Kinetics of the neutralizing antibody response to respiratory syncytial virus infections in a birth cohort

The kinetics of respiratory syncytial virus (RSV) neutralizing antibodies following birth, primary and secondary infections are poorly defined. The aims of the study were to measure and compare neutralizing antibody responses at different time points in a birth cohort followed-up over three RSV epidemics. Rural Kenyan children, recruited at birth between 2002 and 2003, were monitored for RSV infection over three epidemic seasons. Cord and 3-monthly sera, and acute and convalescent sera following RSV infection, were assayed in 28 children by plaque reduction neutralization test (PRNT). Relative to the neutralizing antibody titers of pre-exposure control sera (1.8 log10 PRNT), antibody titers following primary infection were (i) no different in sera collected between 0 and 0.4 months post-infection (1.9 log10 PRNT, P = 0.146), (ii) higher in sera collected between 0.5 and 0.9 (2.8 log10 PRNT, P < 0.0001), 1.0–1.9 (2.5 log10 PRNT, P < 0.0001), and 2.0–2.9 (2.3 log10 PRNT, P < 0.001) months post-infection, and (iii) no different in sera collected at between 3.0 and 3.9 months post-infection (2.0 log10 PRNT, P = 0.052). The early serum neutralizing response to secondary infection (3.02 log10 PRNT) was significantly greater than the early primary response (1.9 log10 PRNT, P < 0.0001). Variation in population-level virus transmission corresponded with changes in the mean cohort-level neutralizing titers. It is concluded that following primary RSV infection the neutralizing antibody response declines to pre-infection levels rapidly (∼3 months) which may facilitate repeat infection. The kinetics of the aggregate levels of acquired antibody reflect seasonal RSV occurrence, age, and infection history

The Impact of a Community Awareness Strategy on Caregiver Treatment Seeking Behaviour and Use of Artemether-Lumefantrine for Febrile Children in Rural Kenya.

BACKGROUND: Access to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen. METHODS: Pre- and post-intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset. RESULTS: There was an increase from 62.8% pre-intervention to 79.4% post-intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1-10.0)]. CONCLUSION: The findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes

Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity

BACKGROUND: The understanding of the epidemiology of severe malaria in African children remains incomplete across the spectrum of Plasmodium falciparum transmission intensities through which communities might expect to transition, as intervention coverage expands. METHODS: Paediatric admission data were assembled from 13 hospitals serving 17 communities between 1990 and 2007. Estimates of Plasmodium falciparum transmission intensity in these communities were assembled to be spatially and temporally congruent to the clinical admission data. The analysis focused on the relationships between community derived parasite prevalence and the age and clinical presentation of paediatric malaria in children aged 0-9 years admitted to hospital. RESULTS: As transmission intensity declined a greater proportion of malaria admissions were in older children. There was a strong linear relationship between increasing transmission intensity and the proportion of paediatric malaria admissions that were infants (R2 = 0.73, p < 0.001). Cerebral malaria was reported among 4% and severe malaria anaemia among 17% of all malaria admissions. At higher transmission intensity cerebral malaria was a less common presentation compared to lower transmission sites. There was no obvious relationship between the proportions of children with severe malaria anaemia and transmission intensity. CONCLUSION: As the intensity of malaria transmission declines in Africa through the scaling up of insecticide-treated nets and other vector control measures a focus of disease prevention among very young children becomes less appropriate. The understanding of the relationship between parasite exposure and patterns of disease risk should be used to adapt malaria control strategies in different epidemiological settings

The clinical burden of malaria in Nairobi: a historical review and contemporary audit

<p>Abstract</p> <p>Background</p> <p>Widespread urbanization over the next 20 years has the potential to drastically change the risk of malaria within Africa. The burden of the disease, its management, risk factors and appropriateness of targeted intervention across varied urban environments in Africa remain largely undefined. This paper presents a combined historical and contemporary review of the clinical burden of malaria within one of Africa's largest urban settlements, Nairobi, Kenya.</p> <p>Methods</p> <p>A review of historical reported malaria case burdens since 1911 within Nairobi was undertaken using archived government and city council reports. Contemporary information on out-patient case burdens due to malaria were assembled from the National Health Management and Information System (HMIS). Finally, an audit of 22 randomly selected health facilities within Nairobi was undertaken covering 12 months 2009-2010. The audit included interviews with health workers, and a checklist of commodities and guidelines necessary to diagnose, treat and record malaria.</p> <p>Results</p> <p>From the 1930's through to the mid-1960's malaria incidence declined coincidental with rapid population growth. During this period malaria notification and prevention were a priority for the city council. From 2001-2008 reporting systems for malaria were inadequate to define the extent or distribution of malaria risk within Nairobi. A more detailed facility review suggests, however that malaria remains a common diagnosis (11% of all paediatric diagnoses made) and where laboratories (n = 15) exist slide positivity rates are on average 15%. Information on the quality of diagnosis, slide reading and whether those reported as positive were imported infections was not established. The facilities and health workers included in this study were not universally prepared to treat malaria according to national guidelines or identify foci of risks due to shortages of national first-line drugs, inadequate record keeping and a view among some health workers (17%) that slide negative patients could still have malaria.</p> <p>Conclusion</p> <p>Combined with historical evidence there is a strong suggestion that very low risks of locally acquired malaria exist today within Nairobi's city limits and this requires further investigation. To be prepared for effective prevention and case-management of malaria among a diverse, mobile population in Nairobi requires a major paradigm shift and investment in improved quality of malaria diagnosis and case management, health system strengthening and case reporting.</p

A systematic review of changing malaria disease burden in sub-Saharan Africa since 2000: comparing model predictions and empirical observations.

BACKGROUND: The most widely used measures of declining burden of malaria across sub-Saharan Africa are predictions from geospatial models. These models apply spatiotemporal autocorrelations and covariates to parasite prevalence data and then use a function of parasite prevalence to predict clinical malaria incidence. We attempted to assess whether trends in malaria cases, based on local surveillance, were similar to those captured by Malaria Atlas Project (MAP) incidence surfaces. METHODS: We undertook a systematic review (PROSPERO International Prospective Register of Systematic Reviews; ID = CRD42019116834) to identify empirical data on clinical malaria in Africa since 2000, where reports covered at least 5 continuous years. The trends in empirical data were then compared with the trends of time-space matched clinical malaria incidence from MAP using the Spearman rank correlation. The correlations (rho) between changes in empirically observed and modelled estimates of clinical malaria were displayed by forest plots and examined by meta-regression. RESULTS: Sixty-seven articles met our inclusion criteria representing 124 sites from 24 African countries. The single most important factor explaining the correlation between empirical observations and modelled predictions was the slope of empirically observed data over time (rho = - 0.989; 95% CI - 0.998, - 0.939; p < 0.001), i.e. steeper declines were associated with a stronger correlation between empirical observations and modelled predictions. Factors such as quality of study, reported measure of malaria and endemicity were only slightly predictive of such correlations. CONCLUSIONS: In many locations, both local surveillance data and modelled estimates showed declines in malaria burden and hence similar trends. However, there was a weak association between individual surveillance datasets and the modelled predictions where stalling in progress or resurgence of malaria burden was empirically observed. Surveillance data were patchy, indicating a need for improved surveillance to strengthen both empiric reporting and modelled predictions

A rapid and reproducible picture of open access health facility data in Africa to support the COVID-19 response

Background: Open data on the locations and services provided by health facilities in some countries have allowed the development of software tools contributing to COVID-19 response. The UN and WHO encourage countries to make health facility location data open, to encourage use and improvement. We provide a summary of open access health facility location data in Africa using re-useable code. We aim to support data analysts developing software tools to address COVID-19 response in individual countries. In Africa there are currently three main sources of such data; 1) direct from national ministries of health, 2) a database for sub-Saharan Africa collated and published by a team from KEMRI-Wellcome Trust Research Programme and now hosted by WHO, and 3) The Global Healthsites Mapping Project in collaboration with OpenStreetMap. Methods: We searched for and documented official national facility location data that were openly available. We developed re-useable open-source R code to summarise and visualise facility location data by country from the three sources. This re-useable code is used to provide a web user interface allowing data exploration through maps and plots of facility type. Results: Out of 53 African countries, seven provide an official open facility list that can be downloaded and analysed reproducibly. Considering all three sources, there are over 185,000 health facility locations available for Africa. However, there are differences and overlaps between sources and a lack of data on capacities and service provision. Conclusions: We suggest that these summaries and tools will encourage greater use of existing health facility location data, incentivise further improvements in the provision of those data by national suppliers, and encourage collaboration within wider data communities. The tools are a part of the afrimapr project, actively developing R building blocks to facilitate the use of health data in Africa

Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation

<p>Abstract</p> <p>Background</p> <p>Clinical malaria has proven an elusive burden to enumerate. Many cases go undetected by routine disease recording systems. Epidemiologists have, therefore, frequently defaulted to actively measuring malaria in population cohorts through time. Measuring the clinical incidence of malaria longitudinally is labour-intensive and impossible to undertake universally. There is a need, therefore, to define a relationship between clinical incidence and the easier and more commonly measured index of infection prevalence: the "parasite rate". This relationship can help provide an informed basis to define malaria burdens in areas where health statistics are inadequate.</p> <p>Methods</p> <p>Formal literature searches were conducted for <it>Plasmodium falciparum </it>malaria incidence surveys undertaken prospectively through active case detection at least every 14 days. The data were abstracted, standardized and geo-referenced. Incidence surveys were time-space matched with modelled estimates of infection prevalence derived from a larger database of parasite prevalence surveys and modelling procedures developed for a global malaria endemicity map. Several potential relationships between clinical incidence and infection prevalence were then specified in a non-parametric Gaussian process model with minimal, biologically informed, prior constraints. Bayesian inference was then used to choose between the candidate models.</p> <p>Results</p> <p>The suggested relationships with credible intervals are shown for the Africa and a combined America and Central and South East Asia regions. In both regions clinical incidence increased slowly and smoothly as a function of infection prevalence. In Africa, when infection prevalence exceeded 40%, clinical incidence reached a plateau of 500 cases per thousand of the population <it>per annum</it>. In the combined America and Central and South East Asia regions, this plateau was reached at 250 cases per thousand of the population <it>per annum</it>. A temporal volatility model was also incorporated to facilitate a closer description of the variance in the observed data.</p> <p>Conclusion</p> <p>It was possible to model a relationship between clinical incidence and <it>P. falciparum </it>infection prevalence but the best-fit models were very noisy reflecting the large variance within the observed opportunistic data sample. This continuous quantification allows for estimates of the clinical burden of <it>P. falciparum </it>of known confidence from wherever an estimate of <it>P. falciparum </it>prevalence is available.</p

The incidence and clinical burden of respiratory syncytial virus disease identified through hospital outpatient presentations in Kenyan children

There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting. Methods We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence. Results Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively. Conclusion The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis

Hospital Mortality - a neglected but rich source of information supporting the transition to higher quality health systems in low and middle income countries.

BACKGROUND: There is increasing focus on the strength of primary health care systems in low and middle-income countries (LMIC). There are important roles for higher quality district hospital care within these systems. These hospitals are also sources of information of considerable importance to health systems, but this role, as with the wider roles of district hospitals, has been neglected. KEY MESSAGES: As we make efforts to develop higher quality health systems in LMIC we highlight the critical importance of district hospitals focusing here on how data on hospital mortality offers value: i) in understanding disease burden; ii) as part of surveillance and impact monitoring; iii) as an entry point to exploring system failures; and iv) as a lens to examine variability in health system performance and possibly as a measure of health system quality in its own right. However, attention needs paying to improving data quality by addressing reporting gaps and cause of death reporting. Ideally enabling the collection of basic, standardised patient level data might support at least simple case-mix and case-severity adjustment helping us understand variation. Better mortality data could support impact evaluation, benchmarking, exploration of links between health system inputs and outcomes and critical scrutiny of geographic variation in quality and outcomes of care. Improved hospital information is a neglected but broadly valuable public good. CONCLUSION: Accurate, complete and timely hospital mortality reporting is a key attribute of a functioning health system. It can support countries' efforts to transition to higher quality health systems in LMIC enabling national and local advocacy, accountability and action

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

Background: Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods: In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results: From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion: We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community