conceptual mapping of a complex adaptive system based on multi-disciplinary expert insights

Funding Information: This study was partially funded by VLIR-UOS. The study sponsors had no role in the study design, the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Publisher Copyright: © 2022, The Author(s).Background: HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system. Methods: We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence. Results: Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and ‘overarching’. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The ‘adherence motivation’ subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The ‘healthcare burden’ subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The ‘ART overreliance’ subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. Conclusions: Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.publishersversionpublishe

Use pattern of maternal health services and determinants of skilled care during delivery in Southern Tanzania: implications for achievement of MDG-5 targets

Almost two decades since the initiation of the Safe motherhood Initiative, Maternal Mortality is still soaring high in most developing countries. In 2000 WHO estimated a life time risk of a maternal death of 1 in 16 in Sub- Saharan Africa while it was only 1 in 2800 in developed countries. This huge discrepancy in the rate of maternal deaths is due to differences in access and use of maternal health care services. It is known that having a skilled attendant at every delivery can lead to marked reductions in maternal mortality. For this reason, the proportion of births attended by skilled health personnel is one of the indicators used to monitor progress towards the achievement of the MDG-5 of improving maternal health. Cross sectional study which employed quantitative research methods. We interviewed 974 women who gave birth within one year prior to the survey. Although almost all (99.8%) attended ANC at least once during their last pregnancy, only 46.7% reported to deliver in a health facility and only 44.5% were assisted during delivery by a skilled attendant. Distance to the health facility (OR = 4.09 (2.72-6.16)), discussion with the male partner on place of delivery (OR = 2.37(1.75-3.22)), advise to deliver in a health facility during ANC (OR = 1.43 (1.25-2.63)) and knowledge of pregnancy risk factors (OR 2.95 (1.65-5.25)) showed significant association with use of skilled care at delivery even after controlling for confounding factors. Use of skilled care during delivery in this district is below the target set by ICPD + of attaining 80% of deliveries attended by skilled personnel by 2005. We recommend the following in order to increase the pace towards achieving the MDG targets: to improve coverage of health facilities, raising awareness for both men and women on danger signs during pregnancy/delivery and strengthening counseling on facility delivery and individual birth preparedness

Use pattern of maternal health services and determinants of skilled care during delivery in Southern Tanzania: implications for achievement of MDG-5 targets

Abstract Background Almost two decades since the initiation of the Safe motherhood Initiative, Maternal Mortality is still soaring high in most developing countries. In 2000 WHO estimated a life time risk of a maternal death of 1 in 16 in Sub- Saharan Africa while it was only 1 in 2800 in developed countries. This huge discrepancy in the rate of maternal deaths is due to differences in access and use of maternal health care services. It is known that having a skilled attendant at every delivery can lead to marked reductions in maternal mortality. For this reason, the proportion of births attended by skilled health personnel is one of the indicators used to monitor progress towards the achievement of the MDG-5 of improving maternal health. Methods Cross sectional study which employed quantitative research methods. Results We interviewed 974 women who gave birth within one year prior to the survey. Although almost all (99.8%) attended ANC at least once during their last pregnancy, only 46.7% reported to deliver in a health facility and only 44.5% were assisted during delivery by a skilled attendant. Distance to the health facility (OR = 4.09 (2.72–6.16)), discussion with the male partner on place of delivery (OR = 2.37(1.75–3.22)), advise to deliver in a health facility during ANC (OR = 1.43 (1.25–2.63)) and knowledge of pregnancy risk factors (OR 2.95 (1.65–5.25)) showed significant association with use of skilled care at delivery even after controlling for confounding factors. Conclusion Use of skilled care during delivery in this district is below the target set by ICPD + of attaining 80% of deliveries attended by skilled personnel by 2005. We recommend the following in order to increase the pace towards achieving the MDG targets: to improve coverage of health facilities, raising awareness for both men and women on danger signs during pregnancy/delivery and strengthening counseling on facility delivery and individual birth preparedness.</p

Factors Associated with HIV Drug Resistance in Dar es Salaam, Tanzania: Analysis of a Complex Adaptive System

HIV drug resistance (HIVDR) is a complex problem with multiple interconnected and context dependent causes. Although the factors influencing HIVDR are known and well-studied, HIVDR remains a threat to the effectiveness of antiretroviral therapy. To understand the complexity of HIVDR, a comprehensive, systems approach is needed. Therefore, a local systems map was developed integrating all reported factors influencing HIVDR in the Dar es Salaam Urban Cohort Study area in Tanzania. The map was designed based on semi-structured interviews and workshops with people living with HIV and local actors who encounter people living with HIV during their daily activities. We visualized the feedback loops driving HIVDR, compared the local map with a systems map for Sub-Saharan Africa, previously constructed from interviews with international HIVDR experts, and suggest potential interventions to prevent HIVDR. We found several interconnected balancing and reinforcing feedback loops related to poverty, stigmatization, status disclosure, self-esteem, knowledge about HIVDR and healthcare system workload, among others, and identified three potential leverage points. Insights from this local systems map were complementary to the insights from the Sub-Saharan systems map showing that both viewpoints are needed to fully understand the system. This study provides a strong baseline for quantitative modelling, and for the identification of context-dependent, complexity-informed leverage points

Ecological and Epidemiological Findings Associated with Zoonotic Rabies Outbreaks and Control in Moshi, Tanzania, 2017–2018

International Journal Environmental Research and Public Health, 2019; 16(2816)Approximately 1500 people die annually due to rabies in the United Republic of Tanzania. Moshi, in the Kilimanjaro Region, reported sporadic cases of human rabies between 2017 and 2018. In response and following a One Health approach, we implemented surveillance, monitoring, as well as a mass vaccinations of domestic pets concurrently in >150 villages, achieving a 74.5% vaccination coverage (n = 29, 885 dogs and cats) by September 2018. As of April 2019, no single human or animal case has been recorded. We have observed a disparity between awareness and knowledge levels of community members on rabies epidemiology. Self-adherence to protective rabies vaccination in animals was poor due to the challenges of costs and distances to vaccination centers, among others. Incidence of dog bites was high and only a fraction (65%) of dog bite victims (humans) received post-exposure prophylaxis. A high proportion of unvaccinated dogs and cats and the relative intense interactions with wild dog species at interfaces were the risk factors for seropositivity to rabies virus infection in dogs. A percentage of the previously vaccinated dogs remained unimmunized and some unvaccinated dogs were seropositive. Evidence of community engagement and multi-coordinated implementation of One Health in Moshi serves as an example of best practice in tackling zoonotic diseases using multi-level government e orts. The district-level establishment of the One Health rapid response team (OHRRT), implementation of a carefully structured routine vaccination campaign, improved health education, and the implementation of barriers between domestic animals and wildlife at the interfaces are necessary to reduce the burden of rabies in Moshi and communities with similar profiles

Ecological and Epidemiological Findings Associated with Zoonotic Rabies Outbreaks and Control in Moshi, Tanzania, 2017–2018

International Journal Environmental Research and Public Health, 2019; 16(2816)Approximately 1500 people die annually due to rabies in the United Republic of Tanzania. Moshi, in the Kilimanjaro Region, reported sporadic cases of human rabies between 2017 and 2018. In response and following a One Health approach, we implemented surveillance, monitoring, as well as a mass vaccinations of domestic pets concurrently in >150 villages, achieving a 74.5% vaccination coverage (n = 29, 885 dogs and cats) by September 2018. As of April 2019, no single human or animal case has been recorded. We have observed a disparity between awareness and knowledge levels of community members on rabies epidemiology. Self-adherence to protective rabies vaccination in animals was poor due to the challenges of costs and distances to vaccination centers, among others. Incidence of dog bites was high and only a fraction (65%) of dog bite victims (humans) received post-exposure prophylaxis. A high proportion of unvaccinated dogs and cats and the relative intense interactions with wild dog species at interfaces were the risk factors for seropositivity to rabies virus infection in dogs. A percentage of the previously vaccinated dogs remained unimmunized and some unvaccinated dogs were seropositive. Evidence of community engagement and multi-coordinated implementation of One Health in Moshi serves as an example of best practice in tackling zoonotic diseases using multi-level government e orts. The district-level establishment of the One Health rapid response team (OHRRT), implementation of a carefully structured routine vaccination campaign, improved health education, and the implementation of barriers between domestic animals and wildlife at the interfaces are necessary to reduce the burden of rabies in Moshi and communities with similar profiles

High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam

Abstract To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ( $$\pm$$ ± standard deviation) was 44.0 ( $$\pm$$ ± 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9–10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34–96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area