Using routine health data to evaluate the impact of indoor residual spraying on malaria transmission in Madagascar.

INTRODUCTION: Indoor residual spraying (IRS) and insecticide-treated bed nets (ITNs) are cornerstone malaria prevention methods in Madagascar. This retrospective observational study uses routine data to evaluate the impacts of IRS overall, sustained IRS exposure over multiple years and level of spray coverage (structures sprayed/found) in nine districts where non-pyrethroid IRS was deployed to complement standard pyrethroid ITNs from 2017 to 2020. METHODS: Multilevel negative-binomial generalised linear models were fit to estimate the effects of IRS exposure overall, consecutive years of IRS exposure and spray coverage level on monthly all-ages population-adjusted malaria cases confirmed by rapid diagnostic test at the health facility level. The study period extended from July 2016 to June 2021. Facilities with missing data and non-geolocated communes were excluded. Facilities in IRS districts were matched with control facilities by propensity score analysis. Models were controlled for ITN survivorship, mass drug administration coverage, precipitation, enhanced vegetation index, seasonal effects and district. Predicted cases under a counterfactual no IRS scenario and number of cases averted by IRS were estimated using the fitted models. RESULTS: Exposure to IRS overall reduced case incidence by an estimated 30.3% from 165.8 cases per 1000 population (95% CI=139.7 to 196.7) under a counterfactual no IRS scenario, to 114.3 (95% CI=96.5 to 135.3) over 12 months post-IRS campaign in nine districts. A third year of IRS reduced malaria cases 30.9% more than a first year (incidence rate ratio (IRR)=0.578, 95% CI=0.578 to 0.825, p<0.001) and 26.7% more than a second year (IRR=0.733, 95% CI=0.611 to 0.878, p=0.001). There was no significant difference between the first and second year (p>0.05). Coverage of 86%-90% was associated with a 19.7% reduction in incidence (IRR=0.803, 95% CI=0.690 to 0.934, p=0.005) compared with coverage ≤85%, although these results were not robust to sensitivity analysis. CONCLUSION: This study demonstrates that non-pyrethroid IRS appears to substantially reduce malaria incidence in Madagascar and that sustained implementation of IRS over three years confers additional benefits.

Status of malaria in pregnancy services in Madagascar 2010-2021: a scoping review.

BACKGROUND: Malaria in pregnancy (MIP) increases the risk of poor maternal and infant outcomes. To reduce these risks, WHO recommends insecticide-treated net (ITN) use, intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), and prompt case management. However, uptake of these interventions remains sub-optimal in Madagascar. A scoping review was conducted to determine the breadth and depth of information available during 2010-2021 about Madagascar's MIP activities and to identify barriers and facilitators to MIP interventions uptake. METHODS: PubMed, Google Scholar, and USAID's files (Development Experience Catalog) were searched using the terms "Madagascar AND pregnancy AND malaria," and reports and materials from stakeholders were collected. Documents in English and French from 2010 to 2021 with data regarding MIP were included. Documents were systematically reviewed and summarized; results were captured in an Excel database. RESULTS: Of 91 project reports, surveys and published articles, 23 (25%) fell within the stated time period and contained relevant data on MIP activities in Madagascar and were categorized accordingly: eight (35%) quality of care, including health facility readiness, provider knowledge and commodity availability; nine (39%) care-seeking behaviour; and, six (26%) prevention of MIP. Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and, one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women's KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers. A 2015 survey of 52 health facilities revealed limited client access to antenatal care due to financial and geographic barriers; two 2018 surveys revealed similar findings. Self-treatment and care-seeking delays were reported even when distance was not a barrier. CONCLUSION: Among the studies and reports on MIP in Madagascar, the scoping review frequently noted barriers that could be mitigated by reducing stockouts, improving provider knowledge and attitudes, refining MIP communication, and improving service access. There is a need for coordinated efforts to address the identified barriers is the key implication of the findings.

Proactive community case management decreased malaria prevalence in rural Madagascar: results from a cluster randomized trial.

BACKGROUND: Malaria remains a leading cause of morbidity and mortality worldwide, with progress in malaria control stalling in recent years. Proactive community case management (pro-CCM) has been shown to increase access to diagnosis and treatment and reduce malaria burden. However, lack of experimental evidence may hinder the wider adoption of this intervention. We conducted a cluster randomized community intervention trial to assess the efficacy of pro-CCM at decreasing malaria prevalence in rural endemic areas of Madagascar. METHODS: Twenty-two fokontany (smallest administrative unit) of the Mananjary district in southeast Madagascar were selected and randomized 1:1 to pro-CCM (intervention) or conventional integrated community case management (iCCM). Residents of all ages in the intervention arm were visited by a community health worker every 2 weeks from March to October 2017 and screened for fever; those with fever were tested by a rapid diagnostic test (RDT) and treated if positive. Malaria prevalence was assessed using RDTs on all consenting study area residents prior to and following the intervention. Hemoglobin was measured among women of reproductive age. Intervention impact was assessed via difference-in-differences analyses using logistic regressions in generalized estimating equations. RESULTS: A total of 27,087 and 20,475 individuals participated at baseline and endline, respectively. Malaria prevalence decreased from 8.0 to 5.4% in the intervention arm for individuals of all ages and from 6.8 to 5.7% in the control arm. Pro-CCM was associated with a significant reduction in the odds of malaria positivity in children less than 15 years (OR = 0.59; 95% CI [0.38-0.91]), but not in older age groups. There was no impact on anemia among women of reproductive age. CONCLUSION: This trial suggests that pro-CCM approaches could help reduce malaria burden in rural endemic areas of low- and middle-income countries, but their impact may be limited to younger age groups with the highest malaria burden. TRIAL REGISTRATION: NCT05223933. Registered on February 4, 2022.

Experiences and perceptions of care-seeking for febrile illness among caregivers, pregnant women, and health providers in eight districts of Madagascar.

BACKGROUND: Prompt diagnosis and treatment of malaria contributes to reduced morbidity, particularly among children and pregnant women; however, in Madagascar, care-seeking for febrile illness is often delayed. To describe factors influencing decisions for prompt care-seeking among caregivers of children aged < 15 years and pregnant women, a mixed-methods assessment was conducted with providers (HP), community health volunteers (CHV) and community members. METHODS: One health district from each of eight malaria-endemic zones of Madagascar were purposefully selected based on reported higher malaria transmission. Within districts, one urban and one rural community were randomly selected for participation. In-depth interviews (IDI) and focus group discussions (FGD) were conducted with caregivers, pregnant women, CHVs and HPs in these 16 communities to describe practices and, for HPs, system characteristics that support or inhibit care-seeking. Knowledge tests on malaria case management guidelines were administered to HPs, and logistics management systems were reviewed. RESULTS: Participants from eight rural and eight urban communities included 31 HPs from 10 public and 8 private Health Facilities (HF), five CHVs, 102 caregivers and 90 pregnant women. All participants in FGDs and IDIs reported that care-seeking for fever is frequently delayed until the ill person does not respond to home treatment or symptoms become more severe. Key care-seeking determinants for caregivers and pregnant women included cost, travel time and distance, and perception that the quality of care in HFs was poor. HPs felt that lack of commodities and heavy workloads hindered their ability to provide quality malaria care services. Malaria commodities were generally more available in public versus private HFs. CHVs were generally not consulted for malaria care and had limited commodities. CONCLUSIONS: Reducing cost and travel time to care and improving the quality of care may increase prompt care-seeking among vulnerable populations experiencing febrile illness. For patients, perceptions and quality of care could be improved with more reliable supplies, extended HF operating hours and staffing, supportive demeanors of HPs and seeking care with CHVs. For providers, malaria services could be improved by increasing the reliability of supply chains and providing additional staffing. CHVs may be an under-utilized resource for sick children.

Tracking of Mammals and Their Fleas for Plague Surveillance in Madagascar, 2018-2019.

Plague, a zoonotic disease caused by the bacterium Yersinia pestis, remains a major public health threat in Madagascar. To better understand the risk of transmission to humans and to guide targeted plague prevention and control measures, a survey of Y. pestis infection and exposure in mammals and their fleas was implemented. Small mammals were captured in five districts of Madagascar ranging in levels of plague endemicity, as measured by notified cases, from none to active foci. Blood and spleen samples and fleas were collected from small mammals for the detection of anti-Y. pestis F1 antibodies by ELISA, F1 antigens by rapid diagnostic tests, and pla, caf1, and inv genes by polymerase chain reaction. Some rodent fleas were kept alive and reared in the insectary to assess susceptibility to insecticides. Blood was also collected from 15 dogs and tested for anti-F1 antibodies. A total of 557 spleens, 484 sera, and 1,539 fleas were collected from 557 rodents and shrews. Nineteen (3.4%) spleens were positive for F1 antigen, most from Toamasina (N = 13), a historical plague focus. One dog was also found seropositive in Toamasina. Twenty-two (4.5%) serologic specimens from small mammals were positive for anti-F1 antibodies. The flea index was highest in the city of Antananarivo (8.8). No flea was positive for Y. pestis DNA. Flea populations exhibited resistance to various insecticides weakening the efficacy of vector control. This study highlights the potential use of animal-based surveillance to identify the risk of plague transmission in endemic and nonendemic foci for targeted prevention and control.

Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018.

BACKGROUND: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. METHODS: Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. RESULTS: Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76. CONCLUSION: PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages.

BACKGROUND: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours. METHODS: Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns. RESULTS: Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5-29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5-14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5-14-year-olds reported fever in the two weeks prior to survey (p = 0.044). CONCLUSIONS: The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.

Malaria case management and elimination readiness in health facilities of five districts of Madagascar in 2018.

BACKGROUND: Madagascar's Malaria National Strategic Plan 2018-2022 calls for progressive malaria elimination beginning in low-incidence districts (< 1 case/1000 population). Optimizing access to prompt diagnosis and quality treatment and improving outbreak detection and response will be critical to success. A malaria elimination readiness assessment (MERA) was performed in health facilities (HFs) of selected districts targeted for malaria elimination. METHODS: A mixed methods survey was performed in September 2018 in five districts of Madagascar. Randomly selected HFs were assessed for availability of malaria commodities and frequency of training and supervision conducted. Health providers (HPs) and community health volunteers (CHVs) were interviewed, and outpatient consultations at HFs were observed. To evaluate elimination readiness, a composite score ranging from 0 to 100 was designed from all study tools and addressed four domains: (1) resource availability, (2) case management (CM), (3) data management and use, and (4) training, supervision, and technical assistance; scores were calculated for each HF catchment area and district based on survey responses. Stakeholder interviews on malaria elimination planning were conducted at national, regional and district levels. RESULTS: A quarter of the 35 HFs surveyed had no rapid diagnostic tests (RDTs). Of 129 patients with reported or recorded fever among 300 consultations observed, HPs tested 56 (43%) for malaria. Three-quarters of the 35 HF managers reviewed data for trends. Only 68% of 41 HPs reported receiving malaria-specific training. Of 34 CHVs surveyed, 24% reported that treating fever was no longer among their responsibilities. Among treating CHVs, 13 (50%) reported having RDTs, and 11 (42%) had anti-malarials available. The average district elimination readiness score was 52 out of 100, ranging from 48 to 57 across districts. Stakeholders identified several challenges to commodity management, malaria CM, and epidemic response related to lack of training and funding disruptions. CONCLUSION: This evaluation highlighted gaps in malaria CM and elimination readiness in Madagascar to address during elimination planning. Strategies are needed that include training, commodity provision, supervision, and support for CHVs. The MERA can be repeated to assess progress in filling identified gaps and is a feasible tool that could be used to assess elimination targets in other countries.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Public Health Management of Persons Under Investigation for Ebola Virus Disease in New York City, 2014-2016.

During 2014-2016, the largest outbreak of Ebola virus disease (EVD) in history occurred in West Africa. The New York City Department of Health and Mental Hygiene (DOHMH) worked with health care providers to prepare for persons under investigation (PUIs) for EVD in New York City. From July 1, 2014, through December 29, 2015, we classified as a PUI a person with EVD-compatible signs or symptoms and an epidemiologic risk factor within 21 days before illness onset. Of 112 persons who met PUI criteria, 74 (66%) sought medical care and 49 (44%) were hospitalized. The remaining 38 (34%) were isolated at home with daily contact by DOHMH staff members. Thirty-two (29%) PUIs received a diagnosis of malaria. Of 10 PUIs tested, 1 received a diagnosis of EVD. Home isolation minimized unnecessary hospitalization. This case study highlights the importance of developing competency among clinical and public health staff managing persons suspected to be infected with a high-consequence pathogen.

Increasing Antibiotic Resistance in Shigella spp. from Infected New York City Residents, New York, USA.

Approximately 20% of Shigella isolates tested in New York City, New York, USA, during 2013-2015 displayed decreased azithromycin susceptibility. Case-patients were older and more frequently male and HIV infected than those with azithromycin-susceptible Shigella infection; 90% identified as men who have sex with men. Clinical interpretation guidelines for azithromycin resistance and outcome studies are needed.

Using Syndromic Surveillance to Investigate Tattoo-Related Skin Infections in New York City.

In response to two isolated cases of Mycobacterium chelonae infections in tattoo recipients where tap water was used to dilute ink, the New York City (NYC) Department of Health and Mental Hygiene conducted an investigation using Emergency Department (ED) syndromic surveillance to assess whether an outbreak was occuring. ED visits with chief complaints containing the key word "tattoo" from November 1, 2012 to March 18, 2013 were selected for study. NYC laboratories were also contacted and asked to report skin or soft tissue cultures in tattoo recipients that were positive for non-tuberculosis mycobacterial infection (NTM). Thirty-one TREDV were identified and 14 (45%) were interviewed to determine if a NTM was the cause for the visit. One ED visit met the case definition and was referred to a dermatologist. This individual was negative for NTM. No tattoo-associated NTM cases were reported by NYC laboratories. ED syndromic surveillance was utilized to investigate a non-reportable condition for which no other data source existed. The results were reassuring that an outbreak of NTM in tattoo recipients was not occurring. In response to concerns about potential NTM infections, the department sent a letter to all licensed tattoo artists advising them not to dilute tattoo ink with tap water.

Surveillance and preparedness for Ebola virus disease -- New York City, 2014.

In July 2014, as the Ebola virus disease (Ebola) epidemic expanded in Guinea, Liberia, and Sierra Leone, an air traveler brought Ebola to Nigeria and two American health care workers in West Africa were diagnosed with Ebola and later medically evacuated to a U.S. hospital. New York City (NYC) is a frequent port of entry for travelers from West Africa, a home to communities of West African immigrants who travel back to their home countries, and a home to health care workers who travel to West Africa to treat Ebola patients. Ongoing transmission of Ebolavirus in West Africa could result in an infected person arriving in NYC. The announcement on September 30 of an Ebola case diagnosed in Texas in a person who had recently arrived from an Ebola-affected country further reinforced the need in NYC for local preparedness for Ebola.

Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose.

BACKGROUND: The duration of protection in children and adults (including health care workers) resulting from the hepatitis B vaccine primary series is unknown. METHODS: To determine the protection afforded by hepatitis B vaccine, Alaska Native persons who had received plasma-derived hepatitis B vaccine when they were >6 months of age were tested for antibody to hepatitis B surface antigen (anti-HBs) 22 years later. Those with levels <10 mIU/mL received 1 dose of recombinant hepatitis B vaccine and were evaluated on the basis of anti-HBs measurements at 10-14 days, 30-60 days, and 1 year. RESULTS: Of 493 participants, 60% (298) had an anti-HBs level >or=10 mIU/mL. A booster dose was administered to 164 persons, and 77% responded with an anti-HBs level >or=10 mIU/mL at 10-14 days, reaching 81% by 60 days. Response to a booster dose was positively correlated with younger age, peak anti-HBs response after primary vaccination, and the presence of detectable anti-HBs before boosting. Considering persons with an anti-HBs level >or=10 mIU/mL at 22 years and those who responded to the booster dose, protection was demonstrated in 87% of the participants. No new acute or chronic hepatitis B virus infections were identified. CONCLUSIONS: The protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 22 years. Booster doses are not needed.

Immunogenicity and reactogenicity of pneumococcal polysaccharide and conjugate vaccines in alaska native adults 55-70 years of age.

BACKGROUND: Vaccination with conjugate vaccines stimulates T cell-dependent immunity, whereas vaccination with polysaccharide vaccines does not. Thus, vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) may offer better protection against invasive pneumococcal disease for older adults than does vaccination with PPV23 alone, which is what is currently recommended. METHODS: Alaska Native adults 55-70 years of age with no previous pneumococcal vaccination were randomized to receive (1) PPV23, (2) PCV7 followed 2 months later by PPV23, or (3) PCV7 followed 6 months later by PPV23. Participants recorded reactions after each vaccination. Serum samples collected during the period from May 2002 through February 2003 were tested for serotype-specific immunoglobulin G (IgG) and for opsonophagocytic activity (OPA) against serotypes 1, 4, 6B, 14, and 19F. RESULTS: Vaccination with PCV7 was well tolerated, but persons receiving PCV7 followed by PPV23 reported more local reactions than those receiving only PPV23. All reactions resolved spontaneously within 72 h of receiving vaccine. The geometric mean IgG concentrations of and the median OPA titers to serotypes 4, 6B, 14, and 19F increased in all groups after 1 dose of either PCV7 or PPV23. Serotype-specific geometric mean IgG concentrations and median OPA titers did not differ between any of the groups after vaccination with PPV23, regardless of whether they had previously received PCV7. CONCLUSIONS: In this study, PCV7 given 2 or 6 months before PPV23 was well tolerated but did not improve immune response to PPV23 in older Alaska Native adults.

Epidemiologic investigation and targeted vaccination initiative in response to an outbreak of meningococcal disease among illicit drug users in Brooklyn, New York.

BACKGROUND: An outbreak of serogroup C meningococcal disease that involved illicit drug users and their contacts occurred in Brooklyn, New York, during 2005 and 2006. METHODS: The objectives of this study were to identify the population at risk for meningococcal disease, describe efforts to interrupt disease transmission, and assess the impact of a vaccine initiative. Descriptive and molecular epidemiological analysis was used to define the extent of the outbreak and the common risk factors among outbreak-related cases. A vaccine initiative that used community-based service providers was targeted to illicit drug users and their close contacts. The vaccine initiative was assessed through cessation of outbreak-related cases and the reduction in carriage rate. RESULTS: The investigation identified 23 outbreak-related cases of serogroup C meningococcal disease; 17 isolates were indistinguishable and 4 isolates were closely related according to pulsed-field gel electrophoresis. Two additional culture-negative cases had epidemiological links to laboratory-confirmed cases. The median age of patients with outbreak-related cases was 41 years, and 19 (83%) of 23 patients reported an association with illicit drug use. There were 7 outbreak-related deaths. Vaccination was administered to 2763 persons at 29 community locations, including methadone treatment centers, syringe-exchange programs, and soup kitchens. Three additional cases of meningococcal disease due to strains with the same pulsed-field gel electrophoresis pattern were identified after the vaccination initiative. CONCLUSIONS: Community-based outbreaks of meningococcal disease are difficult to control, and the decision to vaccinate is not straightforward. Current national guidelines for implementing a vaccination campaign are not strict criteria and cannot be expected to accommodate the myriad of factors that occur in community-based invasive meningococcal disease outbreaks, such as the inability to enumerate the population at risk.

Immunogenicity and reactogenicity to Haemophilus influenzae type B (Hib) conjugate vaccine among rural Alaska adults.

BACKGROUND: Despite routine vaccination and declining disease rates, Haemophilus influenzae type b (Hib) invasive disease still occurs in rural Alaska. Colonization studies indicate persistent transmission of Hib among village residents, including adults. As part of a project to eliminate Hib carriage in three rural villages, we evaluated a cohort of Alaska adults for antibody response and reactogenicity to a single dose of Hib conjugate vaccine (HbOC). METHODS: 75 previously unvaccinated, randomly-selected adults in one village received a single dose of HbOC vaccine and completed a side-effects diary. Sera and oropharyngeal specimens were collected at baseline, two months and one year. RESULTS: No participants were colonized with Hib or reported serious side-effects. At baseline, 97% of adults had IgG anti-PRP concentrations > or = 0.15 microg/mL, 69% > or = 1 microg/mL, and 28% > or = 5 microg/mL. Two months post-vaccination, 100% of participants had concentrations > or = 0.15 microg/mL, 93% > or = 1 microg/mL, and 86% > or = 5 microg/mL. After 1 year, 98% had IgG anti-PRP concentrations > or = 0.15 microg/mL, 86% > or = 1 microg/mL, and 67% > or = 5 microg/mL. GMCs were 1.9, 33.3 and 8.4 microg/mL at baseline, 2 months and 1 year post-vaccine, respectively (p < 0.01). Serum bactericidal activity increased from a baseline geometric mean titer of 2,205 to 8,349 two months post vaccination and declined to 1102 after one year. CONCLUSIONS: HbOC vaccine was immunogenic and well-tolerated among Alaskan adults. Nearly 90% of the adults developed an antibody level associated with protection against Hib colonization which persisted for 1 year in 67% of participants.

Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth.

BACKGROUND: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants. METHODS: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA. RESULTS: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis. CONCLUSIONS: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.

Injection practices in Romania: progress and challenges.

OBJECTIVE: To identify breaks in infection control practices that might put Romanians at risk for transmission of hepatitis B virus (HBV) from injections. METHODS: A standardized questionnaire was administered to a systematic sample of the 1,906 nurses in Vâlcea District, Romania, to collect information on their knowledge, attitudes, and practices regarding injection administration and universal precautions. RESULTS: Of the 180 nurses interviewed, 91% (95% confidence interval [CI95], 86% to 95%) reported having attended training for universal precautions; 58% (CI95, 49% to 67%) accurately reported that HBV remains infectious for at least 1 week in the environment; and 4% (CI95, 2% to 8%) knew that HBV is transmitted more efficiently than HIV through percutaneous exposures. No nurses reported reusing syringes or needles on different patients, but 4 (2%; CI, 1% to 6%) would reuse a syringe and 3 (2%; CI95, 0% to 5%) would reuse a needle on the same patient in an emergency. Fifty-three percent (CI95, 44% to 61%) of nurses reported having a dedicated area for the preparation of injectable medications separate from where blood-contaminated items were handled. Shortages of infection control supplies were common. CONCLUSIONS: Although nurses in Vâlcea do not report reusing injection equipment without sterilization, other unsafe practices occur that may facilitate HBV transmission through injections, including preparing injectable medications in areas potentially contaminated with blood. Inadequate knowledge of blood-borne pathogen transmission and shortages of infection control supplies may contribute to these unsafe practices. Addressing these deficits could improve injection safety in Romania.