Resilience of Rural Households and Communities to Economic Shocks, HIV/AIDS and Recurrent Droughts: The Case of Households and Communities in the Mwami Area, Chipata, Zambia

国際金融機関の指導の下に経済政治改革を実施したサブ・サハラアフリカ諸国の農村経済は、「厳しい、障壁がある、難しい、困難である」等と言及されてきた。これら農村経済は、衰退と住民の貧困増大を経験してきた。その結果は、政策改革で期待された結果とは異なり、国家レベルではその改革のせいだと考えられていたものとも異なっていた。国レベルでは、政治改革は国家経済を安定化させ、過去１０年の間に平均５％の安定した成長を達成させることに貢献した。東部ザンビアのチパタ市にあるムワニ地区でのフィールド調査と文献調査の結果は、国際金融機関の支援によって経済改革を行ったすべてのサブ・サハラアフリカ諸国で報告されたと同様の経済的衰退、地域世帯とコミュニティの貧困の拡大を明らかにするものであった。ザンビアにおける経済政策改革によって、地域の経済環境は経済後退と貧困の拡大という結果をもたらした。これら予期せぬ結果は、農業と地域開発への公共投資の軽視が原因であった。しかし、この状況は経済改革、HIV/AIDS、環境変化の３重苦へ地域世帯が適応できなかったことによってさらに悪化した。農村世帯が農業自由化に対応できなかったことは、近年の旱ばつとHIV/AIDS の負の影響から派生したショックが経済改革と同時に進行したことによる。2000/2001 年及び2001/2002 年の農作期に起こった旱ばつによって、チパタ市ムワニ地区のほとんどの世帯の食料庫が空になり、家畜は回復の目途が立たないほどに打撃を受けた。ハイブリッド・トウモロコシ種子と肥料などの資材価格の上昇は、さらに状況を悪化させ、ほとんどの世帯は主食と換金作物であるトウモロコシの作付面積を減少させた。またHIV/AIDS 患者が出た世帯では、病気や死亡によって最も生産的な労働力の損失というさらなる経済状況の悪化が起こった。この状況は、貧困のプロセスへ移行し、国家経済の主流から取り残されることを意味しており、失望感をつのらせた。この結果、ムワニ地区のほとんどの世帯は森林資源や野生動物などの天然資源採集へ転換した。これらの採集は、伝統的技術に依存し、生産性も高くなく環境の荒廃を保全・改修するものではなかった。これらの天然資源採集は、温度の上昇や雨季の減少等の環境変動下ではとくに持続的ではない。ムワニ地区のみならずザンビアの農村世帯が自由化した経済環境、環境変動、HIV/AIDS などへ適応するための支援が必要とされる。Rural economies in sub-Saharan African countries that undertook economic policy reforms under the auspices of International Financial Institutions have been described as “harsh, challenging, hard and difficult’. These economies have been characterized by decline and increased impoverishment of their inhabitants. Such outcomes are at variance with what was expected of the policy reforms and what has been attributed to them at the national level. At the national level, the policy reforms have been credited with stabilizing the national economies and even robust growth averaging 5% over the last decade.Field investigations in the Mwami Area of Chipata in Eastern Zambia and an extensive review of literature confirms the experience of economic decline and growing impoverishment of rural households and communities reported in all sub-Saharan African countries that reformed their economies with the support of the International Financial Institutions. Economic policy reform in Zambia seem to have helped produce a harsh rural economic environment characterized by economic decline and increased poverty. These unexpected outcomes have been attributed to the neglect of public investment in agriculture and rural development. The situation has, however, been worsened by failure of rural households to adapt to the triple shocks of economic reform, HIV/AIDS and environmental change.Failure of rural households to adapt to the liberalized agricultural regime has been due to the economic reforms having coincided with recurrent droughts and shocks emanating from the adverse effects of HIV/AIDS. Recurrent droughts in the 2000/2001 and 2001/2002 agricultural seasons forced most households in the Mwami Area of Chipata to exhaust their stores, including livestock, which jeopardized their future recovery. The increased cost of agricultural in-puts especially hybrid maize seeds and fertilizers worsened the situation further, as it forced most households to reduce the amount of land devoted to maize, their main staple and commercial crop. For the households touched by the HIV/AIDS pandemic, the grave economic situation was worsened by loss of their most productive labour to ill health and deaths. This state of affairs set off a process of impoverishment and marginalization from the main stream national economy and created a general sense of despair.To make ends meet, most households in the Mwami area had turned to direct exploitation of natural resources, especially the forest and wildlife resources. These resources were, however, being exploited with basic technologies, which neither enhance productivity nor protect or ameliorate environmental degradation. Thus, the livelihoods based on direct exploitation of natural resources with basic technologies are not likely to be sustainable, especially in the light of the environmental change, characterized by increasing surface temperatures and reduced rainy seasons. Measures are therefore needed to help the rural households in the Mwami area and elsewhere in rural Zambia to adapt to the liberalized economic environment, changing environmental conditions and HIV/AIDS

HIV clinical stage progression of patients at 241 outpatient clinics in Democratic Republic of Congo: Disparities by gender, TB status and rurality

Background: HIV clinical care programs are increasingly cognizant of the importance of customizing services according to patients’ clinical stage progression (WHO\u27s four-tiered staging) and other risk assessments. Understanding factors associated with Persons Living with HIV (PLHIV) patients’ progression through the treatment cascade and clinical stages is essential for programs to provide patient-centered, evidence-based services. Methods and materials: To analyze patient characteristics associated with disease progression stages for PLHIV on antiretroviral therapy (ART), this quantitative study used data, from January 2014–June 2019, from 49,460 PLHIV on ART from 241 HIV/AIDS outpatient clinics in 23 health zones in Haut-Katanga and Kinshasa provinces, Democratic Republic of Congo. To assess bivariate and multivariate associations, we performed Chi-square and multinomial logistic regression. Results: Among PLHIV receiving ART, 4.4% were at stage 4, and 30.7% at stage 3. Those at the less severe stages 2 and 1 constituted 22.9% and 41.9%. After controlling for covariates, patients with no TB were significantly more likely than those with TB (p\u3c = .05) to be at stage 1, rather than 3 or 4 (adjusted odds ratio or AOR, 5.73; confidence interval or CI, 4.98–6.59). Other characteristics significantly associated with higher odds of being at stage 1 included being female (AOR, 1.35; CI, 1.29–1.42), and shorter duration on ART (vs. \u3e 40.37 months); for ART duration less than 3.23 months the AOR was 2.47, for 3.23–14.52 months duration the AOR was 2.60, and for 14.53–40.37 months duration the AOR was 1.77 (quartile cut points used). Compared to patients in urban health zones, those in rural (AOR, 0.32) and semi-rural health zones (AOR, 0.79) were less likely to be at stage 1. Conclusion: Significant and substantial variation in HIV clinical progression stage by geographic location and demographic characteristics existed, indicative of the need for targeted efforts to improve the effectiveness of HIV care. Patients with TB coinfection compared to those without coinfection had a much greater risk of being at stage 3 or 4, implying a need for customized approaches and clinical regimens for this high-risk population

Risk Factors for Mortality in Children Hospitalized With Severe Malaria in Northern Zambia: A Retrospective Case-Control Study

Malaria remains a public health crisis in areas where it has resisted control efforts. In Nchelenge District, a high-transmission area in northern Zambia, malaria accounts for more than one-third of pediatric hospitalizations and nearly one-half of hospital deaths in children. To identify risk factors for death due to malaria, we conducted a retrospective, time-matched case-control study of 126 children hospitalized with malaria who died (cases) and 126 children who survived (controls). There were no differences in age, gender, hemoglobin concentration, or prevalence of severe anemia between cases and controls. Children who died were more likely to come from villages located at greater distances from the hospital than children who survived (median 13.5 versus 3.2 km). Each additional kilometer of distance from the hospital increased the odds of death by 4% (odds ratio 1.04, 95% confidence interval 1.01–1.07, P \u3c 0.01). Extent of anemia and admission during periods when blood was unavailable for transfusion were associated with early death (P £ 0.03). Delays in initiation of treatment of severe malaria contribute to the increased odds of death in children referred from more distant health centers, and might be mitigated by transportation improvements, capacity at rural health posts to administer treatment before transfer, hospital triage systems that minimize time to treatment, and reliable blood product stores at referral hospitals

Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania

SummaryThis study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged ≥18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned (‘Serengeti’) strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania

The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains

Background: The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). This pathway emerges after long term failure of therapy, and is increasingly observed in the resource poor world, where antiretroviral therapy is rarely accompanied by intensive virological monitoring. In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring.Results: Single-genome sequencing (SGS) of full-length RT was carried out on sequential samples from an HIV-infected individual enrolled in ART rollout. The emergence of Q151M MDR occurred in the order A62V, V75I, and finally Q151M on the same genome at 4, 17 and 37 months after initiation of therapy, respectively. This was accompanied by a parallel cumulative acquisition of mutations at 20 other codon positions; seven of which were located in the connection subdomain. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. RT domain-swapping of patient and wild-type RTs showed that patient-derived connection subdomains were not associated with reduced NRTI susceptibility. However, the virus expressing patient-derived Q151M RT at 37 months demonstrated similar to 44% replicative capacity of that at 4 months. This was further reduced to similar to 22% when the Q151M-containing DNA pol domain was expressed with wild-type C-terminal domain, but was then fully compensated by coexpression of the coevolved connection subdomain.Conclusions: We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. The acquisition of the Q151M pathway occurred sequentially over a long period of failing NRTI therapy, and was associated with mutations in multiple RT domains

Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV

BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment. METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment. RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L. CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series

BACKGROUND: Since information on the pathology of COVID-19 from sub-Saharan Africa (SSA) remains scarce, the objective of our study was to define the gross pathology and histological features of COVID-19. We report data from 29 whole-body autopsies of COVID-19 deaths occurring in hospitals in Lusaka, Zambia - the first large autopsy case series from Africa. METHODS: We performed a descriptive post-mortem examination study of inpatient COVID-19 related deaths at two hospitals in Lusaka, Zambia. Whole-body autopsies were conducted according to Standard Operating Procedures. Gross and histopathological examinations of all organs were performed. Patient demographics, history, co-morbidities, autopsy gross and microscopic findings, and cause(s) of death were recorded and analyzed using STATA version 14. Variables were grouped and presented as frequencies and percentages. FINDINGS: Autopsies were performed on 29 decedents (mean age = 44 ± 15.8years; age range = 19-82; 17/29 [58.8%] males). 22/29 [75.9%] cases were <55 years of age. A spectrum of pathological manifestations of COVID-19 were seen in all organs. The commonest causes of death were pulmonary thromboembolism (13/29, 45%), Diffuse Alveolar Damage (9/29, 31%), and COVID-19 pneumonia (7/29, 25%). 22/29 (76%) had co-morbidities. Common co-morbidities included HIV (8/29, 28%), Hypertension (6/29, 20%) Tuberculosis (3/29, 10%), Diabetes (3/29, 10%). CONCLUSIONS: A spectrum of gross anatomical and histopathological findings are seen in COVID-19 deaths in hospitalized decedents. These appear broadly similar to those reported from China, Europe and USA. Differences include a younger age group, and co-morbidities of HIV and TB co-infection which require further investigation

An Empirical Approach to Defining Loss to Follow-up Among Patients Enrolled in Antiretroviral Treatment Programs

In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical “days-late” definition of LTFU among patients on ART. Cohort members were classified as either “in care” or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as “best-performing.” Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that ≥60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs

Malaria Knowledge and Bed Net Use in Three Transmission Settings in Southern Africa

Background: Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality in endemic areas. Despite increasing availability, the use of ITNs remains limited in some settings. Poor malaria knowledge is a barrier to the widespread use of ITNs. The goal of this study was to assess the levels of malaria knowledge and evaluate factors associated with bed net use among individuals residing in three regions of southern Africa with different levels of malaria transmission and control. Methods: A cross-sectional study was conducted on a sample of 7535 residents recruited from 2066 households in Mutasa District, Zimbabwe (seasonal malaria transmission), Choma District, Zambia (low transmission) and Nchelenge District, Zambia (high transmission), between March 2012 and March 2017. A standardized questionnaire was used to collect data on demographics, malaria-related knowledge and use of preventive measures. Multivariate logistic regression analyses were used to assess determinants of bed net use. Results: Most of the 3836 adult participants correctly linked mosquito bites to malaria (85.0%), mentioned at least one malaria symptom (95.5%) and knew of the benefit of sleeping under an ITN. Bed net ownership and use were highest in Choma and Nchelenge Districts and lowest in Mutasa District. In multivariate analyses, knowledge of ITNs was associated with a 30-40% increased likelihood of bed net use after adjusting for potential confounders across all sites. Other factors significantly associated with bed net use were age, household size and socioeconomic status, although the direction, strength and size of association varied by study site. Importantly, participants aged 5-14 years had reduced odds of sleeping under a bed net compared to children younger than 5 years. Conclusion: Relevant knowledge of ITNs translated into the expected preventive behaviour of sleeping under a bed net, underscoring the need for continued health messaging on malaria prevention. The implementation and delivery of malaria control and elimination interventions needs to consider socioeconomic equity gaps, and target school-age children to ensure access to and improve utilization of ITNs

Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and formulations

Background: Dispersible paediatric fixed dose combination (FDCs) tablets delivering higher doses of first-line antituberculosis drugs in WHO-recommended weight-bands were introduced in 2015. We report the first pharmacokinetic data for these FDCs in Zambian and South African children in the treatment-shortening SHINE trial. // Methods: Children weighing 4.0-7.9 kg, 8.0-11.9 kg, 12.0-15.9 kg and 16.0-24.9 kg had 1, 2, 3 and 4 tablets daily (rifampicin/isoniazid/pyrazinamide 75/50/150 mg, with or without 100 mg ethambutol, or rifampicin/isoniazid 75/50 mg), respectively. Children 25.0-36.9 kg received doses recommended for adults <37kg (300, 150, 800, 550 mg daily for rifampicin, isoniazid, pyrazinamide, ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. // Results: Of 77 children evaluated, median (IQR) age was 3.7 (1.4-6.6) years, 40 (52%) were male and 20 (26%) HIV-positive. AUC24 for rifampicin, isoniazid, pyrazinamide and ethambutol were 32.5 (20.1-45.1), 16.7 (9.2 - 25.9), 317 (263 - 399) and 9.5 (7.5 – 11.5) mg.h/L, respectively, and lower in children compared to adults for rifampicin in 4.0-7.9 kg, 8-11.9kg and ≥25kg weight-bands, isoniazid in 4.0-7.9kg and ≥25kg, and ethambutol in all five weight-bands. Pyrazinamide exposures were similar to adults. // Conclusions: Recommended weight-band based FDC doses result in lower drug exposures in children in lower weight-bands and in those ≥25kg (on adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current WHO-recommended doses requires further evaluation