The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

SARS-CoV-2 Infection in Pregnant Women and Their Newborns.

There remain a number of uncertainties globally about the risks posed to women who are infected with SARS-CoV-2 during pregnancy. Furthermore, our understanding of the spread of COVID-19 in Sub-Saharan Africa is limited, owing to low testing rates in many parts of the continent. PeriCOVID Africa, in conjunction with the WHO/HRP Alliance, plans to address these knowledge gaps by harnessing research infrastructures in place in five sub-Saharan African countries in order to screen more than 50,000 pregnant women and their infants for SARS-CoV-2, while monitoring pregnancy and neonatal outcomes. We anticipate that the results of this study will provide much needed information about the risks that SARS-CoV-2 poses to pregnant women and their babies, as well as establishing potential routes of mother-to-child transmission

Evaluating the performance of malaria genomics for inferring changes in transmission intensity using transmission modelling

AbstractAdvances in genetic sequencing and accompanying methodological approaches have resulted in pathogen genetics being used in the control of infectious diseases. To utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment. Here we develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The best performing model successfully predicted malaria prevalence with mean absolute error of 0.055, suggesting genetic tools could be used for monitoring the impact of malaria interventions.</jats:p

Technical report on the environmental monitoring of the cage area at the Source of the Nile (SON) Fish Farm for Quarter 4: October – December 2017

The monitoring of water quality and biotic communities at Source of the Nile (SON) fish farm area, for quarter 4 (October – December) was undertaken in December 2017. The activity aimed at assessing possible changes in the water environment at SON cage area. The following parameters were assessed: water physico-chemicals and nutrients, algae, zooplankton, benthic macro invertebrates, and fish communities. Total depth was above 5.0 m (range: 5.63 – 9.74 m) at all sampled points and decreased towards the downstream of cages. Water transparency ranged from 1.26 – 1.48 in the cage area and 1.08 to 1.34 m away from the cages. Within the cage area, Dissolved Oxygen ranged from 5.7 – 6.4 mg/L at the surface, and 5.1 – 6.4 mg/L at the bottom, while in the non-cage areas, the range was 5.5 – 7.5 mg/L at the surface and 2.6 – 7.0 mg/L at the bottom. Temperature ranged from 27.0 – 28.0 o C at the surface and 25.5 – 27.5 o C at the bottom waters for all sites, and were within the optimal range (25 – 32 o C). pH in both surface and bottom waters was above 7.0 (range: 7.5 – 9.2) at all sites. Conductivity within cage area ranged from 100.5 – 102.6 μScm-1 in surface water and 101.8 – 112.1 μScm-1 in bottom water. In the non-cage areas conductivity ranged from 11.0 – 104.4 μScm-1 in surface water and 100.2 – 110.0 μScm-1 at the bottom. Ammonium nitrogen concentration during December was less than 0.02 mg/L at all sites (0.007 – 0.018 mg/L within the cage sites, and 0.012 – 0.019 mg/L in the non-cage sites). Nitrite nitrogen ranged from 0.002 – 0.169 mg/L in the cage area, and 0.003 – 0.057 mg/L in the non-cage areas. Similar to previous records of June and September 2017, nitrate nitrogen concentration generally increased towards the downstream site, being lowest at RPT (0.041 mg/L) and highest at DSC (0.204 mg/L). Soluble reactive phosphorus was less than 0.005 mg/L at all sites, and varied within narrow margin (range: 0.003 – 0.0048 mg/L in cage sites, and 0.0032 – 0.0047 mg/L in non-cage sites). The TP concentration ranged from 0.085 – 0.107 mg/L in the cages, and 0.090 – 0.118 mg/L in the non-cage sites and was higher than recorded in September (0.038 – 0.044 mg/L in the cages and 0.04 to 0.109 mg/L away from cages). Total nitrogen concentration was in the range of 0.138 – 0.553 mg/L within cage area and 0.421 – 0.513 mg/L in non-cage areas. The concentration of TSS ranged from 0.76 – 4.33 mg/L in the cage area and 0.57 – 2.76 mg/L in the non-cage areas. The phytoplankton community was composed of blue-green algae, green algae and diatoms, dominated by blue-green algae. The abundance of algae was higher in the non-cage areas (mean:7.20 ± 2.14 mm3L-1, Range: 5.15 – 10.20 mm3L-1) than recorded in the cage areas (mean: 6.0 ± 0.71 mm3L-1, Range: 5.30 – 6.98 mm3L-1), similar to observations of September 2017 (5.6 mm3L-1 in the non-cage sites). At all sampled points, blue-green algae contributed >70% of total abundance. Total zooplankton abundance ranged from 982,213 – 1,310,830 ind.m-2 in the non-cage sites, and 740,601 – 1,503,130 ind.m-2 in the cage areas. Similar to observations of September 2017, the upper cage site (WIC3 and WIC4) presented lower zooplankton abundance (mean: 788,954 ± 68,381 ind.m-2) when compared to the lower cage site with mean abundance of 1,128,232 ± 530,186 ind.m-2. Like in the previous sampling periods, copepods were the numerically dominant group (92.69 – 97.22 % of total zooplankton abundance) at all sampled points, with no major differences between cage and non-cage areas. The high abundance of copepods was attributed to the abundance of the juvenile stages (copepodites and Nauplius larvae) which contributed 83.72 – 92.78% of the total zooplankton abundance and this was mainly due to the Nauplius larvae (66.4 – 83.2 %). Cladocera relative abundance ranged from 0.32 – 3.98% while that of rotifers ranged from 1.55 – 3.74%. The macro-benthic community comprised molluscs, annelids and arthropods. Taxa richness ranged from 5 – 11 taxa in the cage area, and 7 – 9 taxa in the non-cage areas. The abundance of benthic invertebrates within the cage area ranged from 1,134 – 2,416 ind.m-2 and this was higher than previously recorded in September (294 – 1,415 ind.m-2). In the non-cage sites abundance was in the range of 420 – 3,992 ind.m-2. Oligochaete annelids which are reported to be very tolerant to pollution contributed 0 - 28 % of the abundance of benthos at cage sites and 3 - 20% at the non-cage sites. Diptera made the greatest contribution at almost all sites, with the percent abundance being higher in non-cage sites (40 – 86%) than what was recorded in the cage sites (37 – 82%). Chironomus spp. and Chaoborus sp. were the main contributors to the observed Diptera abundance at all sites. Six fish species, including haplochromines (Nkejje) as a single species group, were recorded in the vicinity of the cages during December 2017. Five fish species were recorded from upstream the cage site, four species from within cage area, and two species from downstream the cages. Overall mean catch rates were 1.8 fish/net/night and 148.6g/net/night compared to 1.7 fish/net/night and 175.4g/net/night recorded in September 2017. By weight, catch rates in December 2017 were highest upstream the cage site (312.1g/net/night) and also by numbers (3.1 fish/net/night). Four species of haplochromines were recorded in the vicinity of the cages during the survey of December 2017 compared to six species recorded in September 2017. The overall catch rate for the haplochromines, in December 2017 was 1.7fish/net/night and 27.5g/net/night compared to 3.4 fish/net/night and 62.3g/net/night recorded in the previous survey of September 2017. Among the fish species examined during December 2017 survey, most of the haplochromine cichlids (88.9%) were mature but only 50% breeding. Only one specimen of L. niloticus was mature and breeding. All S. afrofischeri and S. victoriae specimens examined were mature and in breeding condition while M. kannume was immature. The diet of fishes encountered comprised mostly of fish and insects, which are known natural foods of the fish species. Infection by fish parasites during the survey of December 2017 was not noticed in any fish recorded from the experimental gillnets. The overall observation on concentrations of nutrients, levels of physico-chemical variables, and biotic communities indicated minimal impact of cages on water quality. The farm should therefore continue adhering to the best environmentally sustainable aquaculture practices, especially continuing with fallowing or rotation of cages to allow resident organisms maintain their natural population densities, distribution and community structure in the area; reducing excess uneaten feed and other suspended materials which would impact on nutrient status and biota; as well as wise use of any chemicals in the area

Maternal education is associated with vaccination status of infants less than 6 months in Eastern Uganda: a cohort study

<p>Abstract</p> <p>Background</p> <p>Despite provision of free childhood vaccinations, less than half of all Ugandan infants are fully vaccinated. This study compares women with some secondary schooling to those with only primary schooling with regard to their infants' vaccination status.</p> <p>Methods</p> <p>A community-based prospective cohort study conducted between January 2006 and May 2008 in which 696 pregnant women were followed up to 24 weeks post partum. Information was collected on the mothers' education and vaccination status of the infants.</p> <p>Results</p> <p>At 24 weeks, the following vaccinations had been received: bacille Calmette-Guérin (BCG): 92%; polio-1: 91%; Diphteria-Pertussis-Tetanus-Hepatitis B-Haemophilus Influenza b (DPT-HB-Hib) 3 and polio-3: 63%. About 51% of the infants were fully vaccinated (i.e., had received all the scheduled vaccinations: BCG, polio 0, polio 1, DPT-HB-Hib1, polio 2, DPT-HB-Hib 2, polio 3 and DPT-HB-Hib 3). Only 46% of the infants whose mothers' had 5-7 years of primary education had been fully vaccinated compared to 65% of the infants whose mothers' had some secondary education. Infants whose mothers had some secondary education were less likely to miss the DPT-HB-Hib-2 vaccine (RR: 0.5, 95% CI: 0.3, 0.8), Polio-2 (RR: 0.4, 95%CI: 0.3, 0.7), polio-3 (RR: 0.5, 95%CI: 0.4, 0.7) and DPT-HB-Hib-3 (RR: 0.5, 95%CI: 0.4, 0.7). Other factors showing some association with a reduced risk of missed vaccinations were delivery at a health facility (RR = 0.8; 95%CI: 0.7, 1.0) and use of a mosquito net (RR: 0.8; 95%CI: 0.7, 1.0).</p> <p>Conclusion</p> <p>Infants whose mothers had a secondary education were at least 50% less likely to miss scheduled vaccinations compared to those whose mothers only had primary education. Strategies for childhood vaccinations should specifically target women with low formal education.</p

Seroepidemiology of SARS-CoV-2 in a cohort of pregnant women and their infants in Uganda and Malawi.

BACKGROUND: Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic, though evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are scarce. Limited information is available from countries in sub-Saharan Africa (SSA). The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. OUTCOME: Seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. METHODS: The PeriCOVID study was a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. Maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. In periCOVID Uganda and Malawi nose and throat swabs for SARS-Cov-2 RT-PCR were obtained. RESULTS: In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron), in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes

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

Malaria misdiagnosis in Uganda – implications for policy change

BACKGROUND: In Uganda, like in many other countries traditionally viewed as harbouring very high malaria transmission, the norm has been to recommend that febrile episodes are diagnosed as malaria. In this study, the policy implications of such recommendations are revisited. METHODS: A cross-sectional survey was undertaken at outpatient departments of all health facilities in four Ugandan districts. The routine diagnostic practices were assessed for all patients during exit interviews and a research slide was obtained for later reading. Primary outcome measures were the accuracy of national recommendations and routine malaria diagnosis in comparison with the study definition of malaria (any parasitaemia on expert slide examination in patient with fever) stratified by age and intensity of malaria transmission. Secondary outcome measures were the use, interpretation and accuracy of routine malaria microscopy. RESULTS: 1,763 consultations undertaken by 233 health workers at 188 facilities were evaluated. The prevalence of malaria was 24.2% and ranged between 13.9% in patients >or=5 years in medium-to-high transmission areas to 50.5% for children <5 years in very high transmission areas. Overall, the sensitivity and negative predictive value (NPV) of routine malaria diagnosis were high (89.7% and 91.6% respectively) while the specificity and positive predictive value (PPV) were low (35.6% and 30.8% respectively). However, malaria was under-diagnosed in 39.9% of children less than five years of age in the very high transmission area. At 48 facilities with functional microscopy, the use of malaria slide examination was low (34.5%) without significant differences between age groups, or between patients for whom microscopy is recommended or not. 96.2% of patients with a routine positive slide result were treated for malaria but also 47.6% with a negative result. CONCLUSION: Current recommendations and associated clinical practices result in massive malaria over-diagnosis across all age groups and transmission areas in Uganda. Yet, under-diagnosis is also common in children <5 years. The potential benefits of malaria microscopy are not realized. To address malaria misdiagnosis, Uganda's policy shift from presumptive to parasitological diagnosis should encompass introduction of malaria rapid diagnostic tests and substantial strengthening of malaria microscopy