Leveraging human resources for outbreak analysis: lessons from an international collaboration to support the sub-Saharan African COVID-19 response.

Emerging infectious diseases are a growing threat in sub-Saharan African countries, but the human and technical capacity to quickly respond to outbreaks remains limited. Here, we describe the experience and lessons learned from a joint project with the WHO Regional Office for Africa (WHO AFRO) to support the sub-Saharan African COVID-19 response.In June 2020, WHO AFRO contracted a number of consultants to reinforce the COVID-19 response in member states by providing actionable epidemiological analysis. Given the urgency of the situation and the magnitude of work required, we recruited a worldwide network of field experts, academics and students in the areas of public health, data science and social science to support the effort. Most analyses were performed on a merged line list of COVID-19 cases using a reverse engineering model (line listing built using data extracted from national situation reports shared by countries with the Regional Office for Africa as per the IHR (2005) obligations). The data analysis platform The Renku Project ( https://renkulab.io ) provided secure data storage and permitted collaborative coding.Over a period of 6 months, 63 contributors from 32 nations (including 17 African countries) participated in the project. A total of 45 in-depth country-specific epidemiological reports and data quality reports were prepared for 28 countries. Spatial transmission and mortality risk indices were developed for 23 countries. Text and video-based training modules were developed to integrate and mentor new members. The team also began to develop EpiGraph Hub, a web application that automates the generation of reports similar to those we created, and includes more advanced data analyses features (e.g. mathematical models, geospatial analyses) to deliver real-time, actionable results to decision-makers.Within a short period, we implemented a global collaborative approach to health data management and analyses to advance national responses to health emergencies and outbreaks. The interdisciplinary team, the hands-on training and mentoring, and the participation of local researchers were key to the success of this initiative.

Congenital Toxoplasmosis: Missed Opportunities for Diagnosis and Prevention.

OBJECTIVES: Identify missed opportunities for the prevention and early diagnosis of congenital toxoplasmosis (CT) in infants followed up in a reference center for pediatric infectious diseases (PID) in Rio de Janeiro between January 2007 and December 2016. METHODS: Descriptive study including infants with CT, diagnosis established based on Brazil's Ministry of Health's criteria. All data regarding the infants and their mother's prenatal care were collected from the medical records of the Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG)-a tertiary public pediatric university hospital. The study enrolled infants aged between 0 and 12 months followed up in the PID department of IPPMG and with confirmed infection by Toxoplasma gondii in the period between January 2007 and December 2016. All patients with diagnosis of CT registered in the PID database of the IPPMG and admitted in the above-mentioned period were included in the study. Patients whose records were not available, or who went to just one clinic appointment were excluded. RESULTS: The obstetric history of all 44 women, whose infants (45) were diagnosed with CT, was analyzed. Their median age was 22 years. None had undergone preconception serological testing for toxoplasmosis. Only 20 (45%) of them started antenatal care during the first trimester of gestation, a total of 24 (55%) had more than six antenatal care visits, and 16% of those did not undergo serological testing for toxoplasmosis. None were adequately informed of preventive measures. The diagnosis of acute toxoplasmosis was made in 50% of these pregnancies but 32% of the women were not treated. Only 10 children of these mothers were adequately screened and treated at birth. CONCLUSION: Despite the existence of national recommendations, several opportunities were missed to prevent CT during the antenatal period and to diagnose and treat this condition in the neonatal period.

Factors associated with the development of Congenital Zika Syndrome: a case-control study.

BACKGROUND: We aim to investigate possible maternal- and pregnancy-related factors associated with the development of Congenital Zika Syndrome (CZS) in children of mothers with probable gestational infection. METHODS: This case-control study, we recruited mother-infant pairs between May 2015 and October 2017 in a pediatric infectious disease clinic in Rio de Janeiro. Inclusion criteria required either that the mother reported Zika infection symptoms during pregnancy or that the infant presented with clinical or imaging features of the CZS. Exclusion criteria included detection of an alternative cause for the patient's presentation or negative polymerase chain reaction assays for Zika in all specimens tested within 12 days from the beginning of maternal symptoms. Infants with CZS (CDC definition) were selected as cases and infants without CZS, but with probable maternal Zika virus infection during pregnancy, were selected as controls. Maternal and pregnancy-related informations were collected and their relationship to the presence of congenital anomalies due to CZS was assessed by Fisher exact or Mann-Whitney test. RESULTS: Out of the 42 included neonates, 24 (57.1%) were diagnosed with CZS (cases). The mean maternal age at the birth was 21 years old. The early occurrence of maternal symptoms during pregnancy was the only variable associated with CZS (odds ratio = 0.87, 95% CI: 0.78-0.97). Case's mothers presented symptoms until the 25th week of gestational age (GA), while control's mothers presented until 36th weeks of GA. Income; illicit drug, alcohol, or tobacco use during pregnancy; other infections during pregnancy (including previous dengue infection) were not associated with CZS. CONCLUSIONS: Our study corroborates the hypothesis that Zika virus infection earlier in pregnancy is a risk factor to the occurrence of congenital anomalies in their fetuses.

Antenatal factors related to congenital toxoplasmosis in Rio De Janeiro, Brazil.

BACKGROUND: Toxoplasmosis is one of the main preventable congenital infections in Brazil. This manuscript aims to describe antenatal factors possibly associated with congenital toxoplasmosis (CT). METHODS: This is a case-control study, with data collected from medical records, from infants admitted under one year of age at the Infectious Diseases Clinic of Instituto de Puericultura e Pediatria Martagão Gesteira, reference center from Rio de Janeiro, exposed to toxoplasmosis during their antenatal period. Patients diagnosed with CT were classified as cases and those exposed without infection as controls. RESULTS: A total of 289 patients were followed up in 10 years. CT was confirmed in 43 (14.9%) of which six (14%) were asymptomatic, five (12%) had the classic triad (retinochoroiditis, hydrocephalus and intracranial calcifications), 27/42 (64.3%) had reactive IgM. Even after adjusted for prematurity, cases were born with lower weight (OR 0.49 - IC95% 0.33-0.73). There was a 13% increase in chance of CT per gestational week of the maternal diagnosis. Maternal fever, consumption of poorly washed vegetables during pregnancy, and diagnosis in the third trimester were associated with CT (OR: 6.43, 6.55, and 2.16, respectively). CONCLUSION: Fever during pregnancy, consumption of poorly washed vegetables and diagnosis in the third trimester were associated with CT. Infants with diagnosis of CT were born with lower weight than the controls.

COVID-19 pandemic in Africa's island nations during the first 9 months: a descriptive study of variation in patterns of infection, severe disease, and response measures.

The geographic and economic characteristics unique to island nations create a different set of conditions for, and responses to, the spread of a pandemic compared with those of mainland countries. Here, we aimed to describe the initial period of the COVID-19 pandemic, along with the potential conditions and responses affecting variation in the burden of infections and severe disease burden, across the six island nations of the WHO's Africa region: Cabo Verde, Comoros, Madagascar, Mauritius, São Tomé e Príncipe and Seychelles. We analysed the publicly available COVID-19 data on confirmed cases and deaths from the beginning of the pandemic through 29 November 2020. To understand variation in the course of the pandemic in these nations, we explored differences in their economic statuses, healthcare expenditures and facilities, age and sex distributions, leading health risk factors, densities of the overall and urban populations and the main industries in these countries. We also reviewed the non-pharmaceutical response measures implemented nationally. We found that the burden of SARS-CoV-2 infection was reduced by strict early limitations on movement and biased towards nations where detection capacity was higher, while the burden of severe COVID-19 was skewed towards countries that invested less in healthcare and those that had older populations and greater prevalence of key underlying health risk factors. These findings highlight the need for Africa's island nations to invest more in healthcare and in local testing capacity to reduce the need for reliance on border closures that have dire consequences for their economies.

An in-depth statistical analysis of the COVID-19 pandemic's initial spread in the WHO African region.

During the first wave of the COVID-19 pandemic, sub-Saharan African countries experienced comparatively lower rates of SARS-CoV-2 infections and related deaths than in other parts of the world, the reasons for which remain unclear. Yet, there was also considerable variation between countries. Here, we explored potential drivers of this variation among 46 of the 47 WHO African region Member States in a cross-sectional study. We described five indicators of early COVID-19 spread and severity for each country as of 29 November 2020: delay in detection of the first case, length of the early epidemic growth period, cumulative and peak attack rates and crude case fatality ratio (CFR). We tested the influence of 13 pre-pandemic and pandemic response predictor variables on the country-level variation in the spread and severity indicators using multivariate statistics and regression analysis. We found that wealthier African countries, with larger tourism industries and older populations, had higher peak (p<0.001) and cumulative (p<0.001) attack rates, and lower CFRs (p=0.021). More urbanised countries also had higher attack rates (p<0.001 for both indicators). Countries applying more stringent early control policies experienced greater delay in detection of the first case (p<0.001), but the initial propagation of the virus was slower in relatively wealthy, touristic African countries (p=0.023). Careful and early implementation of strict government policies were likely pivotal to delaying the initial phase of the pandemic, but did not have much impact on other indicators of spread and severity. An over-reliance on disruptive containment measures in more resource-limited contexts is neither effective nor sustainable. We thus urge decision-makers to prioritise the reduction of resource-based health disparities, and surveillance and response capacities in particular, to ensure global resilience against future threats to public health and economic stability.

Serum IgG Titers Against Toxoplasma gondii in Uninfected Infants Exposed In Utero to Toxoplasmosis.

OBJECTIVES: To describe the mean time of decrease of T. gondii IgG titers in uninfected infants exposed in utero to toxoplasmosis. METHODS: A retrospective cohort study was conducted between 2008-2017, among infants under 12 months and exposed in utero to toxoplasmosis. Serial monthly monitoring of serum IgG titers were done till undetectable levels. RESULTS: 240 infants with mean gestational age at diagnosis of 19.2 weeks were included in the study. The mean (range) time for IgG level to become undetectable was 7.9 (0.8-25.0) months. 14 infants became negative between 13-24 months. CONCLUSIONS: Majority of asymptomatic infants exposed in utero to T. gondii become seronegative before 12 months of age.

Complications and Sequelae in Patients With Congenital Microcephaly Associated With Zika Virus Infection: Two-Year Follow-Up.

BACKGROUND: We aim to describe the long term follow-up of a cohort of children exposed in utero to the Zika virus. METHODS: Descriptive study of a cohort of microcephalic children due to Zika virus. Logistic regression was used to evaluate variables associated with worse prognosis epilepsy. RESULTS: We followed 28 children (15 females), with a median follow-up of 24 months (IQR = 12-28). During the follow-up, 1 infant died. The median head circumference at birth was 29 cm (IQR = 27-31). All presented a global developmental delay. The most frequent central nervous system abnormalities were on cortical development in 22 participants; dysgenesis of corpus callosum in 13; ventriculomegaly in 25; and calcifications in 24. A total of 9 presented ocular abnormalities, 4 auditory impairment. During follow-up, 12 presented with sleep disorders, 10 with irritability, and 23 with epilepsy (2 with generalized tonic-clonic, 3 with generalized tonic-clonic and spasms, 12 with spasms, 3 tonic and spasms, and 3 motor focal and spasms). The median age at the begin of the epilepsy was 4 months (IQR = 2-10), the median number of drugs used to control the epilepsy was 2 (IQR = 2-3). Maternal illicit drug use during pregnancy was associated with worse prognosis epilepsy (Lennox-Gastaut syndrome, West syndrome, or status epilepticus). A total of 19 presented with dysphagia, 10 children required gastrostomy. CONCLUSION: Children with microcephaly due to Zika virus presented with several complications during follow-up, as epilepsy, spastic diplegia, and global developmental delay.