Assessing the effect of health system resources on HIV and tuberculosis programmes in Malawi: a modelling study.

BACKGROUND: Malawi is progressing towards UNAIDS and WHO End TB Strategy targets to eliminate HIV/AIDS and tuberculosis. We aimed to assess the prospective effect of achieving these goals on the health and health system of the country and the influence of consumable constraints. METHODS: In this modelling study, we used the Thanzi la Onse (Health for All) model, which is an individual-based multi-disease simulation model that simulates HIV and tuberculosis transmission, alongside other diseases (eg, malaria, non-communicable diseases, and maternal diseases), and gates access to essential medicines according to empirical estimates of availability. The model integrates dynamic disease modelling with health system engagement behaviour, health system use, and capabilities (ie, personnel and consumables). We used 2018 data on the availability of HIV and tuberculosis consumables (for testing, treatment, and prevention) across all facility levels of the country to model three scenarios of HIV and tuberculosis programme scale-up from Jan 1, 2023, to Dec 31, 2033: a baseline scenario, when coverage remains static using existing consumable constraints; a constrained scenario, in which prioritised interventions are scaled up with fixed consumable constraints; and an unconstrained scenario, in which prioritised interventions are scaled up with maximum availability of all consumables related to HIV and tuberculosis care. FINDINGS: With uninterrupted medical supplies, in Malawi, we projected HIV and tuberculosis incidence to decrease to 26 (95% uncertainty interval [UI] 19-35) cases and 55 (23-74) cases per 100 000 person-years by 2033 (from 152 [98-195] cases and 123 [99-160] cases per 100 000 person-years in 2023), respectively, with programme scale-up, averting a total of 12·21 million (95% UI 11·39-14·16) disability-adjusted life-years. However, the effect was compromised by restricted access to key medicines, resulting in approximately 58 700 additional deaths (33 400 [95% UI 22 000-41 000] due to AIDS and 25 300 [19 300-30 400] due to tuberculosis) compared with the unconstrained scenario. Between 2023 and 2033, eliminating HIV treatment stockouts could avert an estimated 12 100 deaths compared with the baseline scenario, and improved access to tuberculosis prevention medications could prevent 5600 deaths in addition to those achieved through programme scale-up alone. With programme scale-up under the constrained scenario, consumable stockouts are projected to require an estimated 14·3 million extra patient-facing hours between 2023 and 2033, mostly from clinical or nursing staff, compared with the unconstrained scenario. In 2033, with enhanced screening, 188 000 (81%) of 232 900 individuals projected to present with active tuberculosis could start tuberculosis treatment within 2 weeks of initial presentation if all required consumables were available, but only 8600 (57%) of 15 100 presenting under the baseline scenario. INTERPRETATION: Ignoring frailties in the health-care system, in particular the potential non-availability of consumables, in projections of HIV and tuberculosis programme scale-up might risk overestimating potential health impacts and underestimating required health system resources. Simultaneous health system strengthening alongside programme scale-up is crucial, and should yield greater benefits to population health while mitigating the strain on a heavily constrained health-care system. FUNDING: Wellcome and UK Research and Innovation as part of the Global Challenges Research Fund.

A new approach to Health Benefits Package design: an application of the Thanzi La Onse model in Malawi.

An efficient allocation of limited resources in low-income settings offers the opportunity to improve population-health outcomes given the available health system capacity. Efforts to achieve this are often framed through the lens of "health benefits packages" (HBPs), which seek to establish which services the public healthcare system should include in its provision. Analytic approaches widely used to weigh evidence in support of different interventions and inform the broader HBP deliberative process however have limitations. In this work, we propose the individual-based Thanzi La Onse (TLO) model as a uniquely-tailored tool to assist in the evaluation of Malawi-specific HBPs while addressing these limitations. By mechanistically modelling-and calibrating to extensive, country-specific data-the incidence of disease, health-seeking behaviour, and the capacity of the healthcare system to meet the demand for care under realistic constraints on human resources for health available, we were able to simulate the health gains achievable under a number of plausible HBP strategies for the country. We found that the HBP emerging from a linear constrained optimisation analysis (LCOA) achieved the largest health gain-∼8% reduction in disability adjusted life years (DALYs) between 2023 and 2042 compared to the benchmark scenario-by concentrating resources on high-impact treatments. This HBP however incurred a relative excess in DALYs in the first few years of its implementation. Other feasible approaches to prioritisation were assessed, including service prioritisation based on patient characteristics, rather than service type. Unlike the LCOA-based HBP, this approach achieved consistent health gains relative to the benchmark scenario on a year- to-year basis, and a 5% reduction in DALYs over the whole period, which suggests an approach based upon patient characteristics might prove beneficial in the future.

Factors associated with medical consumable availability in level 1 facilities in Malawi: a secondary analysis of a facility census.

BACKGROUND: Medical consumable stock-outs negatively affect health outcomes not only by impeding or delaying the effective delivery of services but also by discouraging patients from seeking care. Consequently, supply chain strengthening is being adopted as a key component of national health strategies. However, evidence on the factors associated with increased consumable availability is limited. METHODS: In this study, we used the 2018-19 Harmonised Health Facility Assessment data from Malawi to identify the factors associated with the availability of consumables in level 1 facilities, ie, rural hospitals or health centres with a small number of beds and a sparsely equipped operating room for minor procedures. We estimate a multilevel logistic regression model with a binary outcome variable representing consumable availability (of 130 consumables across 940 facilities) and explanatory variables chosen based on current evidence. Further subgroup analyses are carried out to assess the presence of effect modification by level of care, facility ownership, and a categorisation of consumables by public health or disease programme, Malawi's Essential Medicine List classification, whether the consumable is a drug or not, and level of average national availability. FINDINGS: Our results suggest that the following characteristics had a positive association with consumable availability-level 1b facilities or community hospitals had 64% (odds ratio [OR] 1·64, 95% CI 1·37-1·97) higher odds of consumable availability than level 1a facilities or health centres, Christian Health Association of Malawi and private-for-profit ownership had 63% (1·63, 1·40-1·89) and 49% (1·49, 1·24-1·80) higher odds respectively than government-owned facilities, the availability of a computer had 46% (1·46, 1·32-1·62) higher odds than in its absence, pharmacists managing drug orders had 85% (1·85, 1·40-2·44) higher odds than a drug store clerk, proximity to the corresponding regional administrative office (facilities greater than 75 km away had 21% lower odds [0·79, 0·63-0·98] than facilities within 10 km of the district health office), and having three drug order fulfilments in the 3 months before the survey had 14% (1·14, 1·02-1·27) higher odds than one fulfilment in 3 months. Further, consumables categorised as vital in Malawi's Essential Medicine List performed considerably better with 235% (OR 3·35, 95% CI 1·60-7·05) higher odds than other essential or non-essential consumables and drugs performed worse with 79% (0·21, 0·08-0·51) lower odds than other medical consumables in terms of availability across facilities. INTERPRETATION: Our results provide evidence on the areas of intervention with potential to improve consumable availability. Further exploration of the health and resource consequences of the strategies discussed will be useful in guiding investments into supply chain strengthening. FUNDING: UK Research and Innovation as part of the Global Challenges Research Fund (Thanzi La Onse; reference MR/P028004/1), the Wellcome Trust (Thanzi La Mawa; reference 223120/Z/21/Z), the UK Medical Research Council, the UK Department for International Development, and the EU (reference MR/R015600/1).

The changes in health service utilisation in Malawi during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic and the restriction policies implemented by the Government of Malawi may have disrupted routine health service utilisation. We aimed to find evidence for such disruptions and quantify any changes by service type and level of health care. METHODS: We extracted nationwide routine health service usage data for 2015-2021 from the electronic health information management systems in Malawi. Two datasets were prepared: unadjusted and adjusted; for the latter, unreported monthly data entries for a facility were filled in through systematic rules based on reported mean values of that facility or facility type and considering both reporting rates and comparability with published data. Using statistical descriptive methods, we first described the patterns of service utilisation in pre-pandemic years (2015-2019). We then tested for evidence of departures from this routine pattern, i.e., service volume delivered being below recent average by more than two standard deviations was viewed as a substantial reduction, and calculated the cumulative net differences of service volume during the pandemic period (2020-2021), in aggregate and within each specific facility. RESULTS: Evidence of disruptions were found: from April 2020 to December 2021, services delivered of several types were reduced across primary and secondary levels of care-including inpatient care (-20.03% less total interactions in that period compared to the recent average), immunisation (-17.61%), malnutrition treatment (-34.5%), accidents and emergency services (-16.03%), HIV (human immunodeficiency viruses) tests (-27.34%), antiretroviral therapy (ART) initiations for adults (-33.52%), and ART treatment for paediatrics (-41.32%). Reductions of service volume were greatest in the first wave of the pandemic during April-August 2020, and whereas some service types rebounded quickly (e.g., outpatient visits from -17.7% to +3.23%), many others persisted at lower level through 2021 (e.g., under-five malnutrition treatment from -15.24% to -42.23%). The total reduced service volume between April 2020 and December 2021 was 8 066 956 (-10.23%), equating to 444 units per 1000 persons. CONCLUSION: We have found substantial evidence for reductions in health service delivered in Malawi during the COVID-19 pandemic which may have potential health consequences, the effect of which should inform how decisions are taken in the future to maximise the resilience of healthcare system during similar events.

Modeling Contraception and Pregnancy in Malawi: A Thanzi La Onse Mathematical Modeling Study.

Malawi has high unmet need for contraception with a costed national plan to increase contraception use. Estimating how such investments might impact future population size in Malawi can help policymakers understand effects and value of policies to increase contraception uptake. We developed a new model of contraception and pregnancy using individual-level data capturing complexities of contraception initiation, switching, discontinuation, and failure by contraception method, accounting for differences by individual characteristics. We modeled contraception scale-up via a population campaign to increase initiation of contraception (Pop) and a postpartum family planning intervention (PPFP). We calibrated the model without new interventions to the UN World Population Prospects 2019 medium variant projection of births for Malawi. Without interventions Malawi's population passes 60 million in 2084; with Pop and PPFP interventions. it peaks below 35 million by 2100. We compare contraception coverage and costs, by method, with and without interventions, from 2023 to 2050. We estimate investments in contraception scale-up correspond to only 0.9 percent of total health expenditure per capita though could result in dramatic reductions of current pressures of very rapid population growth on health services, schools, land, and society, helping Malawi achieve national and global health and development goals.

Co-infection of intestinal helminths in humans and animals in the Philippines.

BACKGROUND: A large number of studies have assessed risk factors for infection with soil-transmitted helminths (STH), but few have investigated the interactions between the different parasites or compared these between host species across hosts. Here, we assessed the associations between Ascaris, Trichuris, hookworm, strongyle and Toxocara infections in the Philippines in human and animal hosts. METHODS: Faecal samples were collected from humans and animals (dogs, cats and pigs) in 252 households from four villages in southern Philippines and intestinal helminth infections were assessed by microscopy. Associations between worm species were assessed using multiple logistic regression. RESULTS: Ascaris infections showed a similar prevalence in humans (13.9%) and pigs (13.7%). Hookworm was the most prevalent infection in dogs (48%); the most prevalent infection in pigs was strongyles (42%). The prevalences of hookworm and Toxocara in cats were similar (41%). Statistically significant associations were observed between Ascaris and Trichuris and between Ascaris and hookworm infections in humans, and also between Ascaris and Trichuris infections in pigs. Dual and triple infections were observed, which were more common in dogs, cats and pigs than in humans. CONCLUSIONS: Associations are likely to exist between STH species in humans and animals, possibly due to shared exposures and transmission routes. Individual factors and behaviours will play a key role in the occurrence of co-infections, which will have effects on disease severity. Moreover, the implications of co-infection for the emergence of zoonoses need to be explored further.

Fecundity-Longevity Trade-Off, Vertical Transmission, and Evolution of Virulence in Sterilizing Pathogens.

Sterilizing pathogens are common, yet studies focused on how such pathogens respond adaptively to fecundity reductions caused in their hosts are rare. Here we assume that the infected hosts, as a result of redistributing energy resources saved by reduced fecundity, have increased longevity and focus on exploring the consequences of such a fecundity-longevity trade-off on sterility virulence evolution in the pathogens. We find that the trade-off itself cannot prevent the evolution of full sterilization. Therefore, we allow for vertical transmission and reveal that the fecundity-longevity trade-off strongly determines the threshold efficiency of vertical transmission above which partial host sterilization evolves. Partial sterilization may appear as an intermediate level of sterility virulence or as a stable dimorphism at which avirulent and highly virulent strains coexist. The fecundity-longevity trade-off significantly contributes to determining the actual outcome, in many cases countering predictions made in the absence of this trade-off. It is known that in well-mixed populations, partial sterilization may evolve in pathogens under a combination of horizontal and vertical transmission. Our study highlights that this is independent of the form of horizontal transmission and the type of density dependence in host demography and that the fecundity-longevity trade-off is an important player in sterility virulence evolution.

Host-pathogen dynamics under sterilizing pathogens and fecundity-longevity trade-off in hosts.

Infectious diseases are known to regulate population dynamics, an observation that underlies the use of pathogens as control agents of unwanted populations. Sterilizing rather than lethal pathogens are often suggested so as to avoid unnecessary suffering of the infected hosts. Until recently, models used to assess plausibility of pathogens as potential pest control agents have not included a possibility that reduced fecundity of the infected individuals may save their energy expenditure on reproduction and thus increase their longevity relative to the susceptible ones. Here, we develop a model of host-pathogen interaction that builds on this idea. We analyze the model for a variety of infection transmission functions, revealing that the indirect effect of sterilizing pathogens on mortality of the infected hosts, mediated by a fecundity-longevity trade-off, may cause hosts at endemic equilibria to attain densities higher than when there is no effect of pathogens on host mortality. On the other hand, an opposite outcome occurs when the fecundity-longevity trade-off is concave or when the degree of fecundity reduction by the pathogen is high enough. This points to a possibility that using sterilizing pathogens as agents of pest control may actually be less effective than previously thought, the more so since we also suggest that if sexual selection acts on the host species then the presence of sterilizing pathogens may even enhance host densities above the levels achieved without infection.

Sexually transmitted infections and mate-finding Allee effects.

Infectious diseases can seriously impact dynamics of their host species. In this study, we model and analyze an interaction between a sexually transmitted infection and its animal host population affected by a mate-finding Allee effect. Since mating drives both host reproduction and infection transmission, the Allee effect shapes the transmission rate of the infection which we show takes a saturating form. Our model combining sexually transmitted infections with the mate-finding Allee effect in the host produces quite rich dynamics, including oscillations, several multistability regimes, and infection-induced host extinction. However, many of these complex patterns are restricted to a relatively narrow parameter range. We find that the host extinction occurs at intermediate levels of infection virulence, as well as for Allee effect strengths much lower than when the infection is absent. In both cases, a sequence of events comprising destabilization of an endemic equilibrium, growth of oscillation amplitude, and a heteroclinic bifurcation forms an underlying mechanism. We apply our model to the feline immunodeficiency virus (FIV) in domestic cats.