Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern—particularly Alpha, Beta, Delta, and Omicron—on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

Background: Following the outbreak of chikungunya in the Indian Ocean, the Ministry of Health directed the necessary development of an early outbreak detection system. A disease surveillance team including the Institut Pasteur in Madagascar (IPM) was organized to establish a sentinel syndromic-based surveillance system. The system, which was set up in March 2007, transmits patient data on a daily basis from the various voluntary general practitioners throughout the six provinces of the country to the IPM. We describe the challenges and steps involved in developing a sentinel surveillance system and the well-timed information it provides for improving public health decision-making. Methods: Surveillance was based on data collected from sentinel general practitioners (SGP). The SGPs report the sex, age, visit date and time, and symptoms of each new patient weekly, using forms addressed to the management team. However, the system is original in that SGPs also report data at least once a day, from Monday to Friday (number of fever cases, rapid test confirmed malaria, influenza, arboviral syndromes or diarrhoeal disease), by cellular telephone (encrypted message SMS). Information can also be validated by the management team, by mobile phone. This data transmission costs 120 ariary per day, less than US$1 per month. Results: In 2008, the sentinel surveillance system included 13 health centers, and identified 5 outbreaks. Of the 218,849 visits to SGPs, 12.2% were related to fever syndromes. Of these 26,669 fever cases, 12.3% were related to Dengue-like fever, 11.1% to Influenza-like illness and 9.7% to malaria cases confirmed by a specific rapid diagnostic test. Conclusion: The sentinel surveillance system represents the first nationwide real-time-like surveillance system ever established in Madagascar. Our findings should encourage other African countries to develop their own syndromic surveillance systems. Prompt detection of an outbreak of infectious disease may lead to control measures that limit its impact and help prevent future outbreaks.

Hepatitis E virus (HEV) causes an orofecal disease transmitted through poor hygiene environments, contaminated food (mainly pork products), or by contacts with infected animals. Very little data are currently available regarding the disease in the Southwestern Indian Ocean Islands. We report the first sero- and viro-survey for HEV in human and swine in Madagascar. A seroprevalence rate of 14.1% (60 of 427) was measured in slaughterhouse workers. Seroprevalence to HEV in pigs was estimated to 71.2% (178 of 250), strongly suggesting the existence of a zoonotic cycle. Three out of 250 pig livers (1.2%) tested HEV RNA-positive by quantitative polymerase chain reaction. Phylogenetic analyses based on 1-kb sequences of the ORF 2-3 identified these viruses as HEV genotype 3. Sequences clustered in a distinct Malagasy sub-clade, possibly representative of a new sub-genotype, for which the date of emergence was estimated around 1989. Further studies are needed to confirm other transmission routes of HEV to humans, especially through non-zoonotic cycles.

In 2005, there were outbreaks of febrile polyarthritis due to Chikungunya virus (CHIKV) in the Comoros Islands. CHIKV then spread to other islands in the Indian Ocean: La Réunion, Mauritius, Seychelles and Madagascar. These outbreaks revealed the lack of surveillance and preparedness of Madagascar and other countries. Thus, it was decided in 2007 to establish a syndrome-based surveillance network to monitor dengue-like illness. This study aims to evaluate the use of capillary blood samples blotted on filter papers for molecular diagnosis of CHIKV infection. Venous blood samples can be difficult to obtain and the shipment of serum in appropriate temperature conditions is too costly for most developing countries. Venous blood and dried-blood blotted on filter paper (DBFP) were collected during the last CHIKV outbreak in Madagascar (2010) and as part of our routine surveillance of dengue-like illness. All samples were tested by real-time RT-PCR and results with serum and DBFP samples were compared for each patient. The sensitivity and specificity of tests performed with DBFP, relative to those with venous samples (defined as 100%) were 93.1% (95% CI:[84.7–97.7]) and 94.4% (95% CI:[88.3–97.7]), respectively. The Kappa coefficient 0.87 (95% CI:[0.80–0.94]) was excellent. This study shows that DBFP specimens can be used as a cost-effective alternative sampling method for the surveillance and monitoring of CHIKV circulation and emergence in developing countries, and probably also for other arboviruses. The loss of sensitivity is insignificant and involved a very small number of patients, all with low viral loads. Whether viruses can be isolated from dried blood spots remains to be determined. Chikungunya is a mosquito-transmitted viral disease. No treatment is currently available. The only way to prevent infection is to avoid mosquito bites. Surveillance of circulation by early diagnosis is useful to prevent or limit outbreak. CHIKV, like all RNA viruses, is heat-labile. Consequently, confirmatory diagnosis classically requires blood samples that are transported in appropriate conditions (i.e. at 4°C within 48 hours, in liquid nitrogen, or frozen at −80°C and transported on dry ice) to prevent false negative results. This is not always possible in field conditions in low income countries. Dried blood spots are already used to diagnose parasitic, bacterial and viral infection. We compared venous sample to dried blood sample to make diagnosis of Chikungunya infection. We demonstrate the usefulness of this sampling method for the molecular diagnosis of Chikungunya infection. In particular, dried blood spots were very nearly as suitable as frozen serum specimens for the diagnosis of recent infection by CHIKV.

As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (C_t) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-C_t value infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on C_t value, suggesting that C_t value can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population-level C_t distribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional C_t distributions across three regions in Madagascar. We find that C_t-derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of C_t values could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting.

Three epidemic waves of coronavirus disease-19 (COVID-19) occurred in Madagascar from March 2020 to May 2022, with a positivity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 21% to 33%. Our study aimed to identify the impact of COVID-19 on the epidemiology of seasonal respiratory viruses (RVs) in Madagascar. We used two different specimen sources (SpS). First, 2987 nasopharyngeal (NP) specimens were randomly selected from symptomatic patients between March 2020 and May 2022 who tested negative for SARS-CoV-2 and were tested for 14 RVs by multiplex real-time PCR. Second, 6297 NP specimens were collected between March 2020 and May 2022 from patients visiting our sentinel sites of the influenza sentinel network. The samples were tested for influenza, respiratory syncytial virus (RSV), and SARS-CoV-2. From SpS-1, 19% (569/2987) of samples tested positive for at least one RV. Rhinovirus (6.3%, 187/2987) was the most frequently detected virus during the first two waves, whereas influenza predominated during the third. From SpS-2, influenza, SARS-CoV-2, and RSV accounted for 5.4%, 24.5%, and 39.4% of the detected viruses, respectively. During the study period, we observed three different RV circulation profiles. Certain viruses circulated sporadically, with increased activity in between waves of SARS-CoV-2. Other viruses continued to circulate regardless of the COVID-19 situation. Certain viruses were severely disrupted by the spread of SARS-CoV-2. Our findings underline the importance and necessity of maintaining an integrated disease surveillance system for the surveillance and monitoring of RVs of public health interest.