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Abstract Background Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie. Methods SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region. Findings The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship. Conclusions The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach.

Introduction: Acute viral gastroenteritis is a major public health concern, especially among children younger than 5 years of age. The aim of this study was to determine the occurrence of human astrovirus infection in children with acute gastroenteritis. Methods: Stool specimens were collected from 506 children under 5 years of age hospitalized with acute diarrhoea (289 male and 208 female), and human astrovirus was investigated by RT-PCR. Associations of socio-demographic, clinical, and behavioural conditions with infection were analysed. Results: The overall prevalence of human astrovirus was found to be 10.3%. The mean age of positive cases was 12.41 ± 6.21 months and this was associated with infection (p = 0.013). Children >18 months of age were at three times the risk of infection when compared to those aged 0–6 months (odds ratio (OR) 3.19, 95% confidence interval (CI) 1.15–8.88; p = 0.026). Children living in houses with more than one room (OR 0.60, 95% CI 0.28–0.96; p = 0.036) and mothers using treated water (OR 0.47, 95% CI 0.25–0.86; p = 0.015) were associated with reduced infection. Conclusions: In this study, infection with astrovirus was common in acute gastroenteritis cases among children younger than 5 years of age. Drinking treated water and living in non-crowded environments protected the children from infection.

Abstract Background Malaria in pregnancy is associated with considerable morbidity and mortality. Regular surveillance of artemisinin-based combination therapy tolerance, or molecular makers of resistance, is vital for effective malaria treatment, control and eradication programmes. Plasmodium falciparum multiple drug resistance-1 gene (Pfmdr1) N86Y mutation is associated with reduced susceptibility to lumefantrine. This study assessed the prevalence of Pfmdr1 N86Y in Brazzaville, Republic of Congo. Methods A total 1001 of P. falciparum-infected blood samples obtained from asymptomatic malaria pregnant women having a normal child delivery at the Madibou Integrated Health Centre were analysed. Pfmdr1 N86Y genotyping was conducted using PCR-restriction fragment length polymorphism. Results The wild type Pfmdr1 N86 allele was predominant (> 68%) in this study, whereas a few isolates carrying the either the mutant allele (Pfmdr1 86Y) alone or both alleles (mixed genotype). The dominance of the wildtype allele (pfmdr1 N86) indicates the plausible decline P. falciparum susceptibility to lumefantrine. Conclusion This study gives an update on the prevalence of Pfmdr1 N86Y alleles in Brazzaville, Republic of Congo. It also raises concern on the imminent emergence of resistance against artemether–lumefantrine in this setting. This study underscores the importance to regular artemether–lumefantrine efficacy monitoring to inform the malaria control programme of the Republic of Congo.

On the 8th of May, 2018, an outbreak of Ebola virus disease (EVD) was declared, originating in the Bikoro region of the Democratic Republic of the Congo (DRC) near the border with neighboring Republic of the Congo (ROC). Frequent trade and migration occur between DRC and ROC-based communities residing along the Congo River. In June 2018, a field team was deployed to determine whether Zaire ebolavirus (Ebola virus (EBOV)) was contemporaneously circulating in local bats at the human-animal interface in ROC near the Bikoro EVD outbreak. Samples were collected from bats in the Cuvette and Likouala departments, ROC, bordering the Équateur Province in DRC where the Bikoro EVD outbreak was first detected. EBOV genomic material was not detected in bat-derived samples by targeted quantitative reverse transcription-polymerase chain reaction or by family-level consensus polymerase chain reaction; however, serological data suggests recent exposure to EBOV in bats in the region. We collected serum from 144 bats in the Cuvette department with 6.9% seropositivity against the EBOV glycoprotein and 14.3% seropositivity for serum collected from 27 fruit bats and one Molossinae in the Likouala department. We conclude that proactive investment in longitudinal sampling for filoviruses at the human-animal interface, coupled with ecological investigations are needed to identify EBOV wildlife reservoirs.

Polymorphisms in the genes encoding the merozoite surface proteins msp-1 and msp-2 are widely used markers for characterizing the genetic diversity of Plasmodium falciparum. This study aimed to compare the genetic diversity of circulating parasite strains in rural and urban settings in the Republic of Congo after the introduction of artemisinin-based combination therapy (ACT) in 2006. A cross-sectional survey was conducted from March to September 2021 in rural and urban areas close to Brazzaville, during which Plasmodium infection was detected using microscopy (and nested-PCR for submicroscopic infection). The genes coding for merozoite proteins-1 and -2 were genotyped by allele-specific nested PCR. Totals of 397 (72.4%) and 151 (27.6%) P. falciparum isolates were collected in rural and urban areas, respectively. The K1/msp-1 and FC27/msp-2 allelic families were predominant both in rural (39% and 64%, respectively) and urban (45.4% and 54.5% respectively) areas. The multiplicity of infection (MOI) was higher (p = 0.0006) in rural areas (2.9) compared to urban settings (2.4). The rainy season and the positive microscopic infection were associated with an increase in MOI. These findings reveal a higher P. falciparum genetic diversity and MOI in the rural setting of the Republic of Congo, which is influenced by the season and the participant clinical status.

The creation of global research partnerships is critical to produce shared knowledge for the implementation of the UN 2030 Agenda for Sustainable Development. Sustainability science promotes the coproduction of inter- and transdisciplinary knowledge, with the expectation that studies will be carried out through groups and truly collaborative networks. As a consequence, sustainability research, in particular that published in high impact journals, should lead the way in terms of ethical partnership in scientific collaboration. Here, we examined this issue through a quantitative analysis of the articles published in Nature Sustainability (300 papers by 2135 authors) and Nature (2994 papers by 46,817 authors) from January 2018 to February 2021. Focusing on these journals allowed us to test whether research published under the banner of sustainability science favoured a more equitable involvement of authors from countries belonging to different income categories, by using the journal Nature as a control. While the findings provide evidence of still insufficient involvement of Low-and-Low-Middle-Income-Countries (LLMICs) in Nature Sustainability publications, they also point to promising improvements in the involvement of such authors. Proportionally, there were 4.6 times more authors from LLMICs in Nature Sustainability than in Nature articles, and 68.8-100% of local Global South studies were conducted with host country scientists (reflecting the discouragement of parachute research practices), with local scientists participating in key research steps. We therefore provide evidence of the promising, yet still insufficient, involvement of low-income countries in top sustainability science publications and discuss ongoing initiatives to improve this.

Plasmodium falciparum parasites carrying deletions of histidine-rich protein 2 and 3 genes, pfhrp2 and pfhrp3, respectively, are likely to escape detection via HRP2-based rapid diagnostic tests (RDTs) and, consequently, treatment, posing a major risk to both the health of the infected individual and malaria control efforts. This study assessed the frequency of pfhrp2- and pfhrp3-deleted strains at four different study sites in Central Africa (number of samples analyzed: Gabon N = 534 and the Republic of Congo N = 917) and West Africa (number of samples analyzed: Nigeria N = 466 and Benin N = 120) using a highly sensitive multiplex qPCR. We found low prevalences for pfhrp2 (1%, 0%, 0.03% and 0) and pfhrp3 single deletions (0%, 0%, 0.03% and 0%) at all study sites (Gabon, the Republic of Congo, Nigeria and Benin, respectively). Double-deleted P. falciparum were only found in Nigeria in 1.6% of all internally controlled samples. The results of this pilot investigation do not point towards a high risk for false-negative RDT results due to pfhrp2/pfhrp3 deletions in Central and West African regions. However, as this scenario can change rapidly, continuous monitoring is essential to ensure that RDTs remain a suitable tool for the malaria diagnostic strategy.

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of TB and HIV. As with these dual epidemics, inadequate resources and poor case identification and reporting may be contributing to underestimations of the COVID-19 case burden in SSA. Modelling studies predict that the pandemic-related disruptions in TB and HIV services will result in significant increases in associated morbidity and mortality over the next five years. Furthermore, limited empirical evidence suggests that SARS-CoV-2 coinfections with TB and HIV are associated with increased mortality risk in SSA. However, predictive models require a better evidence-base to accurately define the impact of COVID-19, not only on communicable diseases such as TB and HIV, but on non-communicable disease comorbidities. Further research is needed to assess morbidity and mortality data among both adults and children across the African continent, paying attention to geographic disparities, as well as the clinical and socio-economic determinants of COVID-19 in the setting of TB and/or HIV.

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.

Background: Acute diarrhea is a leading cause of morbidity and mortality among children under five worldwide. As no published data is available on the occurrence of this infection in the Republic of Congo, this study aimed at (1) determining the prevalence and (2) characterizing genotypes of norovirus strains in Brazzaville. Methods: From June 2012 to June 2013, stool samples were collected from hospitalized young children with acute gastroenteritis. A total of 545 samples were tested for GI and GII norovirus infections using nested duplex reverse-transcription–polymerase chain reaction and sequencing. Results: The GI and GII norovirus infection were detected in 148 samples. Males (28%) were not significantly more infected than females (25%). Norovirus infection was found exclusively in children aged under 24 months with a higher prevalence (P = 0,048) in the age group of 7–12 months, and throughout the year with a peak in August and September. Genetic diversity of norovirus strains revealed that GII was the most prevalent (87%). No risk factor was significantly associated with norovirus infection. Conclusion: This study showed that noroviruses are important agents responsible for acute diarrhea in Congolese children and highlights the importance of continued surveillance. Keywords: Norovirus infection, Children, Epidemiology, Republic of Congo

Background: Cytochrome P450 (CYP) enzymes are essential in the metabolism of most drugs used today. Single nucleotide polymorphism(s) occurring in CYP genes can adversely affect drug pharmacokinetics, efficacy, and safety. Individuals carrying the CYP2C8*2 c.805A > T (CYP2C8*2; rs11572103) allele have impaired amodiaquine metabolism, increased risk of amodiaquine-related adverse events, and may promote the selection of drug-resistant parasite strains. This study investigated the distribution of the CYP2C8*2 allele in Brazzaville, Republic of Congo, where artesunate + amodiaquine is used as the second-line treatment for uncomplicated Plasmodium falciparum malaria. Methods: A total of 285 febrile children visiting the Marien Ngouabi paediatric hospital were genotyped for CYP2C8*2 using PCR-restriction fragment length polymorphism (PCR-RFLP). The allele frequencies and genotype distribution were determined. Results: The CYP2C8*2 allele was successfully genotyped in 75% (213/285) of the study participants. The CYP2C8*2A allele had a frequency of 63%, whereas the CYP2C8*2T allele had a frequency of 37%. Genotypes CYP2C8*2AA (rapid metabolizer), CYP2C8*2AT (intermediate metabolizer), and CYP2C8*2TT (poor metabolizer) were observed in 44%, 38%, and 18% of the investigated participants, respectively. Conclusions: This study gives the first description of CYP2C8*2 allele distribution in the Republic of Congo and highlights the potential risk of amodiaquine-related adverse events. Information from this study will be beneficial during pharmacovigilance investigations. Keywords: Cytochrome P450, CYP2C8, Brazzaville, Republic of Congo, Pharmacogenetics

Background: The cytochrome P450 CYP2B6*6 (CYP2B6 c.516G>T; rs3745274) is one of the genetic factors that alters the drug metabolism in antimalarial, antiretroviral and TB first-line drugs. In Central African populations, the distribution of the CYP2B6*6 variant is poorly documented. This study investigated the distribution of CYP2B6 c.516G>T variant among Congolese individuals. Methods: A total of 418 patients with HIV-1 mono-infection, HIV-1 and Tuberculosis coinfection and symptomatic P. falciparum malaria were genotyped for the CYP2B6 c.516G>T SNP using Restriction Fragment Length Polymorphism (RFLP). The allele frequencies and genotype distributions were determined. Results: The CYP2B6 c.516G>T was successfully analysed in 69% (288/418) of the study participants. Among the investigated individuals, the distribution of the major allele CYP2B6*G was 45% and the minor CYP2B6*T allele was 55%. Significant differences in genotype distribution were also observed among the studied individuals. The CYP2B6*GG (rapid metabolizer) genotype was observed in 17% (49/288) followed by CYP2B6*GT (intermediate metabolizer) 55% (159/288) and CYP2B6*TT (poor metabolizers) 28% (80/288). Conclusion: This study contributes to increasing understanding on population pharmacogenetics and may help policy makers regulate treatment guidelines in the Congolese population with a high burden of HIV, Malaria and TB. Keywords: CYP2B6, Cytochrome P 450, HIV, Malaria, Tuberculosis, Republic of Congo

For more than two years after the emergence of COVID-19 (Coronavirus Disease-2019), significant regional differences in morbidity persist. These differences clearly show lower incidence rates in several regions of the African and Asian continents. The work reported here aimed to test the hypothesis of a pre-pandemic natural immunity acquired by some human populations in central and western Africa, which would, therefore, pose the hypothesis of an original antigenic sin with a virus antigenically close to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To identify such pre-existing immunity, sera samples collected before the emergence of COVID-19 were tested to detect the presence of IgG reacting antibodies against SARS-CoV-2 proteins of major significance. Sera samples from French blood donors collected before the pandemic served as a control. The results showed a statistically significant difference of antibodies prevalence between the collected samples in Africa and the control samples collected in France. Given the novelty of our results, our next step consists in highlighting neutralizing antibodies to evaluate their potential for pre-pandemic protective acquired immunity against SARS-CoV-2. In conclusion, our results suggest that, in the investigated African sub-regions, the tested populations could have been potentially and partially pre-exposed, before the COVID-19 pandemic, to the antigens of a yet non-identified Coronaviruses.

BackgroundIn Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa.Methods and findingsThis single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated.ConclusionsPyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria.Trial registrationClinicalTrials.gov NCT03201770.

Background: Reducing the burden of malaria requires better understanding of vector populations, particularly in forested regions where the incidence remains elevated. Here, we characterized malaria vectors in a locality near the Yaoundé international airport, Cameroon, including species composition, abundance, Plasmodium infection rate, insecticide resistance profiles and underlying resistance mechanisms. Methods: Blood-fed adult mosquitoes resting indoors were aspirated from houses in April 2019 at Elende, a locality situated 2 km from the Yaoundé-Nsimalen airport. Female mosquitoes were forced to lay eggs to generate F 1 adults. Bioassays were performed to assess resistance profile to the four insecticides classes. The threshold of insecticide susceptibility was defined above 98% mortality rate and mortality rates below 90% were indicative of confirmed insecticide resistance. Furthermore, the molecular basis of resistance and Plasmodium infection rates were investigated. Results: Anopheles funestus s.s. was the most abundant species in Elende (85%) followed by Anopheles gambiae s.s. (15%) with both having similar sporozoite rate. Both species exhibited high levels of resistance to the pyrethroids, permethrin and deltamethrin (

BackgroundSoil-transmitted helminth (STH) infections remain a public health concern in sub-Saharan Africa. School-based mass drug administration (MDA) using the anthelminthic drug Mebendazole/Albendazole have succeeded in controlling morbidity associated to these diseases but failed to interrupt their transmission. In areas were filarial diseases are co-endemic, another anthelminthic drug (Ivermectin) is distributed to almost the entire population, following the community-directed treatment with ivermectin (CDTI) strategy. Since Ivermectin is a broad spectrum anthelmintic known to be effective against STH, we conducted cross-sectional surveys in two health districts with very contrasting histories of Ivermectin/Albendazole-based PC in order to investigate whether CDTI might have contributed in STH transmission interruption.MethodologyCross-sectional surveys were conducted in two health districts with similar socio-environmental patterns but with very contrasting CDTI histories (Akonolinga health district where CDTI was yet to be implemented vs. Yabassi health district where CDTI has been ongoing for two decades). Stool samples were collected from all volunteers aged >2 years old and analyzed using the Kato-Katz technique. Infections by different STH species were compared between Akonolinga and Yabassi health districts to decipher the impact of Ivermectin/Albendazole-based MDA on STH transmission.Principal findingsA total of 610 and 584 participants aged 2-90 years old were enrolled in Akonolinga and Yabassi health districts, respectively. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found, with prevalence significantly higher in Akonolinga health district (43.3%; 95% CI: 38.1-46.6) compared to Yabassi health district (2.5%; 95% CI: 1.1-5.1) (chi-square: 90.8; df: 1; p < 0.001).Conclusion/significanceThese findings (i) suggest that Mebendazole- or Albendazole-based MDA alone distributed only to at-risk populations might not be enough to eliminate STH, (ii) support the collateral impact of Ivermectin/Albendazole MDA on A. lumbricoides and T. trichiura infections, and (iii) suggest that Ivermectin/Albendazole-based PC could accelerate STH transmission interruption.

Abstract Background Malaria transmission-blocking anti-malarial drugs, such as primaquine, offers an effective strategy for reducing the incidence of falciparum malaria. However, this drug induces haemolytic anaemia among glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. The distribution of G6PD deficiency in Brazzaville, Republic of Congo and the association of G6PD deficiency with haemoglobin levels and blood cell counts were investigated. Methods A total of 212 febrile children were recruited for this study. Plasmodium falciparum diagnosis was conducted by microscopy and nested PCR. Sanger sequencing was used to assess G6PD deficiency by detecting 202G>A (rs1050828) and 376A>G (rs1050829) single nucleotide polymorphisms. Results Two hundred and twelve children were successfully genotyped for G6PD variants. Overall, 13% (27/212) of the children were G6PD deficient and 25% (25/100) females were heterozygous (11 BA− and 14 A+A−). The remaining 160 children had a normal G6PD genotype. The mean red blood and mean platelet counts were significantly lower in hemizygous male (G6PD A−) participants than in normal male (G6PD A+ or B) participants (p

The identification of monkeypox in 3 separate patients in the United Kingdom in September raised media and political attention on an emerging public health threat. Nigeria, whose last confirmed case of monkeypox was in 1978, is currently experiencing an unusually large and outbreak of human monkeypox cases, a ‘One Human-Environmental-Animal Health’ approach is being effectively used to define and tackle the outbreak. As of 13th October 2018, there have been one hundred and sixteen confirmed cases the majority of whom are under 40 years. Over the past 20 years ten Central and West African countries have reported monkeypox cases which have risen exponentially. We review the history and evolution of monkeypox outbreaks in Africa and USA, the changing clinical presentations, and discuss possible factors underlying the increasing numbers being detected including the cessation of smallpox vaccination programs. Major knowledge gaps remain on the epidemiology, host reservoir, and emergence, transmission, pathogenesis and prevention of monkeypoz.

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. Keywords: HIV, AIDS, ARV, HAART, Coverage, Impact, Treatment, Republic of the Congo

Abstract 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.

Abstract Background Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. Methods Blood samples of 431 febrile children aged 1–10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All samples were screened for malaria parasites using nested PCR. Direct sequencing was used to determine the frequency distribution of genetic variants in the anti-malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6, Pfk13) in malaria-positive isolates. Results One-hundred and nineteen (N = 70 from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A relative decrease in the proportion of chloroquine-resistant haplotype (CVIET) from 100% in 2005, 1 year before the introduction and implementation of ACT in 2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug transporter gene, a considerable reduction in the frequency of the mutations N86Y (from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015). Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced to null in 2015. None of the parasites harboured the Pfk13 mutations associated with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new Pfk13 variants are reported among the investigated isolates. Conclusion The implementation of ACT has led to the decline in prevalence of chloroquine-resistant parasites in the Republic of Congo. However, the constant prevalence of the PfMDR1 Y184F mutation, associated with lumefantrine susceptibility, indicate a selective drug pressure still exists. Taken together, this study could serve as the basis for epidemiological studies monitoring the distribution of molecular markers of artemisinin resistance in the Republic of Congo.

Cholera remains a major global public health threat and continuous emergence of new Vibrio cholerae strains is of major concern. We conducted a molecular epidemiological study to detect virulence markers and antimicrobial resistance patterns of V. cholerae isolates obtained from the 2012-2015 cholera outbreaks in Ghana. Archived clinical isolates obtained from the 2012, 2014 and 2015 cholera outbreaks in Ghana were revived by culture and subjected to microscopy, biochemical identification, serotyping, antibiotic susceptibility testing, molecular detection of distinct virulence factors and Multi-Locus Variable-Number of Tandem-Repeat Analysis (MLVA). Of 277 isolates analysed, 168 (60.6%) were confirmed to be V. cholerae and 109 (39.4%) isolates constituted other bacteria (Escherichia coli, Aeromonas sobria, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococci faecalis). Serotyping the V. cholerae isolates identified 151 (89.9%) as Ogawa, 3 (1.8%) as Inaba and 14 (8.3%) as non-O1/O139 serogroup. The O1 serogroup isolates (154/168, 91.7%) carried the cholera toxin ctxB gene as detected by PCR. Additional virulence genes detected include zot, tcpA, ace, rtxC, toxR, rtxA, tcpP, hlyA and tagA. The most common and rare virulence factors detected among the isolates were rtxC (165 isolates) and tcpP (50 isolates) respectively. All isolates from 2014 and 2015 were multidrug resistant against the selected antibiotics. MLVA differentiated the isolates into 2 large unique clones A and B, with each predominating in a particular year. Spatial analysis showed clustering of most isolates at Ablekuma sub-district. Identification of several virulence genes among the two different genotypes of V. cholerae isolates and resistance to first- and second-line antibiotics, calls for scaleup of preventive strategies to reduce transmission, and strengthening of public health laboratories for rapid antimicrobial susceptibility testing to guide accurate treatment. Our findings support the current WHO licensed cholera vaccines which include both O1 Inaba and Ogawa serotypes.

The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major public health challenge in the near future. DM increases the risk of developing TB by two to three times and also increases the risk of TB treatment failure, relapse, and death. The global prevalence of DM is predicted to rise significantly in the next two decades, particularly in some of the low- and middle-income countries with the highest TB burden. Migration may add further complexity to the effort to control the impact on TB of the growing DM pandemic. Migration may increase the risk of DM, although the magnitude of this association varies according to country of origin and ethnic group, due to genetic factors and lifestyle differences. Migrants with TB may have an increased prevalence of DM compared to the native population, and the risk of TB among persons with DM may be higher in migrants than in autochthonous populations. Screening for DM among migrants, screening migrants with DM for active and latent TB, and improving access to DM care, could contribute to mitigate the effects of DM on TB.

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.

Tuberculosis is a leading cause of illness and death in Congo. No data are available about the population structure and transmission dynamics of the Mycobacterium tuberculosis complex strains prevalent in this central Africa country. On the basis of single-nucleotide polymorphisms detected by whole-genome sequencing, we phylogenetically characterized 74 MTBC isolates from Brazzaville, the capital of Congo. The diversity of the study population was high; most strains belonged to the Euro-American lineage, which split into Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X type, and a new dominant sublineage named Congo type (n = 26). Thirty strains were grouped in 5 clusters (each within 12 single-nucleotide polymorphisms), from which 23 belonged to the Congo type. High cluster rates and low genomic diversity indicate recent emergence and transmission of the Congo type, a new Euro-American sublineage of MTBC.

The Republic of Congo is on the World Health Organization (WHO) list of ‘high burden’ countries for tuberculosis (TB) and HIV. TB is the leading cause of death among HIV-infected patients in the Republic of Congo. In this viewpoint, the available data on TB and HIV in the Republic of Congo are reviewed, and the gaps and bottlenecks that the National TB Control Program (NTCP) faces are discussed. Furthermore, priority requirements for developing and implementing TB and HIV collaborative service activities are identified. HIV and TB control programs operate as distinct entities with separate case management plans. The implementation of collaborative TB/HIV activities to evaluate and monitor the management of TB/HIV co-infected individuals remains inefficient in most regions, and these activities are sometimes non-existent. This reveals major challenges that require definition in order to improve the delivery of healthcare. The NTCP lacks adequate resources for optimal implementation of control measures of TB and HIV compliance and outcomes. The importance of aligning and integrating TB and HIV treatment services (including follow-up) and adherence support services through coordinated and collaborative efforts between individual TB and HIV programs is discussed. Aligning and integrating TB and HIV treatment services through coordinated and collaborative efforts between individual TB and HIV programs is required. However, the WHO recommendations are generic, and health services in the Republic of Congo need to tailor their TB and HIV programs according to the availability of resources and operational feasibility. This will also open opportunities for synergizing collaborative TB/HIV research and training activities, which should be prioritized by the donors supporting the TB/HIV programs.

Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host–pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)–those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data from previous and ongoing research studies on MTBC may be inaccurate and inappropriate. A major rethink is required regarding the design and structure of future clinical trials of new interventions. The West, Central, East, and Southern African EDCTP Networks of Excellence provide opportunities to take forward these pan-Africa studies. More investments into molecular, epidemiological, clinical, diagnostic, and immunological studies across the African continent are required to enable further understanding of host–M. africanum interactions, leading to the development of more specific diagnostics, biomarkers, host-directed therapies, and vaccines for TB.

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a ‘One Health’ approach to control such zoonotic pathogens with epidemic potential.

Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2–6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1–15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.

The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti).

Multidrug-resistant TB (MDR-TB) is a major threat to global health security. In 2017, only 50% of patients with MDR-TB who received WHO-recommended treatment were cured. Most MDR-TB patients who recover continue to suffer from functional disability due to long-term lung damage. Whilst new MDR-TB treatment regimens are becoming available, conventional drug therapies need to be complemented with host-directed therapies (HDTs) to reduce tissue damage and improve functional treatment outcomes. This viewpoint highlights recent data on biomarkers, immune cells, circulating effector molecules and genetics which could be utilised for developing personalised HDTs. Novel technologies currently used for cancer therapy which could facilitate in-depth understanding of host genetics and the microbiome in patients with MDR-TB are discussed. Against this background, personalised cell-based HDTs for adjunct MDR-TB treatment to improve clinical outcomes are proposed as a possibility for complementing standard therapy and other HDT agents. Insights into the molecular biology of the mechanisms of action of cellular HDTs may also aid to devise non-cell-based therapies targeting defined inflammatory pathway(s) in Mtb-driven immunopathology. Keywords: Multidrug-resistant tuberculosis, Clinical studies, Host-directed therapies, Personalised medicine, Immunotherapy, Biomarkers

Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from whom new active TB cases will arise. Understanding the spatio-temporal dynamics of host immune responses in LTBI granulomas is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities – where local chronic inflammation leads to immunopathology – can help provide insights into the biological pathways at play in LTBI granulomas. Translational studies using patient material as well as LTBI+ donor-derived tissue samples are instrumental in understanding the various components of granuloma dynamics, immunological landscapes therein and how this could help to identify therapeutic targets. Deep sequencing technologies may aid to decipher the genetic changes in lung granuloma and blood samples from LTBI+ individuals associated with progression to active TB disease. This may lead to advancement of development of targeted Host-Directed Therapies (HDTs) and their evaluation as adjunct TB therapies for improving treatment outcomes for LTBI and pulmonary TB. Keywords: latent tuberculosis infection, granuloma, mutations, immune landscape, host-directed therapies

Linkage studies have revealed a linkage of mild malaria to chromosome 6p21 that contains the NCR3 gene encoding a natural killer cell receptor, whereas NCR3-412G>C (rs2736191) located in its promoter region was found to be associated with malaria in Burkina Faso. Here we confirmed the association of rs2736191 with mild malaria in a Congolese cohort and investigated its potential cis-regulatory effect. Luciferase assay results indicated that rs2736191-G allele had a significantly increased promoter activity compared to rs2736191-C allele. Furthermore, EMSAs demonstrated an altered binding of two nuclear protein complexes to the rs2736191-C allele in comparison to rs2736191-G allele. Finally, after in silico identification of transcription factor candidates, pull-down western blot experiments confirmed that both STAT4 and RUNX3 bind the region encompassing rs2736191 with a higher affinity for the G allele. To our knowledge, this is the first report that explored the functional role of rs2736191. These results support the hypothesis that genetic variation within natural killer cell receptors alters malaria resistance in humans.

BACKGROUND:Pathogens exert selective pressure which may lead to substantial changes in host immune responses. The human complement receptor type 1 (CR1) is an innate immune recognition glycoprotein that regulates the activation of the complement pathway and removes opsonized immune complexes. CR1 genetic variants in exon 29 have been associated with expression levels, C1q or C3b binding and increased susceptibility to several infectious diseases. Five distinct CR1 nucleotide substitutions determine the Knops blood group phenotypes, namely Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-. METHODS:CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana. RESULTS:The distribution of the CR1 alleles, genotypes and haplotypes differed significantly among geographical settings (p≤0.001). CR1 variants rs17047660A/G (McCa/b) and rs17047661A/G (Sl1/Sl2) were exclusively observed to be polymorphic in African populations compared to the groups from Asia and South-America, strongly suggesting that these two SNPs may be subjected to selection. This is further substantiated by a high linkage disequilibrium between the two variants in the Congolese and Ghanaian populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA haplotype was found more frequently among the Brazilian and Vietnamese study groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese populations, while the CR1*AGAGTG haplotype was frequent among Congolese and Ghanaian individuals. CONCLUSION:The African populations included in this study might have a selective advantage conferred to immune genes involved in pathogen recognition and signaling, possibly contributing to disease susceptibility or resistance.

Correction In the original publication [1] the last sentence in the last paragraph under ‘Perspectives and implications’ in the Discussions section needs to be removed. The correct version can be found in this Erratum.

BACKGROUND: In the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (MDR) were reported from the Central Region of Cameroon. This work assesses drug resistant tuberculosis in this region 12 years after reorganization of the National Tuberculosis Control Program (NTCP). METHODS: This cross-sectional study was conducted from April 2010 to March 2011 in Jamot Hospital in Yaoundé, Cameroon. Only patients with smear positive pulmonary tuberculosis were included. Sputa were cultured and subsequently underwent drug susceptibility testing (DST). All consenting individuals were tested for their HIV status. RESULTS: A total of 665 smear positive pulmonary tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2-32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species, DST results were obtained for 576. The overall resistance rate was 10.9% (63/576). The overall resistance rates for single drug resistance were: isoniazid-resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin-resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin-resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug resistant tuberculosis (XDR) was detected. CONCLUSIONS: The data show that reorganization of the NTCP resulted in a strong decrease in streptomycin-resistance and suggest that it prevented the emergence of XDR in the Central Region of Cameroon.