Same day HIV diagnosis and antiretroviral therapy initiation affects retention in Option B+ prevention of mother-to-child transmission services at antenatal care in Zomba District, Malawi.

INTRODUCTION: Data from the Option B+ prevention of mother-to-child transmission (PMTCT) program in Malawi show considerable variation between health facilities in retention on antiretroviral therapy (ART). In a programmatic setting, we studied whether the "model of care," based on the degree of integration of antenatal care (ANC), HIV testing and counselling (HTC) and ART service provision-influenced uptake of and retention on ART. METHODS: We conducted a retrospective cohort study of pregnant women seeking ANC at rural primary health facilities in Zomba District, Malawi. Data were extracted from standardized national ANC registers, ART registers and ART master cards. The "model of care" of Option B+ service delivery was determined at each health facility, based on the degree of integration of ANC, HTC and ART. Full integration (Model 1) of HTC and ART initiation at ANC was compared with integration of HTC only into ANC services (Model 2) with subsequent referral to an existing ART clinic for treatment initiation. RESULTS AND DISCUSSION: A total of 10,528 women were newly registered at ANC between October 2011 and March 2012 in 23 rural health facilities (12 were Model 1 and 11 Model 2). HIV status was ascertained in 8,572 (81%) women. Among 914/8,572 (9%) HIV-positive women enrolling at ANC, 101/914 (11%) were already on ART; of those not on treatment, 456/813 (56%) were started on ART. There was significantly higher ART uptake in Model 1 compared with Model 2 sites (63% vs. 51%; p=0.001), but significantly lower ART retention in Model 1 compared with Model 2 sites (79% vs. 87%; p=0.02). Multivariable analysis showed that initiation of ART on the same day as HIV diagnosis, but not model of care, was independently associated with reduced retention in the first six months (adjusted odds ratio 2.27; 95% CI: 1.34-3.85; p=0.002). CONCLUSIONS: HIV diagnosis and treatment on the same day was associated with reduced retention on ART, independent of the level of PMTCT service integration at ANC

Outcome Assessment of a Dedicated HIV Positive Health Care Worker Clinic at a Central Hospital in Malawi: A Retrospective Observational Study

BACKGROUND: Malawi has one of the world's lowest densities of Health Care Workers (HCW) per capita. This study evaluates outcomes of a dedicated HCW HIV clinic in Malawi, created at Zomba Central Hospital in January 2007. METHODS AND FINDINGS: Retrospective cohort data was analyzed comparing HCW clinic patient baseline characteristics and treatment outcomes at 18 months after inception, against those attending the general HIV clinic. In-depth interviews and focus group discussions were conducted to explore perceptions of patients and caregivers regarding program value, level of awareness and barriers for uptake amongst HCW. 306 patients were enrolled on antiretroviral therapy (ART) in the HCW HIV clinic, 6784 in the general clinic. Significantly (p<0.01) more HCW clients were initiated on ART on the basis of CD4 as opposed to WHO Stage 3/4 (36% vs.23%). Significantly fewer HCW clients defaulted (6% vs.17%), and died (4% vs.12%). The dedicated HCW HIV clinic was perceived as important and convenient in terms of reduced waiting times, and prompt and high quality care. Improved confidentiality was an appreciated quality of the HCW clinic however barriers included fear of being recognized. CONCLUSIONS/SIGNIFICANCE: Outcomes at the HCW clinic appear better compared to the general HIV clinic. The strategy of dedicated clinics to care for health providers is a means of HIV impact mitigation within human resource constrained health systems in high prevalence settings

Outcomes and Diagnostic Processes in Outpatients with Presumptive Tuberculosis in Zomba District, Malawi.

BACKGROUND: In Malawi, outpatients who have presumptive tuberculosis (TB), i.e. fever, night sweats, weight loss and/or any-duration cough (HIV-infected) or cough of at least 2 weeks (HIV-uninfected), are registered in chronic cough registers. They should receive a diagnostic work-up with first-step provider-initiated HIV testing and sputum testing which includes XpertMTB/RIF, following a national algorithm introduced in 2012. METHODS: An operational study, in which we prospectively studied 6-month outcomes of adult outpatients who were registered in chronic cough registers in Zomba Central Hospital and Matawale peri-urban Health Center, between February and September 2013. We recorded implementation of the diagnostic protocol and outcomes at 6 months from registration. RESULTS: Of 348 patients enrolled, 165(47%) were male, median age was 40 years, 72(21%) had previous TB. At registration 154(44%) were known HIV-positive, 34(10%) HIV-negative (26 unconfirmed) and 160(46%) had unknown HIV status; 104(56%) patients with unknown/unconfirmed HIV status underwent HIV testing. At 6 months 191(55%) were HIV-positive, 87(25%) HIV-negative (26 unconfirmed) and 70(20%) still had unknown HIV status. Higher age and registration in Matawale were independently associated with remaining unknown HIV status after 6 months. 62% of patients had sputum tested, including XpertMTB/RIF, according to the algorithm. TB was diagnosed in 54(15%) patients. This was based on XpertMTB/RIF results in 8(15%) diagnosed cases. In 26(48%) TB was diagnosed on clinical grounds. Coverage of ART in HIV-positive patients was 89%. At 6 months, 236(68%) were asymptomatic, 48(14%) symptomatic, 25(7%) had been lost-to-follow-up and 39(11%) had died. Mortality among those HIV-positive, HIV-negative and with unknown HIV-status was 15%, 2% and 10%, respectively. Male gender, being HIV-positive-not-on-ART and not receiving antibiotics were independent risk factors for mortality. CONCLUSION: HIV prevalence among patients with presumptive TB was high (55%). One quarter was not HIV tested and mortality in this group was substantial (10%). The impact of XpertMTB/RIF on TB diagnosis was limited

Implementation of Antiretroviral Therapy for Life in Pregnant/Breastfeeding HIV+ Women (Option B+) Alongside Rollout and Changing Guidelines for ART Initiation in Rural Zimbabwe: The Lablite Project Experience.

BACKGROUND: Lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women (Option B+) was rolled out in Zimbabwe from 2014, with simultaneous raising of the CD4 treatment threshold to 500 cells per cubic millimeter in nonpregnant/breastfeeding adults and children 5 years and over. METHODS: Lablite is an implementation project in Zimbabwe, Malawi, and Uganda evaluating ART rollout. Routine patient-level data were collected for 6 months before and 12 months after Option B+ rollout at a district hospital and 3 primary care facilities in Zimbabwe (2 with outreach ART and 1 with no ART provision before Option B+). RESULTS: Between September 2013 and February 2015, there were 1686 ART initiations in the 4 facilities: 91% adults and 9% children younger than 15 years. In the 3 facilities with established ART, initiations rose from 300 during 6 months before Option B+ to 869 (2.9-fold) and 463 (1.5-fold), respectively, 0-6 months and 6-12 months after Option B+. Post-Option B+, an estimated 43% of pregnant/breastfeeding women needed ART for their own health, based on World Health Organization stage 3/4 or CD4 ≤350 per cubic millimeter (64% for CD4 ≤500). Seventy-four men (22%) and 123 nonpregnant/breastfeeding women (34%) initiated ART with CD4 >350 after the CD4 threshold increase. Estimated 12-month retention on ART was 79% (69%-87%) in Option B+ women (significantly lower in younger women, P = 0.01) versus 93% (91%-95%) in other adults (difference P < 0.001). CONCLUSIONS: There were increased ART initiations in all patient groups after implementation of World Health Organization 2013 guidelines. Retention of Option B+ women was poorer than retention of other adults; younger women require attention because they are more likely to disengage from care

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Towards elimination of mother-to-child transmission of HIV: performance of different models of care for initiating lifelong antiretroviral therapy for pregnant women in Malawi (Option B+).

INTRODUCTION: Malawi introduced a new strategy to improve the effectiveness of prevention of mother-to-child HIV transmission (PMTCT), the Option B+ strategy. We aimed to (i) describe how Option B+ is provided in health facilities in the South East Zone in Malawi, identifying the diverse approaches to service organization (the "model of care") and (ii) explore associations between the "model of care" and health facility-level uptake and retention rates for pregnant women identified as HIV-positive at antenatal (ANC) clinics. METHODS: A health facility survey was conducted in all facilities providing PMTCT/antiretroviral therapy (ART) services in six of Malawi's 28 districts to describe and compare Option B+ service delivery models. Associations of identified models with program performance were explored using facility cohort reports. RESULTS: Among 141 health facilities, four "models of care" were identified: A) facilities where newly identified HIV-positive women are initiated and followed on ART at the ANC clinic until delivery; B) facilities where newly identified HIV-positive women receive only the first dose of ART at the ANC clinic, and are referred to the ART clinic for follow-up; C) facilities where newly identified HIV-positive women are referred from ANC to the ART clinic for initiation and follow-up of ART; and D) facilities serving as ART referral sites (not providing ANC). The proportion of women tested for HIV during ANC was highest in facilities applying Model A and lowest in facilities applying Model B. The highest retention rates were reported in Model C and D facilities and lowest in Model B facilities. In multivariable analyses, health facility factors independently associated with uptake of HIV testing and counselling (HTC) in ANC were number of women per HTC counsellor, HIV test kit availability, and the "model of care" applied; factors independently associated with ART retention were district location, patient volume and the "model of care" applied. CONCLUSIONS: A large variety exists in the way health facilities have integrated PMTCT Option B+ care into routine service delivery. This study showed that the "model of care" chosen is associated with uptake of HIV testing in ANC and retention in care on ART. Further patient-level research is needed to guide policy recommendations

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother–child pairs

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother–child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother–child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD

Healthcare Costs and Life-years Gained From Treatments Within the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) Trial on Cryptococcal Meningitis: A Comparison of Antifungal Induction Strategies in Sub-Saharan Africa

Background Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. Methods Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. Results Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC,$1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC,$2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US$208 (95% confidence interval $91–1210) per life-year saved. Conclusions Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments

Uptake and outcomes of a prevention-of mother-to-child transmission (PMTCT) program in Zomba district, Malawi

<p>Abstract</p> <p>Background</p> <p>HIV prevalence among pregnant women in Malawi is 12.6%, and mother-to-child transmission is a major route of transmission. As PMTCT services have expanded in Malawi in recent years, we sought to determine uptake of services, HIV-relevant infant feeding practices and mother-child health outcomes.</p> <p>Methods</p> <p>A matched-cohort study of HIV-infected and HIV-uninfected mothers and their infants at 18-20 months post-partum in Zomba District, Malawi. 360 HIV-infected and 360 HIV-uninfected mothers were identified through registers. 387 mother-child pairs were included in the study.</p> <p>Results</p> <p>10% of HIV-infected mothers were on HAART before delivery, 27% by 18-20 months post-partum. sd-NVP was taken by 75% of HIV-infected mothers not on HAART, and given to 66% of infants. 18% of HIV-infected mothers followed all current recommended PMTCT options. HIV-infected mothers breastfed fewer months than HIV-uninfected mothers (12 vs.18, respectively; <it>p </it>< 0.01). 19% of exposed versus 5% of unexposed children had died by 18-20 months; <it>p </it>< 0.01. 28% of exposed children had been tested for HIV prior to the study, 76% were tested as part of the study and 11% were found HIV-positive. HIV-free survival by 18-20 months was 66% (95%CI 58-74). There were 11(6%) maternal deaths among HIV-infected mothers only.</p> <p>Conclusion</p> <p>This study shows low PMTCT program efficiency and effectiveness under routine program conditions in Malawi. HIV-free infant survival may have been influenced by key factors, including underuse of HAART, underuse of sd-NVP, and suboptimal infant feeding practices. Maternal mortality among HIV-infected women demands attention; improved maternal survival is a means to improve infant survival.</p

Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). METHODS: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. RESULTS: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. CONCLUSION: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB