions: Overall, the data indicates higher COVID-19 seroprevalence than officially acknowledged, likely implying a considerably lower-case fatality rate than the current national figure of 0.84%. The data also suggests that COVID-19 is predominantly asymptomatic COVID-19 in Ghana. The observed trends mimic clinical trends of infection and imply that the methodology used was appropriate.

Rodents serve as reservoirs and/or vectors for several human infections of high morbidity and mortality in the tropics. Population growth and demographic shifts over the years have increased contact with these mammals, thereby increasing opportunities for disease transmission. In Africa, the burden of rodent-borne diseases is not well described. To investigate human seroprevalence of selected rodent-borne pathogens, sera from 657 healthy adults in ten rural communities in Ghana were analyzed. An in-house enzyme-linked immunosorbent assay (ELISA), for immunoglobulin G (IgG) antibodies to Lassa virus was positive in 34 (5%) of the human samples. Using commercial kits, antibodies to hantavirus serotypes, Puumala and Dobrava, and Leptospira bacteria were detected in 11%, 12% and 21% of the human samples, respectively. Forty percent of residents in rural farming communities in Ghana have measurable antibodies to at least one of the rodent-borne pathogens tested, including antibodies to viral hemorrhagic fever viruses. The high seroprevalence found in rural Ghana to rodent-borne pathogens associated with both sporadic cases and larger disease outbreaks will help define disease threats and inform public health policy to reduce disease burden in underserved populations and deter larger outbreaks. The study was supported by the Global Emerging Infections Surveillance and Response (GEIS) of the U.S. Armed Forces Health Surveillance Center (AFHSC) (C0238_10_N3, C0435_11_N3, C0687_12_N3; C0410_11_RD, C0602_12_RD, and P0108_13_RD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We appreciate the invaluable support of the regional GHS directors and the local GHS nurses. The United States Army Research Institute of Infectious Diseases (USAMRIID) provided assistance in the LASV serology and its confirmatory assays.

Background: Acute respiratory tract infections of viral origin remain a leading cause of morbidity, mortality and economic loss regardless of age or gender. A small number of acute respiratory tract infection cases caused by enterovirus D68 (EV-D68) have been reported regularly to Centers for Disease Control and Prevention since 1987 by countries in North America, Europe and Asia. However, in 2014 and 2015, the number of reported confirmed EV-D68 infections was much greater than in previous years. The National Influenza Centre (NIC), Ghana carries out surveillance of respiratory infections, focusing on those caused by influenza virus; however, there is inadequate information on other viruses causing respiratory infections in Ghana, including EV-D68.Objectives: To investigate the association of EV-D68 with Severe Acute Respiratory Infections (SARI) and Influenza-Like Illness (ILI) in Ghana.Methods: This was a retrospective cross-sectional study which involved archived human respiratory specimens stored at –80 °C at the NIC from 2014 to 2015. Using a random sampling method, oropharyngeal and nasopharyngeal swabs from patients with SARI and ILI that were negative by real-time PCR for human influenza viruses were screened for EV-D68 using real-time reverse transcription-polymerase chain reaction (rRT-PCR).Results: Enterovirus D68 was detected in 4 (2.2%) out of 182 SARI samples tested. EV-D68 was detected in children younger than 5 years (4 – 100% of positives) and was not detected in children older than 5 years. Enterovirus D68 was detected more frequently in SARI cases (3%) than in ILI cases (1.2%).Conclusion: This study has shown for the first time the presence of EV-D68 in acute respiratory infections in Ghana. The results confirmed minimal EV-D68 circulation in the Ghanaian population.

Introduction The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas. Methods Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5–15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment. Results At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09–0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25–0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen. Discussion A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas., Author summary In this study, we provided a single round of total community treatment (TCT) with azithromycin to the population of a sub-district in Ghana (16,287 people) that is endemic for yaws and surrounded by other yaws-endemic communities to determine whether a sustained decrease in yaws prevalence could be achieved up to one year after the intervention. The efficacy of TCT was assessed by performing a clinical evaluation and serological testing of any yaws-like lesions found as well as serological screening of asymptomatic schoolchildren aged 5–15 years pre-TCT and at one year post-TCT. The results indicate that after a single round of high coverage TCT (89%) with azithromycin, the prevalence of active and latent yaws was significantly reduced. We also found that the use of a dual point-of-care immunoassay to detect non-treponemal and treponemal antibodies among school-going children is a practical alternative to laboratory-based serological testing to evaluate the effectiveness of yaws interventions in resource-poor settings.

The synergy between Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome is well established but not so in Buruli ulcer (BU). We screened confirmed BU cases for HIV infection and followed seven BU/HIV-coinfected patients. Management of BU/HIV was based on the World Health Organization guidelines and patient condition. The HIV positivity among BU patients (8.2%; 11/134) was higher compared with that of general patients attending the facility (4.8%; 718/14,863; P = 0.07) and that of pregnant women alone (2.5%; 279/11,125; P = 0.001). All seven BU/HIV-coinfected cases enrolled in the study presented with very large (category III) lesions with four having multiple lesions compared with 54.5% of category III lesions among HIV-negative BU patients. During the recommended BU treatment with streptomycin and rifampicin (SR) all patients developed immune infiltrates including CD4 T cells in their lesions. However, one patient who received antiretroviral therapy (ART) 1 week after beginning SR treatment developed four additional lesions during antibiotic treatment, while two out of the four who did not receive ART died. Further evidence is required to ascertain the most appropriate time to commence ART in relation to SR treatment to minimize paradoxical reactions.

Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and epidemiological surveillance is the foundation of the influenza vaccine virus selection and development process. Although national influenza surveillance and reporting capabilities are being strengthened and expanded, sustaining and building upon recent gains has become a major challenge. Strengthening the vaccine virus selection process additionally requires the continuation of initiatives to improve the timeliness and representativeness of influenza viruses shared by countries for detailed analysis by the WHO Global Influenza Surveillance and Response System (GISRS). Efforts are also continuing at the national, regional, and global levels to better understand the dynamics of influenza transmission in both temperate and tropical regions. Improved understanding of the degree of influenza seasonality in tropical countries of the world should allow for the strengthening of national vaccination policies and use of the most appropriate available vaccines. There remain a number of limitations and difficulties associated with the use of HAI assays for the antigenic characterization and selection of influenza vaccine viruses by WHOCCs. Current approaches to improving the situation include the more-optimal use of HAI and other assays; improved understanding of the data produced by neutralization assays; and increased standardization of serological testing methods. A number of new technologies and associated tools have the potential to revolutionize influenza surveillance and response activities. These include the increasingly routine use of whole genome next-generation sequencing and other high-throughput approaches. Such approaches could not only become key elements in outbreak investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more-equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes.

BACKGROUND: Coital dilution the reduction in the coital frequency per partner when an additional ongoing partner is added may reduce the transmission potential of partnership concurrency for HIV and other sexually transmitted infections. Empirical estimates of dilution especially dilution of sexual acts unprotected by condoms are needed to inform prevention research. METHODS: Sexually active adults in Accra Ghana were recruited in a multistage household probability sample. Degree (number of ongoing partners) total acts and unprotected acts were measured retrospectively for each month in the past year through an event history calendar. Random-effects negative binomial models estimated the association between degree and coital frequency. RESULTS: Compared with person-months with a single partner (monogamy) 2.06 times as many total acts and 1.94 times as many unprotected acts occurred in months with 2 partners. In months with 3 partners 2.90 times as many total acts and 2.39 times as many unprotected acts occurred compared with monogamous months. Total acts but not unprotected acts also declined with partnership duration. CONCLUSIONS: No dilution was observed for total acts with up to 3 concurrent partners but a small amount of dilution was observed for unprotected acts for months with multiple concurrencies. This suggests moderate selective condom use in months with multiple concurrencies. The implications of the observed dilution for future HIV transmission must be investigated with mathematical models.

Introduction : acute respiratory illness contributes significantly to hospitalizations. It causes morbidity and mortality in younger children throughout the world, especially in developing countries. Pneumonia is a lower respiratory infection which causes inflammation of the lung parenchyma and leads to reduced oxygenation, shortness of breath and death. It is caused by a number of infectious agents which includes; viruses, bacteria and fungi. In 2015, pneumonia accounted for about 15% of deaths among children below five years, killing 920,136 children globally. Greater Accra records an estimated 16300 cases of pneumonia annually of which 40% are children under five years. Viral etiological agents responsible for pneumonia are not investigated, with treatment mostly focused on antibiotics. Against this introduction, this study sought to determine the contribution of non-influenza respiratory viruses (Respiratory syncytial virus, human para-influenza and adenovirus) in children under five years hospitalized with pneumonia in the Greater Accra region. Methods : a laboratory-based cross sectional study was conducted where nasopharyngeal (NP) and oropharyngeal (OP) specimen were obtained from children under five years hospitalized with pneumonia in two three health facilities. Specimen were tested via reverse transcription polymerase chain reaction (RT PCR). Data were entered into a Microsoft visual basic interface linked to SQL database. Analysis was performed using STATA v13 and data presented in proportions and charts. Results : a total of 238 nasopharyngeal and oropharyngeal swabs were obtained children under five years hospitalized with pneumonia from February 2013 through to April 2017. The mean age of the participants was 14 months (+/-13months), ranging from 2 to 58months, with 51.3% (122) males being the majority. A total of 60 (25.2%) tested positive for at least one of respiratory syncytial virus, adenovirus, human para-influenza virus 1 and 3. Relatively 39 (16.4%) were positive for RSV, 11 (4.6%) for adenovirus, 8 (3.4%) HPIV-3 and 5 (2.1%) HPIV-1. Conclusion : the study demonstrated the presence of non-influenza respiratory virus namely; RSV, HPIV-1, HPIV-3 and Adenoviruses among children under five years hospitalized with pneumonia in Greater Accra. Hence, non-investigation of these viruses before treatment with antibiotics could lead to a gap in proper patient management.

A research collaboration project in Ghana has joined the MEXT program supported by the Japanese government since 2008. The Noguchi Memorial Institute for Medical Research (NMIMR), the University of Ghana, and Tokyo Medical and Dental University (TMDU) are core parties in the project, and researchers from other institutions also participate temporarily. Two TMDU faculty members are sent to Ghana to manage and implement joint research projects for virology and parasitology, which cover HIV, African trypanosomes, malaria parasites, and vector insects. Along with joint research, mutual exchange activities for young researchers and students have been promoted to develop human resources in tropical infectious disease research. Subjects in our project are all public health concerns both in Ghana and West-Africa and in other parts of the world. Our joint projects have strengthened and promoted global information networks on infectious diseases and the health and welfare of the residents of Ghana and Japan.

Our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in Africa. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009–2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. The potential for novel influenza virus lineages to evolve within Africa warrants intensified influenza surveillance in Africa and other understudied areas.

Militaries are especially susceptible to operationally important outbreaks of acute respiratory infections such as pandemic and seasonal influenza. In addition, militaries play important roles for State Parties working to meet International Health Regulations 2005, particularly in developing countries. In 2009, the U.S. Naval Medical Research Unit No. 3 joined with the Noguchi Memorial Institute for Medical Research and the armed forces of Ghana, Burkina Faso, and Côte d'Ivoire to create or improve influenza surveillance capacities within the militaries. This article describes the process undertaken to achieve this goal. In the Ghana Armed Forces, influenza surveillance for outpatients was instituted at seven medical stations throughout the country and for inpatients at the tertiary referral hospital in Accra. As a result, military sites now contribute around half of the influenza cases detected in Ghana and reported weekly to the World Health Organization. Samples were also collected by the militaries of Côte d'Ivoire and Burkina Faso, although political instability slowed progress. This effort is part of an ongoing strategy to build influenza surveillance capacity within West African militaries in support of military services, global outbreak investigations, International Health Regulations-2005, and the development of country-specific pandemic preparedness plans.

Background Influenza vaccination is recommended by the World Health Organization for high risk groups, yet few data exist on influenza disease burden in West Africa. Methods We estimated medically attended influenza-associated illness rates among residents of Shai-Osudoku and Ningo Pram-Pram Districts (SONPD), Ghana. From May 2013 to April 2015, we conducted prospective surveillance for severe acute respiratory illness (SARI) and influenza-like illness (ILI) in 17 health facilities. In 2015, we conducted a retrospective assessment at an additional 18 health facilities to capture all SONPD SARI and ILI patients during the study period. We applied positivity rates to those not tested to estimate total influenza cases. Results Of 612 SARI patients tested, 58 (9%) were positive for influenza. The estimated incidence of influenza-associated SARI was 30 per 100,000 persons (95% CI: 13-84). Children aged 0 to 4 years had the highest influenza-associated SARI incidence (135 per 100,000 persons, 95% CI: 120-152) and adults aged 25 to 44 years had the lowest (3 per 100,000 persons, 95% CI: 1-7) (p

Background Influenza epidemiology in Africa is generally not well understood. Using syndrome definitions to screen patients for laboratory confirmation of infection is an established means to effectively conduct influenza surveillance. Methods To compare influenza-related epidemiologic data, from October 2010 through March 2013, we enrolled hospitalized severe acute respiratory infection (SARI; fever with respiratory symptoms) and acute febrile illness (AFI; fever without respiratory or other localizing symptoms) patients from three referral hospitals in Ghana. Demographic and epidemiologic data were obtained from enrolled patients after which nasopharyngeal and oropharyngeal swabs were collected, and processed by molecular methods for the presence of influenza viruses. Results Of 730 SARI patients, 59 (8%) were influenza positive; of 543 AFI patients, 34 (6%) were positive for influenza. Both SARI and AFI surveillance yielded influenza A(H3N2) (3% versus 1%), A(H1N1)pdm09 (2% versus 1%), and influenza B (3% versus 4%) in similar proportions. Data from both syndromes show year-round influenza transmission but with increased caseloads associated with the rainy seasons. Conclusions As an appreciable percentage of influenza cases (37%) presented without defined respiratory symptoms, and thus met the AFI but not the SARI definition, it is important to consider broader screening criteria (i.e., AFI) to identify all laboratory-confirmed influenza. The identified influenza transmission seasonality has important implications for the timing of related public health interventions.

Background The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. Methods and Findings We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (, The substantial global burden of influenza infections in children is revealed by Lafond and colleagues. Children in developing countries are 3 times more likely to be hospitalised and treatments vary. This study highlights the need for vaccination programs in the young., Editors' Summary Background Acute lower respiratory infections—bacterial and viral infections of the lungs and airways (the tubes that take oxygen-rich air to the lungs)—are major causes of illness and death in children worldwide. Pneumonia (infection of the lungs) alone is responsible for 15% of deaths among children under five years old and kills nearly one million young children every year. Globally, infections with respiratory syncytial virus and with Streptococcus pneumoniae are associated with about 25% and 18.3%, respectively, of all episodes of severe respiratory infection in young children. Another infectious organism that contributes to the global burden of respiratory disease among children is the influenza virus. Every year, millions of people become infected with this virus, which infects the airways and causes symptoms that include a high temperature, tiredness and weakness, general aches and pains, and a dry chesty cough. Most infected individuals recover quickly, but seasonal influenza outbreaks (epidemics) nevertheless kill about half a million people annually, with the highest burden of severe disease being experienced by elderly people and by children under five years old. Why Was This Study Done? Annual immunization (vaccination) can reduce an individual’s risk of catching influenza, but before a country implements this preventative measure, policymakers need reliable estimates of the burden of influenza in their country. Although such estimates have been calculated for resource-rich countries with temperate climates, where influenza largely occurs in the winter, few estimates of influenza burden are available for resource-limited countries, which has hampered informed consideration of vaccination for influenza prevention in many settings. Recently, however, there has been a global expansion of systematic surveillance and testing for influenza virus among patients admitted to hospital for severe respiratory infection. Here, the researchers use this expanded surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide between 1982 and 2012. Specifically, they undertake a systematic review to identify published research articles on influenza-associated respiratory disease in hospitalized children, and, by aggregating the data from these articles with data collected by hospital-based influenza surveillance, they calculate a pooled estimate of the proportion of children hospitalized with respiratory disease who are positive for influenza. What Did the Researchers Do and Find? Using predefined search criteria, the researchers identified 108 published research articles that provided information on influenza-associated respiratory illness among hospitalized children. In addition, the Global Respiratory Hospitalizations–Influenza Proportion Positive (GRIPP) working group provided 37 hospital-based influenza surveillance datasets. By aggregating the data from these sources using a statistical approach called meta-analysis, the researchers calculated that, overall, influenza was associated with 9.5% of hospitalizations for severe respiratory infection among children under 18 years old worldwide, ranging from 4.8% among children under six months old to 16.4% among children aged 5–17 years. The researchers also calculated that, on average over the study period, influenza resulted in about 374,000 hospitalizations annually among children under one year old (including 228,000 hospitalizations among children less than six months old) and nearly one million hospitalizations annually among children under five years old. Finally, the researchers calculated that influenza-associated hospitalization rates among children under five years old over the study period were more than three times higher in resource-limited countries than in industrialized countries (150 and 48 hospitalizations, respectively, per 100,000 children per year). What Do These Findings Mean? Differences in hospitalization practices, in applications of case definitions, and in influenza testing protocols between settings may affect the accuracy of these findings. Specifically, the approach taken by the researchers may mean that their estimate of the total burden of severe respiratory disease due to influenza is an underestimate of the true situation. Even so, these findings suggest that influenza is an important contributor to hospitalizations for severe respiratory illness among children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could, therefore, reduce the contribution that influenza makes to hospitalizations for respiratory infections among children. Importantly, the estimates of the burden of influenza provided by these findings can now be used by countries considering influenza vaccination programs for children and/or pregnant women to help them investigate the possible health and cost implications of such programs and should also stimulate further research into the development of effective influenza vaccines for young children. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001977. The UK National Health Service Choices website provides information about respiratory infections, seasonal influenza, influenza vaccination, and influenza vaccination in children The World Health Organization provides information on seasonal influenza (in several languages) and on influenza vaccines The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects seasonal influenza, including information about vaccination, and about children, influenza, and vaccination; its website contains a short video about personal experiences of influenza Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination MedlinePlus has links to further information about influenza and about vaccination (in English and Spanish)

Children of HIV-infected mothers experience poor growth, but not much is understood about the extent to which such children are affected. The Research to Improve Infant Nutrition and Growth (RIING) Project used a longitudinal study design to investigate the association between maternal HIV status and growth among Ghanaian infants in the first year of life. Pregnant women in their third trimester were enrolled into three groups: HIV-negative (HIV-N, n = 185), HIV-positive (HIV-P, n = 190) and HIV-unknown (HIV-U, n = 177). Socioeco- nomic data were collected. Infant weight and length were measured at birth and every month until 12 months of age. Weight-for-age (WAZ), weight-for-length (WLZ) and length-for-age (LAZ) z-scores were compared using analysis of covariance. Infant HIV status was not known as most mothers declined to test their children's status at 12 months. Adjusted mean WAZ and LAZ at birth were significantly higher for infants of HIV-N compared with infants of HIV-P mothers. The prevalence of underweight at 12 months in the HIV-N, HIV-P and HIV-U were 6.6%, 27.5% and 9.9% (P < 0.05), respectively. By 12 months, the prevalence of stunting was significantly different (HIV-N = 6.0%, HIV-P = 26.5% and HIV-U = 5.0%, P < 0.05). The adjusted mean SE LAZ (0.57 0.11 vs. -0.95 0.12; P < 0.005) was significantly greater for infants of HIV-N mothers than infants of HIV-P mothers. Maternal HIV is associated with reduce infant growth in weight and length throughout the first year of life. Children of HIV-P mothers living in socioeconomically deprived communities need special support to mitigate any negative effect on growth performance.

Executive summary • For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses.• The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy‐making community of the complexity of influenza vaccine virus selection.• The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs).• Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non‐antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints.• Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines.• Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas.• Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays – for example based upon advanced recombinant DNA and protein technologies – may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development.• Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large‐scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity.• Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well‐characterized banks of age‐stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination.• Advances in high‐throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X‐ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity.• Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non‐mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses.• The adoption of alternative vaccine technologies – such as live‐attenuated, quadrivalent or non‐HA‐based vaccines – has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high‐growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply.• The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.

Background Poor retention can reduce study power and thwart randomization, possibly resulting in biased estimates of effect. Some HIV prevention trials conducted in developing countries have been challenged by high loss to follow-up. Identifying factors associated with non-retention could lead to recruitment of women more likely to remain in the trial, potentially yielding greater efficiency and validity. Methods We summarized retention rates and, using Cox regression, evaluated factors associated with non-retention in four trials of two candidate vaginal microbicides (1% C31G or SAVVY® and 6% cellulose sulfate or CS) conducted in multiple sub-Saharan African countries. We defined retention as completion of the trial, including those with an HIV outcome. Non-retention comprised participants randomized to a study arm who were either lost to follow-up or discontinued prior to infection with HIV. Results 7367 women were enrolled and randomized in the four trials; 7086 are included in this analysis. 1514 (21.4%) participants were either lost to follow-up or had early discontinuation. In the final Cox model, the following baseline factors were associated with non-retention: younger age (hazard ratio [HR] = 0.95); less education (HR = 0.97); condom use at last sex (HR = 1.18); larger number of sex acts in a typical week (HR = 1.01); and baseline candidiasis or bacterial vaginosis (HR = 1.12). Conclusions Younger and less educated women were more difficult to retain in these microbicide trials. But these same traits may be associated with higher HIV infection rates. Enhanced retention methods focused on those at highest risk of non-retention and possibly infection will optimize study efficiency and validity.

Background: Recent reports have shown an expansion of Lassa virus from the area where it was first isolated in Nigeria to other areas of West Africa. Two Ghanaian soldiers on a United Nations peacekeeping mission in Liberia were taken ill with viral haemorrhagic fever syndrome following the death of a sick colleague and were referred to a military hospital in Accra, Ghana, in May 2013. Blood samples from the soldiers and five asymptomatic close contacts were subjected to laboratory investigations.Objective: We report the results of these investigations to highlight the importance of molecular diagnostic applications and the need for heightened awareness about Lassa fever in West Africa.Methods: We used molecular assays on sera from the two patients to identify the causativeorganism. Upon detection of positive signals for Lassa virus ribonucleic material by two differentpolymerase chain reaction assays, sequencing and phylogenetic analyses were performed.Results: The presence of Lassa virus in the soldiers’ blood samples was shown by L-gene segment homology to be the Macenta and las803792 strains previously isolated in Liberia, with close relationships then confirmed by phylogenetic tree construction. The five asymptomatic close contacts were negative for Lassa virus.Conclusions: The Lassa virus strains identified in the two Ghanaian soldiers had molecular epidemiological links to strains from Liberia. Lassa virus was probably responsible for the outbreak of viral haemorrhagic fever in the military camp. These data confirm Lassa fever endemicity in West Africa.

Vitamin A supplementation reduces child mortality and severe morbidity in less developed countries, and the Expanded Program on Immunization (EPI) offers an ideal opportunity to deliver supplements in developing countries. High-dose vitamin A supplementation has been shown to have no effect on the immunogenicity of oral polio vaccine, tetanus toxoid, pertussis, or on measles vaccine given at 9 mo, but a negative effect on measles vaccine administered at 6 mo and a potentiating effect on diphtheria vaccine. Its effect on the antibody response to hepatitis B and Haemophilus influenzae type b antigens has not yet been established. To assess these effects, the present trial was carried out in the Offinso district of Ghana; 1077 infants were enrolled shortly after birth and randomized either to receive or not to receive 15 mg retinol equivalent with vitamin A together with the pentavalent "diphtheria-polio-tetanus-Haemophilus influenzae b-hepatitis B" vaccine at 6, 10, and 14 wk of age. All mothers received a postpartum supplement of 120 mg retinol equivalent vitamin A as per national policy. Blood samples were taken from infants at 6 and 18 wk of age. The results are based on 888 infants (82.4%) who completed the trial. The vitamin A supplementation did not affect the immune response to Haemophilus influenzae type b, but there was a significant improvement in the immune response to hepatitis B vaccine (93.9 vs. 90.2%, P = 0.04). However, given the high percentage of infants with seroprotection in the control group, it is doubtful that inclusion of vitamin A in the EPI would be justified on these grounds alone.

The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF β 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n=14) and progressive infection (n=47), plasma levels of active TGF β 1, INF-γ, TNF-α, IL-10, IL-1β, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n=12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF β 1 and IL-10 were significantly decreased while IL-1β, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF β 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1β, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these findings may have implications for systemic cytokine-based therapies in HIV-1 infection.

Background Lassa fever is a potentially fatal acute viral illness caused by Lassa virus which is carried by rodents and is endemic in some West African countries. Importation of emerging infections such as Lassa fever, Ebola Virus Disease and other viral hemorrhagic fevers into non endemic regions is a growing threat particularly as international travel and commitments in resolving conflicts in endemic countries in the West Africa sub-region continue. Case presentation We report the first two recorded imported cases of Lassa fever among Ghanaian Peace keepers in rural Liberia, who became ill while on Peace keeping mission. They were subsequently evacuated to the UN level IV hospital in Accra, where their illnesses were laboratory confirmed. One of the patients recovered with ribavirin treatment and supportive therapy. No secondary clinical cases occurred in Ghana. Conclusions Healthcare providers at all levels of care should thus have a high index of suspicion for these infectious diseases and adopt standard infection control measures when treating patients in endemic regions or returning travelers from an endemic region with a febrile illness even of a known etiology.