Community-based rehabilitation program for cerebral PALSY (CP) children in North Uganda

Background: CP is a common neurologic disease in children, with a worldwide estimated prevalence of 93 million. Data on the African context are limited. Purpose: This study was aimed at evaluating the efficacy of a mixed outpatient/home physiotherapy program in children with CP admitted to St. Mary's Lacor Hospital (Gulu), the reference center of north Uganda. Methods: This is an observational, uncontrolled, prospective study. All children with CP (aged from 0.5 to 12 years) admitted in the Physiotherapy Unit from January to December 2017 were enrolled. A written consent form (English or Acholi language) was obtained from the mother/ caregiver. Each patient was evaluated at baseline and every two weeks for three months. CP sub-types were defined according to Surveillance of Cerebral Palsy in Europe classification. The child\ub4s abilities were staged through the Gross Motor Function Classification System Expanded and Revised (GMFCS-E&R; scale from I to V, the higher the worse). Changes in motor function were measured through the 66-item version (GMFM-66; scores ranging from 0 to 100, the higher the better). At baseline and subsequent visits, Bobath treatment was applied for 30 minutes by an experienced physiotherapist, who trained the caregiver on customized home exercises following a diary prescription. The functional status reported by the caregiver and the overall compliance were assessed. Changes in GMFCS-E&R and GMFM-66 at 6 and 12 weeks were recorded. The normality of score distributions was tested (Shapiro-Wilks). If confirmed, repeated ANOVA modeling was applied to scores across time points. Results: Fifty-two consecutive children were enrolled (mean age 2.2 years, range 0.5-9.9). Spastic bilateral (19 patients, 36%) and dystonic (16, 31%) were the most common CP sub-types. The main cause of CP were asphyxia during the delivery (26 cases, 50%) and cerebral malaria (10, 19%). Thirty-three/52 cases (67%) presented level V GMFCS-E&R. GMFM-66 mean score at baseline was 19.86 range: 0-52.9. Seventeen/52 (33%) children were assessed at 6 and/or 12 weeks, while 35 (67%) missed at least three study visits (reasons: 28 transportation cost, 2 remote home, 4 other). In 16/17 (94%) patients home exercises were performed correctly. The GMFM-66 mean score increased from 14.8 at baseline to 20.4 and to 24.9 at 6 weeks (p=0.02) and 12 weeks (p=0.00), respectively. The improvement was observed irrespectively from CP sub-type or cause of disability. Conclusion(s): Although on a small number of patients, this study suggests that a mixed outpatient/home physiotherapy program can improve CP disability in compliant children treated in a developing country, like north Uganda. The high drop-out rate and its causes point towards the need for implementing local community programs and/or transport facilities. Implications: These results suggest that a mixed outpatient/home physiotherapy program can benefit children with CP living in developing countries and strengthen the need of a policy aimed at improving the access to the physiotherapy service. In addition, they confirm that neurological damage during the assisted delivery is the major cause of CP in this conte

Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis

BACKGROUND: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. METHODS: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45 000 children younger than 5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January, 2011. In Kilifi, there was a three-dose catch-up campaign for infants (aged <1 year) and a two-dose catch-up campaign for children aged 1-4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. FINDINGS: Between May 1, 2002 and March 31, 2015, 44 771 children aged 2-143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses' strikes. In 2002-03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2-59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2-11 months had received at least two doses of PCV10 and 23 298 (62·3%) of 37 416 children aged 12-59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologically-confirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32-0·86), 0·73 (0·54-0·97), and 0·63 (0·31-1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100 000; this value was reduced by 329 per 100 000 at the point of PCV10 introduction. INTERPRETATION: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10. FUNDING: Gavi, The Vaccine Alliance and Wellcome Trust

Evaluation of a PfHRP2 and a pLDH-based Rapid Diagnostic Test for the Diagnosis of Severe Malaria in 2 Populations of African Children

This comparative study in 1898 children in 2 different African population shows that a pfHRP2-based rapid diagnostic test is a reliable diagnostic for diagnosing severe falciparum malaria in these settings and performs better than routine microscopy or a pLDH based test

Factors influencing implementation of the Ministry of Health-led private medicine retailer programmes on malaria in Kenya

<p>Abstract</p> <p>Background</p> <p>Kenya has experienced a number of retail sector initiatives aimed at improving access to antimalarial medicines. This study explored stakeholders' perceptions of the role of private medicine retailers (PMRs), the value and feasibility of programme goals, perceived programme impact, factors influencing implementation and recommendations in three districts of Kenya.</p> <p>Methods</p> <p>This study was part of a larger evaluation of PMR programmes, including quantitative and qualitative components. The qualitative research was conducted to assess implementation processes and actors' experiences in the programmes, through focus group discussions with trained PMRs and mothers of children under five years, and in-depth interviews with programme managers, trainers and co-trainers.</p> <p>Results</p> <p>PMRs were perceived to provide rapid cheap treatment for non-serious conditions and used as a deliberate and continuously evaluated choice between different treatment sources. All stakeholders supported programme goals and most PMRs described increased customer satisfaction, more rational purchasing of medicine stock and increased medicine sales after participation. Factors undermining programme implementation included a lack of MoH resources to train and monitor large numbers of PMRs, the relative instability of outlets, medicines stocked and retail personnel, the large number of proprietary brands and financial challenges to retailers in stocking antimalarial medicines, and their customers in buying them. Unambiguous national support and a broad range of strategies are important to strengthen the feasibility of change in OTC antimalarial use.</p> <p>Conclusions</p> <p>Understanding the context and implementation processes of PMR programmes and the perspectives of key actors are critical to identifying measures to support their effective implementation. Financial barriers underlie many described challenges, with important implications for policies on subsidies in this sector. In spite of barriers to implementation, increased exposure to programme activities promoted trust and improved relationships between PMRs and their clients and trainers, strengthening feasibility of such interventions. Public information can strengthen PMR training programmes by engaging local communities and may facilitate performance monitoring of PMRs by their clients.</p

Comparison of PfHRP-2/pLDH ELISA, qPCR and microscopy for the detection of Plasmodium events and prediction of sick visits during a malaria vaccine study.

BACKGROUND: Compared to expert malaria microscopy, malaria biomarkers such as Plasmodium falciparum histidine rich protein-2 (PfHRP-2), and PCR provide superior analytical sensitivity and specificity for quantifying malaria parasites infections. This study reports on parasite prevalence, sick visits parasite density and species composition by different diagnostic methods during a phase-I malaria vaccine trial. METHODS: Blood samples for microscopy, PfHRP-2 and Plasmodium lactate dehydrogenase (pLDH) ELISAs and real time quantitative PCR (qPCR) were collected during scheduled (n = 298) or sick visits (n = 38) from 30 adults participating in a 112-day vaccine trial. The four methods were used to assess parasite prevalence, as well as parasite density over a 42-day period for patients with clinical episodes. RESULTS: During scheduled visits, qPCR (39.9%, N = 119) and PfHRP-2 ELISA (36.9%, N = 110) detected higher parasite prevalence than pLDH ELISA (16.8%, N = 50) and all methods were more sensitive than microscopy (13.4%, N = 40). All microscopically detected infections contained P. falciparum, as mono-infections (95%) or with P. malariae (5%). By qPCR, 102/119 infections were speciated. P. falciparum predominated either as monoinfections (71.6%), with P. malariae (8.8%), P. ovale (4.9%) or both (3.9%). P. malariae (6.9%) and P. ovale (1.0%) also occurred as co-infections (2.9%). As expected, higher prevalences were detected during sick visits, with prevalences of 65.8% (qPCR), 60.5% (PfHRP-2 ELISA), 21.1% (pLDH ELISA) and 31.6% (microscopy). PfHRP-2 showed biomass build-up that climaxed (1813±3410 ng/mL SD) at clinical episodes. CONCLUSION: PfHRP-2 ELISA and qPCR may be needed for accurately quantifying the malaria parasite burden. In addition, qPCR improves parasite speciation, whilst PfHRP-2 ELISA is a potential predictor for clinical disease caused by P. falciparum. TRIAL REGISTRATION: ClinicalTrials.gov NCT00666380

Challenges in Diagnosing Paediatric Malaria in Dar es Salaam, Tanzania.

Malaria is a major cause of paediatric morbidity and mortality. As no clinical features clearly differentiate malaria from other febrile illnesses, and malaria diagnosis is challenged by often lacking laboratory equipment and expertise, overdiagnosis and overtreatment is common. Children admitted with fever at the general paediatric wards at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania from January to June 2009 were recruited consecutively and prospectively. Demographic and clinical features were registered. Routine thick blood smear microscopy at MNH was compared to results of subsequent thin blood smear microscopy, and rapid diagnostics tests (RDTs). Genus-specific PCR of Plasmodium mitochondrial DNA was performed on DNA extracted from whole blood and species-specific PCR was done on positive samples. Among 304 included children, 62.6% had received anti-malarials during the last four weeks prior to admission and 65.1% during the hospital stay. Routine thick blood smears, research blood smears, PCR and RDT detected malaria in 13.2%, 6.6%, 25.0% and 13.5%, respectively. Positive routine microscopy was confirmed in only 43% (17/40), 45% (18/40) and 53% (21/40), by research microscopy, RDTs and PCR, respectively. Eighteen percent (56/304) had positive PCR but negative research microscopy. Reported low parasitaemia on routine microscopy was associated with negative research blood slide and PCR. RDT-positive cases were associated with signs of severe malaria. Palmar pallor, low haemoglobin and low platelet count were significantly associated with positive PCR, research microscopy and RDT. The true morbidity attributable to malaria in the study population remains uncertain due to the discrepancies in results among the diagnostic methods. The current routine microscopy appears to result in overdiagnosis of malaria and, consequently, overuse of anti-malarials. Conversely, children with a false positive malaria diagnosis may die because they do not receive treatment for the true cause of their illness. RDTs appear to have the potential to improve routine diagnostics, but the clinical implication of the many RDT-negative, PCR-positive samples needs to be elucidated.\u

How Much Remains Undetected? Probability of Molecular Detection of Human Plasmodia in the Field

BACKGROUND: In malaria endemic areas, most people are simultaneously infected with different parasite clones. Detection of individual clones is hampered when their densities fluctuate around the detection limit and, in case of P. falciparum, by sequestration during part of their life cycle. This has important implications for measures of levels of infection or for the outcome of clinical trials. This study aimed at measuring the detectability of individual P. falciparum and P. vivax parasite clones in consecutive samples of the same patient and at investigating the impact of sampling strategies on basic epidemiological measures such as multiplicity of infection (MOI). METHODS: Samples were obtained in a repeated cross-sectional field survey in 1 to 4.5 years old children from Papua New Guinea, who were followed up in 2-monthly intervals over 16 months. At each follow-up visit, two consecutive blood samples were collected from each child at intervals of 24 hours. Samples were genotyped for the polymorphic markers msp2 for P. falciparum and msp1F3 and MS16 for P. vivax. Observed prevalence and mean MOI estimated from single samples per host were compared to combined data from sampling twice within 24 h. FINDINGS AND CONCLUSION: Estimated detectability was high in our data set (0.79 [95% CI 0.76-0.82] for P. falciparum and, depending on the marker, 0.61 [0.58-0.63] or 0.73 [0.71-0.75] for P. vivax). When genotyping data from sequential samples, collected 24 hours apart, were combined, the increase in measured prevalence was moderate, 6 to 9% of all infections were missed on a single day. The effect on observed MOI was more pronounced, 18 to 31% of all individual clones were not detected in a single bleed. Repeated sampling revealed little difference between detectability of P. falciparum and P. vivax

The evolving SARS-CoV-2 epidemic in Africa: insights from rapidly expanding genomic surveillance

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A new world malaria map: Plasmodium falciparum endemicity in 2010

Background: transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Methods: annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. Results: an estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. Conclusions: the year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 20