Marc C. Tahita

Newcastle disease virus in West Africa: new virulent strains identified in non-commercial farms

Forty-four Newcastle disease virus (NDV) strains, obtained between 2002 and 2007 from different poultry species in Nigeria, Niger, Burkina Faso and Cameroon, were phylogenetically analysed based on partial F sequences. Lineage 2 viruses were genetically identical or similar to the locally used LaSota vaccine strain and were mostly detected in commercial farms. Lineage 1, 3 and 4 strains were only sporadically found, and their origin was less clear. Twenty-one strains from backyard farms and live bird markets formed three new clusters within lineage 5, tentatively named 5f, 5g and 5h. All of these strains were predicted to be virulent based on their F protein cleavage site sequence. Minimal genetic distances between new and previously established sublineages ranged from 9.4 to 15.9%, and minimal distances between the new sublineages were 11.5 to 17.3%. Their high genetic diversity and their presence in three different Sub-Saharan countries suggest that these new sublineages represent the NDV variants indigenous to West Africa.

Phylogenetic Analysis of Human Parvovirus B19 Sequences from Eleven Different Countries Confirms the Predominance of Genotype 1 and Suggests the Spread of Genotype 3b

ABSTRACT Phylogenetic analysis of 166 human parvovirus B19 sequences from 11 different countries attributed 91.57% to genotype 1, 5.42% to genotype 3b, and 3.01% to genotype 3a. Very similar viruses of genotype 1 circulated widely in Europe and Israel. Genotype 3b seems to show an increasing spread outside of Africa.

Genetic Characterization of HPAI (H5N1) Viruses from Poultry and Wild Vultures, Burkina Faso

Genetic analysis of highly pathogenic avian influenza (H5N1) viruses from poultry and hooded vultures in Burkina Faso shows that these viruses belong to 1 of 3 sublineages initially found in Nigeria and later in other African countries. Hooded vultures could potentially be vectors or sentinels of influenza subtype H5N1, as are cats and swans elsewhere.

Phylogenomic Analysis Reveals an Asian Origin for African Burkholderia pseudomallei and Further Supports Melioidosis Endemicity in Africa.

Sporadic melioidosis cases have been reported in the African mainland and Indian Ocean islands, but until recently, these regions were not considered areas where B. pseudomallei is endemic. Given the high mortality rate of melioidosis, it is crucial that this disease be recognized and suspected in all regions of endemicity. Previous work has shown that B. pseudomallei originated in Australia, with subsequent introduction into Asia; however, the precise origin of B. pseudomallei in other tropical regions remains poorly understood. Using whole-genome sequencing, we characterized B. pseudomallei isolates from Madagascar and Burkina Faso. Next, we compared these strains to a global collection of B. pseudomallei isolates to identify their evolutionary origins. We found that African B. pseudomallei strains likely originated from Asia and were closely related to South American strains, reflecting a relatively recent shared evolutionary history. We also identified substantial genetic diversity among African strains, suggesting long-term B. pseudomallei endemicity in this region. ABSTRACT Burkholderia pseudomallei, an environmental bacterium that causes the deadly disease melioidosis, is endemic in northern Australia and Southeast Asia. An increasing number of melioidosis cases are being reported in other tropical regions, including Africa and the Indian Ocean islands. B. pseudomallei first emerged in Australia, with subsequent rare dissemination event(s) to Southeast Asia; however, its dispersal to other regions is not yet well understood. We used large-scale comparative genomics to investigate the origins of three B. pseudomallei isolates from Madagascar and two from Burkina Faso. Phylogenomic reconstruction demonstrates that these African B. pseudomallei isolates group into a single novel clade that resides within the more ancestral Asian clade. Intriguingly, South American strains reside within the African clade, suggesting more recent dissemination from West Africa to the Americas. Anthropogenic factors likely assisted in B. pseudomallei dissemination to Africa, possibly during migration of the Austronesian peoples from Indonesian Borneo to Madagascar ~2,000 years ago, with subsequent genetic diversity driven by mutation and recombination. Our study provides new insights into global patterns of B. pseudomallei dissemination and adds to the growing body of evidence of melioidosis endemicity in Africa. Our findings have important implications for melioidosis diagnosis and management in Africa. IMPORTANCE Sporadic melioidosis cases have been reported in the African mainland and Indian Ocean islands, but until recently, these regions were not considered areas where B. pseudomallei is endemic. Given the high mortality rate of melioidosis, it is crucial that this disease be recognized and suspected in all regions of endemicity. Previous work has shown that B. pseudomallei originated in Australia, with subsequent introduction into Asia; however, the precise origin of B. pseudomallei in other tropical regions remains poorly understood. Using whole-genome sequencing, we characterized B. pseudomallei isolates from Madagascar and Burkina Faso. Next, we compared these strains to a global collection of B. pseudomallei isolates to identify their evolutionary origins. We found that African B. pseudomallei strains likely originated from Asia and were closely related to South American strains, reflecting a relatively recent shared evolutionary history. We also identified substantial genetic diversity among African strains, suggesting long-term B. pseudomallei endemicity in this region.

Four Artemisinin-Based Treatments in African Pregnant Women with Malaria.

BACKGROUND Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa. METHODS We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chain-reaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes. RESULTS The PCR-adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin-piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-adjusted cure rates in the intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin-piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine-artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups). CONCLUSIONS Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-treatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.).

Characterization of Hepatitis Delta Virus in Sub-Saharan Africa

ABSTRACT Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV), and infection with this virus aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study, almost 2,300 blood serum samples from Burkina Faso (n = 1,131), Nigeria (n = 974), Chad (n = 50), and the Central African Republic (n = 118) were screened for HBV and HDV. Among 743 HBsAg-positive serum samples, 74 were positive for HDV antibodies and/or HDV RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be much more common in chronic liver disease patients in the Central African Republic (CAR) than in similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso, the prevalence of HDV antibodies was 10 times higher in the children than in their mothers, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection. The genotyping of 16 full-length and 8 partial HDV strains revealed clade 1 (17/24) in three of the four countries, while clades 5 (5/24) and 6 (2/24) were, at least in this study, confined to Central Nigeria. On the amino acid level, almost all our clade 1 strains exhibited a serine at position 202 in the hepatitis D antigen, supporting the hypothesis of an ancient African HDV-1 subgroup. Further studies are required to understand the public health significance of the highly varied HDV prevalences in different cohorts and countries in sub-Saharan Africa.

Rubella seroprevalence among pregnant women in Burkina Faso

BackgroundDespite the serious consequences of rubella infection during early pregnancy, very little is known about the rubella seroprevalence in a number of African countries including Burkina Faso.MethodsBetween December 2007 and March 2008 serum samples were collected from 341 pregnant women in Bobo (n = 132, urban area) and Houndé (n = 209, rural area) and were tested for rubella-specific IgG antibodies with a commercial ELISA kit.ResultsAn overall seropositivity rate of 95.0% (324/341) was found, with a higher percentage in the urban population and in the oldest age group. Considering an antibody titer of at least 10 International Units per ml as protective, the overall immunity rate in the cohort of pregnant women was 93.3% (318/341).ConclusionsThe high overall seropositivity rate in the absence of routine immunization suggests a continuous transmission of endemic rubella virus in Burkina Faso, posing a threat to non-immune pregnant women.

Profile: Nanoro Health and Demographic Surveillance System

The Nanoro Health and Demographic Surveillance System (HDSS), located in the rural centre of Burkina Faso, was established in 2009 by the Clinical Research Unit of Nanoro with the aim of providing a core framework for clinical trials and also to support the Burkina Faso health authorities in generating epidemiological data that can contribute to the setup and assessment of health interventions. In the baseline of initial census, 54 781 individuals were recorded of whom 56.1% are female. After the initial census, vital events such as pregnancies, births, migrations and deaths have been monitored, and data on individuals and household characteristics are updated during regular 4-monthly household visits. The available data are categorized into demographic, cultural, socio-economic and health information, and are used for monitoring and evaluation of population development issues. As a young site, our objective has been to strengthen our skills and knowledge and share new scientific experiences with INDEPTH and HDSS sites in Burkina Faso. In addition, all data produced by the Nanoro HDSS will be made publicly available through the INDEPTH data sharing system.

Diagnosis of Bacterial Bloodstream Infections: A 16S Metagenomics Approach

Background Bacterial bloodstream infection (bBSI) is one of the leading causes of death in critically ill patients and accurate diagnosis is therefore crucial. We here report a 16S metagenomics approach for diagnosing and understanding bBSI. Methodology/Principal Findings The proof-of-concept was delivered in 75 children (median age 15 months) with severe febrile illness in Burkina Faso. Standard blood culture and malaria testing were conducted at the time of hospital admission. 16S metagenomics testing was done retrospectively and in duplicate on the blood of all patients. Total DNA was extracted from the blood and the V3–V4 regions of the bacterial 16S rRNA genes were amplified by PCR and deep sequenced on an Illumina MiSeq sequencer. Paired reads were curated, taxonomically labeled, and filtered. Blood culture diagnosed bBSI in 12 patients, but this number increased to 22 patients when combining blood culture and 16S metagenomics results. In addition to superior sensitivity compared to standard blood culture, 16S metagenomics revealed important novel insights into the nature of bBSI. Patients with acute malaria or recovering from malaria had a 7-fold higher risk of presenting polymicrobial bloodstream infections compared to patients with no recent malaria diagnosis (p-value = 0.046). Malaria is known to affect epithelial gut function and may thus facilitate bacterial translocation from the intestinal lumen to the blood. Importantly, patients with such polymicrobial blood infections showed a 9-fold higher risk factor for not surviving their febrile illness (p-value = 0.030). Conclusions/Significance Our data demonstrate that 16S metagenomics is a powerful approach for the diagnosis and understanding of bBSI. This proof-of-concept study also showed that appropriate control samples are crucial to detect background signals due to environmental contamination.

Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach

Introduction Non-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness. Methodology We conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis. Principal Findings The plasma metabolome profile of malaria and non-malaria patients revealed fundamental differences in host response, including a differential activation of the hypothalamic-pituitary-adrenal axis. A simple corticosteroid signature was a good classifier of severe malaria and non-malaria febrile patients (AUC 0.82, 95% CI: 0.70–0.93). Patients with BSI were characterized by upregulated plasma bile metabolites; a signature of two bile metabolites was estimated to have a sensitivity of 98.1% (95% CI: 80.2–100) and a specificity of 82.9% (95% CI: 54.7–99.9) to detect BSI in children younger than 5 years. This BSI signature demonstrates that host metabolites can have a superior diagnostic sensitivity compared to pathogen-detecting tests to identify infections characterized by low pathogen load such as BSI. Conclusions This study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings.