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Background: Daily oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, but no study has evaluated combination prevention interventions with PrEP for transgender women (TGW) and men who have sex with men (MSM) who sell sex., Methods: The Combination Prevention Effectiveness (COPE) study was a community-based, non-randomized implementation study in Bangkok and Pattaya, Thailand. Participants were HIV-negative MSM and TGW aged 18-26 years who reported exchanging sex with men in the prior 12 months and who met 2014 U.S. Public Health Service PrEP eligibility criteria. The intervention included quarterly HIV testing, semiannual testing for sexually transmitted infections, provision of condoms with lubricant, and the opportunity to initiate or end daily oral PrEP use at any time during study participation. Participants taking PrEP received monthly adherence counseling and short message service reminders. The primary outcome was HIV incidence rate ratio (IRR) on PrEP vs. not on PrEP. Secondary outcomes were PrEP initiation, PrEP use at 12 months, and PrEP adherence., Findings: From October 2017 to August 2019, 846 participants were enrolled: 531 (62.8%) immediately initiated PrEP; 104 (12.3%) subsequently initiated PrEP, and 211 (24.9%) never initiated PrEP. Among those initiating PrEP within 30 days of enrollment; 85.9% were on PrEP at the 12-months. When taking PrEP, participants reported adherent PrEP use at 94.2% of quarterly assessments. Ten HIV seroconversions occurred without PrEP use (incidence rate [IR] = 3.42 per 100 person-years [PY]; 95% CI = 1.64-6.30), while zero cases occurred with PrEP use (IR = 0.0 per 100PY; 95% CI = 0.0-0.62), with IRR = 0.0 (95% CI = 0.0-0.22; p < 0.001)., Interpretation: Young Thai MSM and TGW who exchange sex can have high PrEP uptake, persistence and adherence, and low HIV incidence when offered in supportive community-based settings., Funding: U.S. National Institute of Allergy and Infectious Diseases; Centers for Disease Control and Prevention., Competing Interests: The study was supported by an R01 from NIAID, NIH (1R01AI118505-01A1) and the CDC Division of HIV Prevention. The study drug, Truvada®, was manufactured and donated by Gilead Sciences, Inc. Gilead Sciences, Inc. had no role in the design of the study nor in the interpretation of study results. The findings and conclusions presented in this paper are those of the authors and do not necessarily represent the views of the NIH, the US CDC, or 10.13039/100007197U.S. Public Health Service. Patrick Sullivan reports support from NIH, CDC, Merck, Gilead Sciences, ViiV Healthcare, Molecular Testing Labs, and Elsevier. James F. Rooney reports support from Gilead Sciences. Rest of the authors declare no competing interests., (© 2023 The Author(s).)

A mass Japanese encephalitis (JE) immunization campaign for children aged 9 months through 12 years was conducted in 2013 in Battambang province, western Cambodia. Vaccinators working at almost 2,000 immunization posts in approximately 800 villages provided vaccinations to almost 310,000 children using one dose of Chengdu Institute of Biological Products' live, attenuated SA14-14-2 JE vaccine (CD-JEV), achieving a coverage rate of greater than 90%. Lessons learned, in general for mass vaccination campaigns and specifically for vaccination with CD-JEV, are described. These observations will be of benefit for public health officials and to help inform planning for future campaigns for JE or other vaccine-preventable diseases in Cambodia and elsewhere., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex., Methods: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n = 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "In the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated., Results: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP., Conclusions: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Japanese encephalitis (JE) virus is the most common cause of vaccine-preventable encephalitis in Asia. The SA14-14-2 JE vaccine manufactured by Chengdu Institute of Biological Products has been shown to be safe and effective in clinical trials and childhood routine immunization programs. However, there are few published reports describing results of surveillance for adverse events following immunization (AEFI) when the vaccine is used in mass campaigns. We describe the results of AEFI surveillance following a 2013 vaccination campaign among almost 310,000 children aged 9 months-12 years in Battambang Province, Cambodia., Methods: Routine AEFI surveillance was strengthened by staff training and supplemented by active hospital surveillance. An AEFI was defined as any sign, symptom, or disease temporally associated (i.e., within 4 weeks) with receipt of the vaccine, irrespective of whether it was considered related to immunization. Data were collected on standardized forms and causality assessments were conducted for serious AEFI., Results: Passive and active surveillance detected 28 AEFI for an overall incidence of 9.0 AEFI per 100,000 doses administered. The most frequent events were vasovagal episodes (n = 7, 25%) and rash (n = 6, 21%), and most other events were common childhood conditions such as fever and vomiting. Three AEFI were classified as serious, including one hypersensitivity reaction and two meningoencephalitis cases. Of these, the hypersensitivity event was the only serious AEFI classified as being consistent with a causal association to immunization., Conclusions: Most reported adverse events were conditions that commonly occur after other childhood vaccinations or independently of vaccination, and in the context of careful monitoring for serious AEFI only one serious event consistent with a causal association with immunization was identified. These results support the good safety profile of the SA14-14-2 JE vaccine, and provide reassuring data as the vaccine's use expands., Competing Interests: The authors have declared that no competing interests exist.

In Thailand, pre-exposure prophylaxis (PrEP) is recommended for human immunodeficiency virus (HIV) prevention among at-risk men who have sex with men (MSM). We modeled the impact of PrEP and condom use as independent and combined interventions on the estimated number of HIV infections among a hypothetical population of 10,000 MSM in Bangkok, Thailand. Our model demonstrated a 92% (95% confidence interval 89.7, 94.2) reduction in HIV infections among Thai MSM who took daily PrEP and self-reported using condoms correctly and consistently (100% condom use). Increased use of PrEP and condoms likely would have a substantial impact on the HIV epidemic in Thailand.

Background: Pre-exposure prophylaxis (PrEP) is highly effective in the prevention of HIV acquisition, particularly for men who have sex with men (MSM). Questions remain on the benefits of PrEP and implementation strategies for those at occupational risk of HIV acquisition in sex work, as well as on methods to support adherence among young people who initiate PrEP., Objective: The Combination Prevention Effectiveness study for young cisgender MSM and transgender women (TGW) aims to assess the effectiveness and cost-effectiveness of a combination intervention among HIV-uninfected young MSM and TGW engaged in sex work in Thailand., Methods: This open-label, nonrandomized assessment compares the relative effectiveness of a combination prevention intervention with and without daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada) PrEP with SMS-based adherence support. HIV-uninfected young MSM and TGW aged 18 to 26 years in Bangkok and Pattaya who self-report selling/exchanging sex at least once in the previous 12 months are recruited by convenience sampling and peer referral and are eligible regardless of their intent to initiate PrEP. At baseline, participants complete a standard assessment for PrEP eligibility and may initiate PrEP then or at any time during study participation. All participants complete a survey and HIV testing at baseline and every 3 months. Participants who initiate PrEP complete monthly pill pickups and may opt-in to SMS reminders. All participants are sent brief weekly SMS surveys to assess behavior with additional adherence questions for those who initiated PrEP. Adherence is defined as use of 4 or more pills within the last 7 days. The analytic plan uses a person-time approach to assess HIV incidence, comparing participant time on oral PrEP to participant time off oral PrEP for 12 to 24 months of follow-up, using a propensity score to control for confounders. Enrollment is based on the goal of observing 620 person-years (PY) on PrEP and 620 PY off PrEP., Results: As of February 2019, 445 participants (417 MSM and 28 TGW) have contributed approximately 168 PY with 95% (73/77) retention at 12 months. 74.2% (330/445) of enrolled participants initiated PrEP at baseline, contributing to 134 PY of PrEP adherence, 1 PY nonadherence, and 33 PY PrEP nonuse/noninitiation. Some social harms, predominantly related to unintentional participant disclosure of PrEP use and peer stigmatization of PrEP and HIV, have been identified., Conclusions: The majority of cisgender MSM and TGW who exchange sex and participate in this study are interested in PrEP, report taking sufficient PrEP, and stay on PrEP, though additional efforts are needed to address community misinformation and stigma. This novel multilevel, open-label study design and person-time approach will allow evaluation of the effectiveness and cost-effectiveness of combination prevention intervention in the contexts of both organized sex work and exchanged sex., International Registered Report Identifier (irrid): RR1-10.2196/15354., (©Andrea L Wirtz, Brian Wilson Weir, Sandra Hsu Hnin Mon, Pachara Sirivongrangson, Tareerat Chemnasiri, Eileen F Dunne, Anchalee Varangrat, Andrew C Hickey, Michele R Decker, Stefan Baral, Kamolnetr Okanurak, Patrick Sullivan, Rachel Valencia, Michael C Thigpen, Timothy H Holtz, Philip A Mock, Betsy Cadwell, Adeola Adeyeye, James F Rooney, Chris Beyrer, Combination Prevention Effectiveness (COPE) Study Team. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 27.01.2020.)

Although group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants worldwide, epidemiologic data and knowledge about risk factors for the disease are lacking from low- to middle-income countries. To determine the epidemiology of invasive GBS disease among young infants in a setting with high maternal HIV infection, we conducted hospital-based surveillance during 2004-2008 in Soweto, South Africa. Overall GBS incidence was 2.72 cases/1,000 live births (1.50 and 1.22, respectively, among infants with early-onset disease [EOD] and late-onset [LOD] disease). Risk for EOD and LOD was higher for HIV-exposed than HIV-unexposed infants. GBS serotypes Ia and III accounted for 84.0% of cases, and 16.9% of infected infants died. We estimate that use of trivalent GBS vaccine (serotypes Ia, Ib, and III) could prevent 2,105 invasive GBS cases and 278 deaths annually among infants in South Africa; therefore, vaccination of all pregnant women in this country should be explored.

Background: Tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women., Method: We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm., Results: A total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <-2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02). Low baseline BMD was associated with being underweight (p = 0.02), having high blood urea nitrogen (p = 0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (p = 0.01), spine -1.62% (p = 0.0002), hip -1.51% (p = 0.003)]., Conclusion: Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons., Trial Registration: ClinicalTrials.gov NCT00448669.

We examined CD4 cell count and plasma viral load patterns among Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2 study) participants who seroconverted, comparing participants assigned to receive tenofovir/emtricitabine with participants assigned to receive placebo. We also evaluated for antiretroviral drug resistance among the breakthrough HIV infections. Among nine seroconverters assigned to tenofovir/emtricitabine and 24 to placebo, there were no significant differences in their CD4 cell count or viral load profiles over time. Of the four participants who seroconverted on-study while receiving tenofovir/emtricitabine, none became infected as a result of drug-resistant HIV; moreover, no resistance mutations emerged following seroconversion.

Background: In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission., Methods: Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks., Results: The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001)., Conclusions: Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.

Background: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain., Methods: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants., Results: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03)., Conclusions: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

Background: We assessed morbidity rates during short intervals that accompanied weaning and cumulative mortality among HIV-exposed, uninfected infants enrolled in the postexposure prophylaxis of infants in Malawi (PEPI-Malawi) trial., Methods: Women were counseled to stop breastfeeding (BF) by 6 months in the PEPI-Malawi trial. HIV-uninfected infants were included in this analysis starting at age 6 months. Breastfeeding and morbidity (illness and/or hospital admission and malnutrition [weight-for-age Z-score, ≤2]) were assessed during age intervals of 6-9, 9-12, and 12-15 months. BF was defined as any BF at the start and end of the interval and no breastfeeding (NBF) was defined as NBF at any time during the interval. The association of NBF with morbidity at each mutually exclusive interval was assessed using Poisson regression models controlling for other factors. Cumulative mortality among infants aged 6-15 months with BF and NBF was assessed using an extended Kaplan-Meier method., Results: At age 6 months, 1761 HIV-uninfected infants were included in the study. The adjusted rate ratios for illnesses and/or hospital admission for NBF, compared with BF, was 1.7 (P < .0001) at 6-9 months, 1.66 (P = .0001) at 9-12 months, and 1.75 (P = .0008) at 12-15 months. The rates of morbidity were consistently higher among NBF infants during each age interval, compared with BF infants. The 15 months cumulative mortality among BF and NBF children was 3.5% and 6.4% (P = .03), respectively., Conclusions: Cessation of BF is associated with acute morbidity events and cumulative mortality. Prolonged BF should be encouraged, in addition to close monitoring of infant health and provision of support services.

Background: This analysis updates and extends efficacy estimates of the PEPI-Malawi trial through age 24 months at study completion in September 2009., Methods: Infants of breastfeeding HIV-infected women were randomized at birth to the following: (1) single-dose nevirapine (NVP) + 1-week zidovudine (ZDV) (control); (2) control + extended daily NVP (ExtNVP) through 14 weeks; (3) control + extended daily NVP + ZDV (ExtNVP/ZDV) through 14 weeks. We estimated rates of HIV infection, death and HIV infection, or death using Kaplan-Meier analysis., Results: This analysis includes 3126 infants uninfected at birth as follows: 1004 control, 1071 ExtNVP, and 1051 ExtNVP/ZDV. By 9 months, HIV infection rates were 5.0% in ExtNVP, 6.0% in ExtNVP/ZDV, and 11.1% in control (P < 0.001 comparing extended regimens with control). At age 24 months, HIV infection rates had risen to ~11% in the extended arms compared with 15.6% in the controls (P < 0.05). The rates of HIV infection or death were also significantly lower in extended arms. There were no differences in severe adverse events with the exception of higher possibly related events in the ExtNVP/ZDV arm., Conclusions: Daily infant antiretroviral prophylaxis reduces postnatal HIV infection by ~70% during the period of prophylaxis. But continued HIV transmission after prophylaxis stops suggests more prolonged infant prophylaxis is needed.

Background: The rate of bacterial meningitis declined by 55% in the United States in the early 1990s, when the Haemophilus influenzae type b (Hib) conjugate vaccine for infants was introduced. More recent prevention measures such as the pneumococcal conjugate vaccine and universal screening of pregnant women for group B streptococcus (GBS) have further changed the epidemiology of bacterial meningitis., Methods: We analyzed data on cases of bacterial meningitis reported among residents in eight surveillance areas of the Emerging Infections Programs Network, consisting of approximately 17.4 million persons, during 1998-2007. We defined bacterial meningitis as the presence of H. influenzae, Streptococcus pneumoniae, GBS, Listeria monocytogenes, or Neisseria meningitidis in cerebrospinal fluid or other normally sterile site in association with a clinical diagnosis of meningitis., Results: We identified 3188 patients with bacterial meningitis; of 3155 patients for whom outcome data were available, 466 (14.8%) died. The incidence of meningitis changed by -31% (95% confidence interval [CI], -33 to -29) during the surveillance period, from 2.00 cases per 100,000 population (95% CI, 1.85 to 2.15) in 1998-1999 to 1.38 cases per 100,000 population (95% CI 1.27 to 1.50) in 2006-2007. The median age of patients increased from 30.3 years in 1998-1999 to 41.9 years in 2006-2007 (P<0.001 by the Wilcoxon rank-sum test). The case fatality rate did not change significantly: it was 15.7% in 1998-1999 and 14.3% in 2006-2007 (P=0.50). Of the 1670 cases reported during 2003-2007, S. pneumoniae was the predominant infective species (58.0%), followed by GBS (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%). An estimated 4100 cases and 500 deaths from bacterial meningitis occurred annually in the United States during 2003-2007., Conclusions: The rates of bacterial meningitis have decreased since 1998, but the disease still often results in death. With the success of pneumococcal and Hib conjugate vaccines in reducing the risk of meningitis among young children, the burden of bacterial meningitis is now borne more by older adults. (Funded by the Emerging Infections Programs, Centers for Disease Control and Prevention.).

Background: The World Health Organization currently recommends initiation of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected lactating women with CD4+ cell counts <350 cells/μL or stage 3 or 4 disease. We analyzed antiretroviral drug resistance in HIV-infected infants in the Post Exposure Prophylaxis of Infants trial whose mothers initiated HAART postpartum (with a regimen of nevirapine [NVP], stavudine, and lamivudine). Infants in the trial received single-dose NVP and a week of zidovudine (ZDV) at birth; some infants also received extended daily NVP prophylaxis, with or without extended ZDV prophylaxis., Methods: We analyzed drug resistance in plasma samples collected from all HIV-infected infants whose mothers started HAART in the first postpartum year. Resistance testing was performed using the first plasma sample collected within 6 months after maternal HAART initiation. Categorical variables were compared by exact or trend tests; continuous variables were compared using rank-sum tests., Results: Multiclass resistance (MCR) was detected in HIV from 11 (29.7%) of 37 infants. Infants were more likely to develop MCR infection if their mothers initiated HAART earlier in the postpartum period (by 14 weeks vs after 14 weeks and up to 6 months vs after 6 months, P = .0009), or if the mother was exclusively breastfeeding at the time of HAART initiation (exclusive breastfeeding vs mixed feeding vs no breastfeeding, P = .003)., Conclusions: Postpartum maternal HAART initiation was associated with acquisition of MCR in HIV-infected breastfeeding infants. The risk was higher among infants whose mothers initiated HAART closer to the time of delivery or were still exclusively breastfeeding when they first reported HAART use.

Background: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention., Methods and Findings: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%)., Conclusions: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.

Approximately 2 billion persons worldwide are infected with schistosomiasis and soil-transmitted helminths (STH), many in areas where endemic malaria transmission coexists. Few data exist on associations between these infections. Nested within a larger clinical trial, primigravid and secundigravid women provided blood samples for human immunodeficiency virus (HIV) testing and peripheral malaria films and stool and urine for evaluation of STH and Schistosoma spp. during their initial antenatal clinic visit. The most common parasitic infections were malaria (37.6%), S. haematobium (32.3%), and hookworm (14.4%); 14.2% of women were HIV-infected. S. haematobium infection was associated with lower malarial parasite densities (344 versus 557 parasites/μL blood; P < 0.05). In multivariate analysis, HIV and hookworm infection were independently associated with malaria infection (adjusted odds ratio = 1.9 and 95% confidence interval = 1.2-3.0 for HIV; adjusted odds ratio = 1.9 and 95% confidence interval = 1.03-3.5 for hookworm). Concurrent helminthic infection had both positive and negative effects on malaria parasitemia among pregnant women in Malawi.

Background: Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant's development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of mother-to-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIV-infected breastfed infants., Methods and Findings: All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR-positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load >1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo)., Conclusions: Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants.

Objective: Single-dose nevirapine (NVP) (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women., Methods: Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, version 1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy., Results: HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, two recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a nonsignificant trend between detection of NVP resistance in breast milk and plasma (P = 0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium more than 10 mmol/l, HIV subtype, or concentration of NVP in breast milk or plasma., Conclusion: NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance.

Background: In the Post-Exposure Prophylaxis of Infants (PEPI)-Malawi trial, most women received single-dose nevirapine (NVP) at delivery, and infants in the extended study arms received single-dose NVP along with 1 week of daily zidovudine (ZDV), followed by either extended daily NVP or extended daily NVP and ZDV up to 14 weeks of age. Although extended NVP prophylaxis reduces the risk of postnatal HIV transmission, it may increase the risk of NVP resistance among infants who are HIV-infected despite prophylaxis., Methods: We analyzed 88 infants in the PEPI-Malawi trial who were HIV-infected in utero and who received prophylaxis for a median of 6 weeks prior to HIV diagnosis. HIV genotyping was performed using the ViroSeq HIV Genotyping System., Results: At 14 weeks of age, the proportion of infants with NVP resistance was lower in the extended NVP and ZDV arm than in the extended NVP arm (28/45, 62.2% vs. 37/43, 86.0%; P = 0.015). None of the infants had ZDV resistance. Addition of extended ZDV to extended NVP was associated with reduced risk of NVP resistance at 14 weeks if prophylaxis was stopped by 6 weeks (54.5 vs. 85.7%, P = 0.007) but not if prophylaxis was continued beyond 6 weeks (83.3 vs. 87.5%, P = 1.00)., Conclusion: Addition of extended ZDV to extended NVP prophylaxis significantly reduced the risk of NVP resistance at 14 weeks in infants who were HIV-infected in utero, provided that HIV infection was diagnosed and the prophylaxis was stopped by 6 weeks of age.

Background: About 500,000 sepsis-related deaths per year arise in the first 3 days of life. On the basis of results from non-randomised studies, use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries. We therefore assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus., Methods: In a trial in Soweto, South Africa, 8011 women (aged 12-51 years) were randomly assigned in a 1:1 ratio to chlorhexidine vaginal wipes or external genitalia water wipes during active labour, and their 8129 newborn babies were assigned to full-body (intervention group) or foot (control group) washes with chlorhexidine at birth, respectively. In a subset of mothers (n=5144), we gathered maternal lower vaginal swabs and neonatal skin swabs after delivery to assess colonisation with potentially pathogenic bacteria. Primary outcomes were neonatal sepsis in the first 3 days of life and vertical transmission of group B streptococcus. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00136370., Findings: Rates of neonatal sepsis did not differ between the groups (chlorhexidine 141 [3%] of 4072 vs control 148 [4%] of 4057; p=0.6518). Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine (217 [54%] of 401) and control groups (234 [55%] of 429] did not differ (efficacy -0.05%, 95% CI -9.5 to 7.9)., Interpretation: Because chlorhexidine intravaginal and neonatal wipes did not prevent neonatal sepsis or the vertical acquisition of potentially pathogenic bacteria among neonates, we need other interventions to reduce childhood mortality., Funding: US Agency for International Development, National Vaccine Program Office and Centers for Disease Control's Antimicrobial Resistance Working Group, and Bill & Melinda Gates Foundation.

Background: The association between postnatal human immunodeficiency virus type 1 (HIV-1) transmission and maternal highly active antiretroviral therapy (HAART) after infant extended antiretroviral prophylaxis was assessed., Methods: A follow-up study was conducted for the Post-Exposure Prophylaxis of Infants trial in Blantyre, Malawi (PEPI-Malawi). In PEPI-Malawi, breast-feeding infants of HIV-infected women were randomized at birth to receive a either control regimen (single-dose nevirapine plus 1 week of zidovudine); the control regimen plus nevirapine to age 14 weeks; or the control regimen plus nevirapine and zidovudine to age 14 weeks. Infant HIV infection, maternal CD4 cell count, and HAART use were determined. Maternal HAART use was categorized as HAART eligible but untreated (CD4 cell count of <250 cells/microL, no HAART received), HAART eligible and treated (CD4 cell count of <250 cells/microL, HAART received), and HAART ineligible (CD4 cell count of 250 cells/microL). The incidence of HIV infection and the association between postnatal HIV transmission and maternal HAART were calculated among infants who were HIV negative at 14 weeks., Results: Of 2318 infants, 130 (5.6%) acquired HIV infection, and 310 mothers (13.4%) received HAART. The rates of HIV transmission (in cases per 100 person-years) were as follows: for the HAART-eligible/untreated category, 10.56 (95% confidence interval [CI], 7.91-13.82); for the HAART-eligible/treated category, 1.79 (95% CI, 0.58-4.18); and for the HAART-ineligible category, 3.66 (95% CI, 2.86-4.61). The HIV transmission rate ratio for the HAART-eligible/treated category versus the HAART-eligible/untreated category, adjusted for infant prophylaxis, was 0.18 (95% CI, 0.07-0.44)., Conclusions: Postnatal HIV transmission continues after cessation of infant prophylaxis. HAART-eligible women should start treatment early for their own health and to reduce postnatal HIV transmission to their infants.

To reduce mother-to-child transmission of human immunodeficiency virus (HIV) in resource-poor settings, the World Health Organization recommends exclusive breast-feeding for 6 months, followed by rapid weaning if replacement feeding is affordable, feasible, available, safe, and sustainable. In the Kisumu Breastfeeding Study (trial registration: Clinicaltrials.gov identifier NCT00146380), infants of HIV-infected mothers who received antiretroviral therapy experienced high rates of diarrhea at weaning. To address this problem, mothers in the Kisumu Breastfeeding Study were given safe water storage vessels, hygiene education, and bleach for household water treatment. We compared the incidence of diarrhea in infants enrolled before (cohort A) and after (cohort B) implementation of the intervention. Cohort B infants experienced less diarrhea than cohort A infants, before and after weaning (P < .001 and P = .047, respectively); however, during the weaning period, there were no differences in the frequency of diarrhea between cohorts (P = 0.89). Testing of stored water in cohort B homes indicated high adherence (monthly range, 80%-95%) to recommended chlorination practices. Among infants who were weaned early, provision of safe water may be insufficient to prevent weaning-associated diarrhea.

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6-8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6-8 weeks of age. Detection of NVP resistance at 6-8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6-8 weeks, or infant sex. NVP resistance was still detected in some infants 6-12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6-8 weeks after sdNVP exposure.

There are limited data describing the concentrations of zidovudine, lamivudine, and nevirapine in nursing infants as a result of transfer via breast milk. The Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal, intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and nevirapine from 34 weeks of gestation to 6 months postpartum. In a pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood spots were collected for drug assay on the day of delivery and at 2, 6, 14, and 24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The median concentrations in breast milk of zidovudine, lamivudine, and nevirapine during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml, respectively. Zidovudine was not detectable in any infant plasma samples obtained after the day of delivery, while the median concentrations in infant plasma samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine, respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations. The extent and effect of infant drug exposure via breast milk must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.

Single-dose (SD) nevirapine (NVP) significantly reduces mother-to-child transmission of human immunodeficiency virus (HIV). We analyzed NVP resistance after receipt of SD NVP in 57 previously SD NVP-naive women, in 34 SD NVP-experienced women, and in 17 HIV-infected infants. The proportion of women infected with variants with resistance mutations, the types of mutations detected, and the frequency and level of K103N were similar in the two groups of women at 6 weeks and 6 months post partum. NVP resistance was detected in a similar proportion of infants born to SD NVP-naive versus SD NVP-experienced women. Repeated use of SD NVP to prevent HIV transmission does not appear to influence NVP resistance.

Background: Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings., Methods: Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth., Results: Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug., Conclusions: Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.), (2008 Massachusetts Medical Society)

Limited information exists on the incidence and characteristics of invasive group A streptococcal (GAS) infections among residents of long-term care facilities (LTCFs). We reviewed cases of invasive GAS infections occurring among persons > or =65 years of age identified through active, population-based surveillance from 1998 through 2003. We identified 1,762 invasive GAS cases among persons > or =65 years, including 1,662 with known residence type (LTCF or community). Incidence of invasive GAS infection among LTCF residents compared to community-based elderly was 41.0 versus 6.9 cases per 100,000 population. LTCF case-patients were 1.5 times as likely to die from the infection as community-based case-patients (33% vs. 21%, p<0.01) but were less often hospitalized (90% vs. 95%, p<0.01). In multivariate logistic regression modeling, LTCF residence remained an independent predictor of death. Additional prevention strategies against GAS infection in this high-risk population are urgently needed.

Background: Single-dose nevirapine (SDNVP) is widely used to prevent mother-to-child HIV transmission in resource-limited settings. Given detection of resistant mutants among women who receive SDNVP, concerns have arisen over the efficacy of SDNVP in repeat pregnancies., Methods: Retrospective data were collected from SDNVP-exposed and -unexposed women from the HIV Network for Prevention 012 trial who subsequently received SDNVP in another pregnancy. Prospective data were collected from pregnant women who were SDNVP exposed or unexposed before delivery. Kaplan-Meier and Cox regression analyses were used to estimate rates of HIV infection and HIV-free survival among infants born to women with or without prior SDNVP exposure., Results: In the retrospective cohort, the infection rates were 11.3% and 16.7% for 104 infants of NVP-exposed and -unexposed mothers, respectively (P = 0.41). In the prospective cohort, among 103 infants of NVP-exposed and -unexposed mothers, the 12-month infant HIV infection rates were 20.5% and 18.7% (P = 0.81) and HIV-free survival rates were 74.4% and 78.1% (P = 0.66), respectively., Conclusions: There was no increased risk of infant HIV infection among SDNVP-exposed women compared with -unexposed women. These findings support current international guidelines to offer SDNVP to HIV-infected pregnant women, regardless of previous SDNVP exposure, when more complex prophylaxis regimens are not available.

Group A streptococci (GAS) are an important cause of severe, life-threatening illness among the elderly population, particularly those individuals residing in long-term care facilities (LTCFs). Outbreaks of GAS infection are potentially devastating in this vulnerable population and often require large-scale control efforts involving LTCF staff, public health officials, and infectious diseases practitioners. Although multiple outbreaks of GAS infection in LTCFs have been described in the medical literature, this topic has not been reviewed for 15 years, and there is a need for updated guidance on how to approach GAS infection outbreak control. We reviewed published documents on GAS infection in LTCFs to describe the current understanding of the disease's epidemiology in this setting, identify techniques for outbreak investigation and prevention, and expose areas where additional research is needed. We highlight well-accepted prevention and control strategies that can be employed during investigation and control of GAS infection outbreaks in LTCFs.

Breastfeeding accounts for up to half of all infant human immunodeficiency virus (HIV) infections worldwide and carries an estimated transmission risk of about 15% when continued into the second year of life. Because replacement feeding is not safely available, culturally acceptable, or affordable in many parts of the world and because breastfeeding provides protection against other causes of infant mortality, approaches that reduce breastfeeding mother-to child transmission of HIV are being explored. These include exclusive breastfeeding for the infant's first few months of life followed by rapid weaning, treatments of expressed milk to inactivate the virus, and antiretroviral prophylaxis taken by the infant or mother during breastfeeding, which are strategies currently being tested in clinical trials. Passive (antibodies) and active (vaccine) immunoprophylaxis will also soon begin to be tested. This paper focuses on current and planned research on strategies to prevent breastfeeding transmission of HIV.

Background: A long-term care facility (LTCF) reported an outbreak of Legionnaires' disease (LD) in September 2004., Methods: We conducted case finding through enhanced surveillance, medical record review (n = 131), and community surveys (n = 258). We cultured water samples from the LTCF and assayed their outdoor air-intake filters for Legionella DNA. We also investigated a cooling tower, the only nearby outdoor aerosol source., Results: Among 7 confirmed cases, 2 LTCF residents never exited, and 2 community residents never entered the LTCF during the incubation period. Among 63 water and biofilm samples collected from throughout the LTCF, we found no evidence of Legionella colonization, either in the potable water or air-handling systems. Conversely, we isolated a common outbreak-causing strain of Legionella pneumophila serogroup 1 from an industrial cooling tower located 0.4 km from the LTCF and recovered L pneumophila DNA from the LTCF's outdoor air-intake filters, suggesting that aerosolized Legionella from the cooling tower most likely entered the LTCF through the air-intake system or, possibly, through open windows., Conclusion: Residents of LTCFs can acquire LD from community sources. A cluster of LD cases among LTCF residents does not necessarily indicate transmission from within the LTCF.

Objective: To identify factors contributing to a cluster of deaths from invasive group A streptococcus (GAS) infection in a nursing home facility and to prevent additional cases., Design: Outbreak investigation., Setting: A 146-bed nursing home facility in northern Nevada., Methods: We defined a case as the isolation of GAS from a normally sterile site in a resident of nursing home A. To identify case patients, we reviewed resident records from nursing home A, the local hospital, and the hospital laboratory. We obtained oropharyngeal and skin lesion swabs from staff and residents to assess GAS colonization and performed emm typing on available isolates. To identify potential risk factors for transmission, we performed a cohort study and investigated concurrent illness among residents and surveyed staff regarding infection control practices., Results: Six residents met the case patient definition; 3 (50%) of them died. Among invasive GAS isolates available for analysis, 2 distinct strains were identified: emm11 (3 isolates) and emm89 (2 isolates). The rate of GAS carriage was 6% among residents and 4% among staff; carriage isolates were emm89 (8 isolates), emm11 (2 isolates), and emm1 (1 isolate). Concurrently, 35 (24%) of the residents developed a respiratory illness of unknown etiology; 41% of these persons died. Twenty-one (30%) of the surveyed employees did not always wash their hands before patient contacts, and 27 (38%) did not always wash their hands between patient contacts., Conclusions: Concurrent respiratory illness likely contributed to an outbreak of invasive GAS infection from 2 strains in a highly susceptible population. This outbreak highlights the importance of appropriate infection control measures, including respiratory hygiene practices, in nursing home facilities.

Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering >or=2 treatment doses of sulfadoxine/pyrimethamine to pregnant women at predefined intervals after quickening (around 18-20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/pyrimethamine use in IPTp programmes in Africa, with 2-4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/pyrimethamine - when delivered as IPTp - has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.