Hospitalizations and Costs Incurred at the Facility Level after Scale-up of Malaria Control: Pre-Post Comparisons from Two Hospitals in Zambia

There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility-level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with < 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions.     

Challenges and prospects for malaria elimination in the Southern Africa region

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, including regions of Southern Africa. Important to effective regional malaria control in Southern Africa is the appreciation that the reductions in malaria have not been achieved uniformly, with some countries experiencing resurgence. Understanding the reasons for sustained low-level malaria transmission in the face of control efforts, why malaria control efforts have not been successful in particular epidemiological settings and the epidemiological and transmission patterns following resurgence are critical to improving further malaria control and possible elimination. The overall goal of the International Center of Excellence for Malaria Research in Southern Africa is to contribute to regional malaria control efforts that can be sustained beyond the duration of the project. This goal will be achieved through a combination of: (1) state-of-the-art research on malaria epidemiology, vector biology and the genetics of the malaria parasite in three different epidemiological settings; (2) collaborations with national malaria control programs to develop locally adapted and sustainable control strategies; and (3) training, career development and capacity building at research institutions throughout the region.     

Recognition of a novel melanotic mutant in a field population of Culex pipiens quinquefasciatus in southern Zambia

Genetic mutations controlling eye color, fat body color, structural abnormalities, and insecticide resistance are common in mosquitoes. We have identified a novel color variant of Culex pipiens quinquefasciatus characterized by a heavily pigmented integument in adult specimens circulating in field populations of this species in southern Zambia. Mosquitoes were collected monthly by pyrethrum spray catch between November and May 2004-05 and 2005-06, with between 25% and 80% of the total Cx. p. quinquefasciatus collections comprising this pigmented variety. The identity of pigmented specimens was morphologically confirmed as Cx. p. quinquefasciatus by examination of orientation of the dorsal and ventral arms of the male genitalia of F1 male progeny reared in the laboratory, and molecularly verified by diagnostic polymerase chain reaction and nicotinamide adenine dinucleotide phosphate dehydrogenase subunit 4 nucleotide sequence homology. Preliminary laboratory rearings indicated that the pigmentation was heritable and not influenced by larval habitat and environmental conditions. Further investigation into the mechanism of the mutation, inheritance patterns, and potential linkage to additional markers is pending.     

The impact of changing the diagnostic algorithm for TB in Manicaland,Zimbabwe

SETTING:Governmental health facilities performing TB diagnostics in Manicaland, Zimbabwe.OBJECTIVE:To investigate the effect of making Xpert® MTB/RIF the primary TB diagnostic for all patients presenting with presumptive TB on 1) the number of samples investigated for TB, 2) the proportion testing TB-positive, and 3) the proportion of unsuccessful results over time.DESIGN:This retrospective study used data from GeneX-pert downloads, laboratory registers and quality assurance reports between 1 January 2017 and 31 December 2018.RESULTS:The total number of Xpert tests performed in Manicaland increased from 3,967 in the first quarter of 2017 to 7,011 in the last quarter of 2018. Mycobacterium tuberculosis DNA was detected in 4.9–8.6% of the samples investigated using Xpert, with a higher yield in 2017 than in 2018. The overall proportion of unsuccessful Xpert assays due to “no results”, errors and invalid results was 6.3%, and highly variable across sites.CONCLUSION:Roll out of more sensitive TB diagnostics does not necessarily result in an increase of microbiologically confirmed TB diagnosis. While the number of samples tested using Xpert increased, the proportion of TB-positive tests decreased. GeneXpert soft- and hardware infrastructure needs to be strengthened to reduce the rate of unsuccessful assays and therefore, costs and staff time.     

A comparative study of the schizontocidal efficacy and safety of artemether versus chloroquine in uncomplicated malaria.

Forty-seven patients with uncomplicated falciparum malaria were randomly assigned to receive either artemether (n = 24), 9.6 mg/kg body weight intramuscularly over five days or chloroquine (n = 23), 25 mg/kg body weight orally. Patients were kept in hospital for seven days followed by review on days 14, 21 and 28. Five patients on chloroquine were withdrawn before day seven due to treatment failure. Of the remaining patients, parasite clearance time was 33.0 +/- 13.6 hours for the artemether group and 63.3 +/- 14.7 hours for patients on chloroquine (p < 0.001). No significant difference was recorded in fever clearance time between the two groups of patients. Recrudescence rate for patients on artemether was 14.3 pc compared to 57.1 pc for the chloroquine group (p < 0.05). No major adverse events were recorded for either treatment group although five patients on artemether had a transient spike of temperature after clearance of parasitaemia. In conclusion, our study has shown that no major adverse events were experienced by patients on artemether and the rate of parasite clearance for the artemether group was superior to that of patients on chloroquine.     

Malaria epidemiology and control in Southern Africa

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, following the scale-up of interventions supported by the Roll Back Malaria Partnership, the President's Malaria Initiative and other partners. It is important to appreciate that the reductions in malaria have not been uniform between and within countries, with some areas experiencing resurgence instead. Furthermore, while interventions have greatly reduced the burden of malaria in many countries, it is also recognized that the malaria decline pre-dated widespread intervention efforts, at least in some cases where data are available. This raises more questions as what other factors may have been contributing to the reduction in malaria transmission and to what extent. The International Center of Excellence for Malaria Research (ICEMR) in Southern Africa aims to better understand the underlying malaria epidemiology, vector ecology and parasite genomics using three contrasting settings of malaria transmission in Zambia and Zimbabwe: an area of successful malaria control, an area of resurgent malaria and an area where interventions have not been effective. The Southern Africa ICEMR will capitalize on the opportunity to investigate the complexities of malaria transmission while adapting to intervention and establish the evidence-base to guide effective and sustainable malaria intervention strategies. Key approaches to attain this goal for the region will include close collaboration with national malaria control programs and contribution to capacity building at the individual, institutional and national levels.     

Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes

Surveillance for drug-resistant parasites in human blood is a major effort in malaria control. Here we report contrasting antifolate resistance polymorphisms in Plasmodium falciparum when parasites in human blood were compared with parasites in Anopheles vector mosquitoes from sleeping huts in rural Zambia. DNA encoding P. falciparum dihydrofolate reductase (EC 1.5.1.3) was amplified by PCR with allele-specific restriction enzyme digestions. Markedly prevalent pyrimethamine-resistant mutants were evident in human P. falciparum infections--S108N (>90%), with N51I, C59R, and 108N+51I+59R triple mutants (30-80%). This resistance level may be from selection pressure due to decades of sulfadoxine/pyrimethamine use in the region. In contrast, cycloguanil-resistant mutants were detected in very low frequency in parasites from human blood samples-S108T (13%), with A16V and 108T+16V double mutants (～4%). Surprisingly, pyrimethamine-resistant mutants were of very low prevalence (2-12%) in the midguts of Anopheles arabiensis vector mosquitoes, but cycloguanil-resistant mutants were highly prevalent-S108T (90%), with A16V and the 108T+16V double mutant (49-57%). Structural analysis of the dihydrofolate reductase by in silico modeling revealed a key difference in the enzyme within the NADPH binding pocket, predicting the S108N enzyme to have reduced stability but the S108T enzyme to have increased stability. We conclude that P. falciparum can bear highly host-specific drug-resistant polymorphisms, most likely reflecting different selective pressures found in humans and mosquitoes. Thus, it may be useful to sample both human and mosquito vector infections to accurately ascertain the epidemiological status of drug-resistant alleles.     

Knowledge, practices, and perceptions about malaria in rural communities of Zimbabwe: relevance to malaria control.

A survey of 411 household heads was undertaken in Gokwe district, Zimbabwe, to assess villagers'' knowledge, practices and perceptions about malaria and their implications for malaria control. Our results show that although the government has sustained an annual indoor insecticide spraying programme for over four decades, about 50% of respondents did not adequately understand its purpose, with 26% believing that the programme was intended to kill domestic pests, not including mosquitos. During the 1991-92 spraying cycle, 72% of the villagers had their homes sprayed. However, 21% of such villagers refused to have some rooms in their homes sprayed. Householders'' understanding of the function of the spraying programme was significantly related to their compliance with it (P < 0.05). A total of 82% of respondents reported not taking any measures to protect themselves from malaria. Taking preventive measures was significantly related to knowledge of the causes of malaria (P < 0.05). The study shows the importance of involving communities in a control programme intended to be to their benefit and of informing them about available options for protection against malaria.     

Cattle, other domestic animal ownership, and distance between dwelling structures are associated with reduced risk of recurrent Plasmodium falciparum infection in southern Zambia

Objectives  To examine the associations between household Plasmodium falciparum infection and a number of factors including domestic animal ownership, potential mosquito breeding sites, indoor darkness, density of people, distance between dwelling structures, and insecticide-treated bed net use.
Methods  Analyses were based on data collected from a household survey conducted in Macha, Zambia. Thirty-four households with recurrent malaria infection in 2005–2008 were selected as case households and compared with 37 control households with no malaria infection randomly selected from the same geographic area. Logistic regression models were used to identify factors associated with household P. falciparum infection.
Results  In multivariate analysis, cattle ownership was associated with reduced risk of P. falciparum infection (adjusted odds ratio = 0.19; 95% CI = 0.05–0.69), as was increased distance between dwelling structures (aOR = 0.26; 95% CI = 0.07–0.98). Ownership of the highest category of cattle, goats, dogs, or cats dramatically reduced the risk of P. falciparum infection (aOR = 0.13; 95% CI = 0.03–0.56).
Conclusion  Domestic animal, in particular cattle, ownership and greater distance between dwelling structures were associated with reduced risk of recurrent P. falciparum infection at the household level. These factors should be further investigated as supplemental measures for malaria control in rural African settings.     

Trial of the ParaSight‐F test for malaria diagnosis in the primary health care system, Zimbabwe

Rapid diagnosis of Plasmodium falciparum malaria remains one of the main limitations to prompt treatment. Diagnosis based on clinical symptoms is decidedly unreliable, especially in areas of seasonal transmission like Zimbabwe. In view of this, the Plasmodium falciparum histidine‐rich protein (HRP‐II) antigen detection assay ( Para Sight‐F test) was tried at 10 health centres in 3 malaria endemicity zones of Zimbabwe, as a malaria diagnostic tool for primary health care. Parasitological evaluations were conducted using thick and thin film microscopy as gold standard, and ease of test operation and practicability to nurses were ascertained by questionnaire. The sensitivity of the test did not vary substantially by endemicity zone and was ≈93%. Specificities were 85, 72 and 92% in the hyperendemic, mesoendemic and hypoendemic zones, respectively. Positive predictive values varied considerably with endemicity, the lowest being in the hypoendemic zone (56%). However, negative predictive values did not change significantly, with a mean of 94%. It was found that the Para Sight‐F test reduced mistreatment for malaria, relative to clinical diagnosis, by up to 81%, especially in the hypoendemic region. Test acceptability evaluations were good.