Incidence of catastrophic expenditures linked to obstetric and neonatal care at 92 facilities in Lubumbashi, Democratic Republic of the Congo, 2015.

BACKGROUND: In the Democratic Republic of the Congo (DRC), more than 93% of users must pay out of pocket for care. Despite the risk of catastrophic expenditures (CE), 94% of births in Lubumbashi are attended by skilled personnel. We aimed to identify risk factors for CE associated with obstetric and neonatal care in this setting, to document coping mechanisms employed by households to pay the price of care, and to identify consequences of CE on households. METHODS: We used mixed methods and conducted both a cross-sectional study and a phenomenological study of women who delivered at 92 health care facilities in all 11 health zones of Lubumbashi. In April and May 2015 we followed 1,627 women and collected data on their health care and household expenses to determine whether they experienced CE, defined as payments that reached or exceeded 40% of a household's capacity to pay. Two months after discharge, we conducted semi-structured interviews with 58 women at their homes to assess the consequences of CE. RESULTS: In all, 261 of 1,627 (16.0%) women experienced CE. Whether a woman or her infant experienced complications was an important contributor to her risk of CE; poverty, younger age, being unmarried, and delivering in a parastatal facility or with more highly trained personnel also increased risk. Among a subset of women with CE interviewed 2 months after discharge, those who were in debt or who had lost their trading income or goods were unable to pay their rent, their children's school fees, or were obliged to reduce food consumption in the household; some had become victims of mistreatment such as verbal abuse, disputes with in-laws, denial of paternity, abandonment by partners, financial deprivation, even divorce. CONCLUSIONS: We found a higher proportion of CE than previously reported in the DRC or in other urban settings in Africa. We suggest that the government and funders in DRC support initiatives to put in place mutual-aid health risk pools and health insurance and introduce and institutionalize free maternal and infant care. We further suggest that the government ensure decent and regular payment of providers and improve the financing and functioning of health care facilities to improve the quality of care and alleviate the burden on users.

Hospital detention of mothers and their infants at a large provincial hospital: a mixed-methods descriptive case study, Lubumbashi, Democratic Republic of the Congo.

BACKGROUND: The practice of detaining people who are unable to pay for health care services they have received is widespread in many parts of the world. We aimed to determine the proportion of women and their infants detained for inability to pay for services received at a provincial hospital in the Democratic Republic of the Congo during a 6-week period in 2016. A secondary objective was to determine clinical and administrative staff attitudes and practices about payment for services and detention. METHODS: This mixed-methods descriptive case study included a cross-sectional survey and interviews with key informants. RESULTS: Over half (52%) of the 85 women who were in the maternity ward at Sendwe Hospital and eligible for discharge between August 5 and September 15, 2016 were detained for 1 to 30 days for outstanding bills of United States dollars (USD) 21 to USD 515. Women who were detained were younger, poorer, and had more obstetric complications and caesarean sections than other women. In addition, over one quarter of the infants born to these women had died during delivery or in the first three days of life. Key informant interviews normalized detention as an unfortunate but inevitable consequence of patient poverty and health system resource constraints. CONCLUSIONS: Detention of women and their infants is common at this hospital in the DRC. This represents a violation of human rights and a systemic failure to ensure that all people have access to essential health services and that they not suffer financial hardship due to the price of those services.

Emergency obstetric and neonatal care availability, use, and quality: a cross-sectional study in the city of Lubumbashi, Democratic Republic of the Congo, 2011.

BACKGROUND: While emergency obstetric and neonatal care (EmONC) is a proxy indicator for monitoring maternal and perinatal mortalities, in Democratic Republic of the Congo (DRC), data on this care is rarely available. In the city of Lubumbashi, the second largest in DRC with an estimated population of 1.5 million, the availability, use and quality of EmONC are not known. This study aimed to assess these elements in Lubumbashi. METHODS: This cross-sectional survey was conducted in April and May 2011. Fifty-three of the 180 health facilities that provide maternity care in Lubumbashi were included in this study. Only health facilities with at least six deliveries per month over the course of 2010 were included. The availability, use and quality of EmONC at each level of the health care system were assessed according to the WHO standards. RESULTS: The availability of EmONC in Lubumbashi falls short of WHO standards. In this study, we found one facility providing Comprehensive EmONC (CEmONC) for a catchment area of 918,819 inhabitants. Apart from the tertiary hospital (Sendwe), no other facility provided all the basic emergency obstetric and neonatal care (BEmONC) signal functions. However, all had carried out at least one of the nine signal functions during the 3 months preceding our survey: 73.6% of 53 facilities had administered parenteral antibiotics, 79.2% had systematically offered oxytocics, 39.6% had administered magnesium sulfate, 73.6% had manually evacuated placentas, 81.1% had removed retained placenta products, 54.7% had revived newborns, 35.8% had performed caesarean sections, and 47.2% had performed blood transfusions. Function 6, vaginal delivery assisted by ventouse or forceps, was performed in only two (3.8%) facilities. If this signal function was not taken into account in our assessment of EmONC availability, there would be five facilities providing CEmONC for 918,819 inhabitants, rather than one. In 2010, all the women in the surveyed facilities with obstetric complications delivered in facilities that had carried out at least one signal function in the 3 months before our survey; 7.0% of these women delivered in the facility which provided CEmONC. Mortality due to direct obstetric causes was 3.9% in the health facility that provided CEmONC. The intrapartum mortality was also high in this facility (5.1%). None of the maternity ward managers in any of the facilities surveyed had received training on the EmONC package. Essential supplies and equipment for performing certain EmONC functions were not available in all the surveyed facilities. CONCLUSION: Audits of maternal and neonatal deaths and near-misses should be established and used as a basis for monitoring the quality of care in Lubumbashi. To reduce maternal and perinatal mortality, it is essential that staff skills regarding EmONC be strengthened, the availability of supplies and equipment be increased, and that care processes be standardized in all health facilities in Lubumbashi.

Obstetric fistula in low-resource countries: an under-valued and under-studied problem--systematic review of its incidence, prevalence, and association with stillbirth.

BACKGROUND: Obstetric fistula (OF) is a serious consequence of prolonged, obstructed labor in settings where emergency obstetric care is limited, but there are few reliable, population-based estimates of the rate of OF. Stillbirth (SB) is another serious consequence of prolonged, obstructed labor, yet the frequency of SB in women with OF is poorly described. Here, we review these data. METHODS: We searched electronic databases and grey literature for articles on OF in low-resource countries published between January 1, 1995, and November 16, 2014, and selected for inclusion 19 articles with original population-based OF incidence or prevalence data and 44 with reports of frequency of SB associated with OF. RESULTS: OF estimates came from medium- and low-HDI countries in South Asia and Africa, and varied considerably; incidence estimates ranged from 0 to 4.09 OF cases per 1000 deliveries, while prevalence estimates were judged more prone to bias and ranged from 0 to 81.0 OF cases per 1000 women. Reported frequency of SB associated with OF ranged from 32.3 % to 100 %, with estimates from the largest studies around 92 %. Study methods and quality were inconsistent. CONCLUSIONS: Reliable data on OF and associated SB in low-resource countries are lacking, underscoring the relative invisibility of these issues. Sound numbers are needed to guide policy and funding responses to these neglected conditions of poverty.

Risk factors for diarrhea hospitalization in Bangladesh, 2000-2008: a case-case study of cholera and shigellosis.

BACKGROUND: Cholera and shigellosis are endemic on the Indian subcontinent. Our objective was to identify cholera-specific risk factors distinct from shigellosis risk factors. METHODS: We conducted a case-case study among hospitalized diarrheal patients, comparing those with cholera and shigellosis in International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) hospitals in Matlab (rural) and Dhaka (urban) between January 1, 2000 and December 31, 2008. RESULTS: Multivariable Poisson regression models revealed that having more than nine years of education, compared to no education, was associated with a 39% (adjusted Risk Ratio [aRR] = 0.61, 95% confidence interval [CI]: 0.40-0.93) decreased risk for cholera hospitalization in Matlab and a 16% (aRR = 0.84, 95% CI: 0.75-0.94) decreased risk in Dhaka. Having a family member with diarrhea in the past seven days increased cholera hospitalization risk by 17% (aRR = 1.17, 95% CI: 1.09-1.26) in Matlab. CONCLUSIONS: Further studies are needed to elucidate the pathway through which education impacts cholera risk in order to create targeted interventions in cholera-endemic areas. Interventions seeking to reduce transmission and facilitate hygienic practices among family members of index cases with diarrhea should be considered, especially in rural cholera endemic settings.

Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys.

The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette-Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-gamma, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters.

Anti-SARS-CoV-2 seroprevalence in King County, WA-Cross-sectional survey, August 2020.

We conducted a seroprevalence survey to estimate the true number of infections with SARS-CoV-2, the virus that causes COVID-19, in King County as of August 2020 by measuring the proportion of residents from who had antibodies against the virus. Participants from 727 households took part in a cross-sectional address-based household survey with random and non-random samples and provided dried blood spots that were tested for total antibody against the viral nucleocapsid protein, with confirmatory testing for immunoglobulin G against the spike protein. The data were weighted to match King County's population based on sex, age group, income, race, and Hispanic status. After weighting and accounting for the accuracy of the tests, our best overall estimate of anti-SARS-CoV-2 seroprevalence in King County as of August 2020 is 3.9% (95% confidence interval (CI) 2.4%-6.0%) with an effective sample size of 589. Comparing seroprevalence with positive test reports, our survey suggests that viral testing underestimated incidence by a factor of about five and suggests that the proportion of cases that were serious (based on hospitalization) or fatal was 2.4% and 0.8%, respectively. Prevalence varied by subgroup; households reporting incomes at or below $100,000 in 2019 had nearly five times higher estimated antibody prevalence than those with incomes above $100,000. Those reporting non-White/non-Asian race had roughly seven times higher estimated antibody prevalence than those reporting White race. This survey was noteworthy for including people of all ages; among all age groups, the weighted estimate of prevalence was highest in older teens and young adults and lowest in young children, although these differences were not statistically significant.

Human Resources for Health-Related Challenges to Ensuring Quality Newborn Care in Low- and Middle-Income Countries: A Scoping Review.

BACKGROUND: A critical shortage of health workers with needed maternal and newborn competencies remains a major challenge for the provision of quality care for mothers and newborns, particularly in low- and middle-income countries. Supply-side challenges related to human resources for health (HRH) worsen shortages and can negatively affect health worker performance and quality of care. This review scoped country-focused sources to identify and map evidence on HRH-related challenges to quality facility-based newborn care provision by nurses and midwives. METHODS: Evidence for this review was collected iteratively, beginning with pertinent World Health Organization documents and extending to articles identified via database and manual reference searches and country reports. Evidence from country-focused sources from 2000 onward was extracted using a data extraction tool that was designed iteratively; thematic analysis was used to map the 10 categories of HRH challenges. FINDINGS: A total of 332 peer-reviewed articles were screened, of which 22 met inclusion criteria. Fourteen additional sources were added from manual reference search and gray literature sources. Evidence has been mapped into 10 categories of HRH-related challenges: (1) lack of health worker data and monitoring; (2) poor health worker preservice education; (3) lack of HW access to evidence-based practice guidelines, continuing education, and continuing professional development; (4) insufficient and inequitable distribution of health workers and heavy workload; (5) poor retention, absenteeism, and rotation of experienced staff; (6) poor work environment, including low salary; (7) limited and poor supervision; (8) low morale, motivation, and attitude, and job dissatisfaction; (9) weaknesses of policy, regulations, management, leadership, governance, and funding; and (10) structural and contextual barriers. CONCLUSION: The mapping provides needed insight that informed new World Health Organization strategies and supporting efforts to address the challenges identified and strengthen human resources for neonatal care, with the ultimate goal of improving newborn care and outcomes.

Commercialization of obstetric and neonatal care in the Democratic Republic of the Congo: A study of the variability in user fees in Lubumbashi, 2014.

OBJECTIVE: In the Democratic Republic of the Congo, insufficient state financing of the health system produced weak progress toward targets of Millennium Development Goals 4 and 5. In Lubumbashi, almost all women pay out-of-pocket for obstetric and neonatal care. As no standard pricing system has been implemented, there is great variation in payments related to childbirth between health facilities and even within the same facility. This work investigates the determinants of this variation. METHODS: We conducted a cross-sectional study including women from admission through discharge at 92 maternity wards in Lubumbashi in March 2014. The women's payments were collected and validated by triangulating interviews of new mothers and nurses with document review. We studied payments related to delivery from the perspective of women delivering. The total was the sum of the payments linked to seeking and accessing care and transport of the woman and companion. The determinants were assessed by multilevel regression. RESULTS: Median payments for delivery varied by type: for an uncomplicated vaginal delivery, US$45 (range, US$17-260); for a complicated vaginal delivery US$60 (US$16-304); and for a Cesarean section, US$338 (US$163-782). Vaginal delivery was more expensive at health centers than in general referral hospitals or polyclinics. Cesarean sections done in corporate polyclinics and hospitals were more expensive than those done in the general referral hospitals. Referral of delivering women, use of more highly trained personnel, and a longer stay in the maternity unit contributed to higher expenses. A vaginal delivery in the private sector was more cost-effective than in the public sector. CONCLUSION: To guarantee universal coverage of high-quality care, we suggest that the government and funders in DRC support health insurance and risk pool initiatives, and introduce and institutionalize free mother and infant care.

Immunization coverage and risk factors for failure to immunize within the Expanded Programme on Immunization in Kenya after introduction of new Haemophilus influenzae type b and hepatitis b virus antigens.

BACKGROUND: Kenya introduced a pentavalent vaccine including the DTP, Haemophilus influenzae type b and hepatitis b virus antigens in Nov 2001 and strengthened immunization services. We estimated immunization coverage before and after introduction, timeliness of vaccination and risk factors for failure to immunize in Kilifi district, Kenya. METHODS: In Nov 2002 we performed WHO cluster-sample surveys of >200 children scheduled for vaccination before or after introduction of pentavalent vaccine. In Mar 2004 we conducted a simple random sample (SRS) survey of 204 children aged 9-23 months. Coverage was estimated by inverse Kaplan-Meier survival analysis of vaccine-card and mothers' recall data and corroborated by reviewing administrative records from national and provincial vaccine stores. The contribution to timely immunization of distance from clinic, seasonal rainfall, mother's age, and family size was estimated by a proportional hazards model. RESULTS: Immunization coverage for three DTP and pentavalent doses was 100% before and 91% after pentavalent vaccine introduction, respectively. By SRS survey, coverage was 88% for three pentavalent doses. The median age at first, second and third vaccine dose was 8, 13 and 18 weeks. Vials dispatched to Kilifi District during 2001-2003 would provide three immunizations for 92% of the birth cohort. Immunization rate ratios were reduced with every kilometre of distance from home to vaccine clinic (HR 0.95, CI 0.91-1.00), rainy seasons (HR 0.73, 95% CI 0.61-0.89) and family size, increasing progressively up to 4 children (HR 0.55, 95% CI 0.41-0.73). CONCLUSION: Vaccine coverage was high before and after introduction of pentavalent vaccine, but most doses were given late. Coverage is limited by seasonal factors and family size.

Effectiveness of Haemophilus influenzae type b Conjugate vaccine introduction into routine childhood immunization in Kenya.

CONTEXT: Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001. OBJECTIVE: To define invasive Hib disease incidence and Hib vaccine program effectiveness in Kenya. DESIGN, SETTING, AND PATIENTS: Culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 through 2005 was linked to demographic surveillance of 38,000 children younger than 5 years in Kilifi District, Kenya. Human immunodeficiency virus (HIV) infection and Hib vaccination status were determined for children with Hib disease admitted 2002-2005. INTERVENTIONS: Introduction of conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10, and 14 weeks beginning November 2001. MAIN OUTCOME MEASURES: Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness. RESULTS: Prior to vaccine introduction, the median age of children with Hib was 8 months; case fatality was 23%. Among children younger than 5 years, the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47, and 7.6 per 100,000, respectively. For children younger than 2 years, incidence was 119, 82, and 16 per 100,000, respectively. In 2004-2005, vaccine effectiveness was 88% (95% confidence interval, 73%-96%) among children younger than 5 years and 87% (95% confidence interval, 66%-96%) among children younger than 2 years. Of 53 children with Hib admitted during 2002-2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received 2 or more doses of vaccine (2 were HIV positive). CONCLUSIONS: In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children younger than 5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction.

Recurrence of legionnaires disease at a hotel in the United States Virgin Islands over a 20-year period.

We investigated 3 cases of legionnaires disease (LD) that developed in travelers who stayed at a hotel in the United States Virgin Islands where cases of LD occurred in 1981-1982 and in 1998. The temperature of the potable water at the hotel was in a range that could optimally support the growth of Legionella species, and the potable water was colonized with Legionella pneumophila in 1981-1982 and in 2002-2003.

Case-control study of non-Hodgkin's lymphoma and hepatitis C virus infection in Egypt.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) has been associated in some studies with increased risk for B-cell non-Hodgkin's lymphoma (NHL). To assess this further, we conducted a case-control study in Egypt, where HCV prevalence is extremely high. METHODS: Cases with B-cell NHL (N = 227) were recruited from the National Cancer Institute of Cairo University, a major referral centre. Controls (N = 227) were patients with fractures being treated at the Kasr El-Aini Orthopaedic Hospital, from the same referral base as the cases, and were frequency-matched by gender, rural versus urban birthplace, and age. Subjects were interviewed about their medical history and possible risk factors, and blood samples were collected for HCV diagnostic tests. Anti-HCV and HCV RNA were determined by enzyme-linked immunoassay and reverse transcription-polymerase chain reaction, respectively. Odds ratios (OR) and 95% CI were calculated from logistic regression models. RESULTS: Overall, 42% of subjects were anti-HCV positive and 33% had HCV RNA. There was a statistically significant unadjusted association of HCV RNA with NHL (OR = 2.3, 95% CI: 1.5, 3.5), which differed slightly by gender (males: OR = 2.1, 95% CI: 1.2, 3.7 versus females: OR = 2.5, 95% CI: 1.3, 4.8). Anti-HCV without HCV RNA was not associated with case status (OR = 0.9, 95% CI: 0.5, 1.6). After adjustment for age, gender, rural versus urban birthplace, and rural versus urban current residence, the association of HCV RNA with the risk of NHL remained statistically significant (OR = 2.9, 95% CI: 1.9, 4.5). CONCLUSIONS: These data support the hypothesis that NHL is a malignant outcome of chronic HCV infection.

Risk factors for severe cholera among children under five in rural and urban Bangladesh, 2000-2008: a hospital-based surveillance study.

BACKGROUND: Children under five bear the largest cholera burden. We therefore sought to identify modifiable risk factors among Bangladeshi children. METHODOLOGY/PRINCIPAL FINDINGS: We used multivariate Poisson regression to assess risk factors for severe cholera among diarrheal patients presenting at hospitals in Matlab (rural) and Dhaka (urban), Bangladesh. Risk increased with age. Compared to those under one, rural and urban four-year-olds had adjusted risk ratios (aRR) of 4.17 (95% confidence interval (CI) 2.43-7.15) and 6.32 (95% CI: 4.63-8.63), respectively. Breastfeeding halved the risk in both rural (aRR = 0.49, 95% CI: 0.35-0.67) and urban (aRR = 0.51, 95% CI: 0.41-0.62) settings. Rural children's risk decreased with maternal education (P-trend: <0.001) and increased among those with a family member with diarrhea in the past week (aRR = 1.61, 95% CI: 1.22-2.14) and those with prior vitamin A supplementation (aRR = 1.65, 95% CI: 1.12-2.43). Urban children whose mothers daily (aRR = 0.41, 95% CI: 0.21-0.79) or occasionally (aRR = 0.55, 95% CI: 0.36-0.84) read a newspaper experienced reduced risk. Urban children from households with incomes between 34-84 USD/month had a 30% increased risk compared to those from households with incomes >84 USD/month. CONCLUSION/SIGNIFICANCE: Increasing age, lower socioeconomic status, and lack of breastfeeding are key correlates of increased risk for cholera hospitalization among those under five in rural and urban Bangladesh. In addition, having a family member with diarrhea in the past week was associated with increased risk among rural children. Continued attention should be directed to the promotion of breastfeeding. Further research is needed to elucidate the relationship between maternal education and cholera risk. Renewed research regarding the use of chemoprophylaxis among family members of cholera cases may be warranted in rural endemic settings.

A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis.

Healthy Indian adult volunteers, with or without a history of leishmaniasis, were evaluated for evidence of previous infection with Leishmania donovani based on the direct agglutination test (DAT). Three cohorts of 6 DAT-negative and 6 DAT-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 5µg, 10µg, or 20µg recombinant Leishmania polyprotein LEISH-F1 antigen+25µg MPL®-SE adjuvant). The study injections were given subcutaneously on days 0, 28, and 56, and the subjects were followed through day 168 for safety and immunological endpoints. The vaccine was safe and well-tolerated in DAT-negative and DAT-positive subjects and induced T-cell production of IFN-γ and other cytokines in response to stimulation with the LEISH-F1 antigen. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without history of previous infection with Leishmania donovani.

Evaluation of ex vivo human immune response against candidate antigens for a visceral leishmaniasis vaccine.

People cured from visceral leishmaniasis (VL) develop protection mediated by Th1-type cellular responses against new infections. We evaluated cytokine responses against 6 defined candidate vaccine antigens in 15 cured VL subjects and 5 healthy endemic controls with no evidence of previous exposure to Leishmania parasites. Of the 6 cytokines examined, only interferon-gamma (IFN-gamma) differentiated cured VL patients from non-exposed individuals, with cured patients mounting a significantly higher IFN-gamma response to a crude parasite antigen preparation. Among candidate vaccine antigens tested, the largest number of cured subjects recognized cysteine proteinase B, leading to heightened IFN-gamma responses, followed by sterol 24-c-methyltransferase. These two antigens were the most immunogenic and protective antigens in a murine VL model, indicating a relationship between T cell recall responses of humans cured from VL and protective efficacy in an experimental model. Further studies may help prioritize antigens for clinical development of a subunit vaccine against VL.

A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with sodium stibogluconate for the treatment of mucosal leishmaniasis.

Adult patients with mucosal leishmaniasis (ML) were enrolled in a randomized, double-blind, placebo-controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20 µg recombinant Leishmania polyprotein LEISH-F1 antigen+25 µg MPL(®)-SE adjuvant) (n=36) or saline placebo (n=12). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received standard chemotherapy with sodium stibogluconate starting on Day 0. The vaccine was safe and well tolerated, and induced both humoral and cell-mediated immune responses. Furthermore, intracellular cytokine staining showed an increase in the proportion of memory LEISH-F1-specific IL-2(+) CD4 T-cells after vaccination, which was associated with clinical cure. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in patients with ML.

A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with meglumine antimoniate for the treatment of cutaneous leishmaniasis.

Forty-four adult patients with cutaneous leishmaniasis (CL) were enrolled in a randomized, double-blind, controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20 µg recombinant Leishmania polyprotein LEISH-F1 antigen+25 µg MPL-SE adjuvant) (n=27), adjuvant alone (n=8), or saline placebo (n=9). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received chemotherapy with meglumine antimoniate starting on Day 0. The vaccine was safe and well tolerated. Nearly all vaccine recipients and no adjuvant-alone or placebo recipients demonstrated an IgG antibody response to LEISH-F1 at Day 84. Also at Day 84, 80% of vaccine recipients were clinically cured, compared to 50% and 38% of adjuvant-alone and placebo recipients. The LEISH-F1+MPL-SE vaccine was safe and immunogenic in CL patients and appeared to shorten their time to cure when used in combination with meglumine antimoniate chemotherapy.

Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis.

Healthy Colombian adult volunteers with no history of leishmaniasis were evaluated for evidence of previous subclinical infection with Leishmania based on the Montenegro skin test (MST). Twelve MST-positive subjects were enrolled in an open-label, uncontrolled clinical trial (the "MST-positive trial") and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 10 microg recombinant Leishmania polyprotein LEISH-F1 antigen [TSA+LmSTI1+LeIF]+25 microg MPL-SE adjuvant). Sixty-eight MST-negative subjects were enrolled in a randomized, double-blind, controlled trial (the "MST-negative trial") and were randomly assigned to receive three injections of either the vaccine (n=34), 10 microg LEISH-F1 protein alone (n=17), or saline placebo (n=17). In both trials, the study injections were given subcutaneously on Days 0, 28, and 56, and subjects were followed for safety and immunological endpoints. The LEISH-F1+MPL-SE vaccine was safe and well tolerated in MST-positive and MST-negative subjects. In both trials, an IFN-gamma response to the LEISH-F1 antigen at Day 84 was observed in more than half of the vaccine recipients. In the MST-negative trial, the IFN-gamma response was significantly more frequent and of greater magnitude in vaccine recipients than in protein-alone or placebo recipients. An IgG antibody response to LEISH-F1 was observed in all vaccine recipients. In both trials, delayed-type hypersensitivity (DTH) to LEISH-F1 was observed in most of the vaccine recipients. In the MST-negative trial, DTH was significantly higher in vaccine than placebo recipients. These clinical trials of the first defined vaccine for leishmaniasis show that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without evidence of previous subclinical infection with Leishmania.