Malaria Burden Stratification in Malawi- A report of a consultative workshop to inform the 2023-2030 Malawi Malaria Strategic Plan.

Background: Malawi's National Malaria Control Programme (NMCP) is developing a new strategic plan for 2023-2030 to combat malaria and recognizes that a blanket approach to malaria interventions is no longer feasible. To inform this new strategy, the NMCP set up a task force comprising 18 members from various sectors, which convened a meeting to stratify the malaria burden in Malawi and recommend interventions for each stratum. Methods: The burden stratification workshop took place from November 29 to December 2, 2022, in Blantyre, Malawi, and collated essential data on malaria burden indicators, such as incidence, prevalence, and mortality. Workshop participants reviewed the malaria burden and intervention coverage data to describe the current status and identified the districts as a appropriate administrative level for stratification and action. Two scenarios were developed for the stratification, based on composites of three variables. Scenario 1 included incidence, prevalence, and under-five all-cause mortality, while Scenario 2 included total malaria cases, prevalence, and under-five all-cause mortality counts. The task force developed four burden strata (highest, high, moderate, and low) for each scenario, resulting in a final list of districts assigned to each stratum. Results: The task force concluded with 10 districts in the highest-burden stratum (Nkhotakota, Salima, Mchinji, Dowa, Ntchisi, Mwanza, Likoma, Lilongwe, Kasungu and Mangochi) 11 districts in the high burden stratum (Chitipa, Rumphi, Nkhata Bay, Dedza, Ntcheu, Neno, Thyolo, Nsanje, Zomba, Mzimba and Mulanje) and seven districts in the moderate burden stratum (Karonga, Chikwawa, Balaka, Machinga, Phalombe, Blantyre, and Chiradzulu). There were no districts in the low-burden stratum. Conclusion: The next steps for the NMCP are to review context-specific issues driving malaria transmission and recommend interventions for each stratum. Overall, this burden stratification workshop provides a critical foundation for developing a successful malaria strategic plan for Malawi.

Consultative meeting that examined alignment and discrepancies between health facility and household survey data in Malawi.

Malawi is midway through its current Malaria Strategic Plan 2017-2022, which aims to reduce malaria incidence and deaths by at least 50% by 2022. Malariometric data are available with health surveillance data housed in District Health Information Software 2 (DHIS2) and household survey data from two recent Malaria Indicator Surveys (MIS) and a Demographic and Health Survey (DHS). Strengths and weaknesses of the data were discussed during a consultative meeting in Lilongwe, Malawi in July 2019. The first 3 days included in-depth exploration and analysis of surveillance and survey data by 13 participants from the National Malaria Control Programme, district health offices, and partner organizations. Key indicators derived from both DHIS2 and MIS/DHS sources were analysed with three case studies, and presented to stakeholders on the fourth day of the meeting. Applications of the findings to programmatic decision-making and strategic plan evaluation were critiqued and discussed.

The effect of HIV and antiretroviral therapy on characteristics of pulmonary tuberculosis in northern Malawi: a cross-sectional study.

BACKGROUND: HIV infection reduces the likelihood that individuals with pulmonary tuberculosis are smear positive and that they have cavitatory disease. Antiretroviral therapy (ART) may shift the pattern of disease to be more similar to that of HIV negative patients. This would aid diagnosis--which often depends on sputum smears--but would also increase infectiousness. We assessed the effect of HIV and ART on smear positivity and cavitatory disease in laboratory-confirmed pulmonary TB patients. METHODS: Three sputum samples were collected per pulmonary TB suspect and were examined using microscopy and culture. Chest radiographs were available for a subset of patients as part of another study. The effect of HIV and ART status on sputum smear positivity and lung cavitation were evaluated using multivariable logistic regression. RESULTS: Of 1024 laboratory-confirmed pulmonary TB patients who were identified between January 2005 and December 2011, 766 had HIV and ART status available. Positive sputum smears were significantly more common among HIV negative individuals than HIV positive individuals (adjusted OR = 2.91, 95% CI 1.53-5.55). Compared to those HIV positive but not on ART, patients on ART were more likely to be smear positive (adjusted OR = 2.33, 95% CI 1.01-5.39) if they had been on ART ≤ 6 months, but only slightly more likely to be smear positive (adjusted OR = 1.43, 95% CI 0.68-2.99) if they were on ART > 6 months. HIV negative patients were more likely than HIV positive patients to have cavitatory disease (adjusted OR = 1.97, 95% CI 1.20-3.23). Patients on ART > 6 months had a slight increase in cavitatory disease compared to HIV positive patients not on ART (adjusted OR = 1.68, CI 0.78-3.63). CONCLUSIONS: HIV infection is associated with less smear positivity and cavitation in pulmonary TB patients. Among HIV positive patients, the use of ART shifts the presentation of disease towards that seen in HIV-negative individuals, which facilitates diagnosis but which also could increase infectiousness.

Association between socioeconomic position and tuberculosis in a large population-based study in rural Malawi.

SETTING: There is increasing interest in social structural interventions for tuberculosis. The association between poverty and tuberculosis is well established in many settings, but less clear in rural Africa. In Karonga District, Malawi, we found an association between higher socioeconomic status and tuberculosis from 1986-1996, independent of HIV status and other factors. OBJECTIVE: To investigate the relationship in the same area in 1997-2010. DESIGN: All adults in the district with new laboratory-confirmed tuberculosis were included. They were compared with community controls, selected concurrently and frequency-matched for age, sex and area. RESULTS: 1707 cases and 2678 controls were interviewed (response rates >95%). The odds of TB were increased in those working in the cash compared to subsistence economy (p<0.001), and with better housing (p-trend=0.006), but decreased with increased asset ownership (p-trend=0.003). The associations with occupation and housing were partly mediated by HIV status, but remained significant. CONCLUSION: Different socioeconomic measures capture different pathways of the association between socioeconomic status and tuberculosis. Subsistence farmers may be relatively unexposed whereas those in the cash economy travel more, and may be more likely to come forward for diagnosis. In this setting "better houses" may be less well ventilated and residents may spend more time indoors.

Molecular detection of mixed infections of Mycobacterium tuberculosis strains in sputum samples from patients in Karonga District, Malawi.

The occurrence of mixed infections of Mycobacterium tuberculosis is no longer disputed. However, their frequency, and the impact they may have on our understanding of tuberculosis (TB) pathogenesis and epidemiology, remains undetermined. Most previous studies of frequency applied genotyping techniques to cultured M. tuberculosis isolates and found mixed infections to be rare. PCR-based techniques may be more sensitive for detecting multiple M. tuberculosis strains and can be applied to sputum. To date, one study in South Africa has used a PCR approach and suggested that mixed infection could be common. We investigated mixed infections in northern Malawi using two lineage-specific PCR assays targeting the Latin American-Mediterranean (LAM) and Beijing lineages. Compared with spoligotyping, the specificity and sensitivity of both assays was 100%. From 160 culture-positive sputa, mixed LAM and non-LAM strains were detected in 4 sputa belonging to 2 (2.8%) patients. Both patients were HIV positive, with no history of TB. Cultured isolates from both patients showed only LAM by PCR and spoligotyping. In a set of 377 cultured isolates, 4 were mixed LAM and non-LAM. Only one showed evidence of more than one M. tuberculosis strain using IS6110-based restriction fragment length polymorphism (IS6110-RFLP) and spoligotyping analyses. Corresponding sputa for the 4 isolates were unavailable. Mixed Beijing and non-Beijing strains were not detected in this study. Mixed infections appear to be rare in our setting and are unlikely to affect findings based on DNA fingerprinting data. Molecular methods, which avoid the selective nature of culture and target distinct strains, are well suited to detection of mixed infections.

Changes in Mycobacterium tuberculosis genotype families over 20 years in a population-based study in Northern Malawi.

BACKGROUND: Despite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection. METHODS AND PRINCIPAL FINDINGS: In a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates were grouped into spoligotype families and lineages following previously published criteria. Time trends, HIV status, drug resistance and outcome were examined by spoligotype family and lineage. In addition, transmissibility was examined among pairs of cases with known epidemiological contact by assessing the proportion of transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity of the M tuberculosis strains. 760 spoligotypes were obtained from smears from 518 patients from 1986-2002, and 377 spoligotypes from cultures from 347 patients from 2005-2008. There was good consistency in patients with multiple specimens. Among 781 patients with first episode tuberculosis, the majority (76%) had Lineage 4 ("European/American") strains; 9% had Lineage 3 ("East-African/Indian"); 8% Lineage 1 ("Indo-Oceanic"); and 2% Lineage 2 ("East-Asian"); others unclassifiable. Over time the proportion of Lineage 4 decreased from >90% to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains were more common in those with HIV infection, even after adjusting for age, sex and year. There were no associations with drug resistance or outcome, and no differences by lineage in the proportion of pairs in which transmission was confirmed. CONCLUSIONS: This is the first study to describe long term trends in the four M. tuberculosis lineages in a population. Lineage 4 has probably been longstanding in this population, with relatively recent introductions and spread of Lineages1-3, perhaps influenced by the HIV epidemic.