Oral cholera vaccine coverage during a preventive door-to-door mass vaccination campaign in Nampula, Mozambique.

BACKGROUND: In addition to improving water, sanitation and hygiene (WASH) measures and optimal case management, the introduction of Oral cholera vaccine (OCV) is a complementary strategy for cholera prevention and control for vulnerable population groups. In October 2016, the Mozambique Ministry of Health implemented a mass vaccination campaign using a two-dose regimen of the Shanchol™ OCV in six high-risk neighborhoods of Nampula city, in Northern Mozambique. Overall 193,403 people were targeted by the campaign, which used a door-to-door strategy. During campaign follow-up, a population survey was conducted to assess: (1) OCV coverage; (2) frequency of adverse events following immunization; (3) vaccine acceptability and (4) reasons for non-vaccination. METHODOLOGY/PRINCIPAL FINDINGS: In the absence of a household listing and clear administrative neighborhood delimitations, we used geospatial technology to select households from satellite images and used the support of community leaders. One person per household was randomly selected for interview. In total, 636 individuals were enrolled in the survey. The overall vaccination coverage with at least one dose (including card and oral reporting) was 69.5% (95%CI: 51.2-88.2) and the two-dose coverage was 51.2% (95%CI: 37.9-64.3). The campaign was well accepted. Among the 185 non-vaccinated individuals, 83 (44.6%) did not take the vaccine because they were absent when the vaccination team visited their houses. Among the 451 vaccinated individuals, 47 (10%) reported minor and non-specific complaints, and 78 (17.3%) mentioned they did not receive any information before the campaign. CONCLUSIONS/SIGNIFICANCE: In spite of overall coverage being slightly lower than expected, the use of a mobile door-to-door strategy remains a viable option even in densely-populated urban settings. Our results suggest that campaigns can be successfully implemented and well accepted in Mozambique in non-emergency contexts in order to prevent cholera outbreaks. These findings are encouraging and complement the previous Mozambican experience related to OCV.

Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011-2015.

BACKGROUND: Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. METHODOLOGY/PRINCIPAL FINDINGS: Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. CONCLUSIONS/SIGNIFICANCE: Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and control efforts during major cholera outbreaks in recent years.

The African cholera surveillance network (Africhol) consortium meeting, 10-11 June 2015, Lomé, Togo.

The fifth annual meeting of the African cholera surveillance network (Africhol) took place on 10-11 June 2015 in Lomé, Togo. Together with international partners, representatives from the 11 member countries -Cameroon, Côte d'Ivoire, Democratic Republic of Congo, Guinea, Kenya, Mozambique, Nigeria, Tanzania, Togo, Uganda, Zimbabwe- and an invited country (Malawi) shared their experience. The meeting featured three sessions: i) cholera surveillance, prevention and control in participating countries, ii) cholera surveillance methodology, such as cholera mapping, cost-effectiveness studies and the issue of overlapping epidemics from different diseases, iii) cholera laboratory diagnostics tools and capacity building. The meeting has greatly benefitted from the input of technical expertise from participating institutions and the observations emerging from the meeting should enable national teams to make recommendations to their respective governments on the most appropriate and effective measures to be taken for the prevention and control of cholera. Recommendations for future activities included collecting precise burden estimates in surveillance sites; modeling cholera burden for Africa; setting up cross-border collaborations; strengthening laboratory capacity for the confirmation of suspected cholera cases and for vaccine impact assessment in settings where oral cholera vaccine would be used; adapting cholera surveillance to concurrent issues (e.g., Ebola); and developing national cholera control plans including rationale vaccination strategies together with other preventive and control measures such as improvements in water, sanitation and hygiene (WASH).

Epidemiology of cholera outbreaks and socio-economic characteristics of the communities in the fishing villages of Uganda: 2011-2015.

BACKGROUND: The communities in fishing villages in the Great Lakes Region of Africa and particularly in Uganda experience recurrent cholera outbreaks that lead to considerable mortality and morbidity. We evaluated cholera epidemiology and population characteristics in the fishing villages of Uganda to better target prevention and control interventions of cholera and contribute to its elimination from those communities. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study between 2011-15 in fishing villages in Uganda. We collected, reviewed and documented epidemiological and socioeconomic data for 10 cholera outbreaks that occurred in fishing communities located along the African Great Lakes and River Nile in Uganda. These outbreaks caused 1,827 suspected cholera cases and 43 deaths, with a Case-Fatality Ratio (CFR) of 2.4%. Though the communities in the fishing villages make up only 5-10% of the Ugandan population, they bear the biggest burden of cholera contributing 58% and 55% of all reported cases and deaths in Uganda during the study period. The CFR was significantly higher among males than females (3.2% vs. 1.3%, p = 0.02). The outbreaks were seasonal with most cases occurring during the months of April-May. Male children under age of 5 years, and 5-9 years had increased risk. Cholera was endemic in some villages with well-defined "hotspots". Practices predisposing communities to cholera outbreaks included: the use of contaminated lake water, poor sanitation and hygiene. Additional factors were: ignorance, illiteracy, and poverty. CONCLUSIONS/SIGNIFICANCE: Cholera outbreaks were a major cause of morbidity and mortality among the fishing communities in Uganda. In addition to improvements in water, sanitation, and hygiene, oral cholera vaccines could play an important role in the prevention and control of these outbreaks, particularly when targeted to high-risk areas and populations. Promotion and facilitation of access to social services including education and reduction in poverty should contribute to cholera prevention, control and elimination in these communities.

Cost-effectiveness analysis of the introduction of the pneumococcal conjugate vaccine (PCV-13) in the Egyptian national immunization program, 2013.

INTRODUCTION: Pneumonia is one of the most important causes of morbidity and mortality in children under 5 in Egypt, and the Ministry of Health of Egypt is considering introducing pneumococcal conjugate vaccine (PCV) in its national immunization program. We performed an economic analysis to evaluate the cost-effectiveness of this vaccine in Egypt and to provide the decision-makers with needed evidence. METHODS: The analysis was done using the TRIVAC model. Data included demographic characteristics, burden of disease, coverage and efficacy of the vaccine, health resource utilization, and costs of pneumococcal disease vaccination and treatment. Whenever possible, we used national or regional data. Two alternatives were compared: (1) general vaccination of children younger than 5 years with the 13-valent pneumococcal conjugate vaccine (PCV13), using a three-dose schedule without booster, and (2) no vaccination. Outcomes of 10 cohorts from birth to 5 years were analyzed. The study was performed from the governmental perspective and selected public health providers. RESULTS: In comparison to no vaccine, the introduction of PCV13 would be cost-effective, with an incremental cost-effectiveness ratio of US$ 3916 per disability-adjusted life-year (DALY) averted (government perspective). The total incremental cost of the PCV vaccination program (10 cohorts) would be approximately US$ 1.09 billion. Over the 10 cohorts, the program would avert 8583 pneumococcal deaths - 42% of all pneumococcal-related deaths. CONCLUSION: The introduction of PCV13 would be a good value for money from the government perspective. It would represent a high-impact public health intervention for Egypt and respond to the National Immunization Technical Advisory Group (NITAG) resolution on reducing pneumonia burden and overall child mortality. Strengthening surveillance will be critical to generating high-quality national data, improving future economic analyses that support evidence-based decisions for introducing vaccines and public health interventions, and to monitoring their impact.

Cost-effectiveness analysis of the introduction of rotavirus vaccine in Iran.

BACKGROUND: Although the mortality from diarrheal diseases has been decreasing dramatically in Iran, it still represents an important proportion of disease burden in children <5 years old. Rotavirus vaccines are among the most effective strategies against diarrheal diseases in specific epidemiological conditions. This study aimed to evaluate the cost-effectiveness of the introduction of rotavirus vaccine (3 doses of pentavalent RotaTeq (RV5)) in Iran, from the viewpoints of Iran's health system and society. METHODS: The TRIVAC decision support model was used to calculate total incremental costs, life years (LYs) gained, and disability-adjusted life years (DALYs) averted due to the vaccination program. Necessary input data were collected from the most valid accessible sources as well as a systematic review and meta-analysis on epidemiological studies. We used WHO guidelines to estimate vaccination cost. An annual discount rate of 3% was considered for both health gain and costs. A deterministic sensitivity analysis was performed for testing the robustness of the models results. RESULTS: Our results indicated that total DALYs potentially lost due to rotavirus diarrhea within 10 years would be 138,161, of which 76,591 could be prevented by rotavirus vaccine. The total vaccination cost for 10 cohorts was estimated to be US$ 499.91 million. Also, US$ 470.61 million would be saved because of preventing outpatient visits and inpatient admissions (cost-saving from the society perspective). We estimated a cost per DALY averted of US$ 2868 for RV5 vaccination, which corresponds to a highly cost-effective strategy from the government perspective. In the sensitivity analysis, all scenarios tested were still cost-saving or highly cost-effective from the society perspective, except in the least favorable scenario and low vaccine efficacy and disease incidence scenario. CONCLUSION: Based on the findings, introduction of rotavirus vaccine is a highly cost-effective strategy from the government perspective. Introducing the vaccine to the national immunization program is an efficient use of available funds to reduce child mortality and morbidity in Iran.

Evidence-based decision-making for vaccine introductions: Overview of the ProVac International Working Group's experience.

INTRODUCTION: Pan American Health Organization's (PAHO) ProVac Initiative aims to strengthen countries' technical capacity to make evidence-based immunization policy. With financial support from the Bill and Melinda Gates Foundation, PAHO established the ProVac International Working Group (IWG), a platform created for two years to transfer the ProVac Initiative's tools and methods to support decisions in non-PAHO regions. METHODS: In 2011, WHO Regional Offices and partner agencies established the IWG to transfer the ProVac framework for new vaccine decision support, including tools and trainings to other regions of the world. During the two year period, PAHO served as the coordinating secretariat and partner agencies played implementing or advisory roles. RESULTS: Fifty nine national professionals from 17 countries received training on the use of economic evaluations to aid vaccine policy making through regional workshops. The IWG provided direct technical support to nine countries to develop cost-effectiveness analyses to inform decisions. All nine countries introduced the new vaccine evaluated or their NITAGs have made a recommendation to the Ministry of Health to introduce the new vaccine. DISCUSSION: Developing countries around the world are increasingly interested in weighing the potential health impact due to new vaccine introduction against the investments required. During the two years, the ProVac approach proved valuable and timely to aid the national decision making processes, even despite the different challenges and idiosyncrasies encountered in each region. The results of this work suggest that: (1) there is great need and demand for technical support and for capacity building around economic evaluations; and (2) the ProVac method of supporting country-owned analyses is as effective in other regions as it has been in the PAHO region. CONCLUSION: Decision support for new vaccine introduction in low- and middle-income countries is critical to guiding the efficient use of resources and prioritizing high impact vaccination programs.

Frequent transient hepatitis C viremia without seroconversion among healthcare workers in Cairo, Egypt.

BACKGROUNDS: With 10% of the general population aged 15-59 years chronically infected with hepatitis C virus (HCV), Egypt is the country with the highest HCV prevalence worldwide. Healthcare workers (HCWs) are therefore at particularly high risk of HCV infection. Our aim was to study HCV infection risk after occupational blood exposure among HCWs in Cairo. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in 2008-2010 at Ain Shams University Hospital, Cairo. HCWs reporting an occupational blood exposure at screening, having neither anti-HCV antibodies (anti-HCV) nor HCV RNA, and exposed to a HCV RNA positive patient, were enrolled in a 6-month prospective cohort with follow-up visits at weeks 2, 4, 8, 12 and 24. During follow-up, anti-HCV, HCV RNA and ALT were tested. Among 597 HCWs who reported a blood exposure, anti-HCV prevalence at screening was 7.2%, not different from that of the general population of Cairo after age-standardization (11.6% and 10.4% respectively, p = 0.62). The proportion of HCV viremia among index patients was 37%. Of 73 HCWs exposed to HCV RNA from index patients, nine (12.3%; 95%CI, 5.8-22.1%) presented transient viremia, the majority of which occurred within the first two weeks after exposure. None of the workers presented seroconversion or elevation of ALT. CONCLUSIONS/SIGNIFICANCE: HCWs of a general University hospital in Cairo were exposed to a highly viremic patient population. They experienced frequent occupational blood exposures, particularly in early stages of training. These exposures resulted in transient viremic episodes without established infection. These findings call for further investigation of potential immune protection against HCV persistence in this high risk group.

Evolution of malaria mortality and morbidity after the emergence of chloroquine resistance in Niakhar, Senegal.

BACKGROUND: Recently, it has been assumed that resistance of Plasmodium to chloroquine increased malaria mortality. The study aimed to assess the impact of chemoresistance on mortality attributable to malaria in a rural area of Senegal, since the emergence of resistance in 1992, whilst chloroquine was used as first-line treatment of malaria, until the change in national anti-malarial policy in 2003. METHODS: The retrospective study took place in the demographic surveillance site (DSS) of Niakhar. Data about malaria morbidity were obtained from health records of three health care facilities, where diagnosis of malaria was based on clinical signs. Source of data concerning malaria mortality were verbal autopsies performed by trained fieldworkers and examined by physicians who identified the probable cause of death. RESULTS: From 1992 to 2004, clinical malaria morbidity represented 39% of total morbidity in health centres. Mean malaria mortality was 2.4 per thousand and 10.4 per thousand among total population and children younger than five years, respectively, and was highest in the 1992-1995 period. It tended to decline from 1992 to 2003 (Trend test, total population p = 0.03, children 0-4 years p = 0.12 - children 1-4 years p = 0.04- children 5-9 years p = 0.01). CONCLUSION: Contrary to what has been observed until 1995, mortality attributable to malaria did not continue to increase dramatically in spite of the growing resistance to chloroquine and its use as first-line treatment until 2003. Malaria morbidity and mortality followed parallel trends and rather fluctuated accordingly to rainfall.

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992-2004).

BACKGROUND: In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006. The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region. METHODS: The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992-2004. RESULTS: Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change. CONCLUSION: The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines.

Comparison of CD8+ T Cell responses to cytomegalovirus between human fetuses and their transmitter mothers.

BACKGROUND: The mechanisms responsible for the increased susceptibility of fetuses to cytomegalovirus (CMV) were studied by comparing CD8(+) T cell responses to the virus in susceptible fetuses to those in their comparatively more resistant mothers. METHODS: Included in the study were 16 transmitter mothers who underwent seroconversion during the first trimester of pregnancy as well as their fetuses, who were positive for CMV in amniotic fluid by polymerase chain reaction at 17-19 weeks of gestation. Fetal and maternal blood samples were collected between the 22nd and 39th week of gestation. Cytotoxic T lymphocytes (CTLs) that had activated (HLA-DR(+)), effector/memory (CD28(-)), and memory (CD18(high)) phenotypes; that stained with the HLA-A2/pp65 or the HLA-B7/pp65 multimer; and that secreted interferon (IFN)- gamma were enumerated by flow cytometry. Viral loads were determined simultaneously. RESULTS: The results showed (1) similar levels of activated, effector/memory, and memory CTLs in fetuses and mothers but a smaller pp65-specific CTL pool in fetuses (median, 0.015% vs. 0.99%; P=.003); (2) similar percentages of CTLs secreting IFN- gamma after stimulation with ionomycin/phorbol myristate acetate in fetuses and mothers but lower percentages of CTLs secreting IFN- gamma after stimulation with a CD3 monoclonal antibody in fetuses (median, 1% vs. 14%; P=.01); and (3) higher viral loads (mean, 17,290 vs. <250 genome equivalents/mL) in fetuses. CONCLUSION: Impaired viral clearance might be related to a defective expansion of the pp65-specific CTL pool and/or to the immaturity of IFN- gamma -secreting cells in fetuses.

Shelf life of predosed plates containing mefloquine, artemisinin, dihydroartemisinin, and artesunate as used for in vitro Plasmodium falciparum susceptibility assessment.

The shelf lives of preserved antimalarial agent-predosed plates according to the type of wrapping and the temperature of storage were studied by measuring the 50% inhibitory concentrations of drug for Plasmodium falciparum 3D7. The shelf life of mefloquine was 8 weeks at 25 degrees C; and those of artesunate, artemisinin, and dihydroartemisinin were a minimum of 24, 12, and 8 weeks, respectively, at 4 degrees C.

Zoledronic Acid and renal toxicity: data from French adverse effect reporting database.

BACKGROUND: Zoledronic acid-associated renal impairment leading to renal failure has been recently reported in a cohort of US patients. However, the presence of such toxicity in other populations has not yet been determined. OBJECTIVE: To analyze French cases of zoledronic acid-associated nephrotoxicity. METHODS: We evaluated available cases with acute deterioration of renal function associated with zoledronic acid therapy drawn from the French Adverse Event Reporting System database until July 1, 2004. RESULTS: We identified 4 men and 3 women between the ages of 52 and 70 years, with multiple myeloma or different types of metastatic cancer, who had experienced renal impairment during zoledronic acid therapy. Four patients developed de novo acute renal failure, while the other 3 patients experienced acute deterioration of preexisting chronic renal failure. Renal failure occurred after various durations of zoledronic acid therapy (1-120 days). Three patients completely recovered and one partially recovered their previous renal function after discontinuation of zoledronic acid, but renal impairment was associated with a fatal outcome in 2 cases; the outcome of the other case was unknown. Our data confirm the previously reported risk factors for zoledronic acid-associated nephrotoxicity such as advanced cancer, multiple myeloma, preexisting renal failure, diabetes, hypertension, and concomitant use of nephrotoxic drugs. CONCLUSIONS: These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.