Evolving epidemiology of poliovirus serotype 2 following withdrawal of the serotype 2 oral poliovirus vaccine.

Although there have been no cases of serotype 2 wild poliovirus for more than 20 years, transmission of serotype 2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the serotype 2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all serotype 2 poliovirus. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimated the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. A novel OPV2, for which two candidates are currently in clinical trials, is urgently required, together with a contingency strategy if this vaccine does not materialize or perform as anticipated.

Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines?

BACKGROUND: The use of 2 live attenuated vaccines (LAV) is recommended to be simultaneous or after an interval of at least four weeks between injections. The primary objective of this study was to compare the humoral response to yellow fever (YF) and measles vaccines among children vaccinated against these two diseases, either simultaneously or separated by an interval of 7-28 days. SUBJECTS AND METHODS: A prospective, multicenter observational study was conducted among children aged 9-15 months. The primary endpoint was the occurrence of positive yellow fever antibodies after YF vaccine by estimating the titers of neutralizing antibodies from venous blood samples. Children vaccinated against YF 7-28 days after receiving the vaccine against measles (test group) were compared with children vaccinated the same day against these two diseases (referent group). RESULTS: Analysis was performed on 284 children. Of them, fifty-four belonged to the test group. Measles serology was positive in 91.7% of children. Neutralizing antibodies against YF were detected in 90.7% of the test group and 92.9 of the referent group (p=0.6). In addition, quantitative analysis of the immune response did not show a lower response to YF vaccination when it took place 1-28 days after measles vaccination. DISCUSSION: In 1965, Petralli showed a lower response to the smallpox vaccine when injected 4-20 days after measles vaccination. Since then, recommendations are to observe an interval of four weeks between LAV not injected on the same day. Other published studies failed to show a significant difference in the immune response to a LAV injected 1-28 days after another LAV. These results suggest that the usual recommendations for immunization with two LAV may not be correct. CONCLUSION: In low income countries, the current policy should be re-evaluated. This re-evaluation should also be applied to travelers to yellow fever endemic countries.

Afriflu--international conference on influenza disease burden in Africa, 1-2 June 2010, Marrakech, Morocco.

The burden of influenza disease is to a large extent unknown for the African continent. Moreover, the interaction of influenza with common infectious diseases in Africa remains poorly described. Solid scientific evidence on the influenza disease burden in Africa is critical for the development of effective influenza vaccine policies. On 1st and 2nd June 2010 in Marrakech, Morocco, over eighty surveillance and influenza experts from 22 African countries as well as Europe and America met at the 'Afriflu' conference to discuss influenza challenges and solutions for the continent. During the meeting, participants exchanged their experiences and discussed a wide variety of topics related to influenza in Africa, including diagnosis, surveillance, epidemiology, and interventions. The meeting concluded with a pledge to improve influenza knowledge and awareness in Africa, with an emphasis on accurate determination of disease burden to help orient public health policies.

Environmental risk factors of West Nile virus infection of horses in the Senegal River basin.

In 2005, a serological study was carried out on horses in five ecologically contrasted zones of the Senegal River basin (Senegal) to assess West Nile virus (WNV) transmission and investigate underlying environmental risk factors. In each study zone, horses were randomly selected and blood samples taken. A land-cover map of the five study areas was built using two satellite ETM+ images. Blood samples were screened by ELISA for anti-WNV IgM and IgG and positive samples were confirmed by seroneutralization. Environmental data were analysed using a principal components analysis. The overall IgG seroprevalence rate was 85% (n=367; 95% CI 0.81-0.89). The proximity to sea water, flooded banks and salted mudflats were identified as protective factors. These environmental components are unfavourable to the presence of Culex mosquitoes suggesting that in Senegal, the distribution of the vector species is more limiting for WNV transmission than for the hosts' distribution.

Human T-cell leukaemia/lymphoma virus type 1-associated infective dermatitis in Africa: a report of five cases from Senegal.

BACKGROUND: Infective dermatitis (ID) is a rare dermatological condition of childhood that has been linked to human T-cell leukaemia/lymphoma virus type 1 (HTLV-1). Most cases have been reported in the Caribbean. Although several million people are estimated to be infected by HTLV-1 in sub-Saharan Africa, no case of ID has been reported in this area. OBJECTIVES: To identify and to describe cases of HTLV-1-associated ID in Senegal, West Africa. METHODS: Over a 3-year period, a serological test for HTLV-1 was performed at a dermatological centre in Dakar, Senegal, in children who presented with a picture suggestive of ID. Complementary haematological, immunological and virological investigations were performed in infected children and in their mothers. RESULTS: Five patients with typical HTLV-1-associated ID were identified, of ages 17, 5, 4, 3 and 3 years; two patients belonged to the same family. They all presented with repeated flares of superinfected dermatitis involving typical sites of ID (mainly the scalp, external ears, nares and eyelids), associated with nasal discharge, and less commonly with a nonspecific papular rash on the face or trunk. Although oral antibiotic therapy always gave effective control of the symptoms, recurrences were constant. A persisting dry dermatitis of the retroauricular folds was common between flares. Infection in the oldest patient was associated with a chronic adult T-cell leukaemia/lymphoma. The mothers of three patients, and the grandmother of another, were all infected by HTLV-1 strains belonging to the Cosmopolitan molecular subtype, with a perfect nucleotide identity of long-terminal repeat and env gp21 genomic regions within each family. CONCLUSIONS: We present the clinical and virological features of the first reported African cases of HTLV-1-associated ID. When compared with data from the Caribbean, infectious features seemed particularly prominent. ID appears to be overlooked in sub-Saharan Africa, where it might be easily confused with common pyoderma. Breast feeding appears to be the origin of HTLV-1 contamination of the children.

Viral load in tissues during the early and chronic phase of non-pathogenic SIVagm infection.

African green monkeys (AGMs) persistently infected with SIVagm do not develop AIDS, although their plasma viremia levels can reach those reported for pathogenic HIV-1 and SIVmac infections. In contrast, the viral burden in lymph nodes in SIVagm-infected AGMs is generally lower in comparison with HIV/SIVmac pathogenic infections, at least during the chronic phase of SIVagm infection. We searched for the primary targets of viral replication, which might account for the high viremias in SIVagm-infected AGMs. We evaluated for the first time during primary infection SIVagm dissemination in various lymphoid and non-lymphoid tissues. Sixteen distinct organs at a time point corresponding to maximal virus production were analyzed for viral RNA and DNA load. At days 8 and 9 p.i., viral RNA could be detected in a wide range of tissues, such as jejunum, spleen, mesenteric lymph nodes, thymus and lung. Quantification of viral DNA and RNA as well as of productively infected cells revealed that viral replication during this early phase takes place mainly in secondary lymphoid organs and in the gut (5 x 10(4)-5 x 10(8) RNA copies/10(6) cells). By 4 years p.i., RNA copy numbers were below detection level in thymus and lung. Secondary lymphoid organs displayed 6 x 10(2)-2 x 10(6) RNA copies/10(6) cells, while some tissue fragments of ileum and jejunum still showed high viral loads (up to 10(9) copies/10(6) cells). Altogether, these results indicate a rapid dissemination of SIVagm into lymphoid tissues, including the small intestine. The latter, despite showing marked regional variations, most likely contributes significantly to the high levels of viremia observed during SIVagm infection.

Frequent substitution polymorphisms in African green monkey CCR5 cluster at critical sites for infections by simian immunodeficiency virus SIVagm, implying ancient virus-host coevolution.

In contrast to humans, several primate species are believed to have harbored simian immunodeficiency viruses (SIVs) since ancient times. In particular, the geographically dispersed species of African green monkeys (AGMs) are all infected with highly diversified SIVagm viruses at high prevalences (greater than 50% of sexually mature individuals) without evident diseases, implying that the progenitor monkeys were infected prior to their dispersal. If this is correct, AGMs would be expected to have accumulated frequent resistance-conferring polymorphisms in host genes that are important for SIV replication. Accordingly, we analyzed the coding sequences of the CCR5 coreceptors from 26 AGMs (52 alleles) in distinct populations of the four species. These samples contained 29 nonsynonymous coding changes and only 15 synonymous nucleotide substitutions, implying intense functional selection. Moreover, 24 of the resulting amino acid substitutions were tightly clustered in the CCR5 amino terminus (D13N in the vervets and Y14N in the tantalus species) or in the first extracellular loop (Q93R and Q93K in all species). The Y14N substitution was extremely frequent in the 12 wild-born African tantalus, with 7 monkeys being homozygous for this substitution and 4 being heterozygous. Although two of these heterozygotes and the only wild-type homozygote were naturally infected with SIVagm, none of the Y14N homozygotes were naturally infected. A focal infectivity assay for SIVagm indicated that all five tested SIVagms efficiently use CCR5 as a coreceptor and that they also use CXCR6 (STRL33/Bonzo) and GPR15 (BOB) with lower efficiencies but not CXCR4. Interestingly, the D13N, Y14N, Q93R, and Q93K substitutions in AGM CCR5 all strongly inhibited infections by the SIVagm isolates in vitro. The Y14N substitution eliminates a tyrosine sulfation site that is important for infections and results in partial N-linked glycosylation (i.e., 60% efficiency) at this position. Nevertheless, the CCR5(Y14N) component that lacks an N-linked oligosaccharide binds the chemokine MIP-lbeta with a normal affinity and is fully active in signal transduction. Similarly, D13N and Q93R substitutions did not interfere with signal transduction. Thus, the common substitution polymorphisms in AGM CCR5 strongly inhibit SIVagm infections while substantially preserving chemokine signaling. In contrast, polymorphisms of human CCR5 are relatively infrequent, and the amino acid substitutions are randomly situated and generally without effects on coreceptor function. These results support an ancient coevolution of AGMs and SIVagm viruses and establish AGMs as a highly informative model for learning about host proteins that play critical roles in immunodeficiency virus infections.

High levels of viral replication during primary simian immunodeficiency virus SIVagm infection are rapidly and strongly controlled in African green monkeys.

In contrast to pathogenic human immunodeficiency virus and simian immunodeficiency virus (SIV) infections, chronic SIVagm infections in African green monkeys (AGMs) are characterized by persistently low peripheral and tissue viral loads that correlate with the lack of disease observed in these animals. We report here data on the dynamics of acute SIVagm infection in AGMs that exhibit remarkable similarities with viral replication patterns observed in peripheral blood during the first 2 weeks of pathogenic SIVmac infections. Plasma viremia was evident at day 3 postinfection (p.i.) in AGMs, and rapid viral replication led by days 7 to 10 to peak viremias characterized by high levels of antigenemia (1.2 to 5 ng of p27/ml of plasma), peripheral DNA viral load (10(4) to 10(5) DNA copies/10(6) peripheral blood mononuclear cells [PBMC]), and plasma RNA viral load (2 x 10(6) to 2 x 10(8) RNA copies/ml). The lymph node (LN) RNA and DNA viral load patterns were similar to those in blood, with peaks observed between day 7 and day 14. These values in LNs (ranging from 3 x 10(5) to 3 x 10(6) RNA copies/10(6) LN cell [LNC] and 10(3) to 10(4) DNA copies/10(6) LNC) were at no time point higher than those observed in the blood. Both in LNs and in blood, rapid and significant decreases were observed in all infected animals after this peak of viral replication. Within 3 to 4 weeks p. i., antigenemia was no longer detectable and peripheral viral loads decreased to values similar to those characteristic of the chronic phase of infection (10(2) to 10(3) DNA copies/10(6) PBMC and 2 x 10(3) to 2 x 10(5) RNA copies/ml of plasma). In LNs, viral loads declined to 5 x 10(1) to 10(3) DNA copies and 10(4) to 3 x 10(5) RNA copies per 10(6) LNC at day 28 p.i. and continued to decrease until day 84 p.i. (<10 to 3 x 10(4) RNA copies/10(6) LNC). Despite extensive viremia during primary infection, neither follicular hyperplasia nor CD8(+) cell infiltration into LN germinal centers was detected. Altogether, these results indicate that the nonpathogenic outcome of SIVagm infection in its natural host is associated with a rapidly induced control of viral replication in response to SIVagm infection, rather than with a poorly replicating virus or a constitutive host genetic resistance to virus replication.

Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia viruses (STLV-I) from various naturally infected monkey species from central and western Africa.

A study of simian T-cell lymphoma/leukemia virus infection, conducted on 747 nonhuman primates belonging to 14 different species in Central and Western Africa, indicated that 4 species (Cercopithecus aethiops, Erythrocebus patas, Papio doguera, and Cercopithecus mona pogonias) had a high prevalence of seropositivity to simian T-cell lymphoma/leukemia virus type I (STLV-I). The other nonhuman primate species, however, had negative or low levels of anti-HTLV-I antibodies. STLV-I pol and env DNA was detected in 12 of 12 different animals among the seropositive species. However, STLV-I pX DNA could be detected in only 10 of 12 animals. Comparative phylogenetic analyses based on 140 bp sequence of the pol gene indicate that these STLV-I isolates were 0-9% divergent from each other and were 3.5-7% divergent from the prototype related human retrovirus HTLV-I (ATK). The West African STLV-I isolates formed a unique phylogenetic cluster as did most of the Central African STLV-I isolates, save for STLV-I (Tan 90). The phylogenetic data indicate that cross species transmission of HTLV-I and STLV-I continued to occur long after their ancestral strain separated from the progenitor to HTLV-II. Comparative amino acid analyses indicated that there was marked conservation of the TAX protein regardless of host species, while the pol and REX proteins exhibited increasing levels of diversity.