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As of 03 January 2021, the WHO African region is the least affected by the coronavirus disease-2019 (COVID-19) pandemic, accounting for only 2.4% of cases and deaths reported globally. However, concerns abound about whether the number of cases and deaths reported from the region reflect the true burden of the disease and how the monitoring of the pandemic trajectory can inform response measures. We retrospectively estimated four key epidemiological parameters (the total number of cases, the number of missed cases, the detection rate and the cumulative incidence) using the COVID-19 prevalence calculator tool developed by Resolve to Save Lives. We used cumulative cases and deaths reported during the period 25 February to 31 December 2020 for each WHO Member State in the region as well as population data to estimate the four parameters of interest. The estimated number of confirmed cases in 42 countries out of 47 of the WHO African region included in this study was 13 947 631 [95% confidence interval (CI): 13 334 620–14 635 502] against 1 889 512 cases reported, representing 13.5% of overall detection rate (range: 4.2% in Chad, 43.9% in Guinea). The cumulative incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was estimated at 1.38% (95% CI: 1.31%–1.44%), with South Africa the highest [14.5% (95% CI: 13.9%–15.2%)] and Mauritius [0.1% (95% CI: 0.099%–0.11%)] the lowest. The low detection rate found in most countries of the WHO African region suggests the need to strengthen SARS-CoV-2 testing capacities and adjusting testing strategies.

Background Inadequate access to quality health care services due to weak health systems and recurrent public health emergencies are impediments to the attainment of Universal Health Coverage and health security in Africa. To discuss these challenges and deliberate on plausible solutions, the World Health Organization Regional Office for Africa, in collaboration with the Government of Cabo Verde, convened the second Africa Health Forum in Praia, Cabo Verde on 26–28 March 2019, under the theme Achieving Universal Health Coverage and Health Security: The Africa We Want to See. Methods The Forum was conducted through technical sessions consisting of high-level, moderated panel discussions on specific themes, some of them preceded by keynote addresses. There were booth exhibitions by Member States, World Health Organization and other organizations to facilitate information exchanges. A Communiqué highlighting the recommendations of the Forum was issued during the closing ceremony. More than 750 participants attended. Relevant information from the report of the Forum and notes by the authors were extracted and synthesized into these proceedings. Conclusions The Forum participants agreed that the role of community engagement and participation in the attainment of Universal Health Coverage, health security and ultimately the Sustainable Development Goals cannot be overemphasized. The public sector of Africa alone cannot achieve these three interrelated goals; other partners, such as the private sector, must be engaged. Technological innovations will be a key driver of the attainment of these goals; hence, there is need to harness the comparative advantages that they offer. Attainment of the three goals is also intertwined – achieving one paves the way for achieving the others. Thus, there is need for integrated public health approaches in the planning and implementation of interventions aimed at achieving them. Recommendations To ensure that the recommendations of this Forum are translated into concrete actions in a sustainable manner, we call on African Ministers of Health to ensure their integration into national health sector policies and strategic documents and to provide the necessary leadership required for their implementation. We also call on partners to mainstream these recommendations into their ongoing support to World Health Organization African Member States.

The Corona Virus Disease 2019 (COVID-19) pandemic has rapidly spread in Africa, with a total of 474,592 confirmed cases by 11thJuly 2020. Consequently, all policy makers and health workers urgently need to be trained and to access the most credible information to contain and mitigate its impact. While the need for rapid training and information dissemination has increased, most of Africa is implementing public health social and physical distancing measures. Responding to this context requires broad partnerships and innovative virtual approaches to disseminate new insights, share best practices, and create networked communities of practice for all teach, and all learn. The World Health Organization (WHO)-Africa region, in collaboration with the Extension for Community Health Outcome (ECHO) Institute at the University of New Mexico Health Sciences Center (UNM HSC), the West Africa college of nurses and the East Central and Southern Africa college of physicians, private professional associations, academia and other partners has embarked on a virtual training programme to support the containment of COVID-19. Between 1stApril 2020 and 10thJuly 2020, about 7,500 diverse health professionals from 172 locations in 58 countries were trained in 15 sessions. Participants were from diverse institutions including: central ministries of health, WHO country offices, provincial and district hospitals and private medical practitioners. A range of critical COVID-19 preparedness and response interventions have been reviewed and discussed. There is a high demand for credible information from credible sources about COVID-19. To mitigate the“epidemic of misinformation”partnerships for virtual trainings and information dissemination leveraging existing learning platforms and networks across Africa will augment preparedness and response to COVID-19.

BACKGROUND The ongoing COVID-19 pandemic in Africa is an urgent public health crisis. Estimated models projected over 150,000 deaths and 4,600,000 hospitalizations in the first year of the disease in the absence of adequate interventions. Therefore, electronic contact tracing and surveillance have critical roles in decreasing COVID-19 transmission; yet, if not conducted properly, these methods can rapidly become a bottleneck for synchronized data collection, case detection, and case management. While the continent is currently reporting relatively low COVID-19 cases, digitized contact tracing mechanisms and surveillance reporting are necessary for standardizing real-time reporting of new chains of infection in order to quickly reverse growing trends and halt the pandemic. OBJECTIVE This paper aims to describe a COVID-19 contact tracing smartphone app that includes health facility surveillance with a real-time visualization platform. The app was developed by the AFRO (African Regional Office) GIS (geographic information system) Center, in collaboration with the World Health Organization (WHO) emergency preparedness and response team. The app was developed through the expertise and experience gained from numerous digital apps that had been developed for polio surveillance and immunization via the WHO’s polio program in the African region. METHODS We repurposed the GIS infrastructures of the polio program and the database structure that relies on mobile data collection that is built on the Open Data Kit. We harnessed the technology for visualization of real-time COVID-19 data using dynamic dashboards built on Power BI, ArcGIS Online, and Tableau. The contact tracing app was developed with the pragmatic considerations of COVID-19 peculiarities. The app underwent testing by field surveillance colleagues to meet the requirements of linking contacts to cases and monitoring chains of transmission. The health facility surveillance app was developed from the knowledge and assessment of models of surveillance at the health facility level for other diseases of public health importance. The Integrated Supportive Supervision app was added as an appendage to the pre-existing paper-based surveillance form. These two mobile apps collected information on cases and contact tracing, alongside alert information on COVID-19 reports at the health facility level; the information was linked to visualization platforms in order to enable actionable insights. RESULTS The contact tracing app and platform were piloted between April and June 2020; they were then put to use in Zimbabwe, Benin, Cameroon, Uganda, Nigeria, and South Sudan, and their use has generated some palpable successes with respect to COVID-19 surveillance. However, the COVID-19 health facility–based surveillance app has been used more extensively, as it has been used in 27 countries in the region. CONCLUSIONS In light of the above information, this paper was written to give an overview of the app and visualization platform development, app and platform deployment, ease of replicability, and preliminary outcome evaluation of their use in the field. From a regional perspective, integration of contact tracing and surveillance data into one platform provides the AFRO with a more accurate method of monitoring countries’ efforts in their response to COVID-19, while guiding public health decisions and the assessment of risk of COVID-19.

The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been unprecedented in its speed and effects. Interruption of its transmission to prevent widespread community transmission is critical because its effects go beyond the number of COVID-19 cases and deaths and affect the health system capacity to provide other essential services. Highlighting the implications of such a situation, the predictions presented here are derived using a Markov chain model, with the transition states and country specific probabilities derived based on currently available knowledge. A risk of exposure, and vulnerability index are used to make the probabilities country specific. The results predict a high risk of exposure in states of small size, together with Algeria, South Africa and Cameroon. Nigeria will have the largest number of infections, followed by Algeria and South Africa. Mauritania would have the fewest cases, followed by Seychelles and Eritrea. Per capita, Mauritius, Seychelles and Equatorial Guinea would have the highest proportion of their population affected, while Niger, Mauritania and Chad would have the lowest. Of the World Health Organization's 1 billion population in Africa, 22% (16%–26%) will be infected in the first year, with 37 (29 – 44) million symptomatic cases and 150 078 (82 735–189 579) deaths. There will be an estimated 4.6 (3.6–5.5) million COVID-19 hospitalisations, of which 139 521 (81 876–167 044) would be severe cases requiring oxygen, and 89 043 (52 253–106 599) critical cases requiring breathing support. The needed mitigation measures would significantly strain health system capacities, particularly for secondary and tertiary services, while many cases may pass undetected in primary care facilities due to weak diagnostic capacity and non-specific symptoms. The effect of avoiding widespread and sustained community transmission of SARS-CoV-2 is significant, and most likely outweighs any costs of preventing such a scenario. Effective containment measures should be promoted in all countries to best manage the COVID-19 pandemic.

Concerns have been expressed about the view point of WHO AFRO concerning research for health in the African Region. WHO AFRO considers research a critical component in the improvement of health in the Africa region. Ensuring the effectiveness of our strategies, policies and programmes requires evidence. In the context of the ongoing COVID-19 outbreak, WHO research interests cover key areas of the response. The WHO AFRO consider research as critical in our efforts at protecting people against health emergencies and pandemics like the COVID-19 and ensuring universal access to proven interventions. In view of this, the WHO has taken steps to strengthen capacity for research in the region. The results of these efforts may take time to manifest but will surely do as we persist in our drive, with support from our partners.

Background: The spread of SARS-CoV-2 has been unprecedented in its speed and effects, within and beyond health It is driven by unique, country-specific socio-e

Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod-borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.

Background Rift Valley fever (RVF) is endemic to the tropical regions of eastern and southern Africa. The seroprevalence of RVF was investigated among the human population in Borno State, Nigeria to determine the occurrence of the disease in the study area in comparison with that of Lassa fever and Crimean-Congo Hemorrhagic fever. Methods Recombinant nucleoprotein (rNP)-based IgG-ELISAs for the detection of serum antibodies against RVF virus (RVFV), Lassa fever virus (LASV), and Crimean-Congo hemorrhagic fever virus (CCHFV) were used to test human sera in Borno State, Nigeria. The presence of neutralizing antibody against the RVFV-glycoprotein-bearing vesicular stomatitis virus pseudotype (RVFVpv) was also determined in the human sera. Results Of the 297 serum samples tested, 42 (14.1%) were positive for the presence of RVFV-IgG and 22 (7.4%) and 7 (2.4%) of the serum samples were positive for antibodies against LASV and CCHFV, respectively. There was a positive correlation between the titers of neutralizing antibodies obtained using RVFVpv and those obtained using the conventional neutralization assay with the attenuated RVFV-MP12 strain. Conclusions The seroprevalence of RVF was significantly higher than that of LASV and CCHF in Borno State, Nigeria. The RVFVpv-based neutralization assay developed in this study has the potential to replace the traditional assays based on live viruses for the diagnosis and seroepidemiological studies of RVF.

BACKGROUND\ud \ud On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern."\ud \ud METHODS\ud \ud By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa - Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14.\ud \ud RESULTS\ud \ud The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R-0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total.\ud \ud CONCLUSIONS\ud \ud These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

Of the 46 countries in the World Health Organization (WHO) African region (AFRO), 43 are implementing Integrated Disease Surveillance and Response (IDSR) guidelines to improve their abilities to detect, confirm, and respond to high-priority communicable and noncommunicable diseases. IDSR provides a framework for strengthening the surveillance, response, and laboratory core capacities required by the revised International Health Regulations [IHR (2005)]. In turn, IHR obligations can serve as a driving force to sustain national commitments to IDSR strategies. The ability to report potential public health events of international concern according to IHR (2005) relies on early warning systems founded in national surveillance capacities. Public health events reported through IDSR to the WHO Emergency Management System in Africa illustrate the growing capacities in African countries to detect, assess, and report infectious and noninfectious threats to public health. The IHR (2005) provide an opportunity to continue strengthening national IDSR systems so they can characterize outbreaks and respond to public health events in the region.

Polymerase chain reaction (PCR) using Pneumocystis carinii-specific primers pAZ 102-H(5'-GTGTACGTTGCAAAGTACTC-3') and pAZ 102-E(5'-GATGGCTGTTTCCAAGCCCA-3') was performed on oropharyngeal washes obtained at autopsy from 22 AIDS children with histologically confirmed P. carinii pneumonia (PCP), and 48 control AIDS children who died from other infections. Fifteen of 22 (68%) PCP samples and none of 48 (0%) control samples had detectable P. carinii DNA (sensitivity 68%; specificity 100%; positive predictive value 100%; negative predictive value 87%). This method requires further validation in clinical practice.

Summary Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod‐borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.

Background: The increase in disease burden has continued to weigh upon health systems in Africa. The role of the laboratory has become increasingly critical in the improvement of health for diagnosis, management and treatment of diseases. In response, the World Health Organization Regional Office for Africa (WHO AFRO) and its partners created the WHO AFRO Stepwise Laboratory (Quality) Improvement Process Towards Accreditation (SLIPTA) program.SLIPTA implementation process: WHO AFRO defined a governance structure with roles and responsibilities for six main stakeholders. Laboratories were evaluated by auditors trained and certified by the African Society for Laboratory Medicine. Laboratory performance was measured using the WHO AFRO SLIPTA scoring checklist and recognition certificates rated with 1–5 stars were issued.Preliminary results: By March 2015, 27 of the 47 (57%) WHO AFRO member states had appointed a SLIPTA focal point and 14 Ministers of Health had endorsed SLIPTA as the desired programme for continuous quality improvement. Ninety-eight auditors from 17 African countries, competent in the Portuguese (3), French (12) and English (83) languages, were trained and certified. The mean score for the 159 laboratories audited between May 2013 and March 2015 was 69% (median 70%; SD 11.5; interquartile range 62–77). Of these audited laboratories, 70% achieved 55% compliance or higher (2 or more stars) and 1% scored at least 95% (5 stars). The lowest scoring sections of the WHO AFRO SLIPTA checklist were sections 6 (Internal Audit) and 10 (Corrective Action), which both had mean scores below 50%.Conclusion: The WHO AFRO SLIPTA is a process that countries with limited resources can adopt for effective implementation of quality management systems. Political commitment, ownership and investment in continuous quality improvement are integral components of the process.

New and re-emerging pathogens with epidemic potential have threatened global health security for the past century.1 As with the recent Ebola Virus Disease (EVD) epidemic, the Zika Virus (ZIKV) outbreak has yet again surprised and overwhelmed the international health community with an unexpected event for which it might have been better prepared.

PROBLEM: Little is known about the burden of influenza in sub-Saharan Africa. Routine influenza surveillance is key to getting a better understanding of the impact of acute respiratory infections on sub-Saharan African populations. APPROACH: A project known as Strengthening Influenza Sentinel Surveillance in Africa (SISA) was launched in Angola, Cameroon, Ghana, Nigeria, Rwanda, Senegal, Sierra Leone and Zambia to help improve influenza sentinel surveillance, including both epidemiological and virological data collection, and to develop routine national, regional and international reporting mechanisms. These countries received technical support through remote supervision and onsite visits. Consultants worked closely with health ministries, the World Health Organization, national influenza laboratories and other stakeholders involved in influenza surveillance LOCAL SETTING: Influenza surveillance systems in the target countries were in different stages of development when SISA was launched. Senegal, for instance, had conducted virological surveillance for years, whereas Sierra Leone had no surveillance activity at all. RELEVANT CHANGES: Working documents such as national surveillance protocols and procedures were developed or updated and training for sentinel site staff and data managers was organized. LESSONS LEARNT: Targeted support to countries can help them strengthen national influenza surveillance, but long-term sustainability can only be achieved with external funding and strong national government leadership.

Human herpesvirus 6, HHV-6, commonly infects children, causing febrile illness and can cause more severe pathology, especially in an immune compromised setting. There are virulence distinctions between variants HHV-6A and B, with evidence for increased severity and neurotropism for HHV-6A. While HHV-6B is the predominant infant infection in USA, Europe and Japan, HHV-6A appears rare. Here HHV-6 prevalence, loads and variant genotypes, in asymptomatic compared to symptomatic infants were investigated from an African region with endemic HIV-1/AIDS. DNA was extracted from blood or sera from asymptomatic infants at 6 and 18 months age in a population-based micronutrient study, and from symptomatic infants hospitalised for febrile disease. DNA was screened by qualitative and quantitative real-time PCR, then genotyped by sequencing at variable loci, U46 (gN) and U47 (gO). HIV-1 serostatus of infants and mothers were also determined. HHV-6 DNA prevalence rose from 15% to 22% (80/371) by 18 months. At 6 months, infants born to HIV-1 positive mothers had lower HHV-6 prevalence (11%, 6/53), but higher HCMV prevalence (25%, 17/67). HHV-6 positive febrile hospitalized infants had higher HIV-1, 57% (4/7), compared to asymptomatic infants, 3% (2/74). HHV-6A was detected exclusively in 86% (48/56) of asymptomatic HHV-6 positive samples genotyped. Co-infections with both strain variants were linked with higher viral loads and found in 13% (7/56) asymptomatic infants and 43% (3/7) HIV-1 positive febrile infants. Overall, the results show HHV-6A as the predominant variant significantly associated with viremic infant-infections in this African population, distinct from other global cohorts, suggesting emergent infections elsewhere.

Human cytomegalovirus, HCMV, was analysed using real-time quantitative PCR in symptomatic or asymptomatic pediatric cohorts from HIV-1 infected, exposed (HIV-1+ mothers), or uninfected groups in Zambia, an HIV-1/AIDS endemic region of Africa. HCMV infections were identified in 94% samples from HIV-1+ respiratory pediatric mortalities, 50% with high DNA loads of 103–108 copies/106 cells. In comparison, HCMV viremia with high DNA loads, indicative of acute infections, were in 10% hospitalised febrile infants, with 50% HIV-1+. Whereas high sera loads were in 1% of asymptomatic infants, with 2% HIV-1+, and higher levels in both HIV-1 infected or exposed, but negative infants. All 8 linked-hypervariable glycoprotein gN–gO genotypes were shown, including identification of a new gN4d group with gO5 linkage (previously only Merlin reference strain), and samples with multiple infections. Overall, this shows global genotypes in Africa (unlike some herpesviruses) and acute pediatric HCMV infections in both HIV-1+ plus exposed, but uninfected infants, an emerging group.

Background: Anecdotal evidence suggests that much of the continuing infection of health care workers (HCWs) with Ebola virus during the current outbreak in Sierra Leone has occurred in settings other than Ebola isolation units, and it is likely that some proportion of acquisition by HCWs occurs outside the workplace. There is a critical need to define more precisely the pathways of Ebola infection among HCWs, to optimise measures for reducing risk during current and future outbreaks. Methods: We conducted a retrospective descriptive study of Ebola acquisition among health workers in Sierra Leone during May-December 2014. The data used were obtained mainly from the national Ebola database, a cross-sectional survey conducted through administration of a structured questionnaire to infected HCWs, and key informant interviews of select health stakeholders. Results: A total of 293 HCWs comprising 277 (95 %) confirmed, 6 (2 %) probable, and 10 (3 %) suspected cases of infection with Ebola virus were enrolled in the study from nine districts of the country. Over half of infected HCWs (153) were nurses; others included laboratory staff (19, 6.5 %), doctors (9, 3.1 %), cleaners and porters (9, 3.1 %), Community Health Officers (8, 2.7 %), and pharmacists (2, 0.7 %). HCW infections were mainly reported from the Western Area (24.9 %), Kailahun (18.4 %), Kenema (17.7 %), and Bombali (13.3 %) districts. Almost half of the infected HCWs (120, 47.4 %) believed that their exposure occurred in a hospital setting. Others believed that they were exposed in the home (48, 19 %), at health centres (45, 17.8 %), or at other types of health facilities (13, 5.1 %). Only 27 (10.7 %) of all HCW infections were associated with Ebola virus disease (EVD) isolation units. Over half (60 %, 150) of infected HCWs said they had been trained in infection prevention and control prior to their infection, whereas 34 % (85) reported that they had not been so trained. Conclusions: This study demonstrated the perception that most HCW infections are associated with general health care and home settings and not with dedicated EVD settings, which should provide substantial reassurance to HCWs that measures in place at dedicated EVD facilities generally provide substantial protection when fully adhered to.

Subclinical mastitis, defined as raised milk sodium/potassium (Na/K) ratio, is associated with poor infant growth and, among HIV-infected women, with increased milk HIV viral load. We conducted a longitudinal cohort study in Lusaka, Zambia, in order to investigate the relative importance of several potential causes of subclinical mastitis: maternal infection, micronutrient deficiencies and poor lactation practice. Women (198 HIV-infected, 189 HIV-uninfected) were recruited at 34 weeks' gestation and followed up to 16 weeks postpartum for collection of information on their health, their infant's health, infant growth and infant feeding practices. Milk samples were collected from each breast at 11 postpartum visits and blood at recruitment and 6 weeks postpartum. The geometric mean milk Na/K ratio and the proportion of women with Na/K ratio > 1.0 in one or both breasts were significantly higher among HIV-infected than among uninfected women. Other factors associated with the higher mean Na/K ratio in univariable analyses were primiparity, high maternal alpha(1)-acid glycoprotein (AGP) at 6 weeks, maternal overall morbidity and specific breast symptoms, preterm delivery, low infant weight or length, infant thrush and non-exclusive breast feeding. In multivariable analyses, primiparity, preterm delivery, breast symptoms, HIV status and raised AGP were associated with the raised Na/K ratio. Thus the main factors associated with subclinical mastitis that are amenable to intervention are poor maternal overall health and breast health. The impact of improved postpartum health care, especially management of maternal infections and especially in primiparous women, on the prevalence of subclinical mastitis and its consequences requires investigation.

Human immunodeficiency virus type-1 (HIV-1) is a leading cause of mortality and morbidity in the world, with almost 46 million people infected globally. HIV-1 subtype C accounts for 55% of these infections. In Zambia, the majority of HIV-1 infections are subtype C. However, to its north most countries have non-subtype C as the most predominant HIV-1 subtype while to its south most of them are predominantly subtype C. The aim of this study was to determine the subtype distribution and to analyze the long terminal repeat (LTR) region of HIV-1 isolates from the northern part of Zambia. We amplified as well as directly sequenced the LTR, gag, and env regions of 78 HIV-1 peripheral blood samples from adult Zambians. Our results show 95% (74/78) of our isolates were HIV-1 subtype C. Furthermore, of the subtype C samples analyzed across the LTR, 61% (25/41) carried 3 NF-kappaB signature binding site sequences.

M. tuberculosis strains were isolated from clinically and bacteriologically confirmed patients to evaluate the susceptibility of clinical M. tuberculosis isolates to fluoroquinolone and to obtain molecular epidemiological information in Zambia,. The pathogens were subjected to susceptibility testing with isoniazid, rifampicin, ethambutol and streptomycin. The minimum inhibitory concentrations to ciprofloxacin, sparfloxacin and levofloxacin were also evaluated. The gyrA, fluoroquinolone resistance-determining region (QRDR), was sequenced and analysed. As a result, three of the 16 strains examined were resistant to isoniazid, rifampicin and⁄or streptomycin. All of the strains were susceptible to ciprofloxacin, levofloxacin and sparfloxacin. However, a unique gyrA gene variation of M. tuberculosis was identified in the isolates. One strain had a mutation (T73A) in QRDR. Additionally, 81.25% (13⁄16) of the strains tested had Thr at codon 88. Several variations of gyrA gene have been reported in relation to drug resistance. The gyrA variation data will be useful as epidemiological information. It may be important to monitor fluoroquinolone susceptibility even in developing countries for use against resistant M. tuberculosis infection, even though no fluoroquinolone resistance was observed in this study.

Heterosexual transmission accounts for the majority of human immunodeficiency virus–1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encoding compact, glycan-restricted envelope glycoproteins. These viruses were also uniquely sensitive to neutralization by antibody from the transmitting partner. Thus, the exposure of neutralizing epitopes, which are lost in chronic infection because of immune escape, appears to be favored in the newly infected host. This reveals characteristics of the envelope glycoprotein that influence HIV-1 transmission and may have implications for vaccine design.

The ability of HIV-1 to evolve resistance to antiretroviral drugs leads to treatment failure. By nucleotide sequencing of HIV-1 subtype B isolates, amino acids responsible for drug resistance have been identified. Less information is available, however, on the extent and distribution of these amino acids in HIV-1 nonsubtype B viruses circulating mainly in developing countries. More HIV-infected patients in the developing world are now using antiretroviral drugs, and hence there is a need to monitor drug resistance mutations in HIV-1 non-subtype B viruses. This study examines the prevalence of drug resistance mutations in 28 antiretroviral drug-naive HIV-1-infected Zambians. HIV-1 proviral DNA was extracted from peripheral blood mononuclear cells. The region encompassing gag p17 to env C2-V3-C3 was amplified by the polymerase chain reaction followed by direct sequencing. Sequence analyses for drug resistance-associated mutations in th e protease and reverse transcriptase genes, and HIV-1 subtyping, were done. Overall, 92.8% of the generated sequences were HIV-1 subtype C. The generated sequences revealed only secondary associated, but no primary, drug-resistance mutations The most frequent secondary mutations in the protease and RT genes were, respectively, I93L(91.7%), L89M (79.2%), M3611V (79%, 4.2%), and R211K (70.8%), S48T (62.5%). The atypical residues M41N (3.6%) and D67A (3.6%) were detected in the RT gene. This study reveals many naturally occurring polymorphisms in HIV-1 subtype C isolates from antiretroviral drug-naive individuals. Such polymorphisms could lead to rapid treatment failure and development of drug-resistant HIV-1 mutants in individuals undergoing antiretroviral therapy.

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpes virus type 8 (HHV-8) is tightly linked to the development of Kaposi's sarcoma, primary effusion lymphoma (PEL) and some cases of multicentric Castleman's disease. Latency-associated nuclear antigen (LANA) is one of a limited number of KSHV genes consistently expressed in these diseases as well as in KSHV-infected cell lines derived from PEL, and has been shown to play crucial role in persistence of KSHV genomes in the infected cells. In this study, we explored the cellular factors that interact with LANA using yeast two-hybrid screening, and isolated a part of gene encoding human myeloid cell nuclear differentiation antigen (MNDA). MNDA is a hematopoietic interferon-inducible nuclear proteins with a HIN-200 family member with conserved 200-amino acid repeats. Immunoprecipitation assay revealed that LANA interacted with MNDA in a mammalian embryonic kidney cell line. MNDA transcript was undetectable in three PEL cell lines by reverse-transcription polymerase chain reaction, but it was induced by interferon α (IFNα). Moreover, LANA and MNDA were co-localized in the nuclei of MNDA-expressing PEL cells. Our results suggest that LANA interacts with MNDA in KSHV-infected cells exposed to IFNα. Such interaction may modulate IFN-mediated host defense activities.

The inappropriate use of anti-tuberculosis drugs has resulted in an increase in the drug resistance. This study was conducted to obtain data related to the spectrum of drug resistant Mycobacterium tuberculosis. A total of 499 strains ofM. tuberculosis were tested for susceptibilities of isoniazid (INH), rifampicin (RFP), ethambutol (EMB) and streptomycin (SM). Totally 225 patients were also evaluated for their clinical manifestations. The primary and acquired resistances were observed in 13.9% and 16.1% to INH, 11.1% and 12.9% to RFP, 6.7% and 9.7% to EMB, and 3.8% and 3.2% to SM respectively. There were no significant differences between primary and acquired resistances. Multi-drug resistance was observed in 22 strains (4.4%). Clinical manifestation, as measured by chest roentgenograms, was similar in patients with either drug-susceptible or resistant strains. The clinical and radiological information was not useful for the prediction of susceptible and resistant strains. The HIV serostatus was not associated with drug susceptibility profiles either. Our study has documented a high incidence of drug resistant M. tuberculosis, with no obvious clinical correlates, which must be considered when implementing a strategy for chemotherapy. As for clinical practices, many defaults during chemotherapy reduced the treatment successes. It is important to assess the efficient implementation of the directly observed treatment with short course chemotherapy (DOTS) and interrupt the further dissemination of resistant M. tuberculosis in the community. The drug resistances must be surveyed continuously to obtain useful clinical perspective and evaluate the effectiveness of tuberculosis control program.

Background: One of the remaining challenges in the prevention of mother-to-child transmission of HIV is to reduce the risk of the transmission during pregnancy. It remains to be investigated which factors affect intrauterine HIV transmission and how they can be identified and addressed during pregnancy. Methods: Granulocyte elastase in the endocervical mucus of HIV-positive pregnant women in Zambia was measured, and its association with intrauterine transmission of HIV-1 from the mother to the fetus was investigated. Results: The intrauterine transmission rate determined by polymerase chain reaction assay of DNA from neonates at birth was 15.3%. The risk for intrauterine transmission was 8.65-fold higher in women who were positive for granulocyte elastase than in those who were negative. Conclusion: We suggest that the women showing positive granulocyte elastase at delivery be strongly suspected of having and if having had chorioamnionitis during pregnancy, which could affect the intrauterine transmission of HIV.

Background Acute respiratory infections remain a leading cause of morbidity and mortality in Sierra Leone; however, similar to other African countries, little is known regarding the contribution of influenza. Routine influenza surveillance is thus a key element to improve understanding of the burden of acute respiratory infections in Africa. In 2011, the World Health Organization (WHO) funded the Strengthening Influenza Sentinel Surveillance in Africa (SISA) project with the goal of developing and strengthening influenza surveillance in eight countries in sub-Saharan Africa, including Sierra Leone. This paper describes the process of establishing a functional Influenza Sentinel Surveillance (ISS) system in Sierra Leone, a post-conflict resource-poor country previously lacking an influenza monitoring system. Methods Sierra Leone utilized a systematic approach, including situational assessment, selection of sentinel sites, preparation of implementation plan, adaptation of the standard operating procedures, supervision and training of staff, and monitoring of influenza surveillance activities. The methods used in Sierra Leone were adapted to its specific context, using the Integrated Disease Surveillance and Response (IDSR) strategy as a platform for establishing ISS. Results The ISS system started functioning in August 2011 with subsequent capacity to contribute surveillance activity data to global influenza databases, FluID and FluNet, demonstrating a functional influenza surveillance system in Sierra Leone within the period of the WHO SISA project support. Several factors were necessary for successful implementation, including a systematic approach, national ownership, appropriate timing and external support. Conclusions The WHO SISA project demonstrated the feasibility of building a functional influenza surveillance system in Sierra Leone, integrated into existing national IDSR system. The ISS system, if sustained long-term, would provide valuable data to determine epidemiological and virological patterns and seasonal trends to assess the influenza disease burden that will ultimately guide national control strategies.

International audience; BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination. We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka Zambia. From May 2000 to November 2002 696 children aged 2-8 months were enrolled. Within 6 months of vaccination 88% of 50 HIV-1-infected children developed antibody levels of greater than or equal to 120 mIU/mL compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination however only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels greater than or equal to 120 mIU/mL compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity. Although HIV-1-infected children showed good primary antibody responses to measles vaccine their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence. (authors modified)

In a longitudinal cohort study we investigated factors contributing to breast milk HIV RNA viral load among lactating women in Lusaka, Zambia. Detailed data from 135 HIV-infected women were collected by questionnaires concerning postpartum maternal and infant health and infant feeding practice. Maternal blood was collected during pregnancy and at 6 weeks postpartum. Milk samples collected from each breast at 10 days and 6 weeks postpartum plus a subset collected at other time points were analyzed for HIV RNA viral load. Increased milk viral load was associated in univariate analyses with maternal symptoms of poor health, raised plasma alpha(1)-acid glycoprotein (AGP) at week 6, raised milk sodium/potassium (Na/K) ratio, postpartum need for antibiotics, preterm delivery, and low birth weight infants. In a multiple regression 49% of variability in mean milk viral load was explained by milk Na/K ratio and need for antibiotics, with borderline contributions from plasma AGP and plasma viral load. Maternal blood hemoglobin or receipt of iron supplements and infant feeding variables such as changing the infant's diet by moving from exclusive to nonexclusive breastfeeding or adding solid foods were not associated with milk viral load. Thus maternal health was the main factor contributing to milk viral load. The lack of effect of feeding practices on milk viral load and the previously determined association of poor maternal health with reduced duration of exclusive breastfeeding in this cohort suggest the relation between exclusive breastfeeding and decreased HIV transmission may be secondary to poor maternal health.

Publisher Summary This chapter reviews properties of the genome of the human herpesvirus-6 (HHV-6) with some updates includingthe general properties of HHV-6 and the closely related HHV-7 and their genomes, besides their complete genomic sequences. There are two strain groups for HHV-6, the prototypes are strain U1102 for HHV-6 variant A (HHV-6A) and strain Z29 for variant B (HHV-6B). HHV-6A strain U1102 was identified and first characterized in the UK and HHV-6B strain Z29 in the USA; both genomes are sequenced. Both HHV-6 and HHV-7 are T lymphotropic and neurotropic. Furthermore, it is likely that in vivo , the lytic and latent cell types that HHV-6 infects are highly specific subsets. Both HHV-6 and HHV-7 have a cellular tropism for T lymphocytes as shown in vivo during viremia from acute infection as well as in vitro . Infection and lytic replication results in a characteristic cytopathic effect of large cells (cytomegalia) and ballooning cells. For HHV-6, some differences upon the serial passage of strain Z29 in culture have been observed including an expansion of repetitive sequences from the origin of lytic replication, terminal direct repeats, het region, and other rearrangements are possible.

Exclusive breastfeeding (EBF) is optimal for infant health and is associated with decreased risk of mother-to-child HIV transmission compared with mixed feeding of breast milk and other foods. To investigate why many women stop EBF before the recommended 6 months, maternal and infant health and infant-feeding data were collected from 177 HIV-infected and 177-uninfected Zambian women regularly from 34 weeks gestation to 16 weeks postpartum. Despite strong support for good breastfeeding practice, only 37% of women were still EBF at week 16. Factors significantly associated with shorter duration of EBF were primiparity, maternal systemic illness, and infant length at 6 weeks. The results suggest that the association of EBF with lower rates of mother-to-child HIV transmission may not be causal but may be secondary to the reduced duration of EBF associated with poor maternal or infant health. Programs supporting EBF should include support for maternal health.

Age-related changes in lymphocyte subsets in HIV-uninfected Zambian children are described. The total lymphocyte count and numbers of CD4+ and CD8+ T-lymphocytes declined with increasing age, while the percentage of CD4+ and CD8+ T-lymphocytes changed little during childhood. Girls between the ages of 12 and 71 months had a higher percentage of CD4+ T-lymphocytes and a higher CD4:CD8 ratio than did boys of a similar age.

The estimated worldwide prevalence of human immunodeficiency virus (HIV) infections topped 52.5 million in June 2003, a mere 20 years after the aetiological agent was shown to be a sexually transmissible virus with a predilection for CD4+ T lymphocytes. More than 22 million people have died of the acquired immunodeficiency syndrome (AIDS) and the condition has in one generation become the most devastating and persistent epidemics in recorded history. More than two thirds of the world total of HIV-infected people live in Sub-Saharan Africa. In Central and Southern Africa at least 20% of the adult population is infected. As these adults die, they leave increasing numbers of orphans. Life expectancy at birth declined by 10 years per decade since the late 1980s to 50 years in the late 1990s, and in Botswana it is estimated to be as low as 33 years by 2010. The epidemic is increasing unabated and prospects for a curative or protective vaccine remain remote. The impact on HIV in Africa has been so profound that it influences political, economic, agriculture/food security, social, education, defence, science and health considerations. The medical and in particular immunology communities in Central Africa have the invidious challenge of on the one hand diagnosing the condition, monitoring its impact and contributing to treatment and management efforts. The science and clinical practice of immunology is challenged to find answers to the epidemic, perhaps including a vaccine. In this review we address the peculiarities of the HIV epidemic in Africa, its epidemiology and immunopathogenesis. We address the effect of the epidemic on individual patients, in their homes, workplaces and the knock-on effects on families and friends of the infected. Respective specialists discuss special groups (women, children) that are predominantly seen in Africa. We also discuss the impact of the epidemic on the clinical practice of medicine in general and challenges faced in the introduction of antiretroviral medicines. We also discuss options available for the diagnosis, treatment and monitoring of HIV-infected patients in this region.

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpes virus type 8 (HHV-8) is tightly linked to the development of Kaposi's sarcoma, primary effusion lymphoma (PEL) and some cases of multicentric Castleman's disease. Latency-associated nuclear antigen (LANA) is one of a limited number of KSHV genes consistently expressed in these diseases as well as in KSHV-infected cell lines derived from PEL, and has been shown to play crucial role in persistence of KSHV genomes in the infected cells. In this study, we explored the cellular factors that interact with LANA using yeast two-hybrid screening, and isolated a part of gene encoding human myeloid cell nuclear differentiation antigen (MNDA). MNDA is a hematopoietic interferon-inducible nuclear proteins with a HIN-200 family member with conserved 200-amino acid repeats. Immunoprecipitation assay revealed that LANA interacted with MNDA in a mammalian embryonic kidney cell line. MNDA transcript was undetectable in three PEL cell lines by reverse-transcription polymerase chain reaction, but it was induced by interferon alpha (IFNalpha). Moreover, LANA and MNDA were co-localized in the nuclei of MNDA-expressing PEL cells. Our results suggest that LANA interacts with MNDA in KSHV-infected cells exposed to IFNalpha. Such interaction may modulate IFN-mediated host defense activities.

Background and objectives: Sexual behavior following voluntary HIV counseling and testing (VCT) is described in 963 cohabiting heterosexual couples with one HIV positive and one HIV negative partner (‘discordant couples’). Biological markers were used to assess the validity of self-report. Methods: Couples were recruited from a same-day VCT center in Lusaka Zambia. Sexual exposures with and without condoms were recorded at 3-monthly intervals. Sperm detected on vaginal smears pregnancy and sexually transmitted diseases (STD) including HIV gonorrhea syphilis and Trichomonas vaginalis were assessed. Results: Less than 3% of couples reported current condom use prior to VCT. In the year after VCT > 80% of reported acts of intercourse in discordant couples included condom use. Reporting 100% condom use was associated with 39–70% reductions in biological markers; however most intervals with reported unprotected sex were negative for all biological markers. Under-reporting was common: 50% of sperm and 32% of pregnancies and HIV transmissions were detected when couples had reported always using condoms. Positive laboratory tests for STD and reported extramarital sex were relatively infrequent. DNA sequencing confirmed that 87% of new HIV infections were acquired from the spouse. Conclusions: Joint VCT prompted sustained but imperfect condom use in HIV discordant couples. Biological markers were insensitive but provided evidence for a significant under-reporting of unprotected sex. Strategies that encourage truthful reporting of sexual behavior and sensitive biological markers of exposure are urgently needed. The impact of prevention programs should be assessed with both behavioral and biological measures. (authors)

Summary Background Accurate information about specific causes of death in African children dying of respiratory illnesses is scarce, and can only be obtained by autopsy. We undertook a study of children who died from respiratory diseases at University Teaching Hospital, Lusaka, Zambia. Methods 137 boys (93 HIV-1-positive, 44 HIV-1-negative], and 127 girls (87 HIV-1-positive, 40 HIV-1-negative) aged between 1 month and younger than 16 years underwent autopsy restricted to the chest cavity. Outcome measures were specific lung diseases, stratified by age and HIV-1 status. Findings The presence of multiple diseases was common. Acute pyogenic pneumonia (population-adjusted prevalence 39·1%, 116/264), Pneumocystis carinii pneumonia (27·5%, 58/264), tuberculosis (18·8%, 54/264), and cytomegalo-virus infection (CMV, 20·2%, 43/264) were the four most common findings overall. The three most frequent findings in the HIV-1-negative group were acute pyogenic pneumonia (50%), tuberculosis (26%), and interstitial pneumonitis (18%); and in the HIV-1-positive group were acute pyogenic pneumonia (41%), P carinii pneumonia (29%), and CMV (22%). HIV-1-positive children more frequently had P carinii pneumonia (odds ratio 5·28, 95% Cl 2·12–15·68, p=0·0001), CMV (7·71, 2·33-40·0, p=0·0002), and shock lung (4·15, 1·20–22·10, p=0·03) than did HIV-1-negative children. 51/58 (88%) cases of P carinii pneumonia were in children younger than 12 months, and five in children aged over 24 months. Tuberculosis was common in all age groups, irrespective of HIV-1 status. Interpretation Most children dying from respiratory diseases have preventable or treatable infectious illnesses. The presence of multiple diseases might make diagnosis difficult. WHO recommendations should therefore be updated with mention of HIV-1-positive children. Improved diagnostic tests for bacterial pathogens, tuberculosis, and P carinii pneumonia are urgently needed. Published online September 3, 2002 http://image.thelancet.com/extras/01artl2073web.pdf

Polymerase chain reaction for Pneumocystis carinii DNA was performed on necropsy lung samples from children by means of P carinii -specific primers.P carinii DNA was identified in 22 of 22 (100%) samples with histologically proven P carinii pneumonia and 13 of 75 (17%) with non-P carinii pneumonia respiratory illness (sensitivity, 100%; specificity, 83%). The low specificity precludes the use of polymerase chain reaction as an alternative to histopathologic diagnosis.

Most human immunodeficiency virus type 1 (HIV-1) transmissions in sub-Saharan Africa are believed to occur between married adults who are discordant for their HIV-1 infection status; however, no studies to date have investigated the molecular epidemiology of such transmission events. Here we report the genetic characterization of HIV-1 strains from 149 transmission pairs that were identified prospectively in a cohort of discordant couples in Lusaka, Zambia. Subgenomic gag , gp120, gp41, and/or long terminal repeat regions were amplified by PCR analysis of uncultured blood samples from both partners and sequenced without interim cloning. Pairwise genetic distances were calculated for the regions analyzed and compared to those of subtype-specific reference sequences as well as local controls. Sequence relationships were also examined by phylogenetic tree analysis. By these approaches, epidemiological linkage was established for the majority of transmission pairs. Viruses from 129 of the 149 couples (87%) were very closely related and clustered together in phylogenetic trees in a statistically highly significant manner. In contrast, viruses from 20 of the 149 couples (13%) were only distantly related in two independent genomic regions, thus ruling out transmission between the two partners. The great majority (95%) of transmitted viruses were of subtype C origin, although representatives of subtypes A, D, G, and J were also identified. There was no evidence for extensive transmission networks within the cohort, although two phylogenetic subclusters of viruses infecting two couples each were identified. Taken together, these data indicate that molecular epidemiological analyses of presumed transmission pairs are both feasible and required to determine behavioral, virological, and immunological correlates of heterosexual transmission in sub-Saharan Africa with a high level of accuracy.