Costs of integrating hepatitis B screening and antiviral prophylaxis into routine antenatal care in Burkina Faso: Treat all versus targeted strategies.

OBJECTIVE: Economic feasibility of eliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in highly endemic African countries remains uncertain. Prevention of MTCT (PMTCT) involves screening pregnant women for hepatitis B surface antigen (HBsAg), identifying those with high viral loads or hepatitis B e antigen (HBeAg), and administering tenofovir prophylaxis to high-risk women. We estimated the costs of integrating PMTCT services into antenatal care in Burkina Faso, based on four different strategies to select women for tenofovir prophylaxis: (1) HBV DNA (≥200 000 IU/mL), (2) HBeAg, (3) hepatitis B core-related antigen rapid diagnostic test (HBcrAg-RDT) and (4) all HBsAg-positive women. METHODS: Using a micro-costing approach, we estimated the incremental economic cost of integrating each strategy into routine antenatal care in 2024, compared to neonatal vaccination alone. Sensitivity analyses explored variations in prevalence, service coverage, test and tenofovir prices. RESULTS: HBcrAg-RDT strategy was the least expensive, with a total economic cost of US$3959689, compared to HBV DNA (US$6128875), HBeAg (US$4135233), and treat-all (US$4141206). The cost per pregnant woman receiving tenofovir prophylaxis varied from US$61.88 (Treat-all) to US$1071.05 (HBV DNA). The Treat-All strategy had the lowest marginal cost due to a higher number of women on tenofovir (66928) compared to HBV DNA (5722), HBeAg (10020), and HBcrAg-RDT (7234). In sensitivity analyses, the treat-all strategy became less expensive when the tenofovir price decreased. CONCLUSION: HBcrAg-RDT minimizes resource use and costs, representing 0.61% of Burkina Faso's 2022 health budget. This study highlights the potential economic feasibility of these strategies and provides valuable resources for conducting cost-effectiveness analyses.

Cost-effectiveness of tenofovir prophylaxis during pregnancy for the elimination of mother-to-child transmission of the hepatitis B virus: real-world analysis from Thailand.

OBJECTIVE: Despite implementing hepatitis B immunoglobulin (HBIG) and vaccination, data suggest it would not be sufficient to reach the elimination targets. Tenofovir disoproxil fumarate (TDF) has been added to the Thai national standards of care for prevention of transmission of the hepatitis B virus during birth. To optimise national strategies in Thailand, we assessed TDF's effectiveness for prevention of mother-to-child transmission and conducted cost-effectiveness analyses of different TDF-based strategies. RESEARCH DESIGN AND METHODS: We retrospectively reviewed medical records of mother and infant pairs whose mothers were positive for hepatitis B e-antigen (HBeAg) and received TDF to prevent maternal transmission of viral hepatitis B during 2018-2020. Based on the available data on transmission rate, we also applied a decision tree to estimate the cost-effectiveness of different TDF-based strategies to eligible mothers. These included: (1) HBIG for all hepatitis B virus (HBV) exposed infants; (2) HBIG for only infants of HBeAg-positive mothers ('HBIG for e-positive') and (3) without HBIG to infants ('HBIG-free'). The incremental cost-effectiveness ratio between the different strategies and baseline intervention without TDF was calculated. The one-way sensitivity analysis was used to adjust prevalence of HBeAg-positive mothers, cost of HBIG, cost of TDF and transmission rate. RESULTS: Of 223 infants enrolled, 212 (95.0%) received HBIG, while 11 (5.0%) did not. None of the infants had chronic HBV infection. The most cost-saving intervention was 'HBIG-free' followed by 'HBIG for e-positive'. The one-way sensitivity demonstrated that the results were reasonably robust to changes. The cost-saving was greater with a higher hepatitis B virus surface antigen (HBsAg) prevalence. The HBIG-free strategy remained best at 0%-1.4% transmission rates, meeting the additional target for eliminations. CONCLUSION: The study is the first cost-effectiveness analyses to provide evidence supporting an HBIG-free strategy in an antiviral era. This approach should be considered to prevent mother-to-child transmission in resource-constrained settings, particularly in countries with a high HBsAg prevalence.

Evaluating the cost-effectiveness of testing pregnant women for penicillin allergy.

INTRODUCTION: True penicillin allergy is rare and is commonly incorrectly reported. In fact, less than five percent of patients who report a penicillin allergy will have a currently active clinically-significant IgE- or T-cell-mediated hypersensitivity when appropriately tested. Penicillin is the agent of choice for intrapartum antibiotic prophylaxis to reduce the risk of group B streptococcus early-onset disease in the newborn. Inaccurate penicillin allergy status may lead to inappropriate antibiotic use, as most alternative drugs are more expensive and broader spectrum than penicillin. Penicillin allergy testing has been found to be safe in pregnancy and cost-effective in other patient populations. OBJECTIVE: To evaluate the cost-effectiveness of penicillin allergy testing and appropriate antibiotic treatment (test then treat strategy) compared to usual care among pregnant women. METHODS: We developed a decision tree to evaluate the cost of providing appropriate care via a test then treat strategy for pregnant women who report a penicillin allergy, compared to usual care. RESULTS: Using the test then treat strategy the additional cost to ensure appropriate care for all pregnant women who report a penicillin allergy, was $1122.38 per person. Adopting a test then treat strategy increased the number of appropriate antibiotic use from 7,843/10,000 to 10,000/10,000 simulations. CONCLUSION: Our results show that a test then treat strategy for pregnant women who report a penicillin allergy is a good-value intervention.

Toward elimination of mother-to-child transmission of HIV in Malawi: Findings from the Malawi Population-based HIV Impact Assessment (2015-2016).

BACKGROUND: Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and breastfeeding women. We used data from the 2015-2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression [VLS]) for HIV-positive women reporting a live birth in the previous 3 years. METHODS: MPHIA was a nationally representative household survey; consenting eligible women aged 15-64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS (<1,000 copies/mL) and undetectable VL (target not detected/below the limit of detection). RESULTS: Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval [CI]: 8.8%-11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%-88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%-98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%-95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%-81.7%) had VLS and 66.5% (95% CI: 59.8%-73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%-58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%-23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%-4.6%) had positive results. CONCLUSIONS: MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence.

BACKGROUND: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. METHODS: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. RESULTS: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. CONCLUSIONS: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

Universal first-trimester cytomegalovirus screening and valaciclovir prophylaxis in pregnant persons: a cost-effectiveness analysis.

BACKGROUND: Recent studies have suggested a possible benefit of valaciclovir prophylaxis to prevent vertical transmission after a positive serologic screen for primary maternal cytomegalovirus infection during pregnancy, although its cost-effectiveness remains uncertain. OBJECTIVE: This study aimed to determine the circumstances under which universal first-trimester maternal serologic screening for maternal cytomegalovirus infection, with valaciclovir prophylaxis to prevent congenital cytomegalovirus, is cost-effective. STUDY DESIGN: This study was a decision analysis from the perspective of the pregnant person to assess whether universal maternal screening in the first trimester of pregnancy, with subsequent valaciclovir prophylaxis (8 g/day from the time of positive serologic screen for primary maternal cytomegalovirus infection to 21 weeks of gestation) for those who are acutely infected, is cost-effective compared with usual care (ie, no routine serologic screening but with amniocentesis if midtrimester sonographic findings suggest cytomegalovirus). For baseline estimates, this study assumed a 35% risk of congenital cytomegalovirus after primary maternal infection and a 71% risk reduction with valaciclovir. This study varied valaciclovir's efficacy to identify whether and at what threshold universal screening would be estimated to be cost-effective, compared with usual care. Monte Carlo analyses were performed. A willingness-to-pay threshold of $100,000/quality-adjusted life year was used to define cost-effectiveness. RESULTS: Under base case estimates, first-trimester universal screening and valaciclovir prophylaxis for seropositive pregnant persons with acute cytomegalovirus infection were not cost-effective, with a cost of $137,854 per maternal quality-adjusted life year but resulted in 14 fewer children affected with cytomegalovirus per 100,000 pregnancies compared with usual care. In 1-way sensitivity analysis, universal screening and treatment were estimated to be the cost-effective strategy if the incidence of primary maternal cytomegalovirus infection exceeds 2.6%, the baseline risk of vertical transmission of cytomegalovirus without prophylaxis is greater than 36.8%, and the risk reduction of vertical transmission of cytomegalovirus with valaciclovir prophylaxis exceeds 75.9%. In Monte Carlo analyses, first-trimester universal serologic screening with valaciclovir prophylaxis was estimated to be the cost-effective strategy in 46.8% of runs. CONCLUSION: Universal first-trimester serologic screening with valaciclovir prophylaxis is not the cost-effective strategy for antenatal management of cytomegalovirus under the base case estimates. Although universal screening is cost-effective in certain circumstances when the efficacy of valaciclovir exceeds the base case, that result was not robust to variation of estimates across their reasonable ranges. These data can inform future studies to evaluate screening and treatment to prevent congenital cytomegalovirus.

Reduction of intrapartum antibiotic prophylaxis by combining risk factor assessment with a rapid bedside intrapartum polymerase chain reaction testing for group B streptococci.

OBJECTIVE: To investigate the impact of administering Intrapartum Antibiotic Prophylaxis (IAP) to laboring women with one or more risk factors for Early Onset Group B Streptococcal neonatal infection (EOGBS) based on the result of a rapid bedside test for Group B Streptococci (GBS). STUDY DESIGN: Quality assessment study. METHODS: Three-hundred-sixty-six laboring women admitted to our maternity ward, with one or more risk factors for EOGBS, were prospectively included. Rectovaginal swab-samples were examined bedside by the GenomEra® GBS Polymerase Chain Reaction (PCR) assay upon admission. Time from administration of IAP to delivery was registered. According to national guidelines, one-hundred-two women mandatorily received IAP independent of the PCR test result fulfilling one of the following three risk factors: prior infant with EOGBS, preterm labor before 35 gestational week, temperature ≥ 38 °C during labor. Women with GBS bacteriuria during current pregnancy, rupture of membranes ≥ 18 h IAP, and preterm labor between 35 and 37 gestational week, received IAP solely if the PCR test was positive. Predictive values were calculated for each risk factor. RESULTS: Previous GBS bacteriuria was strongly associated (PPV = 71%) with a positive GBS PCR test, whilst the corresponding positive percent of ROM > 18 h and of GA 35-37 was only PPV = 16% and 22%, respectively. Seventy-four women, 74/251 (31%), received IAP because they were GBS PCR positive. IAP was thus reduced by about two-thirds compared to the risk-based strategy of offering IAP to all women with one or more risk factors for EOGBS. Two women, 2/254 (0.8%), received inferior care, as they did not receive IAP within the recommended 4 h prior to delivery due to the extra time spend on the test procedure. CONCLUSION: Bedside intrapartum PCR testing of women with risk factors for EOGBS effectively diminishes use of IAP during labor compared to the present risk factor-based strategy alone. In this project, the extra time spend on the PCR test procedure did not lead to noticeable delay in IAP.

Health care costs associated with clinic visits for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania.

ABSTRACT: Early and appropriate antenatal care (ANC) is key for the effectiveness of prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). We evaluated the importance of ANC visits and related service costs for women receiving option B+ to prevent mother-to-child transmission (MTCT) of HIV in Tanzania.A cost analysis from a health care sector perspective was conducted using routine data of 2224 pregnant women newly diagnosed with HIV who gave birth between August 2014 and May 2016 in Dar es Salaam, Tanzania. We evaluated risk of infant HIV infection at 12 weeks postnatally in relation to ANC visits (<4 vs ≥4 visits). Costs for service utilisation were estimated through empirical observations and the World Health Organisation Global Price Reporting Mechanism.Mean gestational age at first ANC visit was 22 (±7) weeks. The average number of ANC/prevention of MTCT visits among the 2224 pregnant women in our sample was 3.6 (95% confidence interval [CI] 3.6-3.7), and 57.3% made ≥4 visits. At 12 weeks postnatally, 2.7% (95% CI 2.2-3.6) of HIV exposed infants had been infected. The risk of MTCT decreased with the number of ANC visits: 4.8% (95% CI 3.6-6.4) if the mother had <4 visits, and 1.0% (95% CI 0.5-1.7) at ≥4. The adjusted MTCT rates decreased by 51% (odds ratio 0.49, 95% CI 0.31-0.77) for each additional ANC visit made. The potential cost-saving was 2.2 US$ per woman at ≥4 visits (84.8 US$) compared to <4 visits (87.0 US$), mainly due to less defaulter tracing.Most pregnant women living with HIV in Dar es Salaam initiated ANC late and >40% failed to adhere to the recommended minimum of 4 visits. Improved ANC attendance would likely lead to fewer HIV-infected infants and reduce both short and long-term health care costs due to less spending on defaulter tracing and future treatment costs for the children.

Assessment of the impact of HIV infection and anti-retroviral treatment on the cardiometabolic health of pregnant mothers and their offspring (ARTMOMSBABES).

BACKGROUND: The risk of cardiovascular diseases (CVDs) is becoming more prevalent in pregnant women though not much data is available for pregnant women with human immunodeficiency virus (HIV). Foetoplacental vascular endothelial dysfunction is thought to be at the origin of chronic diseases such as diabetes and obesity later on in life. Because HIV and anti-retroviral treatment (ARTs) are associated with endothelial dysfunction, children exposed in utero to these conditions may be at greater risk of developing CVDs. Despite the high prevalence of HIV in pregnant South African women, little is known about the effects of ART on the cardiovascular health of the mother and offspring. Hence, the proposed study intends to investigate how HIV/ARTs may affect the cardiovascular health of the mother and offspring at different time points during the pregnancy and up to 2 years after birth. METHODS: A longitudinal case-control study in HIV positive pregnant women on ART and HIV negative pregnant women will be conducted. All pregnant women will be assessed for cardio-metabolic risk factors and markers (lipids, anthropometric and glycaemic indies, oxidative stress), hemodynamic status (blood pressure parameters) and vascular function (arterial compliance, retinal microvasculature, uterine artery mean pulsatility index). Child health will be monitored in utero and postnatally via routine foetal health screening, placental integrity, anthropometry, blood pressure parameters, markers of oxidative stress and endothelial function in cord blood and cardiovascular epigenetic markers in urine. DISCUSSION: There is a paucity of studies in South Africa and sub-Sahara Africa as a whole that utilised a longitudinal study model to assess the effects of ARTs on vascular endothelial changes in pregnant women living with HIV and the cardiometabolic health of their offspring. This study will therefore help to monitor changes in cardiometabolic risk during pregnancy and in children exposed in utero to HIV-infection and ART use. Findings from this study will provide useful information for developing guidelines on the use of ARTs in pregnancy and management of cardiometabolic health of the offspring of HIV positive mothers.

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands.

BACKGROUND: Neonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates. OBJECTIVE: Explore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands. METHODS: We assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017. RESULTS: Under base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands. CONCLUSIONS: A maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.

[Decrease in Group B Streptococcal Infections in Neonates: Analysis of Health Insurance Data 2005 to 2017]. / Rückgang von Infektionen durch Streptokokken der Gruppe B bei Neugeborenen: Analyse von Krankenversicherungsdaten 2005 bis 2017.

BACKGROUND: In the German guidelines for prophylaxis of group B streptococcal (GBS) early onset sepsis in neonates (EOS), GBS screening of all pregnant women has been recommended, but is not yet included in the Maternity Directives. Aim of the study was to identify temporal trends in incidence of EOS and their association to GBS Screening. METHODS: The analysis based on health insurance data of the statutory health insurance provider Barmer from 2005 to 2017 of 313,385 mother-child pairs. Annual frequency of GBS infections in newborns was determined by ICD-10 P36.0. The frequency of maternal GBS colonization was indicated by ICD-10 B95.1, which was used as surrogate for GBS screening. Temporal trends of the risk of EOS in neonates were assessed in logistic regression models. Pearson's correlation coefficient of EOS incidence and the surrogate marker for maternal GBS colonization was calculated. RESULTS: The risk of EOS in neonates caused by GBS has decreased annually by 9.3%, resulting in an overall decrease in the observation period of 72.0%. There was no statistical significant change in the risk for LOS (Late Onset Sepsis). The decrease of EOS could not be explained by temporal changes in Caesarian section, risk factors or preterm delivery. The 3.5 fold increase in the proportion of mothers with documented positive GBS colonization in the same period correlated inversely with the incidence of EOS (r=- 0.75; p=0.002). CONCLUSION: The decrease of EOS in neonates caused by GBS in Germany and the unchanged risk of LOS in neonates may be explained by the increasing application of the GBS Screening in pregnant women.

[Herpes simplex virus infections during pregnancy: epidemiology, clinical presentation and management]. / Infections par les virus herpes simplex pendant la grossesse : épidémiologie, aspects cliniques et prise en charge.

The incidence of herpes simplex virus (HSV) neonatal infection is estimated to be 8.9 per 100,000 live births in Europe. Early treatment with intravenous acyclovir has transformed the prognosis but this infection remains severe since, despite the treatment, mortality is frequent in disseminated diseases and neurological sequelae are frequent when central nervous system is involved. The major risk factor for transmission is the type of maternal infection. In women shedding the virus in their genital tract during childbirth, neonatal infection rates are 44 %, 25 % and 1.3 % in primary, non-primary and recurrent infections, respectively. The goals for the management of this infection during pregnancy encompass 1) the prevention of any contact between the newborn and the maternal virus by suppressing viral replication in the genital tract in late pregnancy and recommending a cesarean section in cases of genital lesions at delivery, and 2) the development of strategies allowing rapid identification and treatment of infected newborns.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

Provider- and patient-level costs associated with providing antiretroviral therapy during the postpartum phase to women living with HIV in South Africa: A cost comparison of three postpartum models of care.

OBJECTIVE: To compare the unit and total costs of three models of ART care for mother-infant pairs during the postpartum phase from provider and patient's perspectives: (i) local standard of care with women in general ART services and infants at well-baby clinics; (ii) women and infants continue to receive care through an integrated maternal and child care approach during the postpartum breastfeeding period; and (iii) referral of women directly to community adherence clubs with their infants receiving care at well-baby clinics. METHODS: Capital and recurrent cost data (relating to buildings, furniture, equipment, personnel, overheads, maintenance, medication, diagnostic tests and immunisations) were collected from a provider's perspective at six sites in Cape Town, South Africa. Patient time, collected via time-and-motion observation and questionnaires, was used to estimate patient perspective costs and is comprised of lost productivity time, time spent travelling and the direct cost of travelling. RESULTS: The cost of postpartum ART visits under models I, II and III was US $13, US $10 and US $7 per visit for a mother-infant pair, respectively, in 2018 US$. The annual costs for the mother-infant pair utilising the average visit frequencies (a mean of 4.5, 6.9 and 6.7 visits postpartum for models I, II and III, respectively) including costs for infant immunisations, visits, medication and diagnostic tests for both mothers and infants were: I - US $222, II - US $335 and III - US $249. Sensitivity analysis to assess the impact of visit frequency on visit cost showed that Model I annual costs would be most costly if visit frequency was equalised. CONCLUSION: This comparative analysis of three models of care provides novel data on unit costs and insight into the costs to provide ART and care to mother-infant pairs during the delicate postpartum phase. These costs may be used to help make decisions around integrated services models and differentiated service delivery for postpartum WLH and their children.

OBJECTIF: Comparer le coût et unitaire et total de trois modèles de soins ART pour les paires mère-enfant pendant la phase post-partum selon les perspectives du fournisseur et du patient: (I) - normes locales des soins avec les femmes dans les services généraux de l'ART et les nourrissons dans les cliniques de bien-être pour bébés; (II) - les femmes et les nourrissons continuent de recevoir des soins via une approche intégrée de soins maternels et infantiles pendant la période d'allaitement post-partum; et (III) - orientation des femmes directement vers les clubs d'adhésion communautaires, leurs nourrissons recevant des soins dans les cliniques de bien-être pour bébés pour bébés. MÉTHODES: Les données sur les coûts d'investissement et les coûts récurrents (relatifs aux bâtiments, au mobilier, à l'équipement, au personnel, aux frais généraux, à l'entretien, aux médicaments, aux tests de diagnostic et aux vaccinations) ont été recueillies selon le point de vue du prestataire sur six sites à Cape Town, en Afrique du Sud. Le temps du patient, recueilli via l'observation du temps et des mouvements et des questionnaires, a été utilisé pour estimer les coûts selon le point de vue du patient, et comprend le temps de productivité perdu, le temps passé en déplacement et le coût direct du déplacement. RÉSULTATS: Le coût des visites ART post-partum dans les modèles I, II et III était respectivement de 13 USD, 10 USD et 7 USD par visite pour une paire mère-enfant en USD de 2018. Les coûts annuels pour la paire mère-enfant en utilisant la fréquence moyenne des visites (une moyenne de 4,5 ; 6,9 et 6,7 visites post-partum pour les modèles I, II et III respectivement), y compris les coûts des vaccinations infantiles, des visites, des médicaments et des tests diagnostiques pour les mères et les nourrissons étaient: I - 222 USD, II - 335 USD et III - 249 USD. L'analyse de sensibilité pour évaluer l'impact de la fréquence des visites sur le coût des visites a montré que les coûts annuels du modèle I seraient les plus élevés si la fréquence des visites était égalisée. CONCLUSIONS: Cette analyse comparative de trois modèles de soins fournit de nouvelles données sur les coûts unitaires et un aperçu des coûts de fourniture de l'ART et de soins aux paires mère-enfant pendant la phase délicate du post-partum. Ces coûts peuvent être utilisés pour aider à la prise des décisions concernant les modèles de services intégrés et la prestation de services différenciés pour les femmes en période de post-partum et leurs enfants.

Costs and Cost Drivers of Providing Option B+ Services to Mother-Baby Pairs for PMTCT of HIV in Health Centre IV Facilities in Jinja District, Uganda.

BACKGROUND: In 2013, the World Health Organization (WHO) revised the 2012 guidelines on use of antiretroviral drugs (ARVs) for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). The new guidelines recommended lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women irrespective of CD4 count or clinical stage (also referred to as Option B+). Uganda started implementing Option B+ in 2012 basing on the 2012 WHO guidelines. Despite the impressive benefits of the Option B+ strategy, implementation challenges, including cost burden and mother-baby pairs lost to follow-up, threatened its overall effectiveness. The researchers were unable to identify any studies conducted to assess costs and cost drivers associated with provision of Option B+ services to mother-baby pairs in HIV care in Uganda. Therefore, this study determined costs and cost drivers of providing Option B+ services to mother-baby pairs over a two-year period (2014-2015) in selected health facilities in Jinja district, Uganda. METHODS: The estimated costs of providing Option B+ to mother-baby pairs derived from the provider perspective were evaluated at four health centres (HC) in Jinja district. A retrospective, ingredient-based costing approach was used to collect data for 2014 as base year using a standardized cost data capture tool. All costs were valued in United States dollars (USD) using the 2014 midyear exchange rate. Costs incurred in the second year (2015) were obtained by inflating the 2014 costs by the ratio of 2015 and 2014 USA Gross Domestic Product (GDP) implicit price deflator. RESULTS: The average total cost of Option B+ services per HC was 66,512.7 (range: 32,168.2-102,831.1) USD over the 2-year period. The average unit cost of Option B+ services per mother-baby pair was USD 441.9 (range: 422.5-502.6). ART for mothers was the biggest driver of total mean costs (percent contribution: 62.6%; range: 56.0%-65.5%) followed by facility personnel (percent contribution: 8.2%; range: 7.7%-11.6%), and facility-level monitoring and quality improvement (percent contribution: 6.0%; range: 3.2%-12.3%). Conclusions and Recommendations. ART for mothers was the major cost driver. Efforts to lower the cost of ART for PMTCT would make delivery of Option B+ affordable and sustainable.

ASSESSMENT OF THE EFFICACY AND SAFETY OF CHLOROQUINE MONOTHERAPY FOR THE TREATMENT OF ACUTE UNCOMPLICATED GESTATIONAL MALARIA CAUSED BY P. VIVAX, CÓRDOBA, COLOMBIA, 2015-2017.

OBJECTIVE: To determine the efficacy of chloroquine monotherapy in Colombian pregnant women with acute uncomplicated malaria vivax (GMV). METHODS: Prospective cohort study in pregnant women who presented of their own accord between February 1, 2015 and December 31, 2017 to malaria or prenatal care centers in two Colombian towns and in whom the diagnosis of Plasmodium vivax was confirmed by means of blood spot test and and quantitative polymerase chain reaction (qPCR). Measured variables included sociodemographics, therapeutic failure (TF) and serious adverse events at 28 days and frequency of recurrence-relap (RR) over a follow-up period of 120 days. The WHO protocol was applied for the assessment of monotherapy with cloroquine (m-CQ) efficacy. RESULTS: Overall, 47 pregnant women were identified. During the 28-day follow-up period there were no losses, and there were two cases of TP (4.2%=2/47). Of the 45 women followed between 29 and 120 days, 11 were lost (24.4%=11/45) and there were 13 cases of RR, with an RR frequency ranging between 29 and 53 % depending on the type of analysis. CONCLUSIONS: Chloroquine is still highly effective as a cure of acute malaria vivax attack in GM in Colombia, and continues to be a good option for the treatment of acute phase GM. The RR frequency is high. Studies are required that evaluate therapeutic alternatives in MG. There is a pressing need for medications and/or procedures that can help reduce this very high risk.

TITULO: EVALUACIÓN DE LA EFICACIA Y SEGURIDAD DE LA MONOTERAPIA CON CLOROQUINA PARA TRATAR MALARIA GESTACIONAL AGUDA NO COMPLICADA DEBIDA P. VIVAX, CÓRDOBA, COLOMBIA, 2015-2017. OBJETIVO: determinar la eficacia y seguridad de la monoterapia con cloroquina en gestantes colombianas con ataque agudo no complicado de malaria vivax (MGV). METODOS: estudio de cohorte prospectiva en pacientes gestantes que consultaron de manera espontánea entre 1 febrero de 2015 y 31 diciembre de 2017 a los puestos de malaria o de control prenatal en dos poblaciones de Colombia, en quienes se confirmó el diagnóstico de Plasmodium vivax mediante gota gruesa y qPCR (quantitative polymerase chain reaction). Se midieron variables sociodemográficas, falla terapéutica (FT) y eventos adversos serios a los 28 días y la frecuencia de recurrencia-recaída (RR) con seguimiento de 120 días. Se aplicó el protocolo de la OMS para evaluar la eficacia de monoterapia con cloroquina (m-CQ). RESULTADOS: se captaron 47 gestantes; en el seguimiento de 28 días no hubo pérdidas y hubo 4,2 % (2/47) de FT. En el seguimiento de 45 mujeres entre los días 29 y 120 hubo 11 pérdidas (24,4 % = 11/45) y 13 RR con frecuencia que varió entre 29 y 53 % según el tipo de análisis. CONCLUSIONES: la cloroquina conserva muy alta eficacia para curar el ataque agudo de malaria vivax en malaria gestacional (MG) en Colombia, y continúa siendo una buena opción para el tratamiento de la fase aguda. La frecuencia de RR es alta. Se requieren estudios que evalúen alternativas terapéuticas en la MG. Hay urgente necesidad de disponer de medicamentos o procedimientos que reduzcan ese altísimo riesgo.

Leprosy: Treatment and management of complications.

In the second article in this continuing medical education series, we review the treatment of leprosy, its immunologic reactions, and important concepts, including disease relapse and drug resistance. A fundamental understanding of the treatment options and management of neuropathic sequelae are essential to reduce disease burden and improve patients' quality of life.

Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono-infected pregnant women during labor by ultra-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Tenofovir (TFV) is a first-line antiviral agent against hepatitis B virus (HBV) and is recommended for the prevention of mother-to-infant transmission of HBV. To study the distribution of TFV in umbilical cord plasma and amniotic fluid of HBV-infected pregnant women, a rapid and sensitive method for TFV determination was developed and validated. METHODS: The quantification method was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The analytes were separated on an Acquity UPLC HSS T3 column under gradient elution with methanol and 0.01% ammonia solution in 10 mM ammonium acetate/water. This is the first reported method for the determination of TFV using alkaline rather than acidic mobile phases. Linearity, accuracy, precision, limit of quantification, specificity and stability were assessed. RESULTS: Detection of TFV was achieved within 4 min. The calibration curves for TFV quantification showed excellent linearity in the range of 1-500 ng/mL. The intra- and interbatch precision and accuracy ranged from -4.35% to 6.92%. This method was successfully applied to determination of samples from 50 HBV mono-infected women undergoing tenofovir disoproxil fumarate therapy. The mean concentrations of TFV in the umbilical cord and amniotic fluid samples were 29.2 (4.6-86) and 470.9 (156-902) ng/mL, respectively, which showed a moderate positive correlation (r = 0.5299, P<0.001). CONCLUSIONS: A simple, rapid but sensitive bioanalytical method to determine TFV concentration in both umbilical cord plasma and amniotic fluid using LC/MS/MS was developed and applied to HBV-infected women during labor who were undergoing TDF therapy, which will help us understand the efficacy and safety of tenofovir during pregnancy.