The Manhiça Health Research Centre, established in 1996 in a rural area of southern Mozambique, currently follows around 92 000 individuals living in approximately 20 000 enumerated and geo-positioned households. Its main strength is the possibility of linking demographic data and clinical data to promote and conduct biomedical research in priority health areas. Socio-demographic data are updated twice a year and clinical data are collected on a daily basis. The data collected in Manhiça HDSS comprises household and individual characteristics, household socio-economic assets, vital data, migration, individual health history and cause of death, among others. Studies conducted in this HDSS contributed to guide the health authorities and decision-making bodies to define or adjust health policies such as the introduction of Mozambique’s expanded programme of immunization with different vaccines (Haemophilus influenzae type b, Pneumococcus) or the development of the concept of Intermittent Preventive Treatment for Infants (IPTi) that led to the World Health Organization recommendation of this method as best practice for the control of malaria among infants. Manhiça’s data can be accessed through a formal request to Diana Quelhas (diana.quelhas@manhica.net) accompanied by a proposal that will be analysed by the Manhiça HDSS internal scientific and ethics committees.

The aim of this study is to estimate the immediate and lasting effects of the 2014–2015 Ebola virus disease (EVD) outbreak on public-sector primary healthcare delivery in Liberia using 7 years of comprehensive routine health information system data. We analyzed 10 key primary healthcare indicators before, during, and after the EVD outbreak using 31,836 facility-month service outputs from 1 January 2010 to 31 December 2016 across a census of 379 public-sector health facilities in Liberia (excluding Montserrado County). All indicators had statistically significant decreases during the first 4 months of the EVD outbreak, with all indicators having their lowest raw mean outputs in August 2014. Decreases in outputs comparing the end of the initial EVD period (September 2014) to May 2014 (pre-EVD) ranged in magnitude from a 67.3% decrease in measles vaccinations (95% CI: −77.9%, −56.8%, p < 0.001) and a 61.4% decrease in artemisinin-based combination therapy (ACT) treatments for malaria (95% CI: −69.0%, −53.8%, p < 0.001) to a 35.2% decrease in first antenatal care (ANC) visits (95% CI: −45.8%, −24.7%, p < 0.001) and a 38.5% decrease in medroxyprogesterone acetate doses (95% CI: −47.6%, −29.5%, p < 0.001). Following the nadir of system outputs in August 2014, all indicators showed statistically significant increases from October 2014 to December 2014. All indicators had significant positive trends during the post-EVD period, with every system output exceeding pre-Ebola forecasted trends for 3 consecutive months by November 2016. Health system outputs lost during and after the EVD outbreak were large and sustained for most indicators. Prior to exceeding pre-EVD forecasted trends for 3 months, we estimate statistically significant cumulative losses of −776,110 clinic visits (95% CI: −1,480,896, −101,357, p = 0.030); −24,449 bacille Calmette–Guérin vaccinations (95% CI: −45,947, −2,020, p = 0.032); −9,129 measles vaccinations (95% CI: −12,312, −5,659, p < 0.001); −17,191 postnatal care (PNC) visits within 6 weeks of birth (95% CI: −28,344, −5,775, p = 0.002); and −101,857 ACT malaria treatments (95% CI: −205,839, −2,139, p = 0.044) due to the EVD outbreak. Other outputs showed statistically significant cumulative losses only through December 2014, including losses of −12,941 first pentavalent vaccinations (95% CI: −20,309, −5,527, p = 0.002); −5,122 institutional births (95% CI: −8,767, −1,234, p = 0.003); and −45,024 acute respiratory infections treated (95% CI: −66,185, −24,019, p < 0.001). Compared to pre-EVD forecasted trends, medroxyprogesterone acetate doses and first ANC visits did not show statistically significant net losses. ACT treatment for malaria was the only indicator with an estimated net increase in system outputs through December 2016, showing an excess of +78,583 outputs (95% CI: −309,417, +450,661, p = 0.634) compared to pre-EVD forecasted trends, although this increase was not statistically significant. However, comparing December 2013 to December 2017, ACT malaria cases have increased 49.2% (95% CI: 33.9%, 64.5%, p < 0.001). Compared to pre-EVD forecasted trends, there remains a statistically significant loss of −15,144 PNC visits within 6 weeks (95% CI: −29,453, −787, p = 0.040) through December 2016. The Liberian public-sector primary healthcare system has made strides towards recovery from the 2014–2015 EVD outbreak. All primary healthcare indicators tracked have recovered to pre-EVD levels as of November 2016. Yet, for most indicators, it took more than 1 year to recover to pre-EVD levels. During this time, large losses of essential primary healthcare services occurred compared to what would have been expected had the EVD outbreak not occurred. The disruption of malaria case management during the EVD outbreak may have resulted in increased malaria cases. Large and sustained investments in public-sector primary care health system strengthening are urgently needed for EVD-affected countries.

Interrupted time-series (ITS) designs are a robust and increasingly popular non-randomized study design for strong causal inference in the evaluation of public health interventions. One of the most common techniques for model parameterization in the analysis of ITS designs is segmented regression, which uses a series of indicators and linear terms to represent the level and trend of the time-series before and after an intervention. In this article, we highlight an important error often presented in tutorials and published peer-reviewed papers using segmented regression parameterization for the analyses of ITS designs. We show that researchers cannot simply use the product between their calendar time variable and the indicator variable indicating pre- versus post-intervention time periods to represent the post-intervention linear segment. If researchers use this often-presented parameterization, they will get an erroneous result for the level change in their time-series. We show that researchers must take care to use the product between their intervention variable and the time elapsed since the start of the intervention, rather than the time since the beginning of their study. Thus, the second linear segment of the time-series indexing the post-intervention level and trend should be zero before intervention implementation and begin by counting from zero, rather than counting from the time elapsed since the beginning of the study. We hope that this article can clarify segmented regression parameterization for the analysis of ITS designs and help researchers avoid confusing and erroneous results in the level changes of their time-series.

Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment. Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I² = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08–1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36–1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6–12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54–2.01), I² = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26–2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52–2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%–3.5%]) and quinine exposures (1.2% [95% CI 0.6%–2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns. Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens. PROSPERO CRD42015032371

Monitoring the HIV epidemic in a defined population is critical for planning treatment and preventive strategies. This is especially important in sub-Saharan Africa, which harbours the highest burden of the disease. To estimate HIV incidence in adults aged 18-47 years old and to investigate spatial variations of HIV prevalence in Manhiça, a semi-rural area of southern Mozambique. Two cross-sectional community-based surveys were conducted in 2010 and 2012 to determine HIV prevalence. Individual participants were randomly selected from the demographic surveillance system in place in the area and voluntary HIV counselling and testing was offered at the household level. HIV incidence was calculated using prevalence estimates from the two sero-surveys. Each participant’s household was geocoded using a global information system. The Spatial Scan Statistics programme was used to identify areas with disproportionate excess in HIV prevalence. A total of 1511 adults were tested. The estimated HIV prevalence in the community was 39.9% in 2010 and 39.7% in 2012. The overall HIV incidence was 3.6 new infections per 100 person-years at risk (PYAR) [95CI 1.56; 7.88], assuming stable epidemic conditions, and tended to be higher in women (4.9/100 PYAR [95CI 1.74; 11.85]) than in men (3.2/PYAR [95CI 1.36; 9.92]). One cluster with significant excess HIV prevalence was identified at the same geographic location in both surveys. This cluster had an HIV prevalence of 79.0% in 2010 and 52.3% in 2012. The findings of these first individually-randomised community-HIV sero-surveys conducted in Mozambique reinforce the need to combine HIV incidence estimates and research on micro geographical infection patterns to guide and consolidate effective prevention strategies.