The current study aimed to generate local data through a standardized questionnaire sent to representatives of primary, secondary, and tertiary health care institutions involved in HIV care. The obtained information helped to understand the level of access to diagnosis of IFD that PLWH have across the Mexican territory. We describe very low access to rapid tests and point-of-care tests in general in Mexican health centers, but more critically in primary care centers, where the utility of these tests is the highest.
Recently, articles have been published on the diagnostic capacities of fungal infections in Africa, Europe and Asia [9, 13, 14]. In Europe, a survey that included 45 countries reported overall good access to diagnostic tools and specifically to rapid tests, but with clear differences according to the country’s Growth Domestic Product [9]. A survey conducted by the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) explored access to diagnostic tools for IFDs in 40 countries and territories of the Asia Pacific Region [13]. Seventy-one percent of the included sites reported PLWH as their target patients. The study found that access to microscopy for IFD diagnosis was reported in 98.3% of the participating sites, and culture based methodologies in 97.4% of them. Additionally, between 60–70% of the centers had availability of CrAg and 21.7% for Histoplasma antigen detection [13]. A continent-wide survey showed that more than 70% of people in African countries had no public access to diagnostic tests for Histoplasma and Pneumocystis and 40% had no access to CrAg [15]. Cryptococcal antigen access was mostly provided by non-governamental organizations and other private health initiatives (15). The HIV-care funding situation in Latin America differs from other regions because Mexico and Latin American Countries in general obtain much less external non-governamental funding compared to some African regions [16]. In 2019, Latin America received a $3.03 billion USD from UNAIDS for HIV prevention and care, which is a less than a third of the amount for Southern Africa ($9.36 billion), and similar to $3.25 billion for the South Pacific Region [16].
Prior studies have evaluated local capacities to diagnose fungal infections in Latin America. One study reported a survey of 129 institutions in 14 countries in Latin America, 83% providing care for PLWH. Mexico participated with nine tertiary care centers. Urinary antigen for Histoplasma was available for 22% of the responders and 75% reported access to CrAg [17]. Another nation-wide survey from Honduras reported a very low access to fungal antigen detection tests, with only two institutions with access to Histoplasma antigen, and three institutions to CrAg lateral flow assay [18]. Many studies in Central America have described the positive impact of including rapid tests on the diagnosis yield of fungal diseases such as histoplasmosis and cryptococcosis [19, 20].
In Guatemala, implementing rapid antigen tests for histoplasmosis improved more than double the diagnostic capacity compared to the exclusive use cultures [21]. Besides an improvement in case detection, there is also evidence that prompt diagnosis of opportunistic infections such as cryptococcosis and histoplasmosis through a rapid test improves survival [20, 22]. Paccoud et al. evaluated the impact in mortality of prior screening with CrAg, in PLWH with a CD4 count < 100 cells/mm3 and confirmed meningeal cryptococosis or cryptococcemia. They found a 17% reduction of mortality in patients screened compared to patients not screened [20]. Medina et al., described the impact of implementing a program of prospective screening for OI in patients with advanced disease in Guatemala. After one year of the implementation, they found a 7% reduction in mortality and 5% increase in targeted treatment for OIs [22]. Rajasingham et al., in their decision analytical model, evaluated histoplasma antigen screening in PLWH with advanced disease, and report that routine screening avoids an estimated 17% deaths in cases of advanced HIV disease [23].
Among PLWH, fungal diseases remain a major cause of morbidity and mortality, mainly due to meningeal cryptococcosis and disseminated histoplasmosis. Thanks to the implementation of screening programs using rapid tests, two recent studies carried out in Guatemala demonstrated that these two IFD have a higher incidence than previously estimated [22, 24, 25]. Coccidioidomycosis is considered endemic in Northern Mexico, histoplasmosis in Mid-Southern Mexico, and cryptococcosis represents one of the three most serious fungal infections in PLWH [26, 27]. These data support the need to have rapid access to identify these fungal etiologies.
We also provide data regarding access to diagnosis of other potentially deadly OI such as mycobacterial infections, including tuberculosis (TB). Tuberculosis was the OI with the highest diagnostic capacity, mainly due to access to GeneXpert (Cepheid), however the diagnostic capacity remained low, at 50%. In a prospective cohort study including patients coinfected with HIV/TB from four different regions of the world (Eastern Europe (EE), Western Europe (WE), Southern Europe (SE) and Latin America (LA)), the proportion of patients with definite TB diagnosis in EE (47%) and LA (40%) was lower than WE (71%) and SE (72%), reflecting poor access to diagnostic tests in those regions [28]. These were also the regions with the lowest median CD4 + T cell count. Although the national TB incidence rate is estimated at 25 cases per 100,000 population [29], this varies widely by geographical region, with highest burden in the poorest regions, and usually in regions with higher HIV/TB coinfection.
We report eight states with more than 50% advanced disease among individuals with new HIV diagnosis. These proportions are similar to the official report on the proportion of patients with < 200 CD4 + T cells by the National Center for Prevention and Control of HIV/AIDS (CENSIDA) [4]. Most of these states are located either at the border with the USA (two states), or the southern region of the country (four states). This latter region is characterized by poorer socioeconomic conditions, with higher proportion of informal labor and indigenous population, and lower education [30]. It is also the region with the highest burden of fungal diseases and should be the region with better access to rapid detection tools. Instead, only one center of the southern area was able to diagnose histoplasmosis and cryptococcosis with rapid tests.
Regarding hepatitis C, we report access to hepatitis serology in less than 65% of the centers: 100% of second and tertiary centers, 45% in primary care facilities. This is of central importance as recently, a nationwide hepatitis C program was implemented by the Mexican government aiming to provide free access to direct-acting antivirals [31]. Certainly, the success in implementing this and any other program will rely on having adequate screening tools at all health care levels and not only at tertiary care institutions. However, it is possible that our survey does not reflect all centers currently screening for hepatitis C, since the number of centers in the program has increased in the last two years.
It is important mentioning that half of the centers has at least one need to send their samples for analysis to another facility. Relying on external laboratories results in long waiting times, reflecting how the lack of local diagnostic resources impacts and delays diagnostic and treatment.
Our study has some limitations. Due to the nature of the study, we reported only information from the centers who replied to our request, and our response rate was 57%. These data might not be representative of every state in the country, particularly for the states where we did not get a reply. For the states who replied with only one or two answers, we generalized the information of the state from only a few answers, and there could also be differences intra-state that could not be perceived in this report. However, we managed to describe the situation for almost three quarters of the states, and we had representation of the poorest states of the country with the highest burden of OIs, as well as representation from the centers with greater capacity of HIV care.
In conclusion, in Mexico, most public HIV-dedicated health care centers lack on-site capacity to diagnose opportunistic infections, specifically fungal infections. Rapid tests and point-of-care tests are frequently unavailable, which is more pronounced in primary care centres. Considering that IFDs still contribute significantly to mortality among PLWH, better access to diagnostic tools in all levels of HIV-care is urgent.
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