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Introduction:Mozambique is one of the poorest nations in the world and its health budget is heavily dependent on external funding. Increasingly, donors prefer to direct their funds through international non-governmental organizations instead of direct donations to the State budget. In the current climate of increased emphasis on health system strengthening, a strong and stable partnership between government and international non-governmental organizations is pivotal for health system strengthening in Mozambique. Methods:the study evaluates the current partnership through a standardized survey to healthcare workers employed by international non-governmental organizations in health (INGO, private) and the ministry of health (MOH, public). Results of the survey have been analyzed only descriptively and no statistical evaluations have been performed. Results:out of the valid 109 responses obtained 55.1% were from MOH cadres and 45.0% from INGO cadres. Most have been in the health sector for more than 5 years. Most of the respondents recognize that INGOs assist the government in strengthening the health system (71.6%), see the internal brain drain to INGOs and salary scale difference as major problems (70.6% and 78.0%); 87.2% reported that the coordination between INGOs and government needs to be improved. MOH cadres perceived the migration of cadres to INGOs and the need for improving coordination as major issues more acutely than their INGO counterparts (80.0% vs. 59.2% and 88.3% vs. 85.7% respectively). INGOs were perceived to offer better quality health services by 51.4% of respondents (of these 69.4% were INGO respondents). The quality of health services was alike between INGOs and MOH for 33% of the respondents. Conclusion:through the various efforts outlined the MOH and INGOs are moving towards an environment of mutual accountability, joint planning and coordination as well as harmonization of activities; but there are still challenges to be addressed. Prioritization and increased funding of the planning unit and planning and cooperation directorate as well as strategies for workforce retention are urgently needed.

Biological control remains unutilized as yet in the framework of Drosophila suzukii Matsumura management. Although several parasitoid species attack the pest under laboratory conditions, information is lacking on their host-finding and dispersal capabilities in natural environments. We tested the effect of repeated parasitoid releases on D. suzukii populations in infested orchards. The pupal parasitoid Trichopria drosophilae (Perkins) was released on different crops at eight sites. Parasitism was monitored using traps placed at various distances from the parasitoid release point (RP). A second experiment was carried out under semi-field conditions to evaluate augmentation of the parasitoid. In both experiments, D. suzukii infestation was evaluated through fruit samplings, both from the plant, and from the ground. In the open field trials, T. drosophilae attacked D. suzukii in traps up to 40 m away from the RP, and pest emergence was significantly reduced within a radius of 10 m at seven out of eight sites. In the semi-field trials, parasitoid releases significantly reduced D. suzukii emergence from ground-sampled fruit, and augmentation enhanced parasitism, increasing the numbers of parasitoids emerging from host pupae. Although further field studies are required, these results suggest that T. drosophilae may be considered a potential biocontrol agent for D. suzukii.

Background. Mass vaccination campaigns of the population aged 1–29 years with 1 dose of group A meningococcal (MenA) conjugate vaccine (PsA-TT, MenAfriVac) in African meningitis belt countries has resulted in the near-disappearance of MenA. The vaccine was tested in clinical trials in Africa and in India and found to be safe and highly immunogenic compared with the group A component of the licensed quadrivalent polysaccharide vaccine (PsACWY). Antibody persistence in Africa and in India was investigated. Methods. A total of 900 subjects aged 2–29 years were followed up for 4 years in Senegal, Mali, and The Gambia (study A). A total of 340 subjects aged 2–10 years were followed up for 1 year in India (study B). In study A, subjects were randomized in a 2:1 ratio, and in study B a 1:1 ratio to receive either PsA-TT or PsACWY. Immunogenicity was evaluated by measuring MenA serum bactericidal antibody (SBA) with rabbit complement and by a group A–specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results. In both studies, substantial SBA decay was observed at 6 months postvaccination in both vaccine groups, although more marked in the PsACWY group. At 1 year and 4 years (only for study A) postvaccination, SBA titers were relatively sustained in the PsA-TT group, whereas a slight increasing trend, more pronounced among the youngest, was observed in the participants aged

Shigellosis is a mild-to-severe diarrheal infection, caused by the genus Shigella, and is responsible for significant morbidity and mortality worldwide. We evaluated the safety and immunogenicity of an investigational Shigella sonnei vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in Kenya, a Shigella-endemic country. This phase 2a, observer-blind, controlled randomized study (NCT02676895) enrolled 74 healthy adults aged 18–45 years, of whom 72 were vaccinated. Participants received, in a 1:1:1 ratio, two vaccinations with the 1790GAHB vaccine at doses of either 1.5/25 μg of O antigen (OAg)/protein (group 1.5/25 μg) or 5.9/100 μg (group 5.9/100 μg) at day (D) 1 and D29, or vaccination with a quadrivalent meningococcal vaccine at D1 and tetanus, diphtheria, and acellular pertussis vaccine at D29 (control group). Solicited and unsolicited adverse events (AEs), serious AEs (SAEs), and AEs of special interest (neutropenia and reactive arthritis) were collected. Anti-S. sonnei lipopolysaccharide (LPS) serum immunoglobulin G (IgG) geometric mean concentrations (GMC) were evaluated at D1, D29, and D57 and compared to anti-S. sonnei LPS antibody levels in convalescent patients naturally exposed to S. sonnei. The percentages of participants with seroresponse were also calculated. The most frequently reported solicited local and systemic AEs across all groups were pain and headache, respectively. Only one case of severe systemic reaction was reported (severe headache after first vaccination in group 5.9/100 μg). Seven and three episodes of neutropenia, assessed as probably or possibly related to vaccination respectively, were reported in the investigational and control groups, respectively. No other SAEs were reported. Despite very high baseline anti-S. sonnei LPS serum IgG levels, the 1790GAHB vaccine induced robust antibody responses. At D29, GMC increased 2.10- and 4.43-fold from baseline in groups 1.5/25 and 5.9/100 μg, respectively, whereas no increase was observed in the control group. Antibody titers at D57 were not statistically different from those at D29. Seroresponse was 68% at D29 and 90% at D57 in group 1.5/25 μg, and 96% after each vaccination in group 5.9/100 μg. The 1790GAHB vaccine was well tolerated and highly immunogenic in a population of African adults, regardless of the GMMA OAg/protein content used.

Exorista larvarum (L.) is a tachinid parasitoid native to the Palearctic region, known as an antagonist of lepidopterous defoliators. This species is suitable to be cultured in vitro, and yields of fecund adults, approaching those usually attained in host larvae, have been previously achieved on artificial media. Direct oviposition by E. larvarum on media has not yet been obtained, and the eggs for the in vitro rearing are routinely removed from parasitized host larvae. However, many eggs are usually laid throughout the cage by captive females and can be retrieved by placing them on artificial media. Storage at low temperatures provides a method for prolonging the development of insects and stockpile them when not needed immediately. We studied the effects of storage at 20 °C (for 5 d or until pupation) or 15 °C (for 5 d or until egg hatching) on the in vitro development of E. larvarum. Lower temperatures were excluded, because previous studies showed a strong negative impact on hatching when the eggs were stored at 5 °C or 10 °C. For the experiments, eggs were removed from hosts and placed on an artificial medium. The results suggested that it is possible to delay the development of the in vitro-reared E. larvarum, which eventually reached the adult stage, although some negative effects on fly quality (i.e., longevity and fecundity) were also observed. Because quality is not an absolute concept, all the situations tested in this study could be appropriate according to the current requirements.

Harmonia axyridis (Pallas) has been introduced either intentionally or accidentally in different areas outside its native range, where it is often regarded as invasive. Dinocampus coccinellae (Schrank) has been recorded to parasitize H. axyridis in the field, both in the native and introduced areas, Italy included. The percent of parasitism found in our field investigation was low (four percent). The effect of exposure time of H. axyridis to D. coccinellae and the impact of parasitization on host longevity, oviposition capacity and egg fertility were evaluated in the laboratory. The acceptance and suitability of H. axyridis as host for D. coccinellae were then studied, in comparison with the native coccinellid Adalia bipunctata (L.), which shares the same ecological niche. The effects of parasitization on female longevity and reproduction capacity in the exotic vs. the indigenous lady beetle were also investigated. The overall results showed that D. coccinellae negatively affected the fitness of H. axyridis, more than that of A. bipunctata. The parasitoid may thus play a marginal role in controlling the populations of the Asian lady beetle, without representing a threat to A. bipunctata.

Drosophila suzukii is an invasive alien pest recently introduced into Europe and North and South America. Several control methods have been tested, and the ability of natural enemies to control this pest has been investigated. This study aimed to identify the main parasitoids of drosophilids in North Italy via field surveys, and to evaluate the ability of some of those species emerged to parasitize D. suzukii compared to indigenous D. melanogaster. A nine-site survey from July to October 2014 that exposed fruit (banana and blueberry) for 7 and 14 days obtained six parasitoid species, ranked from highest abundance: Leptopilina boulardi, L. heterotoma (Hymenoptera: Figitidae), Pachycrepoideus vindemiae (Hymenoptera: Pteromalidae), Trichopria cf. drosophilae (Hymenoptera: Diapriidae), Asobara tabida (Hymenoptera: Braconidae), and Spalangia erythromera (Hymenoptera: Pteromalidae). The presence and abundance of these species varied greatly among the sites and across the season. The field survey results showed a relationship between parasitoids and indigenous Drosophila communities and a high host competition. The ability of larval parasitoids L. boulardi and L. heterotoma and pupal parasitoid T. cf. drosophilae to parasitize the exotic and indigenous hosts was laboratory tested. Both larval parasitoids failed to develop on D. suzukii, but high mortality was recorded in larvae exposed to L. heterotoma. On the contrary, T. cf. drosophilae developed successfully on D. suzukii, with no significant differences between the exotic and indigenous hosts. These results beg further investigations of indigenous enemies, particularly T. cf. drosophilae, for effective biological control of D. suzukii.

The effect of supplementing hemolymph of the black soldier fly, Hermetia illucens (L.), or the Chinese oak silkworm, Antheraea pernyi (Guérin-Méneville), to a basic insect-free artificial medium for the tachinid Exorista larvarum (L.) was investigated. The supplementation (20% w/w) was based on the assumption that insect additives may optimize the media for this parasitoid. Egg hatch, pupal and adult yields, and sex ratio did not differ among the enriched and basic media. Preimaginal development was faster on both hemolymph-enriched media than on the basic medium. Despite the shorter development on the medium supplemented with H. illucens hemolymph than on the basic medium, on the two media puparium weights were comparable. The female flies reared on the medium enriched with H. illucens hemolymph did not lay more eggs, but the latter yielded significantly more puparia compared with the control females. Conversely, the medium enriched with A. pernyi hemolymph yielded lower female puparium weights than the basic medium and produced only one ovipositing female out of the five obtained female adults. These results indicate that the in vitro development of E. larvarum improved when the basic artificial medium was enriched with H. illucens hemolymph, whereas the supplementation with A. pernyi hemolymph negatively affected the quality of the in vitro-reared females.

The “meningitis belt” of sub-Saharan Africa runs across the continent from Senegal to Ethiopia, and this region is prone to major epidemics of meningococcal meningitis, with a high case fatality rate and serious sequelae. Until recently, most epidemics were due to group A Neisseria meningitidis (MenA). The observed reduction in meningococcal meningitis due to MenA has been due to the development of an affordable group A meningococcal vaccine, PsA-TT (MenAfriVac, Serum Institute of India, Ltd). The Meningitis Vaccine Project, a partnership between the World Health Organization (WHO) and PATH, coordinated the development, testing, licensure, and introduction of this vaccine with the aim of eliminating epidemic meningitis attributable to MenA [1–4]. Since 2010, PsA-TT has been introduced into countries across the meningitis belt through mass campaigns [5, 6]. PsA-TT is expected to confer both longer-lasting individual protection and herd protection than MenA polysaccharide vaccines. Ongoing surveillance shows that no cases of MenA meningococcal disease have occurred in vaccinated individuals [6], but the longevity of this protective immune response is not known. Prior to the introduction of PsA-TT into the African countries of the meningitis belt, multiple clinical trials assessed the safety and immunogenicity of PsA-TT. A trial conducted in children aged 12–23 months demonstrated that this vaccine was immunogenic and induced immune memory. However, antibody persistence is key in maintaining direct and indirect protection [7, 8]. We report here on the persistence of MenA-specific antibodies in individuals vaccinated with PsA-TT in early childhood.

Background. The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. Methods. Because of the public–private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. Results. Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. Conclusions. Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. Clinical Trials Registration. ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007).

Clinical Infectious Diseases, 61, ISSN:1058-4838, ISSN:1537-6591

A phase II clinical study was conducted in African toddlers (aged 12 to 23 months), with subjects receiving either investigational meningococcal group A conjugate (PsA-TT), meningococcal ACWY polysaccharide (PsACWY), or Haemophilus influenzae type b (Hib-TT) vaccine. Ten months following vaccination, the 3 study groups were further randomized to receive a dose of PsA-TT, a 1/5 dose of PsACWY, or a dose of Hib-TT vaccine. Group A serum bactericidal antibody (SBA) results have been reported previously, with PsA-TT demonstrating superior immunogenicity versus PsACWY vaccine. Immunogenicity for serogroups W135 and C was assessed by SBA assay to investigate the impact of multiple doses in this age group. Blood samples were taken prior to vaccination, 28 days and 40 weeks post-primary vaccination, and 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY. Subjects who had previously received a full dose of PsACWY had W135 SBA geometric mean titers (GMTs) of 26.1 and 4.4 at 7 and 28 days post-booster vaccination with a 1/5 PsACWY dose, respectively, whereas the W135 SBA GMTs of naive subjects at these time points following vaccination with a 1/5 dose of PsACWY were 861.1 and 14.6, respectively. Similar differences were observed for serogroup C, with SBA GMTs of 99 and 5.9 at 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY, respectively, for naive subjects, compared to 4.1 and 3.2 for previously vaccinated subjects. Immunologic hyporesponsiveness for groups C and W135 was observed following a full dose of PsACWY vaccine at 12 to 23 months of age and a 1/5 dose of PsACWY 10 months later compared to the case for PsACWY-naive subjects receiving a 1/5 dose of PsACWY vaccine. Outbreaks of Neisseria meningitidis group A recur frequently in the African meningitis belt, where they are responsible for high mortality and morbidity. Polysaccharide vaccines against group A have been available since the 1970s, but due to the limitations of these vaccines, polysaccharide-protein conjugate vaccines have been developed. In 2001, the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization (WHO) and the Program for Appropriate Technology in Health (PATH), was created through core funding from the Bill & Melinda Gates Foundation, with the goal of eliminating group A meningococcal epidemics in sub-Saharan Africa through the development and use of a monovalent group A meningococcal conjugate vaccine. A phase I clinical study of a group A meningococcal conjugate vaccine, MenAfriVac

Background: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM197 in European adults. Methodology: Following randomized blinded comparison of single vaccination with either Vi-CRM197 or licensed polysaccharide vaccines (both containing 25•0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM197 (1•25 µg, 5•0 µg and 12•5 µg of Vi antigen) with the polysaccharide vaccine. These studies are registered with ClinicalTrials.gov, number NCT01123941 and NCT01193907. Principal Findings: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM197 induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM197 formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Conclusions: Vi-CRM197 did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.

A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson’s correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a >4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group. Within the African meningitis belt, unpredictable epidemics of meningococcal disease continue to occur every 5 to 15 years. To prevent these epidemics, a novel serogroup A conjugate meningococcal vaccine was developed. The Meningitis Vaccine Project, a partnership between the World Health Organization (WHO) and PATH (Seattle, WA) with core funding from the Bill and Melinda Gates Foundation, was created in 2001 with the goal of eliminating meningococcal epidemics in sub-Saharan Africa through the development, testing and licensure, and widespread use of serogroup A meningococcal conjugate vaccines (11) (http://www.meningvax.org). A group A meningococcal conjugate vaccine using tetanus toxoid as a carrier protein (PsA-TT) was developed at the Serum Institute of India Ltd., using a new licensed conjugation technique from the Center for Biologics Evaluation

The Cry9Aa entomocidal toxin from Bacillus thuringiensis ssp. galleriae (Btg) and an epiphytic Pseudomonas sp. derivative carrying the cloned cry9Aa gene from Btg are active against the pine processionary moth Thaumetopoea pityocampa and the laboratory model species Galleria mellonella. A laboratory study was conducted to investigate the side effects of the Cry9Aa toxin and the engineered bacterium on the post-embryonic development of Exorista larvarum, a larval parasitoid of forest lepidopterous defoliators, cultured in the factitious host G.mellonella. In a first experiment, the purified toxin and the commercial Bt preparation Foray 48B induced a mortality of G. mellonella sixth-instar larvae significantly higher than that of the distilled water control. In parallel, the development of E. larvarum in this host was assessed, but no significant difference was found for any of the parasitoid parameters examined (i.e., eggs oviposited, percentage of puparia and adults and puparial weights). In subsequent experiments, cry9Aa-Pseudomonas suspension significantly increased the mortality of sixth instar G. mellonella larvae compared to untransformed Pseudomonas sp. suspension and distilled water. As to the parasitoid parameters, the cry9Aa-Pseudomonas did not significantly affect the number of oviposited eggs, percentage of puparia and puparial weights. It can be concluded that the postembryonic development of E. larvarum was not affected by host treatment with either Cry9Aa toxin or cry9Aa-Pseudomonas under the laboratory conditions tested. Although direct effects on parasitoid performance have not been shown, indirect effects could still occur and need to be considered in future studies concerning the effects of genetically modified Bt-derivatives.

The environmental impact of genetically modified crops has been the subject of intense research in the past decade. Since the introduction of insect-resistant crops in 1996, cultivation of this group of genetically modified crops has grown substantially. Most insect-resistant varieties, including corn and cotton, have been engineered to express crystal (Cry) toxins. Although several studies concerning the environmental fate of this group of insecticidal toxins have been conducted during the past decade, conflicting information exists dealing with the persistence of Cry toxins in soil. In the present investigation, the persistence of antilepidopteran Cry1Ab and Cry1Ac toxins in two different agricultural soils was studied. The potential of cry1Ab genes to persist in soil was also estimated. The results from this laboratory investigation indicated that the two toxins dissipated rapidly in both the sandy and in the clay loam soil. The two toxins showed similar degradation rates in soil. During the 35-day incubation period, more than 92 and 79% of the initial amount of Cry toxins dissipated in the sandy and clay loam soil, respectively. Extractable fractions of the two toxins were lower in the fine-textured soil with respect to the coarse soil. Reduced recovery efficiency from the clay loam soil and thus bioavailability were presumably involved in the lower decline of Cry toxins in this soil. Investigations conducted with an insect-resistant transgenic corn hybrid showed no detectable levels of cry1Ab genes in soil six months after plant harvest.

An isolate of Pseudomonas sp. (16S rDNA sequence 98% homologous to P. graminis and P. lutea) was isolated from the phyllosphere of black pine in northern Italy and used as a host for the gene encoding the Cry9Aa entomocidal toxin from Bacillus thuringiensis subsp. galleriae. An expression system featuring a synthetic highest-consensus promoter specifically tailored for the regulated induction of cloned genes over a broad range of Gram-negative bacteria was used to drive the production of the introduced toxin. The construct showed effective toxicity toward larvae of the greater wax moth (Galleria mellonella), which was also used as a model system for establishing a number of newly proposed toxicity in indices (LC50 cellulare efficiency, toxin cellular efficiency, GMO efficiency, lethal cellular intake). These were devised in order to express toxicities of entomocidal bacteria in a standard fashion enabling the fine tuning of biocontrol treatments as well as the comparative evaluation of different reports.

Neisseria meningitidisis a major cause of bacterial septicemia and meningitis.Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed inEscherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.