Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children

The standard first-line antiretroviral (ART) regimen in Malawi for both adults and children is a fixed-dose combination tablet containing stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). This regimen has been shown to yield satisfactory virologic and immunologic outcomes in children. Published studies have described insights into discontinuation of first-line regimen and toxicities of ART in adults, but similar studies in paediatric populations are lacking

Low Rates of Mother-to-Child HIV Transmission in a Routine Programmatic Setting in Lilongwe, Malawi

Background The Tingathe program utilizes community health workers to improve prevention of mother-to-child transmission (PMTCT) service delivery. We evaluated the impact of antiretroviral (ARV) regimen and maternal CD4+ count on HIV transmission within the Tingathe program in Lilongwe, Malawi. Methods We reviewed clinical records of 1088 mother-infant pairs enrolled from March 2009 to March 2011 who completed follow-up to first DNA PCR. Eligibility for antiretroviral treatment (ART) was determined by CD4+ cell count (CD4+) for women not yet on ART. ART-eligible women initiated stavudine-lamivudine-nevirapine. Early ART was defined as ART for ≥14 weeks prior to delivery. For women ineligible for ART, optimal ARV prophylaxis was maternal AZT ≥6 weeks+sdNVP, and infant sdNVP+AZT for 1 week. HIV transmission rates were determined for ARV regimens, and factors associated with vertical transmission were identified using bivariate logistic regression. Results Transmission rate at first PCR was 4.1%. Pairs receiving suboptimal ARV prophylaxis were more likely to transmit HIV (10.3%, 95% CI, 5.5–18.1%). ART was associated with reduced transmission (1.4%, 95% CI, 0.6–3.0%), with early ART associated with decreased transmission (no transmission), compared to all other treatment groups (p = 0.001). No association was detected between transmission and CD4+ categories (p = 0.337), trimester of pregnancy at enrollment (p = 0.100), or maternal age (p = 0.164). Conclusion Low rates of MTCT of HIV are possible in resource-constrained settings under routine programmatic conditions. No transmissions were observed among women on ART for more than 14 weeks prior to delivery

Sexually Transmitted Infection (STI) screening, case and contact treatment, and condom promotion resulting in STI Reduction two years later in rural Malawi

As part of a longitudinal cohort study in rural Malawi in 2000, 469 men and 758 women were asked to respond to a series of surveys, were tested for gonorrhea and chlamydia, and received their results and treatment, if applicable, for themselves and up to 2 partners if positive for either sexually transmitted infection (STI). Two years later, in 2002, 328 men and 525 women were again asked to respond to survey questions, tested again for gonorrhea and chlamydia, and were also tested for HIV - of these, 247 men and 453 women had also given urine samples in 2000. In 2000, the gonorrhea and chlamydia prevalence was 6.2% and 5.8% among men, and 3.6% and 4.9% among women. Two years later, prevalence of gonorrhea and chlamydia was 0.7% and 1.4% among men, and 1.3% and 1.1% among women. Although we did not test for HIV in the first round, the HIV prevalence in 2002 was 19.2%. The implications of the findings are discussed in the context of interventions for STI prevention and to reduce HIV transmission in sub-Saharan Africa

Competing risks modeling of length of hospital stay enhances risk-stratification of patient care: application to under-five children hospitalized in Malawi

Introduction Length of hospital stay (LOS), defined as the time from inpatient admission to discharge, death, referral, or abscondment, is one of the key indicators of quality in patient care. Reduced LOS lowers health care expenditure and minimizes the chance of in-hospital acquired infections. Conventional methods for estimating LOS such as the Kaplan-Meier survival curve and the Cox proportional hazards regression for time to discharge cannot account for competing risks such as death, referral, and abscondment. This study applied competing risk methods to investigate factors important for risk-stratifying patients based on LOS in order to enhance patient care. Methods This study analyzed data from ongoing safety surveillance of the malaria vaccine implementation program in Malawi's four district hospitals of Balaka, Machinga, Mchinji, and Ntchisi. Children aged 1–59 months who were hospitalized (spending at least one night in hospital) with a medical illness were consecutively enrolled between 1 November 2019 and 31 July 2021. Sub-distribution-hazard (SDH) ratios for the cumulative incidence of discharge were estimated using the Fine-Gray competing risk model. Results Among the 15,463 children hospitalized, 8,607 (55.7%) were male and 6,856 (44.3%) were female. The median age was 22 months [interquartile range (IQR): 12–33 months]. The cumulative incidence of discharge was 40% lower among HIV-positive children compared to HIV-negative (sub-distribution-hazard ratio [SDHR]: 0.60; [95% CI: 0.46–0.76]; P < 0.001); lower among children with severe and cerebral malaria [SDHR: 0.94; (95% CI: 0.86–0.97); P = 0.04], sepsis or septicemia [SDHR: 0.90; (95% CI: 0.82–0.98); P = 0.027], severe anemia related to malaria [SDHR: 0.54; (95% CI: 0.48–0.61); P < 0.001], and meningitis [SDHR: 0.18; (95% CI: 0.09–0.37); P < 0.001] when compared to non-severe malaria; and also 39% lower among malnourished children compared to those that were well-nourished [SDHR: 0.61; (95% CI: 0.55–0.68); P < 0.001]. Conclusions This study applied the Fine-Gray competing risk approach to more accurately model LOS as the time to discharge when there were significant rates of in-hospital mortality, referrals, and abscondment. Patient care can be enhanced by risk-stratifying by LOS based on children's age, HIV status, diagnosis, and nutritional status

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

BACKGROUND: Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. METHODS: The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. RESULTS: Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher's exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann-Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). CONCLUSION: The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data

The quality and diagnostic value of open narratives in verbal autopsy: a mixed-methods analysis of partnered interviews from Malawi

Background Verbal autopsy (VA), the process of interviewing a deceased’s family or caregiver about signs and symptoms leading up to death, employs tools that ask a series of closed questions and can include an open narrative where respondents give an unprompted account of events preceding death. The extent to which an individual interviewer, who generally does not interpret the data, affects the quality of this data, and therefore the assigned cause of death, is poorly documented. We aimed to examine inter-interviewer reliability of open narrative and closed question data gathered during VA interviews. Methods During the introduction of VA data collection, as part of a larger study in Mchinji district, Malawi, we conducted partner interviews whereby two interviewers independently recorded open narrative and closed questions during the same interview. Closed questions were collected using a smartphone application (mobile-InterVA) and open narratives using pen and paper. We used mixed methods of analysis to evaluate the differences between recorded responses to open narratives and closed questions, causes of death assigned, and additional information gathered by open narrative. Results Eighteen partner interviews were conducted, with complete data for 11 pairs. Comparing closed questions between interviewers, the median number of differences was 1 (IQR: 0.5–3.5) of an average 65 answered; mean inter-interviewer concordance was 92 % (IQR: 92–99 %). Discrepancies in open narratives were summarized in five categories: demographics, history and care-seeking, diagnoses and symptoms, treatment and cultural. Most discrepancies were seen in the reporting of diagnoses and symptoms (e.g., malaria diagnosis); only one pair demonstrated no clear differences. The average number of clinical symptoms reported was 9 in open narratives and 20 in the closed questions. Open narratives contained additional information on health seeking and social issues surrounding deaths, which closed questions did not gather. Conclusions The information gleaned during open narratives was subject to inter-interviewer variability and contained a limited number of symptom indicators, suggesting that their use for assigning cause of death is questionable. However, they contained rich information on care-seeking, healthcare provision and social factors in the lead-up to death, which may be a valuable source of information for promoting accountable health services

Comparison of infant malaria incidence in districts of Maputo province, Mozambique

<p>Abstract</p> <p>Background</p> <p>Malaria is one of the principal health problems in Mozambique, representing 48% of total external consultations and 63% of paediatric hospital admissions in rural and general hospitals with 26.7% of total mortality. <it>Plasmodium falciparum </it>is responsible for 90% of all infections being also the species associated with most severe cases. The aim of this study was to identify zones of high malaria risk, showing their spatially and temporal pattern.</p> <p>Methods</p> <p>Space and time Poison model for the analysis of malaria data is proposed. This model allows for the inclusion of environmental factors: rainfall, temperature and humidity as predictor variables. Modelling and inference use the fully Bayesian approach via Markov Chain Monte Carlo (MCMC) simulation techniques. The methodology is applied to analyse paediatric data arising from districts of Maputo province, Mozambique, between 2007 and 2008.</p> <p>Results</p> <p>Malaria incidence risk is greater for children in districts of Manhiça, Matola and Magude. Rainfall and humidity are significant predictors of malaria incidence. The risk increased with rainfall (relative risk - RR: .006761, 95% interval: .001874, .01304), and humidity (RR: .049, 95% interval: .03048, .06531). Malaria incidence was found to be independent of temperature.</p> <p>Conclusions</p> <p>The model revealed a spatial and temporal pattern of malaria incidence. These patterns were found to exhibit a stable malaria transmission in most non-coastal districts. The findings may be useful for malaria control, planning and management.</p

Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe, Malawi

BackgroundEarly identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children.MethodsThree programme phases are described. During the first phase, Mentorship Only (MO) (March 2007–February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008–February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009–February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011.ResultsDuring MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5–70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p<0.001).During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008.ConclusionsA multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children

The prevalence and contextual correlates of non-communicable diseases among inter-provincial migrants and non-migrants in South Africa

BACKGROUND: The socioeconomic conditions of different environments manifest in varying experiences of illnesses. Even as migrants do transit across these different environments for various reasons, including settlement, they are bound to have peculiar experiences of diseases, which could be traced to lifestyle, gender, adaptation, and reactions to specific social, economic, psychological and climatic conditions. Paying attention to such unique scenarios, our study examines the prevalence and contextual correlates of non-communicable diseases among inter-provincial migrants and non-migrants in South Africa. METHODS: Data was from the National Income Dynamics Study (NIDS), waves 5 of 2017, which comprised of 28,055 respondents aged 15–64 years made up of 22,849 inter-provincial non-migrants and 5206 inter-provincial migrants. A composite dependent/outcome variable of non-communicable diseases (NCDs) was generated for the study and data analysis involved descriptive statistics, chi Square analysis and multilevel logistic regression analysis. RESULTS: More migrants (19.81%) than non-migrants (16.69%) reported prevalence of NCDs. With the exception of household size for migrants and smoking for non-migrants, the prevalence of NCDs showed significant differences in all the community, behavioral, and individual variables. The factors in the full model, which significantly increased odds of NCDs among the migrants and the non-migrants, were older populations, the non-Blacks, and those with higher education levels. On the one hand, being married, having a household with 4–6 persons, and being residents of urban areas significantly increased odds of NCDs among the migrant population. While on the other, living in coastal provinces, being a female, and belonging to the category of those who earn more than 10,000 Rands were significantly associated with increased odds of NCDs among the non-migrants. CONCLUSIONS: These findings, therefore, among other things underscore the need for increased education and awareness campaigns, especially among the older populations on the preventive and mitigative strategies for NCDs. In addition, changes in lifestyles with regard to smoking and physical exercises should be more emphasized in specific contextual situations for the migrant and non-migrant populations, as highlighted by the results of this study

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection