BACKGROUND: Partial artemisinin resistance is suspected if delayed parasite clearance (ie, persistence of parasitaemia on day 3 after treatment initiation) is observed. Validated markers of artemisinin partial resistance in southeast Asia, Plasmodium falciparum kelch13 (Pfkelch13) R561H and P574L, have been reported in Rwanda but no association with parasite clearance has been observed. We aimed to establish the efficacy of artemether-lumefantrine and genetic characterisation of Pfkelch13 alleles and their association with treatment outcomes. METHODS: This open-label, single-arm, multicentre, therapeutic efficacy study was done in 2018 in three Rwandan sites: Masaka, Rukara, and Bugarama. Children aged 6-59 months with P falciparum monoinfection and fever were eligible and treated with a 3-day course of artemether-lumefantrine. Treatment response was monitored for 28 days using weekly microscopy screenings of blood samples for P falciparum. Mutations in Pfkelch13 and P falciparum multidrug resistance-1 (Pfmdr1) genes were characterised in parasites collected from enrolled participants. Analysis of flanking microsatellites surrounding Pfkelch13 was done to define the origins of the R561H mutations. The primary endpoint was PCR-corrected parasitological cure on day 28, as per WHO protocol. FINDINGS: 228 participants were enrolled and 224 (98·2%) reached the study endpoint. PCR-corrected efficacies were 97·0% (95% CI 88-100) in Masaka, 93·8% (85-98) in Rukara, and 97·2% (91-100) in Bugarama. Pfkelch13 R561H mutations were present in 28 (13%) of 218 pre-treatment samples and P574L mutations were present in two (1%) pre-treatment samples. 217 (90%) of the 240 Pfmdr1 haplotypes observed in the pretreatment samples, had either the NFD (N86Y, Y184F, D1246Y) or NYD haplotype. Eight (16%) of 51 participants in Masaka and 12 (15%) of 82 participants in Rukara were microscopically positive 3 days after treatment initiation, which was associated with pre-treatment presence of Pfkelch13 R561H in Masaka (p=0·0005). Genetic analysis of Pfkelch13 R561H mutations suggest their common ancestry and local origin in Rwanda. INTERPRETATION: We confirm evidence of emerging artemisinin partial resistance in Rwanda. Although artemether-lumefantrine remains efficacious, vigilance for decreasing efficacy, further characterisation of artemisinin partial resistance, and evaluation of additional antimalarials in Rwanda should be considered. FUNDING: The US President's Malaria Initiative. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

BACKGROUND: This study aims to determine reported prevalence of hypertensive disorders in pregnancy (HDP) and maternal and neonatal outcomes associated with these disorders among women delivering at selected hospitals across Haiti. METHODS: A retrospective review of 8822 singleton deliveries between January 2012 and December 2014 was conducted at four hospitals in separate Departments across Haiti. Researchers examined the proportion of women with reported HDP (hypertension, preeclampsia, eclampsia) and the association between women with HDP and three neonatal outcomes: low birth weight, preterm birth, and stillbirths; and two maternal outcomes: placental abruption and maternal death in Hopital Albert Schweitzer (HAS). Odds ratios for associations between HDP and perinatal outcomes at HAS were assessed using logistic regression, adjusting for potential confounders. RESULTS: Of the 8822 singleton births included in the study, 510 (5.8%) had a reported HDP (including 285 (55.9%) preeclampsia, 119 (23.3%) eclampsia, and 106 (20.8%) hypertension). Prevalence of HDP among each hospital was: HAS (13.5%), Hopital Immaculee Conception des Cayes (HIC) (3.2%), Fort Liberte (4.3%), and Hopital Sacre Coeur de Milot (HSC) (3.0%). Among women at HAS with HDP, the adjusted odds of having a low birth weight baby was four times that of women without HDP (aOR 4.17, 95% CI 3.19-5.45), more than three times that for stillbirths (aOR 3.51, 95% CI 2.43-5.06), and five times as likely to result in maternal death (aOR 5.13, 95% CI 1.53-17.25). Among the three types of HDP, eclampsia was associated with the greatest odds of adverse events with five times the odds of having a low birth weight baby (aOR 5.00, 95% CI 2.84-8.79), six times the odds for stillbirths (aOR 6.34, 95% CI 3.40-11.82), and more than twelve times as likely to result in maternal death (aOR 12.70, 95% CI 2.33-69.31). CONCLUSIONS: A high prevalence of HDP was found among a cohort of Haitian mothers. HDP was associated with higher rates of adverse maternal and neonatal outcomes in HAS, which is comparable to studies of HDP conducted in high-income countries.

BACKGROUND: The main objective of this study was to determine the frequency and patterns of HIVDR-associated mutations among children <18 months old born to HIV-1-positive mothers enrolled in the prevention of mother-to-child transmission (PMTCT) services in Haiti. METHODS: Between January 1, 2013 and December 31, 2014, HIV-positive remnant dried blood spots (DBS) collected from children under 18 months old for Early Infant Diagnosis (EID) at the National Public Health Laboratory were used for HIV-1 genotyping. HIVDR mutations were analyzed using the Stanford Drug Resistance HIVdb program. RESULTS: Of the 3,555 DBS collected for EID, 360 (10.1%) were HIV-positive and 355 were available for genotyping. Of these, 304 (85.6%) were successfully genotyped and 217 (71.4%) had >/= one DR mutation. Mutations conferring resistance to NRTIs and NNRTIs were present in 40.5% (123) and 69.1% (210), respectively. The most frequent mutations were K103N/S (48.0%), M184V (37.5%), and G190A/S (15.1%), and Y181C/G/V (14.1%). Predicted drug resistance analysis revealed that 68.8% of the children had high-level resistance to NNRTIs and 11.5% had intermediate to high-level resistance to abacavir. CONCLUSIONS: This study showed high rates of resistance to NRTIs and NNRTIs among newly HIV-diagnosed children in Haiti, suggesting that in the era of "option B+" (initiation of lifelong combination antiretroviral therapy to pregnant women with HIV), the majority of children who acquire HIV infection through MTCT have resistant HIV. These results have led the National HIV Program to revise the pediatric guidelines to include protease inhibitors in first-line regimens for all HIV-positive newborns.

INTRODUCTION: Viral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for >/=6 months in five hospitals around Port-au-Prince, Haiti. METHODS: Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures. RESULTS: Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]). CONCLUSIONS: This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after >/= six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.

The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa.

Before the 2010 devastating earthquake and cholera outbreak, Haiti's public health laboratory systems were weak and services were limited. There was no national laboratory strategic plan and only minimal coordination across the laboratory network. Laboratory capacity was further weakened by the destruction of over 25 laboratories and testing sites at the departmental and peripheral levels and the loss of life among the laboratory health-care workers. However, since 2010, tremendous progress has been made in building stronger laboratory infrastructure and training a qualified public health laboratory workforce across the country, allowing for decentralization of access to quality-assured services. Major achievements include development and implementation of a national laboratory strategic plan with a formalized and strengthened laboratory network; introduction of automation of testing to ensure better quality of results and diversify the menu of tests to effectively respond to outbreaks; expansion of molecular testing for tuberculosis, human immunodeficiency virus, malaria, diarrheal and respiratory diseases; establishment of laboratory-based surveillance of epidemic-prone diseases; and improvement of the overall quality of testing. Nonetheless, the progress and gains made remain fragile and require the full ownership and continuous investment from the Haitian government to sustain these successes and achievements.

BACKGROUND: Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. METHODS: Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. RESULTS: Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. CONCLUSION: The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted.

BACKGROUND: Accurate assessment of maternal deaths is difficult in countries lacking standardized data sources for their review. As a first step to investigate suspected maternal deaths, WHO suggests surveillance of "pregnancy-related deaths", defined as deaths of women while pregnant or within 42 days of termination of pregnancy, irrespective of cause. Rapid Ascertainment Process for Institutional Deaths (RAPID), a surveillance tool, retrospectively identifies pregnancy-related deaths occurring in health facilities that may be missed by routine surveillance to assess gaps in reporting these deaths. METHODS: We used RAPID to review pregnancy-related deaths in six tertiary obstetric care facilities in three departments in Haiti. We reviewed registers and medical dossiers of deaths among women of reproductive age occurring in 2014 and 2015 from all wards, along with any additional available dossiers of deaths not appearing in registers, to capture pregnancy status, suspected cause of death, and timing of death in relation to the pregnancy. We used capture-recapture analyses to estimate the true number of in-hospital pregnancy-related deaths in these facilities. RESULTS: Among 373 deaths of women of reproductive age, we found 111 pregnancy-related deaths, 25.2% more than were reported through routine surveillance, and 22.5% of which were misclassified as non-pregnancy-related. Hemorrhage (27.0%) and hypertensive disorders (18.0%) were the most common categories of suspected causes of death, and deaths after termination of pregnancy were statistically significantly more common than deaths during pregnancy or delivery. Data were missing at multiple levels: 210 deaths had an undetermined pregnancy status, 48.7% of pregnancy-related deaths lacked specific information about timing of death in relation to the pregnancy, and capture-recapture analyses in three hospitals suggested that approximately one-quarter of pregnancy-related deaths were not captured by RAPID or routine surveillance. CONCLUSIONS: Across six tertiary obstetric care facilities in Haiti, RAPID identified unreported pregnancy-related deaths, and showed that missing data was a widespread problem. RAPID is a useful tool to more completely identify facility-based pregnancy-related deaths, but its repeated use would require a concomitant effort to systematically improve documentation of clinical findings in medical records. Limitations of RAPID demonstrate the need to use it alongside other tools to more accurately measure and address maternal mortality.

BACKGROUND: Despite improvement, maternal mortality in Haiti remains high at 359/100,000 live births. Improving access to high quality antenatal and postnatal care has been shown to reduce maternal mortality and improve newborn outcomes. Little is known regarding the quality and uptake of antenatal and postnatal care among Haitian women. METHODS: Exit interviews were conducted with all pregnant and postpartum women seeking care from large health facilities (n = 10) in the Nord and Nord-Est department and communes of St. Marc, Verrettes, and Petite Riviere in Haiti over the study period (March-April 2015; 3-4 days/facility). Standard questions related to demographics, previous pregnancies, current pregnancy, and services/satisfaction during the visit were asked. Total number of antenatal visits were abstracted from charts of recently delivered women (n = 1141). Provider knowledge assessments were completed by antenatal and postnatal care providers (n = 39). Frequencies were calculated for descriptive variables and multivariable logistic regression was used to explore predictors of receiving 5 out of 10 counseling messages among pregnant women. RESULTS: Among 894 pregnant women seeking antenatal care, most reported receiving standard clinical service components during their visit (97% were weighed, 80% had fetal heart tones checked), however fewer reported receiving recommended counseling messages (44% counselled on danger signs, 33% on postpartum family planning). Far fewer women were seeking postnatal care (n = 63) and similar service patterns were reported. Forty-three percent of pregnant women report receiving at least 5 out of 10 counseling messages. Pregnant women on a repeat visit and women with greater educational attainment had greater odds of reporting having received 5 out of 10 counseling messages (2nd visit: adjusted odds ratio [aOR] =1.70, 95% confidence interval [CI]: 1.09-2.66; 5+ visit: aOR = 5.44, 95% CI: 2.91-10.16; elementary school certificate: aOR = 2.06, 95% CI: 1.17-3.63; finished secondary school or more aOR = 1.97, 95% CI = 1.05-3.02). Chart reviews indicate 27% of women completed a single antenatal visit and 36% completed the recommended 4 visits. CONCLUSIONS: Antenatal and postnatal care uptake in Haiti is sub-optimal. Despite frequent reports of provision of standard service components, counseling messages are low. Consistent provision of standardized counseling messages with regular provider trainings is recommended to improve quality and uptake of care in Haiti.

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.

OBJECTIVE: In Mozambique, a patient-led Community ART Group model developed by Medecins Sans Frontieres improved retention in care and adherence to antiretroviral therapy (ART) among persons with HIV. We describe the adaptation and implementation of this model within the HIV clinic located in the largest public hospital in Haiti's Southern Department. METHODS: Our adapted model was named Group of 6. Hospital staff enabled stable patients with HIV receiving ART to form community groups with 4-6 members to facilitate monthly ART distribution, track progress and adherence, and provide support. Implementation outcomes included recruitment success, participant retention, group completion of monthly monitoring forms, and satisfaction surveys. RESULTS: Over one year, 80 patients from nine communities enrolled into 15 groups. Six participants left to receive HIV care elsewhere, two moved away, and one died of a non-HIV condition. Group members successfully completed monthly ART distribution and returned 85.6% of the monthly monitoring forms. Members reported that Group of 6 made their HIV management easier and hospital staff reported that it reduced their workload. CONCLUSIONS: We report successful adaptation and implementation of a validated community HIV-care model in Southern Haiti. Group of 6 can reduce barriers to ART adherence, and will be integrated as a routine care option.

Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed.

BACKGROUND: Few data currently exist on health risks faced by public health professionals (PHP) during international travel. We conducted pre- and post-travel health surveys to assess knowledge, attitudes, and practices (KAP), and illnesses among PHP international travelers. METHOD: Anonymous surveys were completed by PHP from a large American public health agency who sought a pre-travel medical consult from September 1, 2009, to September 30, 2010. RESULTS: Surveys were completed by 122 participants; travelers went to 163 countries. Of the 122 respondents, 97 (80%) reported at least one planned health risk activity (visiting rural areas, handling animals, contact with blood or body fluids, visiting malarious areas), and 50 (41%) reported exposure to unanticipated health risks. Of the 62 travelers who visited malarious areas, 14 (23%) reported inconsistent or no use of malaria prophylaxis. Illness during travel was reported by 33 (27%) respondents. CONCLUSIONS: Most of the PHP travelers in our study reported at least one planned health risk activity, and almost half reported exposure to unanticipated health risks, and one-quarter of travelers to malarious areas reported inconsistent or no use of malaria chemoprophylaxis. Our findings highlight that communication and education outreach for PHP to prevent travel-associated illnesses can be improved.

During the early weeks of the cholera outbreak that began in Haiti in October 2010, we conducted a case-control study to identify risk factors. Drinking treated water was strongly protective against illness. Our results highlight the effectiveness of safe water in cholera control.