How prepared is the world? Identifying weaknesses in existing assessment frameworks for global health security through a One Health approach.

The COVID-19 pandemic has exposed faults in the way we assess preparedness and response capacities for public health emergencies. Existing frameworks are limited in scope, and do not sufficiently consider complex social, economic, political, regulatory, and ecological factors. One Health, through its focus on the links among humans, animals, and ecosystems, is a valuable approach through which existing assessment frameworks can be analysed and new ways forward proposed. Although in the past few years advances have been made in assessment tools such as the International Health Regulations Joint External Evaluation, a rapid and radical increase in ambition is required. To sufficiently account for the range of complex systems in which health emergencies occur, assessments should consider how problems are defined across stakeholders and the wider sociopolitical environments in which structures and institutions operate. Current frameworks do little to consider anthropogenic factors in disease emergence or address the full array of health security hazards across the social-ecological system. A complex and interdependent set of challenges threaten human, animal, and ecosystem health, and we cannot afford to overlook important contextual factors, or the determinants of these shared threats. Health security assessment frameworks should therefore ensure that the process undertaken to prioritise and build capacity adheres to core One Health principles and that interventions and outcomes are assessed in terms of added value, trade-offs, and cobenefits across human, animal, and environmental health systems.

Assessment of neutralizing antibody responses after natural SARS-CoV-2 infection and vaccination in congolese individuals.

BACKGROUND: Assessing immune responses after vaccination is part of the evaluation package of vaccine effectiveness in the real world. Regarding SARS-CoV-2, neutralizing antibody levels has been shown to be a good indicator of antibody immune response boosting. So far, limited data have been reported from Africa including in Central Africa. The objective of this study was to provide data on anti-S1 spike total IgG and neutralizing antibodies in vaccinated and non-vaccinated including naturally infected Congolese population during B.1.214.1 and B.1.617.2 variant waves. METHODS: Recruited patients were divided into 4 groups: (1) Naturally infected by the B.1.214.1 variant on January 2021 and followed up until September 2021. These patients have been vaccinated at month 07 and then followed up for 2 months post vaccination; (2) Naturally infected by the B.1.617.2 variant from June 2021; (3) unvaccinated SARS-CoV-2 individuals with no history of prior SARS-CoV-2 infection; (4) fully vaccinated individuals with sinopharm/BBIP-CorV or Janssen/Ad26.COV2.S. SARS-CoV-2 was detected by qRT-PCR and sequenced using Next-Generation Sequencing. ELISA method was used for detecting IgG, and neutralizing Antibody against SARS-CoV-2 antigens using commercial neutralizing assay. RESULTS: Individuals infected by the B.1214.1 variant elicited consistently high IgG titers at 02, 03 and 06 months. Two months post vaccination with BBIP-CorV, participants showed a significant increase by × 2.5 fold (p < 0.0001) of total IgG and X1.5 fold for neutralizing antibody capacity. This study showed that natural infection with B1.617.2 (delta) variant was more immunogenic compared to those being infected with B1.214.2 variant. We found a significantly higher concentration in anti-SARS-CoV-2 IgG (p < 0.0002) and antibodies neutralization capacity (P < 0.0001) in fully vaccinated compared to unvaccinated participants. Two months post vaccination, individuals who received Janssen/Ad26.COV2.S presented higher (p = 0.01) total IgG to spike protein compared to BBIP-CorV. CONCLUSION: Both natural infection and vaccination with BBIP-CorV and Janssen/Ad26.COV2.S induced antibody response in Congolese population. In addition, Janssen/Ad26.COV2.S was more immunogenic than Sinopharm/BBIP-CorV. There is a need to investigate the duration of these antibodies both in previously infected and naive vaccinated Congolese to allow public heath stakeholders to make evidence-based decision on vaccine schedule for the Congolese population.

Increased outbreaks of monkeypox highlight gaps in actual disease burden in Sub-Saharan Africa and in animal reservoirs.

We explain research gaps on Monkeypox (MPX) virus epidemiology in endemic countries and present hypotheses for the recent increase of MPX cases in West Africa as a possible explanation for the current epidemic in Europe, America, and Australia. The detection of >400 MPX cases in less than a month in May 2022, across many countries underscores the epidemic potential of MPX in humans and demonstrates several important research gaps. First, the true burden of MPX in West and Central Africa is poorly understood, although it is critical for prevention and control of future outbreaks. Second, the diversity and extent of the animal reservoir remain unknown. We hypothesize that the synanthropic rodent population has increased in recent years in Africa leading to more human-rodent interactions and thus increased transmission of MPXV. We further hypothesise that nearly 45 years after the end of routine smallpox vaccination, the larger and more interconnected immune-naïve population has crossed a threshold resulting in more sustainable human-to-human transmission of MPXV. The current epidemic in the Western World is possibly a consequence of increased local transmission of MPXV in Africa. A new estimation of the basic and effective reproduction rate (R0 and Re) in different populations is required. National, regional, and international collaborations are needed to address research gaps related to MPX outbreaks.

Chikungunya: Epidemiology, Pathogenesis, Clinical Features, Management, and Prevention.

Chikungunya, a zoonotic disease caused by the Chikungunya virus (CHIKV), is transmitted by infected Aedes spp mosquitoes. CHIKV has now spread to more than 100 countries and is listed on the WHO Blueprint priority pathogens. After an incubation period of 1 to 12 days, symptoms similar to other febrile infections appear, with a sudden onset of high fever, nausea, polyarthralgia, myalgia, widespread skin rash, and conjunctivitis. Serious complications include myocarditis, uveitis, retinitis, hepatitis, acute renal disease, severe bullous lesions, meningoencephalitis, Guillain-Barré syndrome, myelitis, and cranial nerve palsies. Treatment is supportive; there is no specific antiviral treatment and no effective vaccine.

Achieving sustainable development goals for HIV/AIDS in the Republic of the Congo - Progress, obstacles and challenges in HIV/AIDS health services.

The HIV epidemic continues to be a major global public health issue. Since 2012, there has been a paucity of information from the Republic of the Congo on HIV incidence and prevalence rates, national HIV programme effectiveness, highly active antiretroviral therapy (HAART) rollout, patient adherence to treatment, operational and basic science research studies on HIV/AIDS, and donor funding and its impact on the country. A review of the existing literature on HIV in the Republic of the Congo was conducted, focused on prevalence trends, effectiveness of the current national HIV programme, HAART rollout, patient adherence to antiretrovirals (ARVs), resistance to ARVs, the cost of treatment, and operational issues affecting HIV/AIDS programmes in the country. In light of the findings, several important priority areas for scaling-up HIV/AIDS services, programmatic and research activities in the Republic of the Congo are highlighted.

Avoidable waste related to inadequate methods and incomplete reporting of interventions: a systematic review of randomized trials performed in Sub-Saharan Africa.

BACKGROUND: Randomized controlled trials (RCTs) are needed to improve health care in Sub-Saharan Africa (SSA). However, inadequate methods and incomplete reporting of interventions can prevent the transposition of research in practice which leads waste of research. The aim of this systematic review was to assess the avoidable waste in research related to inadequate methods and incomplete reporting of interventions in RCTs performed in SSA. METHODS: We performed a methodological systematic review of RCTs performed in SSA and published between 1 January 2014 and 31 March 2015. We searched PubMed, the Cochrane library and the African Index Medicus to identify reports. We assessed the risk of bias using the Cochrane Risk of Bias tool, and for each risk of bias item, determined whether easy adjustments with no or minor cost could change the domain to low risk of bias. The reporting of interventions was assessed by using standardized checklists based on the Consolidated Standards for Reporting Trials, and core items of the Template for Intervention Description and Replication. Corresponding authors of reports with incomplete reporting of interventions were contacted to obtain additional information. Data were descriptively analyzed. RESULTS: Among 121 RCTs selected, 74 (61%) evaluated pharmacological treatments (PTs), including drugs and nutritional supplements; and 47 (39%) nonpharmacological treatments (NPTs) (40 participative interventions, 1 surgical procedure, 3 medical devices and 3 therapeutic strategies). Overall, the randomization sequence was adequately generated in 76 reports (62%) and the intervention allocation concealed in 48 (39%). The primary outcome was described as blinded in 46 reports (38%), and incomplete outcome data were adequately addressed in 78 (64%). Applying easy methodological adjustments with no or minor additional cost to trials with at least one domain at high risk of bias could have reduced the number of domains at high risk for 24 RCTs (19%). Interventions were completely reported for 73/121 (60%) RCTs: 51/74 (68%) of PTs and 22/47 (46%) of NPTs. Additional information was obtained from corresponding authors for 11/48 reports (22%). CONCLUSION: Inadequate methods and incomplete reporting of published SSA RCTs could be improved by easy and inexpensive methodological adjustments and adherence to reporting guidelines.

Published randomized trials performed in Sub-Saharan Africa focus on high-burden diseases but are frequently funded and led by high-income countries.

BACKGROUND AND OBJECTIVE: In light of funding constraints in Sub-Saharan Africa (SSA), the value of research performed there must be increased. The objective of this study was to describe the epidemiology of published randomized controlled trials (RCTs) performed in SSA. METHODS: We searched PubMed, the Cochrane library, and African Index Medicus to identify reports of all RCTs performed in SSA and published between January 1, 2014 and March 31, 2015. We systematically recorded the country of the affiliation of the corresponding author and the funding source. The overall burden of disease was assessed by 2013 disability-adjusted life years (both sexes, all ages) in percentages for two locations: SSA and high-income countries (HICs). RESULTS: Only 12 of 121 RCTs were conducted in both Sub-Saharan Africa and another region, with 109 of 121 RCTs (90%) having trial centers exclusively located in SSA. The corresponding author's only affiliation was in SSA for 44/109 trials (40%) and was institutions in HICs for almost half of the trials. The funding source was nonprofit for 77/109 trials (70%) and was from HICs for 81% (n = 63/77). Overall, most RCTs targeted diseases with a high burden in SSA; 46% of the trials targeted the five diseases with the highest burden in SSA, mainly malaria (n = 25), HIV/AIDS (n = 24), lower respiratory tract infection (n = 2), diarrheal diseases (n = 3), and preterm birth complications (n = 2). Nevertheless, among the 25 diseases or health-related conditions with the highest burden in SSA, 9 (36%) were not assessed in any RCT. CONCLUSIONS: Published RCTs performed in SSA were mainly funded and led by HIC institutions, although investigations concerned diseases highly prevalent in SSA.

Impact of infectious disease epidemics on tuberculosis diagnostic, management, and prevention services: experiences and lessons from the 2014-2015 Ebola virus disease outbreak in West Africa.

The World Health Organization (WHO) Global Tuberculosis Report 2015 states that 28% of the world's 9.6 million new tuberculosis (TB) cases are in the WHO Africa Region. The Mano River Union (MRU) countries of West Africa-Guinea, Sierra Leone, and Liberia-have made incremental sustained investments into TB control programmes over the past two decades. The devastating Ebola virus disease (EVD) outbreak of 2014-2015 in West Africa impacted significantly on all sectors of the healthcare systems in the MRU countries, including the TB prevention and control programmes. The EVD outbreak also had an adverse impact on the healthcare workforce and healthcare service delivery. At the height of the EVD outbreak, numerous staff members in all MRU countries contracted EBV at the Ebola treatment units and died. Many healthcare workers were also infected in healthcare facilities that were not Ebola treatment units but were national hospitals and peripheral health units that were unprepared for receiving patients with EVD. In all three MRU countries, the disruption to TB services due to the EVD epidemic will no doubt have increased Mycobacterium tuberculosis transmission, TB morbidity and mortality, and decreased patient adherence to TB treatment, and the likely impact will not be known for several years to come. In this viewpoint, the impact that the EVD outbreak had on TB diagnostic, management, and prevention services is described. Vaccination against TB with BCG in children under 5 years of age was affected adversely by the EVD epidemic. The EVD outbreak was a result of global failure and represents yet another 'wake-up call' to the international community, and particularly to African governments, to reach a consensus on new ways of thinking at the national, regional, and global levels for building healthcare systems that can sustain their function during outbreaks. This is necessary so that other disease control programmes (like those for TB, malaria, and HIV) are not compromised during the emergency measures of a severe epidemic.

Malaria burden and case management in the Republic of Congo: limited use and application of rapid diagnostic tests results.

BACKGROUND: There have been few investigations evaluating the burden of malaria disease at district level in the Republic of Congo since the introduction of artemisinin-based combination therapies (ACTs). The main objective of this study was to document laboratory-confirmed cases of malaria using microscopy and/or rapid diagnostic tests (RDTs) in children and pregnant women attending selected health facilities in Brazzaville and Pointe Noire, the two main cities of the country. Secondly, P. falciparum genetic diversity and multiplicity of infection during the malaria transmission season of October 2011 to February 2012 in these areas were described. METHODS: Three and one health facilities were selected in Brazzaville and Pointe-Noire as sentinel sites for malaria surveillance. Children under 15 years of age and pregnant women were enrolled if study criteria were met and lab technicians used RDT and/or microscopy to diagnose malaria. In order to determine the multiplicity of infection, parasite DNA was extracted from RDT cassette and msp2 P.falciparum genotyped. RESULTS: Malaria prevalence among more than 3,000 children and 700 pregnant women ranged from 8 to 29%, and 8 to 24% respectively depending on health center locality. While health workers did not optimize use of RDTs, microscopy remained a reference diagnostic tool. Quality control of malaria diagnosis at the reference laboratory showed acceptable health centre performances. P. falciparum genetic diversity determination using msp2 gene marker ranged from 9 to 20 alleles and remains stable while multiplicity of infection (mean of 1.7clone/infected individual) and parasite densities in clinical isolates were lower than previously reported. CONCLUSIONS: These findings are consistent with a reduction of malaria transmission in the two areas. This study raises the issue of targeted training for health workers and sustained availability of RDTs in order to improve quality of care through optimal use of RDTs.

Africanizing scientific knowledge: the Multilateral Initiative on Malaria as a model?

In November 2009, the fifth Pan African Malaria conference was held in Nairobi. Thirteen years after the founding initiative in Dakar, the first African Secretariat based in Africa (TANZANIA) organized this major event for the malaria community. Looking back, it has been a long way: changes in the research landscape, new funding opportunities came out and establishment of new partnerships between Europe, America and Africa. Goals identified in 1997 have not all been achieved because the critical mass of scientists has not been reached yet. However a new generation of African scientists have emerged through MIM/TDR funding and advocacy for more support remains on the agenda. Could it be rightly stated today that the MIM concept reflects the africanization of malaria research?

Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub-Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness.

Molecular genotyping of baseline and post-treatment recurrent Plasmodium falciparum is recommended to distinguish recrudescent from new infections. However, genotyping performance and adjustment of treatment outcomes have not been evaluated in large field trials. Parasitological outcomes were assessed in nine double-blinded trials of uncomplicated P. falciparum malaria in African children treated with artesunate/placebo plus standard monotherapies. Day 28 failure rates were adjusted by stepwise genotyping the P. falciparum glutamate rich protein (glurp), merozoite surface protein 1 (msp1) and 2 (msp2). We calculated overall and laboratory genotyping performance and compared unadjusted (crude) and PCR-adjusted outcomes. 3455 (93.6%) of 3691 enrolled patients were evaluable by Day 28. 767 (22%) had post-Day 14 recurrent parasitemias of which 686 could be genotyped: 246 were recrudescences, 286 new infections and 154 unresolved. The overall and laboratory genotyping performance were 69 (12-100)% and 78 (50-100)%, respectively. The mean Day 28 crude parasitological failure rate was 44 (range 3-87)%. PCR-adjusted rates were 36 (range 2-86)% if unresolved infections were counted as failures or 33 (range 2-86)% if excluded from analysis. The overall difference between crude Day 28 and Day 14 failure rates was 22% (95% CI 20.3, 24.6) but decreased to 14% (95% CI 12.1, 16.3) if unresolved infections are counted as failures, or to 11% (95% CI 9.8, 16.3) if unresolved infections are excluded from the analysis. Genotyping refined treatment outcomes but diligence is needed in sample collection and analysis to improve its performance. Our findings support the WHO recommendation of PCR genotyping in malaria clinical trials and suggest that stepwise genotyping of only two loci (msp2 and msp1 or glurp) can reliably discriminate recrudescences from new infections.